|
|
|
L-Glu | cerebral cortex projections
subthalamic nucleus (STN) ventroanterior and ventrolateral nuclei of the thalamus |
NMDA![]() AMPA ![]() kainate ![]() mGluRI 1 ![]() mGluRII 2 ![]() mGluRII 3 ![]() mGluRIII 4 ![]() mGluRI 5 ![]() mGluRIII 6 ![]() mGluRIII 7 ![]() mGluRIII 8 ![]() |
N-acetylaspartylglutamate (NAAG), a dipeptide derivative of N-acetylaspartate (NAA) and glutamate (Glu) | present in neurons. Upon neurostimulation, NAAG
is exported to astrocytes
where it activates mGluR3![]() ![]() |
mGluRII 3![]() |
L-Asp |
|
|
|
L-Gly | Gly receptor![]() |
|
g-aminobutyrric acid (GABA) | substantia nigra pars reticulata (SNpr), cerebellum (Purkinje's neurons), striatum, lateral globus pallidus (LGP), hippocampus, spinal cord | GABAA![]() GABAB ![]() GABAC ![]() |
taurine (a sulphur containing amino acid, is the most abundant intracellular amino acid in humans; conditionally essential amino acid for preterm neonate; in healthy individuals the diet is the usual source of taurine; although in the presence of vitamin B6 it is also synthesised from Met and Cys) | GABAA![]() NMDAR ![]() Gly receptor ![]() |
|
|
|
acetylcholine (ACh) | PNS :
|
N![]() M1 ![]() M2 ![]() M3 ![]() M4 ![]() M5 ![]() |
|
|
|
noradrenaline / norepinephrine (NE) | PNS : postganglionic neurons of
orthosympathetic system
CNS : brainstem nuclei
|
... |
dopamine (DA) / prolactin inhibiting factor (PIF) | Sommering's substantia nigra pars compacta
(SNpc; area 9; => striatum),
mesolimbic tract neurons (area 10; => nucleus accumbens) nigrocortical tract neurons (area 10; => cortex) hypothalamopituitary tract neurons |
D1![]() D2 ![]() D3 ![]() D4 ![]() D5 ![]() |
|
|
|
5-hydroxytriptamine
(5-HT)
/ serotonin / enteramine
![]() Plasma free Trp levels increase after meals containing large quantities of FFA, which can displace Trp from plasma proteins : anyway 5-HT release from neurons is regulated by limiting entry into secretory vesicles and intraneuronal 5-HT degradation. |
raphe nuclei, EC cells in Langerhans' islets, fundus and pylorus of stomach, jejunum, ileum, and colon | 5-HT1A![]() 5-HT1B ![]() 5-HT1C / 2C ![]() 5-HT1D ![]() 5-HT1E ![]() 5-HT1F ![]() 5-HT2A / 2 / D ![]() 5-HT2B / 2F ![]() 5-HT3 / M ![]() 5-HT4 ![]() 5-HT5A ![]() 5-HT5B ![]() 5-HT6 ![]() 5-HT7 ![]() |
|
|
|
histamine /
b-aminoethylimidazole
![]() |
mast cells![]() ![]() |
H1![]() H2 ![]() H3 ![]() H4 ![]() |
|
name |
|
|
acylethanolamides (AEs)ref | palmitylethanolamide (PEA) | astrocytes | CB2![]() |
anandamide
(arachidonylethanolamide (AEA))
arachidonic acid ![]() ![]() |
immature dendritic cells, neurons, astrocytes | CB1![]() |
|
homo-g-linolenylethanolamide (HEA) | astrocytes | CB1![]() |
|
docosatetraenylethanolamide (DEA) | astrocytes | CB1![]() |
|
oleylethanolamide (OEA) | small intestine, astrocytes | PPAR-a![]() |
|
myristylethanolamide | |||
palmitelaidylethanolamide | |||
palmitoleylethanolamide | |||
N-palmitoylethanolamine (PalEtn) | immature dendritic cells, neurons | ||
2-arachidonoylglycerol amide (2-AG) | immature dendritic cells, neurons | CB2![]() |
|
oleamide / sleep-inducing factor |
morphine![]() |
neuroblastoma cells and pancreatic carcinoma cells | m3![]() |
|
|
|
advanced
glycation![]()
|
RAGE![]() galectin-3 ![]() macrophage scavenger receptor class A types I and II (SR-A) ![]() CD36 ![]() scavenger receptor class B type I (SR-BI) ![]() LOX-1 ![]() FEEL-1 ![]() FEEL-2 ![]() |
|
|
|||
lysophospholipids (LPs) | lysophosphatidic
acid (LPA) : 3 different stimulus-coupled
cellular pathways for rapid
synthesis and release of this mediator are known.
|
EDG2![]() EDG4 ![]() EDG7 ![]() |
||
=sphingomyelinase=>
? =ceramidase=>
sphingosine =sphingosine
kinase![]() |
EDG1![]() EDG3 ![]() EDG5 ![]() EDG8 ![]() |
|||
1-O-alkyl-2-acyl-sn-glyceryl-3-phosphorylcholine
=PL-A2![]() ![]() ![]() Inactivated by PAF acetylhydrolase. |
PAFR![]() |
|||
lysophosphatidylcholine (LPC) | G2A / LPC1![]() |
|||
sphingosylphosphoryl choline (SPC) | GPR68
/ OGR-1 / SPC1![]() |
|||
psychosine / galactosylsphingosine | GPR65 /
TDAG8![]() |
|||
prostanoids (a subscript is used to indicate the number of double bonds in the fatty acid) | prostaglandins (analogs of the unnatural compound prostanoic acid) | PGG2 | ||
PGH2 | TP![]() |
|||
PGA2 | ||||
PGD2 | DP1![]() DP2 / CRTH2 / GPR44 ![]() PPAR-g ![]() |
|||
9a,11b-PGF2 | ||||
PGD-M | ||||
15-deoxy-D12,14-PGD2 (15dPGD2) | ||||
PGE1 | IP![]() |
|||
PGE2
![]() |
EP1![]() EP2 ![]() EP3 ![]() EP4 ![]() |
|||
PGE3 | ||||
PGE-M | ||||
PGF2a | FP![]() |
|||
PGF-M | ||||
PGI2 / prostacyclin (PC) (have half-lives on the order to seconds to a few minutes) | IP![]() PPAR-g ![]() |
|||
6-keto-PGF1a | ||||
2,3-dinor-6-keto-PGF1a | ||||
PGJ2 | PPAR-g![]() |
|||
5-deoxy-D12,14-PGJ2 (15dPGJ2) | PPAR-g![]() |
|||
leukotrienes.
LTC4,
LTD4 and LTE4 are collectivelly
referred as cysteinyl
leukotrienes or slow-reacting substance of
anaphylaxis (SRS-A).
5,8,11,14,17-eicosapentaenoic acid (EPA) ![]() |
LTA4 | |||
LTB4 (exits cell via ?) | B-LT1
/ P2Y7![]() B-LT2 ![]() PPAR-a ![]() PPAR-g ![]() (intranuclear signaling for negative feedback loop) |
|||
LTC4 (exits
cell via MRP1 and
ABCC1
/
MDR-associated protein type 2 (MRP2)![]() |
cysLT1![]() cysLT2 ![]() |
|||
LTD4 (generated extracellularly) | cysLT1![]() cysLT2 ![]() |
|||
LTE4 (generated extracellularly) | cysLT1![]() cysLT2 ![]() |
|||
thromboxans (analogs of the unnatural compound thrombanoic acid; have half-lives on the order to seconds to a few minutes) | TXA1 | TXA1R![]() |
||
TXA2 | TP![]() |
|||
TXB2 | ||||
2,3-dinor-TXB2 | ||||
lipoxins | LXA4 | FPR-like (FPRL)
1 / ALXR![]() AHR ![]() |
||
aspirin-triggered
lipoxin
(ATL) / 15(R)-epi-LXA4 (due to
acetylation
of COX-2 by acetylsalicylic
acid![]() |
FPR-like (FPRL)
1 / ALXR![]() |
|||
LXB4 | ||||
5-oxo-ETE | ||||
hydroxy-ETE (HETE) | ||||
epoxy (EET) |
|
|
|
|
|
Hematopoietins (4-helix bundles) | erythropoietin (EPO) / hematopoietin / hemopoietin; monomer or dimer of a 165 amino-acid sequence glycoprotein | interstitial cells which are localized around the proximal renal tubule (90%), hepatocytes (10%; higher in fetal liver) macrophages. Paracrine and autocrine functions in endometrial cells in the secretory > proliferative phase, placenta, astrocytes, Sertoli and peritubular myoid cells, and capillary endothelium. Neuronal and glial cells of the central nervous system and in the retinaref1, ref2. Excreted in urine | EPOR![]() |
|
interleukin 2 (IL-2) / BF / EDF / KHF / LMF / LCM factor / LPF / MAF-C I / PFC-EA / SCIF / T-cell growth factor (TCGF) / TCPA / TDF / TGP-3 / TMF / TRF-3 / TSF ; monomer | T lymphocytes | IL-2R![]() |
||
IL-3 / multicolony stimulating factor (multi-CSF); monomer | all classes of T and NK2 lymphocytes, thymic
epithelial cells (TECs),
mast
cells![]() ![]() ![]() |
IL-3R![]() |
||
IL-4 / BCGF-1 / TCGF-2 / B lymphocyte stimulatory factor 1 (BSF-1); monomer : the one interchain disulfide bond is required for biologic activity | Th2
lymphocytes![]() ![]() ![]() ![]() |
IL-4R![]() |
||
IL-5 / BCGF-2 / Eo-CSF ; homodimer | Th2
lymphocytes![]() ![]() ![]() ![]() |
IL-5R![]() |
||
IL-6 / IFN-b2 / B lymphocyte stimulatory factor 2 (BSF-2) / BCDF; monomer | white adipose tissue (30% of plasma IL-6 under
basal conditionsref;
visceral > subcutaneousref),
T
lymphocytes, macrophages, endothelial cells
(stimulated by CRP![]() |
IL-6R![]() |
||
IL-7 / TCGF-b; monomer or dimer | bone marrow, TECs | IL-7R![]() |
||
thymic stromal lymphopoietin (TSLP) | ||||
IL-9 / TCGF-3; monomer | T lymphocytes | IL-9R![]() |
||
IL-11; monomer | stromal fibroblasts in bone marrow | IL-11R![]() |
||
IL-13 / P600; monomer | Th2
lymphocytes![]() ![]() ![]() ![]() |
IL-13R![]() |
||
IL-15 / IL-T; monomer (48 aa-long signal sequence isoform localizes in plasma membrane or is secreted; 21 aa-long signal sequence isoform is found within the cytoplasm or nucleus | activated monocytes and macrophages, dendritic cells, skeletal muscle, kidney, lung, heart, and placenta | IL-15R![]() |
||
IL-31ref | Th2
lymphocytes![]() |
IL-31RA and OSMR![]() |
||
macrophage colony stimulating factor (M-CSF) / CSF-1 | fibroblasts, stimulated endothelial cells, bone-marrow stroma, monocytes, macrophages, T lymphocytes, B lymphocytes, epithelial cells (including TECs) | M-CSFR
/ CD115![]() |
||
granulocyte colony stimulating factor (G-CSF) / CSF-3 ; monomer or dimer | TECs, stromal cells, inducible in tissues from fibroblasts and macrophages and from endothelial cells by inflammatory mediators (IL-1, IL-6, and TNF) in virtually all organs | G-CSFR![]() |
||
granulocyte and macrophage colony stimulating factor (GM-CSF) / CSF-2 / BPA ; monomer or dimer | monocytes, macrophages, all classes of T and NK lymphocytes, epithelial cells (including respiratory epithelial cells, stimulated endothelial cells and TECs), fibroblasts, eosinophils | GM-CSFR![]() soluble GM-CSFR a subunit (sGMRa) arises through alternative splicing or ectodomain shedding by MMPs ![]() |
||
oncostatin M (OSM / OM); monomer | T lymphocytes, activated monocytes and macrophages, bone marrow stromal cells, some lines of mammary carcinoma and myeloma | OSMR![]() LIFR ![]() |
||
leukemia inhibiting factor (LIF); monomer | bone marrow stromal cells, fibroblasts, osteoblasts, TECs, activated T lymphocytes | LIFR![]() |
||
ciliary neurotrophic factor (CNTF) | CNTFR![]() |
|||
neurotrophin 1 (NTF-1 / NT-1) / B-cell stimulatory factor-3 | ||||
cardiotrophin-1 | ||||
Interferons (IFNs) => viral interference within 4÷6 hrs, induction of CXCL10 / IP-10 | type I interferons (=> IRF => ISRE => IFN-stimulated genes (ISGs)) | IFN-a ; 18 paralogous intron-less genes on 9p : 6 of them are pseudogenes; monomer; high diffusibility, induces up-regulation of MHC class I and b2-microglobulin | most cell types : leukocytes (including B lymphocytes and macrophages) | IFNAR1
/ CD118![]() IFNAR2 ![]() |
IFN-b ; b1 and b3 (b2 is now renamed IL-6); low diffusibility, induces up-regulation of MHC class I and b2-microglobulin ; monomer | most cell types : fibroblasts and some epithelia | IFNAR1
/ CD118![]() IFNAR2 ![]() |
||
IFN-k | unstimulated keratinocytes, peripheral blood monocytes, and monocyte-derived dendritic cells (up-regulated by type I and type II IFNs) | IFNAR1
/ CD118![]() IFNAR2 ![]() |
||
IFN-l2 / IL-28A | IL-28
and IL-29
R![]() |
|||
IFN-l3 / IL-28B | ||||
IFN-l1 / IL-29 | ||||
IFN-w1 | IFNAR1
/ CD118![]() IFNAR2 ![]() |
|||
type II interferon | IFN-g / macrophage-activating factor (MAF); homodimer ; 12q; induces temporary expression of MHC class II molecules on fibroblasts and other cell types and up-regulation of MHC class I and b2-microglobulin | Th1
lymphocytes![]() |
IFNGR1
/ CD119![]() IFNGR2 ![]() |
|
immunoglobulin superfamily (IgSF) | B7.1 / CD80 ; dimer | APCs | CD28![]() CD152 / CTLA-4 ![]() |
|
B7.2 / B70 / CD86 | APCs | CD28![]() CD152 / CTLA-4 ![]() |
||
TNF (ligand) superfamily (TNFSF) | TNFSF1 / TNF-b/ lymphotoxin (LT) -a (LT-a) ; a3 homotrimer or a2b1 heterotrimer with LT-b, which anchors it to the cell surface | activated monocytes and macrophages, activated T lymphocytes, B lymphocytes and NK cells and a wide variety of other cells | CD120a
/ p55TNFRI![]() CD120b / p75TNFRII ![]() |
|
TNFSF2 / TNF-a / cachectin ; soluble homotrimer lymphokine capable of causing in vivo hemorrhagic necrosis of certain tumor cells, but not affecting normal cells; it has been used as an experimental anticancer agent. It can also induce shock when bacterial endotoxins cause its release | macrophages, NK cells, B cells, T cells, mast
cells![]() ![]() ![]() ![]() |
CD120a
/ p55TNFRI![]() CD120b / p75TNFRII ![]() |
||
TNFSF3 / LT-b ; a and b isoforms; transmembrane, b3 homotrimer or a1b2 heterotrimer with TNF-b / LT-a, anchoring it to the cell surface | T lymphocytes, B lymphocytes (?) | LTbR![]() HVEM ![]() |
||
TNFSF4 / OX40L / CD134L / gp34 | activated CD4+ T lymphocytes | OX40 /
CD134![]() |
||
TNFSF5 / CD154 / 40L / TRAP ; homotrimer | T lymphocytes, mast
cells![]() |
CD40![]() |
||
the external domain of TNFSF6 / CD178 / CD95L /FasL / Apo-1 (soluble FasL); homotrimer | T lymphocytes, B lymphocytes, eye (choroid![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
CD95
/ Apo1 / Fas![]() |
||
TNFSF7 / CD70 / CD27L / Ki-24 ; homotrimer | activated DC, T and B lymphocytes | CD27![]() |
||
TNFSF8 / CD153 / 30L ; homotrimer | T lymphocytes | CD30![]() |
||
TNFSF9 / CD137L / 4-1BBL ; homotrimer | T lymphocytes, carcinoma cell lines | CD137 /
4-1BB![]() |
||
TNFSF10 / Apo-2L / TL2 / TRAIL ; homotrimer | T lymphocytes, monocytes, eye (corneal epithelium, corneal endothelium, iris, retina pigment epithelium) | death receptors (DR) : with a death domain (DD), expressed on transformed cells decoy receptors (DcR) : with no death domain (DD), expressed on normal cells | ||
TNFSF11 / TRANCE / osteoprotegerin ligand (OPG-L) / RANK ligand (RANK-L) / osteoclast differentiation factor (ODF) ; isoform 1 and 2 ; homotrimer ; expression up-regulated by PTH | stromal cells/osteoblasts, T lymphocytes | RANK![]() OPG ![]() |
||
TNFSF12 / Apo-3L / TWEAK / DR3L ; isoforms 1 and 2 | T lymphocytes, wide tissue distribution | TWEAKR![]() |
||
TNFSF13 / APRIL / TALL-2 (a, b, d and g isoforms ; virus-like structures composed of multiple homotrimers, or heterotrimer with BAFF) | myeloid cells | TACI![]() BCMA ![]() HVEM ![]() CD95 / Apo1 / Fas ![]() |
||
TNFSF13B / TNF210 / BLys / BAFF / THANK / TALL-1 / zTNF4 (soluble and membrane-bound isoforms; homotrimer or heterotrimer with APRIL) | B cell lineage cells | TACI![]() BCMA ![]() BAFF-R / BLyS receptor 3 (BR3) ![]() |
||
TNFSF14 / LIGHT / TL5 / TR2 / LT-g / HVEML | ? | HVEM![]() |
||
TNFSF15 / TL1A / VEGI ; isoforms 1 and 2 | endothelial cells | DR6![]() TRAMP / DR3 ![]() |
||
TNFSF18 / TL6 / GITRL / AITRL | endothelial cells | GITR
/AITR![]() |
||
TNFSF19 / DEDD ; 2 isoforms | ? | ? | ||
anhidrotic ectodermal dysplasia 1 (ED-1) / ectodysplasin A (EDA) | isoform 1 (EDA1) | EDAR![]() |
||
isoform 2 (EDA2) | XEDAR![]() |
|||
IL-10 family | IL-10 / cytokine synthesis inhibitor F ; homodimer => decrease MMPs and proinflammatory cytokine production, induce TIMP-1 expression | Th1
lymphocytes![]() ![]() ![]() |
IL-10R![]() |
|
IL-19 | LPS- or GM-CSF-activated monocytes | IL-19R![]() |
||
IL-20 | monocytes | IL-20R![]() |
||
IL-22 | IL-9 induced Th1
lymphocytes![]() |
IL-22R![]() |
||
IL-24 / MDA-7 | monocytes, T lymphocytes | |||
IL-26 / AK155 | Th1
lymphocytes![]() |
|||
B and T lymphocyte attenuator (BTLA) | induced during activation of T cells, and BTLA
remains expressed on
Th1
lymphocytes![]() |
HVEM![]() B7H4 ![]() |
TGF-b superfamily : all of which are found in hematopoietic tissue, stimulate wound healing, and in vitro are antagonists of lymphopoiesis and myelopoiesis. | NODAL | TGF-bRIB
/ ALK-4![]() activin type IB receptor / ALK-7 ![]() activin type II receptor ![]() |
|
TGF-b1; homo-and heterotrimers | most cell types : chondrocytes (including chondrosarcoma), monocytes, T lymphocytes, B lymphocytes, macrophages, platelets, bone-marrow stroma, eye, testis, glioblastoma | TGF-bR![]() |
|
TGF-b2; homo-and heterotrimers | chondrosarcoma, glioblastoma | TGF-bR![]() |
|
TGF-b3; homo-and heterotrimers | chondrosarcoma | TGF-bR![]() |
|
Mullerian inhibiting factor (MIF) / Mullerian inhibiting substance (MIS) / anti-Mullerian hormone (AMH) | immature Sertoli cells | AMHR![]() |
|
neurturin (NTN / NRTN) | HGFR / c-Met![]() |
||
endometrial bleeding associated factor (EBAF) / left-right determination, factor A encodes a secreted protein that plays a role in left-right asymmetry determination of organ systems during development and in endometrial bleeding. Mutations in this gene have been associated with left-right axis malformations, particularly in the heart and lungs. Some types of infertility have been associated with dysregulated expression of this gene in the endometrium. Alternative processing of this protein can yield 3 different products. This gene is closely linked to both a related family member and a related pseudogene. | |||
transforming growth factor a (TGF-a) : stimulates growth of microvascular endothelial cells | pancreatic endocrine tumors | EGFR![]() |
|
IL-1
family![]() |
IL-1a / BAF / BCAF / EP / lymphocyte-activating factor (LAF) / LEM / macrophage chemotactic factor (MCF) / MNCF / MP / TRF-3 ; monomer | macrophages, dendritic cells, epithelial cells (TECs, endothelial cells, ...), activated B lymphocytes, NK cells | CD121a
/ IL-1RI![]() CD121b / IL-1RII ![]() |
IL-1b
/ catabolin / H1 / OAF ; proteolytically processed
to its active form by
caspase
1 / CASP1 / ICE![]() ![]() |
macrophages, dendritic cells, epithelial cells (TECs, endothelial cells, ...), B lymphocytes, NK cells | CD121a
/ IL-1RI![]() CD121b / IL-1RII ![]() |
|
IL-1 receptor antagonist (IL-1RA / IL-1RN) ; 4 isoforms ; monomer | CD121a
/ IL-1RI![]() ![]() CD121b / IL-1RII ![]() |
||
IL-1d, member 5 | |||
IL-1e, IL-1RA homolog / member 6 / IL-36g | keratinocytes | CD121a
/ IL-1RI![]() ![]() CD121b / IL-1RII ![]() |
|
IL-1z, member 7 ; 5 isoforms | IL-18R![]() IL-18BP (soluble decoy) |
||
IL-1h, h2, member 8 ; 2 isoforms | |||
IL-1rp2, h1, e, member 9 | IL-1R-like
2![]() |
||
IL-1R-like 1 ligand | Th2
lymphocytes![]() |
IL-1R-like
1![]() |
|
IL-18 / IFN-g inducing factor (IGIF) ; monomer | keratinocytes, activated macrophages and Kupffer cells | IL-18R![]() IL-18BP (soluble decoy) |
|
IL-33 | IL-1R-like
1![]() |
||
IL-36a (IL-1F6)ref | IL-36R (IL-1Rrp2)
IL-1RAcP |
||
IL-36b (IL-1F8) / IL-1h | |||
IL-36g (IL-1F9) | |||
IL-36Ra (IL-1F5) | |||
IL-37 |
IL-18Rα chain |
||
IL-38 |
IL 36R |
||
macrophage inhibitory factor / migration inhibition factor (MIF) ; monomer | activated T lymphocytes, pituitary cells, macrophages, eosinophils, fibroblasts, keratinocytes | ||
IL-12
familyref
: heterodimeric cytokines, composed of an a
chain (p19, p28, or p35) and a beta chain (p40 or
Ebi3), and signal through
unique pairings of 5 receptor chains (IL-12Rb1,
IL-12Rb2,
IL-23R, gp130, and WSX-1).
|
IL-12 / NK cell stimulatory factor ; p70 heterodimer with p35A and p40B subunits | B lymphocytes, activated mature DCs, macrophages
not inhibited by IFN-b
or by Fcg bound, naive
T cells, neutrophils![]() |
IL-12R![]() |
IL-23 = heterodimer with IL-12p40B "soluble receptor" subunit + p19a subunit | memory T lymphocytes, monocyte-derived macrophages, DCs, B cells | IL-23R![]() |
|
IL-27 / SF20 (homolog to mouse IL-25) : heterodimer with EBI3/p28 | bone marrow stroma, DCs, monocytes, macrophages, B cells | LY6E
IL-27Ra / WSX1 |
|
IL-35 : heterodimer with p35A/Epstein-Barr virus-induced gene 3 (EBI3) | stimulated human T effector cells, B cell lymphoma, nasopharyngeal carcinoma, and melanoma, murine (but not human) Treg | IL-35R (a unique heterodimer of receptor
chains IL-12Rβ2 and gp130 or homodimers of each
chain)ref |
|
IL-14 / HMW-BCGF | T lymphocytes | ? | |
IL-16 ; homotetramer | CD8+ T lymphocytes, mast
cells![]() ![]() |
CD4![]() |
|
IL-17 / mCTLA-8; monomer | CD4+ (both Th1
lymphocytes![]() ![]() |
IL-17R![]() IL-17RC |
|
IL-17B | IL-17BR![]() |
||
IL-17C | ? | ||
IL-17D | ? | ||
IL-17E / IL-25 (isoforms 1 and 2) | IL-17BR![]() |
||
IL-17F | IL-17RC | ||
IL-21 | T lymphocytes | IL-21R![]() |
|
IL-32ref : 4 splice variants (gamma isoform is the most activeref); induced in human pripheral lymphocytes folowing mitogen stimulation, in human epithelial cells by IFN-g, and in NK cells following exposure to the combination of IL-12 + IL-18; activated by cleavage by proteinase 3 (PR3) | immune tissue | ||
IL-34ref | embryonic brain and heart | M-CSFR
/ CD115![]() |
|
small
inducible
cytokine subfamily E, member 1 (endothelial
monocyte-activating)
(SCYE1) / p43, an auxiliary factor of
mammalian multiaminoacyl-tRNA
synthetases, induces IL-12 production in
macrophages via NF-kB
activation, leading to enhanced IFN-g production
in CD4+ T cells (Th1
lymphocytes![]() |
|||
thrombopoietin (TPO) | constitutively by liver (50%), kidneys and skeletal muscles; inducible in the liver by inflammatory mediators (especially IL-6) and from bone marrow stromal cells by thrombocytopenia | THPO![]() |
|
vascular endothelial growth
factor (VEGFA)
: 4 isoforms :
|
VEGFR1 / Flt-1![]() VEGFR2 / Flk-1 / KDR ![]() Neuropilin 2 (NRP2)ref |
||
VEGFB | VEGFR1 / Flt-1![]() |
||
VEGFC | VEGFR3
/ Flt-4![]() ![]() Neuropilin 2 (NRP2)ref |
||
VEGFD | VEGFR3
/ Flt-4![]() ![]() |
||
VEGFE | VEGFR2
/ Flk-1 / KDR![]() |
||
placental growth factor (PlGF) | VEGFR1 / Flt-1![]() |
||
angiopoietin (Ang-1) | Tie-1![]() CD202b / Tie-2 ![]() |
||
Ang-2 | Tie-1![]() CD202b / Tie-2 ![]() |
||
Ang-3 / angiopoietin-like 1 | widely expressed in adult tissues with mRNA levels highest in highly vascularized tissues | Tie-1![]() CD202b / Tie-2 ![]() |
|
Ang-4 | Tie-1![]() CD202b / Tie-2 ![]() |
||
fibroblast growth factor (FGF-1 / aFGF) | FGFR1![]() FGFR2 ![]() FGFR3 ![]() FGFR4 ![]() |
||
FGF-2 / bFGF | FGFR1![]() FGFR2 ![]() FGFR3 ![]() FGFR4 ![]() |
||
FGF-3 | FGFR1![]() FGFR2 ![]() FGFR3 ![]() FGFR4 ![]() |
||
FGF-4 | FGFR1![]() FGFR2 ![]() FGFR3 ![]() FGFR4 ![]() |
||
FGF-5 | FGFR1![]() FGFR2 ![]() FGFR3 ![]() FGFR4 ![]() |
||
FGF-6 | FGFR1![]() FGFR2 ![]() FGFR3 ![]() FGFR4 ![]() |
||
FGF-7 / keratinocyte growth factor (KGF) | FGFR1![]() FGFR2 ![]() FGFR3 ![]() FGFR4 ![]() |
||
FGF-8 | FGFR1![]() FGFR2 ![]() FGFR3 ![]() FGFR4 ![]() |
||
FGF-9 | FGFR1![]() FGFR2 ![]() FGFR3 ![]() FGFR4 ![]() |
||
FGF-10 / KGF-2 | FGFR1![]() FGFR2 ![]() FGFR3 ![]() FGFR4 ![]() |
||
FGF-11 | FGFR1![]() FGFR2 ![]() FGFR3 ![]() FGFR4 ![]() |
||
FGF-12 | FGFR1![]() FGFR2 ![]() FGFR3 ![]() FGFR4 ![]() |
||
FGF-13 | FGFR1![]() FGFR2 ![]() FGFR3 ![]() FGFR4 ![]() |
||
FGF-14 | FGFR1![]() FGFR2 ![]() FGFR3 ![]() FGFR4 ![]() |
||
FGF-16 | FGFR1![]() FGFR2 ![]() FGFR3 ![]() FGFR4 ![]() |
||
FGF-17 | FGFR1![]() FGFR2 ![]() FGFR3 ![]() FGFR4 ![]() |
||
FGF-18 | FGFR1![]() FGFR2 ![]() FGFR3 ![]() FGFR4 ![]() |
||
FGF-19 | FGFR1![]() FGFR2 ![]() FGFR3 ![]() FGFR4 ![]() |
||
FGF-20 | substantia nigra | FGFR1![]() FGFR2 ![]() FGFR3 ![]() FGFR4 ![]() |
|
FGF-21 | FGFR1![]() FGFR2 ![]() FGFR3 ![]() FGFR4 ![]() |
||
FGF-22 | FGFR1![]() FGFR2 ![]() FGFR3 ![]() FGFR4 ![]() |
||
FGF-23 | FGFR1![]() FGFR2 ![]() FGFR3 ![]() FGFR4 ![]() |
||
epidermal growth factor (EGF)
/ b-urogastrone : a
mitogenic polypeptide originally
extracted from the submandibular glands of male
mice; it is produced by
many cell types and is made in large amounts by
some tumors. It promotes
growth and differentiation, is essential in
embryogenesis, and is also
important in wound healing. It has been found to
be part of a family of
compounds that includes human epidermal growth
factor, transforming growth
factors, and amphiregulin.
|
, cytotrophoblast![]() |
ERBB1
/ EGFR![]() |
|
hepatocyte growth factor (HGF) / scatter factor (SF) : a potent mitogen and inducer of hepatocyte proliferation | nonparenchymal cells in the liver and by mesenchymal cells in many other organs. | HGFR / c-Met![]() |
|
brain-derived neurotrophic factor (BDNF) (in contrast to their slow effect on neuronal survival or differentiation (hours or days), their modulation of synaptic transmission is much faster (seconds or minutes)) | TrkA![]() TrkB ![]() TrkC ![]() p75NTR ![]() |
||
glial-derived neurotrophic factor (GDNF) | TrkA![]() TrkB ![]() TrkC ![]() p75NTR ![]() |
||
pigment epithelium-derived factor (PEDF) / SERPINF1 | |||
persephin | |||
artemin / enovin / neuroblastin | RET![]() |
||
nerve growth factor (NGF) : a protein consisting of two identical polypeptide chains associated with 2 gamma subunits (enzymes) and 2 alpha subunits; first isolated from mouse sarcoma and later from snake venom and mouse salivary glands, it stimulates the growth of sensory and sympathetic nerve cells and of the adrenal medulla and has been found to be secreted by a variety of normal and neoplastic cells, including those in humans. | TrkA![]() TrkB ![]() TrkC ![]() p75NTR ![]() |
||
stem cell factor (SCF) (a.ka. steel factor (SLF) in Mus) | CD117 /
c-Kit![]() |
||
neurotrophin 2 (NTF-2 / NT-2) | |||
neurotrophin 3 (NTF3 / NT-3) / HDNF / NGF-2 | TrkB![]() TrkC ![]() |
||
neurotrophin 4/5 (NTF-4/5 / NT-4/5) | |||
platelet derived growth factor (PDGF) a+a, a+b/ c-sisorb/ c-sis+b/ c-sis: capable of inducing proliferation of vascular endothelial cells, vascular smooth muscle cells, fibroblasts, and glia cells; its action contributes to the repair of damaged vascular walls. | alpha granules of platelets, cytotrophoblast![]() |
PDGFR![]() |
|
connective tissue growth factor (CTGF) / IGF-binding protein 8 (IGFBP8) | |||
FLT3L | FLT-3![]() |
||
neuromedin B | neuromedin
B receptor![]() |
||
neuregulin 1 / heregulin / NDF (4 isoforms) | ERBB1
/ EGFR![]() ERBB2 ![]() ![]() ERBB4 ![]() |
||
neuregulin 2 | ERBB3![]() ERBB4 ![]() |
||
betacellulin (BTC) | ERBB1
/ EGFR![]() ERBB4 ![]() |
||
megakaryocyte potentiating factor (MPF), an isoform of mesothelin | |||
urocortins human homologues of fish urotensin I, are member of the sauvagine/corticotropin-releasing factor/urotensin I family. Each of these 4 genes is highly conserved during evolution and the identity between mammalian and teleost orthologs ranges from >96% for CRF to >55% for SCP. Phylogenetic studies showed that the origin of each of these peptides predates the evolution of tetrapods and teleosts, and that this family of peptide hormones evolved from an ancestor gene that developed the CRF/urocortin and SCP/SRP branches through an early gene duplication event. These 2 ancestral branches then gave rise to additional paralogs through a second round of gene duplication. Consequently, each of these peptides participates in the regulation of stress responses over the 550 million years of vertebrate evolution. The study also suggested that the fight-or-flight and stress-coping responses mediated mainly by CRF types 1 and 2 receptors evolved early in chordate evolution. The CRF/CRF receptor signaling evolved from the same ancestors that also gave rise to the diuretic hormone/diuretic hormone receptors in insects. Thus, a complete inventory of CRF family ligands and their receptors in the genomes of different organisms provides an opportunity to reveal an integrated view of the physiology and pathophysiology of the CRF/SCP family peptides, and offers new insights into the evolution of stress regulation in vertebrates. | urocortin 1 (Ucn 1) | CRHR1![]() CRHR2 ![]() |
|
urocortin II (UcnII) / stresscopin-related peptide (SRP) | CRHR2![]() |
||
urocortin 3 (Ucn 3) / stresscopin (SCP) : CRF type 2 receptor is thought to mediate the stress-coping responses, such as anxiolysis, anorexia, vasodilatation, a positive inotropic action on myocardium and dearousal. Ucn 1 and 3 appear to have important pathophysiological roles in some cardiovascular diseases. Urocortins show 'stress-coping' responses such as anxiolysis and dearousal in the brain. In the periphery, recent studies show the potent effects of urocortins on the cardiovascular and immune systems. In the brain it may be responsible for the effects of stress on appetite. In spite of the gene family name similarity, the product of this gene is not homologous to urotensin II. mRNA expression of urocortin was low during the last weeks of pregnancy in the placenta, myometrium and choriodeciduaref. SCP and UCN are potent activators of the p42/44 MAPK pathway, with SRP able to induce phosphorylation of p42/44 MAPK as well, albeit not as pronouncedref. Adipose tissue expressed urocortin and stresscopin, the predominant ligands of peripheral CRH-R2ref. Human cord blood-derived cultured mast cells (hCBMC) at 10 wk, but not at 2 wk, are IHC positive for CRH and UCNref. A highly significant, but negative, correlation has been found between Ucn levels and gastric inflammation, suggesting that Ucn may exert an antiinflammatory effect in gastric mucosaref. | pituitary gland, adrenal gland, gastrointestinal tract, ovary, spleen, brain, cardiomyocytes and sital tubules | CRHR2![]() |
|
urotensin II (UII) is a vasoactive cyclic undecapeptide originally isolated from the teleost urophysis. It stimulates cardiomyocytes and vascular smooth muscle hypertrophy and also shows inotropic properties. It induces biphasic (brief- and long-lasting) contractions and the brief contraction was mediated by acetylcholine release from ganglionic cholinergic neurons in a segment of guinea-pig ileum The bioactive, mature form contains a cyclic heptapeptide perfectly preserved across species spanning 550 million years of evolution. In man short term cardiovascular responses to administered urotensin II are small or absent. The place of urotensin II in the chronic trophic responses to cardiac and vascular injury and its possible roles as a neurotransmitter and/or regulator of renal and endocrine function remain largely unexplored. Initially found to have potent vasoconstrictive activities in a variety of vessels from diverse species, it has also been shown to exert vasodilatation in certain vessels in the rat and human by various endothelium-dependent mechanisms.Moreover, UII has also been implicated as a mitogen of vascular smooth muscle cells suggesting a deleterious role in atherosclerosis and coronary artery disease. In addition, there is evidence to demonstrate that UII has multiple metabolic effects on cholesterol metabolism, glycemic control and hypertension and therefore may be implicated in the development of insulin resistance and the metabolic syndrome. UII is a potent vasoconstrictor peptide, whose potency is greater than any other vasoconstrictors thus far known. .The common structural feature of U-II peptides from different species is the C-terminal portion, characterized by the disulfide bridged cyclic hexapeptide Cys-Phe-Trp-Lys-Tyr-Cys. The few SAR studies reported to date attributed a critical role to this portion, with the Trp-Lys-Tyr motif appearing as the key determinant of U-II bioactivity. Consequently, this shorter cyclic peptide was used as a template for the development of several synthetic analogues, among which a superagonist, termed P5U: H-Asp-cyclo(Pen-Phe-Trp-Lys-Tyr-Cys)-Val-OH. Conformational studies confirmed the important role of hU-II C-terminal cyclic portion, enabling the development of 3D pharmacophore models. Despite the gene family name similarity, this gene is not homologous to urocortin. Most of the proprotein is cleaved to make the mature peptide. Transcript variants encoding different preproprotein isoforms have been described for this gene. Urotensin II may have an aetiological role in hypertension and its complicationsref. Possible role for U-II in the pathophysiology of atherosclerosisref. In addition to direct effects on the myocardium, U-II may contribute to the increased peripheral vascular tone that is characteristic of human CHFref. levated in the aortic root of congestive heart failure. Cleared at least in part from the microcirculationref. Urotensin II gene may contribute to the genetic susceptibility to type 2 diabetes in Chinese populationref. S89N polymorphism in the UTS2 gene is associated with the development of Type 2 diabetes, via insulin sensitivity, in Japanese subjectsref. ECirculating urotensin-II appears not to play a major role in human congestive heart failure (CHF)ref. Regulative effect of human urotensin-II on cardiovascular systemref. Structure-function analysis and its use in the construction of a ligand-receptor working modelref. Urocortin II exhibits motor suppressive and delayed anxiolytic-like effects, suggesting a time-dependent role in the regulation of stress-related behaviorref | strong expression of urotensin II in the cardiomyocytes, and to a lesser extent in the vascular smooth muscle cells, endothelial cells, and inflammatory cells of patients with end-stage chronic heart failure, central nervous system (a subset of ventral horn motoneuronesref) and many peripheral tissues (including heart, blood vessels, kidneys and endocrine organs) | UTII receptor (UTR) / GPR14 | |
urotensin II (UII)-related peptide (URP) has been isolated from the rat brain and its sequence has been established as H-Ala-Cys-Phe-Trp-Lys-Tyr-Cys-Val-OH (ACFWKYCV) also binds (UTR) |
|
|
|
|
|
a-chemokines : CXC motif (on Homo 4q12-21 chromosome region) | ELRCXC or ELR+ CXC
chemokines (chemotactic
for neutrophils![]() |
CXCL1 / KC / MGSA-a / GRO-1 / GRO-a (GRO-KC in mouse) | activated granulocytes, monocytes, macrophages, epithelial cells, lymphatic endothelial cells (LEC) | CXCR2 /
CDw128b / IL-8RB![]() ![]() Duffy antigen-related receptor for chemokines (DARC) (decoy) |
CXCL2 / GRO-2 / GRO-b / MGSA-b / MIP-2a (GRO-KC in mouse) | activated granulocytes, monocytes, macrophages | CXCR2 /
CDw128b / IL-8RB![]() |
||
CXCL3 / GRO-3 / GRO-g / MGSA-g / MIP-2b (GRO-KC in mouse) | CXCR2 /
CDw128b / IL-8RB![]() |
|||
CXCL5 / ENA-78 (LIX in mouse) | CXCR1 /
CDw128a / IL-8RA![]() CXCR2 / CDw128b / IL-8RB ![]() Duffy antigen-related receptor for chemokines (DARC) (decoy) |
|||
CXCL6/ GCP-2 (Cka-3 in mouse) | CXCR1 /
CDw128a / IL-8RA![]() CXCR2 / CDw128b / IL-8RB ![]() |
|||
CXCL7
/ LDGF-PBP / NAP-2 / CTAP-II (from proteolytic truncation
of connective
tissue-activating peptide III (CTAP-III) (one of several
molecular variants
of -thromboglobulin-antigen (TG-Ag), a group of chemokines
that differ
by their degree of N-terminal truncation) by removing a
stretch of 15 amino
acids from the N terminus of the precursorref1,
ref2.
So far all evidence suggests that cell surface–bound
cathepsin G (CathG),
a chymotryptic serine protease also found in primary neutrophil![]() |
a-granules of activated human platelets![]() |
CXCR1 /
CDw128a / IL-8RA![]() CXCR2 / CDw128b / IL-8RB ![]() |
||
CXCL8 / IL-8 / NAP-1 / TCF / NAF / neutrophil chemotactic factor (NCF) | alveolar macrophage, sweat | CXCR1 /
CDw128a / IL-8RA![]() CXCR2 / CDw128b / IL-8RB ![]() Duffy antigen-related receptor for chemokines (DARC) (decoy) |
||
XXXCXC or ELR- CXC chemokines (chemotactic for lymphocytes; PF4 very efficiently stimulates firm adhesion of neutrophils to endothelial cells as well as the selective exocytosis of secondary granule markersref1, ref2) | CXCL4 / PF4 | megakaryocytes, activated platelets![]() |
a cell surface–expressed chondroitin sulfate proteoglycanref1, ref2 | |
CXCL9 / monokine induced by IFN-g (MIG / MIG-1) (catabolysed by CD26 / DPPIV) | monocytes, macrophages, T lymphocytes, fibroblasts, lymphatic endothelial cells (LEC) | CXCR3 / CD183![]() |
||
CXCL10 / IP-10 (catabolysed by CD26 / DPPIV) | monocytes, macrophages, T lymphocytes, fibroblasts, epithelial cells (including endothelial cells), lymphatic endothelial cells (LEC) | CXCR3 / CD183![]() |
||
CXCL11 / IFN-inducible T cell a chemoattractant (I-TAC) / H174 (catabolysed by CD26 / DPPIV) | CXCR3 / CD183![]() |
|||
CXCL12 / pre-B cell growth-stimulating factor (PBSF) / stromal cell-derived factor 1a (SDF-1a/b) (catabolysed by by marrow serine proteasesref1, ref2 and dipeptidylpeptidase IV (CD26)ref1, ref2) | fibroblasts, HIV-1 infected macrophages | CD184 / CXCR4 / fusin /
LESTR![]() |
||
CXCL13 / BCA-1 / BLC | FDC | CD195 / CXCR5 / BLR-1![]() |
||
CXCL16 / BUNZO / STRC33 / scavenger receptor PSOX (SR-PSOX) | APC (also membrane bound) | CXCR6![]() |
||
chemotactic for monocytes only | CXCL14 / BMAC / BRAK / MIP-2g / bolekine / KEC / KS1 / NJAC | ? | ||
CXCL15 / lungkine in mouse | CD195 / CCR5 / BLR-1![]() |
|||
b-chemokines : CC motif (on Homo 17q11-32 chromosome region; chemotactic for monocytes and plasma cells) | CCL1 / I-309 (TCA-3 / P500 in mouse) | activated T lymphocytes | CCR8![]() |
|
CCL2 / MCF / MCAF / monocyte chemoattractant protein (MCP) / MCP-1 (JE in mouse) | epithelial cell, fibroblast, smooth muscle cells, monocytes, alveolar macrophage, lymphatic endothelial cells (LEC) | CCR2![]() Duffy antigen-related receptor for chemokines (DARC) (decoy) D6 / chemokine binding protein 2 (CBBP) (decoy) |
||
CCL3 / LD78 / MIP-1a (catabolysed by CD26 / DPPIV) | epithelial cells, monocytes, macrophages, T lymphocytes | CCR1![]() CD195 / CCR5 / BLR-1 ![]() |
||
CCL3L1 | CD195 / CCR5 / BLR-1![]() CCR9 ![]() |
|||
CCL4 / AT744.1 / LAG-1 / MIP-1b | monocytes, macrophages, T lymphocytes | CCR1![]() CD195 / CCR5 / BLR-1 ![]() |
||
CCL5 / RANTES (catabolysed by CD26 / DPPIV) | T lymphocytes, activated NKT lymphocytes, epithelial cell,
smooth muscle
cell,eosinophils![]() |
CCR1![]() CCR3 ![]() CD195 / CCR5 / BLR-1 ![]() Duffy antigen-related receptor for chemokines (DARC) (decoy) |
||
CCL6 (C10 / MRP-1 in mouse) | , lymphatic endothelial cells (LEC) | ? | ||
CCL7 / MCP-3 (MARC / FIC in mouse) | epithelial cell, fibroblasts, activated monocytes | CCR1![]() CCR2 ![]() CCR3 ![]() Duffy antigen-related receptor for chemokines (DARC) (decoy) |
||
CCL8 / MCP-2 / HC14 | fibroblasts, activated monocytes | CCR1![]() CCR2 ![]() CCR3 ![]() CD195 / CCR5 / BLR-1 ![]() |
||
CCL9 (MRP-2 / Scya9 / CCF18 / MIP-1gin mouse) | APCs | ? | ||
CCL10 / MIP-1g | ? | |||
CCL11 / eotaxin / eotaxin-1 (catabolysed by CD26 / DPPIV) | epithelial cell (including pneumocytes and endothelial
cell), alveolar
macrophage, smooth muscle cell, fibroblast, eosinophils![]() |
CCR2![]() CCR3 ![]() CD195 / CCR5 / BLR-1 ![]() |
||
CCL12 (MCP-5 in mouse) | CCR2![]() |
|||
CCL13 / MCP-4 / CKb-10 / NCC-1 | epithelial cell (including pneumocytes, enterocytes and activated endothelial cells) | CCR1![]() CCR2 ![]() CCR3 ![]() CD195 / CCR5 / BLR-1 ![]() |
||
CCL14a / HCC-1 / NCC-2 | CCR1![]() CCR3 ![]() CD195 / CCR5 / BLR-1 ![]() |
|||
CCL14b / HCC-3 | CCR1![]() CCR3 ![]() CD195 / CCR5 / BLR-1 ![]() |
|||
CCL15 / HCC-2 / leukotactin / Lkn-1 / MIP-1d / MIP-5 / NCC-3 | CCR1![]() CCR3 ![]() CD195 / CCR5 / BLR-1 ![]() |
|||
CCL16 / HCC-4 / SexCkine / LEC / NCC-4 (LCC-1 in mouse) | CCR1![]() CCR2 ![]() CD195 / CCR5 / BLR-1 ![]() CCR8 ![]() |
|||
CCL17 / thymus and activation-regulated chemokine (TARC) / dendrokine | bronchiolar epithelial cells, thymus, dendritic cells, activated T lymphocytes | CCR4![]() |
||
CCL18 / PARC / DC-CK-1 / MIP-4 / SCYA18 / AMAC-1 | dendritic cells in secondary lymphoid organs | unknown | ||
CCL19 / MIP-3b / EBV-induced gene 1 ligand chemokine (ELC) / exodus-3 / CKb-11 | thymus, lymph nodes, appendix | CCR7 / CDw197![]() |
||
CCL20 / MIP-3a / exodus-1 / LARC | dendritic cells, fetal hepatocytes, activated T lymphocytes | CCR6![]() |
||
CCL21/ 6Ckine / exodus-2 / secondary lymphoid tissue chemokine (SLC) / TCA-4 | TECs, lymph nodes, appendix and spleen, lymphatic endothelial cells (LEC) | CCR7 / CDw197![]() CXCR3 / CD183 ![]() |
||
CCL22 / macrophage-derived chemokine (MDC) / STCP-1 (ABCD-1 in mouse) (catabolysed by CD26 / DPPIV) | smooth muscle cell, dendritic cells, monocytes, alveolar macrophage, bronchiolar epithelium, thymus | CCR4![]() |
||
CCL23 / CKb-8 / MPIF-1 | CCR1![]() |
|||
CCL24 / eotaxin-2 / MPIF-2 | CCR3![]() CCR4 ![]() |
|||
CCL25 / TECK | dendritic cells, thymus, hepatocytes, small bowel | CCR9![]() |
||
CCL26/ eotaxin-3 | CCR3![]() |
|||
CCL27 / CTACK / ALP / ILC (ESkine in mouse; the alternative spliced isoform PESKY lacks a signal peptide and is translocated to the nucleus acting as an intrakine; also ESkine has a NTS) | keratinocytes | CCR10![]() |
||
CCL28 / MEC | mucosal epithelial cells (expecially salivary and mammary glands => in saliva and breast milk) | CCR3![]() CCR10 ![]() |
||
d-chemokines : CXXXC or CX3C motif | CX3CL1 / fractalkine / neurotactin / ABCD-3 | activated endothelial cells | CX3CR1![]() |
|
g-chemokines : C motif (the prefix "X" is used to avoid confusion between g-chemokines receptors and complement receptors !) | XCL1 / lymphotactin (Lptn or Ltn) / SCM-1a / ATAC | NK cells, DN thymocytes, activated CD8+ lymphocytes, lymphatic endothelial cells (LEC) | XCR1![]() |
|
XCL2 / SCM-1b | XCR2![]() |
|||
pleiotrophin / heparin binding growth factor 8 / neurite growth-promoting factor 1 (NGPF1) | ||||
midkine (MDK) / neurite growth-promoting factor (NGPF2) | esophageal carcinoma, astrocytes, |
|
peptide |
|
|
bradykinin (BK) | B1![]() |
||
Lys-BK / kallidin | B1![]() |
||
Lys-des-Arg-BK | B2![]() |
||
endothelins are produced endogenously from preproendothelin to give big endothelins, which are cleaved by endothelin-converting enzymes ECE1 and ECE2 to yield the active protein. | endothelin-1 | endothelial cells, neutrophils![]() ![]() |
ETA![]() ETB ![]() |
endothelin-2 | ETB![]() |
||
endothelin-3 | glomeruli and all the tubule segments | ETB![]() |
|
thrombin | PAR-1![]() PAR-3 ![]() PAR-4 ![]() |
||
Hedgehog
(hh) homologs : the mature signaling
forms (HhNp) are covalently
coupled to cholesterol at their
COOH-terminal ends by the polytopic
transmembrane acyl transferase rasp
/
skinny hedgehog / sightless (ski/sit),
allowing insertion into lipid
rafts![]() |
desert hedgehog (Dhh) homolog (DHH) | during embryogenesis | Hedgehog
interacting
protein (Hip1 / HHIP) (no homolog in Drosophila)
Patched
(ptc)
homolog (PTCH) (contains a
sterol-sensing domain (SSD); binding
removes inhibition on Smoothened
(smo)
homolog (SMOH), which in turn is
redistributed from unidentified
intracellular compartments to the plasma
membrane and whose GLI-mediated
STP
is activated). The Ptc gene itslef is a target
of Hh activity, and
thus Hh effectively promotes its own
sequestration by up-regulating ptc
transcription, a negative feedback mechanism
that restrains its signaling
range.
|
Indian hedgehog (Ihh) homolog (IHH) | during embryogenesis | ||
sonic hedgehog (Shh) homolog (SHH) NTD (secreted isoform generated from autocleavage by the CTD) | during embryogenesis | ||
WNT | WNT1 | during embryogenesis and oncogenesis | Frizzled
homolog
1 (FZD1)![]() Frizzled homolog 2 (FZD2) ![]() Frizzled homolog 3 (FZD3) ![]() Frizzled homolog 4 (FZD4) ![]() Frizzled homolog 5 (FZD5) ![]() Frizzled homolog 6 (FZD6) ![]() Frizzled homolog 7 (FZD7) ![]() Frizzled homolog 8 (FZD8) ![]() Frizzled homolog 9 (FZD9) ![]() Frizzled homolog 10 (FZD10) ![]() + LRP5
/ LRP7 => b-catenin
=> HMGs |
WNT2 | during embryogenesis and oncogenesis | ||
WNT2B / WNT13 | during embryogenesis and oncogenesis | ||
WNT3 | during embryogenesis and oncogenesis | ||
WNT3A | during embryogenesis and oncogenesis | ||
WNT4 | during embryogenesis and oncogenesis | ||
WNT5A | during embryogenesis and oncogenesis | ||
WNT5B | during embryogenesis and oncogenesis | ||
WNT6 | during embryogenesis and oncogenesis | ||
WNT7A | during embryogenesis and oncogenesis | ||
WNT7B | during embryogenesis and oncogenesis | ||
WNT8A | during embryogenesis and oncogenesis | ||
WNT8B | during embryogenesis and oncogenesis | ||
WNT9 | during embryogenesis and oncogenesis | ||
WNT10A | during embryogenesis and oncogenesis | ||
WNT10B / WNT12 | during embryogenesis and oncogenesis | ||
WNT11 | during embryogenesis and oncogenesis | ||
WNT14 | during embryogenesis and oncogenesis | ||
WNT15 | during embryogenesis and oncogenesis | ||
WNT16 | during embryogenesis and oncogenesis | ||
Ephrin A class (anchored to the membrane by a GPI linkage) | Ephrin-A1 | developmental events, particularly in the nervous system. Posttranslational modifications determine whether this protein localizes to the nucleus or the cytoplasm | EphA1![]() EphA2 ![]() EphA4 ![]() EphA5 ![]() EphA7 ![]() EphA8 ![]() |
Ephrin-A2 | EphA1![]() EphA2 ![]() EphA4 ![]() EphA5 ![]() EphA7 ![]() EphA8 ![]() |
||
Ephrin-A3 | EphA1![]() EphA2 ![]() EphA4 ![]() EphA5 ![]() EphA7 ![]() EphA8 ![]() |
||
Ephrin-A4 | EphA1![]() EphA2 ![]() EphA4 ![]() EphA5 ![]() EphA7 ![]() EphA8 ![]() |
||
Ephrin-A5 | EphA1![]() EphA2 ![]() EphA4 ![]() EphA5 ![]() EphA7 ![]() EphA8 ![]() |
||
Ephrin B class (transmembrane proteins) | Ephrin-B1 | EphB1![]() EphB2 ![]() EphB3 ![]() EphB6 ![]() |
|
Ephrin-B2 | EphA3![]() EphB4 ![]() |
||
Ephrin-B3 (forebrain) | EphB1![]() EphB2 ![]() EphB3 ![]() EphB6 ![]() |
||
Jelly belly (Jeb) | anaplastic
lymphoma
kinase (Alk)![]() |
||
HMG proteins | high-mobility group B1 protein (HMGB1) | RAGE![]() |
|
|
|
||
purines | adenosine triphosphate (ATP) | P2X1![]() P2X2 ![]() P2X3 ![]() P2X4 ![]() P2X5 ![]() P2X6 ![]() P2X7 / P2Z ![]() |
||
extracellular derivatives of ATP | adenosine diphosphate (ADP) | P2Y1![]() P2T ![]() |
||
adenosine monophosphate (AMP) | ||||
adenosine (Ado) | P1 | |||
pyrimidines | UTP | P2Y2 / P2U
/ P2N![]() P2Y4 ![]() |
||
UDP | P2Y6![]() cysLT1 ![]() |
|||
the first dinucleotide isolated from living organisms that contains both purine and pyrimidine moieties | uridine adenosine tetraphosphate (Up4A)ref | human endothelial cells obtained from dermal vessels stimulated with adenosine 5'-triphosphate (ATP), uridine 5'-triphosphate (UTP), acetylcholine, endothelin, A23187 and mechanical stress | P2X1![]() ![]() ![]() |
|
endogenous opiates / opioid peptides / endorphins (sensu latu) / narcotics and related peptides (close physiological linkage between the stress axis and opioid system) |
|
|
Tyr-Gly-Gly-Phe | proopiomelanocortin
(POMC) (239 amino acids) =>
|
long interneurons in :
syncytiotrophoblast ![]() |
MC1R![]() MC2R / ACTHR ![]() MC3R ![]() MC4R ![]() MC5R ![]() m ![]() d ![]() k1 ![]() k2 ![]() s1 ![]() s2 ![]() |
They are catabolyzed by leucine aminopeptidase (LAP), carboxypeptidase A (CPA) and dipeptidyl-dipeptidase (DAP) / enkephalinase ![]() ![]() |
CNS : short interneurons in :
|
m![]() d ![]() k1 ![]() k2 ![]() s1 ![]() s2 ![]() |
|
proenkephalin
B
/ prodynorphin
|
|
m![]() d ![]() k1 ![]() k2 ![]() s1 ![]() s2 ![]() |
|
|
hippocampus
cortex periaqueductal grey median raphe superficial dorsal horn rostral ventromedial medulla (RVM) numerous sensory sites |
m![]() d ![]() k1 ![]() k2 ![]() s1 ![]() s2 ![]() ORL-1 ![]() |
|
Tyr-Pro-Trp/Phe | endomorphin 1 (Tyr-Pro-Trp-Phe-NH2) | m![]() |
|
endomorphin 2 (Tyr-Pro-Phe-Phe-NH2) | m![]() |
|
|
|
cortisol
![]() |
zonae fasciculata and reticularis of adrenal cortex | GR![]() MR ![]() |
corticosterone | ||
hydrocortisone |
|
|
|
aldosterone | zona glomerulosa of adrenal cortex | MR![]() |
|
|
|
testosterone
(T)
![]() |
zonae fasciculata and reticularis of adrenal cortex and ovary (50%), androgen-sensitive peripheral tissues (50%; prostate, from androstenedione) | AR![]() |
dihydrotestosterone
(DHT)
is generated by 5a-reductase![]() |
androgen-sensitive peripheral tissues (prostate, from androstenedione and testosterone) | AR![]() |
androstenedione (A) | AR![]() |
|
deihydroepiandrosterone (DHEA) | zonae fasciculata and reticularis of adrenal cortex (90%) | AR![]() |
dehydroepiandrosterone sulfate (DHEA-S) | zonae fasciculata and reticularis of adrenal cortex | AR![]() |
|
|
|
estrone (E1) | premenopausal ovary | |
17b-estradiol
(E2)
![]() |
premenopausal ovary, syncytiotrophoblast![]() |
ERa![]() ERb ![]() |
estriol (E3) | hepatocytes (from estrone and estradiol
in premopausal females), fatty
tissue (from adrenal androstenedione in
postmenopausal females), syncytiotrophoblast![]() |
|
estetrol (E4) |
|
|
|
progesterone
![]() |
corpus
luteum![]() syncytiotrophoblast ![]() |
PR![]() |
|
|
|
all-trans-retinoic acid (ATRA) | retinol![]() |
RARa![]() RARb ![]() RARg ![]() |
9-cis-retinoic acid | retinol![]() |
RXRa![]() RXRb ![]() RXRg ![]() |
3,5,3'-T3 | thyroid epithelial cells | T3Ra![]() T3Rb ![]() |
1a,25-(OH)2-vitamin D3 / calcitriol | vitamin D2![]() ![]() |
VDR![]() |
3-iodothyronamine (T1AM) | thyroid epithelial cells | trace amine
receptor 1 (TAAR1)![]() |
|
|
|
melatonin (MLT) / N-acetyl-5-methoxytryptamine | pineal gland | MLT1![]() MLT2 ![]() |
adrenoglomerulotropin
(AGTH)
/ 6-methoxy-1-methyl-1,2,3,4-tetrahydroharman
/ pinoline /
6-methoxy-1-methyl-1,2,3,4-tetrahydro-b-carboline
![]() |
pineal gland | ? |
adrenaline
/ epinephrine
(E)
![]() |
adrenal medulla | a1A
/
1C![]() a1B ![]() a1D ![]() a2A ![]() a2B ![]() a2C ![]() b1 ![]() b2 ![]() b3 ![]() |
noradrenaline / norepinephrine (NE) | adrenal medulla | a1A
/
1C![]() a1B ![]() a1D ![]() a2A ![]() a2B ![]() a2C ![]() b1 ![]() b2 ![]() b |
|
|
|
|
insulin | b / B cells of Langerhans' islets of endocrine pancreas | InsR![]() |
|
insulin-like growth factors (IGF) / sulfation
factors :
insulin-like growth factor (IGF-1) / non-suppressible insulin-like acting (substance) 1 (NSILA(S)-1) / somatomedin C (SM-C) |
hepatocytes and other mesenchymal tissues | IGF-1R
/ CD221![]() |
|
insulin-like growth factor 2 (IGF-2) / non-suppressible insulin-like acting (substance) 2 (NSILA(S)-2) / somatomedin A (SM-A) / multiplication stimulating activity (MSA) | IGF-2R![]() |
||
insulin-like 3 / relaxin-like factor (RLF) (after proteolytic processing of the C-peptide, consists of a 32-residue-long B-chain and a 26-residue-long A-chain and has a molecular size of 6.25 kDa.) | Leydig cells | ||
insulin-like 4 (precursor that undergoes post-translational cleavage to produce 3 polypeptide chains, A-C, that form tertiary structures composed of either all three chains, or just the A and B chains) | early placental cytotrophoblast and syncytiotrophoblast | ||
preproglucagon
=proconvertase
3
(PC3)=>
|
a / A cells of Langerhans' islets of endocrine pancreas and stomach | glucagon
receptor![]() |
|
preproglucagon
/
enteroglucagon =proconvertase
3
(PC3)=>
|
brain, L cells in jejunum, ileum, and colon | glucagon
receptor![]() GLP1R ![]() GLP2R ![]() |
|
precursor of pancreatic polypeptide (PPY) and pancreatic icosapeptide | PP / F cells of Langerhans' islets of endocrine pancreas head, fundus and pylorus of stomach, and colon | PPYR1![]() |
|
pancreatic polypeptide 2 (PPY2) | PP / F cells of Langerhans' islets of endocrine pancreas head | ||
neuropeptide Y (NPY) | arcuate nucleus neurons producing also AgRP,
cytotrophoblast![]() |
Y1![]() Y2 ![]() Y5 ![]() |
|
peptide YY (PYY) (36 amino acids) : the cleaved subpeptide PYY[3-36] is biologically active and may constitute the majority of circulating PYY-like immunoreactivity. | ileal L cells postprandially in proportion to the calorie content of a meal | Y2![]() |
|
peptide YY 2 (PPY2) / seminalplasmin | |||
atrial natriuretic peptide (ANP) (processed by corin) | atrial cardiomyocytes | NPR1 /
ANP-A / GC-A![]() |
|
brain natriuretic peptide (BNP) (high-MW BNP and low-MW BNP) | ventricular cardiomyocytes | NPR1 /
ANP-A / GC-A![]() |
|
C-type natriuretic peptide (CNP) | tubular cells and glomeruli | NPR2 /
ANP-B / GC-B![]() |
|
adrenomedullin (AM / ADM) | blood vessel endothelial and smooth muscle cells, and microvasculature-rich tissues | adrenomedullin
receptor (ADMR)![]() |
|
guanylin / guanylate cyclase activator 2A | enterocytes, tubular cells | GC-C![]() |
|
uroguanylin / guanylate cyclase activator 2B | enterocytes, tubular cells | GC-C![]() |
|
antidiuretic hormone (ADH) / Arg vasopressin (AVP) (processing of the 168-amino acid human AVP preprohormone by endopeptidase, exopeptidase, monooxygenase, and lyase generates AVP, the carrier protein neurophysin II / VP-neurophysin, and VP-glycopeptide) (human beings & other mammals) | perikarya of magnocellular neurons in the paraventricular nucleus (PVN) and the supraoptic nucleus (SON) (separate from those synthetizing oxytocin), heart blood vessels, adrenal medulla | V1b /
V3![]() ![]() ![]() |
|
lypressin (pigs, marsupials) | |||
phenypressin (macropodids) | |||
vasotocin (nonmammalian vertebrates) | |||
arginine conopressin (Conus striatus) | |||
lysine conopressin (Conus geographicus) | |||
locust subesophageal ganglia peptide | |||
oxytocin (OT) (the carrier protein neurophysin I arises from alternative splicing of the same mRNA) | perikarya of magnocellular neurons in the paraventricular nucleus (PVN) and the supraoptic nucleus (SON) (separate from those synthetizing oxytocin) | OT receptor![]() |
|
TSH-releasing hormone (TRH) (GlpHisPro-NH2) | hypothalamic nuclei, cytotrophoblast![]() |
TRH-R![]() |
|
heterodimeric glycoproteins with common a chain (96 amino acids ; 14 kDa) | thyroid stimulating hormone (TSH) : + b chain (112 amino acids) | thyroid epithelial cells | TSH-R![]() |
follicle-stimulating hormone (FSH) : + b chain (120 amino acids) | gonadotropic cells of anterior pituitary gland | FSH-R![]() |
|
luteinizing hormone (LH) : + bchain (121 amino acids) | gonadotropic cells of anterior pituitary gland | LH / hCG-R![]() |
|
human chorionic gonadotropin (hCG) : + b chains (b1, b2, b3, b5, b7 or b8) (147 amino acids) | syncytiotrophoblast![]() |
LH / hCG-R![]() |
|
gonadotropin-releasing hormone (GnRH) 1 (10 amino acids) | arcuate nucleus and preoptic area of medial
hypothalamus, cytotrophoblast![]() |
GnRH-R![]() |
|
gonadotropin-releasing hormone (GnRH) 2 | brain, T cells | ? | |
follistatin (2 isoforms from alternative splicing : FST317 and FST344) | autocrine and/or paracrine growth factor | activin A
activin AB |
|
follistatin-like 1 (FSTL1) | |||
follistatin-like 2 (FSTL2) / IGFBP7 | |||
follistatin-like 3 (FSTL3) / follistatin-related protein (FSRP) | activin A | ||
somatostatin (SST) : Pro-9 and Pro-5, located near the processing sites (Arg-15 and Arg-2Lys-1) of human prosomatostatin are important for cleavage of the precursor into | d / D cells of
Langerhans' islets of endocrine
pancreas, thymus, cytotrophoblast![]() |
SST1![]() SST2A ![]() SST2B ![]() SST3 ![]() SST4 ![]() SST5 ![]() |
|
cortistatin => | immune cells (up-regulated during differentiation of monocytes into macrophages and dendritic cells), lymphoid tissues, and bone marrow | SST1![]() SST2A ![]() SST2B ![]() SST3 ![]() SST4 ![]() SST5 ![]() GHSR ![]() |
|
calcitonin-1 gene encodes for procalcitonin (PCT) (14 kDa), whose processing generates : | thyroid medullary C cells; TNF-a-stimulated monocytes and granulocytes | calcitonin
receptor![]() |
|
calcitonin gene-related peptide (CGRP) 1 | thyroid, neurons | CGRP receptor![]() |
|
calcitonin gene-related peptide (CGRP) 2 | CGRP receptor![]() |
||
parathormone (PTH) | parathyroid epithelial cells | PTHR1![]() PTHR2 ![]() |
|
PTH-related protein (PTHrp) | 90% of primary prostate and lung spindle cell carcinomas and 50% of primary breast cancers, fetal tissues (parathyroids), low levels in keratinocytes, uterus, mammary glands during lactation | PTHR1![]() |
|
corticotropic releasing factor (CRF) / hormone (CRH) | hypophysary corticotropic cells, cytotrophoblast![]() |
CRHR1![]() CRHR2 ![]() |
|
adrenocorticotropic hormone (ACTH) (from POMC gene) | corticotropic anterior pituitary cells | MC2R / ACTHR![]() |
|
growth hormone releasing hormone (GHRH) | hypothalamic nuclei | GRP39![]() GRP38 / MTLR1 ![]() |
|
ghrelin | stomach | GHSR![]() |
|
growth
hormone
(GH) / somatotropic hormone (STH) 1 (191
amino acids)
|
somatotropic cells of pituitary gland, cytotrophoblast![]() |
GHR![]() |
|
growth hormone (GH) / somatotropic hormone (STH) 2 | somatotropic cells of pituitary gland | GHR![]() |
|
choriosomatomammotropin (hCS) 1 / placental lactogen (hPL) | syncytiotrophoblast![]() |
GHR![]() |
|
choriosomatomammotropin (hCS) 2 | syncytiotrophoblast![]() |
GHR![]() |
|
motilin (Mo / MTL) | Mo cells in jejunum and ileum | GRP38
/ MTLR1![]() |
|
relaxin 1 (RLX1) | RLXR![]() |
||
relaxin 2 (RLX2) | RLXR![]() |
||
relaxin 3 (RLX3) | RLXR![]() |
||
inhibin A (= inhibin a or bC homodimer) | pituitary | activins
and inhibin
receptor![]() |
|
inhibin B = | |||
activin A (= inhibin bA homodimer) | autocrine and/or paracrine growth factor in pituitary, testis, epididymis and prostate | activins
and inhibin
receptor![]() follistatin follistatin-like 3 (FSLT3) |
|
activin AB (= inhibin bA and bB heterodimer) | autocrine and/or paracrine growth factor in pituitary, testis, epididymis and prostate | activins
and inhibin
receptor![]() follistatin |
|
bone morphogenetic proteins (BMPs) | bone morphogenetic protein (BMP) 1 | BMP
receptor![]() |
|
bone morphogenetic protein (BMP) 2 | BMP
receptor![]() |
||
bone morphogenetic protein (BMP) 3 | BMP
receptor![]() |
||
bone morphogenetic protein (BMP) 4 | BMP
receptor![]() |
||
bone morphogenetic protein (BMP) 5 | BMP
receptor![]() |
||
bone morphogenetic protein (BMP) 6 | BMP
receptor![]() |
||
bone morphogenetic protein (BMP) 7 | BMP
receptor![]() |
||
bone morphogenetic protein (BMP) 8 | BMP
receptor![]() |
||
bone morphogenetic protein (BMP) 9 | BMP
receptor![]() |
||
bone morphogenetic protein (BMP) 10 | BMP
receptor![]() |
||
bone morphogenetic protein (BMP) 11 | BMP
receptor![]() |
||
bone morphogenetic protein (BMP) 15 | BMP
receptor![]() |
||
galanin | galanin
receptor 1![]() galanin receptor 2 ![]() galanin receptor 3 ![]() |
||
kisspeptins derive from the product of KiSS-1 : common RF-amide C terminus | kisspeptin 13 | GRP54![]() |
|
kisspeptin 14 | |||
kisspeptin 54 / metastin | placenta, melanoma | ||
xenin consists of the N-terminal 25 amino acids of alpha-COP | |||
secretin | S cells in jejunum and ileum | secretin
receptor![]() |
|
vasointestinal peptide (VIP) precursor encodes : | VIPR1 / PACAPR2![]() VIPR2 ![]() |
||
helodermin![]() |
thyroid parafollicular C cells | ||
pituitary adenylate cyclase activating hormone (PACAP) | VIPR1 / PACAPR2![]() VIPR2 ![]() PACAPR1 ![]() |
||
cholecystokinin (CCK) / pancreozymin | I cells in jejunum and ileum | CCK1 /
CCKA![]() CCK2 / CCKB ![]() |
|
neurotensin | N cells in ileum | neurotensin
receptor
1![]() neurotensin receptor 2 ![]() |
|
agouti-related peptide (AgRP) homolog (2 isoforms which differ in 5'UTRs) | arcuate nucleus neurons producing also NPY | antagonist on | |
cocaine- and amphetamine-regulated transcript (CART) | arcuate nucleus neurons producing also a-MSH | ? | |
repulsive guidance molecule (RGM) domain family, member A | neogenin (NGN)homolog 1 (chicken) is a dependence receptor inducing cell death in the absence of RGM, whereas the presence of RGM inhibits this effectref | ||
gastrin | G cells in pylorus and duodenum, TG cells in jejunum | CCK2 /
CCKB![]() |
|
gastrin-releasing peptide (GRP) / bombesine | GRP / bombesine
receptor![]() |
||
gastric inhibitory polypeptide (GIP) / glucose-dependent insulinotropic peptide (GIP) | K cells of the duodenum, jejunum, and ileum | GIP receptor![]() |
|
prolactin (PRL) (199 amino acids) | lactotropic cells of pituitary gland, placenta, decidua and endometrium in the second half of the menstrual cycle | PRLR![]() |
|
leptin | white adipocytesref, stomachref, placentaref, brainref, and pituitary glandref | LEPR![]() |
|
adiponectin (APM1) / adipocyte complement-related protein of 30 kDa (ACRP30) / adipocyte, C1Q and collagen domain containing (ACDC) | adipocytes | adipoR1![]() adipoR2 ![]() |
|
visfatin (for visceral fat protein) | visceral adipocytes | ||
resistin family : the characteristic feature of this family is the C-terminal stretch of 10 cys residues with identical spacing. | resistin (RETN) | adipocytes | ? |
resistin-like b (RETNLB) | colon and small intestine | ? | |
resistin-like g (RETNLG) | ? | ? | |
angiotensinogen
==
|
hepatocytes | AT1a![]() AT1b ![]() AT2 ![]() |
|
endosulfines (for endogenous sulfonylureas) | a-endosulfine (ENSA) (121-amino acids protein of 19 kDa) | muscle, brain, and d cells of pancreas | ABCC8 /
sulfonylurea receptor 1 (SUR1)![]() voltage-gated calcium channels ![]() |
b-endosulfine (ENSB) (more basic, only from ovine and porcine brain) |
islet amyloid polypeptide (IAPP) / amylin | b cells of pancreas | ||
Klotho protein functions as a circulating hormone that binds to a cell-surface receptor and represses intracellular signals of insulin and IGF1, an evolutionarily conserved mechanism for extending life span. Alleviation of aging-like phenotypes in Klotho-deficient mice was observed by perturbing insulin/IGF1 signaling, suggesting that Klotho-mediated inhibition of insulin/IGF1 signaling contributes to its anti-aging properties. Klotho protein may function as an anti-aging hormone in mammalsref |
Notch
homolog 1 (NOTCH1) : member of a Type 1
transmembrane receptor
family that shares structural characteristics including
an extracellular
domain consisting of multiple EGF-like repeats, and an
intracellular domain
consisting of multiple, different domain types. Notch
family members play
a role in a variety of developmental processes by
controlling cell fate
decisions.
The extracellular domain contains a variable number of epidermal growth factor (EGF)–like repeats involved in ligand binding, and 3 Lin-12/Notch repeats involved in Notch heterodimerization. The intracellular domain contains a RAM23 motif involved in binding Notch downstream signaling proteins, 7 cdc10/ankyrin repeats also involved in mediating downstream signaling, and a PEST domain involved in Notch protein degradation. |
delta-like
1
(DLL1)
delta-like 1 homolog (DLK1) delta-like 3 (DLL3) delta-like 4 (DLL4) deltex homolog 1 (DTX1) hairy and enhancer of split 1 (HES1) jagged 1 (JAG1) jagged 2 (JAG2) Within the extracellular domain, Jagged family members contain a cysteine-rich region likely involved in the control of Notch receptor binding specificity, as well as a von Willebrand factor type C domain likely involved in ligand dimerization. These motifs are not present in Dll family members. Extracellular motifs common to all Notch ligands include a single Delta/Serrate/Lag-2 (DSL) domain involved in receptor binding, as well as a variable number of EGF-like repeats that may stabilize receptor binding. |
|
|
GRK1 / rhodopsin kinase (RK) | rhodopsin![]() |
GRK2 / bARK1 | b1-AR![]() |
GRK3 / bARK2 | b2-AR![]() |
GRK4 / IT-11 | unidentified |
GRK5 | b2-AR![]() |
GRK6 | b2-AR![]() |
GRK7 | unidentified |
b-arrestin 1 (A and B isoforms) | b1-AR![]() |
b-arrestin 2 | b1-AR![]() |
X arrestin / arrestin 3 | rhodopsin![]() |
S-arrestin / S antigen | rhodopsin![]() |
AKAP78 => cytoskeleton | |
ezrin => cytoskeleton | |
MAP2 => cytoskeleton | |
AKAP1 / AKAP84 / AKAP149 => mitochondria | |
AKAP2 | |
AKAP3 / AKAP110 | |
AKAP4 / AKAP82 | |
AKAP5 / AKAP75 / KAP79 (h) => membranes (it drives also AC, PP2B and PKC) | |
AKAP6 / AKAP100 => ER | |
AKAP7 / AKAP15 / AKAP18 => L-type Ca2+ channels | |
AKAP8 / 95 / n150 => nucleus | |
AKAP9
/ AKAP450 / AKAP350 / CG-NAP / Yotiao => drives
PKA and PP1
to NR1 subunit of NMDA
receptor![]() |
|
AKAP11 / AKAP220 => peroxisome | |
AKAP12 / AKAP250 / gravin | |
AKAP13 | |
AKAP85 => Golgi apparatus | |
AKAP150 (m) => membranes |
|
|
for |
|