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EPHA8

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From Wikipedia, the free encyclopedia

Protein-coding gene in the species Homo sapiens

EPHA8

Available structures

PDB

Ortholog search:PDBe RCSB

List of PDB id codes
1UCV,1X5L,3KUL

Identifiers

Aliases

EPHA8, EEK, EK3, HEK3, EPH receptor A8

External IDs

OMIM:176945;MGI:109378;HomoloGene:22436;GeneCards:EPHA8;OMA:EPHA8 - orthologs

Gene location (Human)

Chr.	Chromosome 1 (human)^[1]

Band	1p36.12	Start	22,563,489bp^[1]
Band	1p36.12	End	22,603,595bp^[1]

Gene location (Mouse)

Chr.	Chromosome 4 (mouse)^[2]

Band	4\|4 D3	Start	136,929,419bp^[2]
Band	4\|4 D3	End	136,956,816bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

endothelial cell

gonad

spleen

hypothalamus

secondary oocyte

mesencephalon

substantia nigra

prefrontal cortex

cingulate gyrus

anterior cingulate cortex

Top expressed in

neural layer of retina

cerebellar cortex

Ileal epithelium

perirhinal cortex

visual cortex

superior frontal gyrus

lacrimal groove

primary visual cortex

entorhinal cortex

lens

More reference expression data

BioGPS

n/a

Gene ontology
Molecular function	transferase activity nucleotide binding protein kinase activity kinase activity transmembrane receptor protein tyrosine kinase activity protein tyrosine kinase activity ATP binding ephrin receptor activity GPI-linked ephrin receptor activity receptor tyrosine kinase transmembrane signaling receptor activity transmembrane-ephrin receptor activity
Cellular component	integral component of membrane endosome cell projection early endosome membrane membrane integral component of plasma membrane plasma membrane neuron projection cytoplasm receptor complex
Biological process	phosphorylation transmembrane receptor protein tyrosine kinase signaling pathway nervous system development multicellular organism development protein phosphorylation cell adhesion peptidyl-tyrosine phosphorylation substrate-dependent cell migration protein autophosphorylation axon guidance neuron projection development regulation of cell adhesion regulation of cell adhesion mediated by integrin neuron remodeling positive regulation of phosphatidylinositol 3-kinase activity ephrin receptor signaling pathway positive regulation of MAPK cascade cellular response to follicle-stimulating hormone stimulus negative regulation of signal transduction cell differentiation negative regulation of apoptotic process positive regulation of ERK1 and ERK2 cascade
Sources:Amigo /QuickGO

Orthologs

Species

Human

Mouse

Entrez


2046


13842

Ensembl


ENSG00000070886


ENSMUSG00000028661

UniProt


P29322


O09127

RefSeq (mRNA)


NM_001006943 NM_020526


NM_007939

RefSeq (protein)


NP_001006944 NP_065387


NP_031965

Location (UCSC)

Chr 1: 22.56 – 22.6 Mb

Chr 4: 136.93 – 136.96 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Ephrin type-A receptor 8 is aprotein that in humans is encoded by theEPHA8gene.^[5]^[6]

Function

[edit]

This gene encodes a member of theephrin receptor subfamily of theprotein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. The protein encoded by this gene functions as a receptor for ephrin A2, A3 and A5 and plays a role in short-range contact-mediatedaxonal guidance during development of the mammalian nervous system.^[6]

Interactions

[edit]

EPHA8 has been shown tointeract withFYN.^[7]

References

[edit]

^^a ^b ^cGRCh38: Ensembl release 89: ENSG00000070886 –Ensembl, May 2017
^^a ^b ^cGRCm38: Ensembl release 89: ENSMUSG00000028661 –Ensembl, May 2017
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^Chan J, Watt VM (Aug 1991). "eek and erk, new members of the eph subclass of receptor protein-tyrosine kinases".Oncogene.6 (6):1057–61.PMID 1648701.
^^a ^b"Entrez Gene: EPHA8 EPH receptor A8".
^Choi S, Park S (Sep 1999). "Phosphorylation at Tyr-838 in the kinase domain of EphA8 modulates Fyn binding to the Tyr-615 site by enhancing tyrosine kinase activity".Oncogene.18 (39):5413–22.doi:10.1038/sj.onc.1202917.PMID 10498895.S2CID 11001580.

Flanagan JG, Vanderhaeghen P (1998). "The ephrins and Eph receptors in neural development".Annu. Rev. Neurosci.21:309–45.doi:10.1146/annurev.neuro.21.1.309.PMID 9530499.
Holland SJ, Peles E, Pawson T, Schlessinger J (1998)."Cell-contact-dependent signalling in axon growth and guidance: Eph receptor tyrosine kinases and receptor protein tyrosine phosphatase beta".Curr. Opin. Neurobiol.8 (1):117–27.doi:10.1016/S0959-4388(98)80015-9.PMID 9568399.S2CID 34141508.
Zhou R (1998). "The Eph family receptors and ligands".Pharmacol. Ther.77 (3):151–81.doi:10.1016/S0163-7258(97)00112-5.PMID 9576626.
Holder N, Klein R (1999). "Eph receptors and ephrins: effectors of morphogenesis".Development.126 (10):2033–44.doi:10.1242/dev.126.10.2033.PMID 10207129.
Wilkinson DG (2000). "Eph receptors and ephrins: Regulators of guidance and assembly".A Survey of Cell Biology. International Review of Cytology. Vol. 196. pp. 177–244.doi:10.1016/S0074-7696(00)96005-4.ISBN 978-0-12-364600-2.PMID 10730216.{{cite book}}:|journal= ignored (help)
Xu Q, Mellitzer G, Wilkinson DG (2001)."Roles of Eph receptors and ephrins in segmental patterning".Philos. Trans. R. Soc. Lond. B Biol. Sci.355 (1399):993–1002.doi:10.1098/rstb.2000.0635.PMC 1692797.PMID 11128993.
Wilkinson DG (2001). "Multiple roles of EPH receptors and ephrins in neural development".Nat. Rev. Neurosci.2 (3):155–64.doi:10.1038/35058515.PMID 11256076.S2CID 205014301.
Nakamoto T, Kain KH, Ginsberg MH (2004)."Neurobiology: New connections between integrins and axon guidance".Curr. Biol.14 (3): R121–3.Bibcode:2004CBio...14.R121N.doi:10.1016/j.cub.2004.01.020.PMID 14986683.S2CID 2957639.
Yamaguchi Y, Pasquale EB (2004). "Eph receptors in the adult brain".Curr. Opin. Neurobiol.14 (3):288–96.doi:10.1016/j.conb.2004.04.003.PMID 15194108.S2CID 26196696.
Murai KK, Pasquale EB (2004). "Eph receptors, ephrins, and synaptic function".The Neuroscientist.10 (4):304–14.doi:10.1177/1073858403262221.PMID 15271258.S2CID 23900846.
Park S, Sánchez MP (1997). "The Eek receptor, a member of the Eph family of tyrosine protein kinases, can be activated by three different Eph family ligands".Oncogene.14 (5):533–42.doi:10.1038/sj.onc.1200857.PMID 9053851.S2CID 21779523.
Park S, Frisén J, Barbacid M (1997)."Aberrant axonal projections in mice lacking EphA8 (Eek) tyrosine protein kinase receptors".EMBO J.16 (11):3106–14.doi:10.1093/emboj/16.11.3106.PMC 1169929.PMID 9214628.
Ephnomenclaturecommittee (1997)."Unified nomenclature for Eph family receptors and their ligands, the ephrins. Eph Nomenclature Committee".Cell.90 (3):403–4.doi:10.1016/S0092-8674(00)80500-0.PMID 9267020.S2CID 26773768.
Lemke G (1998). "A coherent nomenclature for Eph receptors and their ligands".Mol. Cell. Neurosci.9 (5–6):331–2.doi:10.1006/mcne.1997.0630.PMID 9361271.S2CID 6608696.
Choi S, Park S (1999). "Phosphorylation at Tyr-838 in the kinase domain of EphA8 modulates Fyn binding to the Tyr-615 site by enhancing tyrosine kinase activity".Oncogene.18 (39):5413–22.doi:10.1038/sj.onc.1202917.PMID 10498895.S2CID 11001580.

v t e PDB gallery
1ucv: Sterile alpha motif (SAM) domain of ephrin type-A receptor 8 1x5l: Solution structure of the second fn3 domain of Eph receptor A8 protein

Protein kinases:tyrosine kinases (EC 2.7.10)

Receptor tyrosine kinases (EC 2.7.10.1)

Growth factor receptors

EGF receptor family	EGFR ERBB2 ERBB3 ERBB4
Insulin receptor family	IGF1R INSR INSRR
PDGF receptor family	CSF1R FLT3 KIT PDGFR (PDGFRA PDGFRB)
FGF receptor family	FGFR1 FGFR2 FGFR3 FGFR4
VEGF receptors family	VEGFR1 VEGFR2 VEGFR3
HGF receptor family	MET RON
Trk receptor family	NTRK1 NTRK2 NTRK3

EPH receptor family

LTK receptor family

TIE receptor family

ROR receptor family

DDR receptor family

PTK7 receptor family

PTK7

RYK receptor family

MuSK receptor family

MUSK

ROS receptor family

ROS1

AATYK receptor family

AXL receptor family

RET receptor family

uncategorised

STYK1

Non-receptor tyrosine kinases (EC 2.7.10.2)

ABL family	ABL1 ARG
ACK family	ACK1 TNK1
CSK family	CSK MATK
FAK family	FAK PYK2
FES family	FES FER
FRK family	FRK BRK SRMS
JAK family	JAK1 JAK2 JAK3 TYK2
SRC-A family	SRC FGR FYN YES1
SRC-B family	BLK HCK LCK LYN
TEC family	TEC BMX BTK ITK TXK
SYK family	SYK ZAP70

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1Oxidoreductases (list) EC2Transferases (list) EC3Hydrolases (list) EC4Lyases (list) EC5Isomerases (list) EC6Ligases (list) EC7Translocases (list)

Growth factor receptor modulators

Angiopoietin

Agonists:Angiopoietin 1
Angiopoietin 4

Antagonists:Angiopoietin 2
Angiopoietin 3

Kinase inhibitors:Altiratinib
CE-245677
Rebastinib

Antibodies:Evinacumab (against angiopoietin 3)
Nesvacumab (against angiopoietin 2)

CNTF

EGF (ErbB)

EGF (ErbB1/HER1)	Agonists:Amphiregulin Betacellulin EGF (urogastrone) Epigen Epiregulin Heparin-binding EGF-like growth factor (HB-EGF) Murodermin Nepidermin Transforming growth factor alpha (TGFα) Kinase inhibitors:Afatinib Agerafenib Brigatinib Canertinib Dacomitinib Erlotinib Gefitinib Grandinin Icotinib Lapatinib Neratinib Osimertinib Vandetanib WHI-P 154 Antibodies:Cetuximab Depatuxizumab Depatuxizumab mafodotin Futuximab Imgatuzumab Matuzumab Necitumumab Nimotuzumab Panitumumab Zalutumumab
ErbB2/HER2	Agonists:Unknown/none Antibodies:Ertumaxomab Pertuzumab Trastuzumab Trastuzumab deruxtecan Trastuzumab duocarmazine Trastuzumab emtansine Kinase inhibitors:Afatinib Lapatinib Mubritinib Neratinib Tucatinib
ErbB3/HER3	Agonists:Neuregulins (heregulins) (1,2,6 (neuroglycan C)) Antibodies:Duligotumab Patritumab Seribantumab
ErbB4/HER4	Agonists:Betacellulin Epigen Heparin-binding EGF-like growth factor (HB-EGF) Neuregulins (heregulins) (1,2,3,4,5 (tomoregulin, TMEFF))

FGF

FGFR1	Agonists:Ersofermin FGF (1,2 (bFGF),3,4,5,6,8,10 (KGF2),20) Repifermin Selpercatinib Trafermin Velafermin
FGFR2	Agonists:Ersofermin FGF (1,2 (bFGF),3,4,5,6,7 (KGF),8,9,10 (KGF2),17,18,22) Palifermin Repifermin Selpercatinib Sprifermin Trafermin Antibodies:Aprutumab Aprutumab ixadotin Kinase inhibitors:Infigratinib
FGFR3	Agonists:Ersofermin FGF (1,2 (bFGF),4,8,9,18,23) Selpercatinib Sprifermin Trafermin Antibodies:Burosumab (against FGF23)
FGFR4	Agonists:Ersofermin FGF (1,2 (bFGF),4,6,8,9,19) Trafermin
Unsorted	Agonists:FGF15/19

HGF (c-Met)

Agonists:Fosgonimeton
Hepatocyte growth factor

Potentiators:Dihexa (PNB-0408)

IGF

IGF-1	Agonists:des(1-3)IGF-1 Insulin-like growth factor-1 (somatomedin C) IGF-1 LR3 Insulin-like growth factor-2 (somatomedin A) Insulin Mecasermin Mecasermin rinfabate Kinase inhibitors:BMS-754807 Linsitinib NVP-ADW742 NVP-AEW541 OSl-906 Antibodies:AVE-1642 Cixutumumab Dalotuzumab Figitumumab Ganitumab Robatumumab R1507 Teprotumumab Xentuzumab (against IGF-1 and IGF-2)
IGF-2	Agonists:Insulin-like growth factor-2 (somatomedin A) Antibodies:Dusigitumab Xentuzumab (against IGF-1 and IGF-2)
Others	Binding proteins:IGFBP (1,2,3,4,5,6,7) Cleavage products/derivatives with unknown target:Glypromate (GPE, (1-3)IGF-1) Trofinetide

LNGF (p75^NTR)

Antibodies:Against NGF:ABT-110 (PG110)
ASP-6294
Fasinumab
Frunevetmab
Fulranumab
MEDI-578
Ranevetmab
Tanezumab

Aptamers:Against NGF:RBM-004

Decoy receptors:LEVI-04 (p75^NTR-Fc)

PDGF

Agonists:Becaplermin
Platelet-derived growth factor (A,B,C,D)

RET (GFL)

GFRα1	Agonists:Glial cell line-derived neurotrophic factor (GDNF) Liatermin Kinase inhibitors:Vandetanib
GFRα2	Agonists:Neurturin (NRTN) Kinase inhibitors:Vandetanib
GFRα3	Agonists:Artemin (ARTN) Kinase inhibitors:Vandetanib
GFRα4	Agonists:Persephin (PSPN) Kinase inhibitors:Vandetanib
Unsorted	Kinase inhibitors:Agerafenib

SCF (c-Kit)

Agonists:Ancestim
Stem cell factor

TGFβ

Seehere instead.

Trk

TrkA	Agonists:Amitriptyline BNN-20 BNN-27 Cenegermin DHEA DHEA-S Gambogic amide NGF Tavilermide Antagonists:ALE-0540 Dexamethasone FX007 Testosterone Negative allosteric modulators:VM-902A Kinase inhibitors:Altiratinib AZD-6918 CE-245677 CH-7057288 DS-6051 Entrectinib GZ-389988 K252a Larotrectinib Lestaurtinib Milciclib ONO-4474 ONO-5390556 PLX-7486 Rebastinib SNA-120 (pegylated K252a)) Antibodies:Against TrkA:GBR-900;Against NGF:ABT-110 (PG110) ASP-6294 Fasinumab Frunevetmab Fulranumab MEDI-578 Ranevetmab Tanezumab Aptamers:Against NGF:RBM-004 Decoy receptors:ReN-1820 (TrkAd5)
TrkB	Agonists:3,7-DHF 3,7,8,2'-THF 4'-DMA-7,8-DHF 7,3'-DHF 7,8-DHF 7,8,2'-THF 7,8,3'-THF Amitriptyline BDNF BNN-20 Deoxygedunin Deprenyl Diosmetin DMAQ-B1 HIOC LM22A-4 N-Acetylserotonin NT-3 NT-4 Norwogonin (5,7,8-THF) R7 R13 TDP6 Antagonists:ANA-12 Cyclotraxin B Gossypetin (3,5,7,8,3',4'-HHF) Ligands:DHEA Kinase inhibitors:Altiratinib AZD-6918 CE-245677 CH-7057288 DS-6051 Entrectinib GZ-389988 K252a Larotrectinib Lestaurtinib ONO-4474 ONO-5390556 PLX-7486
TrkC	Agonists:BNN-20 DHEA NT-3 Kinase inhibitors:Altiratinib AZD-6918 CE-245677 CH-7057288 DS-6051 Entrectinib GZ-389988 K252a Larotrectinib Lestaurtinib ONO-4474 ONO-5390556 PLX-7486