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UniProtKB - P21709 (EPHA1_HUMAN)

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Protein

Ephrin type-A receptor 1

Gene

EPHA1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Binds with a low affinity EFNA3 and EFNA4 and with a high affinity to EFNA1 which most probably constitutes its cognate/functional ligand. Upon activation by EFNA1 induces cell attachment to the extracellular matrix inhibiting cell spreading and motility through regulation of ILK and downstream RHOA and RAC. Plays also a role in angiogenesis and regulates cell proliferation. May play a role in apoptosis.3 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei656ATPPROSITE-ProRule annotation1
Active sitei749Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi630 – 638ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • protein kinase activity Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • transmembrane-ephrin receptor activity Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • activation of GTPase activity Source: UniProtKB
  • angiogenesis Source: UniProtKB-KW
  • cell surface receptor signaling pathway Source: UniProtKB
  • ephrin receptor signaling pathway Source: Reactome
  • negative regulation of cell migration Source: UniProtKB
  • negative regulation of protein kinase activity Source: UniProtKB
  • peptidyl-tyrosine phosphorylation Source: UniProtKB
  • positive regulation of angiogenesis Source: UniProtKB
  • positive regulation of cell-matrix adhesion Source: UniProtKB
  • positive regulation of cell migration Source: UniProtKB
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of stress fiber assembly Source: UniProtKB
  • protein autophosphorylation Source: UniProtKB
  • regulation of GTPase activity Source: UniProtKB
  • somatic stem cell population maintenance Source: Reactome
  • substrate adhesion-dependent cell spreading Source: UniProtKB
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionKinase, Receptor, Transferase, Tyrosine-protein kinase
Biological processAngiogenesis, Cell adhesion
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1 2681
ReactomeiR-HSA-2682334 EPH-Ephrin signaling
R-HSA-2892247 POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation
R-HSA-3928663 EPHA-mediated growth cone collapse
R-HSA-3928665 EPH-ephrin mediated repulsion of cells
SignaLinkiP21709
SIGNORiP21709

Names & Taxonomyi

Protein namesi
Recommended name:
Ephrin type-A receptor 1 (EC:2.7.10.1)
Short name:
hEpha1
Alternative name(s):
EPH tyrosine kinase
EPH tyrosine kinase 1
Erythropoietin-producing hepatoma receptor
Tyrosine-protein kinase receptor EPH
Gene namesi
Name:EPHA1
Synonyms:EPH, EPHT, EPHT1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000146904.8
HGNCiHGNC:3385 EPHA1
MIMi179610 gene
neXtProtiNX_P21709

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini26 – 547ExtracellularSequence analysisAdd BLAST522
Transmembranei548 – 568HelicalSequence analysisAdd BLAST21
Topological domaini569 – 976CytoplasmicSequence analysisAdd BLAST408

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi2041
OpenTargetsiENSG00000146904
PharmGKBiPA27817

Chemistry databases

ChEMBLiCHEMBL5810
GuidetoPHARMACOLOGYi1821

Polymorphism and mutation databases

BioMutaiEPHA1
DMDMi317373566

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Sequence analysisAdd BLAST25
ChainiPRO_000001679826 – 976Ephrin type-A receptor 1Add BLAST951

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi414N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei599Phosphotyrosine; by autocatalysisSequence analysis1
Modified residuei605Phosphotyrosine; by autocatalysisSequence analysis1
Modified residuei781Phosphotyrosine; by autocatalysisSequence analysis1
Modified residuei906PhosphoserineCombined sources1
Modified residuei910PhosphoserineCombined sources1
Modified residuei930Phosphotyrosine; by autocatalysisSequence analysis1

Post-translational modificationi

Phosphorylated. Autophosphorylation is stimulated by its ligand EFNA1.
Ubiquitinated.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP21709
MaxQBiP21709
PaxDbiP21709
PeptideAtlasiP21709
PRIDEiP21709
ProteomicsDBi53891

PTM databases

iPTMnetiP21709
PhosphoSitePlusiP21709

Expressioni

Tissue specificityi

Overexpressed in several carcinomas.

Gene expression databases

BgeeiENSG00000146904
CleanExiHS_EPHA1
GenevisibleiP21709 HS

Organism-specific databases

HPAiCAB026144

Interactioni

Subunit structurei

Homodimer. Forms a signaling complex with LCK; PTK2B/PYK2 and PI3-kinase upon activation by EFNA1; regulates T-lymphocytes migration. Interacts (via SAM domain) with ILK (via ANK repeats); stimulated by EFNA1 but independent of the kinase activity of EPHA1. Interacts (kinase activity-dependent) with PTK2/FAK1.2 Publications

GO - Molecular functioni

  • protein kinase binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi108355, 92 interactors
CORUMiP21709
DIPiDIP-34886N
IntActiP21709, 7 interactors
STRINGi9606.ENSP00000275815

Chemistry databases

BindingDBiP21709

Structurei

Secondary structure

1976
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi538 – 540Combined sources3
Helixi545 – 570Combined sources26
Helixi918 – 924Combined sources7
Helixi928 – 930Combined sources3
Helixi931 – 936Combined sources6
Helixi942 – 945Combined sources4
Helixi950 – 955Combined sources6
Helixi961 – 973Combined sources13

3D structure databases

ProteinModelPortaliP21709
SMRiP21709
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP21709

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 209Eph LBDPROSITE-ProRule annotationAdd BLAST183
Domaini332 – 445Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST114
Domaini447 – 538Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST92
Domaini624 – 884Protein kinasePROSITE-ProRule annotationAdd BLAST261
Domaini913 – 976SAMPROSITE-ProRule annotationAdd BLAST64

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi974 – 976PDZ-bindingSequence analysis3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi191 – 329Cys-richAdd BLAST139

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0196 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000118975
HOGENOMiHOG000233856
HOVERGENiHBG062180
InParanoidiP21709
KOiK05102
OMAiQAYEDPA
OrthoDBiEOG091G00W0
PhylomeDBiP21709
TreeFamiTF315363

Family and domain databases

CDDicd10479 EphR_LBD_A1, 1 hit
cd00063 FN3, 2 hits
Gene3Di2.60.120.260, 1 hit
2.60.40.10, 2 hits
InterProiView protein in InterPro
IPR027936 Eph_TM
IPR034251 EphA1_rcpt_lig-bd
IPR001090 Ephrin_rcpt_lig-bd_dom
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR008979 Galactose-bd-like_sf
IPR009030 Growth_fac_rcpt_cys_sf
IPR013783 Ig-like_fold
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001660 SAM
IPR013761 SAM/pointed_sf
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR011641 Tyr-kin_ephrin_A/B_rcpt-like
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
IPR016257 Tyr_kinase_ephrin_rcpt
IPR001426 Tyr_kinase_rcpt_V_CS
PfamiView protein in Pfam
PF14575 EphA2_TM, 1 hit
PF01404 Ephrin_lbd, 1 hit
PF00041 fn3, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PF00536 SAM_1, 1 hit
PIRSFiPIRSF000666 TyrPK_ephrin_receptor, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00615 EPH_lbd, 1 hit
SM01411 Ephrin_rec_like, 1 hit
SM00060 FN3, 2 hits
SM00454 SAM, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF47769 SSF47769, 1 hit
SSF49265 SSF49265, 1 hit
SSF49785 SSF49785, 1 hit
SSF56112 SSF56112, 1 hit
SSF57184 SSF57184, 2 hits
PROSITEiView protein in PROSITE
PS01186 EGF_2, 1 hit
PS51550 EPH_LBD, 1 hit
PS50853 FN3, 2 hits
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00109 PROTEIN_KINASE_TYR, 1 hit
PS00790 RECEPTOR_TYR_KIN_V_1, 1 hit
PS00791 RECEPTOR_TYR_KIN_V_2, 1 hit
PS50105 SAM_DOMAIN, 1 hit

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P21709-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MERRWPLGLG LVLLLCAPLP PGARAKEVTL MDTSKAQGEL GWLLDPPKDG 
        60         70         80         90        100
WSEQQQILNG TPLYMYQDCP MQGRRDTDHW LRSNWIYRGE EASRVHVELQ 
       110        120        130        140        150
FTVRDCKSFP GGAGPLGCKE TFNLLYMESD QDVGIQLRRP LFQKVTTVAA 
       160        170        180        190        200
DQSFTIRDLV SGSVKLNVER CSLGRLTRRG LYLAFHNPGA CVALVSVRVF 
       210        220        230        240        250
YQRCPETLNG LAQFPDTLPG PAGLVEVAGT CLPHARASPR PSGAPRMHCS 
       260        270        280        290        300
PDGEWLVPVG RCHCEPGYEE GGSGEACVAC PSGSYRMDMD TPHCLTCPQQ 
       310        320        330        340        350
STAESEGATI CTCESGHYRA PGEGPQVACT GPPSAPRNLS FSASGTQLSL 
       360        370        380        390        400
RWEPPADTGG RQDVRYSVRC SQCQGTAQDG GPCQPCGVGV HFSPGARGLT 
       410        420        430        440        450
TPAVHVNGLE PYANYTFNVE AQNGVSGLGS SGHASTSVSI SMGHAESLSG 
       460        470        480        490        500
LSLRLVKKEP RQLELTWAGS RPRSPGANLT YELHVLNQDE ERYQMVLEPR 
       510        520        530        540        550
VLLTELQPDT TYIVRVRMLT PLGPGPFSPD HEFRTSPPVS RGLTGGEIVA 
       560        570        580        590        600
VIFGLLLGAA LLLGILVFRS RRAQRQRQQR QRDRATDVDR EDKLWLKPYV 
       610        620        630        640        650
DLQAYEDPAQ GALDFTRELD PAWLMVDTVI GEGEFGEVYR GTLRLPSQDC 
       660        670        680        690        700
KTVAIKTLKD TSPGGQWWNF LREATIMGQF SHPHILHLEG VVTKRKPIMI 
       710        720        730        740        750
ITEFMENGAL DAFLREREDQ LVPGQLVAML QGIASGMNYL SNHNYVHRDL 
       760        770        780        790        800
AARNILVNQN LCCKVSDFGL TRLLDDFDGT YETQGGKIPI RWTAPEAIAH 
       810        820        830        840        850
RIFTTASDVW SFGIVMWEVL SFGDKPYGEM SNQEVMKSIE DGYRLPPPVD 
       860        870        880        890        900
CPAPLYELMK NCWAYDRARR PHFQKLQAHL EQLLANPHSL RTIANFDPRM 
       910        920        930        940        950
TLRLPSLSGS DGIPYRTVSE WLESIRMKRY ILHFHSAGLD TMECVLELTA 
       960        970 
EDLTQMGITL PGHQKRILCS IQGFKD
Length:976
Mass (Da):108,127
Last modified:January 11, 2011 - v4
Checksum:i91EFCA69FFE17826
GO
Isoform 2 (identifier: P21709-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     446-490: ESLSGLSLRL...YELHVLNQDE → DPTLSLWTPR...APKPWGEPDL
     491-976: Missing.

Show »
Length:490
Mass (Da):52,618
Checksum:iC7BF2D396EE54F05
GO
Isoform 3 (identifier: P21709-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     446-474: ESLSGLSLRLVKKEPRQLELTWAGSRPRS → GERLRGAGTGTWWRQKGLRPQNKLMGRKP
     475-976: Missing.

Show »
Length:474
Mass (Da):51,069
Checksum:i6D263B013A90E9B5
GO

Sequence cautioni

The sequence AAA36747 differs from that shown. Reason: Frameshift at positions 582, 595 and 601.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti398G → A in AAD43440 (PubMed:10369740).Curated1
Sequence conflicti398G → A in CAA81796 (Ref. 8) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_028265160V → A6 PublicationsCorresponds to variant dbSNP:rs4725617Ensembl.1
Natural variantiVAR_042115351R → C1 PublicationCorresponds to variant dbSNP:rs56006153Ensembl.1
Natural variantiVAR_028266492R → Q1 PublicationCorresponds to variant dbSNP:rs11768549Ensembl.1
Natural variantiVAR_042116575R → Q1 PublicationCorresponds to variant dbSNP:rs35719334Ensembl.1
Natural variantiVAR_042117585A → T1 PublicationCorresponds to variant dbSNP:rs34178823Ensembl.1
Natural variantiVAR_042118697P → L1 PublicationCorresponds to variant dbSNP:rs34372369Ensembl.1
Natural variantiVAR_042119703E → K in a breast pleomorphic lobular carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_042120807S → R1 PublicationCorresponds to variant dbSNP:rs56244405Ensembl.1
Natural variantiVAR_028267900M → VCombined sources7 PublicationsCorresponds to variant dbSNP:rs6967117Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_056010446 – 490ESLSG…LNQDE → DPTLSLWTPRVTVRPVSETG EERTEATRADLGGVPAPKPW GEPDL in isoform 2. 1 PublicationAdd BLAST45
Alternative sequenceiVSP_056011446 – 474ESLSG…SRPRS → GERLRGAGTGTWWRQKGLRP QNKLMGRKP in isoform 3. 1 PublicationAdd BLAST29
Alternative sequenceiVSP_056012475 – 976Missing in isoform 3. 1 PublicationAdd BLAST502
Alternative sequenceiVSP_056013491 – 976Missing in isoform 2. 1 PublicationAdd BLAST486

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M18391 mRNA Translation: AAA36747.1 Frameshift.
AF101171
, AF101165, AF101166, AF101167, AF101168, AF101169, AF101170 Genomic DNA Translation: AAD43440.1
EU826604 mRNA Translation: ACF47640.1
EU826605 mRNA Translation: ACF47641.1
AC092214 Genomic DNA Translation: AAS07458.1
CH236959 Genomic DNA Translation: EAL23789.1
CH471198 Genomic DNA Translation: EAW51846.1
CH471198 Genomic DNA Translation: EAW51847.1
BC130291 mRNA Translation: AAI30292.1
Z27409 mRNA Translation: CAA81796.1
CCDSiCCDS5884.1 [P21709-1]
PIRiA34076
RefSeqiNP_005223.4, NM_005232.4 [P21709-1]
UniGeneiHs.89839

Genome annotation databases

EnsembliENST00000275815; ENSP00000275815; ENSG00000146904 [P21709-1]
ENST00000645847; ENSP00000494931; ENSG00000284816 [P21709-1]
GeneIDi2041
KEGGihsa:2041
UCSCiuc003wcz.3 human [P21709-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiEPHA1_HUMAN
AccessioniPrimary (citable) accession number: P21709
Secondary accession number(s): A1L3V3
, B5A966, B5A967, Q15405
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: January 11, 2011
Last modified: June 20, 2018
This is version 200 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

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