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Protein

Ephrin type-A receptor 4

Gene

EPHA4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor tyrosine kinase which binds membrane-bound ephrin 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. Highly promiscuous, it has the unique property among Eph receptors to bind and to be physiologically activated by both GPI-anchored ephrin-A and transmembrane ephrin-B ligands including EFNA1 and EFNB3. Upon activation by ephrin ligands, modulates cell morphology and integrin-dependent cell adhesion through regulation of the Rac, Rap and Rho GTPases activity. Plays an important role in the development of the nervous system controlling different steps of axonal guidance including the establishment of the corticospinal projections. May also control the segregation of motor and sensory axons during neuromuscular circuit development. In addition to its role in axonal guidance plays a role in synaptic plasticity. Activated by EFNA1 phosphorylates CDK5 at 'Tyr-15' which in turn phosphorylates NGEF regulating RHOA and dendritic spine morphogenesis. In the nervous system, plays also a role in repair after injury preventing axonal regeneration and in angiogenesis playing a role in central nervous system vascular formation. Additionally, its promiscuity makes it available to participate in a variety of cell-cell signaling regulating for instance the development of the thymic epithelium.1 Publication

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei653 – 6531ATPPROSITE-ProRule annotation
Active sitei746 – 7461Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi627 – 6359ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • DH domain binding Source: UniProtKB
  • GPI-linked ephrin receptor activity Source: UniProtKB
  • PH domain binding Source: UniProtKB
  • protein kinase activity Source: UniProtKB
  • transmembrane-ephrin receptor activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Cell adhesion, Neurogenesis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1. 2681.
ReactomeiREACT_264068. EPH-Ephrin signaling.
REACT_264198. EPH-ephrin mediated repulsion of cells.
REACT_264548. EPHA-mediated growth cone collapse.
SignaLinkiP54764.

Names & Taxonomyi

Protein namesi
Recommended name:
Ephrin type-A receptor 4 (EC:2.7.10.1)
Alternative name(s):
EPH-like kinase 8
Short name:
EK8
Short name:
hEK8
Tyrosine-protein kinase TYRO1
Tyrosine-protein kinase receptor SEK
Gene namesi
Name:EPHA4
Synonyms:HEK8, SEK, TYRO1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:3388. EPHA4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini20 – 547528ExtracellularSequence AnalysisAdd
BLAST
Transmembranei548 – 56922HelicalSequence AnalysisAdd
BLAST
Topological domaini570 – 986417CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Endosome, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi40 – 401Q → A: 10-fold reduced affinity for EFNB2; when associated with A-42. 1 Publication
Mutagenesisi42 – 421E → A: 10-fold reduced affinity for EFNB2; when associated with A-40. 1 Publication

Organism-specific databases

PharmGKBiPA27820.

Polymorphism and mutation databases

BioMutaiEPHA4.
DMDMi1711371.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1919Sequence AnalysisAdd
BLAST
Chaini20 – 986967Ephrin type-A receptor 4PRO_0000016807Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi235 – 2351N-linked (GlcNAc...)Sequence Analysis
Glycosylationi340 – 3401N-linked (GlcNAc...)Sequence Analysis
Glycosylationi408 – 4081N-linked (GlcNAc...)Sequence Analysis
Glycosylationi545 – 5451N-linked (GlcNAc...)Sequence Analysis
Modified residuei596 – 5961Phosphotyrosine; by autocatalysisBy similarity
Modified residuei602 – 6021Phosphotyrosine; by autocatalysisBy similarity
Modified residuei779 – 7791Phosphotyrosine; by autocatalysisSequence Analysis
Modified residuei928 – 9281Phosphotyrosine; by autocatalysisSequence Analysis

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP54764.
PaxDbiP54764.
PeptideAtlasiP54764.
PRIDEiP54764.

PTM databases

PhosphoSiteiP54764.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiP54764.
CleanExiHS_EPHA4.
ExpressionAtlasiP54764. baseline and differential.
GenevisibleiP54764. HS.

Organism-specific databases

HPAiCAB028368.

Interactioni

Subunit structurei

Heterotetramer upon binding of the ligand. The heterotetramer is composed of an ephrin dimer and a receptor dimer. Oligomerization is probably required to induce biological responses. Interacts (phosphorylated at position Tyr-602) with FYN. Interacts with CDK5, CDK5R1 and NGEF; upon activation by EFNA1 induces NGEF phosphorylation by the kinase CDK5. Interacts with CHN1; effector of EPHA4 in axon guidance linking EPHA4 activation to RAC1 regulation (By similarity). Interacts (via PDZ motif) with SIPA1L1 (via PDZ domain); controls neuronal morphology through regulation of the RAP1 (RAP1A or RAP1B) and RAP2 (RAP2A, RAP2B or RAP2C) GTPases.By similarity3 Publications

Protein-protein interaction databases

BioGridi108357. 31 interactions.
DIPiDIP-48294N.
IntActiP54764. 2 interactions.
STRINGi9606.ENSP00000281821.

Structurei

Secondary structure

1
986
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi30 – 356Combined sources
Helixi36 – 383Combined sources
Turni40 – 423Combined sources
Beta strandi46 – 6217Combined sources
Beta strandi65 – 739Combined sources
Beta strandi76 – 783Combined sources
Beta strandi82 – 854Combined sources
Beta strandi93 – 964Combined sources
Beta strandi97 – 1059Combined sources
Helixi108 – 1103Combined sources
Turni115 – 1173Combined sources
Beta strandi120 – 13011Combined sources
Beta strandi131 – 1333Combined sources
Helixi139 – 1413Combined sources
Beta strandi143 – 1497Combined sources
Beta strandi154 – 1574Combined sources
Turni159 – 1624Combined sources
Beta strandi164 – 17310Combined sources
Beta strandi178 – 18912Combined sources
Beta strandi191 – 20212Combined sources
Beta strandi207 – 2093Combined sources
Beta strandi212 – 2143Combined sources
Beta strandi226 – 2305Combined sources
Beta strandi237 – 24812Combined sources
Beta strandi257 – 2626Combined sources
Beta strandi266 – 2694Combined sources
Beta strandi272 – 2754Combined sources
Beta strandi304 – 3063Combined sources
Beta strandi333 – 3408Combined sources
Beta strandi343 – 3497Combined sources
Beta strandi361 – 3688Combined sources
Turni373 – 3753Combined sources
Beta strandi385 – 3884Combined sources
Beta strandi390 – 3934Combined sources
Beta strandi395 – 4017Combined sources
Beta strandi405 – 41612Combined sources
Beta strandi418 – 4236Combined sources
Helixi426 – 4283Combined sources
Beta strandi429 – 4357Combined sources
Beta strandi447 – 4526Combined sources
Beta strandi457 – 4615Combined sources
Beta strandi473 – 48311Combined sources
Beta strandi489 – 50012Combined sources
Beta strandi508 – 51710Combined sources
Beta strandi528 – 5314Combined sources
Turni538 – 5403Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2LW8NMR-A29-209[»]
2WO1X-ray1.85A/B30-202[»]
2WO2X-ray2.45A30-202[»]
2WO3X-ray2.35A30-202[»]
3CKHX-ray2.80A/B29-209[»]
3GXUX-ray2.50A29-203[»]
4BK4X-ray3.65A/B20-547[»]
4BK5X-ray4.00A20-547[»]
4BKAX-ray5.30A20-547[»]
4BKFX-ray4.65A/B20-547[»]
4M4PX-ray2.08A27-543[»]
4M4RX-ray3.13A/C/E/G27-543[»]
4W4ZX-ray2.41A/B/C/D29-204[»]
4W50X-ray2.42A/B/C/D29-204[»]
ProteinModelPortaliP54764.
SMRiP54764. Positions 27-981.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP54764.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini30 – 209180Eph LBDPROSITE-ProRule annotationAdd
BLAST
Domaini328 – 439112Fibronectin type-III 1PROSITE-ProRule annotationAdd
BLAST
Domaini440 – 53798Fibronectin type-III 2PROSITE-ProRule annotationAdd
BLAST
Domaini621 – 882262Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini911 – 97565SAMPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi984 – 9863PDZ-bindingSequence Analysis

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi191 – 325135Cys-richAdd
BLAST

Domaini

The protein kinase domain mediates interaction with NGEF.By similarity

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.PROSITE-ProRule annotation
Contains 1 Eph LBD (Eph ligand-binding) domain.PROSITE-ProRule annotation
Contains 2 fibronectin type-III domains.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 SAM (sterile alpha motif) domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118975.
HOGENOMiHOG000233856.
HOVERGENiHBG062180.
InParanoidiP54764.
KOiK05105.
OMAiDWIPREG.
PhylomeDBiP54764.
TreeFamiTF315608.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
2.60.120.260. 1 hit.
2.60.40.10. 2 hits.
InterProiIPR027936. Eph_TM.
IPR030602. EphA4.
IPR001090. Ephrin_rcpt_lig-bd_dom.
IPR003961. FN3_dom.
IPR008979. Galactose-bd-like.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR011510. SAM_2.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016257. Tyr_kinase_ephrin_rcpt.
IPR001426. Tyr_kinase_rcpt_V_CS.
[Graphical view]
PANTHERiPTHR24416:SF25. PTHR24416:SF25. 1 hit.
PfamiPF14575. EphA2_TM. 1 hit.
PF01404. Ephrin_lbd. 1 hit.
PF00041. fn3. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
PF07647. SAM_2. 1 hit.
[Graphical view]
PIRSFiPIRSF000666. TyrPK_ephrin_receptor. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00615. EPH_lbd. 1 hit.
SM00060. FN3. 2 hits.
SM00454. SAM. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
SSF49265. SSF49265. 1 hit.
SSF49785. SSF49785. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51550. 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.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P54764-1) [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
MAGIFYFALF SCLFGICDAV TGSRVYPANE VTLLDSRSVQ GELGWIASPL
60 70 80 90 100
EGGWEEVSIM DEKNTPIRTY QVCNVMEPSQ NNWLRTDWIT REGAQRVYIE
110 120 130 140 150
IKFTLRDCNS LPGVMGTCKE TFNLYYYESD NDKERFIREN QFVKIDTIAA
160 170 180 190 200
DESFTQVDIG DRIMKLNTEI RDVGPLSKKG FYLAFQDVGA CIALVSVRVF
210 220 230 240 250
YKKCPLTVRN LAQFPDTITG ADTSSLVEVR GSCVNNSEEK DVPKMYCGAD
260 270 280 290 300
GEWLVPIGNC LCNAGHEERS GECQACKIGY YKALSTDATC AKCPPHSYSV
310 320 330 340 350
WEGATSCTCD RGFFRADNDA ASMPCTRPPS APLNLISNVN ETSVNLEWSS
360 370 380 390 400
PQNTGGRQDI SYNVVCKKCG AGDPSKCRPC GSGVHYTPQQ NGLKTTKVSI
410 420 430 440 450
TDLLAHTNYT FEIWAVNGVS KYNPNPDQSV SVTVTTNQAA PSSIALVQAK
460 470 480 490 500
EVTRYSVALA WLEPDRPNGV ILEYEVKYYE KDQNERSYRI VRTAARNTDI
510 520 530 540 550
KGLNPLTSYV FHVRARTAAG YGDFSEPLEV TTNTVPSRII GDGANSTVLL
560 570 580 590 600
VSVSGSVVLV VILIAAFVIS RRRSKYSKAK QEADEEKHLN QGVRTYVDPF
610 620 630 640 650
TYEDPNQAVR EFAKEIDASC IKIEKVIGVG EFGEVCSGRL KVPGKREICV
660 670 680 690 700
AIKTLKAGYT DKQRRDFLSE ASIMGQFDHP NIIHLEGVVT KCKPVMIITE
710 720 730 740 750
YMENGSLDAF LRKNDGRFTV IQLVGMLRGI GSGMKYLSDM SYVHRDLAAR
760 770 780 790 800
NILVNSNLVC KVSDFGMSRV LEDDPEAAYT TRGGKIPIRW TAPEAIAYRK
810 820 830 840 850
FTSASDVWSY GIVMWEVMSY GERPYWDMSN QDVIKAIEEG YRLPPPMDCP
860 870 880 890 900
IALHQLMLDC WQKERSDRPK FGQIVNMLDK LIRNPNSLKR TGTESSRPNT
910 920 930 940 950
ALLDPSSPEF SAVVSVGDWL QAIKMDRYKD NFTAAGYTTL EAVVHVNQED
960 970 980
LARIGITAIT HQNKILSSVQ AMRTQMQQMH GRMVPV
Length:986
Mass (Da):109,860
Last modified:October 1, 1996 - v1
Checksum:i0C39C1152EDDD46F
GO
Isoform 2 (identifier: P54764-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-53: MAGIFYFALFSCLFGICDAVTGSRVYPANEVTLLDSRSVQGELGWIASPLEGG → MK

Note: No experimental confirmation available.
Show »
Length:935
Mass (Da):104,507
Checksum:i588D6FDA5FCCDCE4
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti71 – 711Q → P in BAF82995 (PubMed:14702039).Curated
Sequence conflicti102 – 1021K → R in BAF82995 (PubMed:14702039).Curated
Sequence conflicti137 – 1371I → V in BAG35298 (PubMed:14702039).Curated
Sequence conflicti362 – 3621Y → H in BAF82995 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti269 – 2691R → Q.1 Publication
Corresponds to variant rs35084379 [ dbSNP | Ensembl ].
VAR_042135
Natural varianti370 – 3701G → E in a bladder carcinoma NOS sample; somatic mutation. 1 Publication
VAR_042136
Natural varianti399 – 3991S → F in a metastatic melanoma sample; somatic mutation. 1 Publication
VAR_042137
Natural varianti953 – 9531R → K.
Corresponds to variant rs35341687 [ dbSNP | Ensembl ].
VAR_049721

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 5353MAGIF…PLEGG → MK in isoform 2. 1 PublicationVSP_056016Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L36645 mRNA. Translation: AAA74246.1.
AK290306 mRNA. Translation: BAF82995.1.
AK300772 mRNA. Translation: BAH13344.1.
AK312380 mRNA. Translation: BAG35298.1.
AC010899 Genomic DNA. No translation available.
AC079834 Genomic DNA. No translation available.
BC105000 mRNA. Translation: AAI05001.1.
BC105002 mRNA. Translation: AAI05003.1.
CCDSiCCDS2447.1. [P54764-1]
PIRiI78844.
RefSeqiNP_004429.1. NM_004438.4. [P54764-1]
UniGeneiHs.371218.

Genome annotation databases

EnsembliENST00000281821; ENSP00000281821; ENSG00000116106. [P54764-1]
ENST00000409938; ENSP00000386829; ENSG00000116106. [P54764-1]
GeneIDi2043.
KEGGihsa:2043.
UCSCiuc002vmq.3. human. [P54764-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L36645 mRNA. Translation: AAA74246.1.
AK290306 mRNA. Translation: BAF82995.1.
AK300772 mRNA. Translation: BAH13344.1.
AK312380 mRNA. Translation: BAG35298.1.
AC010899 Genomic DNA. No translation available.
AC079834 Genomic DNA. No translation available.
BC105000 mRNA. Translation: AAI05001.1.
BC105002 mRNA. Translation: AAI05003.1.
CCDSiCCDS2447.1. [P54764-1]
PIRiI78844.
RefSeqiNP_004429.1. NM_004438.4. [P54764-1]
UniGeneiHs.371218.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2LW8NMR-A29-209[»]
2WO1X-ray1.85A/B30-202[»]
2WO2X-ray2.45A30-202[»]
2WO3X-ray2.35A30-202[»]
3CKHX-ray2.80A/B29-209[»]
3GXUX-ray2.50A29-203[»]
4BK4X-ray3.65A/B20-547[»]
4BK5X-ray4.00A20-547[»]
4BKAX-ray5.30A20-547[»]
4BKFX-ray4.65A/B20-547[»]
4M4PX-ray2.08A27-543[»]
4M4RX-ray3.13A/C/E/G27-543[»]
4W4ZX-ray2.41A/B/C/D29-204[»]
4W50X-ray2.42A/B/C/D29-204[»]
ProteinModelPortaliP54764.
SMRiP54764. Positions 27-981.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108357. 31 interactions.
DIPiDIP-48294N.
IntActiP54764. 2 interactions.
STRINGi9606.ENSP00000281821.

Chemistry

BindingDBiP54764.
ChEMBLiCHEMBL3988.
GuidetoPHARMACOLOGYi1824.

PTM databases

PhosphoSiteiP54764.

Polymorphism and mutation databases

BioMutaiEPHA4.
DMDMi1711371.

Proteomic databases

MaxQBiP54764.
PaxDbiP54764.
PeptideAtlasiP54764.
PRIDEiP54764.

Protocols and materials databases

DNASUi2043.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000281821; ENSP00000281821; ENSG00000116106. [P54764-1]
ENST00000409938; ENSP00000386829; ENSG00000116106. [P54764-1]
GeneIDi2043.
KEGGihsa:2043.
UCSCiuc002vmq.3. human. [P54764-1]

Organism-specific databases

CTDi2043.
GeneCardsiGC02M222248.
HGNCiHGNC:3388. EPHA4.
HPAiCAB028368.
MIMi602188. gene.
neXtProtiNX_P54764.
PharmGKBiPA27820.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118975.
HOGENOMiHOG000233856.
HOVERGENiHBG062180.
InParanoidiP54764.
KOiK05105.
OMAiDWIPREG.
PhylomeDBiP54764.
TreeFamiTF315608.

Enzyme and pathway databases

BRENDAi2.7.10.1. 2681.
ReactomeiREACT_264068. EPH-Ephrin signaling.
REACT_264198. EPH-ephrin mediated repulsion of cells.
REACT_264548. EPHA-mediated growth cone collapse.
SignaLinkiP54764.

Miscellaneous databases

ChiTaRSiEPHA4. human.
EvolutionaryTraceiP54764.
GeneWikiiEPH_receptor_A4.
GenomeRNAii2043.
NextBioi35463929.
PROiP54764.
SOURCEiSearch...

Gene expression databases

BgeeiP54764.
CleanExiHS_EPHA4.
ExpressionAtlasiP54764. baseline and differential.
GenevisibleiP54764. HS.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
2.60.120.260. 1 hit.
2.60.40.10. 2 hits.
InterProiIPR027936. Eph_TM.
IPR030602. EphA4.
IPR001090. Ephrin_rcpt_lig-bd_dom.
IPR003961. FN3_dom.
IPR008979. Galactose-bd-like.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR011510. SAM_2.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016257. Tyr_kinase_ephrin_rcpt.
IPR001426. Tyr_kinase_rcpt_V_CS.
[Graphical view]
PANTHERiPTHR24416:SF25. PTHR24416:SF25. 1 hit.
PfamiPF14575. EphA2_TM. 1 hit.
PF01404. Ephrin_lbd. 1 hit.
PF00041. fn3. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
PF07647. SAM_2. 1 hit.
[Graphical view]
PIRSFiPIRSF000666. TyrPK_ephrin_receptor. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00615. EPH_lbd. 1 hit.
SM00060. FN3. 2 hits.
SM00454. SAM. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
SSF49265. SSF49265. 1 hit.
SSF49785. SSF49785. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51550. 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.
[Graphical view]
ProtoNetiSearch...

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  1. "cDNA cloning and tissue distribution of five human EPH-like receptor protein-tyrosine kinases."
    Fox G.M., Holst P.L., Chute H.T., Lindberg R.A., Janssen A.M., Basu R., Welcher A.A.
    Oncogene 10:897-905(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Fetal brain.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Tissue: Amygdala and Tongue.
  3. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
    Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
    , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
    Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Brain.
  5. "Unified nomenclature for Eph family receptors and their ligands, the ephrins."
    Eph nomenclature committee
    Cell 90:403-404(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NOMENCLATURE.
  6. "The EphA4 receptor regulates neuronal morphology through SPAR-mediated inactivation of Rap GTPases."
    Richter M., Murai K.K., Bourgin C., Pak D.T., Pasquale E.B.
    J. Neurosci. 27:14205-14215(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SIPA1L1.
  7. "Cdk5 regulates EphA4-mediated dendritic spine retraction through an ephexin1-dependent mechanism."
    Fu W.Y., Chen Y., Sahin M., Zhao X.S., Shi L., Bikoff J.B., Lai K.O., Yung W.H., Fu A.K., Greenberg M.E., Ip N.Y.
    Nat. Neurosci. 10:67-76(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF CDK5, AUTOPHOSPHORYLATION.
  8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  9. "Crystal structure and NMR binding reveal that two small molecule antagonists target the high affinity ephrin-binding channel of the EphA4 receptor."
    Qin H., Shi J., Noberini R., Pasquale E.B., Song J.
    J. Biol. Chem. 283:29473-29484(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 29-209.
  10. "Structural plasticity of EPH receptor A4 facilitates cross-class ephrin signaling."
    Bowden T.A., Aricescu A.R., Nettleship J.E., Siebold C., Rahman-Huq N., Owens R.J., Stuart D.I., Jones E.Y.
    Structure 17:1386-1397(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 30-202 IN COMPLEX WITH EFNA2 OR EFNB2, LIGAND-BINDING.
  11. "Structural characterization of the EphA4-Ephrin-B2 complex reveals new features enabling Eph-ephrin binding promiscuity."
    Qin H., Noberini R., Huan X., Shi J., Pasquale E.B., Song J.
    J. Biol. Chem. 285:644-654(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 29-203 IN COMPLEX WITH EFNB2, MUTAGENESIS OF GLN-40 AND GLU-42.
  12. "Patterns of somatic mutation in human cancer genomes."
    Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
    , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
    Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLN-269; GLU-370 AND PHE-399.

Entry informationi

Entry nameiEPHA4_HUMAN
AccessioniPrimary (citable) accession number: P54764
Secondary accession number(s): A8K2P1
, B2R601, B7Z6Q8, Q2M380
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: June 24, 2015
This is version 164 of the entry and version 1 of the sequence. [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 2
    Human chromosome 2: 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

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.