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Protein

Ephrin type-A receptor 6

Gene

EPHA6

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

Functioni

Receptor tyrosine kinase which binds promiscuously GPI-anchored 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 (By similarity).By similarity

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei663ATPPROSITE-ProRule annotation1
Active sitei798Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi637 – 645ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS01350-MONOMER.
ReactomeiR-HSA-2682334. EPH-Ephrin signaling.
R-HSA-3928663. EPHA-mediated growth cone collapse.
R-HSA-3928665. EPH-ephrin mediated repulsion of cells.
SignaLinkiQ9UF33.
SIGNORiQ9UF33.

Names & Taxonomyi

Protein namesi
Recommended name:
Ephrin type-A receptor 6 (EC:2.7.10.1)
Alternative name(s):
EPH homology kinase 2
Short name:
EHK-2
EPH-like kinase 12
Short name:
EK12
Gene namesi
Name:EPHA6
Synonyms:EHK2, HEK12
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:19296. EPHA6.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini23 – 550ExtracellularSequence analysisAdd BLAST528
Transmembranei551 – 571HelicalSequence analysisAdd BLAST21
Topological domaini572 – 1036CytoplasmicSequence analysisAdd BLAST465

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi285220.
OpenTargetsiENSG00000080224.
PharmGKBiPA134866684.

Chemistry databases

ChEMBLiCHEMBL4526.
GuidetoPHARMACOLOGYi1826.

Polymorphism and mutation databases

DMDMi97048747.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
ChainiPRO_000023568423 – 1036Ephrin type-A receptor 6Add BLAST1014

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi343N-linked (GlcNAc...)Sequence analysis1
Glycosylationi397N-linked (GlcNAc...)Sequence analysis1
Glycosylationi410N-linked (GlcNAc...)Sequence analysis1
Modified residuei606Phosphotyrosine; by autocatalysisSequence analysis1
Modified residuei612Phosphotyrosine; by autocatalysisSequence analysis1
Modified residuei831Phosphotyrosine; by autocatalysisSequence analysis1
Modified residuei978Phosphotyrosine; by autocatalysisSequence analysis1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ9UF33.
PaxDbiQ9UF33.
PeptideAtlasiQ9UF33.
PRIDEiQ9UF33.

PTM databases

iPTMnetiQ9UF33.
PhosphoSitePlusiQ9UF33.

Expressioni

Tissue specificityi

Expressed in brain and testis.1 Publication

Gene expression databases

BgeeiENSG00000080224.
CleanExiHS_EPHA6.
ExpressionAtlasiQ9UF33. baseline and differential.
GenevisibleiQ9UF33. HS.

Organism-specific databases

HPAiHPA007397.
HPA058047.

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 (By similarity).By similarity

Protein-protein interaction databases

BioGridi130049. 3 interactors.
STRINGi9606.ENSP00000374323.

Chemistry databases

BindingDBiQ9UF33.

Structurei

3D structure databases

ProteinModelPortaliQ9UF33.
SMRiQ9UF33.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini34 – 212Eph LBDPROSITE-ProRule annotationAdd BLAST179
Domaini331 – 441Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST111
Domaini442 – 537Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST96
Domaini631 – 944Protein kinasePROSITE-ProRule annotationAdd BLAST314
Domaini961 – 1025SAMPROSITE-ProRule annotationAdd BLAST65

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1034 – 1036PDZ-bindingSequence analysis3

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

eggNOGiKOG0196. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118975.
HOGENOMiHOG000233858.
HOVERGENiHBG062180.
InParanoidiQ9UF33.
KOiK05107.

Family and domain databases

CDDicd00063. FN3. 2 hits.
Gene3Di1.10.150.50. 1 hit.
2.60.120.260. 1 hit.
2.60.40.10. 2 hits.
InterProiIPR027936. Eph_TM.
IPR001090. Ephrin_rcpt_lig-bd_dom.
IPR003961. FN3_dom.
IPR008979. Galactose-bd-like.
IPR009030. Growth_fac_rcpt_.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001660. SAM.
IPR013761. SAM/pointed.
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.
[Graphical view]
PfamiPF14575. EphA2_TM. 1 hit.
PF01404. Ephrin_lbd. 1 hit.
PF00041. fn3. 2 hits.
PF07714. Pkinase_Tyr. 2 hits.
PF00536. SAM_1. 1 hit.
[Graphical view]
PIRSFiPIRSF000666. TyrPK_ephrin_receptor. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00615. EPH_lbd. 1 hit.
SM01411. Ephrin_rec_like. 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. 2 hits.
SSF57184. SSF57184. 2 hits.
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 (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: Q9UF33-1) [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
MGGCEVREFL LQFGFFLPLL TAWPGDCSHV SNNQVVLLDT TTVLGELGWK
60 70 80 90 100
TYPLNGWDAI TEMDEHNRPI HTYQVCNVME PNQNNWLRTN WISRDAAQKI
110 120 130 140 150
YVEMKFTLRD CNSIPWVLGT CKETFNLFYM ESDESHGIKF KPNQYTKIDT
160 170 180 190 200
IAADESFTQM DLGDRILKLN TEIREVGPIE RKGFYLAFQD IGACIALVSV
210 220 230 240 250
RVFYKKCPFT VRNLAMFPDT IPRVDSSSLV EVRGSCVKSA EERDTPKLYC
260 270 280 290 300
GADGDWLVPL GRCICSTGYE EIEGSCHACR PGFYKAFAGN TKCSKCPPHS
310 320 330 340 350
LTYMEATSVC QCEKGYFRAE KDPPSMACTR PPSAPRNVVF NINETALILE
360 370 380 390 400
WSPPSDTGGR KDLTYSVICK KCGLDTSQCE DCGGGLRFIP RHTGLINNSV
410 420 430 440 450
IVLDFVSHVN YTFEIEAMNG VSELSFSPKP FTAITVTTDQ DAPSLIGVVR
460 470 480 490 500
KDWASQNSIA LSWQAPAFSN GAILDYEIKY YEKEHEQLTY SSTRSKAPSV
510 520 530 540 550
IITGLKPATK YVFHIRVRTA TGYSGYSQKF EFETGDETSD MAAEQGQILV
560 570 580 590 600
IATAAVGGFT LLVILTLFFL ITGRCQWYIK AKMKSEEKRR NHLQNGHLRF
610 620 630 640 650
PGIKTYIDPD TYEDPSLAVH EFAKEIDPSR IRIERVIGAG EFGEVCSGRL
660 670 680 690 700
KTPGKREIPV AIKTLKGGHM DRQRRDFLRE ASIMGQFDHP NIIRLEGVVT
710 720 730 740 750
KRSFPAIGVE AFCPSFLRAG FLNSIQAPHP VPGGGSLPPR IPAGRPVMIV
760 770 780 790 800
VEYMENGSLD SFLRKHDGHF TVIQLVGMLR GIASGMKYLS DMGYVHRDLA
810 820 830 840 850
ARNILVNSNL VCKVSDFGLS RVLEDDPEAA YTTTGGKIPI RWTAPEAIAY
860 870 880 890 900
RKFSSASDAW SYGIVMWEVM SYGERPYWEM SNQDVILSIE EGYRLPAPMG
910 920 930 940 950
CPASLHQLML HCWQKERNHR PKFTDIVSFL DKLIRNPSAL HTLVEDILVM
960 970 980 990 1000
PESPGEVPEY PLFVTVGDWL DSIKMGQYKN NFVAAGFTTF DLISRMSIDD
1010 1020 1030
IRRIGVILIG HQRRIVSSIQ TLRLHMMHIQ EKGFHV
Length:1,036
Mass (Da):116,379
Last modified:May 14, 2014 - v3
Checksum:i53402C6DCD7CD32C
GO
Isoform 2 (identifier: Q9UF33-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-514: Missing.
     515-538: IRVRTATGYSGYSQKFEFETGDET → MKDSPFQVTKLYWLNEKWDFIASA
     835-848: GGKIPIRWTAPEAI → DLFQTLTLNLCYSA
     849-1036: Missing.

Show »
Length:334
Mass (Da):37,274
Checksum:iDF89BC8423AC1A60
GO
Isoform 3 (identifier: Q9UF33-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-514: Missing.
     515-538: IRVRTATGYSGYSQKFEFETGDET → MKDSPFQVTKLYWLNEKWDFIASA
     835-912: GGKIPIRWTA...ASLHQLMLHC → RPTNHNKEQS...TLTLNLCYSA
     913-1036: Missing.

Show »
Length:398
Mass (Da):44,466
Checksum:i6A414ED81CCC5C47
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_042149704F → S.1 Publication1
Natural variantiVAR_055991711A → V.Corresponds to variant rs4857276dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0184731 – 514Missing in isoform 2 and isoform 3. 1 PublicationAdd BLAST514
Alternative sequenceiVSP_018474515 – 538IRVRT…TGDET → MKDSPFQVTKLYWLNEKWDF IASA in isoform 2 and isoform 3. 1 PublicationAdd BLAST24
Alternative sequenceiVSP_054716835 – 912GGKIP…LMLHC → RPTNHNKEQSELVKEDGLES LCEQCESSSGYGTGLVLMWK RNRRAMGASGQTRKQCDKRD NPPTDLFQTLTLNLCYSA in isoform 3. CuratedAdd BLAST78
Alternative sequenceiVSP_018475835 – 848GGKIP…APEAI → DLFQTLTLNLCYSA in isoform 2. 1 PublicationAdd BLAST14
Alternative sequenceiVSP_018476849 – 1036Missing in isoform 2. 1 PublicationAdd BLAST188
Alternative sequenceiVSP_054717913 – 1036Missing in isoform 3. CuratedAdd BLAST124

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL133666 mRNA. Translation: CAB63775.1.
AC109782 Genomic DNA. No translation available.
AC108714 Genomic DNA. No translation available.
AC110717 Genomic DNA. No translation available.
AC134730 Genomic DNA. No translation available.
AC135369 Genomic DNA. No translation available.
AC119745 Genomic DNA. No translation available.
AC107482 Genomic DNA. No translation available.
AC117470 Genomic DNA. No translation available.
AC130510 Genomic DNA. No translation available.
AC117439 Genomic DNA. No translation available.
CCDSiCCDS54616.1. [Q9UF33-2]
CCDS63697.1. [Q9UF33-3]
PIRiT43450.
RefSeqiNP_001265229.1. NM_001278300.1. [Q9UF33-3]
NP_775926.1. NM_173655.3. [Q9UF33-2]
UniGeneiHs.272208.
Hs.653244.

Genome annotation databases

EnsembliENST00000502694; ENSP00000423950; ENSG00000080224. [Q9UF33-2]
ENST00000514100; ENSP00000421711; ENSG00000080224. [Q9UF33-3]
GeneIDi285220.
KEGGihsa:285220.
UCSCiuc003drr.6. human. [Q9UF33-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL133666 mRNA. Translation: CAB63775.1.
AC109782 Genomic DNA. No translation available.
AC108714 Genomic DNA. No translation available.
AC110717 Genomic DNA. No translation available.
AC134730 Genomic DNA. No translation available.
AC135369 Genomic DNA. No translation available.
AC119745 Genomic DNA. No translation available.
AC107482 Genomic DNA. No translation available.
AC117470 Genomic DNA. No translation available.
AC130510 Genomic DNA. No translation available.
AC117439 Genomic DNA. No translation available.
CCDSiCCDS54616.1. [Q9UF33-2]
CCDS63697.1. [Q9UF33-3]
PIRiT43450.
RefSeqiNP_001265229.1. NM_001278300.1. [Q9UF33-3]
NP_775926.1. NM_173655.3. [Q9UF33-2]
UniGeneiHs.272208.
Hs.653244.

3D structure databases

ProteinModelPortaliQ9UF33.
SMRiQ9UF33.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi130049. 3 interactors.
STRINGi9606.ENSP00000374323.

Chemistry databases

BindingDBiQ9UF33.
ChEMBLiCHEMBL4526.
GuidetoPHARMACOLOGYi1826.

PTM databases

iPTMnetiQ9UF33.
PhosphoSitePlusiQ9UF33.

Polymorphism and mutation databases

DMDMi97048747.

Proteomic databases

EPDiQ9UF33.
PaxDbiQ9UF33.
PeptideAtlasiQ9UF33.
PRIDEiQ9UF33.

Protocols and materials databases

DNASUi285220.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000502694; ENSP00000423950; ENSG00000080224. [Q9UF33-2]
ENST00000514100; ENSP00000421711; ENSG00000080224. [Q9UF33-3]
GeneIDi285220.
KEGGihsa:285220.
UCSCiuc003drr.6. human. [Q9UF33-1]

Organism-specific databases

CTDi285220.
DisGeNETi285220.
GeneCardsiEPHA6.
HGNCiHGNC:19296. EPHA6.
HPAiHPA007397.
HPA058047.
MIMi600066. gene.
neXtProtiNX_Q9UF33.
OpenTargetsiENSG00000080224.
PharmGKBiPA134866684.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0196. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118975.
HOGENOMiHOG000233858.
HOVERGENiHBG062180.
InParanoidiQ9UF33.
KOiK05107.

Enzyme and pathway databases

BioCyciZFISH:HS01350-MONOMER.
ReactomeiR-HSA-2682334. EPH-Ephrin signaling.
R-HSA-3928663. EPHA-mediated growth cone collapse.
R-HSA-3928665. EPH-ephrin mediated repulsion of cells.
SignaLinkiQ9UF33.
SIGNORiQ9UF33.

Miscellaneous databases

ChiTaRSiEPHA6. human.
GeneWikiiEPHA6.
GenomeRNAii285220.
PROiQ9UF33.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000080224.
CleanExiHS_EPHA6.
ExpressionAtlasiQ9UF33. baseline and differential.
GenevisibleiQ9UF33. HS.

Family and domain databases

CDDicd00063. FN3. 2 hits.
Gene3Di1.10.150.50. 1 hit.
2.60.120.260. 1 hit.
2.60.40.10. 2 hits.
InterProiIPR027936. Eph_TM.
IPR001090. Ephrin_rcpt_lig-bd_dom.
IPR003961. FN3_dom.
IPR008979. Galactose-bd-like.
IPR009030. Growth_fac_rcpt_.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001660. SAM.
IPR013761. SAM/pointed.
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.
[Graphical view]
PfamiPF14575. EphA2_TM. 1 hit.
PF01404. Ephrin_lbd. 1 hit.
PF00041. fn3. 2 hits.
PF07714. Pkinase_Tyr. 2 hits.
PF00536. SAM_1. 1 hit.
[Graphical view]
PIRSFiPIRSF000666. TyrPK_ephrin_receptor. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00615. EPH_lbd. 1 hit.
SM01411. Ephrin_rec_like. 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. 2 hits.
SSF57184. SSF57184. 2 hits.
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...

Entry informationi

Entry nameiEPHA6_HUMAN
AccessioniPrimary (citable) accession number: Q9UF33
Secondary accession number(s): D6RAL5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: May 14, 2014
Last modified: November 30, 2016
This is version 140 of the entry and version 3 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: 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. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

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 one 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.