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Q9UF33 (EPHA6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:EPHA6
Synonyms:EHK2, HEK12
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1036 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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.

Catalytic activity

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

Subunit structure

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.

Subcellular location

Membrane; Single-pass type I membrane protein By similarity.

Tissue specificity

Expressed in brain and testis. Ref.3

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.

Contains 1 Eph LBD (Eph ligand-binding) domain.

Contains 2 fibronectin type-III domains.

Contains 1 protein kinase domain.

Contains 1 SAM (sterile alpha motif) domain.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9UF33-1)

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.
Isoform 2 (identifier: Q9UF33-2)

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.
Isoform 3 (identifier: Q9UF33-3)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Chain23 – 10361014Ephrin type-A receptor 6
PRO_0000235684

Regions

Topological domain23 – 550528Extracellular Potential
Transmembrane551 – 57121Helical; Potential
Topological domain572 – 1036465Cytoplasmic Potential
Domain34 – 212179Eph LBD
Domain331 – 441111Fibronectin type-III 1
Domain442 – 53796Fibronectin type-III 2
Domain631 – 944314Protein kinase
Domain961 – 102565SAM
Nucleotide binding637 – 6459ATP By similarity
Motif1034 – 10363PDZ-binding Potential

Sites

Active site7981Proton acceptor By similarity
Binding site6631ATP By similarity

Amino acid modifications

Modified residue6061Phosphotyrosine; by autocatalysis Potential
Modified residue6121Phosphotyrosine; by autocatalysis Potential
Modified residue8311Phosphotyrosine; by autocatalysis Potential
Modified residue9781Phosphotyrosine; by autocatalysis Potential
Glycosylation3431N-linked (GlcNAc...) Potential
Glycosylation3971N-linked (GlcNAc...) Potential
Glycosylation4101N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 514514Missing in isoform 2 and isoform 3.
VSP_018473
Alternative sequence515 – 53824IRVRT…TGDET → MKDSPFQVTKLYWLNEKWDF IASA in isoform 2 and isoform 3.
VSP_018474
Alternative sequence835 – 91278GGKIP…LMLHC → RPTNHNKEQSELVKEDGLES LCEQCESSSGYGTGLVLMWK RNRRAMGASGQTRKQCDKRD NPPTDLFQTLTLNLCYSA in isoform 3.
VSP_054716
Alternative sequence835 – 84814GGKIP…APEAI → DLFQTLTLNLCYSA in isoform 2.
VSP_018475
Alternative sequence849 – 1036188Missing in isoform 2.
VSP_018476
Alternative sequence913 – 1036124Missing in isoform 3.
VSP_054717
Natural variant7041F → S. Ref.4
VAR_042149
Natural variant7111A → V.
Corresponds to variant rs4857276 [ dbSNP | Ensembl ].
VAR_055991

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 14, 2014. Version 3.
Checksum: 53402C6DCD7CD32C

FASTA1,036116,379
        10         20         30         40         50         60 
MGGCEVREFL LQFGFFLPLL TAWPGDCSHV SNNQVVLLDT TTVLGELGWK TYPLNGWDAI 

        70         80         90        100        110        120 
TEMDEHNRPI HTYQVCNVME PNQNNWLRTN WISRDAAQKI YVEMKFTLRD CNSIPWVLGT 

       130        140        150        160        170        180 
CKETFNLFYM ESDESHGIKF KPNQYTKIDT IAADESFTQM DLGDRILKLN TEIREVGPIE 

       190        200        210        220        230        240 
RKGFYLAFQD IGACIALVSV RVFYKKCPFT VRNLAMFPDT IPRVDSSSLV EVRGSCVKSA 

       250        260        270        280        290        300 
EERDTPKLYC GADGDWLVPL GRCICSTGYE EIEGSCHACR PGFYKAFAGN TKCSKCPPHS 

       310        320        330        340        350        360 
LTYMEATSVC QCEKGYFRAE KDPPSMACTR PPSAPRNVVF NINETALILE WSPPSDTGGR 

       370        380        390        400        410        420 
KDLTYSVICK KCGLDTSQCE DCGGGLRFIP RHTGLINNSV IVLDFVSHVN YTFEIEAMNG 

       430        440        450        460        470        480 
VSELSFSPKP FTAITVTTDQ DAPSLIGVVR KDWASQNSIA LSWQAPAFSN GAILDYEIKY 

       490        500        510        520        530        540 
YEKEHEQLTY SSTRSKAPSV IITGLKPATK YVFHIRVRTA TGYSGYSQKF EFETGDETSD 

       550        560        570        580        590        600 
MAAEQGQILV IATAAVGGFT LLVILTLFFL ITGRCQWYIK AKMKSEEKRR NHLQNGHLRF 

       610        620        630        640        650        660 
PGIKTYIDPD TYEDPSLAVH EFAKEIDPSR IRIERVIGAG EFGEVCSGRL KTPGKREIPV 

       670        680        690        700        710        720 
AIKTLKGGHM DRQRRDFLRE ASIMGQFDHP NIIRLEGVVT KRSFPAIGVE AFCPSFLRAG 

       730        740        750        760        770        780 
FLNSIQAPHP VPGGGSLPPR IPAGRPVMIV VEYMENGSLD SFLRKHDGHF TVIQLVGMLR 

       790        800        810        820        830        840 
GIASGMKYLS DMGYVHRDLA ARNILVNSNL VCKVSDFGLS RVLEDDPEAA YTTTGGKIPI 

       850        860        870        880        890        900 
RWTAPEAIAY RKFSSASDAW SYGIVMWEVM SYGERPYWEM SNQDVILSIE EGYRLPAPMG 

       910        920        930        940        950        960 
CPASLHQLML HCWQKERNHR PKFTDIVSFL DKLIRNPSAL HTLVEDILVM PESPGEVPEY 

       970        980        990       1000       1010       1020 
PLFVTVGDWL DSIKMGQYKN NFVAAGFTTF DLISRMSIDD IRRIGVILIG HQRRIVSSIQ 

      1030 
TLRLHMMHIQ EKGFHV 

« Hide

Isoform 2 [UniParc].

Checksum: DF89BC8423AC1A60
Show »

FASTA33437,274
Isoform 3 [UniParc].

Checksum: 6A414ED81CCC5C47
Show »

FASTA39844,466

References

« Hide 'large scale' references
[1]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Testis.
[2]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"Differential gene expression of Eph receptors and ephrins in benign human tissues and cancers."
Hafner C., Schmitz G., Meyer S., Bataille F., Hau P., Langmann T., Dietmaier W., Landthaler M., Vogt T.
Clin. Chem. 50:490-499(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[4]"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. expand/collapse author list , 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: VARIANT [LARGE SCALE ANALYSIS] SER-704.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS54616.1. [Q9UF33-2]
PIRT43450.
RefSeqNP_001265229.1. NM_001278300.1. [Q9UF33-3]
NP_775926.1. NM_173655.3. [Q9UF33-2]
UniGeneHs.653244.

3D structure databases

ProteinModelPortalQ9UF33.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid130049. 1 interaction.
STRING9606.ENSP00000374323.

Chemistry

BindingDBQ9UF33.
ChEMBLCHEMBL2363043.
GuidetoPHARMACOLOGY1826.

PTM databases

PhosphoSiteQ9UF33.

Polymorphism databases

DMDM97048747.

Proteomic databases

PaxDbQ9UF33.
PRIDEQ9UF33.

Protocols and materials databases

DNASU285220.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000502694; ENSP00000423950; ENSG00000080224.
ENST00000514100; ENSP00000421711; ENSG00000080224.
GeneID285220.
KEGGhsa:285220.
UCSCuc010how.1. human. [Q9UF33-1]

Organism-specific databases

CTD285220.
GeneCardsGC03P096533.
HGNCHGNC:19296. EPHA6.
HPAHPA007397.
HPA058047.
MIM600066. gene.
neXtProtNX_Q9UF33.
PharmGKBPA134866684.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233858.
HOVERGENHBG062180.
InParanoidQ9UF33.
KOK05107.
OrthoDBEOG7VTDM6.
PhylomeDBQ9UF33.

Enzyme and pathway databases

SignaLinkQ9UF33.

Gene expression databases

ArrayExpressQ9UF33.
BgeeQ9UF33.
CleanExHS_EPHA6.
GenevestigatorQ9UF33.

Family and domain databases

Gene3D1.10.150.50. 1 hit.
2.60.120.260. 1 hit.
2.60.40.10. 2 hits.
InterProIPR027936. Eph_TM.
IPR001090. Ephrin_rcpt_lig-bd_dom.
IPR003961. Fibronectin_type3.
IPR008979. Galactose-bd-like.
IPR009030. Growth_fac_rcpt_N_dom.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR021129. SAM_type1.
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]
PfamPF14575. 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]
PIRSFPIRSF000666. TyrPK_ephrin_receptor. 1 hit.
PRINTSPR00109. TYRKINASE.
SMARTSM00615. EPH_lbd. 1 hit.
SM00060. FN3. 2 hits.
SM00454. SAM. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF47769. SSF47769. 1 hit.
SSF49265. SSF49265. 1 hit.
SSF49785. SSF49785. 1 hit.
SSF56112. SSF56112. 2 hits.
SSF57184. SSF57184. 2 hits.
PROSITEPS51550. 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]
ProtoNetSearch...

Other

GeneWikiEPHA6.
GenomeRNAi285220.
NextBio35493297.
PROQ9UF33.
SOURCESearch...

Entry information

Entry nameEPHA6_HUMAN
AccessionPrimary (citable) accession number: Q9UF33
Secondary accession number(s): D6RAL5
Entry history
Integrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: May 14, 2014
Last modified: July 9, 2014
This is version 117 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM