Q9UF33 (EPHA6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	EPHA6
Synonyms:	EHK2, HEK12

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1035 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	integral to plasma membrane Inferred from electronic annotation. Source: InterPro
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ephrin receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 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:
     1-513: Missing.
     514-536: IRVRTATGYSGYSQKFEFETGDE → MKDSPFQVTKLYWLNEKWDFIAS
     834-847: GGKIPIRWTAPEAI → DLFQTLTLNLCYSA
     848-1035: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 22	22	Potential
	Chain	23 – 1035	1013	Ephrin type-A receptor 6		PRO_0000235684
Regions
	Topological domain	23 – 549	527	Extracellular Potential
	Transmembrane	550 – 570	21	Helical; Potential
	Topological domain	571 – 1035	465	Cytoplasmic Potential
	Domain	33 – 211	179	Eph LBD
	Domain	330 – 434	105	Fibronectin type-III 1
	Domain	438 – 533	96	Fibronectin type-III 2
	Domain	630 – 943	314	Protein kinase
	Domain	960 – 1024	65	SAM
	Nucleotide binding	636 – 644	9	ATP By similarity
	Motif	1033 – 1035	3	PDZ-binding Potential
Sites
	Active site	797	1	Proton acceptor By similarity
	Binding site	662	1	ATP By similarity
Amino acid modifications
	Modified residue	605	1	Phosphotyrosine; by autocatalysis Potential
	Modified residue	611	1	Phosphotyrosine; by autocatalysis Potential
	Modified residue	830	1	Phosphotyrosine; by autocatalysis Potential
	Modified residue	977	1	Phosphotyrosine; by autocatalysis Potential
	Glycosylation	342	1	N-linked (GlcNAc...) Potential
	Glycosylation	396	1	N-linked (GlcNAc...) Potential
	Glycosylation	409	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 513	513	Missing in isoform 2.		VSP_018473
	Alternative sequence	514 – 536	23	IRVRT…ETGDE → MKDSPFQVTKLYWLNEKWDF IAS in isoform 2.		VSP_018474
	Alternative sequence	834 – 847	14	GGKIP…APEAI → DLFQTLTLNLCYSA in isoform 2.		VSP_018475
	Alternative sequence	848 – 1035	188	Missing in isoform 2.		VSP_018476
	Natural variant	703	1	F → S. Ref.4		VAR_042149
	Natural variant	710	1	A → V. Corresponds to variant rs4857276 [ dbSNP | Ensembl ].		VAR_055991
Experimental info
	Sequence conflict	597 – 598	2	CK → LR in CAB63775. Ref.1
	Sequence conflict	701	1	S → R in CAB63775. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 16, 2006. Version 2. Checksum: 4D58757D9F4CF178	FASTA	1,035	116,116
	10 20 30 40 50 60 MGGCEVREFL LQFGFFLPLL TAWPGDCSHV SNQVVLLDTT TVLGELGWKT YPLNGWDAIT 70 80 90 100 110 120 EMDEHNRPIH TYQVCNVMEP NQNNWLRTNW ISRDAAQKIY VEMKFTLRDC NSIPWVLGTC 130 140 150 160 170 180 KETFNLFYME SDESHGIKFK PNQYTKIDTI AADESFTQMD LGDRILKLNT EIREVGPIER 190 200 210 220 230 240 KGFYLAFQDI GACIALVSVR VFYKKCPFTV RNLAMFPDTI PRVDSSSLVE VRGSCVKSAE 250 260 270 280 290 300 ERDTPKLYCG ADGDWLVPLG RCICSTGYEE IEGSCHACRP GFYKAFAGNT KCSKCPPHSL 310 320 330 340 350 360 TYMEATSVCQ CEKGYFRAEK DPPSMACTGP PSAPRNVVFN INETALILEW SPPSDTGGRK 370 380 390 400 410 420 DLTYSVICKK CGLDTSQCED CGGGLRFIPR HTGLINNSVI VLDFVSHVNY TFEIEAMNGV 430 440 450 460 470 480 SELSFSPKPF TAITVTTDHD APSLIGMMRK DWASQNSIAL SWQAPAFSNG AILDYEIKYY 490 500 510 520 530 540 EKEHEQLTYS STRSKAPSVI ITGLKPATKY VFHIRVRTAT GYSGYSQKFE FETGDEASDM 550 560 570 580 590 600 AAEQGQILVI ATAAVGGFTL LVILTLFFLI TGRCQWYIKA KMKSEEKRRN HLQNGHCKFP 610 620 630 640 650 660 GIKTYIDPDT YEDPSLAVHE FAKEIDPSRI RIERVIGAGE FGEVCSGRLK TPGKREIPVA 670 680 690 700 710 720 IKTLKGGHMD RQRRDFLREA SIMGQFDHPN IIRLEGVVTK SSFPAIGVEA FCPSFLRAGF 730 740 750 760 770 780 LNSIQAPHPV PGGGSLPPRI PAGRPVMIVV EYMENGSLDS FLRKHDGHFT VIQLVGMLRG 790 800 810 820 830 840 IASGMKYLSD MGYVHRDLAA RNILVNSNLV CKVSDFGLSR VLEDDPEAAY TTTGGKIPIR 850 860 870 880 890 900 WTAPEAIAYR KFSSASDAWS YGIVMWEVMS YGERPYWEMS NQDVILSIEE GYRLPAPMGC 910 920 930 940 950 960 PASLHQLMLH CWQKERNHRP KFTDIVSFLD KLIRNPSALH TLVEDILVMP ESPGEVPEYP 970 980 990 1000 1010 1020 LFVTVGDWLD SIKMGQYKNN FVAAGFTTFD LISRMSIEDI RRIGVILIGH QRRIVSSIQT 1030 LRLHMMHIQE KGFHV
	Isoform 2 [UniParc]. Checksum: DE9F93BC43795CF0	FASTA	334	37,167
	10 20 30 40 50 60 MKDSPFQVTK LYWLNEKWDF IASASDMAAE QGQILVIATA AVGGFTLLVI LTLFFLITGR 70 80 90 100 110 120 CQWYIKAKMK SEEKRRNHLQ NGHCKFPGIK TYIDPDTYED PSLAVHEFAK EIDPSRIRIE 130 140 150 160 170 180 RVIGAGEFGE VCSGRLKTPG KREIPVAIKT LKGGHMDRQR RDFLREASIM GQFDHPNIIR 190 200 210 220 230 240 LEGVVTKSSF PAIGVEAFCP SFLRAGFLNS IQAPHPVPGG GSLPPRIPAG RPVMIVVEYM 250 260 270 280 290 300 ENGSLDSFLR KHDGHFTVIQ LVGMLRGIAS GMKYLSDMGY VHRDLAARNI LVNSNLVCKV 310 320 330 SDFGLSRVLE DDPEAAYTTT DLFQTLTLNL CYSA

References

	« Hide 'large scale' referencesShow '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. , 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. , 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-703.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AL133666 mRNA. Translation: CAB63775.1. AC109782 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.
IPI	IPI00981691. IPI01011681.
PIR	T43450.
RefSeq	NP_775926.1. NM_173655.2.
UniGene	Hs.653244.
3D structure databases
ProteinModelPortal	Q9UF33.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000374323.
PTM databases
PhosphoSite	Q9UF33.
Polymorphism databases
DMDM	97048747.
Proteomic databases
PaxDb	Q9UF33.
PRIDE	Q9UF33.
Protocols and materials databases
DNASU	285220.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000502694; ENSP00000423950; ENSG00000080224.
GeneID	285220.
KEGG	hsa:285220.
UCSC	uc010how.1. human.
Organism-specific databases
CTD	285220.
GeneCards	GC03P096533.
HGNC	HGNC:19296. EPHA6.
HPA	HPA007397.
MIM	600066. gene.
neXtProt	NX_Q9UF33.
PharmGKB	PA134866684.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000233858.
HOVERGEN	HBG062180.
InParanoid	Q9UF33.
KO	K05107.
Enzyme and pathway databases
Pathway_Interaction_DB	epha_fwdpathway. EPHA forward signaling. ephrina_ephapathway. EphrinA-EPHA pathway.
Gene expression databases
ArrayExpress	Q9UF33.
Bgee	Q9UF33.
CleanEx	HS_EPHA6.
Genevestigator	Q9UF33.
GermOnline	ENSG00000080224. Homo sapiens.
Family and domain databases
Gene3D	1.10.150.50. 1 hit. 2.60.40.10. 2 hits.
InterPro	IPR001090. Ephrin_rcpt_lig-bd_dom. IPR003961. Fibronectin_type3. IPR008979. Galactose-bd-like. IPR009030. Growth_fac_rcpt. IPR013783. Ig-like_fold. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_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]
Pfam	PF01404. Ephrin_lbd. 1 hit. PF00041. fn3. 2 hits. PF07714. Pkinase_Tyr. 2 hits. PF00536. SAM_1. 1 hit. [Graphical view]
PIRSF	PIRSF000666. TyrPK_ephrin_receptor. 1 hit.
PRINTS	PR00109. TYRKINASE.
SMART	SM00615. EPH_lbd. 1 hit. SM00060. FN3. 2 hits. SM00454. SAM. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF49265. FN_III-like. 2 hits. SSF49785. Gal_bind_like. 1 hit. SSF57184. Grow_fac_recept. 1 hit. SSF56112. Kinase_like. 1 hit. SSF47769. SAM_homology. 1 hit.
PROSITE	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. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q9UF33.
ChEMBL	CHEMBL4526.
GenomeRNAi	285220.
NextBio	95357.
SOURCE	Search...

Entry information

Entry name

EPHA6_HUMAN

Accession

Primary (citable) accession number: Q9UF33

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 16, 2006
Last sequence update:	May 16, 2006
Last modified:	May 1, 2013
This is version 104 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.