Reviewed, UniProtKB/Swiss-Prot P29322 (EPHA8_HUMAN)

Names and origin

Protein names

Recommended name:
    Ephrin type-A receptor 8
    EC=2.7.10.1
Alternative name(s):
    Tyrosine-protein kinase receptor EEK
    EPH- and ELK-related kinase
    HEK3

Gene names

Name:	EPHA8
Synonyms:	EEK, KIAA1459

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1005 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Receptor for members of the ephrin-A family.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Interacts with FYN By similarity. Interacts with ANKS1B.
Subcellular location	Membrane; Single-pass type I membrane protein.
Post-translational modification	Phosphorylation on Tyr-616 is critical for association with FYN By similarity. Phosphorylation on Tyr-839 modulates tyrosine kinase activity By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily. 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	Polymorphism
Domain	Repeat Signal Transmembrane
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	protein amino acid phosphorylation Ref.3 Traceable author statement. Source: ProtInc transmembrane receptor protein tyrosine kinase signaling pathway Inferred from electronic annotation. Source: InterPro
Cellular component	integral to membrane Ref.3 Traceable author statement. Source: ProtInc plasma membrane Ref.3 Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ephrin receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 30

30

Potential

Chain

31 – 1005

975

Ephrin type-A receptor 8

PRO_0000016822

Regions

Topological domain

31 – 542

512

Extracellular Potential

Transmembrane

543 – 563

21

Potential

Topological domain

564 – 1005

442

Cytoplasmic Potential

Domain

328 – 430

103

Fibronectin type-III 1

Domain

436 – 531

96

Fibronectin type-III 2

Domain

635 – 896

262

Protein kinase

Domain

930 – 994

65

SAM

Nucleotide binding

641 – 649

9

ATP By similarity

Motif

1003 – 1005

3

PDZ-binding Potential

Compositional bias

191 – 325

135

Cys-rich

Sites

Active site

760

1

Proton acceptor By similarity

Binding site

667

1

ATP By similarity

Amino acid modifications

Modified residue

616

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

839

1

Phosphotyrosine; by autocatalysis By similarity

Glycosylation

340

1

N-linked (GlcNAc...) Potential

Glycosylation

407

1

N-linked (GlcNAc...) Potential

Glycosylation

432

1

N-linked (GlcNAc...) Potential

Natural variations

Natural variant

45

1

G → S

VAR_042153

Natural variant

60

1

V → L

VAR_042154

Natural variant

123

1

N → K in a breast infiltrating ductal carcinoma sample; somatic mutation. Ref.6

VAR_042155

Natural variant

179

1

R → C in a gastric adenocarcinoma sample; somatic mutation. Ref.6

VAR_042156

Natural variant

198

1

R → L in a lung adenocarcinoma sample; somatic mutation. Ref.6

VAR_042157

Natural variant

444

1

V → M: dbSNP rs2295021.

VAR_022107

Natural variant

612

1

E → Q: dbSNP rs999765. Ref.2

VAR_024514

Natural variant

860

1

P → L in a metastatic melanoma sample; somatic mutation. Ref.6

VAR_042158

Experimental info

Sequence conflict

237

1

S → L in BAA95983. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

1005

Helix Strand Turn

Details...

Beta strand

456 – 460

5

Beta strand

472 – 482

11

Beta strand

488 – 499

12

Beta strand

507 – 510

4

Beta strand

512 – 516

5

Beta strand

527 – 530

4

Helix

935 – 941

7

Helix

945 – 947

3

Helix

948 – 953

6

Helix

959 – 962

4

Helix

967 – 973

7

Helix

978 – 995

18

Sequences

	Sequence		Length	Mass (Da)
	P29322-1 [UniParc]. Last modified October 18, 2001. Version 2. Checksum: 6FBF85535E4212B3	FASTA	1,005	111,003
	10 20 30 40 50 60 MAPARGRLPP ALWVVTAAAA AATCVSAARG EVNLLDTSTI HGDWGWLTYP AHGWDSINEV 70 80 90 100 110 120 DESFQPIHTY QVCNVMSPNQ NNWLRTSWVP RDGARRVYAE IKFTLRDCNS MPGVLGTCKE 130 140 150 160 170 180 TFNLYYLESD RDLGASTQES QFLKIDTIAA DESFTGADLG VRRLKLNTEV RSVGPLSKRG 190 200 210 220 230 240 FYLAFQDIGA CLAILSLRIY YKKCPAMVRN LAAFSEAVTG ADSSSLVEVR GQCVRHSEER 250 260 270 280 290 300 DTPKMYCSAE GEWLVPIGKC VCSAGYEERR DACVACELGF YKSAPGDQLC ARCPPHSHSA 310 320 330 340 350 360 APAAQACHCD LSYYRAALDP PSSACTRPPS APVNLISSVN GTSVTLEWAP PLDPGGRSDI 370 380 390 400 410 420 TYNAVCRRCP WALSRCEACG SGTRFVPQQT SLVQASLLVA NLLAHMNYSF WIEAVNGVSD 430 440 450 460 470 480 LSPEPRRAAV VNITTNQAAP SQVVVIRQER AGQTSVSLLW QEPEQPNGII LEYEIKYYEK 490 500 510 520 530 540 DKEMQSYSTL KAVTTRATVS GLKPGTRYVF QVRARTSAGC GRFSQAMEVE TGKPRPRYDT 550 560 570 580 590 600 RTIVWICLTL ITGLVVLLLL LICKKRHCGY SKAFQDSDEE KMHYQNGQAP PPVFLPLHHP 610 620 630 640 650 660 PGKLPEPQFY AEPHTYEEPG RAGRSFTREI EASRIHIEKI IGSGDSGEVC YGRLRVPGQR 670 680 690 700 710 720 DVPVAIKALK AGYTERQRRD FLSEASIMGQ FDHPNIIRLE GVVTRGRLAM IVTEYMENGS 730 740 750 760 770 780 LDTFLRTHDG QFTIMQLVGM LRGVGAGMRY LSDLGYVHRD LAARNVLVDS NLVCKVSDFG 790 800 810 820 830 840 LSRVLEDDPD AAYTTTGGKI PIRWTAPEAI AFRTFSSASD VWSFGVVMWE VLAYGERPYW 850 860 870 880 890 900 NMTNRDVISS VEEGYRLPAP MGCPHALHQL MLDCWHKDRA QRPRFSQIVS VLDALIRSPE 910 920 930 940 950 960 SLRATATVSR CPPPAFVRSC FDLRGGSGGG GGLTVGDWLD SIRMGRYRDH FAAGGYSSLG 970 980 990 1000 MVLRMNAQDV RALGITLMGH QKKILGSIQT MRAQLTSTQG PRRHL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	"Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O. DNA Res. 7:143-150(2000) [PubMed: 10819331] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 153-1005, VARIANT GLN-612. Tissue: Brain.
[3]	"eek and erk, new members of the eph subclass of receptor protein-tyrosine kinases." Chan J., Watt V.M. Oncogene 6:1057-1061(1991) [PubMed: 1648701] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 706-726.
[4]	"Identification of phosphotyrosine binding domain-containing proteins as novel downstream targets of the EphA8 signaling function." Shin J., Gu C., Park E., Park S. Mol. Cell. Biol. 27:8113-8126(2007) [PubMed: 17875921] [Abstract] Cited for: INTERACTION WITH ANKS1B.
[5]	"Solution structure of the second FN3 domain and of sterile alpha motif (SAM) domain of EPH receptor A8 protein." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 437-534 AND 932-1000.
[6]	"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: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-45; LEU-60; LYS-123; CYS-179; LEU-198 AND LEU-860.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AL035703 Genomic DNA. Translation: CAB81612.1.
AB040892 mRNA. Translation: BAA95983.1.
X59291 Genomic DNA. Translation: CAA41980.1. Different initiation.

IPI

IPI00021274.

PIR

S23361.

RefSeq

NP_065387.1.

UniGene

Hs.283613

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1UCV	NMR	-	A	933-1000	[»]
1X5L	NMR	-	A	437-534	[»]

SMR

P29322. Positions 617-903.

ModBase

Search...

Protein-protein interaction databases

STRING

P29322.

PTM databases

PhosphoSite

P29322.

Proteomic databases

PRIDE

P29322.

Genome annotation databases

Ensembl

ENST00000166244; ENSP00000166244; ENSG00000070886; Homo sapiens. [Genome view]
ENST00000374644; ENSP00000363775; ENSG00000070886; Homo sapiens. [Genome view]

GeneID

2046.

UCSC

uc001bfx.1. human.

Organism-specific databases

CTD

2046.

GeneCards

GC01P022762.

HGNC

HGNC:3391. EPHA8.

HPA

CAB009660.

MIM

176945. gene.

PharmGKB

PA27823.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P29322.

HOVERGEN

P29322.

OMA

CARCPLH.

Enzyme and pathway databases

BRENDA

2.7.10.1. 247.

Pathway_Interaction_DB

epha_fwdpathway. EPHA forward signaling.
ephrina_ephapathway. EphrinA-EPHA pathway.

Gene expression databases

ArrayExpress

P29322.

Bgee

P29322.

CleanEx

HS_EPHA8.

Genevestigator

P29322.

GermOnline

ENSG00000070886. Homo sapiens.

Family and domain databases

InterPro

IPR013032. EGF-like_reg_CS.
IPR001090. Ephrin_rcpt_lig-bd.
IPR008957. Fibronectin_typ-III-like_fold.
IPR003961. FN_III.
IPR003962. FnIII_subd.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR001660. SAM.
IPR013761. SAM_type.
IPR001245. Tyr_pkinase.
IPR008266. Tyr_pkinase_AS.
IPR016257. TyrPK_ephrin_receptor.
IPR001426. YKase_receptorV_CS.
[Graphical view]

Gene3D

G3DSA:2.60.40.30. FN_III-like. 2 hits.
G3DSA:1.10.150.50. SAM_type. 1 hit.

Pfam

PF01404. Ephrin_lbd. 1 hit.
PF00041. fn3. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
PF00536. SAM_1. 1 hit.
[Graphical view]

PIRSF

PIRSF000666. TyrPK_ephrin_receptor. 1 hit.

PRINTS

PR00014. FNTYPEIII.
PR00109. TYRKINASE.

ProDom

PD001495. Ephrin_receptor. 1 hit.
PD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00615. EPH_lbd. 1 hit.
SM00060. FN3. 2 hits.
SM00454. SAM. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]

PROSITE

PS01186. EGF_2. 1 hit. Uncertain.
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 Resources

NextBio

8315.

SOURCE

Search...

Entry information

Entry name

EPHA8_HUMAN

Accession

Primary (citable) accession number: P29322
Secondary accession number(s): Q9NUA9, Q9P269

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	October 18, 2001
Last modified:	November 3, 2009
This is version 110 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.