Reviewed, UniProtKB/Swiss-Prot P21709 (EPHA1_HUMAN)

Names and origin

Protein names

Recommended name:
    Ephrin type-A receptor 1
    EC=2.7.10.1
Alternative name(s):
    Tyrosine-protein kinase receptor EPH

Gene names

Name:	EPHA1
Synonyms:	EPH, EPHT, EPHT1

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	976 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. Binds with a low affinity to ephrin-A1.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Overexpressed in several carcinomas.
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 Inferred from electronic annotation. Source: InterPro transmembrane receptor protein tyrosine kinase signaling pathway Inferred from electronic annotation. Source: InterPro
Cellular component	integral to plasma membrane Ref.1 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 protein binding 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 – 23

23

Potential

Chain

24 – 976

953

Ephrin type-A receptor 1

PRO_0000016798

Regions

Topological domain

24 – 547

524

Extracellular Potential

Transmembrane

548 – 568

21

Potential

Topological domain

569 – 976

408

Cytoplasmic Potential

Domain

332 – 437

106

Fibronectin type-III 1

Domain

446 – 535

90

Fibronectin type-III 2

Domain

624 – 884

261

Protein kinase

Domain

913 – 976

64

SAM

Nucleotide binding

630 – 638

9

ATP By similarity

Motif

974 – 976

3

PDZ-binding Potential

Compositional bias

191 – 329

139

Cys-rich

Sites

Active site

749

1

Proton acceptor By similarity

Binding site

656

1

ATP By similarity

Amino acid modifications

Modified residue

33

1

Phosphothreonine Ref.6

Modified residue

34

1

Phosphoserine Ref.6

Modified residue

599

1

Phosphotyrosine; by autocatalysis Potential

Modified residue

605

1

Phosphotyrosine; by autocatalysis Potential

Modified residue

780

1

Phosphothreonine

Modified residue

781

1

Phosphotyrosine; by autocatalysis Potential

Modified residue

906

1

Phosphoserine

Modified residue

908

1

Phosphoserine

Modified residue

910

1

Phosphoserine

Modified residue

919

1

Phosphoserine

Modified residue

930

1

Phosphotyrosine; by autocatalysis Potential

Glycosylation

338

1

N-linked (GlcNAc...) Potential

Glycosylation

414

1

N-linked (GlcNAc...) Potential

Glycosylation

478

1

N-linked (GlcNAc...) Potential

Natural variations

Natural variant

160

1

A → V: dbSNP rs4725617. Ref.3 Ref.8

VAR_028265

Natural variant

351

1

R → C: dbSNP rs56006153. Ref.8

VAR_042115

Natural variant

492

1

R → Q: dbSNP rs11768549. Ref.8

VAR_028266

Natural variant

575

1

R → Q: dbSNP rs35719334. Ref.8

VAR_042116

Natural variant

585

1

A → T: dbSNP rs34178823. Ref.8

VAR_042117

Natural variant

697

1

P → L: dbSNP rs34372369. Ref.8

VAR_042118

Natural variant

703

1

E → K in a breast pleomorphic lobular carcinoma sample; somatic mutation. Ref.8

VAR_042119

Natural variant

807

1

S → R: dbSNP rs56244405. Ref.8

VAR_042120

Natural variant

900

1

V → M: dbSNP rs6967117. Ref.3 Ref.8

VAR_028267

Experimental info

Sequence conflict

398

1

G → A Ref.2

Sequence conflict

398

1

G → A Ref.4

Sequence conflict

581 – 616

36

QRDRA…ALDFT → HVTAPPMWIERTSCAEALCG TSRHTRTLHREPWTLPGGWS NFPS in AAA36747. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

976

Helix Strand Turn

Details...

Helix

918 – 924

7

Helix

928 – 930

3

Helix

931 – 936

6

Helix

942 – 945

4

Helix

950 – 955

6

Helix

964 – 971

8

Sequences

	Sequence		Length	Mass (Da)
	P21709-1 [UniParc]. Last modified May 10, 2004. Version 3. Checksum: 9F8F2D6A8E683D95	FASTA	976	108,067
	10 20 30 40 50 60 MERRWPLGLG LVLLLCAPLP PGARAKEVTL MDTSKAQGEL GWLLDPPKDG WSEQQQILNG 70 80 90 100 110 120 TPLYMYQDCP MQGRRDTDHW LRSNWIYRGE EASRVHVELQ FTVRDCKSFP GGAGPLGCKE 130 140 150 160 170 180 TFNLLYMESD QDVGIQLRRP LFQKVTTVAA DQSFTIRDLA SGSVKLNVER CSLGRLTRRG 190 200 210 220 230 240 LYLAFHNPGA CVALVSVRVF YQRCPETLNG LAQFPDTLPG PAGLVEVAGT CLPHARASPR 250 260 270 280 290 300 PSGAPRMHCS PDGEWLVPVG RCHCEPGYEE GGSGEACVAC PSGSYRMDMD TPHCLTCPQQ 310 320 330 340 350 360 STAESEGATI CTCESGHYRA PGEGPQVACT GPPSAPRNLS FSASGTQLSL RWEPPADTGG 370 380 390 400 410 420 RQDVRYSVRC SQCQGTAQDG GPCQPCGVGV HFSPGARGLT TPAVHVNGLE PYANYTFNVE 430 440 450 460 470 480 AQNGVSGLGS SGHASTSVSI SMGHAESLSG LSLRLVKKEP RQLELTWAGS RPRSPGANLT 490 500 510 520 530 540 YELHVLNQDE ERYQMVLEPR VLLTELQPDT TYIVRVRMLT PLGPGPFSPD HEFRTSPPVS 550 560 570 580 590 600 RGLTGGEIVA VIFGLLLGAA LLLGILVFRS RRAQRQRQQR QRDRATDVDR EDKLWLKPYV 610 620 630 640 650 660 DLQAYEDPAQ GALDFTRELD PAWLMVDTVI GEGEFGEVYR GTLRLPSQDC KTVAIKTLKD 670 680 690 700 710 720 TSPGGQWWNF LREATIMGQF SHPHILHLEG VVTKRKPIMI ITEFMENGAL DAFLREREDQ 730 740 750 760 770 780 LVPGQLVAML QGIASGMNYL SNHNYVHRDL AARNILVNQN LCCKVSDFGL TRLLDDFDGT 790 800 810 820 830 840 YETQGGKIPI RWTAPEAIAH RIFTTASDVW SFGIVMWEVL SFGDKPYGEM SNQEVMKSIE 850 860 870 880 890 900 DGYRLPPPVD CPAPLYELMK NCWAYDRARR PHFQKLQAHL EQLLANPHSL RTIANFDPRV 910 920 930 940 950 960 TLRLPSLSGS DGIPYRTVSE WLESIRMKRY ILHFHSAGLD TMECVLELTA EDLTQMGITL 970 PGHQKRILCS IQGFKD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel putative tyrosine kinase receptor encoded by the eph gene." Hirai H., Maru Y., Hagiwara K., Nishida J., Takaku F. Science 238:1717-1720(1987) [PubMed: 2825356] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Genomic structure of the EPHA1 receptor tyrosine kinase gene." Owshalimpur D., Kelley M.J. Mol. Cell. Probes 13:169-173(1999) [PubMed: 10369740] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS VAL-160 AND MET-900.
[4]	"An EGFR/eph chimeric receptor possesses ligand stimulated tyrosine kinase activity and promotes cell growth." Tuzi N.L. Submitted (MAY-1994) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 286-976. Tissue: Placenta.
[5]	"Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules." Zhang Y., Wolf-Yadlin A., Ross P.L., Pappin D.J., Rush J., Lauffenburger D.A., White F.M. Mol. Cell. Proteomics 4:1240-1250(2005) [PubMed: 15951569] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-781, MASS SPECTROMETRY. Tissue: Epithelium.
[6]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-33 AND SER-34, MASS SPECTROMETRY. Tissue: Epithelium.
[7]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-780; TYR-781; SER-906; SER-908; SER-910 AND SER-919, MASS SPECTROMETRY.
[8]	"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] VAL-160; CYS-351; GLN-492; GLN-575; THR-585; LEU-697; LYS-703; ARG-807 AND MET-900.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M18391 mRNA. Translation: AAA36747.1. Sequence problems.
AF101171 , AF101165, AF101166, AF101167, AF101168, AF101169, AF101170 Genomic DNA. Translation: AAD43440.1.
AC092214 Genomic DNA. Translation: AAS07458.1.
Z27409 mRNA. Translation: CAA81796.1.

IPI

IPI00294250.

PIR

A34076.

RefSeq

NP_005223.4.

UniGene

Hs.89839

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2K1K	NMR	-	A/B	536-573	[»]
2K1L	NMR	-	A/B	536-573	[»]
3HIL	X-ray	2.00	A/B	911-974	[»]
3KKA	X-ray	2.40	A/B	911-974	[»]

SMR

P21709. Positions 26-203, 292-536, 451-538, 616-896, 625-935.

ModBase

Search...

Protein-protein interaction databases

STRING

P21709.

PTM databases

PhosphoSite

P21709.

Proteomic databases

PRIDE

P21709.

Genome annotation databases

Ensembl

ENST00000275815; ENSP00000275815; ENSG00000146904; Homo sapiens. [Genome view]

GeneID

2041.

KEGG

hsa:2041.

Organism-specific databases

CTD

2041.

GeneCards

GC07M142798.

H-InvDB

HIX0033699.

HGNC

HGNC:3385. EPHA1.

MIM

179610. gene.

PharmGKB

PA27817.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG755340.

HOVERGEN

P21709.

InParanoid

P21709.

Enzyme and pathway databases

BRENDA

2.7.10.1. 247.

Pathway_Interaction_DB

epha_fwdpathway. EPHA forward signaling.

Gene expression databases

ArrayExpress

P21709.

Bgee

P21709.

CleanEx

HS_EPHA1.

Genevestigator

P21709.

GermOnline

ENSG00000146904. Homo sapiens.

Family and domain databases

InterPro

IPR001090. Ephrin_rcpt_lig-bd.
IPR008957. Fibronectin_typ-III-like_fold.
IPR003961. FN_III.
IPR008979. Galactose-bd-like.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001660. SAM.
IPR010993. SAM_homology.
IPR013761. SAM_type.
IPR021129. SAM_type1.
IPR020635. Tyr_Pkinase_cat_dom.
IPR020685. Tyr_prot_kinase.
IPR008266. Tyr_prot_kinase_AS.
IPR016257. Tyr_prot_kinase_ephrin_rcpt.
IPR001426. Tyr_prot_kinase_rcpt_V_CS.
[Graphical view]

Gene3D

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

PANTHER

PTHR23256. Tyr_prot_kinase. 1 hit.

Pfam

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

PIRSF

PIRSF000666. TyrPK_ephrin_receptor. 1 hit.

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

8291.

SOURCE

Search...

Entry information

Entry name

EPHA1_HUMAN

Accession

Primary (citable) accession number: P21709
Secondary accession number(s): Q15405

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1991
Last sequence update:	May 10, 2004
Last modified:	February 9, 2010
This is version 122 of the entry and version 3 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.