Reviewed, UniProtKB/Swiss-Prot P54756 (EPHA5_HUMAN)

Names and origin

Protein names

Recommended name:
    Ephrin type-A receptor 5
    EC=2.7.10.1
Alternative name(s):
    Tyrosine-protein kinase receptor EHK-1
    EPH homology kinase 1
    Receptor protein-tyrosine kinase HEK7

Gene names

Name:	EPHA5
Synonyms:	EHK1, HEK7

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	1037 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 to ephrin-A1, -A2, -A3, -A4 and -A5.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Almost exclusively expressed in the nervous system.
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	Alternative splicing 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
Gene Ontology (GO)
Biological process	protein amino acid phosphorylation Traceable author statement. Source: UniProtKB transmembrane receptor protein tyrosine kinase signaling pathway Inferred from electronic annotation. Source: InterPro
Cellular component	integral to membrane Traceable author statement. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW transmembrane-ephrin receptor activity Ref.3 Traceable author statement. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: P54756-1)

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: P54756-2)

The sequence of this isoform differs from the canonical sequence as follows:
     597-619: SCCECGCGRASSLCAVAHPSLIW → R

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 24

24

Potential

Chain

25 – 1037

1013

Ephrin type-A receptor 5

PRO_0000016812

Regions

Topological domain

25 – 573

549

Extracellular Potential

Transmembrane

574 – 594

21

Potential

Topological domain

595 – 1037

443

Cytoplasmic Potential

Domain

357 – 459

103

Fibronectin type-III 1

Domain

469 – 559

91

Fibronectin type-III 2

Domain

675 – 936

262

Protein kinase

Domain

965 – 1029

65

SAM

Nucleotide binding

681 – 689

9

ATP By similarity

Motif

1035 – 1037

3

PDZ-binding Potential

Compositional bias

220 – 354

135

Cys-rich

Sites

Active site

800

1

Proton acceptor By similarity

Binding site

707

1

ATP By similarity

Amino acid modifications

Modified residue

650

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

656

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

833

1

Phosphotyrosine; by autocatalysis Potential

Modified residue

982

1

Phosphotyrosine; by autocatalysis By similarity

Glycosylation

264

1

N-linked (GlcNAc...) Potential

Glycosylation

299

1

N-linked (GlcNAc...) Potential

Glycosylation

369

1

N-linked (GlcNAc...) Potential

Glycosylation

423

1

N-linked (GlcNAc...) Potential

Glycosylation

436

1

N-linked (GlcNAc...) Potential

Glycosylation

461

1

N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence

597 – 619

23

SCCEC…PSLIW → R in isoform 2.

VSP_002999

Natural variant

81

1

N → T: dbSNP rs33932471.

VAR_042138

Natural variant

235

1

S → A Ref.5

VAR_042139

Natural variant

330

1

E → Q Ref.5

VAR_042140

Natural variant

417

1

R → Q in a lung adenocarcinoma sample; somatic mutation. Ref.5

VAR_042141

Natural variant

503

1

E → K in a lung large cell carcinoma sample; somatic mutation. Ref.5

VAR_042142

Natural variant

506

1

Y → C Ref.5

VAR_045912

Natural variant

582

1

G → E in a lung adenocarcinoma sample; somatic mutation. Ref.5

VAR_042143

Natural variant

672

1

A → T: dbSNP rs36050417.

VAR_042144

Natural variant

673

1

S → T Ref.5

VAR_042145

Natural variant

856

1

T → I in a lung squamous cell carcinoma sample; somatic mutation. Ref.5

VAR_042146

Natural variant

959

1

H → R Ref.5

VAR_042147

Natural variant

1032

1

N → S in a lung large cell carcinoma sample; somatic mutation. Ref.5

VAR_042148

Experimental info

Sequence conflict

11

1

R → H in CAA64700. Ref.1

Sequence conflict

506

1

Y → H in CAA64700. Ref.1

Sequence conflict

616

1

S → I in CAA64700. Ref.1

Sequence conflict

642

1

S → I in CAA64700. Ref.1

Secondary structure

1

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1037

Helix Strand Turn

Details...

Helix

663 – 665

3

Helix

672 – 674

3

Beta strand

675 – 683

9

Beta strand

685 – 694

10

Beta strand

702 – 708

7

Helix

715 – 728

14

Beta strand

739 – 743

5

Beta strand

745 – 748

4

Beta strand

750 – 754

5

Helix

761 – 766

6

Turn

767 – 770

4

Helix

774 – 793

20

Helix

803 – 805

3

Beta strand

806 – 808

3

Beta strand

814 – 816

3

Helix

842 – 844

3

Helix

847 – 852

6

Helix

857 – 873

17

Turn

878 – 881

4

Helix

884 – 893

10

Helix

905 – 914

10

Helix

919 – 921

3

Helix

925 – 936

12

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 2, 2008. Version 2. Checksum: 22A8D1BF43902C7E	FASTA	1,037	114,777
	10 20 30 40 50 60 MRGSGPRGAG RRRPPSGGGD TPITPASLAG CYSAPRRAPL WTCLLLCAAL RTLLASPSNE 70 80 90 100 110 120 VNLLDSRTVM GDLGWIAFPK NGWEEIGEVD ENYAPIHTYQ VCKVMEQNQN NWLLTSWISN 130 140 150 160 170 180 EGASRIFIEL KFTLRDCNSL PGGLGTCKET FNMYYFESDD QNGRNIKENQ YIKIDTIAAD 190 200 210 220 230 240 ESFTELDLGD RVMKLNTEVR DVGPLSKKGF YLAFQDVGAC IALVSVRVYY KKCPSVVRHL 250 260 270 280 290 300 AVFPDTITGA DSSQLLEVSG SCVNHSVTDE PPKMHCSAEG EWLVPIGKCM CKAGYEEKNG 310 320 330 340 350 360 TCQVCRPGFF KASPHIQSCG KCPPHSYTHE EASTSCVCEK DYFRRESDPP TMACTRPPSA 370 380 390 400 410 420 PRNAISNVNE TSVFLEWIPP ADTGGRKDVS YYIACKKCNS HAGVCEECGG HVRYLPRQSG 430 440 450 460 470 480 LKNTSVMMVD LLAHTNYTFE IEAVNGVSDL SPGARQYVSV NVTTNQAAPS PVTNVKKGKI 490 500 510 520 530 540 AKNSISLSWQ EPDRPNGIIL EYEIKYFEKD QETSYTIIKS KETTITAEGL KPASVYVFQI 550 560 570 580 590 600 RARTAAGYGV FSRRFEFETT PVFAASSDQS QIPVIAVSVT VGVILLAVVI GVLLSGSCCE 610 620 630 640 650 660 CGCGRASSLC AVAHPSLIWR CGYSKAKQDP EEEKMHFHNG HSKLPGVRTY IDPHTYEDPN 670 680 690 700 710 720 QAVHEFAKEI EASCITIERV IGAGEFGEVC SGRLKLPGKR ELPVAIKTLK VGYTEKQRRD 730 740 750 760 770 780 FLGEASIMGQ FDHPNIIHLE GVVTKSKPVM IVTEYMENGS LDTFLKKNDG QFTVIQLVGM 790 800 810 820 830 840 LRGISAGMKY LSDMGYVHRD LAARNILINS NLVCKVSDFG LSRVLEDDPE AAYTTRGGKI 850 860 870 880 890 900 PIRWTAPEAI AFRKFTSASD VWSYGIVMWE VVSYGERPYW EMTNQDVIKA VEEGYRLPSP 910 920 930 940 950 960 MDCPAALYQL MLDCWQKERN SRPKFDEIVN MLDKLIRNPS SLKTLVNASC RVSNLLAEHS 970 980 990 1000 1010 1020 PLGSGAYRSV GEWLEAIKMG RYTEIFMENG YSSMDAVAQV TLEDLRRLGV TLVGHQKKIM 1030 NSLQEMKVQL VNGMVPL
	Isoform 2. Checksum: 7925DFEA9D53AB79	FASTA	1,015	112,598
	10 20 30 40 50 60 MRGSGPRGAG RRRPPSGGGD TPITPASLAG CYSAPRRAPL WTCLLLCAAL RTLLASPSNE 70 80 90 100 110 120 VNLLDSRTVM GDLGWIAFPK NGWEEIGEVD ENYAPIHTYQ VCKVMEQNQN NWLLTSWISN 130 140 150 160 170 180 EGASRIFIEL KFTLRDCNSL PGGLGTCKET FNMYYFESDD QNGRNIKENQ YIKIDTIAAD 190 200 210 220 230 240 ESFTELDLGD RVMKLNTEVR DVGPLSKKGF YLAFQDVGAC IALVSVRVYY KKCPSVVRHL 250 260 270 280 290 300 AVFPDTITGA DSSQLLEVSG SCVNHSVTDE PPKMHCSAEG EWLVPIGKCM CKAGYEEKNG 310 320 330 340 350 360 TCQVCRPGFF KASPHIQSCG KCPPHSYTHE EASTSCVCEK DYFRRESDPP TMACTRPPSA 370 380 390 400 410 420 PRNAISNVNE TSVFLEWIPP ADTGGRKDVS YYIACKKCNS HAGVCEECGG HVRYLPRQSG 430 440 450 460 470 480 LKNTSVMMVD LLAHTNYTFE IEAVNGVSDL SPGARQYVSV NVTTNQAAPS PVTNVKKGKI 490 500 510 520 530 540 AKNSISLSWQ EPDRPNGIIL EYEIKYFEKD QETSYTIIKS KETTITAEGL KPASVYVFQI 550 560 570 580 590 600 RARTAAGYGV FSRRFEFETT PVFAASSDQS QIPVIAVSVT VGVILLAVVI GVLLSGRRCG 610 620 630 640 650 660 YSKAKQDPEE EKMHFHNGHS KLPGVRTYID PHTYEDPNQA VHEFAKEIEA SCITIERVIG 670 680 690 700 710 720 AGEFGEVCSG RLKLPGKREL PVAIKTLKVG YTEKQRRDFL GEASIMGQFD HPNIIHLEGV 730 740 750 760 770 780 VTKSKPVMIV TEYMENGSLD TFLKKNDGQF TVIQLVGMLR GISAGMKYLS DMGYVHRDLA 790 800 810 820 830 840 ARNILINSNL VCKVSDFGLS RVLEDDPEAA YTTRGGKIPI RWTAPEAIAF RKFTSASDVW 850 860 870 880 890 900 SYGIVMWEVV SYGERPYWEM TNQDVIKAVE EGYRLPSPMD CPAALYQLML DCWQKERNSR 910 920 930 940 950 960 PKFDEIVNML DKLIRNPSSL KTLVNASCRV SNLLAEHSPL GSGAYRSVGE WLEAIKMGRY 970 980 990 1000 1010 TEIFMENGYS SMDAVAQVTL EDLRRLGVTL VGHQKKIMNS LQEMKVQLVN GMVPL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Extensive splice variation and localization of the EHK-1 receptor tyrosine kinase in adult human brain and glial tumors." Miescher G.C., Taylor V., Olivieri G., Mindermann T., Shrock E., Steck A.J. Brain Res. Mol. Brain Res. 46:17-24(1997) [PubMed: 9191074] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"cDNA cloning and tissue distribution of five human EPH-like receptor protein-tyrosine kinases." Fox G.M., Holst P.L., Chute H.T., Lindberg R.A., Janssen A.M., Basu R., Welcher A.A. Oncogene 10:897-905(1995) [PubMed: 7898931] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 25-1037. Tissue: Brain.
[4]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-833, MASS SPECTROMETRY.
[5]	"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] THR-81; ALA-235; GLN-330; GLN-417; LYS-503; CYS-506; GLU-582; THR-672; THR-673; ILE-856; ARG-959 AND SER-1032.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

X95425 mRNA. Translation: CAA64700.1.
AC018683 Genomic DNA. No translation available.
AC104137 Genomic DNA. No translation available.
AC105923 Genomic DNA. No translation available.
AC115223 Genomic DNA. No translation available.
L36644 mRNA. Translation: AAA74245.1.

IPI

IPI00008290.
IPI00215945.

UniGene

Hs.654492

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2R2P	X-ray	2.40	A	653-939	[»]

SMR

P54756. Positions 655-953.

ModBase

Search...

PTM databases

PhosphoSite

P54756.

Proteomic databases

PRIDE

P54756.

Genome annotation databases

Ensembl

ENSG00000145242. Homo sapiens. [Contig view]

KEGG

hsa:2044.

Organism-specific databases

GeneCards

GC04M065872.

H-InvDB

HIX0024608.

HGNC

HGNC:3389. EPHA5.

MIM

600004. gene.

PharmGKB

PA27821.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P54756.

HOVERGEN

P54756.

Enzyme and pathway databases

BRENDA

2.7.10.1. 247.

Pathway_Interaction_DB

epha_fwdpathway. EPHA forward signaling.
ephrinarevpathway. Ephrin A reverse signaling.
ephrina_ephapathway. EphrinA-EPHA pathway.

Gene expression databases

ArrayExpress

P54756.

Bgee

P54756.

CleanEx

HS_EPHA5.

GermOnline

ENSG00000145242. Homo sapiens.

Family and domain databases

InterPro

IPR015215. BmKX.
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

PF09132. BmKX. 1 hit.
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

8305.

SOURCE

Search...

Entry information

Entry name

EPHA5_HUMAN

Accession

Primary (citable) accession number: P54756

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	September 2, 2008
Last modified:	June 16, 2009
This is version 101 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)