Q60750 (EPHA1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ephrin type-A receptor 1
Short name=mEpha1
EC=2.7.10.1

Alternative name(s):
Embryonic stem cell kinase
Tyrosine-protein kinase receptor ESK

Gene names

Name:	Epha1
Synonyms:	Esk

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	977 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 tyrosine kinase which binds promiscuously membrane-bound 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. Binds with a low affinity EFNA3 and EFNA4 and with a high affinity to EFNA1 which most probably constitutes its cognate/functional ligand. Upon activation by EFNA1 induces cell attachment to the extracellular matrix inhibiting cell spreading and motility through regulation of ILK and downstream RHOA and RAC. Plays also a role in angiogenesis and regulates cell proliferation. May play a role in apoptosis. Ref.5
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Homodimer. Forms a signaling complex with LCK; PTK2B/PYK2 and PI3-kinase upon activation by EFNA1; regulates T-lymphocytes migration. Interacts (via SAM domain) with ILK (via ANK repeats); stimulated by EFNA1 but independent of the kinase activity of EPHA1. Interacts (kinase activity-dependent) with PTK2/FAK1 By similarity.
Subcellular location	Cell membrane; Single-pass type I membrane protein By similarity.
Tissue specificity	Preferentially expressed in epithelial cells including skin, kidney, liver and thymus. Ref.1 Ref.5
Post-translational modification	Phosphorylated. Autophosphorylation is stimulated by its ligand EFNA1 By similarity. Ref.4
Disruption phenotype	Mice display a partially-penetrant uterovaginal and tail development defects. The uterovaginal defect is due to a defect in apoptosis during development. Ref.5
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
Biological process	Angiogenesis Cell adhesion
Cellular component	Cell membrane Membrane
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	activation of Rho GTPase activity Inferred from sequence or structural similarity. Source: UniProtKB angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of cell migration Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of protein kinase activity Inferred from sequence or structural similarity. Source: UniProtKB peptidyl-tyrosine phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of angiogenesis Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell migration Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell-matrix adhesion Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of stress fiber assembly Inferred from direct assay. Source: UniProtKB protein autophosphorylation Inferred from sequence or structural similarity. Source: UniProtKB regulation of Rac GTPase activity Inferred from sequence or structural similarity. Source: UniProtKB substrate adhesion-dependent cell spreading Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	integral to plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW transmembrane-ephrin receptor activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 26

26

Potential

Chain

27 – 977

951

Ephrin type-A receptor 1 By similarity

PRO_0000016799

Regions

Topological domain

27 – 548

522

Extracellular Potential

Transmembrane

549 – 569

21

Helical; Potential

Topological domain

570 – 977

408

Cytoplasmic Potential

Domain

28 – 210

183

Eph LBD

Domain

333 – 438

106

Fibronectin type-III 1

Domain

447 – 536

90

Fibronectin type-III 2

Domain

625 – 885

261

Protein kinase

Domain

914 – 977

64

SAM

Nucleotide binding

631 – 639

9

ATP By similarity

Motif

975 – 977

3

PDZ-binding Potential

Compositional bias

192 – 330

139

Cys-rich

Sites

Active site

750

1

Proton acceptor By similarity

Binding site

657

1

ATP By similarity

Amino acid modifications

Modified residue

34

1

Phosphothreonine By similarity

Modified residue

35

1

Phosphoserine By similarity

Modified residue

600

1

Phosphotyrosine; by autocatalysis Potential

Modified residue

606

1

Phosphotyrosine; by autocatalysis Potential

Modified residue

781

1

Phosphothreonine By similarity

Modified residue

782

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

907

1

Phosphoserine By similarity

Modified residue

909

1

Phosphoserine By similarity

Modified residue

911

1

Phosphoserine Ref.4

Modified residue

920

1

Phosphoserine By similarity

Glycosylation

415

1

N-linked (GlcNAc...) Potential

Glycosylation

479

1

N-linked (GlcNAc...) Potential

Experimental info

Sequence conflict

163

1

G → D in AAG12206. Ref.1

Sequence conflict

422

1

S → P in AAC52384. Ref.3

Sequence conflict

504

1

L → R in AAC52384. Ref.3

Sequence conflict

521

1

T → A in AAC52384. Ref.3

Sequence conflict

590

1

D → G in AAC52384. Ref.3

Sequence conflict

636

1

F → Y in AAC52384. Ref.3

Sequence conflict

660

1

K → R in AAC52384. Ref.3

Sequence conflict

720

1

D → G in AAC52384. Ref.3

Sequence conflict

769

1

F → L in AAC52384. Ref.3

Sequence conflict

797

1

E → G in AAC52384. Ref.3

Sequence conflict

817

1

M → T in AAG12206. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

977

Helix Strand Turn

Details...

Beta strand

456 – 460

5

Beta strand

463 – 467

5

Beta strand

481 – 487

7

Beta strand

492 – 506

15

Beta strand

512 – 520

9

Beta strand

522 – 524

3

Beta strand

532 – 535

4

Sequences

	Sequence		Length	Mass (Da)
	Q60750 [UniParc]. Last modified May 10, 2004. Version 2. Checksum: AB78D6E6C8B2E7F4	FASTA	977	108,578
	10 20 30 40 50 60 MERRWPLGLA LLLLLLCAPL PPGARAEEVT LMDTSTAQGE LGWLLDPPET GWSEVQQMLN 70 80 90 100 110 120 GTPLYMYQDC PIQEGGDTDH WLRSNWIYRG EEASRIYVEL QFTVRDCKSF PGGAGPLGCK 130 140 150 160 170 180 ETFNLFYMES DQDVGIQLRR PLFQKVTTVA ADQSFTIRDL ASGSVKLNVE RCSLGHLTRR 190 200 210 220 230 240 GLYLAFHNPG SCVALVSVRV FYQRCAETVH GLAHFPDTLP GPGGLVEVAG TCLSHAQISL 250 260 270 280 290 300 GSSGTPRMHC SPDGEWLVPV GQCQCEPGYE ESSGNVGCTA CPTGFYRVDM NTLRCLKCPQ 310 320 330 340 350 360 HSIAESEGST ICTCENGHYR APGEGPQVAC TRPPSAPQNL SFSTSGTQLS LRWEPPRDTG 370 380 390 400 410 420 GRHDIRYSVE CLQCRGIAQD GGPCQPCGKG VHFSPAASGL TTSTVQVQGL EPYANYTFTV 430 440 450 460 470 480 KSQNRVSGLD SSSPSSASLS INMGHAESLS GLSLKLVKKE PRQLELTWAG SRPRNPGGNL 490 500 510 520 530 540 SYELHVLNQD EEWHQMVLEP RVLLTKLQPD TTYIVRVRTL TPLGPGPFSP DHEFRTSPPV 550 560 570 580 590 600 SRSLTGGEIV AVIFGLLLGI ALLIGIYVFR SRRGQRQRQQ RQRERTTNVD REDKLWLKPY 610 620 630 640 650 660 VDLQAYEDPA QGALDFAQEL DPAWLIVDTV IGEGEFGEVY RGALRLPSQD CKTVAIKTLK 670 680 690 700 710 720 DTSPDGYWWN FLREATIMGQ FNHPHILRLE GVITKRKPIM IITEFMENGA LDAFLKERED 730 740 750 760 770 780 QLAPGQLVAM LLGIASGMNC LSGHNYVHRD LAARNILVNQ NLCCKVSDFG LTRLLDDFDG 790 800 810 820 830 840 TYETQGGKIP IRWTAPEAIA HRIFTTASDV WSFGIVMWEV LSFGDKPYGE MSNQEVMKSI 850 860 870 880 890 900 EDGYRLPPPV DCPAPLYELM KNCWAYDRAR RPHFLQLQAH LEQLLTDPHS LRTIANFDPR 910 920 930 940 950 960 VTLRLPSLSG SDGIPYRSVS EWLESIRMKR YILHFRSAGL DTMECVLELT AEDLTQMGIT 970 LPGHQKRILC SIQGFKD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of the Epha1 receptor tyrosine kinase: expression in epithelial tissues." Coulthard M.G., Lickliter J.D., Subanesan N., Chen K., Webb G.C., Lowry A.J., Koblar S., Bottema C.D., Boyd A.W. Growth Factors 18:303-317(2001) [PubMed: 11519828] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, EFNA1 LIGAND-BINDING.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Skin.
[3]	"Embryonic stem cells express multiple Eph-subfamily receptor tyrosine kinases." Lickliter J.D., Smith F.M., Olsson J.E., Mackwell K.L., Boyd A.W. Proc. Natl. Acad. Sci. U.S.A. 93:145-150(1996) [PubMed: 8552593] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 281-814. Strain: 129/Sv.
[4]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed: 17242355] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-911, MASS SPECTROMETRY. Tissue: Liver.
[5]	"Generation and characterization of EphA1 receptor tyrosine kinase reporter knockout mice." Duffy S.L., Coulthard M.G., Spanevello M.D., Herath N.I., Yeadon T.M., McCarron J.K., Carter J.C., Tonks I.D., Kay G.F., Phillips G.E., Boyd A.W. Genesis 46:553-561(2008) [PubMed: 18802966] [Abstract] Cited for: DISRUPTION PHENOTYPE, FUNCTION IN APOPTOSIS, TISSUE SPECIFICITY.
[6]	"The solution structure of the second fibronectin type III domain of mouse ephrin type-A receptor 1." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 446-539.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF131197 mRNA. Translation: AAG12206.1.
AK028478 mRNA. Translation: BAC25971.1.
U18084 mRNA. Translation: AAC52384.1.

IPI

IPI00120222.

RefSeq

NP_076069.2. NM_023580.4.

UniGene

Mm.133330.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1X5A	NMR	-	A	446-539	[»]

ProteinModelPortal

Q60750.

SMR

Q60750. Positions 25-539, 611-906, 912-975.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-7013408.

STRING

Q60750.

PTM databases

PhosphoSite

Q60750.

Proteomic databases

PRIDE

Q60750.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000073387; ENSMUSP00000073099; ENSMUSG00000029859.

GeneID

13835.

KEGG

mmu:13835.

UCSC

uc009brc.1. mouse.

Organism-specific databases

CTD

2041.

MGI

MGI:107381. Epha1.

Phylogenomic databases

eggNOG

roNOG06293.

HOGENOM

HBG755340.

HOVERGEN

HBG062180.

InParanoid

Q60750.

OMA

AYEDPAQ.

OrthoDB

EOG42BX7S.

PhylomeDB

Q60750.

Gene expression databases

ArrayExpress

Q60750.

Bgee

Q60750.

CleanEx

MM_EPHA1.

Genevestigator

Q60750.

GermOnline

ENSMUSG00000029859. Mus musculus.

Family and domain databases

InterPro

IPR001090. Ephrin_rcpt_lig-bd.
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.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016257. Tyr_kinase_ephrin_rcpt.
IPR001426. Tyr_kinase_rcpt_V_CS.
[Graphical view]

Gene3D

G3DSA:2.60.40.10. Ig-like_fold. 2 hits.
G3DSA:1.10.150.50. SAM_type. 1 hit.

KO

K05102.

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

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

PS01186. EGF_2. 1 hit. Uncertain.
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

NextBio

284652.

SOURCE

Search...

Entry information

Entry name

EPHA1_MOUSE

Accession

Primary (citable) accession number: Q60750
Secondary accession number(s): Q8CED9, Q9ESJ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	May 10, 2004
Last modified:	January 25, 2012
This is version 121 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program