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Q60750 (EPHA1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length977 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.4

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.4

Post-translational modification

Phosphorylated. Autophosphorylation is stimulated by its ligand EFNA1 By similarity.

Ubiquitinated By similarity.

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.4

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 processAngiogenesis
Cell adhesion
   Cellular componentCell membrane
Membrane
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMGlycoprotein
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of Rho GTPase activity

Inferred from sequence or structural similarity. Source: UniProtKB

angiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

cell surface receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

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 PubMed 12775584. 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_componentintegral component of plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

transmembrane-ephrin receptor activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626 Potential
Chain27 – 977951Ephrin type-A receptor 1 By similarity
PRO_0000016799

Regions

Topological domain27 – 548522Extracellular Potential
Transmembrane549 – 56921Helical; Potential
Topological domain570 – 977408Cytoplasmic Potential
Domain28 – 210183Eph LBD
Domain333 – 446114Fibronectin type-III 1
Domain448 – 53992Fibronectin type-III 2
Domain625 – 885261Protein kinase
Domain914 – 97764SAM
Nucleotide binding631 – 6399ATP By similarity
Motif975 – 9773PDZ-binding Potential
Compositional bias192 – 330139Cys-rich

Sites

Active site7501Proton acceptor By similarity
Binding site6571ATP By similarity

Amino acid modifications

Modified residue6001Phosphotyrosine; by autocatalysis Potential
Modified residue6061Phosphotyrosine; by autocatalysis Potential
Modified residue7821Phosphotyrosine; by autocatalysis By similarity
Modified residue9071Phosphoserine By similarity
Modified residue9111Phosphoserine By similarity
Glycosylation4151N-linked (GlcNAc...) Potential
Glycosylation4791N-linked (GlcNAc...) Potential

Experimental info

Sequence conflict1631G → D in AAG12206. Ref.1
Sequence conflict4221S → P in AAC52384. Ref.3
Sequence conflict5041L → R in AAC52384. Ref.3
Sequence conflict5211T → A in AAC52384. Ref.3
Sequence conflict5901D → G in AAC52384. Ref.3
Sequence conflict6361F → Y in AAC52384. Ref.3
Sequence conflict6601K → R in AAC52384. Ref.3
Sequence conflict7201D → G in AAC52384. Ref.3
Sequence conflict7691F → L in AAC52384. Ref.3
Sequence conflict7971E → G in AAC52384. Ref.3
Sequence conflict8171M → T in AAG12206. Ref.1

Secondary structure

............... 977
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q60750 [UniParc].

Last modified May 10, 2004. Version 2.
Checksum: AB78D6E6C8B2E7F4

FASTA977108,578
        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 

« Hide

References

« Hide '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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 281-814.
Strain: 129/Sv.
[4]"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] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION IN APOPTOSIS, TISSUE SPECIFICITY.
[5]"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.
RefSeqNP_076069.2. NM_023580.4.
UniGeneMm.133330.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1X5ANMR-A446-539[»]
ProteinModelPortalQ60750.
SMRQ60750. Positions 25-539, 615-975.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199468. 1 interaction.
IntActQ60750. 4 interactions.
MINTMINT-7013408.

PTM databases

PhosphoSiteQ60750.

Proteomic databases

PaxDbQ60750.
PRIDEQ60750.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000073387; ENSMUSP00000073099; ENSMUSG00000029859.
GeneID13835.
KEGGmmu:13835.
UCSCuc009brc.1. mouse.

Organism-specific databases

CTD2041.
MGIMGI:107381. Epha1.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00740000115081.
HOGENOMHOG000233856.
HOVERGENHBG062180.
InParanoidQ60750.
KOK05102.
OMAQAYEDPA.
OrthoDBEOG7VTDM6.
PhylomeDBQ60750.
TreeFamTF315363.

Gene expression databases

BgeeQ60750.
CleanExMM_EPHA1.
GenevestigatorQ60750.

Family and domain databases

Gene3D1.10.150.50. 1 hit.
2.60.120.260. 1 hit.
2.60.40.10. 2 hits.
InterProIPR027936. Eph_TM.
IPR001090. Ephrin_rcpt_lig-bd_dom.
IPR003961. Fibronectin_type3.
IPR008979. Galactose-bd-like.
IPR009030. Growth_fac_rcpt_N_dom.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_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]
PfamPF14575. EphA2_TM. 1 hit.
PF01404. Ephrin_lbd. 1 hit.
PF00041. fn3. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
PF00536. SAM_1. 1 hit.
[Graphical view]
PIRSFPIRSF000666. TyrPK_ephrin_receptor. 1 hit.
PRINTSPR00109. TYRKINASE.
SMARTSM00615. EPH_lbd. 1 hit.
SM00060. FN3. 2 hits.
SM00454. SAM. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF47769. SSF47769. 1 hit.
SSF49265. SSF49265. 1 hit.
SSF49785. SSF49785. 1 hit.
SSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 1 hit.
PROSITEPS01186. EGF_2. 1 hit.
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]
ProtoNetSearch...

Other

EvolutionaryTraceQ60750.
NextBio284652.
PROQ60750.
SOURCESearch...

Entry information

Entry nameEPHA1_MOUSE
AccessionPrimary (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: April 16, 2014
This is version 142 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot