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Reviewed, UniProtKB/Swiss-Prot Q03137 (EPHA4_MOUSE)

Last modified June 16, 2009. Version 108. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Ephrin type-A receptor 4
    EC=2.7.10.1
Alternative name(s):
    Tyrosine-protein kinase receptor SEK
    MPK-3
Gene names
Name: Epha4
Synonyms: Sek, Sek1
OrganismMus musculus (Mouse)
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

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Protein attributes

Sequence length986 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Receptor for members of the ephrin-A family. Binds to ephrin-A1, -A4 and -A5. Binds more poorly to ephrin-A2 and -A3. May play a role in a signal transduction process involved in hindbrain pattern formation.

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Subunit structure

Interacts with the src family kinase, p59-Fyn, through the major phosphorylation site at position Tyr-602 By similarity. Interacts with NGEF/ephexin-1.

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

Found in both the 10-day embryonic brain and body tissues. Highest expression in the adult brain and retina and also detectable in kidney, lung, skeletal muscle and thymus. Not detected in heart and liver. In the embryonic brain, expressed in the developing cortex of the telencephalon and major cortical tracts. Also expressed in the hippocampus, fornix and striatal cells and tracts. In the diencephalon, strongly expressed in thalamus, hypothalamus and thalamo-cortical projection. Also expressed in red nuclei of the mesencephalon and in the cerebellum. In the spinal cord, persistent expression occurs in the dorsal funiculus and ventral gray matter. Ref.5

Domain

The protein kinase domain mediates interaction with NGEF/ephexin-1.

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.

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Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Long (identifier: Q03137-1)

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 Short (identifier: Q03137-2)

The sequence of this isoform differs from the canonical sequence as follows:
     783-832: Missing.
Note: No experimental confirmation available.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919 Potential
Chain20 – 986967Ephrin type-A receptor 4
PRO_0000016808

Regions

Topological domain20 – 547528Extracellular Potential
Transmembrane548 – 56922 Potential
Topological domain570 – 986417Cytoplasmic Potential
Domain328 – 431104Fibronectin type-III 1
Domain441 – 53292Fibronectin type-III 2
Domain621 – 882262Protein kinase
Domain911 – 97565SAM
Nucleotide binding627 – 6359ATP By similarity
Motif984 – 9863PDZ-binding Potential
Compositional bias191 – 325135Cys-rich

Sites

Active site7461Proton acceptor By similarity
Binding site6531ATP By similarity

Amino acid modifications

Modified residue5961Phosphotyrosine; by autocatalysis Ref.3 Ref.6
Modified residue6021Phosphotyrosine; by autocatalysis Ref.3 Ref.6
Modified residue7791Phosphotyrosine; by autocatalysis Potential
Modified residue9281Phosphotyrosine; by autocatalysis Potential
Glycosylation2351N-linked (GlcNAc...) Potential
Glycosylation3401N-linked (GlcNAc...) Potential
Glycosylation4081N-linked (GlcNAc...) Potential
Glycosylation4231N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence783 – 83250Missing in isoform Short.
VSP_002998

Experimental info

Mutagenesis6351V → M: Loss of phosphorylation. No effect on interaction with NGEF/ephexin-1. Ref.4

Secondary structure

1 ............. 986
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
Isoform Long [UniParc].

Last modified October 1, 1994. Version 1.
Checksum: D16AD8B85668C80E

FASTA986109,802
        10         20         30         40         50         60 
MAGIFYFILF SFLFGICDAV TGSRVYPANE VTLLDSRSVQ GELGWIASPL EGGWEEVSIM 

        70         80         90        100        110        120 
DEKNTPIRTY QVCNVMEASQ NNWLRTDWIT REGAQRVYIE IKFTLRDCNS LPGVMGTCKE 

       130        140        150        160        170        180 
TFNLYYYESD NDKERFIRES QFGKTDTIAA DESFTQVDIG DRIMKLNTEI RDVGPLSKKG 

       190        200        210        220        230        240 
FYLAFQDVGA CIALVSVRVF YKKCPLTVRN LAQFPDTITG ADTSSLVEVR GSCVNNSEEK 

       250        260        270        280        290        300 
DVPKMYCGAD GEWLVPIGNC LCNAGHEEQN GECQACKIGY YKALSTDASC AKCPPHSYSV 

       310        320        330        340        350        360 
WEGATSCTCD RGFFRADNDA ASMPCTRPPS APLNLISNVN ETSVNLEWSS PQNTGGRQDI 

       370        380        390        400        410        420 
SYNVVCKKCG AGDPSKCRPC GSGVHYTPQQ NGLKTTRVSI TDLLAHTNYT FEIWAVNGVS 

       430        440        450        460        470        480 
KYNPSPDQSV SVTVTTNQAA PSSIALVQAK EVTRYSVALA WLEPDRPNGV ILEYEVKYYE 

       490        500        510        520        530        540 
KDQNERSYRI VRTAARNTDI KGLNPLTSYV FHVRARTAAG YGDFSEPLEV TTNTVPSRII 

       550        560        570        580        590        600 
GDGANSTVLL VSVSGSVVLV VILIAAFVIS RRRSKYSKAK QEADEEKHLN QGVRTYVDPF 

       610        620        630        640        650        660 
TYEDPNQAVR EFAKEIDASC IKIEKVIGVG EFGEVCSGRL KVPGKREICV AIKTLKAGYT 

       670        680        690        700        710        720 
DKQRRDFLSE ASIMGQFDHP NIIHLEGVVT KCKPVMIITE YMENGSLDAF LRKNDGRFTV 

       730        740        750        760        770        780 
IQLVGMLRGI GSGMKYLSDM SYVHRDLAAR NILVNSNLVC KVSDFGMSRV LEDDPEAAYT 

       790        800        810        820        830        840 
TRGGKIPIRW TAPEAIAYRK FTSASDVWSY GIVMWEVMSY GERPYWDMSN QDVIKAIEEG 

       850        860        870        880        890        900 
YRLPPPMDCP IALHQLMLDC WQKERSDRPK FGQIVNMLDK LIRNPNSLKR TGSESSRPNT 

       910        920        930        940        950        960 
ALLDPSSPEF SAVVSVGDWL QAIKMDRYKD NFTAAGYTTL EAVVHMSQDD LARIGITAIT 

       970        980 
HQNKILSSVQ AMRTQMQQMH GRMVPV

« Hide

Isoform Short.

Checksum: 6F0CA18BC5FFBC62
Show »

FASTA936103,972

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References

« Hide 'large scale' references
[1]"An Eph-related receptor protein tyrosine kinase gene segmentally expressed in the developing mouse hindbrain."
Gilardi-Hebenstreit P., Nieto M.A., Frain M., Mattei M.-G., Chestier A., Wilkinson D.G., Charnay P.
Oncogene 7:2499-2506(1992) [PubMed: 1281307] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: C57BL/6.
Tissue: Embryonic brain.
[2]Erratum
Gilardi-Hebenstreit P., Nieto M.A., Frain M., Mattei M.-G., Chestier A., Wilkinson D.G., Charnay P.
Oncogene 8:1103-1103(1993) [PubMed: 8455939] [Abstract]
[3]"A juxtamembrane autophosphorylation site in the Eph family receptor tyrosine kinase, Sek, mediates high affinity interaction with p59fyn."
Ellis C., Kasmi F., Ganju P., Walls E., Panayotou G., Reith A.D.
Oncogene 12:1727-1736(1996) [PubMed: 8622893] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-596 AND TYR-602.
[4]"EphA receptors regulate growth cone dynamics through the novel guanine nucleotide exchange factor ephexin."
Shamah S.M., Lin M.Z., Goldberg J.L., Estrach S., Sahin M., Hu L., Bazalakova M., Neve R.L., Corfas G., Debant A., Greenberg M.E.
Cell 105:233-244(2001) [PubMed: 11336673] [Abstract]
Cited for: INTERACTION WITH NGEF, MUTAGENESIS OF VAL-635.
[5]"Developmental expression of EphA4-tyrosine kinase receptor in the mouse brain and spinal cord."
Greferath U., Canty A.J., Messenger J., Murphy M.
Mech. Dev. 119:S231-S238(2002) [PubMed: 14516691] [Abstract]
Cited for: TISSUE SPECIFICITY.
[6]"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain."
Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.
J. Proteome Res. 7:311-318(2008) [PubMed: 18034455] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-596 AND TYR-602, MASS SPECTROMETRY.
Tissue: Brain.
+Additional computationally mapped references.

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Cross-references

Sequence databases

X65138 mRNA. Translation: CAA46268.1.
X57241 mRNA. Translation: CAA40517.1.
S57168 mRNA. Translation: AAB25836.1.
IPIIPI00129198.
IPI00230383.
PIRS78059.
RefSeqNP_031962.2.
UniGeneMm.400747

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1B0XX-ray2.00A890-981[»]
2HELX-ray2.35A591-896[»]
2I8Jmodel-@594-888[»]
SMRQ03137. Positions 613-888.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP:1019N.
IntActQ03137. 5 interactions.

PTM databases

PhosphoSiteQ03137.

Proteomic databases

PRIDEQ03137.

Genome annotation databases

EnsemblENSMUSG00000026235. Mus musculus. [Contig view]
GeneID13838.
KEGGmmu:13838.

Organism-specific databases

MGIMGI:98277. Epha4.

Phylogenomic databases

HOGENOMQ03137.
HOVERGENQ03137.

Enzyme and pathway databases

BRENDA2.7.10.1. 244.

Gene expression databases

ArrayExpressQ03137.
BgeeQ03137.
CleanExMM_EPHA4.
GermOnlineENSMUSG00000026235. Mus musculus.

Family and domain databases

InterProIPR001090. 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.
IPR011510. SAM_2.
IPR013761. SAM_type.
IPR001245. Tyr_pkinase.
IPR008266. Tyr_pkinase_AS.
IPR016257. TyrPK_ephrin_receptor.
IPR001426. YKase_receptorV_CS.
[Graphical view]
Gene3DG3DSA:2.60.40.30. FN_III-like. 2 hits.
G3DSA:1.10.150.50. SAM_type. 1 hit.
PfamPF01404. Ephrin_lbd. 1 hit.
PF00041. fn3. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
PF07647. SAM_2. 1 hit.
[Graphical view]
PIRSFPIRSF000666. TyrPK_ephrin_receptor. 1 hit.
PRINTSPR00014. FNTYPEIII.
PR00109. TYRKINASE.
ProDomPD001495. Ephrin_receptor. 1 hit.
PD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00615. EPH_lbd. 1 hit.
SM00060. FN3. 2 hits.
SM00454. SAM. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
PROSITEPS50853. 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 Resources

NextBio284664.
SOURCESearch...

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Entry information

Entry nameEPHA4_MOUSE
AccessionPrimary (citable) accession number: Q03137
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: October 1, 1994
Last modified: June 16, 2009
This is version 108 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

MGD cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents