Q60629 (EPHA5_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ephrin type-A receptor 5
EC=2.7.10.1

Alternative name(s):
Brain-specific kinase
CEK-7
EPH homology kinase 1
Short name=EHK-1

Gene names

Name:	Epha5
Synonyms:	Bsk, Ehk1

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	876 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 GPI-anchored 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. Among GPI-anchored ephrin-A ligands, EFNA5 most probably constitutes the cognate/functional ligand for EPHA5. Functions as an axon guidance molecule during development and may be involved in the development of the retinotectal, entorhino-hippocampal and hippocamposeptal pathways. Together with EFNA5 plays also a role in synaptic plasticity in adult brain through regulation of synaptogenesis. Beside its function in the nervous system, the interaction of EPHA5 with EFNA5 mediates communication between pancreatic islet cells to regulate glucose-stimulated insulin secretion. Ref.3 Ref.4
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Heterotetramer upon binding of the ligand. The heterotetramer is composed of an ephrin dimer and a receptor dimer. Oligomerization is probably required to induce biological responses By similarity.
Subcellular location	Cell membrane; Single-pass type I membrane protein. Cell projection › axon By similarity. Cell projection › dendrite By similarity.
Tissue specificity	Specifically expressed in the brain. Highly expressed in hippocampus, tenia tecta, indusium griseum and piriform cortex. The highest level of expression is found in the CA3 region of the hippocampus and the pyramidal cell layer of the piriform cortex. In addition, elevated levels of expression are also found in amygdala, medial septum, nucleus of the diagonal band, and in olfactory bulb. Expressed in pancreatic islet cells (at protein level). Ref.1 Ref.4
Developmental stage	Within the developing nervous system, the expression is very dynamic. At E16.5 expressed predominantly in the primordial cortex of the telencephalon. Besides the midbrain it is also expressed in the hypothalamus, and the neurohypophysis. Non neuronal expression domains include the ectoderm of the branchial arches, the ectoderm and mesenchyme surrounding the dorsal root ganglia, the intervertebral disks, maxillary and mandibulary mesenchymal elements as well as the nasal mesenchyme and ectoderm. Ref.1
Post-translational modification	Phosphorylated. Phosphorylation is stimulated by the ligand EFNA5. Dephosphorylation upon stimulation by glucose, inhibits EPHA5 forward signaling and results in insulin secretion. Ref.3 Ref.4 Ref.5 Ref.6
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily. Contains 1 Eph LBD (Eph ligand-binding) domain. Contains 1 fibronectin type-III domain. Contains 1 protein kinase domain. Contains 1 SAM (sterile alpha motif) domain.

Ontologies

Keywords
Biological process	Neurogenesis
Cellular component	Cell membrane Cell projection Membrane
Domain	Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	axon guidance Inferred from direct assay Ref.3. Source: UniProtKB cAMP-mediated signaling Inferred from sequence or structural similarity. Source: UniProtKB hippocampus development Inferred from direct assay Ref.3. Source: UniProtKB positive regulation of CREB transcription factor activity Inferred from sequence or structural similarity. Source: UniProtKB regulation of Rac GTPase activity Inferred from direct assay Ref.4. Source: UniProtKB regulation of actin cytoskeleton organization Inferred from direct assay Ref.4. Source: UniProtKB regulation of insulin secretion involved in cellular response to glucose stimulus Inferred from direct assay Ref.4. Source: UniProtKB
Cellular component	axon Inferred from electronic annotation. Source: UniProtKB-SubCell dendrite Inferred from sequence or structural similarity. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW GPI-linked ephrin receptor activity Inferred from direct assay Ref.4. Source: UniProtKB protein binding Inferred from physical interaction. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 26	26	By similarity
	Chain	27 – 876	850	Ephrin type-A receptor 5		PRO_0000016813
Regions
	Topological domain	27 – 412	386	Extracellular Potential
	Transmembrane	413 – 433	21	Helical; Potential
	Topological domain	434 – 876	443	Cytoplasmic Potential
	Domain	62 – 240	179	Eph LBD
	Domain	307 – 397	91	Fibronectin type-III
	Domain	514 – 775	262	Protein kinase
	Domain	804 – 868	65	SAM
	Nucleotide binding	520 – 528	9	ATP By similarity
	Motif	874 – 876	3	PDZ-binding Potential
Sites
	Active site	639	1	Proton acceptor By similarity
	Binding site	546	1	ATP By similarity
Amino acid modifications
	Modified residue	489	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	495	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	672	1	Phosphotyrosine; by autocatalysis Potential
	Modified residue	821	1	Phosphotyrosine; by autocatalysis By similarity
	Glycosylation	266	1	N-linked (GlcNAc...) Potential
	Glycosylation	301	1	N-linked (GlcNAc...) Potential
Experimental info
	Sequence conflict	532	1	R → C in AAA17038. Ref.1
	Sequence conflict	697	1	S → A in AAA17038. Ref.1
	Sequence conflict	855	1	Q → QK in AAA17038. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q60629 [UniParc]. Last modified October 19, 2011. Version 2. Checksum: D6539F74DCB6B763	FASTA	876	97,056
	10 20 30 40 50 60 MRGSGPRGAG HRRTQGRGGG DDTPRVPASL AGCYSAPLKG PLWTCLLLCA ALRTLLASPS 70 80 90 100 110 120 NEVNLLDSRT VMGDLGWIAF PKNGWEEIGE VDENYAPIHT YQVCKVMEQN QNNWLLTSWI 130 140 150 160 170 180 SNEGASRIFI ELKFTLRDCN SLPGGLGTCK ETFNMYYFES DDENGRSIKE NQYIKIDTIA 190 200 210 220 230 240 ADESFTELDL GDRVMKLNTE VRDVGPLSKK GFYLAFQDVG ACIALVSVRV YYKKCPSVVR 250 260 270 280 290 300 HLAIFPDTIT GADSSQLLEV SGSCVNHSVT DDPPKMHCSA EGEWLVPIGK CMCKAGYEEK 310 320 330 340 350 360 NGTCQAPSPV TNVKKGKIAK NSISLSWQEP DRPNGIILEY EIKYFEKDQE TSYTIIKSKE 370 380 390 400 410 420 TSITAEGLKP ASVYVFQIRA RTAAGYGVFS RRFEFETTPV SVAASNDQSQ IPIIAVSVTV 430 440 450 460 470 480 GVILLAVMIG FLLSGSCCDC GCGRASSLCA VAHPSLIWRC GYSKAKQDPE EEKMHFHNGH 490 500 510 520 530 540 IKLPGVRTYI DPHTYEDPNQ AVHEFAKEIE ASCITIERVI GAGEFGEVCS GRLKLPGKRE 550 560 570 580 590 600 LPVAIKTLKV GYTEKQRRDF LGEASIMGQF DHPNIIHLEG VVTKSKPVMI VTEYMENGSL 610 620 630 640 650 660 DTFLKKNDGQ FTVIQLVGML RGIAAGMKYL SDMGYVHRDL AARNILINSN LVCKVSDFGL 670 680 690 700 710 720 SRVLEDDPEA AYTTRGGKIP IRWTAPEAIA FRKFTSSSDV WSYGIVMWEV VSYGERPYWE 730 740 750 760 770 780 MTNQDVIKAV EEGYRLPSPM DCPAALYQLM LDCWQKDRNS RPKFDEIVNM LDKLIRNPSS 790 800 810 820 830 840 LKTLVNASSR VSTLLAEHGS LGSGAYRSVG EWLEAIKMGR YTEIFMENGY SSMDAVAQVT 850 860 870 LEDLRRLGVT LVGHQKKIMS SLQEMKVQMV NGMVPV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of Bsk, a growth factor receptor-like tyrosine kinase associated with the limbic system." Zhou R., Copeland T.D., Kromer L.F., Schulz N.T. J. Neurosci. Res. 37:129-143(1994) [PubMed: 8145300] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. Strain: BALB/c. Tissue: Brain.
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed: 19468303] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6.
[3]	"Mistargeting hippocampal axons by expression of a truncated Eph receptor." Yue Y., Chen Z.Y., Gale N.W., Blair-Flynn J., Hu T.J., Yue X., Cooper M., Crockett D.P., Yancopoulos G.D., Tessarollo L., Zhou R. Proc. Natl. Acad. Sci. U.S.A. 99:10777-10782(2002) [PubMed: 12124402] [Abstract] Cited for: FUNCTION IN AXON GUIDANCE, PHOSPHORYLATION.
[4]	"EphA-Ephrin-A-mediated beta cell communication regulates insulin secretion from pancreatic islets." Konstantinova I., Nikolova G., Ohara-Imaizumi M., Meda P., Kucera T., Zarbalis K., Wurst W., Nagamatsu S., Lammert E. Cell 129:359-370(2007) [PubMed: 17448994] [Abstract] Cited for: FUNCTION IN INSULIN SECRETION, TISSUE SPECIFICITY, PHOSPHORYLATION, DEPHOSPHORYLATION.
[5]	"Quantitative time-resolved phosphoproteomic analysis of mast cell signaling." Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R. J. Immunol. 179:5864-5876(2007) [PubMed: 17947660] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-672, MASS SPECTROMETRY. Tissue: Mast cell.
[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-489; TYR-495 AND TYR-672, MASS SPECTROMETRY. Tissue: Brain.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U07357 mRNA. Translation: AAA17038.1. AC101956 Genomic DNA. No translation available. AC114638 Genomic DNA. No translation available. AC129220 Genomic DNA. No translation available. AC132597 Genomic DNA. No translation available.
IPI	IPI00309958.
PIR	I48967.
RefSeq	NP_031963.2. NM_007937.3.
UniGene	Mm.137991. Mm.438006.
3D structure databases
ProteinModelPortal	Q60629.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q60629. 1 interaction.
STRING	Q60629.
PTM databases
PhosphoSite	Q60629.
Proteomic databases
PRIDE	Q60629.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000053733; ENSMUSP00000060646; ENSMUSG00000029245.
GeneID	13839.
KEGG	mmu:13839.
UCSC	uc008xwv.2. mouse.
Organism-specific databases
MGI	MGI:99654. Epha5.
Phylogenomic databases
HOVERGEN	HBG062180.
OrthoDB	EOG4894KT.
Enzyme and pathway databases
BRENDA	2.7.10.1. 3474.
Gene expression databases
ArrayExpress	Q60629.
Bgee	Q60629.
CleanEx	MM_EPHA5.
Genevestigator	Q60629.
GermOnline	ENSMUSG00000029245. Mus musculus.
Family and domain databases
InterPro	IPR001090. Ephrin_rcpt_lig-bd. IPR003961. Fibronectin_type3. IPR008979. Galactose-bd-like. 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. IPR001426. Tyr_kinase_rcpt_V_CS. [Graphical view]
Gene3D	G3DSA:2.60.40.10. Ig-like_fold. 1 hit. G3DSA:1.10.150.50. SAM_type. 1 hit.
KO	K05106.
Pfam	PF01404. Ephrin_lbd. 1 hit. PF00041. fn3. 1 hit. PF07714. Pkinase_Tyr. 1 hit. PF00536. SAM_1. 1 hit. [Graphical view]
PRINTS	PR00109. TYRKINASE.
SMART	SM00615. EPH_lbd. 1 hit. SM00060. FN3. 1 hit. SM00454. SAM. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF49265. FN_III-like. 1 hit. SSF49785. Gal_bind_like. 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. 1 hit. 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
SOURCE	Search...

Entry information

Entry name

EPHA5_MOUSE

Accession

Primary (citable) accession number: Q60629
Secondary accession number(s): E9QPV2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	October 19, 2011
Last modified:	January 25, 2012
This is version 122 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program