Reviewed, UniProtKB/Swiss-Prot O09127 (EPHA8_MOUSE)

Names and origin

Protein names

Recommended name:
    Ephrin type-A receptor 8
    EC=2.7.10.1
Alternative name(s):
    Tyrosine-protein kinase receptor EEK
    EPH- and ELK-related kinase

Gene names

Name:	Epha8
Synonyms:	Eek

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

Protein attributes

Sequence length	1004 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. Interacts at least with ephrin-A2, -A3, and -A5.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Interacts with ANKS1B By similarity. Interacts with FYN.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Central nervous system.
Post-translational modification	Phosphorylation on Tyr-615 is critical for association with FYN. Phosphorylation on Tyr-838 modulates tyrosine kinase activity.
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
Domain	Repeat Signal Transmembrane
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Glycoprotein Phosphoprotein
Gene Ontology (GO)
Biological process	protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro transmembrane receptor protein tyrosine kinase signaling pathway Inferred from electronic annotation. Source: InterPro
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ephrin receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 27	27	Potential
	Chain	28 – 1004	977	Ephrin type-A receptor 8		PRO_0000016823
Regions
	Topological domain	28 – 541	514	Extracellular Potential
	Transmembrane	542 – 562	21	Potential
	Topological domain	563 – 1004	442	Cytoplasmic Potential
	Domain	327 – 429	103	Fibronectin type-III 1
	Domain	435 – 530	96	Fibronectin type-III 2
	Domain	634 – 895	262	Protein kinase
	Domain	929 – 993	65	SAM
	Nucleotide binding	640 – 648	9	ATP By similarity
	Motif	1002 – 1004	3	PDZ-binding Potential
	Compositional bias	190 – 324	135	Cys-rich
Sites
	Active site	759	1	Proton acceptor By similarity
	Binding site	666	1	ATP By similarity
Amino acid modifications
	Modified residue	615	1	Phosphotyrosine; by autocatalysis Ref.2
	Modified residue	838	1	Phosphotyrosine; by autocatalysis Ref.2
	Glycosylation	339	1	N-linked (GlcNAc...) Potential
	Glycosylation	406	1	N-linked (GlcNAc...) Potential
	Glycosylation	431	1	N-linked (GlcNAc...) Potential
Experimental info
	Mutagenesis	615	1	Y → F: Reduced association with FYN. Ref.2
	Mutagenesis	838	1	Y → F: Reduced tyrosine kinase activity. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	O09127-1 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: 8530E800290FE502	FASTA	1,004	110,764
	10 20 30 40 50 60 MAPARARLSP ALWVVTAAAA ATCVSAGRGE VNLLDTSTIH GDWGWLTYPA HGWDSINEVD 70 80 90 100 110 120 ESFRPIHTYQ VCNVMSPNQN NWLRTNWVPR DGARRVYAEI KFTLRDCNSI PGVLGTCKET 130 140 150 160 170 180 FNLHYLESDR DLGASTQESQ FLKIDTIAAD ESFTGADLGV RRLKLNTEVR GVGPLSKRGF 190 200 210 220 230 240 YLAFQDIGAC LAILSLRIYY KKCPAMVRNL AAFSEAVTGA DSSSLVEVRG QCVRHSEERD 250 260 270 280 290 300 TPKMYCSAEG EWLVPIGKCV CSAGYEERRD ACMACELGFY KSAPGDQLCA RCPPHSHSAT 310 320 330 340 350 360 PAAQTCRCDL SYYRAALDPP SAACTRPPSA PVNLISSVNG TSVTLEWAPP LDPGGRSDIT 370 380 390 400 410 420 YNAVCRRCPW ALSHCEACGS GTRFVPQQTS LAQASLLVAN LLAHMNYSFW IEAVNGVSNL 430 440 450 460 470 480 SPEPRSAAVV NITTNQAAPS QVVVIRQERA GQTSVSLLWQ EPEQPNGIIL EYEIKYYEKD 490 500 510 520 530 540 KEMQSYSTLK AVTTRATVSG LKPGTRYVFQ VRARTSAGCG RFSQAMEVET GKPRPRYDTR 550 560 570 580 590 600 TIVWICLTLI TGLVVLLLLL ICKKRHCGYS KAFQDSDEEK MHYQNGQAPP PVFLPLNHPP 610 620 630 640 650 660 GKFPETQFSA EPHTYEEPGR AGRSFTREIE ASRIHIEKII GSGESGEVCY GRLQVPGQRD 670 680 690 700 710 720 VPVAIKALKA GYTERQRQDF LSEAAIMGQF DHPNIIRLEG VVTRGRLAMI VTEYMENGSL 730 740 750 760 770 780 DAFLRTHDGQ FTIVQLVGML RGVGAGMRYL SDLGYIHRDL AARNVLVDGR LVCKVSDFGL 790 800 810 820 830 840 SRALEDDPEA AYTTAGGKIP IRWTAPEAIA FRTFSSASDV WSFGVVMWEV LAYGERPYWN 850 860 870 880 890 900 MTNQDVISSV EEGYRLPAPM GCPRALHQLM LDCWHKDRAQ RPRFAHVVSV LDALVHSPES 910 920 930 940 950 960 LRATATVSRC PPPAFARSCF DLRAGGSGNG DLTVGDWLDS IRMGRYRDHF AAGGYSSLGM 970 980 990 1000 VLRMNAQDVR ALGITLMGHQ KKILGSIQTM RAQLSSTQGR RRHL

References

[1]	"The Eek receptor, a member of the Eph family of tyrosine protein kinases, can be activated by three different Eph family ligands." Park S., Sanchez M.P. Oncogene 14:533-542(1997) [PubMed: 9053851] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Phosphorylation at Tyr-838 in the kinase domain of EphA8 modulates Fyn binding to the Tyr-615 site by enhancing tyrosine kinase activity." Choi S., Park S. Oncogene 18:5413-5422(1999) [PubMed: 10498895] [Abstract] Cited for: PHOSPHORYLATION AT TYR-615 AND TYR-838, MUTAGENESIS OF TYR-615 AND TYR-838.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U72207 mRNA. Translation: AAB39218.1.
IPI	IPI00263411.
RefSeq	NP_031965.2.
UniGene	Mm.1390
3D structure databases
HSSP	HSSP built from PDB template 1JPA based on UniProtKB P54763.
SMR	O09127. Positions 433-533, 925-999.
ModBase	Search...
PTM databases
PhosphoSite	O09127.
Genome annotation databases
Ensembl	ENSMUSG00000028661. Mus musculus. [Contig view]
GeneID	13842.
KEGG	mmu:13842.
Organism-specific databases
MGI	MGI:109378. Epha8.
Phylogenomic databases
HOGENOM	O09127.
HOVERGEN	O09127.
Enzyme and pathway databases
BRENDA	2.7.10.1. 244.
Gene expression databases
ArrayExpress	O09127.
Bgee	O09127.
CleanEx	MM_EPHA8.
GermOnline	ENSMUSG00000028661. Mus musculus.
Family and domain databases
InterPro	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	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	284680.
SOURCE	Search...

Entry information

Entry name

EPHA8_MOUSE

Accession

Primary (citable) accession number: O09127

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	July 1, 1997
Last modified:	June 16, 2009
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)