P29321 (EPHA8_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ephrin type-A receptor 8
EC=2.7.10.1

Alternative name(s):
EPH- and ELK-related kinase
Tyrosine-protein kinase receptor EEK

Gene names

Name:	Epha8
Synonyms:	Eek

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	372 AA.
Sequence status	Fragment.
Protein existence	Evidence at transcript 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. The GPI-anchored ephrin-A EFNA2, EFNA3, and EFNA5 are able to activate EPHA8 through phosphorylation. With EFNA5 may regulate integrin-mediated cell adhesion and migration on fibronectin substrate but also neurite outgrowth. During development of the nervous system plays also a role in axon guidance. Downstream effectors of the EPHA8 signaling pathway include FYN which promotes cell adhesion upon activation by EPHA8 and the MAP kinases in the stimulation of neurite outgrowth By similarity.
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. May also form heterodimers with other ephrin receptors. Interacts with FYN; possible downstream effector of EPHA8 in regulation of cell adhesion. Interacts with PIK3CG; regulates integrin-mediated cell adhesion to substrate. Interacts with TIAM1; regulates clathrin-mediated endocytosis of EPHA8. Interacts with ANKS1A and ANKS1B; EPHA8 kinase activity-independent but stimulated by EPHA8 ubiquitination By similarity.
Subcellular location	Cell membrane By similarity; Single-pass type I membrane protein By similarity. Cell projection By similarity. Early endosome membrane By similarity. Note: Undergoes clathrin-mediated endocytosis upon EFNA5-binding and is targeted to early endosomes By similarity.
Tissue specificity	Most abundant in brain.
Post-translational modification	Phosphorylated. Phosphorylation is stimulated upon binding of its ligands including EFNA2, EFNA3 and EFNA5. Autophosphorylation on Tyr-206 modulates tyrosine kinase activity By similarity. Ubiquitinated. Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation. ANKS1A prevents ubiquitination and degradation By similarity.
Sequence similarities	Contains 1 protein kinase domain. Contains 1 SAM (sterile alpha motif) domain.

Ontologies

Keywords
Biological process	Cell adhesion Neurogenesis
Cellular component	Cell membrane Cell projection Endosome Membrane
Ligand	ATP-binding Nucleotide-binding
Molecular function	Developmental protein Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	axon guidance Inferred from sequence or structural similarity. Source: UniProtKB cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW neuron remodeling Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of MAPKKK cascade Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of phosphatidylinositol 3-kinase activity Inferred from sequence or structural similarity. Source: UniProtKB protein autophosphorylation Inferred from sequence or structural similarity. Source: UniProtKB regulation of cell adhesion mediated by integrin Inferred from sequence or structural similarity. Source: UniProtKB substrate-dependent cell migration Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	early endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB neuron projection 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 sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	‹1 – 372	›372	Ephrin type-A receptor 8		PRO_0000160273
Regions
	Domain	2 – 263	262	Protein kinase
	Domain	297 – 372	76	SAM
	Nucleotide binding	8 – 16	9	ATP By similarity
	Motif	370 – 372	3	PDZ-binding Potential
Sites
	Active site	127	1	Proton acceptor By similarity
	Binding site	34	1	ATP By similarity
Amino acid modifications
	Modified residue	206	1	Phosphotyrosine; by autocatalysis By similarity
Experimental info
	Non-terminal residue	1	1

Sequences

	Sequence		Length	Mass (Da)
	P29321 [UniParc]. Last modified December 1, 1992. Version 1. Checksum: C8FDCFB5A6904BA5	FASTA	372	41,233
	10 20 30 40 50 60 RIHIEKIIGS GESGEVCYGR LQVPGQRDVP VAIKALKAGY TERQRQDFLR EAAIMGQFDH 70 80 90 100 110 120 PNIIRLEGVV TRGRLAMIVT EYMENGSLDA FLRTHDGQFT ILQLVGMLKG VGAGMRYLSD 130 140 150 160 170 180 LGYIHRDLAA RNILVDGRLV CKVSDFGLSR ALEDDPEAAY TTAGGKIPIR WTAPEAIAFR 190 200 210 220 230 240 TFSSASDVWS FGVVMWEVLA YGERPYWNMT NQDVISSVEE GYRLPAPMGC PRALHQLMLD 250 260 270 280 290 300 CWHKDRAQRP RFSHVVSVLE ALVHSPESLR ATATVSRCPA PAFARSCFDL RAGGNGNGDL 310 320 330 340 350 360 TVGDWLDSIR MGRYRDHFAA GGYSSLGMVL HMNAQDVRAL GITLMGHQKK ILGSIQTMRS 370 QLSCTQGPRR HL

References

[1]	"eek and erk, new members of the eph subclass of receptor protein-tyrosine kinases." Chan J., Watt V.M. Oncogene 6:1057-1061(1991) [PubMed: 1648701] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Wistar. Tissue: Brain.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X59290 mRNA. Translation: CAA41979.1.
IPI	IPI00359105.
PIR	S23363.
UniGene	Rn.62934.
3D structure databases
ProteinModelPortal	P29321.
SMR	P29321. Positions 2-266, 293-367.
ModBase	Search...
Protein-protein interaction databases
STRING	P29321.
PTM databases
PhosphoSite	P29321.
Proteomic databases
PRIDE	P29321.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Organism-specific databases
RGD	708543. Epha8.
Phylogenomic databases
eggNOG	maNOG18501.
GeneTree	ENSGT00600000084150.
HOVERGEN	HBG062180.
InParanoid	P29321.
OrthoDB	EOG4MCWZJ.
Gene expression databases
ArrayExpress	P29321.
Genevestigator	P29321.
GermOnline	ENSRNOG00000013036. Rattus norvegicus.
Family and domain databases
InterPro	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. [Graphical view]
Gene3D	G3DSA:1.10.150.50. SAM_type. 1 hit.
Pfam	PF07714. Pkinase_Tyr. 1 hit. PF00536. SAM_1. 1 hit. [Graphical view]
PRINTS	PR00109. TYRKINASE.
SMART	SM00454. SAM. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit. SSF47769. SAM_homology. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00109. PROTEIN_KINASE_TYR. 1 hit. PS00790. RECEPTOR_TYR_KIN_V_1. Partial match. PS00791. RECEPTOR_TYR_KIN_V_2. Partial match. PS50105. SAM_DOMAIN. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

EPHA8_RAT

Accession

Primary (citable) accession number: P29321

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	December 1, 1992
Last modified:	December 14, 2011
This is version 110 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program