P29322 · EPHA8_HUMAN
- ProteinEphrin type-A receptor 8
- GeneEPHA8
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1005 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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 also plays 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 + L-tyrosyl-[protein] = ADP + H+ + O-phospho-L-tyrosyl-[protein]
Features
Showing features for binding site, active site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | dendrite | |
Cellular Component | early endosome membrane | |
Cellular Component | neuron projection | |
Cellular Component | plasma membrane | |
Molecular Function | ATP binding | |
Molecular Function | ephrin receptor activity | |
Molecular Function | GPI-linked ephrin receptor activity | |
Molecular Function | growth factor binding | |
Molecular Function | transmembrane-ephrin receptor activity | |
Biological Process | axon guidance | |
Biological Process | cell adhesion | |
Biological Process | cellular response to follicle-stimulating hormone stimulus | |
Biological Process | ephrin receptor signaling pathway | |
Biological Process | neuron projection development | |
Biological Process | neuron remodeling | |
Biological Process | positive regulation of MAPK cascade | |
Biological Process | positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | |
Biological Process | regulation of cell adhesion | |
Biological Process | regulation of cell adhesion mediated by integrin | |
Biological Process | substrate-dependent cell migration |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameEphrin type-A receptor 8
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP29322
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Single-pass type I membrane protein
Note: Undergoes clathrin-mediated endocytosis upon EFNA5-binding and is targeted to early endosomes.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 28-542 | Extracellular | ||||
Sequence: ARGEVNLLDTSTIHGDWGWLTYPAHGWDSINEVDESFQPIHTYQVCNVMSPNQNNWLRTSWVPRDGARRVYAEIKFTLRDCNSMPGVLGTCKETFNLYYLESDRDLGASTQESQFLKIDTIAADESFTGADLGVRRLKLNTEVRSVGPLSKRGFYLAFQDIGACLAILSLRIYYKKCPAMVRNLAAFSEAVTGADSSSLVEVRGQCVRHSEERDTPKMYCSAEGEWLVPIGKCVCSAGYEERRDACVACELGFYKSAPGDQLCARCPPHSHSAAPAAQACHCDLSYYRAALDPPSSACTRPPSAPVNLISSVNGTSVTLEWAPPLDPGGRSDITYNAVCRRCPWALSRCEACGSGTRFVPQQTSLVQASLLVANLLAHMNYSFWIEAVNGVSDLSPEPRRAAVVNITTNQAAPSQVVVIRQERAGQTSVSLLWQEPEQPNGIILEYEIKYYEKDKEMQSYSTLKAVTTRATVSGLKPGTRYVFQVRARTSAGCGRFSQAMEVETGKPRPRYDTRT | ||||||
Transmembrane | 543-563 | Helical | ||||
Sequence: IVWICLTLITGLVVLLLLLIC | ||||||
Topological domain | 564-1005 | Cytoplasmic | ||||
Sequence: KKRHCGYSKAFQDSDEEKMHYQNGQAPPPVFLPLHHPPGKLPEPQFYAEPHTYEEPGRAGRSFTREIEASRIHIEKIIGSGDSGEVCYGRLRVPGQRDVPVAIKALKAGYTERQRRDFLSEASIMGQFDHPNIIRLEGVVTRGRLAMIVTEYMENGSLDTFLRTHDGQFTIMQLVGMLRGVGAGMRYLSDLGYVHRDLAARNVLVDSNLVCKVSDFGLSRVLEDDPDAAYTTTGGKIPIRWTAPEAIAFRTFSSASDVWSFGVVMWEVLAYGERPYWNMTNRDVISSVEEGYRLPAPMGCPHALHQLMLDCWHKDRAQRPRFSQIVSVLDALIRSPESLRATATVSRCPPPAFVRSCFDLRGGSGGGGGLTVGDWLDSIRMGRYRDHFAAGGYSSLGMVLRMNAQDVRALGITLMGHQKKILGSIQTMRAQLTSTQGPRRHL |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_042153 | 45 | in dbSNP:rs45498698 | |||
Sequence: G → S | ||||||
Natural variant | VAR_042154 | 60 | in dbSNP:rs56402644 | |||
Sequence: V → L | ||||||
Natural variant | VAR_042155 | 123 | in a breast infiltrating ductal carcinoma sample; somatic mutation | |||
Sequence: N → K | ||||||
Natural variant | VAR_042156 | 179 | in a gastric adenocarcinoma sample; somatic mutation; dbSNP:rs1557556639 | |||
Sequence: R → C | ||||||
Natural variant | VAR_042157 | 198 | in a lung adenocarcinoma sample; somatic mutation | |||
Sequence: R → L | ||||||
Natural variant | VAR_061292 | 321 | in dbSNP:rs56656925 | |||
Sequence: P → L | ||||||
Natural variant | VAR_022107 | 444 | in dbSNP:rs2295021 | |||
Sequence: V → M | ||||||
Natural variant | VAR_024514 | 612 | in dbSNP:rs999765 | |||
Sequence: E → Q | ||||||
Natural variant | VAR_042158 | 860 | in a metastatic melanoma sample; somatic mutation | |||
Sequence: P → L |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,310 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, glycosylation, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-27 | |||||
Sequence: MAPARGRLPPALWVVTAAAAAATCVSA | ||||||
Chain | PRO_0000016822 | 28-1005 | Ephrin type-A receptor 8 | |||
Sequence: ARGEVNLLDTSTIHGDWGWLTYPAHGWDSINEVDESFQPIHTYQVCNVMSPNQNNWLRTSWVPRDGARRVYAEIKFTLRDCNSMPGVLGTCKETFNLYYLESDRDLGASTQESQFLKIDTIAADESFTGADLGVRRLKLNTEVRSVGPLSKRGFYLAFQDIGACLAILSLRIYYKKCPAMVRNLAAFSEAVTGADSSSLVEVRGQCVRHSEERDTPKMYCSAEGEWLVPIGKCVCSAGYEERRDACVACELGFYKSAPGDQLCARCPPHSHSAAPAAQACHCDLSYYRAALDPPSSACTRPPSAPVNLISSVNGTSVTLEWAPPLDPGGRSDITYNAVCRRCPWALSRCEACGSGTRFVPQQTSLVQASLLVANLLAHMNYSFWIEAVNGVSDLSPEPRRAAVVNITTNQAAPSQVVVIRQERAGQTSVSLLWQEPEQPNGIILEYEIKYYEKDKEMQSYSTLKAVTTRATVSGLKPGTRYVFQVRARTSAGCGRFSQAMEVETGKPRPRYDTRTIVWICLTLITGLVVLLLLLICKKRHCGYSKAFQDSDEEKMHYQNGQAPPPVFLPLHHPPGKLPEPQFYAEPHTYEEPGRAGRSFTREIEASRIHIEKIIGSGDSGEVCYGRLRVPGQRDVPVAIKALKAGYTERQRRDFLSEASIMGQFDHPNIIRLEGVVTRGRLAMIVTEYMENGSLDTFLRTHDGQFTIMQLVGMLRGVGAGMRYLSDLGYVHRDLAARNVLVDSNLVCKVSDFGLSRVLEDDPDAAYTTTGGKIPIRWTAPEAIAFRTFSSASDVWSFGVVMWEVLAYGERPYWNMTNRDVISSVEEGYRLPAPMGCPHALHQLMLDCWHKDRAQRPRFSQIVSVLDALIRSPESLRATATVSRCPPPAFVRSCFDLRGGSGGGGGLTVGDWLDSIRMGRYRDHFAAGGYSSLGMVLRMNAQDVRALGITLMGHQKKILGSIQTMRAQLTSTQGPRRHL | ||||||
Glycosylation | 340 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 407 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 432 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Modified residue | 616 | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | ||||||
Modified residue | 839 | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y |
Post-translational modification
Phosphorylated. Phosphorylation is stimulated upon binding of its ligands including EFNA2, EFNA3 and EFNA5. Autophosphorylation on Tyr-616 is critical for association with FYN. Autophosphorylation on Tyr-839 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).
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
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 (By similarity).
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
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
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 31-209 | Eph LBD | ||||
Sequence: EVNLLDTSTIHGDWGWLTYPAHGWDSINEVDESFQPIHTYQVCNVMSPNQNNWLRTSWVPRDGARRVYAEIKFTLRDCNSMPGVLGTCKETFNLYYLESDRDLGASTQESQFLKIDTIAADESFTGADLGVRRLKLNTEVRSVGPLSKRGFYLAFQDIGACLAILSLRIYYKKCPAMVR | ||||||
Domain | 328-438 | Fibronectin type-III 1 | ||||
Sequence: PPSAPVNLISSVNGTSVTLEWAPPLDPGGRSDITYNAVCRRCPWALSRCEACGSGTRFVPQQTSLVQASLLVANLLAHMNYSFWIEAVNGVSDLSPEPRRAAVVNITTNQA | ||||||
Domain | 439-534 | Fibronectin type-III 2 | ||||
Sequence: APSQVVVIRQERAGQTSVSLLWQEPEQPNGIILEYEIKYYEKDKEMQSYSTLKAVTTRATVSGLKPGTRYVFQVRARTSAGCGRFSQAMEVETGKP | ||||||
Region | 564-570 | Mediates interaction with ANKS1A and ANKS1B | ||||
Sequence: KKRHCGY | ||||||
Region | 589-644 | Mediates interaction with PIK3CG and required for endocytosis | ||||
Sequence: APPPVFLPLHHPPGKLPEPQFYAEPHTYEEPGRAGRSFTREIEASRIHIEKIIGSG | ||||||
Domain | 635-896 | Protein kinase | ||||
Sequence: IHIEKIIGSGDSGEVCYGRLRVPGQRDVPVAIKALKAGYTERQRRDFLSEASIMGQFDHPNIIRLEGVVTRGRLAMIVTEYMENGSLDTFLRTHDGQFTIMQLVGMLRGVGAGMRYLSDLGYVHRDLAARNVLVDSNLVCKVSDFGLSRVLEDDPDAAYTTTGGKIPIRWTAPEAIAFRTFSSASDVWSFGVVMWEVLAYGERPYWNMTNRDVISSVEEGYRLPAPMGCPHALHQLMLDCWHKDRAQRPRFSQIVSVLDALI | ||||||
Domain | 930-994 | SAM | ||||
Sequence: GGGLTVGDWLDSIRMGRYRDHFAAGGYSSLGMVLRMNAQDVRALGITLMGHQKKILGSIQTMRAQ | ||||||
Motif | 1003-1005 | PDZ-binding | ||||
Sequence: RHL |
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 2 isoforms produced by Alternative splicing.
P29322-1
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.
- Name1
- Length1,005
- Mass (Da)111,003
- Last updated2001-10-18 v2
- Checksum6FBF85535E4212B3
P29322-2
- Name2
Sequence caution
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 237 | in Ref. 3; BAA95983 | ||||
Sequence: S → L | ||||||
Alternative sequence | VSP_041946 | 439-495 | in isoform 2 | |||
Sequence: APSQVVVIRQERAGQTSVSLLWQEPEQPNGIILEYEIKYYEKDKEMQSYSTLKAVTT → GRRRNSVPQRPGPPASPASDPSRDQSSAGDVLWAFRQVPLWPCAPHQDPELEALHCL | ||||||
Alternative sequence | VSP_041947 | 496-1005 | in isoform 2 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AL035703 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC038796 EMBL· GenBank· DDBJ | AAH38796.1 EMBL· GenBank· DDBJ | mRNA | ||
BC072417 EMBL· GenBank· DDBJ | AAH72417.2 EMBL· GenBank· DDBJ | mRNA | ||
AB040892 EMBL· GenBank· DDBJ | BAA95983.1 EMBL· GenBank· DDBJ | mRNA | ||
X59291 EMBL· GenBank· DDBJ | CAA41980.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation |