Q06418 · TYRO3_HUMAN
- ProteinTyrosine-protein kinase receptor TYRO3
- GeneTYRO3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids890 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including TULP1 or GAS6. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of TYRO3 on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with PIK3R1 and thereby enhances PI3-kinase activity. Activates the AKT survival pathway, including nuclear translocation of NF-kappa-B and up-regulation of transcription of NF-kappa-B-regulated genes. TYRO3 signaling plays a role in various processes such as neuron protection from excitotoxic injury, platelet aggregation and cytoskeleton reorganization. Also plays an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3.
(Microbial infection) Acts as a receptor for lassa virus and lymphocytic choriomeningitis virus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope.
(Microbial infection) Acts as a receptor for Ebolavirus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope.
Catalytic activity
- ATP + L-tyrosyl-[protein] = ADP + H+ + O-phospho-L-tyrosyl-[protein]
Features
Showing features for binding site, active site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTyrosine-protein kinase receptor TYRO3
- 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 accessionQ06418
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Single-pass type I membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 41-429 | Extracellular | ||||
Sequence: AGLKLMGAPVKLTVSQGQPVKLNCSVEGMEEPDIQWVKDGAVVQNLDQLYIPVSEQHWIGFLSLKSVERSDAGRYWCQVEDGGETEISQPVWLTVEGVPFFTVEPKDLAVPPNAPFQLSCEAVGPPEPVTIVWWRGTTKIGGPAPSPSVLNVTGVTQSTMFSCEAHNLKGLASSRTATVHLQALPAAPFNITVTKLSSSNASVAWMPGADGRALLQSCTVQVTQAPGGWEVLAVVVPVPPFTCLLRDLVPATNYSLRVRCANALGPSPYADWVPFQTKGLAPASAPQNLHAIRTDSGLILEWEEVIPEAPLEGPLGPYKLSWVQDNGTQDELTVEGTRANLTGWDPQKDLIVRVCVSNAVGCGPWSQPLVVSSHDRAGQQGPPHSRTSW | ||||||
Transmembrane | 430-450 | Helical | ||||
Sequence: VPVVLGVLTALVTAAALALIL | ||||||
Topological domain | 451-890 | Cytoplasmic | ||||
Sequence: LRKRRKETRFGQAFDSVMARGEPAVHFRAARSFNRERPERIEATLDSLGISDELKEKLEDVLIPEQQFTLGRMLGKGEFGSVREAQLKQEDGSFVKVAVKMLKADIIASSDIEEFLREAACMKEFDHPHVAKLVGVSLRSRAKGRLPIPMVILPFMKHGDLHAFLLASRIGENPFNLPLQTLIRFMVDIACGMEYLSSRNFIHRDLAARNCMLAEDMTVCVADFGLSRKIYSGDYYRQGCASKLPVKWLALESLADNLYTVQSDVWAFGVTMWEIMTRGQTPYAGIENAEIYNYLIGGNRLKQPPECMEDVYDLMYQCWSADPKQRPSFTCLRMELENILGQLSVLSASQDPLYINIERAEEPTAGGSLELPGRDQPYSGAGDGSGMGAVGGTPSDCRYILTPGGLAEQPGQAEHQPESPLNETQRLLLLQQGLLPHSSC |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_045886 | 21 | in dbSNP:rs17854578 | |||
Sequence: P → L | ||||||
Mutagenesis | 99 | Abolishes dimerization. | ||||
Sequence: I → R | ||||||
Natural variant | VAR_045887 | 346 | in dbSNP:rs12148316 | |||
Sequence: I → N | ||||||
Natural variant | VAR_045888 | 542 | in dbSNP:rs17857363 | |||
Sequence: G → S | ||||||
Natural variant | VAR_045889 | 815 | in dbSNP:rs1042057 | |||
Sequence: A → V | ||||||
Natural variant | VAR_045890 | 819 | in dbSNP:rs17854579 | |||
Sequence: L → M | ||||||
Natural variant | VAR_045891 | 824 | in dbSNP:rs17857364 | |||
Sequence: R → G | ||||||
Natural variant | VAR_041876 | 831 | ||||
Sequence: A → T |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 962 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, disulfide bond, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Signal | 1-40 | UniProt | |||||
Sequence: MALRRSMGRPGLPPLPLPPPPRLGLLLAALASLLLPESAA | |||||||
Chain | PRO_0000024478 | 41-890 | UniProt | Tyrosine-protein kinase receptor TYRO3 | |||
Sequence: AGLKLMGAPVKLTVSQGQPVKLNCSVEGMEEPDIQWVKDGAVVQNLDQLYIPVSEQHWIGFLSLKSVERSDAGRYWCQVEDGGETEISQPVWLTVEGVPFFTVEPKDLAVPPNAPFQLSCEAVGPPEPVTIVWWRGTTKIGGPAPSPSVLNVTGVTQSTMFSCEAHNLKGLASSRTATVHLQALPAAPFNITVTKLSSSNASVAWMPGADGRALLQSCTVQVTQAPGGWEVLAVVVPVPPFTCLLRDLVPATNYSLRVRCANALGPSPYADWVPFQTKGLAPASAPQNLHAIRTDSGLILEWEEVIPEAPLEGPLGPYKLSWVQDNGTQDELTVEGTRANLTGWDPQKDLIVRVCVSNAVGCGPWSQPLVVSSHDRAGQQGPPHSRTSWVPVVLGVLTALVTAAALALILLRKRRKETRFGQAFDSVMARGEPAVHFRAARSFNRERPERIEATLDSLGISDELKEKLEDVLIPEQQFTLGRMLGKGEFGSVREAQLKQEDGSFVKVAVKMLKADIIASSDIEEFLREAACMKEFDHPHVAKLVGVSLRSRAKGRLPIPMVILPFMKHGDLHAFLLASRIGENPFNLPLQTLIRFMVDIACGMEYLSSRNFIHRDLAARNCMLAEDMTVCVADFGLSRKIYSGDYYRQGCASKLPVKWLALESLADNLYTVQSDVWAFGVTMWEIMTRGQTPYAGIENAEIYNYLIGGNRLKQPPECMEDVYDLMYQCWSADPKQRPSFTCLRMELENILGQLSVLSASQDPLYINIERAEEPTAGGSLELPGRDQPYSGAGDGSGMGAVGGTPSDCRYILTPGGLAEQPGQAEHQPESPLNETQRLLLLQQGLLPHSSC | |||||||
Glycosylation | 63 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Disulfide bond | 64↔117 | UniProt | |||||
Sequence: CSVEGMEEPDIQWVKDGAVVQNLDQLYIPVSEQHWIGFLSLKSVERSDAGRYWC | |||||||
Disulfide bond | 160↔203 | UniProt | |||||
Sequence: CEAVGPPEPVTIVWWRGTTKIGGPAPSPSVLNVTGVTQSTMFSC | |||||||
Glycosylation | 191 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Glycosylation | 230 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Glycosylation | 240 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Glycosylation | 293 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Glycosylation | 366 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Glycosylation | 380 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Modified residue | 466 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 466 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 681 | UniProt | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | |||||||
Modified residue | 685 | UniProt | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | |||||||
Modified residue | 686 | UniProt | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | |||||||
Modified residue | 804 | UniProt | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | |||||||
Modified residue | 818 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 818 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 849 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 869 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 869 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 874 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 889 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Autophosphorylated.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Abundant in the brain and lower levels in other tissues.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Monomer and homodimer. Interacts (via N-terminus) with extracellular ligands TULP1 and GAS6 (By similarity).
Interacts with PIK3R1; this interaction increases PI3-kinase activity (By similarity).
Interacts with PIK3R1; this interaction increases PI3-kinase activity (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q06418 | GRB2 P62993 | 4 | EBI-3951628, EBI-401755 | |
BINARY | Q06418 | HSP90AB1 P08238 | 2 | EBI-3951628, EBI-352572 | |
BINARY | Q06418 | KLK4 Q9Y5K2 | 3 | EBI-3951628, EBI-10224152 | |
BINARY | Q06418 | KRT40 Q6A162 | 3 | EBI-3951628, EBI-10171697 | |
BINARY | Q06418 | KRTAP10-7 P60409 | 3 | EBI-3951628, EBI-10172290 | |
BINARY | Q06418 | KRTAP10-8 P60410 | 3 | EBI-3951628, EBI-10171774 | |
BINARY | Q06418 | KRTAP10-9 P60411 | 3 | EBI-3951628, EBI-10172052 | |
BINARY | Q06418 | KRTAP4-2 Q9BYR5 | 3 | EBI-3951628, EBI-10172511 | |
BINARY | Q06418 | KRTAP5-9 P26371 | 5 | EBI-3951628, EBI-3958099 | |
BINARY | Q06418 | KRTAP9-2 Q9BYQ4 | 3 | EBI-3951628, EBI-1044640 | |
BINARY | Q06418 | MDFI Q99750 | 3 | EBI-3951628, EBI-724076 | |
BINARY | Q06418 | VWC2L B2RUY7 | 3 | EBI-3951628, EBI-11747707 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 41-128 | Ig-like C2-type 1 | ||||
Sequence: AGLKLMGAPVKLTVSQGQPVKLNCSVEGMEEPDIQWVKDGAVVQNLDQLYIPVSEQHWIGFLSLKSVERSDAGRYWCQVEDGGETEIS | ||||||
Domain | 139-220 | Ig-like C2-type 2 | ||||
Sequence: PFFTVEPKDLAVPPNAPFQLSCEAVGPPEPVTIVWWRGTTKIGGPAPSPSVLNVTGVTQSTMFSCEAHNLKGLASSRTATVH | ||||||
Domain | 227-320 | Fibronectin type-III 1 | ||||
Sequence: APFNITVTKLSSSNASVAWMPGADGRALLQSCTVQVTQAPGGWEVLAVVVPVPPFTCLLRDLVPATNYSLRVRCANALGPSPYADWVPFQTKGL | ||||||
Domain | 325-416 | Fibronectin type-III 2 | ||||
Sequence: APQNLHAIRTDSGLILEWEEVIPEAPLEGPLGPYKLSWVQDNGTQDELTVEGTRANLTGWDPQKDLIVRVCVSNAVGCGPWSQPLVVSSHDR | ||||||
Domain | 518-790 | Protein kinase | ||||
Sequence: FTLGRMLGKGEFGSVREAQLKQEDGSFVKVAVKMLKADIIASSDIEEFLREAACMKEFDHPHVAKLVGVSLRSRAKGRLPIPMVILPFMKHGDLHAFLLASRIGENPFNLPLQTLIRFMVDIACGMEYLSSRNFIHRDLAARNCMLAEDMTVCVADFGLSRKIYSGDYYRQGCASKLPVKWLALESLADNLYTVQSDVWAFGVTMWEIMTRGQTPYAGIENAEIYNYLIGGNRLKQPPECMEDVYDLMYQCWSADPKQRPSFTCLRMELENIL | ||||||
Region | 815-837 | Disordered | ||||
Sequence: AGGSLELPGRDQPYSGAGDGSGM | ||||||
Region | 851-871 | Disordered | ||||
Sequence: LTPGGLAEQPGQAEHQPESPL |
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length890
- Mass (Da)96,905
- Last updated1996-10-01 v1
- ChecksumF9EC675077C4E8F1
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 29-36 | in Ref. 3; AAC50070 | ||||
Sequence: Missing | ||||||
Sequence conflict | 285 | in Ref. 4; BAA21781 | ||||
Sequence: L → F | ||||||
Sequence conflict | 293 | in Ref. 4; BAA21781 | ||||
Sequence: N → I | ||||||
Sequence conflict | 341 | in Ref. 4; BAA21781 | ||||
Sequence: E → V | ||||||
Sequence conflict | 812 | in Ref. 4; BAA21781 | ||||
Sequence: E → D |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U05682 EMBL· GenBank· DDBJ | AAA19236.1 EMBL· GenBank· DDBJ | mRNA | ||
D17517 EMBL· GenBank· DDBJ | BAA04467.1 EMBL· GenBank· DDBJ | mRNA | ||
U18934 EMBL· GenBank· DDBJ | AAC50070.1 EMBL· GenBank· DDBJ | mRNA | ||
D50479 EMBL· GenBank· DDBJ | BAA21781.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC049368 EMBL· GenBank· DDBJ | AAH49368.1 EMBL· GenBank· DDBJ | mRNA | ||
BC051756 EMBL· GenBank· DDBJ | AAH51756.1 EMBL· GenBank· DDBJ | mRNA | ||
X72886 EMBL· GenBank· DDBJ | CAA51396.1 EMBL· GenBank· DDBJ | mRNA |