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Q06418 (TYRO3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 147. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tyrosine-protein kinase receptor TYRO3

EC=2.7.10.1
Alternative name(s):
Tyrosine-protein kinase BYK
Tyrosine-protein kinase DTK
Tyrosine-protein kinase RSE
Tyrosine-protein kinase SKY
Tyrosine-protein kinase TIF
Gene names
Name:TYRO3
Synonyms:BYK, DTK, RSE, SKY, TIF
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length890 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Plays also 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. Ref.10 Ref.12

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Subunit structure

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. Ref.8 Ref.13

Subcellular location

Cell membrane; Single-pass type I membrane protein.

Tissue specificity

Abundant in the brain and lower levels in other tissues.

Post-translational modification

Autophosphorylated. Ref.7

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. AXL/UFO subfamily.

Contains 2 fibronectin type-III domains.

Contains 2 Ig-like C2-type (immunoglobulin-like) domains.

Contains 1 protein kinase domain.

Sequence caution

The sequence BAA21781.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processCell adhesion
   Cellular componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DomainImmunoglobulin domain
Repeat
Signal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic cell clearance

Inferred from sequence or structural similarity. Source: UniProtKB

cell adhesion

Non-traceable author statement Ref.2. Source: UniProtKB

forebrain cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

natural killer cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of inflammatory response

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of innate immune response

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of lymphocyte activation

Inferred from electronic annotation. Source: Ensembl

negative regulation of neuron apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of toll-like receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

neuron cellular homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

ovulation cycle

Inferred from sequence or structural similarity. Source: UniProtKB

peptidyl-tyrosine phosphorylation

Inferred from direct assay Ref.7. Source: GOC

phosphatidylinositol 3-kinase signaling

Non-traceable author statement PubMed 10627473. Source: UniProtKB

platelet activation

Inferred from sequence or structural similarity. Source: UniProtKB

platelet aggregation

Inferred from sequence or structural similarity. Source: UniProtKB

protein autophosphorylation

Inferred from direct assay Ref.1Ref.7. Source: UniProtKB

protein kinase B signaling

Inferred from sequence or structural similarity. Source: UniProtKB

secretion by cell

Inferred from sequence or structural similarity. Source: UniProtKB

signal transduction

Non-traceable author statement Ref.1. Source: UniProtKB

signal transduction by phosphorylation

Non-traceable author statement Ref.1. Source: GOC

spermatogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

substrate adhesion-dependent cell spreading

Inferred from sequence or structural similarity. Source: UniProtKB

vagina development

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentendoplasmic reticulum membrane

Inferred from sequence or structural similarity. Source: UniProtKB

integral component of plasma membrane

Non-traceable author statement Ref.1. Source: UniProtKB

nuclear envelope

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

phosphatidylinositol 3-kinase binding

Inferred from physical interaction PubMed 10627473. Source: UniProtKB

protein tyrosine kinase activity

Inferred from direct assay Ref.7. Source: UniProtKB

receptor signaling protein tyrosine kinase activity

Non-traceable author statement Ref.1. Source: UniProtKB

transmembrane receptor protein tyrosine kinase activity

Non-traceable author statement Ref.1. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 4040 Potential
Chain41 – 890850Tyrosine-protein kinase receptor TYRO3
PRO_0000024478

Regions

Topological domain41 – 429389Extracellular Potential
Transmembrane430 – 45021Helical; Potential
Topological domain451 – 890440Cytoplasmic Potential
Domain41 – 12888Ig-like C2-type 1
Domain139 – 22082Ig-like C2-type 2
Domain227 – 32094Fibronectin type-III 1
Domain325 – 41692Fibronectin type-III 2
Domain518 – 790273Protein kinase
Nucleotide binding524 – 5329ATP By similarity

Sites

Active site6551Proton acceptor By similarity
Binding site5501ATP By similarity

Amino acid modifications

Modified residue6811Phosphotyrosine; by autocatalysis By similarity
Modified residue6851Phosphotyrosine; by autocatalysis By similarity
Modified residue6861Phosphotyrosine; by autocatalysis By similarity
Modified residue8041Phosphotyrosine; by autocatalysis By similarity
Glycosylation631N-linked (GlcNAc...) Potential
Glycosylation1911N-linked (GlcNAc...) Potential
Glycosylation2301N-linked (GlcNAc...) Potential
Glycosylation2401N-linked (GlcNAc...) Potential
Glycosylation2931N-linked (GlcNAc...) Potential
Glycosylation3661N-linked (GlcNAc...) Potential
Glycosylation3801N-linked (GlcNAc...) Potential
Disulfide bond64 ↔ 117 Ref.13
Disulfide bond160 ↔ 203 Ref.13

Natural variations

Natural variant211P → L. Ref.5
Corresponds to variant rs17854578 [ dbSNP | Ensembl ].
VAR_045886
Natural variant3461I → N.
Corresponds to variant rs12148316 [ dbSNP | Ensembl ].
VAR_045887
Natural variant5421G → S. Ref.5
Corresponds to variant rs17857363 [ dbSNP | Ensembl ].
VAR_045888
Natural variant8151A → V. Ref.3
Corresponds to variant rs1042057 [ dbSNP | Ensembl ].
VAR_045889
Natural variant8191L → M. Ref.5
Corresponds to variant rs17854579 [ dbSNP | Ensembl ].
VAR_045890
Natural variant8241R → G. Ref.5
Corresponds to variant rs17857364 [ dbSNP | Ensembl ].
VAR_045891
Natural variant8311A → T. Ref.14
VAR_041876

Experimental info

Mutagenesis991I → R: Abolishes dimerization. Ref.13
Sequence conflict29 – 368Missing in AAC50070. Ref.3
Sequence conflict2851L → F in BAA21781. Ref.4
Sequence conflict2931N → I in BAA21781. Ref.4
Sequence conflict3411E → V in BAA21781. Ref.4
Sequence conflict8121E → D in BAA21781. Ref.4

Secondary structure

................................... 890
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q06418 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: F9EC675077C4E8F1

FASTA89096,905
        10         20         30         40         50         60 
MALRRSMGRP GLPPLPLPPP PRLGLLLAAL ASLLLPESAA AGLKLMGAPV KLTVSQGQPV 

        70         80         90        100        110        120 
KLNCSVEGME EPDIQWVKDG AVVQNLDQLY IPVSEQHWIG FLSLKSVERS DAGRYWCQVE 

       130        140        150        160        170        180 
DGGETEISQP VWLTVEGVPF FTVEPKDLAV PPNAPFQLSC EAVGPPEPVT IVWWRGTTKI 

       190        200        210        220        230        240 
GGPAPSPSVL NVTGVTQSTM FSCEAHNLKG LASSRTATVH LQALPAAPFN ITVTKLSSSN 

       250        260        270        280        290        300 
ASVAWMPGAD GRALLQSCTV QVTQAPGGWE VLAVVVPVPP FTCLLRDLVP ATNYSLRVRC 

       310        320        330        340        350        360 
ANALGPSPYA DWVPFQTKGL APASAPQNLH AIRTDSGLIL EWEEVIPEAP LEGPLGPYKL 

       370        380        390        400        410        420 
SWVQDNGTQD ELTVEGTRAN LTGWDPQKDL IVRVCVSNAV GCGPWSQPLV VSSHDRAGQQ 

       430        440        450        460        470        480 
GPPHSRTSWV PVVLGVLTAL VTAAALALIL LRKRRKETRF GQAFDSVMAR GEPAVHFRAA 

       490        500        510        520        530        540 
RSFNRERPER IEATLDSLGI SDELKEKLED VLIPEQQFTL GRMLGKGEFG SVREAQLKQE 

       550        560        570        580        590        600 
DGSFVKVAVK MLKADIIASS DIEEFLREAA CMKEFDHPHV AKLVGVSLRS RAKGRLPIPM 

       610        620        630        640        650        660 
VILPFMKHGD LHAFLLASRI GENPFNLPLQ TLIRFMVDIA CGMEYLSSRN FIHRDLAARN 

       670        680        690        700        710        720 
CMLAEDMTVC VADFGLSRKI YSGDYYRQGC ASKLPVKWLA LESLADNLYT VQSDVWAFGV 

       730        740        750        760        770        780 
TMWEIMTRGQ TPYAGIENAE IYNYLIGGNR LKQPPECMED VYDLMYQCWS ADPKQRPSFT 

       790        800        810        820        830        840 
CLRMELENIL GQLSVLSASQ DPLYINIERA EEPTAGGSLE LPGRDQPYSG AGDGSGMGAV 

       850        860        870        880        890 
GGTPSDCRYI LTPGGLAEQP GQAEHQPESP LNETQRLLLL QQGLLPHSSC 

« Hide

References

« Hide 'large scale' references
[1]"RSE, a novel receptor-type tyrosine kinase with homology to Axl/Ufo, is expressed at high levels in the brain."
Mark M.R., Scadden D.T., Wang Z., Gu Q., Goddard A., Godowski P.J.
J. Biol. Chem. 269:10720-10728(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Cloning of the cDNA for a novel receptor tyrosine kinase, Sky, predominantly expressed in brain."
Ohashi K., Mizuno K., Kuma K., Miyata T., Nakamura T.
Oncogene 9:699-705(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Isolation and characterization of the human DTK receptor tyrosine kinase."
Crosier K.E., Hall L.R., Lewis P.M., Morris C.M., Wood C.R., Morris J.C., Crosier P.S.
Growth Factors 11:137-144(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-815.
Tissue: Brain.
[4]"A tyrosine kinase-like molecule is localized in the nuclear membrane of neurons: hippocampal behavior under stress."
Kajii Y., Ninomiya D., Kato M., Mizuguchi M., Saji M., Katsumoto T., Ohno K., Takashima S., Onodera K.
Biol. Cell 88:45-54(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS LEU-21; SER-542; MET-819 AND GLY-824.
Tissue: Skin and Testis.
[6]"The human TYRO3 gene and pseudogene are located in chromosome 15q14-q25."
Polvi A., Armstrong E., Lai C., Lemke G., Huebner K., Spritz R.A., Giuda L.C., Nicholls R.D., Alitalo K.
Gene 134:289-293(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 519-720.
[7]"Autophosphorylation activity and association with Src family kinase of Sky receptor tyrosine kinase."
Toshima J., Ohashi K., Iwashita S., Mizuno K.
Biochem. Biophys. Res. Commun. 209:656-663(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: AUTOPHOSPHORYLATION.
[8]"Reevaluation of the roles of protein S and Gas6 as ligands for the receptor tyrosine kinase Rse/Tyro 3."
Godowski P.J., Mark M.R., Chen J., Sadick M.D., Raab H., Hammonds R.G.
Cell 82:355-358(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GAS6.
[9]"Signalling and functional diversity within the Axl subfamily of receptor tyrosine kinases."
Hafizi S., Dahlback B.
Cytokine Growth Factor Rev. 17:295-304(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[10]"Tyro3 family-mediated cell entry of Ebola and Marburg viruses."
Shimojima M., Takada A., Ebihara H., Neumann G., Fujioka K., Irimura T., Jones S., Feldmann H., Kawaoka Y.
J. Virol. 80:10109-10116(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS CELL ENTRY FACTOR IN FILOVIRUS INFECTION.
[11]"Immunobiology of the TAM receptors."
Lemke G., Rothlin C.V.
Nat. Rev. Immunol. 8:327-336(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[12]"Potentiating role of Gas6 and Tyro3, Axl and Mer (TAM) receptors in human and murine platelet activation and thrombus stabilization."
Cosemans J.M., Van Kruchten R., Olieslagers S., Schurgers L.J., Verheyen F.K., Munnix I.C., Waltenberger J., Angelillo-Scherrer A., Hoylaerts M.F., Carmeliet P., Heemskerk J.W.
J. Thromb. Haemost. 8:1797-1808(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PLATELET ACTIVATION.
[13]"Ligand recognition and homophilic interactions in Tyro3: structural insights into the Axl/Tyro3 receptor tyrosine kinase family."
Heiring C., Dahlbaeck B., Muller Y.A.
J. Biol. Chem. 279:6952-6958(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) OF 41-222, SUBUNIT, INTERACTION WITH GAS6, MUTAGENESIS OF ILE-99, DISULFIDE BONDS.
[14]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] THR-831.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U05682 mRNA. Translation: AAA19236.1.
D17517 mRNA. Translation: BAA04467.1.
U18934 mRNA. Translation: AAC50070.1.
D50479 mRNA. Translation: BAA21781.1. Different initiation.
BC049368 mRNA. Translation: AAH49368.1.
BC051756 mRNA. Translation: AAH51756.1.
X72886 mRNA. Translation: CAA51396.1.
PIRA53743.
I38912.
RefSeqNP_006284.2. NM_006293.3.
UniGeneHs.381282.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1RHFX-ray1.96A/B41-222[»]
ProteinModelPortalQ06418.
SMRQ06418. Positions 47-410, 509-792.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113152. 12 interactions.
IntActQ06418. 5 interactions.
STRING9606.ENSP00000263798.

Chemistry

BindingDBQ06418.
ChEMBLCHEMBL5314.
GuidetoPHARMACOLOGY1836.

PTM databases

PhosphoSiteQ06418.

Polymorphism databases

DMDM1717829.

Proteomic databases

PaxDbQ06418.
PRIDEQ06418.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000263798; ENSP00000263798; ENSG00000092445.
GeneID7301.
KEGGhsa:7301.
UCSCuc001zof.2. human.

Organism-specific databases

CTD7301.
GeneCardsGC15P041851.
HGNCHGNC:12446. TYRO3.
MIM600341. gene.
neXtProtNX_Q06418.
PharmGKBPA37097.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOVERGENHBG006346.
InParanoidQ06418.
KOK05116.
OMADNGTQGE.
PhylomeDBQ06418.
TreeFamTF317402.

Enzyme and pathway databases

BRENDA2.7.10.1. 2681.
SignaLinkQ06418.

Gene expression databases

ArrayExpressQ06418.
BgeeQ06418.
CleanExHS_TYRO3.
GenevestigatorQ06418.

Family and domain databases

Gene3D2.60.40.10. 4 hits.
InterProIPR003961. Fibronectin_type3.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PfamPF00041. fn3. 2 hits.
PF07679. I-set. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSPR00109. TYRKINASE.
SMARTSM00060. FN3. 2 hits.
SM00409. IG. 1 hit.
SM00408. IGc2. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF49265. SSF49265. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS50853. FN3. 2 hits.
PS50835. IG_LIKE. 2 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ06418.
GeneWikiTYRO3.
GenomeRNAi7301.
NextBio28553.
PROQ06418.
SOURCESearch...

Entry information

Entry nameTYRO3_HUMAN
AccessionPrimary (citable) accession number: Q06418
Secondary accession number(s): O14953, Q86VR3
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: April 16, 2014
This is version 147 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM