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Protein

Tyrosine-protein kinase receptor TYRO3

Gene

TYRO3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 SOCS3.1 Publication
(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 (PubMed:25277499, PubMed:22156524, PubMed:22673088). Acts as a receptor for ebolavirus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope (PubMed:17005688).4 Publications

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei550ATPPROSITE-ProRule annotation1
Active sitei655Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi524 – 532ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • phosphatidylinositol 3-kinase binding Source: UniProtKB
  • protein tyrosine kinase activity Source: UniProtKB
  • receptor signaling protein tyrosine kinase activity Source: UniProtKB
  • transmembrane receptor protein tyrosine kinase activity Source: UniProtKB
  • virus receptor activity Source: UniProtKB-KW

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Host cell receptor for virus entry, Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Cell adhesion, Host-virus interaction

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS01772-MONOMER.
BRENDAi2.7.10.1. 2681.
SignaLinkiQ06418.
SIGNORiQ06418.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:TYRO3
Synonyms:BYK, DTK, RSE, SKY, TIF
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:12446. TYRO3.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini41 – 429ExtracellularSequence analysisAdd BLAST389
Transmembranei430 – 450HelicalSequence analysisAdd BLAST21
Topological domaini451 – 890CytoplasmicSequence analysisAdd BLAST440

GO - Cellular componenti

  • endoplasmic reticulum membrane Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • nuclear envelope Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi99I → R: Abolishes dimerization. 1 Publication1

Organism-specific databases

DisGeNETi7301.
OpenTargetsiENSG00000092445.
PharmGKBiPA37097.

Chemistry databases

ChEMBLiCHEMBL5314.
GuidetoPHARMACOLOGYi1836.

Polymorphism and mutation databases

BioMutaiTYRO3.
DMDMi1717829.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 40Sequence analysisAdd BLAST40
ChainiPRO_000002447841 – 890Tyrosine-protein kinase receptor TYRO3Add BLAST850

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi63N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi64 ↔ 117PROSITE-ProRule annotation1 Publication
Disulfide bondi160 ↔ 203PROSITE-ProRule annotation1 Publication
Glycosylationi191N-linked (GlcNAc...)Sequence analysis1
Glycosylationi230N-linked (GlcNAc...)Sequence analysis1
Glycosylationi240N-linked (GlcNAc...)Sequence analysis1
Glycosylationi293N-linked (GlcNAc...)Sequence analysis1
Glycosylationi366N-linked (GlcNAc...)Sequence analysis1
Glycosylationi380N-linked (GlcNAc...)Sequence analysis1
Modified residuei466PhosphoserineCombined sources1
Modified residuei681Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei685Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei686Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei804Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei818PhosphoserineCombined sources1
Modified residuei869PhosphoserineBy similarity1

Post-translational modificationi

Autophosphorylated.

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ06418.
MaxQBiQ06418.
PaxDbiQ06418.
PeptideAtlasiQ06418.
PRIDEiQ06418.

PTM databases

iPTMnetiQ06418.
PhosphoSitePlusiQ06418.

Expressioni

Tissue specificityi

Abundant in the brain and lower levels in other tissues.

Gene expression databases

BgeeiENSG00000092445.
CleanExiHS_TYRO3.
ExpressionAtlasiQ06418. baseline and differential.
GenevisibleiQ06418. HS.

Organism-specific databases

HPAiHPA071245.

Interactioni

Subunit structurei

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).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
KLK4Q9Y5K23EBI-3951628,EBI-10224152
KRT40Q6A1623EBI-3951628,EBI-10171697
KRTAP10-7P604093EBI-3951628,EBI-10172290
KRTAP10-8P604103EBI-3951628,EBI-10171774
KRTAP10-9P604113EBI-3951628,EBI-10172052
KRTAP4-2Q9BYR53EBI-3951628,EBI-10172511
KRTAP5-9P263714EBI-3951628,EBI-3958099
MDFIQ997503EBI-3951628,EBI-724076

GO - Molecular functioni

  • phosphatidylinositol 3-kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi113152. 27 interactors.
IntActiQ06418. 14 interactors.
STRINGi9606.ENSP00000263798.

Chemistry databases

BindingDBiQ06418.

Structurei

Secondary structure

1890
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi50 – 55Combined sources6
Beta strandi60 – 68Combined sources9
Beta strandi74 – 78Combined sources5
Beta strandi85 – 94Combined sources10
Beta strandi97 – 106Combined sources10
Helixi109 – 111Combined sources3
Beta strandi113 – 121Combined sources9
Beta strandi131 – 136Combined sources6
Beta strandi140 – 143Combined sources4
Beta strandi148 – 150Combined sources3
Beta strandi156 – 163Combined sources8
Beta strandi165 – 167Combined sources3
Beta strandi170 – 175Combined sources6
Beta strandi183 – 192Combined sources10
Beta strandi199 – 207Combined sources9
Beta strandi210 – 213Combined sources4
Beta strandi217 – 221Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1RHFX-ray1.96A/B41-222[»]
ProteinModelPortaliQ06418.
SMRiQ06418.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ06418.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini41 – 128Ig-like C2-type 1Add BLAST88
Domaini139 – 220Ig-like C2-type 2Add BLAST82
Domaini227 – 320Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST94
Domaini325 – 416Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST92
Domaini518 – 790Protein kinasePROSITE-ProRule annotationAdd BLAST273

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. AXL/UFO subfamily.PROSITE-ProRule annotation
Contains 2 fibronectin type-III domains.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IG6I. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00810000125384.
HOVERGENiHBG006346.
InParanoidiQ06418.
KOiK05116.
OMAiGMEDPEM.
OrthoDBiEOG091G016X.
PhylomeDBiQ06418.
TreeFamiTF317402.

Family and domain databases

CDDicd00063. FN3. 2 hits.
Gene3Di2.60.40.10. 4 hits.
InterProiIPR003961. FN3_dom.
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]
PfamiPF00041. fn3. 2 hits.
PF07679. I-set. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSiPR00109. TYRKINASE.
SMARTiSM00060. FN3. 2 hits.
SM00409. IG. 2 hits.
SM00408. IGc2. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 2 hits.
SSF49265. SSF49265. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50853. 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]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q06418-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MALRRSMGRP GLPPLPLPPP PRLGLLLAAL ASLLLPESAA AGLKLMGAPV
60 70 80 90 100
KLTVSQGQPV KLNCSVEGME EPDIQWVKDG AVVQNLDQLY IPVSEQHWIG
110 120 130 140 150
FLSLKSVERS DAGRYWCQVE DGGETEISQP VWLTVEGVPF FTVEPKDLAV
160 170 180 190 200
PPNAPFQLSC EAVGPPEPVT IVWWRGTTKI GGPAPSPSVL NVTGVTQSTM
210 220 230 240 250
FSCEAHNLKG LASSRTATVH LQALPAAPFN ITVTKLSSSN ASVAWMPGAD
260 270 280 290 300
GRALLQSCTV QVTQAPGGWE VLAVVVPVPP FTCLLRDLVP ATNYSLRVRC
310 320 330 340 350
ANALGPSPYA DWVPFQTKGL APASAPQNLH AIRTDSGLIL EWEEVIPEAP
360 370 380 390 400
LEGPLGPYKL SWVQDNGTQD ELTVEGTRAN LTGWDPQKDL IVRVCVSNAV
410 420 430 440 450
GCGPWSQPLV VSSHDRAGQQ GPPHSRTSWV PVVLGVLTAL VTAAALALIL
460 470 480 490 500
LRKRRKETRF GQAFDSVMAR GEPAVHFRAA RSFNRERPER IEATLDSLGI
510 520 530 540 550
SDELKEKLED VLIPEQQFTL GRMLGKGEFG SVREAQLKQE DGSFVKVAVK
560 570 580 590 600
MLKADIIASS DIEEFLREAA CMKEFDHPHV AKLVGVSLRS RAKGRLPIPM
610 620 630 640 650
VILPFMKHGD LHAFLLASRI GENPFNLPLQ TLIRFMVDIA CGMEYLSSRN
660 670 680 690 700
FIHRDLAARN CMLAEDMTVC VADFGLSRKI YSGDYYRQGC ASKLPVKWLA
710 720 730 740 750
LESLADNLYT VQSDVWAFGV TMWEIMTRGQ TPYAGIENAE IYNYLIGGNR
760 770 780 790 800
LKQPPECMED VYDLMYQCWS ADPKQRPSFT CLRMELENIL GQLSVLSASQ
810 820 830 840 850
DPLYINIERA EEPTAGGSLE LPGRDQPYSG AGDGSGMGAV GGTPSDCRYI
860 870 880 890
LTPGGLAEQP GQAEHQPESP LNETQRLLLL QQGLLPHSSC
Length:890
Mass (Da):96,905
Last modified:October 1, 1996 - v1
Checksum:iF9EC675077C4E8F1
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti29 – 36Missing in AAC50070 (PubMed:7857658).Curated8
Sequence conflicti285L → F in BAA21781 (PubMed:9175267).Curated1
Sequence conflicti293N → I in BAA21781 (PubMed:9175267).Curated1
Sequence conflicti341E → V in BAA21781 (PubMed:9175267).Curated1
Sequence conflicti812E → D in BAA21781 (PubMed:9175267).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04588621P → L.1 PublicationCorresponds to variant rs17854578dbSNPEnsembl.1
Natural variantiVAR_045887346I → N.Corresponds to variant rs12148316dbSNPEnsembl.1
Natural variantiVAR_045888542G → S.1 PublicationCorresponds to variant rs17857363dbSNPEnsembl.1
Natural variantiVAR_045889815A → V.1 PublicationCorresponds to variant rs1042057dbSNPEnsembl.1
Natural variantiVAR_045890819L → M.1 PublicationCorresponds to variant rs17854579dbSNPEnsembl.1
Natural variantiVAR_045891824R → G.1 PublicationCorresponds to variant rs17857364dbSNPEnsembl.1
Natural variantiVAR_041876831A → T.1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS10080.1.
PIRiA53743.
I38912.
RefSeqiNP_001317193.1. NM_001330264.1.
NP_006284.2. NM_006293.3.
UniGeneiHs.381282.

Genome annotation databases

EnsembliENST00000263798; ENSP00000263798; ENSG00000092445.
GeneIDi7301.
KEGGihsa:7301.
UCSCiuc001zof.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS10080.1.
PIRiA53743.
I38912.
RefSeqiNP_001317193.1. NM_001330264.1.
NP_006284.2. NM_006293.3.
UniGeneiHs.381282.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1RHFX-ray1.96A/B41-222[»]
ProteinModelPortaliQ06418.
SMRiQ06418.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113152. 27 interactors.
IntActiQ06418. 14 interactors.
STRINGi9606.ENSP00000263798.

Chemistry databases

BindingDBiQ06418.
ChEMBLiCHEMBL5314.
GuidetoPHARMACOLOGYi1836.

PTM databases

iPTMnetiQ06418.
PhosphoSitePlusiQ06418.

Polymorphism and mutation databases

BioMutaiTYRO3.
DMDMi1717829.

Proteomic databases

EPDiQ06418.
MaxQBiQ06418.
PaxDbiQ06418.
PeptideAtlasiQ06418.
PRIDEiQ06418.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263798; ENSP00000263798; ENSG00000092445.
GeneIDi7301.
KEGGihsa:7301.
UCSCiuc001zof.3. human.

Organism-specific databases

CTDi7301.
DisGeNETi7301.
GeneCardsiTYRO3.
HGNCiHGNC:12446. TYRO3.
HPAiHPA071245.
MIMi600341. gene.
neXtProtiNX_Q06418.
OpenTargetsiENSG00000092445.
PharmGKBiPA37097.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IG6I. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00810000125384.
HOVERGENiHBG006346.
InParanoidiQ06418.
KOiK05116.
OMAiGMEDPEM.
OrthoDBiEOG091G016X.
PhylomeDBiQ06418.
TreeFamiTF317402.

Enzyme and pathway databases

BioCyciZFISH:HS01772-MONOMER.
BRENDAi2.7.10.1. 2681.
SignaLinkiQ06418.
SIGNORiQ06418.

Miscellaneous databases

ChiTaRSiTYRO3. human.
EvolutionaryTraceiQ06418.
GeneWikiiTYRO3.
GenomeRNAii7301.
PROiQ06418.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000092445.
CleanExiHS_TYRO3.
ExpressionAtlasiQ06418. baseline and differential.
GenevisibleiQ06418. HS.

Family and domain databases

CDDicd00063. FN3. 2 hits.
Gene3Di2.60.40.10. 4 hits.
InterProiIPR003961. FN3_dom.
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]
PfamiPF00041. fn3. 2 hits.
PF07679. I-set. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSiPR00109. TYRKINASE.
SMARTiSM00060. FN3. 2 hits.
SM00409. IG. 2 hits.
SM00408. IGc2. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 2 hits.
SSF49265. SSF49265. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50853. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiTYRO3_HUMAN
AccessioniPrimary (citable) accession number: Q06418
Secondary accession number(s): O14953, Q86VR3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 30, 2016
This is version 173 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.