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Protein

Tyrosine-protein kinase receptor TYRO3

Gene

TYRO3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.3 Publications
(Microbial infection) Acts as a receptor for Ebolavirus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope.1 Publication

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 heterodimerization activity Source: Ensembl
  • protein tyrosine kinase activity Source: UniProtKB
  • transmembrane receptor protein tyrosine kinase activity Source: UniProtKB
  • virus receptor activity Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Molecular functionHost cell receptor for virus entry, Kinase, Receptor, Transferase, Tyrosine-protein kinase
Biological processCell adhesion, Host-virus interaction
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000092445.11
HGNCiHGNC:12446 TYRO3
MIMi600341 gene
neXtProtiNX_Q06418

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

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...) asparagineSequence analysis1
Disulfide bondi64 ↔ 117PROSITE-ProRule annotation1 Publication
Disulfide bondi160 ↔ 203PROSITE-ProRule annotation1 Publication
Glycosylationi191N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi230N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi240N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi293N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi366N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi380N-linked (GlcNAc...) asparagineSequence 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
ProteomicsDBi58444

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

Show more details

GO - Molecular functioni

  • phosphatidylinositol 3-kinase binding Source: UniProtKB
  • protein heterodimerization activity Source: Ensembl

Protein-protein interaction databases

BioGridi113152, 28 interactors
IntActiQ06418, 17 interactors
MINTiQ06418
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

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

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IG6I Eukaryota
COG0515 LUCA
GeneTreeiENSGT00810000125384
HOVERGENiHBG006346
InParanoidiQ06418
KOiK05116
OMAiDHAGQQG
OrthoDBiEOG091G016X
PhylomeDBiQ06418
TreeFamiTF317402

Family and domain databases

CDDicd00063 FN3, 2 hits
Gene3Di2.60.40.10, 4 hits
InterProiView protein in InterPro
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR013098 Ig_I-set
IPR003599 Ig_sub
IPR003598 Ig_sub2
IPR011009 Kinase-like_dom_sf
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
PfamiView protein in Pfam
PF00041 fn3, 2 hits
PF07679 I-set, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00060 FN3, 2 hits
SM00409 IG, 2 hits
SM00408 IGc2, 2 hits
SM00219 TyrKc, 1 hit
SUPFAMiSSF48726 SSF48726, 2 hits
SSF49265 SSF49265, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50853 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

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 → L1 PublicationCorresponds to variant dbSNP:rs17854578Ensembl.1
Natural variantiVAR_045887346I → N. Corresponds to variant dbSNP:rs12148316Ensembl.1
Natural variantiVAR_045888542G → S1 PublicationCorresponds to variant dbSNP:rs17857363Ensembl.1
Natural variantiVAR_045889815A → V1 PublicationCorresponds to variant dbSNP:rs1042057Ensembl.1
Natural variantiVAR_045890819L → M1 PublicationCorresponds to variant dbSNP:rs17854579Ensembl.1
Natural variantiVAR_045891824R → G1 PublicationCorresponds to variant dbSNP:rs17857364Ensembl.1
Natural variantiVAR_041876831A → T1 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

Similar proteinsi

Entry informationi

Entry nameiTYRO3_HUMAN
AccessioniPrimary (citable) accession number: Q06418
Secondary accession number(s): O14953, Q86VR3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: June 20, 2018
This is version 183 of the entry and version 1 of the sequence. See 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

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