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Protein

Tyrosine-protein kinase receptor TYRO3

Gene

Tyro3

Organism
Rattus norvegicus (Rat)
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 (By similarity).By similarity

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei540ATPPROSITE-ProRule annotation1
Active sitei645Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi514 – 522ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Cell adhesion

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1. 5301.

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase receptor TYRO3 (EC:2.7.10.1)
Alternative name(s):
Tyrosine-protein kinase SKY
Gene namesi
Name:Tyro3
Synonyms:Sky
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3923. Tyro3.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini31 – 419ExtracellularSequence analysisAdd BLAST389
Transmembranei420 – 440HelicalSequence analysisAdd BLAST21
Topological domaini441 – 880CytoplasmicSequence analysisAdd BLAST440

GO - Cellular componenti

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

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 30Sequence analysisAdd BLAST30
ChainiPRO_000002448031 – 880Tyrosine-protein kinase receptor TYRO3Add BLAST850

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi53N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi54 ↔ 107PROSITE-ProRule annotation
Glycosylationi75N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi150 ↔ 193PROSITE-ProRule annotation
Glycosylationi181N-linked (GlcNAc...)Sequence analysis1
Glycosylationi220N-linked (GlcNAc...)Sequence analysis1
Glycosylationi230N-linked (GlcNAc...)Sequence analysis1
Glycosylationi283N-linked (GlcNAc...)Sequence analysis1
Glycosylationi356N-linked (GlcNAc...)Sequence analysis1
Glycosylationi370N-linked (GlcNAc...)Sequence analysis1
Modified residuei456PhosphoserineBy similarity1
Modified residuei671Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei675Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei676Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei794Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei808PhosphoserineBy similarity1
Modified residuei859PhosphoserineCombined sources1

Post-translational modificationi

Autophosphorylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP55146.
PRIDEiP55146.

PTM databases

iPTMnetiP55146.
PhosphoSitePlusiP55146.

Expressioni

Tissue specificityi

Abundant in the brain and lower levels in other tissues.

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

GO - Molecular functioni

  • phosphatidylinositol 3-kinase binding Source: RGD

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000007656.

Structurei

3D structure databases

ProteinModelPortaliP55146.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini31 – 118Ig-like C2-type 1Add BLAST88
Domaini129 – 210Ig-like C2-type 2Add BLAST82
Domaini217 – 310Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST94
Domaini315 – 406Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST92
Domaini508 – 785Protein kinasePROSITE-ProRule annotationAdd BLAST278

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.
HOGENOMiHOG000231685.
HOVERGENiHBG006346.
InParanoidiP55146.
KOiK05116.
PhylomeDBiP55146.

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.

P55146-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MALRRSMGRP GLRPLLLAGL ASLLLPGSAA AGLKLMGAPV KMTVSQGQPV
60 70 80 90 100
KLNCSVEGMD DPDIHWMKDG AVVQNASQVS ISISEQNWIG LLSLKSAERS
110 120 130 140 150
DAGLYWCQVK DGEETKISQS VWLTVEGVPF FTVEPKDLAV PPNVPFQLSC
160 170 180 190 200
EAVGPPEPVT IFWWRGPTKV GGPASSPSVL NVTGVTQRTE FSCEAHNIKG
210 220 230 240 250
LATSRPAIIR LQAPPAAPFN ITVTTISSSN ASVAWVPGAD GLALLHSCTV
260 270 280 290 300
QVAHAPGEWE ALAVVVPVPP FTCLLRNLAP ATNYSLRVRC ANALGPSPYG
310 320 330 340 350
DWVPFQTKGL APARAPQNFH AIRTDSGLIL EWEEVIPEDP GEGPLGPYKL
360 370 380 390 400
SWVQENGTQD ELMVEGTTAN LTDWDPQKDL VLRVCASNAI GDGPWSQPLV
410 420 430 440 450
VSSHDHAGRQ GPPHSRTSWV PVVLGVLTAL ITAAALALIL LRKRRKETRF
460 470 480 490 500
GQAFDSVMAR GEPAVHFRAA RSFNRERPER IEATLDSLGI SDELKEKLED
510 520 530 540 550
VLIPEQQFTL GRMLGKGEFG SVREAQLKQE DGSFVKVAVK MLKADIIASS
560 570 580 590 600
DIEEFLREAA CMKEFDHPHV AKLVGVSLRS RAKGRLPIPM VILPFMKHGD
610 620 630 640 650
LHAFLLASRI GENPFNLPLQ TLVRFMVDIA CGMEYLSSRN FIHRDLAARN
660 670 680 690 700
CMLAEDMTVC VADFGLSRKI YSGDYYRQGC ASKLPVKWLA LESLADNLYT
710 720 730 740 750
VHSDVWAFGV TMWEIMTRGQ TPYAGIENAE IYNYLISGNR LKQPPECMEE
760 770 780 790 800
VYDLMYQCWS ADPKQRPSFT CLRMELENIL GHLSVLSTSQ DPLYINIERA
810 820 830 840 850
GQPAENGSPE LPCGEQSSSE AGDGSGMGAI GGIPSDCRYI FSPGGLAESP
860 870 880
GQLEQQPESP LNENQRLLLL QQGLLPHSSC
Length:880
Mass (Da):95,919
Last modified:October 1, 1996 - v1
Checksum:iC3751E86AAE5FA5B
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D37880 mRNA. Translation: BAA07119.1.
PIRiJC4166.
RefSeqiNP_058788.1. NM_017092.1.
UniGeneiRn.8883.

Genome annotation databases

GeneIDi25232.
KEGGirno:25232.
UCSCiRGD:3923. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D37880 mRNA. Translation: BAA07119.1.
PIRiJC4166.
RefSeqiNP_058788.1. NM_017092.1.
UniGeneiRn.8883.

3D structure databases

ProteinModelPortaliP55146.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000007656.

PTM databases

iPTMnetiP55146.
PhosphoSitePlusiP55146.

Proteomic databases

PaxDbiP55146.
PRIDEiP55146.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi25232.
KEGGirno:25232.
UCSCiRGD:3923. rat.

Organism-specific databases

CTDi7301.
RGDi3923. Tyro3.

Phylogenomic databases

eggNOGiENOG410IG6I. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000231685.
HOVERGENiHBG006346.
InParanoidiP55146.
KOiK05116.
PhylomeDBiP55146.

Enzyme and pathway databases

BRENDAi2.7.10.1. 5301.

Miscellaneous databases

PROiP55146.

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_RAT
AccessioniPrimary (citable) accession number: P55146
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 30, 2016
This is version 143 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.