ID YES_MOUSE Reviewed; 541 AA.
AC Q04736;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 27-MAR-2024, entry version 226.
DE RecName: Full=Tyrosine-protein kinase Yes;
DE EC=2.7.10.2;
DE AltName: Full=Proto-oncogene c-Yes;
DE AltName: Full=p61-Yes;
GN Name=Yes1; Synonyms=Yes;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=8437854;
RA Klages S., Adam D., Eiseman E., Fargnoli J., Dymecki S.M., Desiderio S.V.,
RA Bolen J.B.;
RT "Molecular cloning and analysis of cDNA encoding the murine c-yes tyrosine
RT protein kinase.";
RL Oncogene 8:713-719(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 391-458.
RX PubMed=8206383; DOI=10.1016/0378-1119(94)90106-6;
RA Hebert B., Bergeron J., Tijssen P., Potworowski E.F.;
RT "Protein tyrosine kinases transcribed in a murine thymic medullary
RT epithelial cell line.";
RL Gene 143:257-260(1994).
RN [4]
RP INTERACTION WITH CSF1R.
RX PubMed=7681396; DOI=10.1002/j.1460-2075.1993.tb05735.x;
RA Courtneidge S.A., Dhand R., Pilat D., Twamley G.M., Waterfield M.D.,
RA Roussel M.F.;
RT "Activation of Src family kinases by colony stimulating factor-1, and their
RT association with its receptor.";
RL EMBO J. 12:943-950(1993).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=7958873; DOI=10.1101/gad.8.17.1999;
RA Stein P.L., Vogel H., Soriano P.;
RT "Combined deficiencies of Src, Fyn, and Yes tyrosine kinases in mutant
RT mice.";
RL Genes Dev. 8:1999-2007(1994).
RN [6]
RP PHOSPHORYLATION AT TYR-32.
RX PubMed=9058199; DOI=10.1093/oxfordjournals.jbchem.a021551;
RA Ariki M., Tanabe O., Usui H., Hayashi H., Inoue R., Nishito Y.,
RA Kagamiyama H., Takeda M.;
RT "Identification of autophosphorylation sites in c-Yes purified from rat
RT liver plasma membranes.";
RL J. Biochem. 121:104-111(1997).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-535, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26979622; DOI=10.1038/ncomms10880;
RA Sprowl J.A., Ong S.S., Gibson A.A., Hu S., Du G., Lin W., Li L.,
RA Bharill S., Ness R.A., Stecula A., Offer S.M., Diasio R.B., Nies A.T.,
RA Schwab M., Cavaletti G., Schlatter E., Ciarimboli G., Schellens J.H.M.,
RA Isacoff E.Y., Sali A., Chen T., Baker S.D., Sparreboom A., Pabla N.;
RT "A phosphotyrosine switch regulates organic cation transporters.";
RL Nat. Commun. 7:10880-10880(2016).
RN [10]
RP STRUCTURE BY NMR OF 62-167.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the SH3_1 domain of Yamaguchi sarcoma viral (v-Yes)
RT oncogene homolog 1.";
RL Submitted (APR-2008) to the PDB data bank.
CC -!- FUNCTION: Non-receptor protein tyrosine kinase that is involved in the
CC regulation of cell growth and survival, apoptosis, cell-cell adhesion,
CC cytoskeleton remodeling, and differentiation. Stimulation by receptor
CC tyrosine kinases (RTKs) including EGFR, PDGFR, CSF1R and FGFR leads to
CC recruitment of YES1 to the phosphorylated receptor, and activation and
CC phosphorylation of downstream substrates. Upon EGFR activation,
CC promotes the phosphorylation of PARD3 to favor epithelial tight
CC junction assembly. Participates in the phosphorylation of specific
CC junctional components such as CTNND1 by stimulating the FYN and FER
CC tyrosine kinases at cell-cell contacts. Upon T-cell stimulation by
CC CXCL12, phosphorylates collapsin response mediator protein 2/DPYSL2 and
CC induces T-cell migration. Participates in CD95L/FASLG signaling pathway
CC and mediates AKT-mediated cell migration. Plays a role in cell cycle
CC progression by phosphorylating the cyclin dependent kinase 4/CDK4 thus
CC regulating the G1 phase. Also involved in G2/M progression and
CC cytokinesis (By similarity). Catalyzes phosphorylation of organic
CC cation transporter OCT2 which induces its transport activity
CC (PubMed:26979622). {ECO:0000250, ECO:0000269|PubMed:26979622}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- SUBUNIT: Interacts with YAP1. Interacts with FASLG. Interacts with
CC CTNND1; this interaction allows YES1-mediated activation of FYN and FER
CC and subsequent phosphorylation of CTNND1 (By similarity). Interacts
CC with CSF1R. Interacts with IL6ST/gp130 (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:P07947, ECO:0000269|PubMed:7681396}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome {ECO:0000250}.
CC Cytoplasm, cytosol {ECO:0000250}. Note=Newly synthesized protein
CC initially accumulates in the Golgi region and traffics to the plasma
CC membrane through the exocytic pathway. {ECO:0000250}.
CC -!- PTM: Phosphorylation by CSK on the C-terminal tail maintains the enzyme
CC in an inactive state. Autophosphorylation at Tyr-424 maintains enzyme
CC activity by blocking CSK-mediated inhibition (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Palmitoylation at Cys-3 promotes membrane localization.
CC {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Knouckout mice show reduced OCT2 tyrosine
CC phosphorylation and reduced OCT2-mediated TEA renal secretion
CC (PubMed:26979622). Knouckout mice are protected from oxaliplatin-
CC induced acute sensory neuropathy (PubMed:26979622). Mice are viable,
CC fertile, and display no apparent phenotypes. This lack of phenotype may
CC be attributable to compensatory roles of the other SRC-family members.
CC {ECO:0000269|PubMed:26979622, ECO:0000269|PubMed:7958873}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. SRC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; X67677; CAA47909.1; -; mRNA.
DR EMBL; BC010594; AAH10594.1; -; mRNA.
DR EMBL; L25762; AAA40020.1; -; mRNA.
DR CCDS; CCDS39061.1; -.
DR PIR; I48318; S31645.
DR RefSeq; NP_001192061.1; NM_001205132.1.
DR RefSeq; NP_001192062.1; NM_001205133.1.
DR RefSeq; NP_033561.1; NM_009535.3.
DR PDB; 2YT6; NMR; -; A=71-167.
DR PDB; 5MTJ; X-ray; 1.95 A; A=147-260.
DR PDBsum; 2YT6; -.
DR PDBsum; 5MTJ; -.
DR AlphaFoldDB; Q04736; -.
DR SMR; Q04736; -.
DR BioGRID; 204615; 7.
DR IntAct; Q04736; 4.
DR MINT; Q04736; -.
DR STRING; 10090.ENSMUSP00000072154; -.
DR GlyGen; Q04736; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q04736; -.
DR PhosphoSitePlus; Q04736; -.
DR SwissPalm; Q04736; -.
DR jPOST; Q04736; -.
DR PaxDb; 10090-ENSMUSP00000072154; -.
DR PeptideAtlas; Q04736; -.
DR ProteomicsDB; 299631; -.
DR Pumba; Q04736; -.
DR Antibodypedia; 3819; 582 antibodies from 37 providers.
DR DNASU; 22612; -.
DR Ensembl; ENSMUST00000072311.13; ENSMUSP00000072154.7; ENSMUSG00000014932.16.
DR Ensembl; ENSMUST00000168707.6; ENSMUSP00000132161.3; ENSMUSG00000014932.16.
DR Ensembl; ENSMUST00000202543.4; ENSMUSP00000144001.2; ENSMUSG00000014932.16.
DR GeneID; 22612; -.
DR KEGG; mmu:22612; -.
DR UCSC; uc008wzs.2; mouse.
DR AGR; MGI:99147; -.
DR CTD; 7525; -.
DR MGI; MGI:99147; Yes1.
DR VEuPathDB; HostDB:ENSMUSG00000014932; -.
DR eggNOG; KOG0197; Eukaryota.
DR GeneTree; ENSGT00940000154920; -.
DR InParanoid; Q04736; -.
DR OMA; ESNEWHF; -.
DR OrthoDB; 1614410at2759; -.
DR PhylomeDB; Q04736; -.
DR TreeFam; TF351634; -.
DR BRENDA; 2.7.10.2; 3474.
DR Reactome; R-MMU-1227986; Signaling by ERBB2.
DR Reactome; R-MMU-1433557; Signaling by SCF-KIT.
DR Reactome; R-MMU-1433559; Regulation of KIT signaling.
DR Reactome; R-MMU-2029481; FCGR activation.
DR Reactome; R-MMU-210990; PECAM1 interactions.
DR Reactome; R-MMU-389356; CD28 co-stimulation.
DR Reactome; R-MMU-389513; CTLA4 inhibitory signaling.
DR Reactome; R-MMU-3928662; EPHB-mediated forward signaling.
DR Reactome; R-MMU-3928663; EPHA-mediated growth cone collapse.
DR Reactome; R-MMU-3928665; EPH-ephrin mediated repulsion of cells.
DR Reactome; R-MMU-912631; Regulation of signaling by CBL.
DR BioGRID-ORCS; 22612; 3 hits in 80 CRISPR screens.
DR ChiTaRS; Yes1; mouse.
DR EvolutionaryTrace; Q04736; -.
DR PRO; PR:Q04736; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q04736; Protein.
DR Bgee; ENSMUSG00000014932; Expressed in lumbar dorsal root ganglion and 248 other cell types or tissues.
DR ExpressionAtlas; Q04736; baseline and differential.
DR Genevisible; Q04736; MM.
DR GO; GO:0005884; C:actin filament; IDA:MGI.
DR GO; GO:0005813; C:centrosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0099091; C:postsynaptic specialization, intracellular component; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; ISO:MGI.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0001784; F:phosphotyrosine residue binding; ISO:MGI.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:MGI.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0036120; P:cellular response to platelet-derived growth factor stimulus; IDA:MGI.
DR GO; GO:0071300; P:cellular response to retinoic acid; IDA:MGI.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IGI:MGI.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0010827; P:regulation of glucose transmembrane transport; IDA:MGI.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd05069; PTKc_Yes; 1.
DR CDD; cd09933; SH2_Src_family; 1.
DR CDD; cd12007; SH3_Yes; 1.
DR Gene3D; 3.30.505.10; SH2 domain; 1.
DR Gene3D; 2.30.30.40; SH3 Domains; 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR035751; Yes_SH3.
DR PANTHER; PTHR24418; TYROSINE-PROTEIN KINASE; 1.
DR PANTHER; PTHR24418:SF90; TYROSINE-PROTEIN KINASE YES; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF00018; SH3_1; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00452; SH3DOMAIN.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00326; SH3; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR SUPFAM; SSF55550; SH2 domain; 1.
DR SUPFAM; SSF50044; SH3-domain; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell membrane; Cytoplasm; Cytoskeleton; Kinase;
KW Lipoprotein; Membrane; Myristate; Nucleotide-binding; Palmitate;
KW Phosphoprotein; Proto-oncogene; Reference proteome; SH2 domain; SH3 domain;
KW Transferase; Tyrosine-protein kinase.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..541
FT /note="Tyrosine-protein kinase Yes"
FT /id="PRO_0000088182"
FT DOMAIN 89..150
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 156..253
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 275..528
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 394
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 281..289
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 303
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 32
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:9058199"
FT MOD_RES 334
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P07947"
FT MOD_RES 343
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P07947"
FT MOD_RES 424
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P07947"
FT MOD_RES 535
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18034455"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250"
FT LIPID 3
FT /note="S-palmitoyl cysteine; in membrane form"
FT /evidence="ECO:0000250"
FT STRAND 93..98
FT /evidence="ECO:0007829|PDB:2YT6"
FT STRAND 115..120
FT /evidence="ECO:0007829|PDB:2YT6"
FT STRAND 127..134
FT /evidence="ECO:0007829|PDB:2YT6"
FT STRAND 137..140
FT /evidence="ECO:0007829|PDB:2YT6"
FT TURN 142..144
FT /evidence="ECO:0007829|PDB:2YT6"
FT STRAND 145..150
FT /evidence="ECO:0007829|PDB:2YT6"
FT TURN 152..154
FT /evidence="ECO:0007829|PDB:2YT6"
FT STRAND 157..160
FT /evidence="ECO:0007829|PDB:5MTJ"
FT HELIX 163..170
FT /evidence="ECO:0007829|PDB:5MTJ"
FT STRAND 180..184
FT /evidence="ECO:0007829|PDB:5MTJ"
FT STRAND 186..188
FT /evidence="ECO:0007829|PDB:5MTJ"
FT STRAND 192..200
FT /evidence="ECO:0007829|PDB:5MTJ"
FT TURN 201..203
FT /evidence="ECO:0007829|PDB:5MTJ"
FT STRAND 204..214
FT /evidence="ECO:0007829|PDB:5MTJ"
FT STRAND 216..218
FT /evidence="ECO:0007829|PDB:5MTJ"
FT STRAND 220..223
FT /evidence="ECO:0007829|PDB:5MTJ"
FT STRAND 226..230
FT /evidence="ECO:0007829|PDB:5MTJ"
FT HELIX 231..240
FT /evidence="ECO:0007829|PDB:5MTJ"
FT STRAND 245..247
FT /evidence="ECO:0007829|PDB:5MTJ"
SQ SEQUENCE 541 AA; 60630 MW; 9A773C39D2119EA6 CRC64;
MGCIKSKENK SPAIKYTPEN LTEPVSPSAS HYGVEHATVA PTSSTKGASV NFNSLSMTPF
GGSSGVTPFG GASSSFSVVS SSYPTGLTGG VTIFVALYDY EARTTEDLSF KKGERFQIIN
NTEGDWWEAR SIATGKSGYI PSNYVVPADS IQAEEWYFGK MGRKDAERLL LNPGNQRGIF
LVRESETTKG AYSLSIRDWD EVRGDNVKHY KIRKLDNGGY YITTRAQFDT LQKLVKHYTE
HADGLCHKLT TVCPTVKPQT QGLAKDAWEI PRESLRLEVK LGQGCFGEVW MGTWNGTTKV
AIKTLKPGTM MPEAFLQEAQ IMKKLRHDKL VPLYAVVSEE PIYIVTEFMS KGSLLDFLKE
GDGKYLKLPQ LVDMAAQIAD GMAYIERMNY IHRDLRAANI LVGENLICKI ADFGLARLIE
DNEYTARQGA KFPIKWTAPE AALYGRFTIK SDVWSFGILQ TELVTKGRVP YPGMVNREVL
EQVERGYRMP CPQGCPESLH ELMNLCWKKD PDERPTFEYI QSFLEDYFTA TEPQYQPGEN
L
//
