UniProtKB - P07947 (YES_HUMAN)
Protein
Tyrosine-protein kinase Yes
Gene
YES1
Organism
Homo sapiens (Human)
Status
Functioni
Non-receptor protein tyrosine kinase that is involved in the regulation of cell growth and survival, apoptosis, cell-cell adhesion, cytoskeleton remodeling, and differentiation. Stimulation by receptor tyrosine kinases (RTKs) including EGRF, PDGFR, CSF1R and FGFR leads to recruitment of YES1 to the phosphorylated receptor, and activation and phosphorylation of downstream substrates. Upon EGFR activation, promotes the phosphorylation of PARD3 to favor epithelial tight junction assembly. Participates in the phosphorylation of specific junctional components such as CTNND1 by stimulating the FYN and FER tyrosine kinases at cell-cell contacts. Upon T-cell stimulation by CXCL12, phosphorylates collapsin response mediator protein 2/DPYSL2 and induces T-cell migration. Participates in CD95L/FASLG signaling pathway and mediates AKT-mediated cell migration. Plays a role in cell cycle progression by phosphorylating the cyclin-dependent kinase 4/CDK4 thus regulating the G1 phase. Also involved in G2/M progression and cytokinesis.5 Publications
Catalytic activityi
- EC:2.7.10.2PROSITE-ProRule annotation
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 305 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 396 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 283 – 291 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- enzyme binding Source: UniProtKB
- ion channel binding Source: BHF-UCL
- non-membrane spanning protein tyrosine kinase activity Source: GO_Central
- phosphotyrosine residue binding Source: CAFA
- protein tyrosine kinase activity Source: Reactome
- signaling receptor binding Source: GO_Central
GO - Biological processi
- cell differentiation Source: GO_Central
- cellular protein modification process Source: ProtInc
- ephrin receptor signaling pathway Source: Reactome
- Fc-gamma receptor signaling pathway involved in phagocytosis Source: Reactome
- innate immune response Source: GO_Central
- leukocyte migration Source: Reactome
- peptidyl-tyrosine autophosphorylation Source: GO_Central
- regulation of cell population proliferation Source: GO_Central
- regulation of vascular permeability Source: BHF-UCL
- T cell costimulation Source: Reactome
- transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
Keywordsi
Molecular function | Kinase, Transferase, Tyrosine-protein kinase |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.10.2, 2681 |
PathwayCommonsi | P07947 |
Reactomei | R-HSA-1227986, Signaling by ERBB2 R-HSA-1433557, Signaling by SCF-KIT R-HSA-1433559, Regulation of KIT signaling R-HSA-2029481, FCGR activation R-HSA-210990, PECAM1 interactions R-HSA-2682334, EPH-Ephrin signaling R-HSA-389356, CD28 co-stimulation R-HSA-389513, CTLA4 inhibitory signaling R-HSA-3928662, EPHB-mediated forward signaling R-HSA-3928663, EPHA-mediated growth cone collapse R-HSA-3928665, EPH-ephrin mediated repulsion of cells R-HSA-8940973, RUNX2 regulates osteoblast differentiation R-HSA-912631, Regulation of signaling by CBL R-HSA-9664323, FCGR3A-mediated IL10 synthesis R-HSA-9664422, FCGR3A-mediated phagocytosis R-HSA-9670439, Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants |
SignaLinki | P07947 |
SIGNORi | P07947 |
Names & Taxonomyi
Protein namesi | Recommended name: Tyrosine-protein kinase Yes (EC:2.7.10.2)Alternative name(s): Proto-oncogene c-Yes p61-Yes |
Gene namesi | Name:YES1 Synonyms:YES |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:12841, YES1 |
MIMi | 164880, gene |
neXtProti | NX_P07947 |
VEuPathDBi | HostDB:ENSG00000176105.13 |
Subcellular locationi
Cytosol
Cytoskeleton
Plasma membrane
Note: Newly synthesized protein initially accumulates in the Golgi region and traffics to the plasma membrane through the exocytic pathway.
Cytoskeleton
- microtubule organizing center Source: UniProtKB-SubCell
Cytosol
- cytosol Source: HPA
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Golgi apparatus
- Golgi apparatus Source: UniProtKB
Plasma Membrane
- extrinsic component of cytoplasmic side of plasma membrane Source: GO_Central
- plasma membrane Source: UniProtKB
Other locations
- focal adhesion Source: UniProtKB
Keywords - Cellular componenti
Cell membrane, Cytoplasm, Cytoskeleton, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 426 | Y → F: About 50% loss of CSK-mediated inhibition. 1 Publication | 1 |
Keywords - Diseasei
Proto-oncogeneOrganism-specific databases
DisGeNETi | 7525 |
OpenTargetsi | ENSG00000176105 |
PharmGKBi | PA37432 |
Miscellaneous databases
Pharosi | P07947, Tclin |
Chemistry databases
ChEMBLi | CHEMBL2073 |
DrugBanki | DB01254, Dasatinib DB12010, Fostamatinib |
DrugCentrali | P07947 |
GuidetoPHARMACOLOGYi | 2284 |
Genetic variation databases
BioMutai | YES1 |
DMDMi | 125870 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | Removed | |||
ChainiPRO_0000088181 | 2 – 543 | Tyrosine-protein kinase YesAdd BLAST | 542 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Lipidationi | 2 | N-myristoyl glycineBy similarity | 1 | |
Lipidationi | 3 | S-palmitoyl cysteine; in membrane formBy similarity | 1 | |
Modified residuei | 21 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 32 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 40 | PhosphoserineCombined sources | 1 | |
Modified residuei | 336 | PhosphotyrosineCombined sources | 1 | |
Modified residuei | 345 | PhosphotyrosineCombined sources | 1 | |
Modified residuei | 426 | Phosphotyrosine; by autocatalysis1 Publication | 1 | |
Modified residuei | 446 | PhosphotyrosineCurated | 1 | |
Modified residuei | 537 | Phosphotyrosine; by CSKCombined sources | 1 |
Post-translational modificationi
Phosphorylation by CSK on the C-terminal tail maintains the enzyme in an inactive state. Autophosphorylation at Tyr-426 maintains enzyme activity by blocking CSK-mediated inhibition.3 Publications
Palmitoylation at Cys-3 promotes membrane localization.By similarity
Keywords - PTMi
Lipoprotein, Myristate, Palmitate, PhosphoproteinProteomic databases
EPDi | P07947 |
jPOSTi | P07947 |
MassIVEi | P07947 |
MaxQBi | P07947 |
PaxDbi | P07947 |
PeptideAtlasi | P07947 |
PRIDEi | P07947 |
ProteomicsDBi | 52044 |
PTM databases
iPTMneti | P07947 |
PhosphoSitePlusi | P07947 |
SwissPalmi | P07947 |
Expressioni
Tissue specificityi
Expressed in the epithelial cells of renal proximal tubules and stomach as well as hematopoietic cells in the bone marrow and spleen in the fetal tissues. In adult, expressed in epithelial cells of the renal proximal tubules and present in keratinocytes in the basal epidermal layer of epidermis.2 Publications
Gene expression databases
Bgeei | ENSG00000176105, Expressed in secondary oocyte and 244 other tissues |
ExpressionAtlasi | P07947, baseline and differential |
Genevisiblei | P07947, HS |
Organism-specific databases
HPAi | ENSG00000176105, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with YAP1 and CSF1R (By similarity).
Interacts with CTNND1; this interaction allows YES1-mediated activation of FYN and FER and subsequent phosphorylation of CTNND1 (By similarity).
Interacts with FASLG.
Interacts with IL6ST/gp130 (PubMed:25731159).
By similarity2 PublicationsBinary interactionsi
P07947
GO - Molecular functioni
- enzyme binding Source: UniProtKB
- ion channel binding Source: BHF-UCL
- phosphotyrosine residue binding Source: CAFA
- signaling receptor binding Source: GO_Central
Protein-protein interaction databases
BioGRIDi | 113357, 216 interactors |
CORUMi | P07947 |
DIPi | DIP-33849N |
ELMi | P07947 |
IntActi | P07947, 153 interactors |
MINTi | P07947 |
STRINGi | 9606.ENSP00000462468 |
Chemistry databases
BindingDBi | P07947 |
Miscellaneous databases
RNActi | P07947, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P07947 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P07947 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 91 – 152 | SH3PROSITE-ProRule annotationAdd BLAST | 62 | |
Domaini | 158 – 255 | SH2PROSITE-ProRule annotationAdd BLAST | 98 | |
Domaini | 277 – 530 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 254 |
Sequence similaritiesi
Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.PROSITE-ProRule annotation
Keywords - Domaini
SH2 domain, SH3 domainPhylogenomic databases
eggNOGi | KOG0197, Eukaryota |
GeneTreei | ENSGT00940000154920 |
HOGENOMi | CLU_000288_7_2_1 |
InParanoidi | P07947 |
OrthoDBi | 539311at2759 |
PhylomeDBi | P07947 |
TreeFami | TF351634 |
Family and domain databases
CDDi | cd12007, SH3_Yes, 1 hit |
Gene3Di | 3.30.505.10, 1 hit |
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR001245, Ser-Thr/Tyr_kinase_cat_dom IPR000980, SH2 IPR036860, SH2_dom_sf IPR036028, SH3-like_dom_sf IPR001452, SH3_domain IPR008266, Tyr_kinase_AS IPR020635, Tyr_kinase_cat_dom IPR035751, Yes_SH3 |
Pfami | View protein in Pfam PF07714, PK_Tyr_Ser-Thr, 1 hit PF00017, SH2, 1 hit PF00018, SH3_1, 1 hit |
PRINTSi | PR00401, SH2DOMAIN PR00452, SH3DOMAIN PR00109, TYRKINASE |
SMARTi | View protein in SMART SM00252, SH2, 1 hit SM00326, SH3, 1 hit SM00219, TyrKc, 1 hit |
SUPFAMi | SSF50044, SSF50044, 1 hit SSF55550, SSF55550, 1 hit SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00109, PROTEIN_KINASE_TYR, 1 hit PS50001, SH2, 1 hit PS50002, SH3, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
P07947-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MGCIKSKENK SPAIKYRPEN TPEPVSTSVS HYGAEPTTVS PCPSSSAKGT
60 70 80 90 100
AVNFSSLSMT PFGGSSGVTP FGGASSSFSV VPSSYPAGLT GGVTIFVALY
110 120 130 140 150
DYEARTTEDL SFKKGERFQI INNTEGDWWE ARSIATGKNG YIPSNYVAPA
160 170 180 190 200
DSIQAEEWYF GKMGRKDAER LLLNPGNQRG IFLVRESETT KGAYSLSIRD
210 220 230 240 250
WDEIRGDNVK HYKIRKLDNG GYYITTRAQF DTLQKLVKHY TEHADGLCHK
260 270 280 290 300
LTTVCPTVKP QTQGLAKDAW EIPRESLRLE VKLGQGCFGE VWMGTWNGTT
310 320 330 340 350
KVAIKTLKPG TMMPEAFLQE AQIMKKLRHD KLVPLYAVVS EEPIYIVTEF
360 370 380 390 400
MSKGSLLDFL KEGDGKYLKL PQLVDMAAQI ADGMAYIERM NYIHRDLRAA
410 420 430 440 450
NILVGENLVC KIADFGLARL IEDNEYTARQ GAKFPIKWTA PEAALYGRFT
460 470 480 490 500
IKSDVWSFGI LQTELVTKGR VPYPGMVNRE VLEQVERGYR MPCPQGCPES
510 520 530 540
LHELMNLCWK KDPDERPTFE YIQSFLEDYF TATEPQYQPG ENL
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketJ3QRU1 | J3QRU1_HUMAN | Tyrosine-protein kinase | YES1 | 548 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_041879 | 198 | I → V1 PublicationCorresponds to variant dbSNP:rs34580680Ensembl. | 1 | |
Natural variantiVAR_041880 | 282 | K → R1 PublicationCorresponds to variant dbSNP:rs35126906Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M15990 mRNA Translation: AAA35735.1 AP001178 Genomic DNA No translation available. CH471113 Genomic DNA Translation: EAX01709.1 CH471113 Genomic DNA Translation: EAX01710.1 BC048960 mRNA Translation: AAH48960.1 |
CCDSi | CCDS11824.1 |
PIRi | A26714, TVHUYS |
RefSeqi | NP_005424.1, NM_005433.3 XP_016881449.1, XM_017025960.1 |
Genome annotation databases
Ensembli | ENST00000314574; ENSP00000324740; ENSG00000176105 ENST00000584307; ENSP00000462468; ENSG00000176105 |
GeneIDi | 7525 |
KEGGi | hsa:7525 |
UCSCi | uc002kky.4, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M15990 mRNA Translation: AAA35735.1 AP001178 Genomic DNA No translation available. CH471113 Genomic DNA Translation: EAX01709.1 CH471113 Genomic DNA Translation: EAX01710.1 BC048960 mRNA Translation: AAH48960.1 |
CCDSi | CCDS11824.1 |
PIRi | A26714, TVHUYS |
RefSeqi | NP_005424.1, NM_005433.3 XP_016881449.1, XM_017025960.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2HDA | X-ray | 1.90 | A | 91-152 | [»] | |
SMRi | P07947 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 113357, 216 interactors |
CORUMi | P07947 |
DIPi | DIP-33849N |
ELMi | P07947 |
IntActi | P07947, 153 interactors |
MINTi | P07947 |
STRINGi | 9606.ENSP00000462468 |
Chemistry databases
BindingDBi | P07947 |
ChEMBLi | CHEMBL2073 |
DrugBanki | DB01254, Dasatinib DB12010, Fostamatinib |
DrugCentrali | P07947 |
GuidetoPHARMACOLOGYi | 2284 |
PTM databases
iPTMneti | P07947 |
PhosphoSitePlusi | P07947 |
SwissPalmi | P07947 |
Genetic variation databases
BioMutai | YES1 |
DMDMi | 125870 |
Proteomic databases
EPDi | P07947 |
jPOSTi | P07947 |
MassIVEi | P07947 |
MaxQBi | P07947 |
PaxDbi | P07947 |
PeptideAtlasi | P07947 |
PRIDEi | P07947 |
ProteomicsDBi | 52044 |
Protocols and materials databases
Antibodypediai | 3819, 479 antibodies |
DNASUi | 7525 |
Genome annotation databases
Ensembli | ENST00000314574; ENSP00000324740; ENSG00000176105 ENST00000584307; ENSP00000462468; ENSG00000176105 |
GeneIDi | 7525 |
KEGGi | hsa:7525 |
UCSCi | uc002kky.4, human |
Organism-specific databases
CTDi | 7525 |
DisGeNETi | 7525 |
GeneCardsi | YES1 |
HGNCi | HGNC:12841, YES1 |
HPAi | ENSG00000176105, Low tissue specificity |
MIMi | 164880, gene |
neXtProti | NX_P07947 |
OpenTargetsi | ENSG00000176105 |
PharmGKBi | PA37432 |
VEuPathDBi | HostDB:ENSG00000176105.13 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0197, Eukaryota |
GeneTreei | ENSGT00940000154920 |
HOGENOMi | CLU_000288_7_2_1 |
InParanoidi | P07947 |
OrthoDBi | 539311at2759 |
PhylomeDBi | P07947 |
TreeFami | TF351634 |
Enzyme and pathway databases
BRENDAi | 2.7.10.2, 2681 |
PathwayCommonsi | P07947 |
Reactomei | R-HSA-1227986, Signaling by ERBB2 R-HSA-1433557, Signaling by SCF-KIT R-HSA-1433559, Regulation of KIT signaling R-HSA-2029481, FCGR activation R-HSA-210990, PECAM1 interactions R-HSA-2682334, EPH-Ephrin signaling R-HSA-389356, CD28 co-stimulation R-HSA-389513, CTLA4 inhibitory signaling R-HSA-3928662, EPHB-mediated forward signaling R-HSA-3928663, EPHA-mediated growth cone collapse R-HSA-3928665, EPH-ephrin mediated repulsion of cells R-HSA-8940973, RUNX2 regulates osteoblast differentiation R-HSA-912631, Regulation of signaling by CBL R-HSA-9664323, FCGR3A-mediated IL10 synthesis R-HSA-9664422, FCGR3A-mediated phagocytosis R-HSA-9670439, Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants |
SignaLinki | P07947 |
SIGNORi | P07947 |
Miscellaneous databases
BioGRID-ORCSi | 7525, 19 hits in 905 CRISPR screens |
ChiTaRSi | YES1, human |
EvolutionaryTracei | P07947 |
GeneWikii | YES1 |
GenomeRNAii | 7525 |
Pharosi | P07947, Tclin |
PROi | PR:P07947 |
RNActi | P07947, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000176105, Expressed in secondary oocyte and 244 other tissues |
ExpressionAtlasi | P07947, baseline and differential |
Genevisiblei | P07947, HS |
Family and domain databases
CDDi | cd12007, SH3_Yes, 1 hit |
Gene3Di | 3.30.505.10, 1 hit |
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR001245, Ser-Thr/Tyr_kinase_cat_dom IPR000980, SH2 IPR036860, SH2_dom_sf IPR036028, SH3-like_dom_sf IPR001452, SH3_domain IPR008266, Tyr_kinase_AS IPR020635, Tyr_kinase_cat_dom IPR035751, Yes_SH3 |
Pfami | View protein in Pfam PF07714, PK_Tyr_Ser-Thr, 1 hit PF00017, SH2, 1 hit PF00018, SH3_1, 1 hit |
PRINTSi | PR00401, SH2DOMAIN PR00452, SH3DOMAIN PR00109, TYRKINASE |
SMARTi | View protein in SMART SM00252, SH2, 1 hit SM00326, SH3, 1 hit SM00219, TyrKc, 1 hit |
SUPFAMi | SSF50044, SSF50044, 1 hit SSF55550, SSF55550, 1 hit SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00109, PROTEIN_KINASE_TYR, 1 hit PS50001, SH2, 1 hit PS50002, SH3, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | YES_HUMAN | |
Accessioni | P07947Primary (citable) accession number: P07947 Secondary accession number(s): A6NLB3, D3DUH1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1988 |
Last sequence update: | January 23, 2007 | |
Last modified: | February 10, 2021 | |
This is version 235 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - Human chromosome 18
Human chromosome 18: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families