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UniProtKB - P07947 (YES_HUMAN)

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Protein

Tyrosine-protein kinase Yes

Gene

YES1

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

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

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei305ATPPROSITE-ProRule annotation1
Active sitei396Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi283 – 291ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • enzyme binding Source: UniProtKB
  • epidermal growth factor receptor binding Source: Ensembl
  • ion channel binding Source: BHF-UCL
  • non-membrane spanning protein tyrosine kinase activity Source: BHF-UCL
  • phosphotyrosine residue binding Source: CAFA
  • protein tyrosine kinase activity Source: Reactome
  • signaling receptor binding Source: GO_Central
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionKinase, Transferase, Tyrosine-protein kinase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2 2681
ReactomeiR-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
SignaLinkiP07947
SIGNORiP07947

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 18

Organism-specific databases

EuPathDBiHostDB:ENSG00000176105.13
HGNCiHGNC:12841 YES1
MIMi164880 gene
neXtProtiNX_P07947

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

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi426Y → F: About 50% loss of CSK-mediated inhibition. 1 Publication1

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi7525
OpenTargetsiENSG00000176105
PharmGKBiPA37432

Chemistry databases

ChEMBLiCHEMBL2073
DrugBankiDB01254 Dasatinib
GuidetoPHARMACOLOGYi2284

Polymorphism and mutation databases

BioMutaiYES1
DMDMi125870

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved
ChainiPRO_00000881812 – 543Tyrosine-protein kinase YesAdd BLAST542

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineBy similarity1
Lipidationi3S-palmitoyl cysteine; in membrane formBy similarity1
Modified residuei21PhosphothreonineCombined sources1
Modified residuei32PhosphotyrosineBy similarity1
Modified residuei40PhosphoserineCombined sources1
Modified residuei336PhosphotyrosineCombined sources1
Modified residuei345PhosphotyrosineCombined sources1
Modified residuei426Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei446PhosphotyrosineCurated1
Modified residuei537Phosphotyrosine; by CSKCombined sources1

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, Phosphoprotein

Proteomic databases

EPDiP07947
MaxQBiP07947
PaxDbiP07947
PeptideAtlasiP07947
PRIDEiP07947
ProteomicsDBi52044

PTM databases

iPTMnetiP07947
PhosphoSitePlusiP07947
SwissPalmiP07947

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

BgeeiENSG00000176105
CleanExiHS_YES1
ExpressionAtlasiP07947 baseline and differential
GenevisibleiP07947 HS

Organism-specific databases

HPAiCAB004370
HPA026480

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.By similarity1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • epidermal growth factor receptor binding Source: Ensembl
  • ion channel binding Source: BHF-UCL
  • phosphotyrosine residue binding Source: CAFA
  • signaling receptor binding Source: GO_Central
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi113357, 127 interactors
CORUMiP07947
DIPiDIP-33849N
ELMiP07947
IntActiP07947, 92 interactors
MINTiP07947
STRINGi9606.ENSP00000324740

Chemistry databases

BindingDBiP07947

Structurei

Secondary structure

1543
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi93 – 100Combined sources8
Beta strandi117 – 121Combined sources5
Beta strandi126 – 133Combined sources8
Turni134 – 136Combined sources3
Beta strandi139 – 143Combined sources5
Helixi144 – 146Combined sources3
Beta strandi147 – 149Combined sources3

3D structure databases

ProteinModelPortaliP07947
SMRiP07947
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP07947

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini91 – 152SH3PROSITE-ProRule annotationAdd BLAST62
Domaini158 – 255SH2PROSITE-ProRule annotationAdd BLAST98
Domaini277 – 530Protein kinasePROSITE-ProRule annotationAdd BLAST254

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG0197 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000118938
HOGENOMiHOG000233858
HOVERGENiHBG008761
InParanoidiP07947
KOiK05705
PhylomeDBiP07947
TreeFamiTF351634

Family and domain databases

CDDicd12007 SH3_Yes, 1 hit
Gene3Di3.30.505.10, 1 hit
InterProiView 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
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 1 hit
PF00017 SH2, 1 hit
PF00018 SH3_1, 1 hit
PRINTSiPR00401 SH2DOMAIN
PR00452 SH3DOMAIN
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00252 SH2, 1 hit
SM00326 SH3, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF50044 SSF50044, 1 hit
SSF55550 SSF55550, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView 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

Sequencei

Sequence statusi: Complete.

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

P07947-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:543
Mass (Da):60,801
Last modified:January 23, 2007 - v3
Checksum:iA2B376084686BBCD
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041879198I → V1 PublicationCorresponds to variant dbSNP:rs34580680Ensembl.1
Natural variantiVAR_041880282K → 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
CCDSiCCDS11824.1
PIRiA26714 TVHUYS
RefSeqiNP_005424.1, NM_005433.3
XP_016881449.1, XM_017025960.1
UniGeneiHs.194148

Genome annotation databases

EnsembliENST00000314574; ENSP00000324740; ENSG00000176105
ENST00000584307; ENSP00000462468; ENSG00000176105
GeneIDi7525
KEGGihsa:7525
UCSCiuc002kky.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiYES_HUMAN
AccessioniPrimary (citable) accession number: P07947
Secondary accession number(s): A6NLB3, D3DUH1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: January 23, 2007
Last modified: July 18, 2018
This is version 215 of the entry and version 3 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 18
    Human chromosome 18: 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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