EzCatDB: M00339
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DB codeM00339
RLCP classification3.103.130000.1162 : Transfer
CATH domainDomain 11.-.-.-
Domain 21.-.-.-
Domain 33.30.505.10 : SHC Adaptor Protein
Domain 43.30.200.20 : Phosphorylase Kinase; domain 1
Domain 51.10.510.10 : Transferase(Phosphotransferase); domain 1Catalytic domain
E.C.2.7.10.2

CATH domainRelated DB codes (homologues)
1.10.510.10 : Transferase(Phosphotransferase); domain 1M00125,M00124,M00131,T00224,M00127,M00129,M00130,M00132,M00136,M00196,M00197,M00198,M00304,M00323,M00325,M00326,M00327,M00328,M00329,M00330,M00331,M00332,M00333,M00335,M00344
3.30.200.20 : Phosphorylase Kinase; domain 1M00125,M00124,M00131,T00224,M00127,M00129,M00130,M00132,M00136,M00196,M00197,M00198,M00304,M00323,M00325,M00326,M00327,M00328,M00329,M00330,M00331,M00332,M00333,M00335,M00344,D00298
3.30.505.10 : SHC Adaptor ProteinM00183,M00043,M00130,M00148,T00256,M00304,M00333,M00344,T00221

Enzyme Name
UniProtKBKEGG

P07332
Protein nameTyrosine-protein kinase Fes/FpsNon-specific protein-tyrosine kinase
ATP:protein-tyrosine O-phosphotransferase (ambiguous)
Cytoplasmic protein tyrosine kinase
FER
FES
FPS
Protein-tyrosine kinase (ambiguous)
SynonymsEC 2.7.10.2
Feline sarcoma/Fujinami avian sarcoma oncogene homolog
Proto-oncogene c-Fes
Proto-oncogene c-Fps
p93c-fes
RefSeqNP_001137255.1 (Protein)
NM_001143783.1 (DNA/RNA sequence)
NP_001137256.1 (Protein)
NM_001143784.1 (DNA/RNA sequence)
NP_001137257.1 (Protein)
NM_001143785.1 (DNA/RNA sequence)
NP_001996.1 (Protein)
NM_002005.3 (DNA/RNA sequence)
PfamPF00611 (FCH)
PF07714 (Pkinase_Tyr)
PF00017 (SH2)
[Graphical view]


UniProtKB:Accession NumberP07332
Entry nameFES_HUMAN
ActivityATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
SubunitHomooligomer. Interacts with BCR. Interacts (when activated, via coiled coil domain) with TRIM28. Interacts (via SH2 domain) with phosphorylated EZR, MS4A2/FCER1B and HCLS1/HS1. Interacts with phosphorylated KIT. Interacts with FLT3. Interacts (via FCH domain) with soluble tubulin. Interacts (via SH2 domain) with microtubules.
Subcellular locationCytoplasm > cytosol. Cytoplasm > cytoskeleton. Cell membrane, Peripheral membrane protein, Cytoplasmic side. Cytoplasmic vesicle. Golgi apparatus. Cell junction > focal adhesion. Note: Distributed throughout the cytosol when the kinase is not activated. Association with microtubules requires activation of the kinase activity. Shuttles between focal adhesions and cell-cell contacts in epithelial cells. Recruited to the lateral cell membrane in polarized epithelial cells by interaction with phosphorylated EZR. Detected at tubular membrane structures in the cytoplasm and at the cell periphery.
Cofactor

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00305C00002C00585C00008C01167
CompoundMagnesiumATP[protein]-L-tyrosineADP[protein]-L-tyrosine phosphate
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotidearomatic ring (only carbon atom),peptide/proteinamine group,nucleotidearomatic ring (only carbon atom),peptide/protein,phosphate group/phosphate ion
ChEBI18420
15422

16761

PubChem888
5957

6022

             
4dylA01UnboundUnboundUnboundUnboundUnbound
4dylA02UnboundUnboundUnboundUnboundUnbound
1wquA00UnboundUnboundUnboundUnboundUnbound
2dcrA00UnboundUnboundUnboundUnboundUnbound
3bkbA01UnboundUnboundUnboundUnboundUnbound
3cblA01UnboundUnboundUnboundUnboundUnbound
3cd3A01UnboundUnboundUnboundUnboundUnbound
4e93A01UnboundUnboundUnboundUnboundUnbound
3bkbA02UnboundUnboundUnboundUnboundUnbound
3cblA02UnboundUnboundUnboundUnboundUnbound
3cd3A02UnboundUnboundUnboundUnboundUnbound
4e93A02UnboundUnboundUnboundUnboundUnbound
3bkbA03UnboundUnboundUnboundUnboundUnbound
3cblA03UnboundUnboundAnalogue:ACE-ILE-TYR-GLU-SER-LEU(chain B)UnboundUnbound
3cd3A03UnboundUnboundAnalogue:ACE-ILE-TYR-GLU-SER-LEU(chain B)UnboundUnbound
4e93A03UnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Literature [11]
pdbCatalytic residuesCofactor-binding residuesModified residuescomment
            
4dylA01 
 
 
 
4dylA02 
 
 
 
1wquA00               
 
 
 
2dcrA00               
 
 
 
3bkbA01               
 
 
 
3cblA01               
 
 
 
3cd3A01               
 
 
 
4e93A01               
 
 
 
3bkbA02               
 
 
 
3cblA02               
 
 
invisible 487-488, 496-500, 516-519, 538-542
3cd3A02               
 
 
invisible 486-488, 496-500, 507-510, 516-519, 538-540
4e93A02               
 
 
invisible 487-488
3bkbA03ASP 683;ARG 687
ASN 688;ASP 701
TYR 713(auto-phosphorylation)
 
3cblA03ASP 683;ARG 687
ASN 688;ASP 701
TYR 713(auto-phosphorylation)
 
3cd3A03ASP 683;ARG 687
ASN 688;ASP 701
PTR 713(auto-phosphorylation)
 
4e93A03ASP 683;ARG 687
ASN 688;ASP 701
                             
invisible 708-721


references
[1]
PubMed ID8334128
JournalBiochemistry
Year1993
Volume32
Pages6995-7001
AuthorsFang F, Ahmad S, Lei J, Klecker RW, Trepel JB, Smithgall TE, Glazer RI
TitleEffect of the mutation of tyrosine 713 in p93c-fes on its catalytic activity and ability to promote myeloid differentiation in K562 cells.
[2]
CommentsPHOSPHORYLATION AT TYR-713, CATALYTIC ACTIVITY, MUTAGENESIS OF TYR-713.
PubMed ID7687763
JournalOncogene
Year1993
Volume8
Pages2283-92
AuthorsHjermstad SJ, Peters KL, Briggs SD, Glazer RI, Smithgall TE
TitleRegulation of the human c-fes protein tyrosine kinase (p93c-fes) by its src homology 2 domain and major autophosphorylation site (Tyr-713).
[3]
PubMed ID8663427
JournalJ Biol Chem
Year1996
Volume271
Pages17519-25
AuthorsRogers JA, Read RD, Li J, Peters KL, Smithgall TE
TitleAutophosphorylation of the Fes tyrosine kinase. Evidence for an intermolecular mechanism involving two kinase domain tyrosine residues.
[4]
PubMed ID9218495
JournalJ Biol Chem
Year1997
Volume272
Pages18498-503
AuthorsRead RD, Lionberger JM, Smithgall TE
TitleOligomerization of the Fes tyrosine kinase. Evidence for a coiled-coil domain in the unique N-terminal region.
[5]
PubMed ID10567558
JournalMol Cell Biol
Year1999
Volume19
Pages8335-43
AuthorsCheng H, Rogers JA, Dunham NA, Smithgall TE
TitleRegulation of c-Fes tyrosine kinase and biological activities by N-terminal coiled-coil oligomerization domains.
[6]
CommentsFUNCTION IN CELL PROLIFERATION AND CELL SPREADING, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, SUBUNIT, DOMAIN, MUTAGENESIS OF LEU-145 AND LEU-334.
PubMed ID11509660
JournalMol Cell Biol
Year2001
Volume21
Pages6170-80
AuthorsCheng HY, Schiavone AP, Smithgall TE
TitleA point mutation in the N-terminal coiled-coil domain releases c-Fes tyrosine kinase activity and survival signaling in myeloid leukemia cells.
[7]
CommentsREVIEW.
PubMed ID11994747
JournalNat Rev Mol Cell Biol
Year2002
Volume3
Pages278-89
AuthorsGreer P
TitleClosing in on the biological functions of Fps/Fes and Fer.
[8]
PubMed ID12653561
JournalBiochemistry
Year2003
Volume42
Pages3567-74
AuthorsTakashima Y, Delfino FJ, Engen JR, Superti-Furga G, Smithgall TE
TitleRegulation of c-Fes tyrosine kinase activity by coiled-coil and SH2 domains: analysis with Saccharomyces cerevisiae.
[9]
CommentsSTRUCTURE BY NMR OF 450-550.
PubMed ID15929003
JournalJ Biomol NMR
Year2005
Volume31
Pages357-61
AuthorsScott A, Pantoja-Uceda D, Koshiba S, Inoue M, Kigawa T, Terada T, Shirouzu M, Tanaka A, Sugano S, Yokoyama S, Guntert P
TitleSolution structure of the Src homology 2 domain from the human feline sarcoma oncogene Fes.
Related PDB1wqu
Related UniProtKBP07332
[10]
PubMed ID17017791
JournalJ Am Chem Soc
Year2006
Volume128
Pages13112-22
AuthorsLopez-Mendez B, Guntert P
TitleAutomated protein structure determination from NMR spectra.
Related PDB2dcr
Related UniProtKBP07332
[11]
CommentsX-RAY CRYSTALLOGRAPHY (1.78 ANGSTROMS) OF 448-822 OF UNPHOSPHORYLATED APOPROTEIN AND IN COMPLEX WITH STAUROSPORINE AND A SUBSTRATE PEPTIDE, CATALYTIC ACTIVITY, ENZYME REGULATION, PHOSPHORYLATION AT TYR-713, NMR SPECTROSCOPY, MUTAGENESIS OF GLY-463 AND ARG-483.
PubMed ID18775312
JournalCell
Year2008
Volume134
Pages793-803
AuthorsFilippakopoulos P, Kofler M, Hantschel O, Gish GD, Grebien F, Salah E, Neudecker P, Kay LE, Turk BE, Superti-Furga G, Pawson T, Knapp S
TitleStructural coupling of SH2-kinase domains links Fes and Abl substrate recognition and kinase activation.
Related PDB3bkb,3cbl,3cd3
Related UniProtKBP07332
[12]
CommentsSUBUNIT, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-713, PHOSPHORYLATION BY HCK, DOMAIN.
PubMed ID19382747
JournalBiochemistry
Year2009
Volume48
Pages4780-8
AuthorsShaffer JM, Hellwig S, Smithgall TE
TitleBimolecular fluorescence complementation demonstrates that the c-Fes protein-tyrosine kinase forms constitutive oligomers in living cells.
[13]
CommentsFUNCTION, INTERACTION WITH MS4A2/FCER1B AND HCLS1/HS1, SUBCELLULAR LOCATION, PHOSPHORYLATION, INTERACTION WITH PHOSPHOINOSITIDE-CONTAINING MEMBRANES, MUTAGENESIS OF 113-ARG-LYS-114.
PubMed ID19001085
JournalMol Cell Biol
Year2009
Volume29
Pages389-401
AuthorsMcPherson VA, Everingham S, Karisch R, Smith JA, Udell CM, Zheng J, Jia Z, Craig AW
TitleContributions of F-BAR and SH2 domains of Fes protein tyrosine kinase for coupling to the FcepsilonRI pathway in mast cells.
[14]
CommentsREVIEW.
PubMed ID21622225
JournalFront Biosci
Year2011
Volume17
Pages3146-55
AuthorsHellwig S, Smithgall TE
TitleStructure and regulation of the c-Fes protein-tyrosine kinase.
[15]
PubMed ID22201778
JournalFront Biosci
Year2012
Volume17
Pages861-75
AuthorsCraig AW
TitleFES/FER kinase signaling in hematopoietic cells and leukemias.
[16]
PubMed ID22520759
JournalChem Biol
Year2012
Volume19
Pages529-40
AuthorsHellwig S, Miduturu CV, Kanda S, Zhang J, Filippakopoulos P, Salah E, Deng X, Choi HG, Zhou W, Hur W, Knapp S, Gray NS, Smithgall TE
TitleSmall-molecule inhibitors of the c-Fes protein-tyrosine kinase.
Related PDB4e93

comments
This enzyme belongs to Fes/Fps subfamily of nonreceptor protein tyrosine kinases. (Fes indicates feline sarcoma, whereas Fps indicates Fujinami poultry sarcoma.) This enzyme is a proto-oncogene product.
This enzyme is composed of N-terminal F-BAR domain, FX domain, Src homology 2 (SH2) domain, and C-terminal kinase domain.
The catalytic domain of this enzyme is homologous to that of proto-oncogene tyrosine-protein kinase ABL1 (M00130 in EzCatDB).
The N-terminal F-BAR domain must be necessary for oligomerization of this enzyme (see [4] and [15]).
The SH2 domain can enhance the catalytic activity and substrate recognition of the kinase domain (see [11]). According to the literature [11], binding of a phosphorylated ligand to the SH2 domain can stabilize the interaction between the SH2 domain and the kinase domain.
Autophosphorylation of Tyr713 in the kinase domain stimulates the catalytic activity (see [2]). According to the literature [11], phosphorylation of activation segment at Tyr713 and binding of substrate molecule to the linase domain stabilize the conformation of active site suitable for catalysis.

createdupdated
2012-06-252012-12-18


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Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
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