FES_FELCA
ID FES_FELCA Reviewed; 820 AA.
AC P14238;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 2.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Tyrosine-protein kinase Fes/Fps;
DE EC=2.7.10.2;
DE AltName: Full=Proto-oncogene c-Fes;
GN Name=FES; Synonyms=FPS;
OS Felis catus (Cat) (Felis silvestris catus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Feliformia; Felidae; Felinae; Felis.
OX NCBI_TaxID=9685;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3553615; DOI=10.1128/jvi.61.6.2009-2016.1987;
RA Roebroek A.J.M., Schalken J.A., Onnekink C., Bloemers H.P.J.,
RA van de Ven W.J.M.;
RT "Structure of the feline c-fes/fps proto-oncogene: genesis of a retroviral
RT oncogene.";
RL J. Virol. 61:2009-2016(1987).
CC -!- FUNCTION: Tyrosine-protein kinase that acts downstream of cell surface
CC receptors and plays a role in the regulation of the actin cytoskeleton,
CC microtubule assembly, cell attachment and cell spreading. Plays a role
CC in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated
CC signaling in mast cells. Acts down-stream of the activated FCER1
CC receptor and the mast/stem cell growth factor receptor KIT. Plays a
CC role in the regulation of mast cell degranulation. Plays a role in the
CC regulation of cell differentiation and promotes neurite outgrowth in
CC response to NGF signaling. Plays a role in cell scattering and cell
CC migration in response to HGF-induced activation of EZR. Phosphorylates
CC BCR and down-regulates BCR kinase activity. Phosphorylates HCLS1/HS1,
CC PECAM1, STAT3 and TRIM28 (By similarity). {ECO:0000250}.
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 -!- ACTIVITY REGULATION: Kinase activity is tightly regulated. Activated in
CC response to signaling from a cell surface receptor. Activation probably
CC requires binding of a substrate via the SH2 domain, plus
CC autophosphorylation at Tyr-711. Present in an inactive form in the
CC absence of activating stimuli (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homooligomer. Interacts with BCR. Interacts (when activated,
CC via coiled coil domain) with TRIM28. Interacts (via SH2 domain) with
CC phosphorylated EZR, MS4A2/FCER1B and HCLS1/HS1. Interacts with
CC phosphorylated KIT. Interacts with FLT3. Interacts (via F-BAR domain)
CC with soluble tubulin. Interacts (via SH2 domain) with microtubules (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250}. Cytoplasm,
CC cytoskeleton {ECO:0000250}. Cell membrane {ECO:0000250}; Peripheral
CC membrane protein {ECO:0000250}; Cytoplasmic side {ECO:0000250}.
CC Cytoplasmic vesicle {ECO:0000250}. Golgi apparatus {ECO:0000250}. Cell
CC junction, focal adhesion {ECO:0000250}. Note=Distributed throughout the
CC cytosol when the kinase is not activated. Association with microtubules
CC requires activation of the kinase activity. Shuttles between focal
CC adhesions and cell-cell contacts in epithelial cells. Recruited to the
CC lateral cell membrane in polarized epithelial cells by interaction with
CC phosphorylated EZR. Detected at tubular membrane structures in the
CC cytoplasm and at the cell periphery (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The coiled coil domains are important for regulating the kinase
CC activity. They mediate homooligomerization and probably also
CC interaction with other proteins (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The N-terminal region including the first coiled coil domain
CC mediates interaction with phosphoinositide-containing membranes.
CC {ECO:0000250}.
CC -!- PTM: Autophosphorylated on Tyr-711 in response to FGF2. Phosphorylated
CC by LYN in response to FCER1 activation. Phosphorylated by HCK (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Fes/fps subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; M16705; AAA30808.1; -; Genomic_DNA.
DR EMBL; M16666; AAA30808.1; JOINED; Genomic_DNA.
DR EMBL; M16667; AAA30808.1; JOINED; Genomic_DNA.
DR EMBL; M16668; AAA30808.1; JOINED; Genomic_DNA.
DR EMBL; M16669; AAA30808.1; JOINED; Genomic_DNA.
DR EMBL; M16670; AAA30808.1; JOINED; Genomic_DNA.
DR EMBL; M16671; AAA30808.1; JOINED; Genomic_DNA.
DR EMBL; M16706; AAA30808.1; JOINED; Genomic_DNA.
DR EMBL; M16672; AAA30808.1; JOINED; Genomic_DNA.
DR EMBL; M16673; AAA30808.1; JOINED; Genomic_DNA.
DR EMBL; M16674; AAA30808.1; JOINED; Genomic_DNA.
DR EMBL; M16698; AAA30808.1; JOINED; Genomic_DNA.
DR EMBL; M16700; AAA30808.1; JOINED; Genomic_DNA.
DR EMBL; M16701; AAA30808.1; JOINED; Genomic_DNA.
DR EMBL; M16702; AAA30808.1; JOINED; Genomic_DNA.
DR EMBL; M16704; AAA30808.1; JOINED; Genomic_DNA.
DR PIR; A27824; TVCTFF.
DR AlphaFoldDB; P14238; -.
DR SMR; P14238; -.
DR STRING; 9685.ENSFCAP00000005663; -.
DR eggNOG; KOG0194; Eukaryota.
DR InParanoid; P14238; -.
DR Proteomes; UP000011712; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0015630; C:microtubule cytoskeleton; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0034987; F:immunoglobulin receptor binding; ISS:UniProtKB.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; ISS:UniProtKB.
DR GO; GO:0035091; F:phosphatidylinositol binding; ISS:UniProtKB.
DR GO; GO:0004713; F:protein tyrosine kinase activity; ISS:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0006935; P:chemotaxis; IBA:GO_Central.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:2000251; P:positive regulation of actin cytoskeleton reorganization; ISS:UniProtKB.
DR GO; GO:0031116; P:positive regulation of microtubule polymerization; ISS:UniProtKB.
DR GO; GO:0045639; P:positive regulation of myeloid cell differentiation; ISS:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:0030155; P:regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:0045595; P:regulation of cell differentiation; ISS:UniProtKB.
DR GO; GO:2000145; P:regulation of cell motility; ISS:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; ISS:UniProtKB.
DR GO; GO:0043304; P:regulation of mast cell degranulation; ISS:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd10361; SH2_Fps_family; 1.
DR Gene3D; 1.20.1270.60; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR027267; AH/BAR_dom_sf.
DR InterPro; IPR031160; F_BAR.
DR InterPro; IPR001060; FCH_dom.
DR InterPro; IPR035849; Fes/Fps/Fer_SH2.
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; IPR016250; Tyr-prot_kinase_Fes/Fps.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR Pfam; PF00611; FCH; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF00017; SH2; 1.
DR PIRSF; PIRSF000632; TyrPK_fps; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00055; FCH; 1.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF103657; SSF103657; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51741; F_BAR; 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.
PE 3: Inferred from homology;
KW ATP-binding; Cell junction; Cell membrane; Coiled coil; Cytoplasm;
KW Cytoplasmic vesicle; Cytoskeleton; Golgi apparatus; Kinase; Lipid-binding;
KW Membrane; Nucleotide-binding; Phosphoprotein; Proto-oncogene;
KW Reference proteome; SH2 domain; Transferase; Tumor suppressor;
KW Tyrosine-protein kinase.
FT CHAIN 1..820
FT /note="Tyrosine-protein kinase Fes/Fps"
FT /id="PRO_0000088085"
FT DOMAIN 1..258
FT /note="F-BAR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01077"
FT DOMAIN 458..547
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 559..820
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..298
FT /note="Important for interaction with membranes containing
FT phosphoinositides"
FT /evidence="ECO:0000250"
FT REGION 392..418
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 123..163
FT /evidence="ECO:0000255"
FT COILED 318..389
FT /evidence="ECO:0000255"
FT ACT_SITE 681
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 565..573
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 588
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 65
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P07332"
FT MOD_RES 259
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P07332"
FT MOD_RES 406
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P07332"
FT MOD_RES 409
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P07332"
FT MOD_RES 419
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P07332"
FT MOD_RES 711
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P07332"
FT MOD_RES 714
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P07332"
SQ SEQUENCE 820 AA; 92975 MW; F3A52B750236834E CRC64;
MGFSSELCSP QGHGAVQQMQ EAELRLLEGM RKWMAQRVKS DREYAGLLHH MSLQDGGGRG
TGPYSPISQS WAEITSQTEG LSRLLRQHAE DLNSGPLSKL GLLIRERQQL RKTYSEQWQQ
LQQELTKTHN QDIEKLKSQY RALARDSAQA RRKYQEASKD KDRDKAKDKY VRSLWKLFAH
HNRYVLGVRA AQLHHHHHHQ LMLPGLLQSL QDLHQEMACI LKEILQEYLE ISSLVQDEVV
AIHLEMAAAV ARIQPEAEYQ GFLRQYGSTP DVPPCVTFDE SLLEEGEPLE PGELQLNELT
VESVQHTLTS VTDELTVATQ TVLSRQEAVA QLQRELQNEE QNTHPRERVQ LLAKKQVLQE
ALQALQVALC SQAKLQAQRE LLQAKLEQLG PGEPPPVLLL QDDRHSTSSS EQEREGGRTP
TLEILKSHIS GIFRPKFSLP PPLQLVPEVQ KPLHEQLWYH GALPRAEVAE LLTHSGDFLV
RESQGKQEYV LSVLWDGQPR HFIIESADNL YRLEGDGFAS IPLLVDHLLR SQQPLTKKSG
IVLNRAVPKD KWVLNHEDLV LGEQIGRGNF GEVFSGRLRA DNTLVAVKSC RETLPPDIKA
KFLQEAKILK QYSHPNIVRL IGVCTQKQPI YIVMELVQGG DFLTFLRTEG ARLRMKTLLQ
MVGDAAAGME YLESKCCIHR DLAARNCLVT EKNVLKISDF GMSREEADGI YAASGGLRQV
PVKWTAPEAL NYGRYSSESD VWSFGILLWE TFSLGASPYP NLSNQQTREF VEKGGRLPCP
ELCPDAVFRL MEQCWAYEPG QRPSFSAIYQ ELQSIRKRHR
