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 27-MAR-2024, entry version 159. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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.ENSFCAP00000053376; -. DR PaxDb; 9685-ENSFCAP00000005663; -. DR eggNOG; KOG0194; Eukaryota. DR InParanoid; P14238; -. DR Proteomes; UP000011712; Unplaced. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; ISS:UniProtKB. DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW. DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell. 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:0007155; P:cell adhesion; IBA:GO_Central. DR GO; GO:0006935; P:chemotaxis; IBA:GO_Central. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; 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 CDD; cd07685; F-BAR_Fes; 1. DR CDD; cd10361; SH2_Fps_family; 1. DR Gene3D; 1.20.1270.60; Arfaptin homology (AH) domain/BAR domain; 1. DR Gene3D; 1.10.287.160; HR1 repeat; 1. DR Gene3D; 3.30.505.10; SH2 domain; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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 PANTHER; PTHR24418; TYROSINE-PROTEIN KINASE; 1. DR PANTHER; PTHR24418:SF197; TYROSINE-PROTEIN KINASE FES_FPS; 1. 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; BAR/IMD domain-like; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF55550; SH2 domain; 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 //