ID   FER_CANLF               Reviewed;         823 AA.
AC   Q9TTY2;
DT   28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   27-MAR-2024, entry version 141.
DE   RecName: Full=Tyrosine-protein kinase Fer;
DE            EC=2.7.10.2;
DE   AltName: Full=Proto-oncogene c-Fer;
DE   AltName: Full=p94-Fer;
GN   Name=FER;
OS   Canis lupus familiaris (Dog) (Canis familiaris).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX   NCBI_TaxID=9615;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Prostate;
RX   PubMed=10687853; DOI=10.1016/s0303-7207(99)00205-1;
RA   Allard P., Zoubeidi A., Nguyen L.T., Tessier S., Tanguay S., Chevrette M.,
RA   Aprikian A., Chevalier S.;
RT   "Links between Fer tyrosine kinase expression levels and prostate cell
RT   proliferation.";
RL   Mol. Cell. Endocrinol. 159:63-77(2000).
CC   -!- FUNCTION: Tyrosine-protein kinase that acts downstream of cell surface
CC       receptors for growth factors and plays a role in the regulation of the
CC       actin cytoskeleton, microtubule assembly, lamellipodia formation, cell
CC       attachment and cell migration. Acts downstream of EGFR, PDGFRA and
CC       PDGFRB. Acts downstream of EGFR to promote activation of NF-kappa-B and
CC       cell proliferation. Acts downstream of the activated FCER1 receptor and
CC       plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-
CC       mediated signaling in mast cells. Plays a role in the regulation of
CC       mast cell degranulation. Phosphorylates CTTN, CTNND1, PTK2/FAK1, GAB1,
CC       PECAM1 and PTPN11 (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   -!- SUBUNIT: Homotrimer. Interacts with CTNND1, EGFR, FLT3, IRS1, PECAM1,
CC       PIK3R1 and PDGFR. Interacts (via SH2 domain) with CTTN. Component of a
CC       complex that contains at least FER, CTTN and PTK2/FAK1 (By similarity).
CC       {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cytoplasm, cytoskeleton
CC       {ECO:0000250}. Cell membrane {ECO:0000250}; Peripheral membrane protein
CC       {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Cell projection
CC       {ECO:0000250}. Cell junction {ECO:0000250}. Membrane {ECO:0000250};
CC       Peripheral membrane protein {ECO:0000250}; Cytoplasmic side
CC       {ECO:0000250}. Nucleus {ECO:0000250}. Cytoplasm, cell cortex
CC       {ECO:0000250}. Note=Associated with the chromatin. Detected on
CC       microtubules in polarized and motile vascular endothelial cells.
CC       Colocalizes with F-actin at the cell cortex. Colocalizes with PECAM1
CC       and CTNND1 at nascent cell-cell contacts (By similarity).
CC       {ECO:0000250}.
CC   -!- DOMAIN: The coiled coil domains mediate homooligomerization and are
CC       required for location at microtubules. {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. {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; AF187884; AAF00543.1; -; mRNA.
DR   RefSeq; NP_001003141.1; NM_001003141.1.
DR   AlphaFoldDB; Q9TTY2; -.
DR   SMR; Q9TTY2; -.
DR   STRING; 9615.ENSCAFP00000011047; -.
DR   PaxDb; 9612-ENSCAFP00000011047; -.
DR   GeneID; 403754; -.
DR   KEGG; cfa:403754; -.
DR   CTD; 2241; -.
DR   eggNOG; KOG0194; Eukaryota.
DR   InParanoid; Q9TTY2; -.
DR   OrthoDB; 2903566at2759; -.
DR   Proteomes; UP000002254; Unplaced.
DR   Proteomes; UP000694429; Unplaced.
DR   Proteomes; UP000694542; Unplaced.
DR   Proteomes; UP000805418; Unplaced.
DR   GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR   GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR   GO; GO:0042995; C:cell projection; IEA:UniProtKB-SubCell.
DR   GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR   GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004713; F:protein tyrosine kinase activity; IBA:GO_Central.
DR   GO; GO:0007155; P:cell adhesion; IBA:GO_Central.
DR   GO; GO:0006935; P:chemotaxis; IBA:GO_Central.
DR   GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0043304; P:regulation of mast cell degranulation; IBA:GO_Central.
DR   CDD; cd07686; F-BAR_Fer; 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; IPR037452; Fer_F-BAR.
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:SF227; TYROSINE-PROTEIN KINASE FER; 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   2: Evidence at transcript level;
KW   ATP-binding; Cell junction; Cell membrane; Cell projection; Coiled coil;
KW   Cytoplasm; Cytoskeleton; Kinase; Lipid-binding; Membrane;
KW   Nucleotide-binding; Nucleus; Phosphoprotein; Proto-oncogene;
KW   Reference proteome; SH2 domain; Transferase; Tyrosine-protein kinase.
FT   CHAIN           1..823
FT                   /note="Tyrosine-protein kinase Fer"
FT                   /id="PRO_0000260824"
FT   DOMAIN          1..259
FT                   /note="F-BAR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01077"
FT   DOMAIN          460..550
FT                   /note="SH2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT   DOMAIN          563..816
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          1..300
FT                   /note="Important for interaction with membranes containing
FT                   phosphoinositides"
FT                   /evidence="ECO:0000250"
FT   COILED          123..185
FT                   /evidence="ECO:0000255"
FT   COILED          301..390
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        684
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10028"
FT   BINDING         569..577
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         591
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         402
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P16591"
FT   MOD_RES         434
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P16591"
FT   MOD_RES         615
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P70451"
FT   MOD_RES         714
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:P70451"
SQ   SEQUENCE   823 AA;  94611 MW;  33E88A6A15B37897 CRC64;
     MGFGSDLKNS HEAVLKLQDW ELRLLETVKK FMALRIKSDK EYASTLQNLC NQVDKESTVQ
     MNYVSNVSKS WLLMIQQTEQ LSRIMKTHAE DLNSGPLHRL TMMIKDKQQV KKSFIGVHQQ
     IEAEMIKVTK TELEKLKSSY RQLIKEMNSA KEKYKEALAK GKETEKAKER YDKATMKLHV
     LHNQYVLALK GAQLHQNQYY DTTLPLLLDS LQKMQEEMIK ALKGIFDEYS QITSLVTEEI
     VNVHKEIQMS VEQIDPSTEY NNFIDVHRTT AAKEQEIEFD TSLLEENENL QANEIMWNNL
     TAESLQVMLK TLAEELIQTQ QMLVNKEEAV LELEKRIEES SKTCEKKSDI VLLLSQKQTL
     EELKQSVQQL RCTEAKFTAQ KELLEQKVQE NEGKEPPPVV NYEEDARSVT SMERKERLSK
     FESIRHSIAG IIRSPKSALG SSTFSDTIPI SEKPLAEQDW YHGAIPRIEA QDLLKQQGDF
     LVRESHGKPG EYVLSVYSDG QRRHFIIQFV DNLYRFEGTG FSNIPQLIDH HYTTKQVITK
     KSGVVLLNPI PKDKKWVLNH EDVTLGELLG KGNFGEVYKG ILKDKTAVAV KTCKEDLPQE
     LKIKFLQEAK ILKQYDHPNI VKLIGVCTQR QPIYIIMELV PGGDFLSFLR KKKDEIKLKQ
     LVKFSLDAAS GMSYLESKNC IHRDLAARNC LVGENNVLKI SDFGMSRQED GGVYSSSGLK
     QIPIKWTAPE ALNYGRYSSE SDVWSFGILL WETFSLGVCP YPGMTNQQAT EQVERGYRIS
     APQHCPEDIF KIMMKCWDYK PENRPKFSEL QKELTVIKKK VTQ
//