FRK1_CAEEL
ID FRK1_CAEEL Reviewed; 390 AA.
AC Q22146;
DT 14-OCT-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Fer-related kinase 1 {ECO:0000303|PubMed:15958510};
DE EC=2.7.10.2 {ECO:0000269|PubMed:15958510};
DE AltName: Full=Fer oncogene-related kinase 1 {ECO:0000312|WormBase:T04B2.2a};
GN Name=frk-1 {ECO:0000312|WormBase:T04B2.2a};
GN ORFNames=T04B2.2 {ECO:0000312|WormBase:T04B2.2a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH HMP-2, SUBCELLULAR
RP LOCATION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP ASP-308.
RX PubMed=15958510; DOI=10.1242/dev.01900;
RA Putzke A.P., Hikita S.T., Clegg D.O., Rothman J.H.;
RT "Essential kinase-independent role of a Fer-like non-receptor tyrosine
RT kinase in Caenorhabditis elegans morphogenesis.";
RL Development 132:3185-3195(2005).
RN [3] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20805471; DOI=10.1073/pnas.1006600107;
RA Putzke A.P., Rothman J.H.;
RT "Repression of Wnt signaling by a Fer-type nonreceptor tyrosine kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:16154-16159(2010).
CC -!- FUNCTION: Non-receptor tyrosine-protein kinase which plays a role in
CC morphogenesis by regulating the epidermal enclosure of the embryo,
CC independently of its kinase activity (PubMed:15958510). Prevents
CC hyperactivation of the Wnt signaling pathway during endoderm
CC development, probably by preventing hmp-2 nuclear translocation
CC (PubMed:20805471). {ECO:0000269|PubMed:15958510,
CC ECO:0000269|PubMed:20805471}.
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:0000269|PubMed:15958510};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:15958510};
CC -!- SUBUNIT: Interacts with hmp-2. {ECO:0000269|PubMed:15958510}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15958510}. Cytoplasm
CC {ECO:0000269|PubMed:15958510}. Cell junction
CC {ECO:0000269|PubMed:15958510}. Cell membrane
CC {ECO:0000269|PubMed:15958510}; Peripheral membrane protein
CC {ECO:0000269|PubMed:15958510}. Note=Localizes to the nucleus during
CC cell division in the early embryo and in seam cells and in the
CC developing germline at the larval stage. Localizes in the cytoplasm and
CC at the cell-cell contacts during embryo enclosure and elongation.
CC Nuclear exclusion during elongation is regulated by integrin alpha
CC subunit pat-3 and beta-catenin hmp-2. {ECO:0000269|PubMed:15958510}.
CC -!- DEVELOPMENTAL STAGE: Expressed in early embryo and, during later stages
CC of embryogenesis, in epithelial cells, body wall muscle, germline and
CC mature sperm. {ECO:0000269|PubMed:15958510}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes a disruption in
CC the dorsal intercalation and ventral migration of epidermal cells,
CC preventing enclosure and elongation of the embryo. Epidermal cells tend
CC to round up and appear to be defective in adhesion (PubMed:15958510).
CC In addition, causes partial nuclear re-localization of hmp-2 in the
CC embryonic epidermis and the production of supernumerary gut nuclei
CC probably resulting from epithelial cell hyperproliferation
CC (PubMed:20805471). {ECO:0000269|PubMed:15958510,
CC ECO:0000269|PubMed:20805471}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Fes/fps subfamily. {ECO:0000305}.
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DR EMBL; BX284604; CAA92609.1; -; Genomic_DNA.
DR PIR; T24437; T24437.
DR RefSeq; NP_001255459.1; NM_001268530.1.
DR AlphaFoldDB; Q22146; -.
DR SMR; Q22146; -.
DR STRING; 6239.T04B2.2b; -.
DR PaxDb; Q22146; -.
DR PeptideAtlas; Q22146; -.
DR PRIDE; Q22146; -.
DR EnsemblMetazoa; T04B2.2a.1; T04B2.2a.1; WBGene00001487.
DR EnsemblMetazoa; T04B2.2a.2; T04B2.2a.2; WBGene00001487.
DR GeneID; 191635; -.
DR CTD; 191635; -.
DR WormBase; T04B2.2a; CE03609; WBGene00001487; frk-1.
DR eggNOG; KOG0194; Eukaryota.
DR GeneTree; ENSGT00970000196256; -.
DR HOGENOM; CLU_000288_7_2_1; -.
DR OMA; YLERSKC; -.
DR OrthoDB; 670700at2759; -.
DR PhylomeDB; Q22146; -.
DR Reactome; R-CEL-399954; Sema3A PAK dependent Axon repulsion.
DR Reactome; R-CEL-399956; CRMPs in Sema3A signaling.
DR PRO; PR:Q22146; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00001487; Expressed in adult organism and 1 other tissue.
DR GO; GO:0005911; C:cell-cell junction; IDA:WormBase.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0005886; C:plasma membrane; IDA:WormBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008013; F:beta-catenin binding; IPI:WormBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0004672; F:protein kinase activity; IDA:WormBase.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IGI:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0098609; P:cell-cell adhesion; IMP:WormBase.
DR GO; GO:0010172; P:embryonic body morphogenesis; IMP:WormBase.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0051782; P:negative regulation of cell division; IMP:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:WormBase.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:WormBase.
DR GO; GO:0045604; P:regulation of epidermal cell differentiation; IMP:WormBase.
DR GO; GO:0032880; P:regulation of protein localization; IMP:WormBase.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd10361; SH2_Fps_family; 1.
DR Gene3D; 3.30.505.10; -; 1.
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; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF00017; SH2; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56112; SSF56112; 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 1: Evidence at protein level;
KW ATP-binding; Cell junction; Cell membrane; Cytoplasm; Kinase; Manganese;
KW Membrane; Metal-binding; Nucleotide-binding; Nucleus; Reference proteome;
KW SH2 domain; Transferase; Tyrosine-protein kinase.
FT CHAIN 1..390
FT /note="Fer-related kinase 1"
FT /evidence="ECO:0000305"
FT /id="PRO_0000433994"
FT DOMAIN 23..119
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 131..386
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 252
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 137..145
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 161
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MUTAGEN 308
FT /note="D->R: Loss of kinase activity. No defect in embryo
FT enclosure and elongation."
FT /evidence="ECO:0000269|PubMed:15958510"
SQ SEQUENCE 390 AA; 44692 MW; 8371D488D5C7FEC0 CRC64;
MGTVEKSSNN DASVTDDIRS AEYYHGMVPR QDAEGFLKRE GDFLVRKTEQ MPGKVVLAMS
VRVTDELCRH FMLNMDPTSN KFYFEHTHQE STISELINWH MTTKTPISAA SGAKIRRPME
RSPWLINHDS IVANKKLGEG AFGDVFIAEL DQGGKQEVAV KTMRAEATRE ARLRFMKEAR
LMRKYQHKHV VKLIGVAIHE HPLMIVMEYC PNGSLLSHLK KNKVSLIEKL RFTTEAADGI
AYLERSKCIH RDIAARNCLL SAKNELKISD FGMSDNKDEI KDETLEKVPI KWLAPETMQE
KVYTHKTDIW TFGVLVWEIY SDGAEPYPGL TKIQTRAKIV VNDYRMKMPD GTHPTVADVV
TGTCWQKNPE KRSTMDSIHK KLREFYESKK
