FRK_RAT
ID FRK_RAT Reviewed; 506 AA.
AC Q62662;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Tyrosine-protein kinase FRK;
DE EC=2.7.10.2;
DE AltName: Full=FYN-related kinase;
DE AltName: Full=Gastrointestinal-associated kinase;
DE Short=GASK;
DE AltName: Full=Gastrointestinal-associated tyrosine kinase;
DE Short=GTK;
GN Name=Frk; Synonyms=Gask;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Small intestine;
RX PubMed=8760296;
RA Sunitha I., Avigan M.I.;
RT "The apical membranes of maturing gut columnar epithelial cells contain the
RT enzymatically active form of a newly identified fyn-related tyrosine
RT kinase.";
RL Oncogene 13:547-559(1996).
RN [2]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Small intestine;
RX PubMed=8167158; DOI=10.1016/0167-4889(94)90260-7;
RA Sunitha I., Avigan M.I.;
RT "A newly identified tyrosine kinase is preferentially expressed in the
RT gastrointestinal tract.";
RL Biochim. Biophys. Acta 1221:348-352(1994).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Non-receptor tyrosine-protein kinase that negatively
CC regulates cell proliferation. Positively regulates PTEN protein
CC stability through phosphorylation of PTEN on 'Tyr-336', which in turn
CC prevents its ubiquitination and degradation, possibly by reducing its
CC binding to NEDD4. May function as a tumor suppressor (By similarity).
CC {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: Interacts (via the SH3-domain) with PTEN. Interacts with RB1
CC (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Note=Predominantly found in the nucleus, with a small fraction found in
CC the cell periphery. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Highly expressed in stomach, small intestine and
CC colon. Concentrated in the brush border membranes of epithelial cells,
CC throughout the maturation axis of the adult small intestine.
CC {ECO:0000269|PubMed:8167158, ECO:0000269|PubMed:8760296}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. SRC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; U09583; AAC52725.1; -; mRNA.
DR PIR; S43515; S43515.
DR RefSeq; NP_077344.1; NM_024368.1.
DR RefSeq; XP_006256579.1; XM_006256517.3.
DR AlphaFoldDB; Q62662; -.
DR SMR; Q62662; -.
DR STRING; 10116.ENSRNOP00000000653; -.
DR iPTMnet; Q62662; -.
DR PhosphoSitePlus; Q62662; -.
DR PaxDb; Q62662; -.
DR GeneID; 79209; -.
DR KEGG; rno:79209; -.
DR UCSC; RGD:621423; rat.
DR CTD; 2444; -.
DR RGD; 621423; Frk.
DR VEuPathDB; HostDB:ENSRNOG00000000543; -.
DR eggNOG; KOG0197; Eukaryota.
DR HOGENOM; CLU_000288_7_2_1; -.
DR InParanoid; Q62662; -.
DR OMA; SSHEGWW; -.
DR OrthoDB; 539311at2759; -.
DR PhylomeDB; Q62662; -.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR Reactome; R-RNO-8948751; Regulation of PTEN stability and activity.
DR PRO; PR:Q62662; -.
DR Proteomes; UP000002494; Chromosome 20.
DR Bgee; ENSRNOG00000000543; Expressed in duodenum and 16 other tissues.
DR Genevisible; Q62662; RN.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:RGD.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEP:RGD.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd10369; SH2_Src_Frk; 1.
DR Gene3D; 3.30.505.10; -; 1.
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; IPR035805; SH2_Frk.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
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 Pfam; PF00018; SH3_1; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00452; SH3DOMAIN.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00326; SH3; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF50044; SSF50044; 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.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cytoplasm; Kinase; Lipoprotein; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; SH2 domain; SH3 domain; Transferase;
KW Tumor suppressor; Tyrosine-protein kinase.
FT CHAIN 1..506
FT /note="Tyrosine-protein kinase FRK"
FT /id="PRO_0000260827"
FT DOMAIN 43..111
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 117..209
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 235..492
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 355
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 241..249
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 263
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 179
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P42685"
FT MOD_RES 388
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q922K9"
SQ SEQUENCE 506 AA; 58166 MW; 69F471DE4F974D82 CRC64;
MGSVCMRLWA YLQPFLPCWS QEADKSVVIE NPGAYCPPEA NRSQGQYFVA LFDYEARTAE
DLSFHAGDKL QVLDTSHEGW WLARHLEKKG PGLGQQLQGY IPSNYVAEDR SLQAEPWFFG
AIKRADAEKQ LLYSENQTGA FLIRESESQK GDFSLSVLDE GVVKHYRIRR LDEGGFFLTR
RKTFSTLNEF VNYYTTTSDG LCVKLEKPCL KIQVPTPFDL SYKTVDQWEI DRNSIQLLKR
LGSGQFGEVW EGLWNNTTPV AVKTLKPGSM DPNDFLREAQ IMKSLRHPKL IQLYAVCTLE
DPIYIITELM RHGSLQEYLQ NDGGSKIRLT QQVDMAAQVA SGMAYLESQN YIHRDLAARN
VLVGEHNIYK VADFGLARVF KVDNEDIYES KHEIKLPVKW TAPEAIRTNK FSIKSDVWSF
GILLYEIITY GKMPYSGMTG AQVIHMLGQN YRLPQPSNCP EQFYSIMMEC WNVEPKQRPT
FETLHWKLED YFEPDSSYSD TNNFIN
