FRK_MOUSE
ID FRK_MOUSE Reviewed; 512 AA.
AC Q922K9; Q61364; Q61745;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Tyrosine-protein kinase FRK;
DE EC=2.7.10.2;
DE AltName: Full=Beta-cell Src-homology tyrosine kinase;
DE Short=BSK;
DE AltName: Full=FYN-related kinase;
DE AltName: Full=Intestine tyrosine kinase;
GN Name=Frk; Synonyms=Bsk, Iyk;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ; TISSUE=Mammary gland;
RX PubMed=7733928; DOI=10.1006/bbrc.1995.1540;
RA Thuveson M., Albrecht D., Zuercher G., Andres A., Ziemiecki A.;
RT "iyk, a novel intracellular protein tyrosine kinase differentially
RT expressed in the mouse mammary gland and intestine.";
RL Biochem. Biophys. Res. Commun. 209:582-589(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=7835707; DOI=10.1016/0378-1119(94)00718-8;
RA Oberg-Welsh C., Welsh M.;
RT "Cloning of BSK, a murine FRK homologue with a specific pattern of tissue
RT distribution.";
RL Gene 152:239-242(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney, Mammary gland, and Skin;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=12077350; DOI=10.1128/mcb.22.14.5235-5247.2002;
RA Chandrasekharan S., Qiu T.H., Alkharouf N., Brantley K., Mitchell J.B.,
RA Liu E.T.;
RT "Characterization of mice deficient in the Src family nonreceptor tyrosine
RT kinase Frk/rak.";
RL Mol. Cell. Biol. 22:5235-5247(2002).
RN [6]
RP PHOSPHORYLATION AT TYR-394.
RX PubMed=15186217; DOI=10.1042/bj20040285;
RA Welsh M., Welsh C., Ekman M., Dixelius J., Hagerkvist R., Anneren C.,
RA Akerblom B., Mahboobi S., Chandrasekharan S., Liu E.T.;
RT "The tyrosine kinase FRK/RAK participates in cytokine-induced islet cell
RT cytotoxicity.";
RL Biochem. J. 382:261-268(2004).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP STRUCTURE BY NMR OF 50-220.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the SH3 and SH2 domains of FYN-related kinase.";
RL Submitted (OCT-2006) to the PDB data bank.
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: Expressed in intestinal tract, fetal and adult
CC islets of Langerhans, kidney, liver and lung.
CC {ECO:0000269|PubMed:7733928, ECO:0000269|PubMed:7835707}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable and do not show any histological
CC abnormalities in epithelial tissues or develop any pathological and/or
CC metabolic disorders associated with the failure of epithelial organs.
CC {ECO:0000269|PubMed:12077350}.
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; Z48757; CAA88658.1; -; mRNA.
DR EMBL; L36132; AAA65197.1; -; mRNA.
DR EMBL; AK028855; BAC26155.1; -; mRNA.
DR EMBL; AK052614; BAC35063.1; -; mRNA.
DR EMBL; AK166379; BAE38741.1; -; mRNA.
DR EMBL; BC007137; AAH07137.1; -; mRNA.
DR CCDS; CCDS23781.1; -.
DR PIR; I49552; I49552.
DR RefSeq; NP_001153016.1; NM_001159544.1.
DR RefSeq; NP_034367.2; NM_010237.3.
DR RefSeq; XP_006512597.1; XM_006512534.3.
DR RefSeq; XP_006512598.1; XM_006512535.3.
DR RefSeq; XP_006512599.1; XM_006512536.3.
DR PDB; 2D8J; NMR; -; A=52-115.
DR PDB; 2DLY; NMR; -; A=113-220.
DR PDBsum; 2D8J; -.
DR PDBsum; 2DLY; -.
DR AlphaFoldDB; Q922K9; -.
DR BMRB; Q922K9; -.
DR SMR; Q922K9; -.
DR STRING; 10090.ENSMUSP00000130289; -.
DR iPTMnet; Q922K9; -.
DR PhosphoSitePlus; Q922K9; -.
DR MaxQB; Q922K9; -.
DR PaxDb; Q922K9; -.
DR PeptideAtlas; Q922K9; -.
DR PRIDE; Q922K9; -.
DR ProteomicsDB; 267502; -.
DR Antibodypedia; 32472; 583 antibodies from 35 providers.
DR DNASU; 14302; -.
DR Ensembl; ENSMUST00000019913; ENSMUSP00000019913; ENSMUSG00000019779.
DR Ensembl; ENSMUST00000170771; ENSMUSP00000130289; ENSMUSG00000019779.
DR GeneID; 14302; -.
DR KEGG; mmu:14302; -.
DR UCSC; uc007euy.2; mouse.
DR CTD; 2444; -.
DR MGI; MGI:103265; Frk.
DR VEuPathDB; HostDB:ENSMUSG00000019779; -.
DR eggNOG; KOG0197; Eukaryota.
DR GeneTree; ENSGT00940000156987; -.
DR HOGENOM; CLU_000288_7_2_1; -.
DR InParanoid; Q922K9; -.
DR OMA; SSHEGWW; -.
DR OrthoDB; 539311at2759; -.
DR PhylomeDB; Q922K9; -.
DR TreeFam; TF351634; -.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR Reactome; R-MMU-8948751; Regulation of PTEN stability and activity.
DR BioGRID-ORCS; 14302; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Frk; mouse.
DR EvolutionaryTrace; Q922K9; -.
DR PRO; PR:Q922K9; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q922K9; protein.
DR Bgee; ENSMUSG00000019779; Expressed in seminal vesicle and 182 other tissues.
DR Genevisible; Q922K9; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
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:MGI.
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 3D-structure; ATP-binding; Cytoplasm; Kinase; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; SH2 domain; SH3 domain; Transferase;
KW Tumor suppressor; Tyrosine-protein kinase.
FT CHAIN 1..512
FT /note="Tyrosine-protein kinase FRK"
FT /id="PRO_0000260826"
FT DOMAIN 49..117
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 123..215
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 241..498
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 361
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 247..255
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 269
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 185
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P42685"
FT MOD_RES 394
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15186217"
FT CONFLICT 154
FT /note="S -> T (in Ref. 1; CAA88658)"
FT /evidence="ECO:0000305"
FT CONFLICT 237
FT /note="D -> H (in Ref. 1; CAA88658)"
FT /evidence="ECO:0000305"
FT CONFLICT 335
FT /note="L -> F (in Ref. 1; CAA88658 and 2; AAA65197)"
FT /evidence="ECO:0000305"
FT CONFLICT 509
FT /note="N -> K (in Ref. 1; CAA88658 and 2; AAA65197)"
FT /evidence="ECO:0000305"
FT STRAND 52..58
FT /evidence="ECO:0007829|PDB:2D8J"
FT STRAND 63..67
FT /evidence="ECO:0007829|PDB:2D8J"
FT STRAND 76..80
FT /evidence="ECO:0007829|PDB:2D8J"
FT STRAND 83..91
FT /evidence="ECO:0007829|PDB:2D8J"
FT STRAND 103..108
FT /evidence="ECO:0007829|PDB:2D8J"
FT TURN 109..111
FT /evidence="ECO:0007829|PDB:2D8J"
FT STRAND 112..114
FT /evidence="ECO:0007829|PDB:2D8J"
FT HELIX 116..120
FT /evidence="ECO:0007829|PDB:2DLY"
FT STRAND 122..124
FT /evidence="ECO:0007829|PDB:2DLY"
FT HELIX 130..137
FT /evidence="ECO:0007829|PDB:2DLY"
FT STRAND 138..141
FT /evidence="ECO:0007829|PDB:2DLY"
FT STRAND 147..151
FT /evidence="ECO:0007829|PDB:2DLY"
FT STRAND 153..157
FT /evidence="ECO:0007829|PDB:2DLY"
FT STRAND 159..167
FT /evidence="ECO:0007829|PDB:2DLY"
FT STRAND 169..176
FT /evidence="ECO:0007829|PDB:2DLY"
FT STRAND 178..180
FT /evidence="ECO:0007829|PDB:2DLY"
FT STRAND 182..185
FT /evidence="ECO:0007829|PDB:2DLY"
FT STRAND 188..192
FT /evidence="ECO:0007829|PDB:2DLY"
FT HELIX 193..200
FT /evidence="ECO:0007829|PDB:2DLY"
FT STRAND 205..209
FT /evidence="ECO:0007829|PDB:2DLY"
SQ SEQUENCE 512 AA; 58844 MW; B79A0BC07B9EC5F8 CRC64;
MGSVCVRLWA YLQPFLPCWS QEADKSVVIE NPGAFCPPEA PRSQEPERSH GQYFVALFDY
QARTAEDLSF RAGDKLQVLD TSHEGWWLAR HLEKKGTGLG QQLQGYIPSN YVAEDRSLQA
EPWFFGAIKR ADAEKQLLYS ENQTGAFLIR ESESQKGDFS LSVLDEGVVK HYRIRRLDEG
GFFLTRRKVF STLNEFVNYY TTTSDGLCVK LEKPCLKIQV PTPFDLSYKT ADQWEIDRNS
IQLLKRLGSG QFGEVWEGLW NNTTPVAVKT LKPGSMDPND FLREAQIMKS LRHPKLIQLY
AVCTLEDPIY IITELMRHGS LQEYLQNDGG SKIHLIQQVD MAAQVASGMA YLESQNYIHR
DLAARNVLVG EHNIYKVADF GLARVFKVDN EDIYESKHEI KLPVKWTAPE AIRTNKFSIK
SDVWSFGILL YEIITYGKMP YSGMTGAQVI QMLSQNYRLP QPSNCPQQFY SIMLECWNVE
PKQRPTFETL HWKLEDYFET DCSYSDTNNF IN
