FRAT1_HUMAN
ID FRAT1_HUMAN Reviewed; 279 AA.
AC Q92837; Q5JTI1; Q8NE74; Q8TDW9;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 3.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Proto-oncogene FRAT1;
DE AltName: Full=Frequently rearranged in advanced T-cell lymphomas 1;
DE Short=FRAT-1;
GN Name=FRAT1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9034327; DOI=10.1093/emboj/16.3.441;
RA Jonkers J., Korswagen H.C., Acton D., Breuer M., Berns A.;
RT "Activation of a novel proto-oncogene, Frat1, contributes to progression of
RT mouse T-cell lymphomas.";
RL EMBO J. 16:441-450(1997).
RN [2]
RP SEQUENCE REVISION TO 170.
RA Jonkers J., Korswagen H.C., Acton D., Breuer M., Berns A.;
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lung;
RX PubMed=11894125;
RA Saitoh T., Mine T., Katoh M.;
RT "Molecular cloning and expression of proto-oncogene FRAT1 in human
RT cancer.";
RL Int. J. Oncol. 20:785-789(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC TISSUE=Testis;
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [6]
RP INTERACTION WITH DVL1, AND ROLE IN WNT SIGNALING.
RX PubMed=12556519; DOI=10.1074/jbc.m213265200;
RA Hino S., Michiue T., Asashima M., Kikuchi A.;
RT "Casein kinase I epsilon enhances the binding of Dvl-1 to Frat-1 and is
RT essential for Wnt-3a-induced accumulation of beta-catenin.";
RL J. Biol. Chem. 278:14066-14073(2003).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 198-223 IN COMPLEX WITH GSK-3.
RX PubMed=11738041; DOI=10.1016/s0969-2126(01)00679-7;
RA Bax B., Carter P.S., Lewis C., Guy A.R., Bridges A., Tanner R., Pettman G.,
RA Mannix C., Culbert A.A., Brown M.J.B., Smith D.G., Reith A.D.;
RT "The structure of phosphorylated GSK-3beta complexed with a peptide,
RT FRATtide, that inhibits beta-catenin phosphorylation.";
RL Structure 9:1143-1152(2001).
CC -!- FUNCTION: Positively regulates the Wnt signaling pathway by stabilizing
CC beta-catenin through the association with GSK-3. May play a role in
CC tumor progression and collaborate with PIM1 and MYC in lymphomagenesis.
CC {ECO:0000269|PubMed:12556519}.
CC -!- SUBUNIT: Binds DVL1. Binds GSK-3 and prevent GSK-3-dependent
CC phosphorylation. {ECO:0000269|PubMed:11738041}.
CC -!- INTERACTION:
CC Q92837; P49840: GSK3A; NbExp=3; IntAct=EBI-3934879, EBI-1044067;
CC Q92837; P49841: GSK3B; NbExp=5; IntAct=EBI-3934879, EBI-373586;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- PTM: Phosphorylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the GSK-3-binding protein family. {ECO:0000305}.
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DR EMBL; U58975; AAB97096.2; -; mRNA.
DR EMBL; AB074890; BAB86352.1; -; mRNA.
DR EMBL; AL355490; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC034476; AAH34476.1; -; mRNA.
DR CCDS; CCDS7455.1; -.
DR RefSeq; NP_005470.2; NM_005479.3.
DR PDB; 1GNG; X-ray; 2.60 A; X/Y=188-226.
DR PDB; 3ZRK; X-ray; 2.37 A; X/Y=197-226.
DR PDB; 3ZRL; X-ray; 2.48 A; X/Y=197-226.
DR PDB; 3ZRM; X-ray; 2.49 A; X/Y=197-226.
DR PDB; 4AFJ; X-ray; 1.98 A; X/Y=197-226.
DR PDB; 5OY4; X-ray; 3.20 A; X/Y=1-279.
DR PDBsum; 1GNG; -.
DR PDBsum; 3ZRK; -.
DR PDBsum; 3ZRL; -.
DR PDBsum; 3ZRM; -.
DR PDBsum; 4AFJ; -.
DR PDBsum; 5OY4; -.
DR AlphaFoldDB; Q92837; -.
DR SMR; Q92837; -.
DR BioGRID; 115340; 17.
DR ComplexPortal; CPX-459; Nuclear export complex FRAT1-GSK3B.
DR IntAct; Q92837; 19.
DR STRING; 9606.ENSP00000360060; -.
DR iPTMnet; Q92837; -.
DR PhosphoSitePlus; Q92837; -.
DR BioMuta; FRAT1; -.
DR DMDM; 51338813; -.
DR MassIVE; Q92837; -.
DR PaxDb; Q92837; -.
DR PeptideAtlas; Q92837; -.
DR PRIDE; Q92837; -.
DR ProteomicsDB; 75521; -.
DR Antibodypedia; 30839; 119 antibodies from 27 providers.
DR DNASU; 10023; -.
DR Ensembl; ENST00000371021.5; ENSP00000360060.3; ENSG00000165879.9.
DR GeneID; 10023; -.
DR KEGG; hsa:10023; -.
DR MANE-Select; ENST00000371021.5; ENSP00000360060.3; NM_005479.4; NP_005470.2.
DR UCSC; uc001knc.2; human.
DR CTD; 10023; -.
DR DisGeNET; 10023; -.
DR GeneCards; FRAT1; -.
DR HGNC; HGNC:3944; FRAT1.
DR HPA; ENSG00000165879; Low tissue specificity.
DR MIM; 602503; gene.
DR neXtProt; NX_Q92837; -.
DR OpenTargets; ENSG00000165879; -.
DR PharmGKB; PA28361; -.
DR VEuPathDB; HostDB:ENSG00000165879; -.
DR eggNOG; ENOG502T09T; Eukaryota.
DR GeneTree; ENSGT00390000007081; -.
DR HOGENOM; CLU_101225_1_0_1; -.
DR InParanoid; Q92837; -.
DR OMA; PCRQHPE; -.
DR OrthoDB; 1477860at2759; -.
DR PhylomeDB; Q92837; -.
DR TreeFam; TF330804; -.
DR PathwayCommons; Q92837; -.
DR Reactome; R-HSA-196299; Beta-catenin phosphorylation cascade.
DR Reactome; R-HSA-4641262; Disassembly of the destruction complex and recruitment of AXIN to the membrane.
DR SignaLink; Q92837; -.
DR SIGNOR; Q92837; -.
DR BioGRID-ORCS; 10023; 16 hits in 1081 CRISPR screens.
DR ChiTaRS; FRAT1; human.
DR EvolutionaryTrace; Q92837; -.
DR GeneWiki; FRAT1; -.
DR GenomeRNAi; 10023; -.
DR Pharos; Q92837; Tbio.
DR PRO; PR:Q92837; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q92837; protein.
DR Bgee; ENSG00000165879; Expressed in blood and 142 other tissues.
DR Genevisible; Q92837; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal.
DR GO; GO:1904886; P:beta-catenin destruction complex disassembly; IDA:ComplexPortal.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IGI:WormBase.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IGI:WormBase.
DR GO; GO:0046825; P:regulation of protein export from nucleus; IDA:ComplexPortal.
DR DisProt; DP02373; -.
DR IDEAL; IID00093; -.
DR InterPro; IPR008014; GSK3-bd.
DR PANTHER; PTHR35154; PTHR35154; 1.
DR Pfam; PF05350; GSK-3_bind; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Phosphoprotein; Proto-oncogene;
KW Reference proteome; Wnt signaling pathway.
FT CHAIN 1..279
FT /note="Proto-oncogene FRAT1"
FT /id="PRO_0000087332"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 56..76
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 136..200
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 198..220
FT /note="Involved in GSK-3 binding"
FT REGION 228..279
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 9..24
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 186..200
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 88
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 249
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70339"
FT MOD_RES 252
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70339"
FT CONFLICT 58
FT /note="H -> D (in Ref. 1; AAB97096)"
FT /evidence="ECO:0000305"
FT CONFLICT 179
FT /note="S -> P (in Ref. 5; AAH34476)"
FT /evidence="ECO:0000305"
FT HELIX 201..209
FT /evidence="ECO:0007829|PDB:4AFJ"
FT HELIX 212..219
FT /evidence="ECO:0007829|PDB:4AFJ"
SQ SEQUENCE 279 AA; 29093 MW; 629AFD6CEA1DC0BD CRC64;
MPCRREEEEE AGEEAEGEEE EEDSFLLLQQ SVALGSSGEV DRLVAQIGET LQLDAAQHSP
ASPCGPPGAP LRAPGPLAAA VPADKARSPA VPLLLPPALA ETVGPAPPGV LRCALGDRGR
VRGRAAPYCV AELATGPSAL SPLPPQADLD GPPGAGKQGI PQPLSGPCRR GWLRGAAASR
RLQQRRGSQP ETRTGDDDPH RLLQQLVLSG NLIKEAVRRL HSRRLQLRAK LPQRPLLGPL
SAPVHEPPSP RSPRAACSDP GASGRAQLRT GDGVLVPGS
