FBH1_MOUSE
ID FBH1_MOUSE Reviewed; 1042 AA.
AC Q8K2I9; Q8C444; Q99KS0; Q9CTC6; Q9QZG7;
DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=F-box DNA helicase 1 {ECO:0000303|PubMed:24108124};
DE EC=3.6.4.12 {ECO:0000250|UniProtKB:Q8NFZ0};
DE AltName: Full=F-box only protein 18;
GN Name=Fbh1 {ECO:0000303|PubMed:24108124};
GN Synonyms=Fbx18, Fbxo18 {ECO:0000312|MGI:MGI:1354699};
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 [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Embryo, and Hippocampus;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 138-1042 (ISOFORMS 1/2).
RX PubMed=10531037; DOI=10.1016/s0960-9822(00)80021-4;
RA Winston J.T., Koepp D.M., Zhu C., Elledge S.J., Harper J.W.;
RT "A family of mammalian F-box proteins.";
RL Curr. Biol. 9:1180-1182(1999).
RN [4]
RP FUNCTION, AND INTERACTION WITH RAD51.
RX PubMed=24108124; DOI=10.1074/jbc.m113.484493;
RA Simandlova J., Zagelbaum J., Payne M.J., Chu W.K., Shevelev I., Hanada K.,
RA Chatterjee S., Reid D.A., Liu Y., Janscak P., Rothenberg E., Hickson I.D.;
RT "FBH1 helicase disrupts RAD51 filaments in vitro and modulates homologous
RT recombination in mammalian cells.";
RL J. Biol. Chem. 288:34168-34180(2013).
CC -!- FUNCTION: 3'-5' DNA helicase and substrate-recognition component of the
CC SCF(FBH1) E3 ubiquitin ligase complex that plays a key role in response
CC to stalled/damaged replication forks (By similarity). Involved in
CC genome maintenance by acting as an anti-recombinogenic helicase and
CC preventing extensive strand exchange during homologous recombination:
CC promotes RAD51 filament dissolution from stalled forks, thereby
CC inhibiting homologous recombination and preventing excessive
CC recombination (PubMed:24108124). Also promotes cell death and DNA
CC double-strand breakage in response to replication stress: together with
CC MUS81, promotes the endonucleolytic DNA cleavage following prolonged
CC replication stress via its helicase activity, possibly to eliminate
CC cells with excessive replication stress. Plays a major role in
CC remodeling of stalled DNA forks by catalyzing fork regression, in which
CC the fork reverses and the two nascent DNA strands anneal. In addition
CC to the helicase activity, also acts as the substrate-recognition
CC component of the SCF(FBH1) E3 ubiquitin ligase complex, a complex that
CC mediates ubiquitination of RAD51, leading to regulate RAD51 subcellular
CC location (By similarity). {ECO:0000250|UniProtKB:Q8NFZ0,
CC ECO:0000269|PubMed:24108124}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12;
CC Evidence={ECO:0000250|UniProtKB:Q8NFZ0};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q8NFZ0}.
CC -!- SUBUNIT: Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase
CC complex SCF(FBH1) composed of CUL1, SKP1, RBX1 and FBH1 (By
CC similarity). Interacts with RPA2 (By similarity). Interacts with RAD51
CC (PubMed:24108124). Interacts (via PIP-box and RanBP2-type zinc finger)
CC with PCNA (By similarity). {ECO:0000250|UniProtKB:Q8NFZ0,
CC ECO:0000269|PubMed:24108124}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8NFZ0}.
CC Chromosome {ECO:0000250|UniProtKB:Q8NFZ0}. Note=Accumulates at sites of
CC DNA damage or replication stress. PCNA is required for localization to
CC DNA damage sites. Localizes to the nucleoplasm in absence of DNA
CC damage. {ECO:0000250|UniProtKB:Q8NFZ0}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8K2I9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8K2I9-2; Sequence=VSP_009716, VSP_009717;
CC -!- DOMAIN: The PIP-box mediates the interaction with PCNA.
CC {ECO:0000250|UniProtKB:Q8NFZ0}.
CC -!- PTM: Ubiquitinated. Ubiquitination by the DCX(DTL) complex, also named
CC CRL4(CDT2), leading to its degradation: ubiquitination takes place
CC after its localization to DNA damage sites, possibly to facilitate the
CC translesion synthesis (TLS) pathway. {ECO:0000250|UniProtKB:Q8NFZ0}.
CC -!- SIMILARITY: Belongs to the helicase family. UvrD subfamily.
CC {ECO:0000305}.
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DR EMBL; AK003964; BAB23095.1; -; mRNA.
DR EMBL; AK083118; BAC38767.1; -; mRNA.
DR EMBL; BC004036; AAH04036.1; -; mRNA.
DR EMBL; BC031393; AAH31393.1; -; mRNA.
DR EMBL; AF184275; AAF03151.1; -; mRNA.
DR CCDS; CCDS15688.1; -. [Q8K2I9-1]
DR RefSeq; NP_056607.1; NM_015792.2. [Q8K2I9-1]
DR AlphaFoldDB; Q8K2I9; -.
DR STRING; 10090.ENSMUSP00000071495; -.
DR iPTMnet; Q8K2I9; -.
DR PhosphoSitePlus; Q8K2I9; -.
DR MaxQB; Q8K2I9; -.
DR PaxDb; Q8K2I9; -.
DR PeptideAtlas; Q8K2I9; -.
DR PRIDE; Q8K2I9; -.
DR ProteomicsDB; 270955; -. [Q8K2I9-1]
DR ProteomicsDB; 270956; -. [Q8K2I9-2]
DR Antibodypedia; 1236; 108 antibodies from 24 providers.
DR DNASU; 50755; -.
DR Ensembl; ENSMUST00000071564; ENSMUSP00000071495; ENSMUSG00000058594. [Q8K2I9-1]
DR GeneID; 50755; -.
DR KEGG; mmu:50755; -.
DR UCSC; uc008ijc.1; mouse. [Q8K2I9-1]
DR UCSC; uc008ije.1; mouse. [Q8K2I9-2]
DR CTD; 84893; -.
DR MGI; MGI:1354699; Fbh1.
DR VEuPathDB; HostDB:ENSMUSG00000058594; -.
DR eggNOG; KOG2108; Eukaryota.
DR GeneTree; ENSGT00390000011669; -.
DR HOGENOM; CLU_009740_0_0_1; -.
DR InParanoid; Q8K2I9; -.
DR OMA; CERCVWT; -.
DR PhylomeDB; Q8K2I9; -.
DR TreeFam; TF329020; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 50755; 2 hits in 110 CRISPR screens.
DR ChiTaRS; Fbh1; mouse.
DR PRO; PR:Q8K2I9; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q8K2I9; protein.
DR Bgee; ENSMUSG00000058594; Expressed in granulocyte and 257 other tissues.
DR ExpressionAtlas; Q8K2I9; baseline and differential.
DR Genevisible; Q8K2I9; MM.
DR GO; GO:0000785; C:chromatin; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0043138; F:3'-5' DNA helicase activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0003678; F:DNA helicase activity; ISO:MGI.
DR GO; GO:0015616; F:DNA translocase activity; ISO:MGI.
DR GO; GO:0003690; F:double-stranded DNA binding; ISS:UniProtKB.
DR GO; GO:0003697; F:single-stranded DNA binding; ISS:UniProtKB.
DR GO; GO:0008219; P:cell death; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0000737; P:DNA catabolic process, endonucleolytic; ISO:MGI.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; ISS:UniProtKB.
DR GO; GO:0035562; P:negative regulation of chromatin binding; IMP:MGI.
DR GO; GO:2000042; P:negative regulation of double-strand break repair via homologous recombination; IMP:UniProtKB.
DR GO; GO:1902231; P:positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0000725; P:recombinational repair; IBA:GO_Central.
DR GO; GO:0031297; P:replication fork processing; IMP:UniProtKB.
DR GO; GO:0048478; P:replication fork protection; IMP:UniProtKB.
DR GO; GO:0072429; P:response to intra-S DNA damage checkpoint signaling; IMP:MGI.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR014017; DNA_helicase_UvrD-like_C.
DR InterPro; IPR000212; DNA_helicase_UvrD/REP.
DR InterPro; IPR036047; F-box-like_dom_sf.
DR InterPro; IPR001810; F-box_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR11070; PTHR11070; 1.
DR Pfam; PF12937; F-box-like; 1.
DR Pfam; PF13361; UvrD_C; 1.
DR SMART; SM00256; FBOX; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF81383; SSF81383; 1.
DR PROSITE; PS50181; FBOX; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Chromosome; DNA damage; DNA repair;
KW DNA-binding; Helicase; Hydrolase; Nucleotide-binding; Nucleus;
KW Reference proteome; Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1..1042
FT /note="F-box DNA helicase 1"
FT /id="PRO_0000119902"
FT DOMAIN 207..256
FT /note="F-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080"
FT DOMAIN 441..704
FT /note="UvrD-like helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00560"
FT REGION 31..53
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 165..185
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 57..64
FT /note="PIP-box"
FT /evidence="ECO:0000250|UniProtKB:Q8NFZ0"
FT MOTIF 806..810
FT /note="APIM motif"
FT /evidence="ECO:0000250|UniProtKB:Q8NFZ0"
FT BINDING 462..469
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00560"
FT VAR_SEQ 1..74
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_009716"
FT VAR_SEQ 865..1042
FT /note="EYILGTVHKAKGLEFDTVHVLDDFVKVPCARHNLAQLPHFRVESFSEDEWNL
FT LYVAVTRAKKRLIMTKSLENILTLAGEYFLQAELTSNVLKTGVVHCCVGQCNNTIPVDT
FT ILTMKKLPITYSNRKENKGGYLCHSCAEQRIGPLAFLTASPEQVRAMERTVEDIVLPRQ
FT EALLFLVF -> GKESGCYLPSKRRSRWFLEVSLHLYLPEAVL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_009717"
FT CONFLICT 369
FT /note="P -> A (in Ref. 2; AAH04036)"
FT /evidence="ECO:0000305"
FT CONFLICT 376
FT /note="P -> A (in Ref. 2; AAH04036)"
FT /evidence="ECO:0000305"
FT CONFLICT 800
FT /note="D -> E (in Ref. 1; BAB23095)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1042 AA; 118298 MW; 3F6427D19F5B295F CRC64;
MRRFKRKHLT VVDCHHLARS HLAVTQPFSQ RWTNRDPNHG LYPRPRTKGR NRGRGCQRYI
SEFFLAGHQH CTNDMAKSNS VGQDSCQDAE GDMILTAESS CTLPQVDNGE ARLGSSGSAQ
PARKRAHCFE EATESGQWDG VTKKTPRHRL FPSCSRLREA RQGAEDSLSQ CSPVPGEAGR
DIEDIGPDPL PDSYYGLLGM LPCQEVPSHI CRLPSEVLRH IFAFLPVEDL YWNLSLVCHL
WREIINDPLF IPWKKLYHRY LINEEQAVSK VDGILSSHGI EKDSDLCVLN LIRYTATTKC
SPSVDPERVL WSLRDHPLLL EAEACMRQQL PDLYAAAGGI NVWALVAAMV LLSSCVNDIQ
HLLFCLRRPS STVTMPDVTE TLYCIAVLLY AMREKGINIS NRIHYNIFYC LYLQENSCTQ
ATKVTEEPSV WPGKKTSIQL THEQQLILNH KMEPLQVVKI MAFAGTGKTS TLVKYAEKWS
QSRFLYVTFN KSIAKQAELV FPSNVICKTF HSMAYSHVGR KYQLKKKLNL FKLTPFMVNS
VLAEGKGGFI RAKLVCKTLE NFFASADEEL TIDHVPIWCK NSHGQRVMVE QSEKLNGVLE
ASRLWDNMRK LGECKEEAYQ MTHDGYLKLW QLSKPLLASF DAIFVDEAQD CTPAIMNIVL
SQPCGKIFVG DPHQQIYTFR GAVNALFTVP HTHVFYLTQS FRFGVEIAYV GATILDVCKR
VRKKTLVGGN HQSGIRGDIK GQVALLSRTN ANVFDEAVRV TEGESPARIH LIGGIKSFGL
DRIIDIWTLL QPEEERRKRD LIIKDRFIRR WVHKEGFSGF KRYVTAAEDK ELEAKIAVVE
KYNIRIPELV ERIERCHIDD LDFAEYILGT VHKAKGLEFD TVHVLDDFVK VPCARHNLAQ
LPHFRVESFS EDEWNLLYVA VTRAKKRLIM TKSLENILTL AGEYFLQAEL TSNVLKTGVV
HCCVGQCNNT IPVDTILTMK KLPITYSNRK ENKGGYLCHS CAEQRIGPLA FLTASPEQVR
AMERTVEDIV LPRQEALLFL VF
