FBH1_HUMAN
ID FBH1_HUMAN Reviewed; 1043 AA.
AC Q8NFZ0; Q5JVB0; Q5JVB1; Q7Z4Q6; Q7Z4R0; Q8N1P5; Q8N586; Q96E82; Q96K67;
AC Q96SW7; Q9UFB2;
DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=F-box DNA helicase 1 {ECO:0000303|PubMed:11956208};
DE Short=hFBH1 {ECO:0000303|PubMed:11956208, ECO:0000303|PubMed:23393192};
DE EC=3.6.4.12 {ECO:0000269|PubMed:11956208};
DE AltName: Full=F-box only protein 18 {ECO:0000312|HGNC:HGNC:13620};
GN Name=FBH1 {ECO:0000312|HGNC:HGNC:13620}; Synonyms=FBX18, FBXO18;
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] (ISOFORM 2), FUNCTION, CATALYTIC ACTIVITY,
RP INTERACTION WITH SKP1, AND IDENTIFICATION IN SCF COMPLEX.
RX PubMed=11956208; DOI=10.1074/jbc.m201612200;
RA Kim J., Kim J.-H., Lee S.-H., Kim D.-H., Kang H.-Y., Bae S.-H., Pan Z.-Q.,
RA Seo Y.-S.;
RT "The novel human DNA helicase hFBH1 is an F-box protein.";
RL J. Biol. Chem. 277:24530-24537(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Choriocarcinoma, and Testis;
RA Zan Q., Guo J.H., Yu L.;
RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Mammary gland, Testis carcinoma, and Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, Pancreas, and 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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 763-1043 (ISOFORMS 1/2).
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
RP FUNCTION.
RX PubMed=17724085; DOI=10.1128/mcb.00963-07;
RA Chiolo I., Saponaro M., Baryshnikova A., Kim J.H., Seo Y.S., Liberi G.;
RT "The human F-Box DNA helicase FBH1 faces Saccharomyces cerevisiae Srs2 and
RT postreplication repair pathway roles.";
RL Mol. Cell. Biol. 27:7439-7450(2007).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN SCF COMPLEX, AND
RP MUTAGENESIS OF 227-LEU-PRO-228 AND ASP-647.
RX PubMed=19736316; DOI=10.1083/jcb.200812138;
RA Fugger K., Mistrik M., Danielsen J.R., Dinant C., Falck J., Bartek J.,
RA Lukas J., Mailand N.;
RT "Human Fbh1 helicase contributes to genome maintenance via pro- and anti-
RT recombinase activities.";
RL J. Cell Biol. 186:655-663(2009).
RN [10]
RP POSSIBLE INVOLVEMENT IN MELANOMAS.
RX PubMed=23466708; DOI=10.4161/cc.24165;
RA Jeong Y.T., Cermak L., Guijarro M.V., Hernando E., Pagano M.;
RT "FBH1 protects melanocytes from transformation and is deregulated in
RT melanomas.";
RL Cell Cycle 12:1128-1132(2013).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN SCF COMPLEX, INTERACTION
RP WITH RPA2, AND MUTAGENESIS OF SER-56; 227-LEU-PRO-228; SER-583 AND ASP-647.
RX PubMed=23319600; DOI=10.1083/jcb.201209002;
RA Jeong Y.T., Rossi M., Cermak L., Saraf A., Florens L., Washburn M.P.,
RA Sung P., Schildkraut C.L., Schildkraut C., Pagano M.;
RT "FBH1 promotes DNA double-strand breakage and apoptosis in response to DNA
RT replication stress.";
RL J. Cell Biol. 200:141-149(2013).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP FUNCTION.
RX PubMed=23361013; DOI=10.1038/ncomms2395;
RA Fugger K., Chu W.K., Haahr P., Kousholt A.N., Beck H., Payne M.J.,
RA Hanada K., Hickson I.D., Sorensen C.S.;
RT "FBH1 co-operates with MUS81 in inducing DNA double-strand breaks and cell
RT death following replication stress.";
RL Nat. Commun. 4:1423-1423(2013).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH RAD51, AND UBIQUITINATION.
RX PubMed=23393192; DOI=10.1093/nar/gkt056;
RA Masuda-Ozawa T., Hoang T., Seo Y.S., Chen L.F., Spies M.;
RT "Single-molecule sorting reveals how ubiquitylation affects substrate
RT recognition and activities of FBH1 helicase.";
RL Nucleic Acids Res. 41:3576-3587(2013).
RN [15]
RP UBIQUITINATION, SUBCELLULAR LOCATION, DOMAIN, INTERACTION WITH PCNA, AND
RP MUTAGENESIS OF 60-ILE--PHE-64; 63-PHE-PHE-64 AND 807-LYS--ILE-809.
RX PubMed=23677613; DOI=10.1093/nar/gkt397;
RA Bacquin A., Pouvelle C., Siaud N., Perderiset M., Salome-Desnoulez S.,
RA Tellier-Lebegue C., Lopez B., Charbonnier J.B., Kannouche P.L.;
RT "The helicase FBH1 is tightly regulated by PCNA via CRL4(Cdt2)-mediated
RT proteolysis in human cells.";
RL Nucleic Acids Res. 41:6501-6513(2013).
RN [16]
RP FUNCTION, AND MUTAGENESIS OF ASP-647.
RX PubMed=25772361; DOI=10.1016/j.celrep.2015.02.028;
RA Fugger K., Mistrik M., Neelsen K.J., Yao Q., Zellweger R., Kousholt A.N.,
RA Haahr P., Chu W.K., Bartek J., Lopes M., Hickson I.D., Soerensen C.S.;
RT "FBH1 catalyzes regression of stalled replication forks.";
RL Cell Rep. 10:1749-1757(2015).
RN [17]
RP FUNCTION, PATHWAY, AND IDENTIFICATION IN SCF COMPLEX.
RX PubMed=25585578; DOI=10.1038/ncomms6931;
RA Chu W.K., Payne M.J., Beli P., Hanada K., Choudhary C., Hickson I.D.;
RT "FBH1 influences DNA replication fork stability and homologous
RT recombination through ubiquitylation of RAD51.";
RL Nat. Commun. 6:5931-5931(2015).
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 (PubMed:11956208,
CC PubMed:23393192). Involved in genome maintenance by acting as an anti-
CC recombinogenic helicase and preventing extensive strand exchange during
CC homologous recombination: promotes RAD51 filament dissolution from
CC stalled forks, thereby inhibiting homologous recombination and
CC preventing excessive recombination (PubMed:17724085, PubMed:19736316).
CC Also promotes cell death and DNA double-strand breakage in response to
CC replication stress: together with MUS81, promotes the endonucleolytic
CC DNA cleavage following prolonged replication stress via its helicase
CC activity, possibly to eliminate cells with excessive replication stress
CC (PubMed:23319600, PubMed:23361013). Plays a major role in remodeling of
CC stalled DNA forks by catalyzing fork regression, in which the fork
CC reverses and the two nascent DNA strands anneal (PubMed:25772361). In
CC addition to the helicase activity, also acts as the substrate-
CC recognition component of the SCF(FBH1) E3 ubiquitin ligase complex, a
CC complex that mediates ubiquitination of RAD51, leading to regulate
CC RAD51 subcellular location (PubMed:25585578).
CC {ECO:0000269|PubMed:11956208, ECO:0000269|PubMed:17724085,
CC ECO:0000269|PubMed:19736316, ECO:0000269|PubMed:23319600,
CC ECO:0000269|PubMed:23361013, ECO:0000269|PubMed:25585578,
CC ECO:0000269|PubMed:25772361}.
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:0000269|PubMed:11956208, ECO:0000269|PubMed:23393192};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:25585578}.
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
CC (PubMed:11956208, PubMed:19736316, PubMed:23319600). Interacts with
CC RAD51 (PubMed:23393192). Interacts with RPA2 (PubMed:23319600).
CC Interacts (via PIP-box and RanBP2-type zinc finger) with PCNA
CC (PubMed:23677613). {ECO:0000269|PubMed:11956208,
CC ECO:0000269|PubMed:19736316, ECO:0000269|PubMed:23319600,
CC ECO:0000269|PubMed:23393192, ECO:0000269|PubMed:23677613}.
CC -!- INTERACTION:
CC Q8NFZ0; O00213-2: APBB1; NbExp=3; IntAct=EBI-724767, EBI-13307975;
CC Q8NFZ0; P28799: GRN; NbExp=3; IntAct=EBI-724767, EBI-747754;
CC Q8NFZ0; P42858: HTT; NbExp=6; IntAct=EBI-724767, EBI-466029;
CC Q8NFZ0; P12931: SRC; NbExp=4; IntAct=EBI-724767, EBI-621482;
CC Q8NFZ0; O76024: WFS1; NbExp=3; IntAct=EBI-724767, EBI-720609;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19736316,
CC ECO:0000269|PubMed:23677613}. Chromosome {ECO:0000269|PubMed:19736316,
CC ECO:0000269|PubMed:23319600, ECO:0000269|PubMed:23677613}.
CC Note=Accumulates at sites of DNA damage or replication stress
CC (PubMed:19736316, PubMed:23677613). PCNA is required for localization
CC to DNA damage sites (PubMed:23677613). Localizes to the nucleoplasm in
CC absence of DNA damage (PubMed:23677613). {ECO:0000269|PubMed:19736316,
CC ECO:0000269|PubMed:23677613}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8NFZ0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NFZ0-2; Sequence=VSP_037942;
CC -!- DOMAIN: The PIP-box mediates the interaction with PCNA.
CC {ECO:0000269|PubMed:23677613}.
CC -!- PTM: Ubiquitinated (PubMed:23393192, PubMed:23677613). Ubiquitination
CC by the DCX(DTL) complex, also named CRL4(CDT2), leading to its
CC degradation: ubiquitination takes place after its localization to DNA
CC damage sites, possibly to facilitate the translesion synthesis (TLS)
CC pathway (PubMed:23677613). {ECO:0000269|PubMed:23393192,
CC ECO:0000269|PubMed:23677613}.
CC -!- DISEASE: Note=Defects in FBH1 are frequently observed in melanomas,
CC resulting in increased survival in response to replicative stress. Its
CC inactivation may play a role in oncogenic transformation.
CC {ECO:0000269|PubMed:23466708}.
CC -!- SIMILARITY: Belongs to the helicase family. UvrD subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAM73631.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB55073.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB55154.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF380349; AAM73631.1; ALT_INIT; mRNA.
DR EMBL; AF454502; AAP97700.1; -; mRNA.
DR EMBL; AF456237; AAP97705.1; -; mRNA.
DR EMBL; AK027381; BAB55073.1; ALT_INIT; mRNA.
DR EMBL; AK027496; BAB55154.1; ALT_INIT; mRNA.
DR EMBL; AK095343; BAC04535.1; -; mRNA.
DR EMBL; AL137186; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471072; EAW86426.1; -; Genomic_DNA.
DR EMBL; BC012762; AAH12762.2; -; mRNA.
DR EMBL; BC032674; AAH32674.2; -; mRNA.
DR EMBL; BC113377; AAI13378.1; -; mRNA.
DR EMBL; AL133069; CAB61392.1; -; mRNA.
DR CCDS; CCDS7072.1; -. [Q8NFZ0-1]
DR CCDS; CCDS7073.1; -. [Q8NFZ0-2]
DR PIR; T42669; T42669.
DR RefSeq; NP_001245381.1; NM_001258452.1.
DR RefSeq; NP_001245382.1; NM_001258453.1.
DR RefSeq; NP_116196.3; NM_032807.4. [Q8NFZ0-2]
DR RefSeq; NP_835363.1; NM_178150.2. [Q8NFZ0-1]
DR RefSeq; XP_011518050.1; XM_011519748.2. [Q8NFZ0-2]
DR AlphaFoldDB; Q8NFZ0; -.
DR BioGRID; 124333; 25.
DR CORUM; Q8NFZ0; -.
DR IntAct; Q8NFZ0; 19.
DR MINT; Q8NFZ0; -.
DR STRING; 9606.ENSP00000369335; -.
DR GlyGen; Q8NFZ0; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8NFZ0; -.
DR PhosphoSitePlus; Q8NFZ0; -.
DR BioMuta; FBXO18; -.
DR DMDM; 45476952; -.
DR EPD; Q8NFZ0; -.
DR jPOST; Q8NFZ0; -.
DR MassIVE; Q8NFZ0; -.
DR MaxQB; Q8NFZ0; -.
DR PaxDb; Q8NFZ0; -.
DR PeptideAtlas; Q8NFZ0; -.
DR PRIDE; Q8NFZ0; -.
DR ProteomicsDB; 73393; -. [Q8NFZ0-1]
DR ProteomicsDB; 73394; -. [Q8NFZ0-2]
DR Antibodypedia; 1236; 108 antibodies from 24 providers.
DR DNASU; 84893; -.
DR Ensembl; ENST00000362091.9; ENSP00000355415.4; ENSG00000134452.20. [Q8NFZ0-1]
DR Ensembl; ENST00000379999.6; ENSP00000369335.5; ENSG00000134452.20. [Q8NFZ0-2]
DR GeneID; 84893; -.
DR KEGG; hsa:84893; -.
DR MANE-Select; ENST00000362091.9; ENSP00000355415.4; NM_178150.3; NP_835363.1.
DR UCSC; uc001iis.5; human. [Q8NFZ0-1]
DR CTD; 84893; -.
DR DisGeNET; 84893; -.
DR GeneCards; FBH1; -.
DR HGNC; HGNC:13620; FBH1.
DR HPA; ENSG00000134452; Low tissue specificity.
DR MIM; 607222; gene.
DR neXtProt; NX_Q8NFZ0; -.
DR OpenTargets; ENSG00000134452; -.
DR PharmGKB; PA134948258; -.
DR VEuPathDB; HostDB:ENSG00000134452; -.
DR eggNOG; KOG2108; Eukaryota.
DR GeneTree; ENSGT00390000011669; -.
DR InParanoid; Q8NFZ0; -.
DR OrthoDB; 245505at2759; -.
DR PhylomeDB; Q8NFZ0; -.
DR TreeFam; TF329020; -.
DR PathwayCommons; Q8NFZ0; -.
DR SignaLink; Q8NFZ0; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 84893; 9 hits in 1121 CRISPR screens.
DR ChiTaRS; FBXO18; human.
DR GenomeRNAi; 84893; -.
DR Pharos; Q8NFZ0; Tbio.
DR PRO; PR:Q8NFZ0; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q8NFZ0; protein.
DR Bgee; ENSG00000134452; Expressed in apex of heart and 175 other tissues.
DR ExpressionAtlas; Q8NFZ0; baseline and differential.
DR Genevisible; Q8NFZ0; HS.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0043138; F:3'-5' DNA helicase activity; IDA: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; IDA:UniProtKB.
DR GO; GO:0015616; F:DNA translocase activity; IDA:MGI.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:UniProtKB.
DR GO; GO:0003697; F:single-stranded DNA binding; IDA:UniProtKB.
DR GO; GO:0008219; P:cell death; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0000737; P:DNA catabolic process, endonucleolytic; IMP: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; IEA:Ensembl.
DR GO; GO:2000042; P:negative regulation of double-strand break repair via homologous recombination; IDA:UniProtKB.
DR GO; GO:1902231; P:positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage; IMP:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:MGI.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0000725; P:recombinational repair; IBA:GO_Central.
DR GO; GO:0031297; P:replication fork processing; IDA:UniProtKB.
DR GO; GO:0048478; P:replication fork protection; ISS: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 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 Phosphoprotein; Reference proteome; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1..1043
FT /note="F-box DNA helicase 1"
FT /id="PRO_0000119901"
FT DOMAIN 138..184
FT /note="F-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080"
FT DOMAIN 442..705
FT /note="UvrD-like helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00560"
FT REGION 30..56
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 101..191
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 57..64
FT /note="PIP-box"
FT /evidence="ECO:0000269|PubMed:23677613"
FT MOTIF 807..811
FT /note="APIM motif"
FT /evidence="ECO:0000269|PubMed:23677613"
FT COMPBIAS 143..174
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 463..470
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00560"
FT MOD_RES 124
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1
FT /note="M -> MSYEVTSGCHWTCQVPESCDNGLHCAGPLGHLHRRCQRTSAHLLVFT
FT EHAEM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11956208"
FT /id="VSP_037942"
FT MUTAGEN 56
FT /note="S->A: No effect; when associated with A-583."
FT /evidence="ECO:0000269|PubMed:23319600"
FT MUTAGEN 60..64
FT /note="IPEFF->APAAA: In PIPdeg3A; reduced ubiquitination."
FT /evidence="ECO:0000269|PubMed:23677613"
FT MUTAGEN 63..64
FT /note="FF->AA: Impaired localization to DNA damage sites in
FT response to UV irradiation."
FT /evidence="ECO:0000269|PubMed:23677613"
FT MUTAGEN 227..228
FT /note="LP->AA: Impairs formation of the SCF(FBH1) complex
FT and impairs accumulation on single-stranded DNA."
FT /evidence="ECO:0000269|PubMed:19736316,
FT ECO:0000269|PubMed:23319600"
FT MUTAGEN 583
FT /note="S->A: No effect; when associated with A-56."
FT /evidence="ECO:0000269|PubMed:23319600"
FT MUTAGEN 647
FT /note="D->N: Abolishes helicase activity and prevents
FT accumulation on single-stranded DNA."
FT /evidence="ECO:0000269|PubMed:19736316,
FT ECO:0000269|PubMed:23319600, ECO:0000269|PubMed:25772361"
FT MUTAGEN 807..809
FT /note="KFI->AAA: Impaired localization to DNA damage sites
FT in response to UV irradiation."
FT /evidence="ECO:0000269|PubMed:23677613"
FT CONFLICT 234
FT /note="W -> R (in Ref. 3; BAC04535)"
FT /evidence="ECO:0000305"
FT CONFLICT 339
FT /note="Missing (in Ref. 2; AAP97700 and 3; BAB55154)"
FT /evidence="ECO:0000305"
FT CONFLICT 425
FT /note="K -> N (in Ref. 2; AAP97705)"
FT /evidence="ECO:0000305"
FT CONFLICT 844
FT /note="N -> S (in Ref. 3; BAC04535)"
FT /evidence="ECO:0000305"
FT CONFLICT 984
FT /note="P -> L (in Ref. 2; AAP97700 and 3; BAB55154)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1043 AA; 117686 MW; E20EB343E9D05C4D CRC64;
MRRFKRKHLT AIDCQHLARS HLAVTQPFGQ RWTNRDPNHG LYPKPRTKRG SRGQGSQRCI
PEFFLAGKQP CTNDMAKSNS VGQDSCQDSE GDMIFPAESS CALPQEGSAG PGSPGSAPPS
RKRSWSSEEE SNQATGTSRW DGVSKKAPRH HLSVPCTRPR EARQEAEDST SRLSAESGET
DQDAGDVGPD PIPDSYYGLL GTLPCQEALS HICSLPSEVL RHVFAFLPVE DLYWNLSLVC
HLWREIISDP LFIPWKKLYH RYLMNEEQAV SKVDGILSNC GIEKESDLCV LNLIRYTATT
KCSPSVDPER VLWSLRDHPL LPEAEACVRQ HLPDLYAAAG GVNIWALVAA VVLLSSSVND
IQRLLFCLRR PSSTVTMPDV TETLYCIAVL LYAMREKGIN ISNRIHYNIF YCLYLQENSC
TQATKVKEEP SVWPGKKTIQ LTHEQQLILN HKMEPLQVVK IMAFAGTGKT STLVKYAEKW
SQSRFLYVTF NKSIAKQAER VFPSNVICKT FHSMAYGHIG RKYQSKKKLN LFKLTPFMVN
SVLAEGKGGF IRAKLVCKTL ENFFASADEE LTIDHVPIWC KNSQGQRVMV EQSEKLNGVL
EASRLWDNMR KLGECTEEAH QMTHDGYLKL WQLSKPSLAS FDAIFVDEAQ DCTPAIMNIV
LSQPCGKIFV GDPHQQIYTF RGAVNALFTV PHTHVFYLTQ SFRFGVEIAY VGATILDVCK
RVRKKTLVGG NHQSGIRGDA KGQVALLSRT NANVFDEAVR VTEGEFPSRI HLIGGIKSFG
LDRIIDIWIL LQPEEERRKQ NLVIKDKFIR RWVHKEGFSG FKRYVTAAED KELEAKIAVV
EKYNIRIPEL VQRIEKCHIE DLDFAEYILG TVHKAKGLEF DTVHVLDDFV KVPCARHNLP
QLPHFRVESF SEDEWNLLYV AVTRAKKRLI MTKSLENILT LAGEYFLQAE LTSNVLKTGV
VRCCVGQCNN AIPVDTVLTM KKLPITYSNR KENKGGYLCH SCAEQRIGPL AFLTASPEQV
RAMERTVENI VLPRHEALLF LVF
