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Protein

F-box DNA helicase 1

Gene

Fbxo18

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

3'-5' DNA helicase and substrate-recognition component of the SCF(FBXO18) E3 ubiquitin ligase complex that plays a key role in response to stalled/damaged replication forks (By similarity). Involved in genome maintenance by acting as an anti-recombinogenic helicase and preventing extensive strand exchange during homologous recombination: promotes RAD51 filament dissolution from stalled forks, thereby inhibiting homologous recombination and preventing excessive recombination (PubMed:24108124). Also promotes cell death and DNA double-strand breakage in response to replication stress: together with MUS81, promotes the endonucleolytic DNA cleavage following prolonged replication stress via its helicase activity, possibly to eliminate cells with excessive replication stress. Plays a major role in remodeling of stalled DNA forks by catalyzing fork regression, in which the fork reverses and the two nascent DNA strands anneal. In addition to the helicase activity, also acts as the substrate-recognition component of the SCF(FBXO18) E3 ubiquitin ligase complex, a complex that mediates ubiquitination of RAD51, leading to regulate RAD51 subcellular location (By similarity).By similarity1 Publication

Catalytic activityi

ATP + H2O = ADP + phosphate.By similarity

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.By similarity
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi462 – 4698ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

  • cell death Source: UniProtKB
  • cellular response to DNA damage stimulus Source: UniProtKB
  • DNA catabolic process, endonucleolytic Source: MGI
  • double-strand break repair via homologous recombination Source: UniProtKB
  • negative regulation of chromatin binding Source: MGI
  • negative regulation of double-strand break repair via homologous recombination Source: UniProtKB
  • positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage Source: MGI
  • positive regulation of protein phosphorylation Source: MGI
  • protein ubiquitination Source: UniProtKB
  • replication fork processing Source: UniProtKB
  • replication fork protection Source: UniProtKB
  • response to intra-S DNA damage checkpoint signaling Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Helicase, Hydrolase

Keywords - Biological processi

DNA damage, DNA repair, Ubl conjugation pathway

Keywords - Ligandi

ATP-binding, DNA-binding, Nucleotide-binding

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
F-box DNA helicase 11 Publication (EC:3.6.4.12By similarity)
Alternative name(s):
F-box only protein 18
Gene namesi
Name:Fbxo18Imported
Synonyms:Fbh11 Publication, Fbx18
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1354699. Fbxo18.

Subcellular locationi

  • Nucleus By similarity
  • Chromosome By similarity

  • Note: Accumulates at sites of DNA damage or replication stress. PCNA is required for localization to DNA damage sites. Localizes to the nucleoplasm in absence of DNA damage.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10421042F-box DNA helicase 1PRO_0000119902Add
BLAST

Post-translational modificationi

Ubiquitinated. Ubiquitination by the DCX(DTL) complex, also named CRL4(CDT2), leading to its degradation: ubiquitination takes place after its localization to DNA damage sites, possibly to facilitate the translesion synthesis (TLS) pathway.By similarity

Keywords - PTMi

Ubl conjugation

Proteomic databases

MaxQBiQ8K2I9.
PaxDbiQ8K2I9.
PeptideAtlasiQ8K2I9.
PRIDEiQ8K2I9.

PTM databases

iPTMnetiQ8K2I9.
PhosphoSiteiQ8K2I9.

Expressioni

Gene expression databases

BgeeiENSMUSG00000058594.
CleanExiMM_FBXO18.
ExpressionAtlasiQ8K2I9. baseline and differential.
GenevisibleiQ8K2I9. MM.

Interactioni

Subunit structurei

Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXO18) composed of CUL1, SKP1, RBX1 and FBXO18 (By similarity). Interacts with RPA2 (By similarity). Interacts with RAD51 (PubMed:24108124). Interacts (via PIP-box and RanBP2-type zinc finger) with PCNA (By similarity).By similarity1 Publication

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000071495.

Structurei

3D structure databases

ProteinModelPortaliQ8K2I9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini207 – 25650F-boxPROSITE-ProRule annotationAdd
BLAST
Domaini441 – 704264UvrD-like helicase ATP-bindingPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi57 – 648PIP-boxBy similarity
Motifi806 – 8105APIM motifBy similarity

Domaini

The PIP-box mediates the interaction with PCNA.By similarity

Sequence similaritiesi

Belongs to the helicase family. UvrD subfamily.Curated
Contains 1 F-box domain.PROSITE-ProRule annotation
Contains 1 uvrD-like helicase ATP-binding domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2108. Eukaryota.
COG0210. LUCA.
GeneTreeiENSGT00390000011669.
HOGENOMiHOG000231864.
HOVERGENiHBG051568.
InParanoidiQ8K2I9.
KOiK10300.
OMAiVFPSNVI.
OrthoDBiEOG091G00Y7.
PhylomeDBiQ8K2I9.
TreeFamiTF329020.

Family and domain databases

Gene3Di3.40.50.300. 3 hits.
InterProiIPR014017. DNA_helicase_UvrD-like_C.
IPR000212. DNA_helicase_UvrD/REP.
IPR001810. F-box_dom.
IPR027417. P-loop_NTPase.
IPR014016. UvrD-like_ATP-bd.
[Graphical view]
PANTHERiPTHR11070. PTHR11070. 1 hit.
PfamiPF12937. F-box-like. 1 hit.
PF00580. UvrD-helicase. 1 hit.
PF13361. UvrD_C. 1 hit.
[Graphical view]
SMARTiSM00256. FBOX. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 3 hits.
SSF81383. SSF81383. 1 hit.
PROSITEiPS50181. FBOX. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8K2I9-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRRFKRKHLT VVDCHHLARS HLAVTQPFSQ RWTNRDPNHG LYPRPRTKGR
60 70 80 90 100
NRGRGCQRYI SEFFLAGHQH CTNDMAKSNS VGQDSCQDAE GDMILTAESS
110 120 130 140 150
CTLPQVDNGE ARLGSSGSAQ PARKRAHCFE EATESGQWDG VTKKTPRHRL
160 170 180 190 200
FPSCSRLREA RQGAEDSLSQ CSPVPGEAGR DIEDIGPDPL PDSYYGLLGM
210 220 230 240 250
LPCQEVPSHI CRLPSEVLRH IFAFLPVEDL YWNLSLVCHL WREIINDPLF
260 270 280 290 300
IPWKKLYHRY LINEEQAVSK VDGILSSHGI EKDSDLCVLN LIRYTATTKC
310 320 330 340 350
SPSVDPERVL WSLRDHPLLL EAEACMRQQL PDLYAAAGGI NVWALVAAMV
360 370 380 390 400
LLSSCVNDIQ HLLFCLRRPS STVTMPDVTE TLYCIAVLLY AMREKGINIS
410 420 430 440 450
NRIHYNIFYC LYLQENSCTQ ATKVTEEPSV WPGKKTSIQL THEQQLILNH
460 470 480 490 500
KMEPLQVVKI MAFAGTGKTS TLVKYAEKWS QSRFLYVTFN KSIAKQAELV
510 520 530 540 550
FPSNVICKTF HSMAYSHVGR KYQLKKKLNL FKLTPFMVNS VLAEGKGGFI
560 570 580 590 600
RAKLVCKTLE NFFASADEEL TIDHVPIWCK NSHGQRVMVE QSEKLNGVLE
610 620 630 640 650
ASRLWDNMRK LGECKEEAYQ MTHDGYLKLW QLSKPLLASF DAIFVDEAQD
660 670 680 690 700
CTPAIMNIVL SQPCGKIFVG DPHQQIYTFR GAVNALFTVP HTHVFYLTQS
710 720 730 740 750
FRFGVEIAYV GATILDVCKR VRKKTLVGGN HQSGIRGDIK GQVALLSRTN
760 770 780 790 800
ANVFDEAVRV TEGESPARIH LIGGIKSFGL DRIIDIWTLL QPEEERRKRD
810 820 830 840 850
LIIKDRFIRR WVHKEGFSGF KRYVTAAEDK ELEAKIAVVE KYNIRIPELV
860 870 880 890 900
ERIERCHIDD LDFAEYILGT VHKAKGLEFD TVHVLDDFVK VPCARHNLAQ
910 920 930 940 950
LPHFRVESFS EDEWNLLYVA VTRAKKRLIM TKSLENILTL AGEYFLQAEL
960 970 980 990 1000
TSNVLKTGVV HCCVGQCNNT IPVDTILTMK KLPITYSNRK ENKGGYLCHS
1010 1020 1030 1040
CAEQRIGPLA FLTASPEQVR AMERTVEDIV LPRQEALLFL VF
Length:1,042
Mass (Da):118,298
Last modified:October 1, 2002 - v1
Checksum:i3F6427D19F5B295F
GO
Isoform 2 (identifier: Q8K2I9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-74: Missing.
     865-1042: EYILGTVHKA...RQEALLFLVF → GKESGCYLPSKRRSRWFLEVSLHLYLPEAVL

Note: No experimental confirmation available.
Show »
Length:821
Mass (Da):92,965
Checksum:iB0F62C184B619FA6
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti369 – 3691P → A in AAH04036 (PubMed:15489334).Curated
Sequence conflicti376 – 3761P → A in AAH04036 (PubMed:15489334).Curated
Sequence conflicti800 – 8001D → E in BAB23095 (PubMed:16141072).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 7474Missing in isoform 2. 1 PublicationVSP_009716Add
BLAST
Alternative sequencei865 – 1042178EYILG…LFLVF → GKESGCYLPSKRRSRWFLEV SLHLYLPEAVL in isoform 2. 1 PublicationVSP_009717Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK003964 mRNA. Translation: BAB23095.1.
AK083118 mRNA. Translation: BAC38767.1.
BC004036 mRNA. Translation: AAH04036.1.
BC031393 mRNA. Translation: AAH31393.1.
AF184275 mRNA. Translation: AAF03151.1.
CCDSiCCDS15688.1. [Q8K2I9-1]
RefSeqiNP_056607.1. NM_015792.1. [Q8K2I9-1]
UniGeneiMm.24088.

Genome annotation databases

EnsembliENSMUST00000071564; ENSMUSP00000071495; ENSMUSG00000058594. [Q8K2I9-1]
GeneIDi50755.
KEGGimmu:50755.
UCSCiuc008ijc.1. mouse. [Q8K2I9-1]
uc008ije.1. mouse. [Q8K2I9-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK003964 mRNA. Translation: BAB23095.1.
AK083118 mRNA. Translation: BAC38767.1.
BC004036 mRNA. Translation: AAH04036.1.
BC031393 mRNA. Translation: AAH31393.1.
AF184275 mRNA. Translation: AAF03151.1.
CCDSiCCDS15688.1. [Q8K2I9-1]
RefSeqiNP_056607.1. NM_015792.1. [Q8K2I9-1]
UniGeneiMm.24088.

3D structure databases

ProteinModelPortaliQ8K2I9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000071495.

PTM databases

iPTMnetiQ8K2I9.
PhosphoSiteiQ8K2I9.

Proteomic databases

MaxQBiQ8K2I9.
PaxDbiQ8K2I9.
PeptideAtlasiQ8K2I9.
PRIDEiQ8K2I9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000071564; ENSMUSP00000071495; ENSMUSG00000058594. [Q8K2I9-1]
GeneIDi50755.
KEGGimmu:50755.
UCSCiuc008ijc.1. mouse. [Q8K2I9-1]
uc008ije.1. mouse. [Q8K2I9-2]

Organism-specific databases

CTDi84893.
MGIiMGI:1354699. Fbxo18.

Phylogenomic databases

eggNOGiKOG2108. Eukaryota.
COG0210. LUCA.
GeneTreeiENSGT00390000011669.
HOGENOMiHOG000231864.
HOVERGENiHBG051568.
InParanoidiQ8K2I9.
KOiK10300.
OMAiVFPSNVI.
OrthoDBiEOG091G00Y7.
PhylomeDBiQ8K2I9.
TreeFamiTF329020.

Enzyme and pathway databases

UniPathwayiUPA00143.

Miscellaneous databases

PROiQ8K2I9.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000058594.
CleanExiMM_FBXO18.
ExpressionAtlasiQ8K2I9. baseline and differential.
GenevisibleiQ8K2I9. MM.

Family and domain databases

Gene3Di3.40.50.300. 3 hits.
InterProiIPR014017. DNA_helicase_UvrD-like_C.
IPR000212. DNA_helicase_UvrD/REP.
IPR001810. F-box_dom.
IPR027417. P-loop_NTPase.
IPR014016. UvrD-like_ATP-bd.
[Graphical view]
PANTHERiPTHR11070. PTHR11070. 1 hit.
PfamiPF12937. F-box-like. 1 hit.
PF00580. UvrD-helicase. 1 hit.
PF13361. UvrD_C. 1 hit.
[Graphical view]
SMARTiSM00256. FBOX. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 3 hits.
SSF81383. SSF81383. 1 hit.
PROSITEiPS50181. FBOX. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFBH1_MOUSE
AccessioniPrimary (citable) accession number: Q8K2I9
Secondary accession number(s): Q8C444
, Q99KS0, Q9CTC6, Q9QZG7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 15, 2004
Last sequence update: October 1, 2002
Last modified: September 7, 2016
This is version 107 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.