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Protein

F-box DNA helicase 1

Gene

Fbxo18

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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)DescriptionActionsGraphical viewLength
Nucleotide bindingi462 – 469ATPPROSITE-ProRule annotation8

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

Keywordsi

Molecular functionDNA-binding, Helicase, Hydrolase
Biological processDNA damage, DNA repair, Ubl conjugation pathway
LigandATP-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi

Organism-specific databases

MGIiMGI:1354699 Fbxo18

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Chromosome, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001199021 – 1042F-box DNA helicase 1Add BLAST1042

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

PaxDbiQ8K2I9
PeptideAtlasiQ8K2I9
PRIDEiQ8K2I9

PTM databases

iPTMnetiQ8K2I9
PhosphoSitePlusiQ8K2I9

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
SMRiQ8K2I9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini207 – 256F-boxPROSITE-ProRule annotationAdd BLAST50
Domaini441 – 704UvrD-like helicase ATP-bindingPROSITE-ProRule annotationAdd BLAST264

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi57 – 64PIP-boxBy similarity8
Motifi806 – 810APIM motifBy similarity5

Domaini

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

Sequence similaritiesi

Belongs to the helicase family. UvrD subfamily.Curated

Phylogenomic databases

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

Family and domain databases

InterProiView protein in InterPro
IPR014017 DNA_helicase_UvrD-like_C
IPR000212 DNA_helicase_UvrD/REP
IPR036047 F-box-like_dom_sf
IPR001810 F-box_dom
IPR027417 P-loop_NTPase
PANTHERiPTHR11070 PTHR11070, 1 hit
PfamiView protein in Pfam
PF12937 F-box-like, 1 hit
PF13361 UvrD_C, 1 hit
SMARTiView protein in SMART
SM00256 FBOX, 1 hit
SUPFAMiSSF52540 SSF52540, 3 hits
SSF81383 SSF81383, 1 hit
PROSITEiView protein in PROSITE
PS50181 FBOX, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti369P → A in AAH04036 (PubMed:15489334).Curated1
Sequence conflicti376P → A in AAH04036 (PubMed:15489334).Curated1
Sequence conflicti800D → E in BAB23095 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0097161 – 74Missing in isoform 2. 1 PublicationAdd BLAST74
Alternative sequenceiVSP_009717865 – 1042EYILG…LFLVF → GKESGCYLPSKRRSRWFLEV SLHLYLPEAVL in isoform 2. 1 PublicationAdd BLAST178

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_015792.2 [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

Entry informationi

Entry nameiFBH1_MOUSE
AccessioniPrimary (citable) accession number: Q8K2I9
Secondary accession number(s): Q8C444
, Q99KS0, Q9CTC6, Q9QZG7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 15, 2004
Last sequence update: October 1, 2002
Last modified: April 25, 2018
This is version 116 of the entry and version 1 of the sequence. See 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

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