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Protein

F-box DNA helicase 1

Gene

FBXO18

Organism
Homo sapiens (Human)
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 (PubMed:11956208, PubMed:23393192). 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:17724085, PubMed:19736316). 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 (PubMed:23319600, PubMed:23361013). 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 (PubMed:25772361). 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 (PubMed:25585578).7 Publications

Catalytic activityi

ATP + H2O = ADP + phosphate.2 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.1 Publication
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 bindingi463 – 4708ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • 3'-5' DNA helicase activity Source: UniProtKB
  • ATP binding Source: UniProtKB-KW
  • ATP-dependent DNA helicase activity Source: InterPro
  • DNA helicase activity Source: UniProtKB
  • DNA translocase activity Source: MGI
  • double-stranded DNA binding Source: UniProtKB
  • single-stranded DNA binding Source: UniProtKB

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: Ensembl
  • 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:3.6.4.121 Publication)
Short name:
hFBH12 Publications
Alternative name(s):
F-box only protein 18Imported
Gene namesi
Name:FBXO18Imported
Synonyms:FBH11 Publication, FBX18
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:13620. FBXO18.

Subcellular locationi

GO - Cellular componenti

  • chromatin Source: UniProtKB
  • nucleus Source: UniProtKB
  • SCF ubiquitin ligase complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleus

Pathology & Biotechi

Involvement in diseasei

Defects in FBXO18 are frequently observed in melanomas, resulting in increased survival in response to replicative stress. Its inactivation may play a role in oncogenic transformation.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi56 – 561S → A: No effect; when associated with A-583. 1 Publication
Mutagenesisi60 – 645IPEFF → APAAA in PIPdeg3A; reduced ubiquitination. 1 Publication
Mutagenesisi63 – 642FF → AA: Impaired localization to DNA damage sites in response to UV irradiation. 1 Publication
Mutagenesisi227 – 2282LP → AA: Impairs formation of the SCF(FBXO18) complex and impairs accumulation on single-stranded DNA. 2 Publications
Mutagenesisi583 – 5831S → A: No effect; when associated with A-56. 1 Publication
Mutagenesisi647 – 6471D → N: Abolishes helicase activity and prevents accumulation on single-stranded DNA. 3 Publications
Mutagenesisi807 – 8093KFI → AAA: Impaired localization to DNA damage sites in response to UV irradiation. 1 Publication

Organism-specific databases

PharmGKBiPA134948258.

Polymorphism and mutation databases

BioMutaiFBXO18.
DMDMi45476952.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10431043F-box DNA helicase 1PRO_0000119901Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei124 – 1241PhosphoserineCombined sources

Post-translational modificationi

Ubiquitinated (PubMed:23393192, PubMed:23677613). 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 (PubMed:23677613).2 Publications

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ8NFZ0.
MaxQBiQ8NFZ0.
PaxDbiQ8NFZ0.
PeptideAtlasiQ8NFZ0.
PRIDEiQ8NFZ0.

PTM databases

iPTMnetiQ8NFZ0.
PhosphoSiteiQ8NFZ0.

Expressioni

Gene expression databases

BgeeiENSG00000134452.
ExpressionAtlasiQ8NFZ0. baseline and differential.
GenevisibleiQ8NFZ0. HS.

Organism-specific databases

HPAiHPA002844.

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 (PubMed:11956208, PubMed:19736316, PubMed:23319600). Interacts with RAD51 (PubMed:23393192). Interacts with RPA2 (PubMed:23319600). Interacts (via PIP-box and RanBP2-type zinc finger) with PCNA (PubMed:23677613).5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
SRCP129314EBI-724767,EBI-621482

Protein-protein interaction databases

BioGridi124333. 19 interactions.
IntActiQ8NFZ0. 12 interactions.
STRINGi9606.ENSP00000369335.

Structurei

3D structure databases

ProteinModelPortaliQ8NFZ0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini138 – 18447F-boxPROSITE-ProRule annotationAdd
BLAST
Domaini442 – 705264UvrD-like helicase ATP-bindingPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi57 – 648PIP-box1 Publication
Motifi807 – 8115APIM motif1 Publication

Domaini

The PIP-box mediates the interaction with PCNA.1 Publication

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.
HOVERGENiHBG051568.
InParanoidiQ8NFZ0.
KOiK10300.
OMAiVFPSNVI.
OrthoDBiEOG091G00Y7.
PhylomeDBiQ8NFZ0.
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]
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: Q8NFZ0-1) [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 AIDCQHLARS HLAVTQPFGQ RWTNRDPNHG LYPKPRTKRG
60 70 80 90 100
SRGQGSQRCI PEFFLAGKQP CTNDMAKSNS VGQDSCQDSE GDMIFPAESS
110 120 130 140 150
CALPQEGSAG PGSPGSAPPS RKRSWSSEEE SNQATGTSRW DGVSKKAPRH
160 170 180 190 200
HLSVPCTRPR EARQEAEDST SRLSAESGET DQDAGDVGPD PIPDSYYGLL
210 220 230 240 250
GTLPCQEALS HICSLPSEVL RHVFAFLPVE DLYWNLSLVC HLWREIISDP
260 270 280 290 300
LFIPWKKLYH RYLMNEEQAV SKVDGILSNC GIEKESDLCV LNLIRYTATT
310 320 330 340 350
KCSPSVDPER VLWSLRDHPL LPEAEACVRQ HLPDLYAAAG GVNIWALVAA
360 370 380 390 400
VVLLSSSVND IQRLLFCLRR PSSTVTMPDV TETLYCIAVL LYAMREKGIN
410 420 430 440 450
ISNRIHYNIF YCLYLQENSC TQATKVKEEP SVWPGKKTIQ LTHEQQLILN
460 470 480 490 500
HKMEPLQVVK IMAFAGTGKT STLVKYAEKW SQSRFLYVTF NKSIAKQAER
510 520 530 540 550
VFPSNVICKT FHSMAYGHIG RKYQSKKKLN LFKLTPFMVN SVLAEGKGGF
560 570 580 590 600
IRAKLVCKTL ENFFASADEE LTIDHVPIWC KNSQGQRVMV EQSEKLNGVL
610 620 630 640 650
EASRLWDNMR KLGECTEEAH QMTHDGYLKL WQLSKPSLAS FDAIFVDEAQ
660 670 680 690 700
DCTPAIMNIV LSQPCGKIFV GDPHQQIYTF RGAVNALFTV PHTHVFYLTQ
710 720 730 740 750
SFRFGVEIAY VGATILDVCK RVRKKTLVGG NHQSGIRGDA KGQVALLSRT
760 770 780 790 800
NANVFDEAVR VTEGEFPSRI HLIGGIKSFG LDRIIDIWIL LQPEEERRKQ
810 820 830 840 850
NLVIKDKFIR RWVHKEGFSG FKRYVTAAED KELEAKIAVV EKYNIRIPEL
860 870 880 890 900
VQRIEKCHIE DLDFAEYILG TVHKAKGLEF DTVHVLDDFV KVPCARHNLP
910 920 930 940 950
QLPHFRVESF SEDEWNLLYV AVTRAKKRLI MTKSLENILT LAGEYFLQAE
960 970 980 990 1000
LTSNVLKTGV VRCCVGQCNN AIPVDTVLTM KKLPITYSNR KENKGGYLCH
1010 1020 1030 1040
SCAEQRIGPL AFLTASPEQV RAMERTVENI VLPRHEALLF LVF
Length:1,043
Mass (Da):117,686
Last modified:March 15, 2004 - v2
Checksum:iE20EB343E9D05C4D
GO
Isoform 2 (identifier: Q8NFZ0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MSYEVTSGCHWTCQVPESCDNGLHCAGPLGHLHRRCQRTSAHLLVFTEHAEM

Note: No experimental confirmation available.
Show »
Length:1,094
Mass (Da):123,375
Checksum:iF2A3ED56FBC690B4
GO

Sequence cautioni

The sequence AAM73631 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAB55073 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAB55154 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti234 – 2341W → R in BAC04535 (PubMed:14702039).Curated
Sequence conflicti339 – 3391Missing in AAP97700 (Ref. 2) Curated
Sequence conflicti339 – 3391Missing in BAB55154 (PubMed:14702039).Curated
Sequence conflicti425 – 4251K → N in AAP97705 (Ref. 2) Curated
Sequence conflicti844 – 8441N → S in BAC04535 (PubMed:14702039).Curated
Sequence conflicti984 – 9841P → L in AAP97700 (Ref. 2) Curated
Sequence conflicti984 – 9841P → L in BAB55154 (PubMed:14702039).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 11M → MSYEVTSGCHWTCQVPESCD NGLHCAGPLGHLHRRCQRTS AHLLVFTEHAEM in isoform 2. 1 PublicationVSP_037942

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF380349 mRNA. Translation: AAM73631.1. Different initiation.
AF454502 mRNA. Translation: AAP97700.1.
AF456237 mRNA. Translation: AAP97705.1.
AK027381 mRNA. Translation: BAB55073.1. Different initiation.
AK027496 mRNA. Translation: BAB55154.1. Different initiation.
AK095343 mRNA. Translation: BAC04535.1.
AL137186 Genomic DNA. Translation: CAI41073.1.
AL137186 Genomic DNA. Translation: CAI41074.1.
CH471072 Genomic DNA. Translation: EAW86426.1.
BC012762 mRNA. Translation: AAH12762.2.
BC032674 mRNA. Translation: AAH32674.2.
BC113377 mRNA. Translation: AAI13378.1.
AL133069 mRNA. Translation: CAB61392.1.
CCDSiCCDS7072.1. [Q8NFZ0-1]
CCDS7073.1. [Q8NFZ0-2]
PIRiT42669.
RefSeqiNP_001245381.1. NM_001258452.1.
NP_001245382.1. NM_001258453.1.
NP_116196.3. NM_032807.4. [Q8NFZ0-2]
NP_835363.1. NM_178150.2. [Q8NFZ0-1]
XP_011518050.1. XM_011519748.2. [Q8NFZ0-2]
UniGeneiHs.498543.

Genome annotation databases

EnsembliENST00000362091; ENSP00000355415; ENSG00000134452. [Q8NFZ0-1]
ENST00000379999; ENSP00000369335; ENSG00000134452. [Q8NFZ0-2]
GeneIDi84893.
KEGGihsa:84893.
UCSCiuc001iis.5. human. [Q8NFZ0-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF380349 mRNA. Translation: AAM73631.1. Different initiation.
AF454502 mRNA. Translation: AAP97700.1.
AF456237 mRNA. Translation: AAP97705.1.
AK027381 mRNA. Translation: BAB55073.1. Different initiation.
AK027496 mRNA. Translation: BAB55154.1. Different initiation.
AK095343 mRNA. Translation: BAC04535.1.
AL137186 Genomic DNA. Translation: CAI41073.1.
AL137186 Genomic DNA. Translation: CAI41074.1.
CH471072 Genomic DNA. Translation: EAW86426.1.
BC012762 mRNA. Translation: AAH12762.2.
BC032674 mRNA. Translation: AAH32674.2.
BC113377 mRNA. Translation: AAI13378.1.
AL133069 mRNA. Translation: CAB61392.1.
CCDSiCCDS7072.1. [Q8NFZ0-1]
CCDS7073.1. [Q8NFZ0-2]
PIRiT42669.
RefSeqiNP_001245381.1. NM_001258452.1.
NP_001245382.1. NM_001258453.1.
NP_116196.3. NM_032807.4. [Q8NFZ0-2]
NP_835363.1. NM_178150.2. [Q8NFZ0-1]
XP_011518050.1. XM_011519748.2. [Q8NFZ0-2]
UniGeneiHs.498543.

3D structure databases

ProteinModelPortaliQ8NFZ0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124333. 19 interactions.
IntActiQ8NFZ0. 12 interactions.
STRINGi9606.ENSP00000369335.

PTM databases

iPTMnetiQ8NFZ0.
PhosphoSiteiQ8NFZ0.

Polymorphism and mutation databases

BioMutaiFBXO18.
DMDMi45476952.

Proteomic databases

EPDiQ8NFZ0.
MaxQBiQ8NFZ0.
PaxDbiQ8NFZ0.
PeptideAtlasiQ8NFZ0.
PRIDEiQ8NFZ0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000362091; ENSP00000355415; ENSG00000134452. [Q8NFZ0-1]
ENST00000379999; ENSP00000369335; ENSG00000134452. [Q8NFZ0-2]
GeneIDi84893.
KEGGihsa:84893.
UCSCiuc001iis.5. human. [Q8NFZ0-1]

Organism-specific databases

CTDi84893.
GeneCardsiFBXO18.
HGNCiHGNC:13620. FBXO18.
HPAiHPA002844.
MIMi607222. gene.
neXtProtiNX_Q8NFZ0.
PharmGKBiPA134948258.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2108. Eukaryota.
COG0210. LUCA.
GeneTreeiENSGT00390000011669.
HOVERGENiHBG051568.
InParanoidiQ8NFZ0.
KOiK10300.
OMAiVFPSNVI.
OrthoDBiEOG091G00Y7.
PhylomeDBiQ8NFZ0.
TreeFamiTF329020.

Enzyme and pathway databases

UniPathwayiUPA00143.

Miscellaneous databases

ChiTaRSiFBXO18. human.
GenomeRNAii84893.
PROiQ8NFZ0.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000134452.
ExpressionAtlasiQ8NFZ0. baseline and differential.
GenevisibleiQ8NFZ0. HS.

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]
SUPFAMiSSF52540. SSF52540. 3 hits.
SSF81383. SSF81383. 1 hit.
PROSITEiPS50181. FBOX. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFBH1_HUMAN
AccessioniPrimary (citable) accession number: Q8NFZ0
Secondary accession number(s): Q5JVB0
, Q5JVB1, Q7Z4Q6, Q7Z4R0, Q8N1P5, Q8N586, Q96E82, Q96K67, Q96SW7, Q9UFB2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 15, 2004
Last sequence update: March 15, 2004
Last modified: September 7, 2016
This is version 135 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. 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.