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Protein

F-box only protein 6

Gene

FBXO6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Substrate-recognition component of some SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complexes. Involved in endoplasmic reticulum-associated degradation pathway (ERAD) for misfolded lumenal proteins by recognizing and binding sugar chains on unfolded glycoproteins that are retrotranlocated into the cytosol and promoting their ubiquitination and subsequent degradation. Able to recognize and bind denatured glycoproteins, which are modified with not only high-mannose but also complex-type oligosaccharides. Also recognizes sulfated glycans. Also involved in DNA damage response by specifically recognizing activated CHEK1 (phosphorylated on 'Ser-345'), promoting its ubiquitination and degradation. Ubiquitination of CHEK1 is required to insure that activated CHEK1 does not accumulate as cells progress through S phase, or when replication forks encounter transient impediments during normal DNA replication.2 Publications

Pathwayi: protein ubiquitination

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

GO - Molecular functioni

GO - Biological processi

  • DNA damage checkpoint Source: UniProtKB
  • DNA repair Source: UniProtKB
  • ER-associated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • glycoprotein catabolic process Source: Ensembl
  • protein polyubiquitination Source: Reactome
  • proteolysis Source: ProtInc
  • response to unfolded protein Source: UniProtKB-KW
  • SCF-dependent proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

DNA damage, DNA repair, Ubl conjugation pathway, Unfolded protein response

Enzyme and pathway databases

BioCyciZFISH:ENSG00000116663-MONOMER.
ReactomeiR-HSA-390471. Association of TriC/CCT with target proteins during biosynthesis.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
F-box only protein 6
Alternative name(s):
F-box protein that recognizes sugar chains 2
F-box/G-domain protein 2
Gene namesi
Name:FBXO6
Synonyms:FBG2, FBS2, FBX6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:13585. FBXO6.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • endoplasmic reticulum quality control compartment Source: Ensembl
  • SCF ubiquitin ligase complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi241 – 242YW → AA: Abolishes interaction with glycosylated concanavalin-A in vitro. 1 Publication2

Organism-specific databases

DisGeNETi26270.
OpenTargetsiENSG00000116663.
PharmGKBiPA28046.

Polymorphism and mutation databases

BioMutaiFBXO6.
DMDMi24636846.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001198821 – 293F-box only protein 6Add BLAST293

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei258PhosphoserineCombined sources1
Modified residuei284PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9NRD1.
MaxQBiQ9NRD1.
PaxDbiQ9NRD1.
PeptideAtlasiQ9NRD1.
PRIDEiQ9NRD1.

PTM databases

iPTMnetiQ9NRD1.
PhosphoSitePlusiQ9NRD1.

Expressioni

Gene expression databases

BgeeiENSG00000116663.
CleanExiHS_FBXO6.
ExpressionAtlasiQ9NRD1. baseline and differential.
GenevisibleiQ9NRD1. HS.

Organism-specific databases

HPAiHPA051175.

Interactioni

Subunit structurei

Interacts with VCP (By similarity). Part of a SCF (SKP1-cullin-F-box) protein ligase complex. Interacts with CHEK1 and CUL1.By similarity2 Publications

Protein-protein interaction databases

BioGridi117654. 622 interactors.
IntActiQ9NRD1. 5 interactors.
STRINGi9606.ENSP00000365944.

Structurei

3D structure databases

ProteinModelPortaliQ9NRD1.
SMRiQ9NRD1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini10 – 57F-boxPROSITE-ProRule annotationAdd BLAST48
Domaini78 – 259FBAPROSITE-ProRule annotationAdd BLAST182

Sequence similaritiesi

Contains 1 F-box domain.PROSITE-ProRule annotation
Contains 1 FBA (F-box associated) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IK6V. Eukaryota.
ENOG4111MF5. LUCA.
GeneTreeiENSGT00390000003865.
HOGENOMiHOG000231084.
HOVERGENiHBG003593.
InParanoidiQ9NRD1.
KOiK10100.
OMAiEMCLKSQ.
OrthoDBiEOG091G0G3L.
PhylomeDBiQ9NRD1.
TreeFamiTF320527.

Family and domain databases

Gene3Di2.60.120.260. 1 hit.
InterProiIPR007397. F-box-assoc_dom.
IPR001810. F-box_dom.
IPR008979. Galactose-bd-like.
[Graphical view]
PfamiPF12937. F-box-like. 1 hit.
PF04300. FBA. 1 hit.
[Graphical view]
SMARTiSM01198. FBA. 1 hit.
SM00256. FBOX. 1 hit.
[Graphical view]
SUPFAMiSSF49785. SSF49785. 1 hit.
SSF81383. SSF81383. 1 hit.
PROSITEiPS51114. FBA. 1 hit.
PS50181. FBOX. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9NRD1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDAPHSKAAL DSINELPENI LLELFTHVPA RQLLLNCRLV CSLWRDLIDL
60 70 80 90 100
MTLWKRKCLR EGFITKDWDQ PVADWKIFYF LRSLHRNLLR NPCAEEDMFA
110 120 130 140 150
WQIDFNGGDR WKVESLPGAH GTDFPDPKVK KYFVTSYEMC LKSQLVDLVA
160 170 180 190 200
EGYWEELLDT FRPDIVVKDW FAARADCGCT YQLKVQLASA DYFVLASFEP
210 220 230 240 250
PPVTIQQWNN ATWTEVSYTF SDYPRGVRYI LFQHGGRDTQ YWAGWYGPRV
260 270 280 290
TNSSIVVSPK MTRNQASSEA QPGQKHGQEE AAQSPYRAVV QIF
Length:293
Mass (Da):33,933
Last modified:October 1, 2000 - v1
Checksum:iEA4235CD9CCD80FF
GO

Sequence cautioni

The sequence AAF04470 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAI20215 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti18E → D in AAF04470 (PubMed:10531035).Curated1
Sequence conflicti51M → L in AAF04470 (PubMed:10531035).Curated1
Sequence conflicti61E → K in AAF04470 (PubMed:10531035).Curated1
Sequence conflicti96E → N in AAF04470 (PubMed:10531035).Curated1
Sequence conflicti114E → D in AAF04470 (PubMed:10531035).Curated1
Sequence conflicti123D → E in AAF04470 (PubMed:10531035).Curated1
Sequence conflicti132Y → S in AAF04470 (PubMed:10531035).Curated1
Sequence conflicti139M → L in AAF04470 (PubMed:10531035).Curated1
Sequence conflicti143 – 144SQ → WE in AAF04470 (PubMed:10531035).Curated2
Sequence conflicti149 – 152VAEG → LADR in AAF04470 (PubMed:10531035).Curated4
Sequence conflicti287R → G in AAF04470 (PubMed:10531035).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04903960R → Q.Corresponds to variant rs3125818dbSNPEnsembl.1
Natural variantiVAR_022158201P → T.Corresponds to variant rs2294639dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF129536 mRNA. Translation: AAF04470.1. Different initiation.
AF233223 mRNA. Translation: AAF67153.1.
AK314989 mRNA. Translation: BAG37485.1.
AL031731 Genomic DNA. Translation: CAI20214.1.
AL031731 Genomic DNA. Translation: CAI20215.1. Sequence problems.
CH471130 Genomic DNA. Translation: EAW71696.1.
BC020880 mRNA. Translation: AAH20880.1.
CCDSiCCDS133.1.
RefSeqiNP_060908.1. NM_018438.5.
XP_005263505.1. XM_005263448.4.
XP_005263506.1. XM_005263449.4.
XP_005263508.1. XM_005263451.4.
XP_006710634.1. XM_006710571.3.
XP_011539534.1. XM_011541232.2.
XP_016856496.1. XM_017001007.1.
UniGeneiHs.464419.

Genome annotation databases

EnsembliENST00000376753; ENSP00000365944; ENSG00000116663.
GeneIDi26270.
KEGGihsa:26270.
UCSCiuc001aso.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Functional Glycomics Gateway - Glycan Binding

hFBG2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF129536 mRNA. Translation: AAF04470.1. Different initiation.
AF233223 mRNA. Translation: AAF67153.1.
AK314989 mRNA. Translation: BAG37485.1.
AL031731 Genomic DNA. Translation: CAI20214.1.
AL031731 Genomic DNA. Translation: CAI20215.1. Sequence problems.
CH471130 Genomic DNA. Translation: EAW71696.1.
BC020880 mRNA. Translation: AAH20880.1.
CCDSiCCDS133.1.
RefSeqiNP_060908.1. NM_018438.5.
XP_005263505.1. XM_005263448.4.
XP_005263506.1. XM_005263449.4.
XP_005263508.1. XM_005263451.4.
XP_006710634.1. XM_006710571.3.
XP_011539534.1. XM_011541232.2.
XP_016856496.1. XM_017001007.1.
UniGeneiHs.464419.

3D structure databases

ProteinModelPortaliQ9NRD1.
SMRiQ9NRD1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117654. 622 interactors.
IntActiQ9NRD1. 5 interactors.
STRINGi9606.ENSP00000365944.

PTM databases

iPTMnetiQ9NRD1.
PhosphoSitePlusiQ9NRD1.

Polymorphism and mutation databases

BioMutaiFBXO6.
DMDMi24636846.

Proteomic databases

EPDiQ9NRD1.
MaxQBiQ9NRD1.
PaxDbiQ9NRD1.
PeptideAtlasiQ9NRD1.
PRIDEiQ9NRD1.

Protocols and materials databases

DNASUi26270.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000376753; ENSP00000365944; ENSG00000116663.
GeneIDi26270.
KEGGihsa:26270.
UCSCiuc001aso.4. human.

Organism-specific databases

CTDi26270.
DisGeNETi26270.
GeneCardsiFBXO6.
HGNCiHGNC:13585. FBXO6.
HPAiHPA051175.
MIMi605647. gene.
neXtProtiNX_Q9NRD1.
OpenTargetsiENSG00000116663.
PharmGKBiPA28046.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IK6V. Eukaryota.
ENOG4111MF5. LUCA.
GeneTreeiENSGT00390000003865.
HOGENOMiHOG000231084.
HOVERGENiHBG003593.
InParanoidiQ9NRD1.
KOiK10100.
OMAiEMCLKSQ.
OrthoDBiEOG091G0G3L.
PhylomeDBiQ9NRD1.
TreeFamiTF320527.

Enzyme and pathway databases

UniPathwayiUPA00143.
BioCyciZFISH:ENSG00000116663-MONOMER.
ReactomeiR-HSA-390471. Association of TriC/CCT with target proteins during biosynthesis.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

ChiTaRSiFBXO6. human.
GeneWikiiFBXO6.
GenomeRNAii26270.
PROiQ9NRD1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000116663.
CleanExiHS_FBXO6.
ExpressionAtlasiQ9NRD1. baseline and differential.
GenevisibleiQ9NRD1. HS.

Family and domain databases

Gene3Di2.60.120.260. 1 hit.
InterProiIPR007397. F-box-assoc_dom.
IPR001810. F-box_dom.
IPR008979. Galactose-bd-like.
[Graphical view]
PfamiPF12937. F-box-like. 1 hit.
PF04300. FBA. 1 hit.
[Graphical view]
SMARTiSM01198. FBA. 1 hit.
SM00256. FBOX. 1 hit.
[Graphical view]
SUPFAMiSSF49785. SSF49785. 1 hit.
SSF81383. SSF81383. 1 hit.
PROSITEiPS51114. FBA. 1 hit.
PS50181. FBOX. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFBX6_HUMAN
AccessioniPrimary (citable) accession number: Q9NRD1
Secondary accession number(s): B1AK42, B2RC88, Q9UKT3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 2002
Last sequence update: October 1, 2000
Last modified: November 30, 2016
This is version 141 of the entry and version 1 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 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. 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.