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Protein

Cullin-3

Gene

Cul3

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

Functioni

Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1 (By similarity). The functional specificity of the BCR complex depends on the BTB domain-containing protein as the substrate recognition component. BCR(KLHL42) is involved in ubiquitination of KATNA1. BCR(SPOP) is involved in ubiquitination of BMI1/PCGF4, BRMS1, H2AFY and DAXX, GLI2 and GLI3. Can also form a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOPL or the heterodimer formed by SPOP and SPOPL; these complexes have lower ubiquitin ligase activity. BCR(KLHL9-KLHL13) controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. BCR(KLHL3) acts as a regulator of ion transport in the distal nephron; by mediating ubiquitination of WNK4. The BCR(KLHL20) E3 ubiquitin ligase complex is involved in interferon response and anterograde Golgi to endosome transport: it mediates both ubiquitination leading to degradation and 'Lys-33'-linked ubiquitination. The BCR(KLHL21) E3 ubiquitin ligase complex regulates localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and mediates the ubiquitination of AURKB. The BCR(KLHL22) ubiquitin ligase complex mediates monoubiquitination of PLK1, leading to PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation. The BCR(KLHL25) ubiquitin ligase complex is involved in translational homeostasis by mediating ubiquitination and subsequent degradation of hypophosphorylated EIF4EBP1 (4E-BP1). Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus involved in regulation of G1/S transition (By similarity). Involved in the ubiquitination of KEAP1, ENC1 and KLHL41. BCR(KLHL12) is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B). In concert with ATF2 and RBX1, promotes degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM (By similarity). The BCR(KCTD17) E3 ubiquitin ligase complex mediates ubiquitination and degradation of TCHP, a down-regulator of cilium assembly, thereby inducing ciliogenesis (By similarity).By similarity1 Publication

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

  • cyclin binding Source: MGI
  • POZ domain binding Source: UniProtKB
  • protein heterodimerization activity Source: MGI
  • protein homodimerization activity Source: MGI
  • ubiquitin protein ligase binding Source: GO_Central
  • ubiquitin-protein transferase activity Source: Ensembl

GO - Biological processi

  • cell migration Source: UniProtKB
  • cell morphogenesis Source: MGI
  • cell projection organization Source: UniProtKB-KW
  • COPII vesicle coating Source: UniProtKB
  • embryonic cleavage Source: UniProtKB
  • ER to Golgi vesicle-mediated transport Source: UniProtKB
  • fibroblast apoptotic process Source: MGI
  • gastrulation Source: MGI
  • integrin-mediated signaling pathway Source: UniProtKB
  • in utero embryonic development Source: MGI
  • liver morphogenesis Source: MGI
  • mitotic cell cycle Source: MGI
  • mitotic metaphase plate congression Source: UniProtKB
  • negative regulation of cyclin-dependent protein serine/threonine kinase by cyclin degradation Source: MGI
  • negative regulation of Rho protein signal transduction Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • positive regulation of cytokinesis Source: UniProtKB
  • positive regulation of mitotic metaphase/anaphase transition Source: UniProtKB
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • protein monoubiquitination Source: UniProtKB
  • protein polyubiquitination Source: UniProtKB
  • protein ubiquitination Source: UniProtKB
  • protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: GO_Central
  • regulation of transcription from RNA polymerase II promoter Source: MGI
  • stem cell division Source: UniProtKB
  • stress fiber assembly Source: UniProtKB
  • trophectodermal cellular morphogenesis Source: MGI
  • Wnt signaling pathway Source: MGI
Complete GO annotation...

Keywords - Biological processi

Cilium biogenesis/degradation, ER-Golgi transport, Transport, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-MMU-4641258. Degradation of DVL.
R-MMU-5632684. Hedgehog 'on' state.
R-MMU-5658442. Regulation of RAS by GAPs.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Cullin-3
Short name:
CUL-3
Gene namesi
Name:Cul3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:1347360. Cul3.

Subcellular locationi

GO - Cellular componenti

  • Cul3-RING ubiquitin ligase complex Source: UniProtKB
  • cullin-RING ubiquitin ligase complex Source: GO_Central
  • cytoplasm Source: MGI
  • extracellular exosome Source: MGI
  • Golgi apparatus Source: MGI
  • Golgi membrane Source: MGI
  • membrane Source: MGI
  • nucleus Source: MGI
  • polar microtubule Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Golgi apparatus, Nucleus

Pathology & Biotechi

Disruption phenotypei

Null deficient mice are not viable. Extraembryonic ectoderm shows a greatly increased number of cells in S phase. In the trophectoderm cells are blocked to entry into S phase. Embryonic stem (ES) cells form tightly packed cell clusters with prominent actin cables and aberrant adhesions. ES cells are retained in proliferation, yet retain their pluripotency.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 768767Cullin-3PRO_0000119794Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineBy similarity
Modified residuei585 – 5851PhosphoserineBy similarity
Cross-linki712 – 712Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8)By similarity

Post-translational modificationi

Neddylated. Attachment of NEDD8 is required for the E3 ubiquitin-protein ligase activity of the BCR E3 ligase complex. Deneddylated via its interaction with the COP9 signalosome (CSN) complex (By similarity).By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9JLV5.
MaxQBiQ9JLV5.
PaxDbiQ9JLV5.
PRIDEiQ9JLV5.

PTM databases

iPTMnetiQ9JLV5.
PhosphoSiteiQ9JLV5.

Expressioni

Tissue specificityi

Widely expressed, with highest expression in brain, spleen and testis. In the testis, it is mainly expressed in spermatids.2 Publications

Gene expression databases

BgeeiQ9JLV5.
CleanExiMM_CUL3.
ExpressionAtlasiQ9JLV5. baseline and differential.
GenevisibleiQ9JLV5. MM.

Interactioni

Subunit structurei

Forms neddylation-dependent homodimers. Component of multiple BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes formed of CUL3, RBX1 and a variable BTB domain-containing protein acting as both, adapter to cullin and substrate recognition subunit. The BCR complex may be active as a heterodimeric complex, in which NEDD8, covalently attached to one CUL3 molecule, binds to the C-terminus of a second CUL3 molecule. Interacts with RBX1, RNF7, CYCE and TIP120A/CAND1. Part of the BCR(SPOP) containing SPOP, and of BCR containing homodimeric SPOPL or the heterodimer formed by SPOP and SPOPL. Component of the BCR(KLHL21) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL21 and RBX1. Component of the BCR(KLHL22) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL22 and RBX1. Component of the BCR(KLHL25) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL25 and RBX1. Part of the probable BCR(KLHL9-KLHL13) complex with BTB domain proteins KLHL9 and KLHL13. Part of the BCR(KLHL41) complex containing KLHL41. Component of the BCR(KLHL12) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL12 and RBX1. Component of the BCR(KLHL3) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL3 and RBX1 (Probable). Part of the BCR(ENC1) complex containing ENC1. Part of a complex consisting of BMI1/PCGF4, CUL3 and SPOP. Part of a complex consisting of BRMS1, CUL3 and SPOP. Part of a complex consisting of H2AFY, CUL3 and SPOP. Component of the BCR(KLHL42) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL42. Interacts with KLHL42 (via the BTB domain). Interacts with KATNA1; the interaction is enhanced by KLHL42. Interacts with KCTD5, KLHL9, KLHL11, KLHL13, GAN, ZBTB16, KLHL3, KLHL15, KLHL20, KLHL36, GMCL1P1, BTBD1. Part of a complex that contains CUL3, RBX1 and GAN. Interacts (via BTB domain) with KLHL17; the interaction regulates surface GRIK2 expression. Interacts with KCTD7. Part of the BCR(GAN) complex containing GAN. Part of the BCR(KEAP1) complex containing KEAP1 (By similarity). Interacts with KLHL10. Interacts with KAT5 and ATF2 (By similarity). Interacts with DCUN1D3 (By similarity). Interacts with KCTD17 in the BCR(KCTD17) E3 ubiquitin ligase complex, at least composed of CUL3, KCTD17 and RBX1 (By similarity).By similarityCurated

GO - Molecular functioni

  • cyclin binding Source: MGI
  • POZ domain binding Source: UniProtKB
  • protein heterodimerization activity Source: MGI
  • protein homodimerization activity Source: MGI
  • ubiquitin protein ligase binding Source: GO_Central

Protein-protein interaction databases

BioGridi205013. 75 interactions.
IntActiQ9JLV5. 47 interactions.
MINTiMINT-4092667.
STRINGi10090.ENSMUSP00000130738.

Structurei

Secondary structure

1
768
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni699 – 7013Combined sources
Helixi702 – 71413Combined sources
Beta strandi716 – 7183Combined sources
Helixi719 – 72911Combined sources
Helixi738 – 75013Combined sources
Beta strandi753 – 7564Combined sources
Beta strandi761 – 7666Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1IUYNMR-A678-768[»]
ProteinModelPortaliQ9JLV5.
SMRiQ9JLV5. Positions 17-768.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9JLV5.

Family & Domainsi

Sequence similaritiesi

Belongs to the cullin family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2167. Eukaryota.
COG5647. LUCA.
GeneTreeiENSGT00760000119212.
HOVERGENiHBG003619.
InParanoidiQ9JLV5.
KOiK03869.
OMAiHKIRAPR.
OrthoDBiEOG7C5M7H.
TreeFamiTF105858.

Family and domain databases

Gene3Di1.10.10.10. 2 hits.
InterProiIPR016157. Cullin_CS.
IPR016158. Cullin_homology.
IPR001373. Cullin_N.
IPR019559. Cullin_neddylation_domain.
IPR016159. Cullin_repeat-like_dom.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00888. Cullin. 1 hit.
PF10557. Cullin_Nedd8. 1 hit.
[Graphical view]
SMARTiSM00182. CULLIN. 1 hit.
SM00884. Cullin_Nedd8. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
SSF74788. SSF74788. 1 hit.
SSF75632. SSF75632. 1 hit.
PROSITEiPS01256. CULLIN_1. 1 hit.
PS50069. CULLIN_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9JLV5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSNLSKGTGS RKDTKMRIRA FPMTMDEKYV NSIWDLLKNA IQEIQRKNNS
60 70 80 90 100
GLSFEELYRN AYTMVLHKHG EKLYTGLREV VTEHLINKVR EDVLNSLNNN
110 120 130 140 150
FLQTLNQAWN DHQTAMVMIR DILMYMDRVY VQQNNVENVY NLGLIIFRDQ
160 170 180 190 200
VVRYGCIRDH LRQTLLDMIA RERKGEVVDR GAIRNACQML MILGLEGRSV
210 220 230 240 250
YEEDFEAPFL EMSAEFFQME SQKFLAENSA SVYIKKVEAR INEEIERVMH
260 270 280 290 300
CLDKSTEEPI VKVVERELIS KHMKTIVEME NSGLVHMLKN GKTEDLACMY
310 320 330 340 350
KLFSRVPNGL KTMCECMSCY LREQGKALVS EEGEGKNPVD YIQGLLDLKS
360 370 380 390 400
RFDRFLQESF NNDRLFKQTI AGDFEYFLNL NSRSPEYLSL FIDDKLKKGV
410 420 430 440 450
KGLTEQEVET ILDKAMVLFR FMQEKDVFER YYKQHLARRL LTNKSVSDDS
460 470 480 490 500
EKNMISKLKT ECGCQFTSKL EGMFRDMSIS NTTMDEFRQH LQATGVSLGG
510 520 530 540 550
VDLTVRVLTT GYWPTQSATP KCNIPPAPRH AFEIFRRFYL AKHSGRQLTL
560 570 580 590 600
QHHMGSADLN ATFYGPVKKE DGSEVGVGGA QVTGSNTRKH ILQVSTFQMT
610 620 630 640 650
ILMLFNNREK YTFEEIQQET DIPERELVRA LQSLACGKPT QRVLTKEPKS
660 670 680 690 700
KEIESGHIFT VNDQFTSKLH RVKIQTVAAK QGESDPERKE TRQKVDDDRK
710 720 730 740 750
HEIEAAIVRI MKSRKKMQHN VLVAEVTQQL KARFLPSPVV IKKRIEGLIE
760
REYLARTPED RKVYTYVA
Length:768
Mass (Da):88,948
Last modified:October 1, 2000 - v1
Checksum:i841E20407BD076A3
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF129738 mRNA. Translation: AAF36500.1.
BC027304 mRNA. Translation: AAH27304.1.
CCDSiCCDS15094.1.
RefSeqiNP_001300657.1. NM_001313728.1.
NP_057925.1. NM_016716.5.
UniGeneiMm.12665.
Mm.456495.
Mm.487303.

Genome annotation databases

EnsembliENSMUST00000163119; ENSMUSP00000130738; ENSMUSG00000004364.
GeneIDi26554.
KEGGimmu:26554.
UCSCiuc007brc.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF129738 mRNA. Translation: AAF36500.1.
BC027304 mRNA. Translation: AAH27304.1.
CCDSiCCDS15094.1.
RefSeqiNP_001300657.1. NM_001313728.1.
NP_057925.1. NM_016716.5.
UniGeneiMm.12665.
Mm.456495.
Mm.487303.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1IUYNMR-A678-768[»]
ProteinModelPortaliQ9JLV5.
SMRiQ9JLV5. Positions 17-768.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi205013. 75 interactions.
IntActiQ9JLV5. 47 interactions.
MINTiMINT-4092667.
STRINGi10090.ENSMUSP00000130738.

PTM databases

iPTMnetiQ9JLV5.
PhosphoSiteiQ9JLV5.

Proteomic databases

EPDiQ9JLV5.
MaxQBiQ9JLV5.
PaxDbiQ9JLV5.
PRIDEiQ9JLV5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000163119; ENSMUSP00000130738; ENSMUSG00000004364.
GeneIDi26554.
KEGGimmu:26554.
UCSCiuc007brc.1. mouse.

Organism-specific databases

CTDi8452.
MGIiMGI:1347360. Cul3.

Phylogenomic databases

eggNOGiKOG2167. Eukaryota.
COG5647. LUCA.
GeneTreeiENSGT00760000119212.
HOVERGENiHBG003619.
InParanoidiQ9JLV5.
KOiK03869.
OMAiHKIRAPR.
OrthoDBiEOG7C5M7H.
TreeFamiTF105858.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-MMU-4641258. Degradation of DVL.
R-MMU-5632684. Hedgehog 'on' state.
R-MMU-5658442. Regulation of RAS by GAPs.

Miscellaneous databases

ChiTaRSiCul3. mouse.
EvolutionaryTraceiQ9JLV5.
PROiQ9JLV5.
SOURCEiSearch...

Gene expression databases

BgeeiQ9JLV5.
CleanExiMM_CUL3.
ExpressionAtlasiQ9JLV5. baseline and differential.
GenevisibleiQ9JLV5. MM.

Family and domain databases

Gene3Di1.10.10.10. 2 hits.
InterProiIPR016157. Cullin_CS.
IPR016158. Cullin_homology.
IPR001373. Cullin_N.
IPR019559. Cullin_neddylation_domain.
IPR016159. Cullin_repeat-like_dom.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00888. Cullin. 1 hit.
PF10557. Cullin_Nedd8. 1 hit.
[Graphical view]
SMARTiSM00182. CULLIN. 1 hit.
SM00884. Cullin_Nedd8. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
SSF74788. SSF74788. 1 hit.
SSF75632. SSF75632. 1 hit.
PROSITEiPS01256. CULLIN_1. 1 hit.
PS50069. CULLIN_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Levy N., Agulnik A.I., Boettger-Tong H., Bishop C.E.
    Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: C57BL/6J.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Mammary gland.
  3. "Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian cells."
    Singer J.D., Gurian-West M., Clurman B., Roberts J.M.
    Genes Dev. 13:2375-2387(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, INTERACTION WITH CYCE, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
  4. "Cullin3 is a KLHL10-interacting protein preferentially expressed during late spermiogenesis."
    Wang S., Zheng H., Esaki Y., Kelly F., Yan W.
    Biol. Reprod. 74:102-108(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, INTERACTION WITH KLHL10.
  5. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen and Testis.
  6. "Ubiquitin-dependent regulation of COPII coat size and function."
    Jin L., Pahuja K.B., Wickliffe K.E., Gorur A., Baumgartel C., Schekman R., Rape M.
    Nature 482:495-500(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  7. "Solution structure of the cullin-3 homologue."
    RIKEN structural genomics initiative (RSGI)
    Submitted (OCT-2003) to the PDB data bank
    Cited for: STRUCTURE BY NMR OF 678-768.

Entry informationi

Entry nameiCUL3_MOUSE
AccessioniPrimary (citable) accession number: Q9JLV5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: October 1, 2000
Last modified: July 6, 2016
This is version 131 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

3D-structure, 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  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.