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Protein

Cullin-3

Gene

Cul3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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 (By similarity). BCR complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (By similarity). As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme (By similarity). 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 (By similarity). BCR(KLHL42) is involved in ubiquitination of KATNA1 (By similarity). BCR(SPOP) is involved in ubiquitination of BMI1/PCGF4, BRMS1, H2AFY and DAXX, GLI2 and GLI3 (By similarity). 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 (By similarity). BCR(KLHL9-KLHL13) controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis (By similarity). 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) (PubMed:22358839). BCR(KLHL3) acts as a regulator of ion transport in the distal nephron; by mediating ubiquitination of WNK4 (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity). The BCR(KLHL25) ubiquitin ligase complex is involved in translational homeostasis by mediating ubiquitination and subsequent degradation of hypophosphorylated EIF4EBP1 (4E-BP1) (By similarity). The BCR(KBTBD8) complex acts by mediating monoubiquitination of NOLC1 and TCOF1, leading to remodel the translational program of differentiating cells in favor of neural crest specification (By similarity). 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 (By similarity). 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). The BCR(KLHL24) E3 ubiquitin ligase complex mediates ubiquitination of KRT14, controls KRT14 levels during keratinocytes differentiation, and is essential for skin integrity (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
  • Notch 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

  • anaphase-promoting complex-dependent catabolic process Source: MGI
  • 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 Rho protein signal transduction Source: UniProtKB
  • negative regulation of transcription by RNA polymerase II Source: MGI
  • nuclear protein quality control by the ubiquitin-proteasome system Source: UniProtKB
  • positive regulation of cytokinesis Source: UniProtKB
  • positive regulation of mitotic metaphase/anaphase transition Source: UniProtKB
  • positive regulation of protein ubiquitination Source: MGI
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: MGI
  • protein destabilization Source: MGI
  • protein monoubiquitination Source: UniProtKB
  • protein polyubiquitination Source: UniProtKB
  • protein ubiquitination Source: UniProtKB
  • regulation of transcription by RNA polymerase II Source: MGI
  • stem cell division Source: UniProtKB
  • stress fiber assembly Source: UniProtKB
  • trophectodermal cellular morphogenesis Source: MGI
  • ubiquitin-dependent protein catabolic process Source: UniProtKB
  • Wnt signaling pathway Source: MGI

Keywordsi

Biological processCilium 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-8951664 Neddylation
R-MMU-983168 Antigen processing: Ubiquitination & Proteasome degradation
UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
Cullin-3
Short name:
CUL-3
Gene namesi
Name:Cul3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi

Organism-specific databases

MGIiMGI:1347360 Cul3

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

Cell projection, Cilium, Cytoplasm, Flagellum, 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)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001197942 – 768Cullin-3Add BLAST767

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineBy similarity1
Modified residuei585PhosphoserineBy similarity1
Cross-linki712Glycyl 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 complex. Deneddylated via its interaction with the COP9 signalosome (CSN) complex.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9JLV5
MaxQBiQ9JLV5
PaxDbiQ9JLV5
PRIDEiQ9JLV5

PTM databases

iPTMnetiQ9JLV5
PhosphoSitePlusiQ9JLV5

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

BgeeiENSMUSG00000004364
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. 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 (By similarity). 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. 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 a complex consisting of H2AFY, CUL3 and SPOP. Component of the BCR(KLHL42) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL42. Component of the BCR(KBTBD8) E3 ubiquitin ligase complex, at least composed of CUL3, KBTBD8 and RBX1. 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, GMCL2, 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. Interacts with KLHL10 (By similarity). Interacts with KAT5 and ATF2. Interacts with DCUN1D3. Interacts with KCTD17 in the BCR(KCTD17) E3 ubiquitin ligase complex, at least composed of CUL3, KCTD17 and RBX1. Interacts (when neddylated) with ARIH1; leading to activate the E3 ligase activity of ARIH1 (By similarity). Interacts with COPS9 (By similarity). Interacts with PPP2R5B; this interaction is indirect and mediated through KLHL15-binding and leads to PPP2R5B proteasomal degradation (By similarity). Interacts with RBBP8/CtIP; this interaction is indirect and mediated through KLHL15-binding and leads to RBBP8 proteasomal degradation (By similarity). Interacts with KLHL24 in the BCR(KLHL24) E3 ubiquitin ligase complex, composed of CUL3, RBX1 and KLHL24.By similarity

GO - Molecular functioni

  • cyclin binding Source: MGI
  • Notch 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, 80 interactors
CORUMiQ9JLV5
IntActiQ9JLV5, 51 interactors
MINTiQ9JLV5
STRINGi10090.ENSMUSP00000130738

Structurei

Secondary structure

1768
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni699 – 701Combined sources3
Helixi702 – 714Combined sources13
Beta strandi716 – 718Combined sources3
Helixi719 – 729Combined sources11
Helixi738 – 750Combined sources13
Beta strandi753 – 756Combined sources4
Beta strandi761 – 766Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1IUYNMR-A678-768[»]
ProteinModelPortaliQ9JLV5
SMRiQ9JLV5
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
OMAiTSTFWPM
OrthoDBiEOG091G02DP
TreeFamiTF105858

Family and domain databases

Gene3Di1.10.10.10, 1 hit
InterProiView protein in InterPro
IPR016157 Cullin_CS
IPR016158 Cullin_homology
IPR036317 Cullin_homology_sf
IPR001373 Cullin_N
IPR019559 Cullin_neddylation_domain
IPR016159 Cullin_repeat-like_dom_sf
IPR036388 WH-like_DNA-bd_sf
IPR036390 WH_DNA-bd_sf
PfamiView protein in Pfam
PF00888 Cullin, 1 hit
PF10557 Cullin_Nedd8, 1 hit
SMARTiView protein in SMART
SM00182 CULLIN, 1 hit
SM00884 Cullin_Nedd8, 1 hit
SUPFAMiSSF46785 SSF46785, 1 hit
SSF74788 SSF74788, 1 hit
SSF75632 SSF75632, 1 hit
PROSITEiView protein in PROSITE
PS01256 CULLIN_1, 1 hit
PS50069 CULLIN_2, 1 hit

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

Entry informationi

Entry nameiCUL3_MOUSE
AccessioniPrimary (citable) accession number: Q9JLV5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: October 1, 2000
Last modified: May 23, 2018
This is version 149 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

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

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