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Protein

Cullin-1

Gene

Cul1

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

Functioni

Core component of multiple cullin-RING-based SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. SCF complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins. In the SCF complex, serves as a rigid scaffold that organizes the SKP1-F-box protein and RBX1 subunits. 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 exchange of the substrate recognition component is mediated by TIP120A/CAND1. The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of CTNNB1 and participate in Wnt signaling. SCF(FBXW11) directs ubiquitination of phosphorylated NFKBIA. SCF(BTRC) directs ubiquitination of NFKBIB, NFKBIE, ATF4, SMAD3, SMAD4, CDC25A, FBXO5 and probably NFKB2. SCF(BTRC) and/or SCF(FBXW11) direct ubiquitination of CEP68. SCF(SKP2) directs ubiquitination of phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. SCF(SKP2) directs ubiquitination of ORC1, CDT1, RBL2, ELF4, CDKN1A, RAG2, FOXO1A, and probably MYC and TAL1. SCF(FBXW7) directs ubiquitination of cyclin E, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1. SCF(FBXW2) directs ubiquitination of GCM1. SCF(FBXO32) directs ubiquitination of MYOD1. SCF(FBXO7) directs ubiquitination of BIRC2 and DLGAP5. SCF(FBXO33) directs ubiquitination of YBX1. SCF(FBXO1) directs ubiquitination of BCL6 and DTL but does not seem to direct ubiquitination of TP53. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(CCNF) directs ubiquitination of CCP110. SCF(FBXL3) and SCF(FBXL21) direct ubiquitination of CRY1 and CRY2. SCF(FBXO9) directs ubiquitination of TTI1 and TELO2. SCF(FBXO10) directs ubiquitination of BCL2.By similarity

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

  • animal organ morphogenesis Source: MGI
  • apoptotic process Source: MGI
  • cell proliferation Source: MGI
  • protein monoubiquitination Source: MGI
  • protein ubiquitination Source: MGI
  • SCF-dependent proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
  • ubiquitin-dependent protein catabolic process Source: MGI
  • viral process Source: UniProtKB-KW

Keywordsi

Biological processHost-virus interaction, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-MMU-1169091 Activation of NF-kappaB in B cells
R-MMU-1170546 Prolactin receptor signaling
R-MMU-174113 SCF-beta-TrCP mediated degradation of Emi1
R-MMU-187577 SCF(Skp2)-mediated degradation of p27/p21
R-MMU-195253 Degradation of beta-catenin by the destruction complex
R-MMU-202424 Downstream TCR signaling
R-MMU-2565942 Regulation of PLK1 Activity at G2/M Transition
R-MMU-2871837 FCERI mediated NF-kB activation
R-MMU-5607761 Dectin-1 mediated noncanonical NF-kB signaling
R-MMU-5607764 CLEC7A (Dectin-1) signaling
R-MMU-5610780 Degradation of GLI1 by the proteasome
R-MMU-5610785 GLI3 is processed to GLI3R by the proteasome
R-MMU-5676590 NIK-->noncanonical NF-kB signaling
R-MMU-5684264 MAP3K8 (TPL2)-dependent MAPK1/3 activation
R-MMU-68949 Orc1 removal from chromatin
R-MMU-69231 Cyclin D associated events in G1
R-MMU-8854050 FBXL7 down-regulates AURKA during mitotic entry and in early mitosis
R-MMU-8939902 Regulation of RUNX2 expression and activity
R-MMU-8951664 Neddylation
R-MMU-9020702 Interleukin-1 signaling
R-MMU-917937 Iron uptake and transport
R-MMU-983168 Antigen processing: Ubiquitination & Proteasome degradation
UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
Cullin-1
Short name:
CUL-1
Gene namesi
Name:Cul1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:1349658 Cul1

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001197881 – 776Cullin-1Add BLAST776

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei63Omega-N-methylarginineCombined sources1
Cross-linki720Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8)By similarity

Post-translational modificationi

Neddylated; which enhances the ubiquitination activity of SCF. Deneddylated via its interaction with the COP9 signalosome (CSN) complex.1 Publication
(Microbial infection) Deneddylated by murine cytomegalovirus M48 leading to a S-phase-like environment that is required for efficient replication of the viral genome.1 Publication

Keywords - PTMi

Isopeptide bond, Methylation, Ubl conjugation

Proteomic databases

EPDiQ9WTX6
MaxQBiQ9WTX6
PaxDbiQ9WTX6
PeptideAtlasiQ9WTX6
PRIDEiQ9WTX6

PTM databases

iPTMnetiQ9WTX6
PhosphoSitePlusiQ9WTX6

Expressioni

Tissue specificityi

Embryo fibroblasts and embryo preadipocytes.1 Publication

Gene expression databases

BgeeiENSMUSG00000029686
CleanExiMM_CUL1
ExpressionAtlasiQ9WTX6 baseline and differential
GenevisibleiQ9WTX6 MM

Interactioni

Subunit structurei

Component of multiple SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complexes formed of CUL1, SKP1, RBX1 and a variable F-box domain-containing protein as substrate-specific subunit. Component of the SCF(FBXW11) complex containing FBXW11. Component of the SCF(SKP2) complex containing SKP2, in which it interacts directly with SKP1, SKP2 and RBX1. Component of the SCF(FBXW2) complex containing FBXW2. Component of the SCF(FBXO32) complex containing FBXO32. Component of the probable SCF(FBXO7) complex containing FBXO7. Component of the SCF(FBXO11) complex containing FBXO11. Component of the SCF(FBXO10) complex containing FBXO10. Component of the SCF(FBXO25) complex containing FBXO25. Component of the SCF(FBXO33) complex containing FBXO33. Component of the probable SCF(FBXO4) complex containing FBXO4. Component of the SCF(FBXO44) complex, composed of SKP1, CUL1 and FBXO44. Component of the SCF(BTRC) complex, composed of SKP1, CUL1 and BTRC. This complex binds phosphorylated NFKBIA. Part of a SCF complex consisting of CUL1, RBX1, SKP1 and FBXO2. Component of a SCF(SKP2)-like complex containing CUL1, SKP1, TRIM21 and SKP2. Component of the SCF(FBXO17) complex, composed of SKP1, CUL1 and FBXO17. Component of the SCF(FBXO27) complex, composed of SKP1, CUL1 and FBXO27. Component of the SCF(CCNF) complex consisting of CUL1, RBX1, SKP1 and CCNF. Component of the SCF(FBXL3) complex composed of CUL1, SKP1, RBX1 and FBXL3. Component of the SCF(FBXL21) complex composed of CUL1, SKP1, RBX1 and FBXL21. Component of the SCF(FBXO9) composed of CUL1, SKP1, RBX1 and FBXO9. Component of the SCF(FBXW7) composed of CUL1, SKP1, RBX1 and FBXW7. Interacts with CHEK2; mediates CHEK2 ubiquitination and regulates its function. Part of a complex with TIP120A/CAND1 and RBX1. The unneddylated form interacts with TIP120A/CAND1 and the interaction mediates the exchange of the F-box substrate-specific subunit. Can self-associate. Interacts with FBXW8. Interacts with RNF7. Interacts with CUL7; the interaction seems to be mediated by FBXW8. Interacts with TRIM21. Interacts with DCUN1D3 (By similarity). Interacts with COPS2. Interacts with CEP68 as part of the SCF(FBXW11) complex; the interaction is probably mediated by FBXW11 and the complex also contains CDK5RAP2 and PCNT (By similarity). Interacts (when neddylated) with ARIH1; leading to activate the E3 ligase activity of ARIH1 (By similarity). Interacts with COPS9 (By similarity). Interacts with KAT7, probably as part of an SCF complex; the interaction mediates KAT7 ubiquitination (PubMed:23319590). Interacts with NOTCH2 (By similarity).By similarity8 Publications
(Microbial infection) Interacts with murine cytomegalovirus M48.1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi205088, 60 interactors
CORUMiQ9WTX6
DIPiDIP-39799N
IntActiQ9WTX6, 41 interactors
MINTiQ9WTX6
STRINGi10090.ENSMUSP00000031697

Structurei

3D structure databases

ProteinModelPortaliQ9WTX6
SMRiQ9WTX6
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the cullin family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2166 Eukaryota
COG5647 LUCA
GeneTreeiENSGT00760000119212
HOGENOMiHOG000176713
HOVERGENiHBG106177
InParanoidiQ9WTX6
KOiK03347
OMAiTTHKHIE
OrthoDBiEOG091G02WR
PhylomeDBiQ9WTX6
TreeFamiTF101151

Family and domain databases

Gene3Di1.10.10.10, 2 hits
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.

Q9WTX6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSSNRSQNPH GLKQIGLDQI WDDLRAGIQQ VYTRQSMAKS RYMELYTHVY
60 70 80 90 100
NYCTSVHQSN QARGAGVPPS KSKKGQTPGG AQFVGLELYK RLKEFLKNYL
110 120 130 140 150
TNLLKDGEDL MDESVLKFYT QQWEDYRFSS KVLNGICAYL NRHWVRRECD
160 170 180 190 200
EGRKGIYEIY SLALVTWRDC LFRPLNKQVT NAVLKLIEKE RNGETINTRL
210 220 230 240 250
ISGVVQSYVE LGLNEDDAFA KGPTLTVYKE SFESQFLADT ERFYTRESTE
260 270 280 290 300
FLQQNPVTEY MKKAEARLLE EQRRVQVYLH ESTQDELARK CEQVLIEKHL
310 320 330 340 350
EIFHTEFQNL LDADKNEDLG RMYNLVSRIQ DGLGELKKLL ETHIHNQGLA
360 370 380 390 400
AIEKCGEAAL NDPKMYVQTV LDVHKKYNAL VMSAFNNDAG FVAALDKACG
410 420 430 440 450
RFINNNAVTK MAQSSSKSPE LLARYCDSLL KKSSKNPEEA ELEDTLNQVM
460 470 480 490 500
VVFKYIEDKD VFQKFYAKML AKRLVHQNSA SDDAEASMIS KLKQACGFEY
510 520 530 540 550
TSKLQRMFQD IGVSKDLNEQ FKKHLTNSEP LDLDFSIQVL SSGSWPFQQS
560 570 580 590 600
CTFALPSELE RSYQRFTAFY ASRHSGRKLT WLYQLSKGEL VTNCFKNRYT
610 620 630 640 650
LQASTFQMAI LLQYNTEDAY TVQQLTDSTQ IKMDILAQVL QILLKSKLLV
660 670 680 690 700
LEDENANVDE VELKPDTLIK LYLGYKNKKL RVNINVPMKT EQKQEQETTH
710 720 730 740 750
KNIEEDRKLL IQAAIVRIMK MRKVLKHQQL LGEVLTQLSS RFKPRVPVIK
760 770
KCIDILIEKE YLERVDGEKD TYSYLA
Length:776
Mass (Da):89,692
Last modified:November 1, 1999 - v1
Checksum:i3E1F8B63C6E498F4
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti74K → R in AAD34471 (Ref. 2) Curated1
Sequence conflicti249T → S in AAD34471 (Ref. 2) Curated1
Sequence conflicti308Q → H in AAD34471 (Ref. 2) Curated1
Sequence conflicti334G → R in AAD34471 (Ref. 2) Curated1
Sequence conflicti640 – 663LQILL…DEVEL → YRFTEVEIAGLRDEMPMLMR WM in AAD34471 (Ref. 2) CuratedAdd BLAST24

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF083216 mRNA Translation: AAD16038.1
AF176910 mRNA Translation: AAD52657.1
AF136441 mRNA Translation: AAD34471.1
BC029260 mRNA Translation: AAH29260.1
CCDSiCCDS20095.1
RefSeqiNP_036172.1, NM_012042.3
XP_006506251.1, XM_006506188.3
XP_006506252.1, XM_006506189.3
XP_006506253.1, XM_006506190.3
UniGeneiMm.87611

Genome annotation databases

EnsembliENSMUST00000031697; ENSMUSP00000031697; ENSMUSG00000029686
GeneIDi26965
KEGGimmu:26965
UCSCiuc009bsz.1 mouse

Similar proteinsi

Entry informationi

Entry nameiCUL1_MOUSE
AccessioniPrimary (citable) accession number: Q9WTX6
Secondary accession number(s): Q9WUI7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: November 1, 1999
Last modified: May 23, 2018
This is version 148 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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