Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Cullin-1

Gene

CUL1

Organism
Homo sapiens (Human)
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 (PubMed:27565346). 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 (PubMed:25704143, PubMed:25503564). 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 BCL2.11 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

Keywordsi

Biological processHost-virus interaction, Ubl conjugation pathway

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000055130-MONOMER
ReactomeiR-HSA-1169091 Activation of NF-kappaB in B cells
R-HSA-1170546 Prolactin receptor signaling
R-HSA-174113 SCF-beta-TrCP mediated degradation of Emi1
R-HSA-187577 SCF(Skp2)-mediated degradation of p27/p21
R-HSA-195253 Degradation of beta-catenin by the destruction complex
R-HSA-202424 Downstream TCR signaling
R-HSA-2122947 NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition
R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2644607 Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling
R-HSA-2871837 FCERI mediated NF-kB activation
R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-400253 Circadian Clock
R-HSA-5607761 Dectin-1 mediated noncanonical NF-kB signaling
R-HSA-5607764 CLEC7A (Dectin-1) signaling
R-HSA-5610780 Degradation of GLI1 by the proteasome
R-HSA-5610783 Degradation of GLI2 by the proteasome
R-HSA-5610785 GLI3 is processed to GLI3R by the proteasome
R-HSA-5676590 NIK-->noncanonical NF-kB signaling
R-HSA-5684264 MAP3K8 (TPL2)-dependent MAPK1/3 activation
R-HSA-68949 Orc1 removal from chromatin
R-HSA-69231 Cyclin D associated events in G1
R-HSA-8854050 FBXL7 down-regulates AURKA during mitotic entry and in early mitosis
R-HSA-8939902 Regulation of RUNX2 expression and activity
R-HSA-8951664 Neddylation
R-HSA-9020702 Interleukin-1 signaling
R-HSA-917937 Iron uptake and transport
R-HSA-9604323 Negative regulation of NOTCH4 signaling
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiQ13616
SIGNORiQ13616
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
Cullin-1
Short name:
CUL-1
Gene namesi
Name:CUL1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000055130.15
HGNCiHGNC:2551 CUL1
MIMi603134 gene
neXtProtiNX_Q13616

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

Pathology & Biotechi

Organism-specific databases

DisGeNETi8454
OpenTargetsiENSG00000055130
PharmGKBiPA27047

Polymorphism and mutation databases

BioMutaiCUL1
DMDMi19863257

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001197871 – 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)3 Publications

Post-translational modificationi

Neddylated; which enhances the ubiquitination activity of SCF and prevents binding of the inhibitor CAND1. Deneddylated via its interaction with the COP9 signalosome (CSN) complex (PubMed:10597293, PubMed:10713156, PubMed:15537541, PubMed:18805092).7 Publications
(Microbial infection) Deneddylated by Epstein-Barr virus BPLF1 leading to a S-phase-like environment that is required for efficient replication of the viral genome (PubMed:20190741).1 Publication

Keywords - PTMi

Isopeptide bond, Methylation, Ubl conjugation

Proteomic databases

EPDiQ13616
MaxQBiQ13616
PaxDbiQ13616
PeptideAtlasiQ13616
PRIDEiQ13616
ProteomicsDBi59604

PTM databases

iPTMnetiQ13616
PhosphoSitePlusiQ13616

Expressioni

Tissue specificityi

Expressed in lung fibroblasts.1 Publication

Gene expression databases

BgeeiENSG00000055130 Expressed in 220 organ(s), highest expression level in secondary oocyte
CleanExiHS_CUL1
ExpressionAtlasiQ13616 baseline and differential
GenevisibleiQ13616 HS

Organism-specific databases

HPAiCAB002676
HPA064584

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(FBXO10) complex containing FBXO10. Component of the SCF(FBXO11) complex containing FBXO11. 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 COPS2. Interacts with DCUN1D3. 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 (PubMed:25503564). Interacts (when neddylated) with ARIH1; leading to activate the E3 ligase activity of ARIH1 (PubMed:24076655, PubMed:27565346). Interacts with COPS9 isoform 2 (PubMed:23776465). Interacts with UBXN1 (PubMed:28152074). Interacts with KAT7, probably as part of an SCF complex; the interaction mediates KAT7 ubiquitination (By similarity). Interacts with NOTCH2 (PubMed:29149593).By similarity28 Publications
(Microbial infection) Interacts with Epstein-Barr virus BPLF1.1 Publication
(Microbial infection) Interacts with Human adenovirus early E1A protein; this interaction inhibits RBX1-CUL1-dependent elongation reaction of ubiquitin chains by the SCF(FBXW7) complex.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114032, 734 interactors
CORUMiQ13616
DIPiDIP-17013N
IntActiQ13616, 98 interactors
MINTiQ13616
STRINGi9606.ENSP00000326804

Structurei

Secondary structure

1776
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ13616
SMRiQ13616
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13616

Family & Domainsi

Sequence similaritiesi

Belongs to the cullin family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2166 Eukaryota
COG5647 LUCA
GeneTreeiENSGT00760000119212
HOGENOMiHOG000176713
HOVERGENiHBG106177
InParanoidiQ13616
KOiK03347
OMAiTTHKHIE
OrthoDBiEOG091G02WR
PhylomeDBiQ13616
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

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.iShow all

Q13616-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSSTRSQNPH 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):89,679
Last modified:August 14, 2001 - v2
Checksum:i6625A1FFA7799BBA
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0C4DGX4A0A0C4DGX4_HUMAN
Cullin-1
CUL1
752Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti59 – 82Missing in AAC50544 (PubMed:8681378).CuratedAdd BLAST24
Sequence conflicti726K → R in CAD97651 (PubMed:17974005).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U58087 mRNA Translation: AAC50544.1
AF062536 mRNA Translation: AAC36681.1
BX537409 mRNA Translation: CAD97651.1
AC005229 Genomic DNA Translation: AAM49153.1
CH471146 Genomic DNA Translation: EAW80074.1
BC125119 mRNA Translation: AAI25120.1
BC125120 mRNA Translation: AAI25121.1
CCDSiCCDS34772.1
RefSeqiNP_003583.2, NM_003592.2
XP_005250117.1, XM_005250060.4
XP_011514931.1, XM_011516629.2
XP_011514932.1, XM_011516630.2
XP_011514933.1, XM_011516631.2
XP_011514934.1, XM_011516632.2
UniGeneiHs.146806

Genome annotation databases

EnsembliENST00000325222; ENSP00000326804; ENSG00000055130
ENST00000409469; ENSP00000387160; ENSG00000055130
ENST00000602748; ENSP00000473318; ENSG00000055130
GeneIDi8454
KEGGihsa:8454
UCSCiuc003wey.4 human

Similar proteinsi

Entry informationi

Entry nameiCUL1_HUMAN
AccessioniPrimary (citable) accession number: Q13616
Secondary accession number(s): D3DWG3
, O60719, Q08AL6, Q8IYW1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: August 14, 2001
Last modified: September 12, 2018
This is version 184 of the entry and version 2 of the sequence. See 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

3D-structure, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again