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Protein

Cullin-2

Gene

Cul2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Core component of multiple cullin-RING-based ECS (ElonginB/C-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of target proteins. May serve as a rigid scaffold in the complex and 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 ECS complex depends on the substrate recognition component. ECS(VHL) mediates the ubiquitination of hypoxia-inducible factor (HIF) (By similarity).By similarity

Pathwayi

GO - Molecular functioni

GO - Biological processi

  • protein catabolic process Source: MGI
  • protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: GO_Central
Complete GO annotation...

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiREACT_276107. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
REACT_343568. Antigen processing: Ubiquitination & Proteasome degradation.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Cullin-2
Short name:
CUL-2
Gene namesi
Name:Cul2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 18

Organism-specific databases

MGIiMGI:1918995. Cul2.

Subcellular locationi

GO - Cellular componenti

  • Cul2-RING ubiquitin ligase complex Source: MGI
  • nucleolus Source: MGI
  • nucleoplasm Source: MGI
  • VCB complex Source: Ensembl
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 745745Cullin-2PRO_0000119791Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei393 – 3931N6-acetyllysine1 Publication
Modified residuei661 – 6611PhosphothreonineBy similarity
Cross-linki689 – 689Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8)By similarity

Post-translational modificationi

CBC(VHL) complex formation seems to promote neddylation. Deneddylated via its interaction with the COP9 signalosome (CSN) complex.

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ9D4H8.
PaxDbiQ9D4H8.
PRIDEiQ9D4H8.

PTM databases

PhosphoSiteiQ9D4H8.

Expressioni

Gene expression databases

BgeeiQ9D4H8.
CleanExiMM_CUL2.
ExpressionAtlasiQ9D4H8. baseline and differential.
GenevestigatoriQ9D4H8.

Interactioni

Subunit structurei

Component of multiple ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes formed of CUL2, Elongin BC (TCEB1 and TCEB2), RBX1 and a variable substrate-specific adapter. Component of the ECS(VHL) or CBC(VHL) complex containing VHL. Component of the ECS(MED8) complex with the probable substrate recognition component MED8. Component of the ECS(LRR1) complex with the probable substrate recognition component LRR1. Component of a probable ECS E3 ubiquitin-protein ligase complex containing CUL2, RBX1, TCEB1, TCEB2 and FEM1B. Part of an E3 ubiquitin-protein ligase complex including ZYG11B, CUL2 and Elongin BC. Part of an E3 ubiquitin-protein ligase complex including ZYG11BL, CUL2 and Elongin BC. Interacts with RBX1, RNF7, FEM1B and TIP120A/CAND1. Interacts with COPS2, and MED8. Interacts with human respiratory syncytial virus (HRSV) protein NS1. Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, TCEB2 and CUL2. Interacts with KLHDC10; which may be an E3 ubiquitin ligase complex substrate recognition component.2 Publications

Protein-protein interaction databases

BioGridi214895. 6 interactions.
IntActiQ9D4H8. 7 interactions.
MINTiMINT-4092642.

Structurei

3D structure databases

ProteinModelPortaliQ9D4H8.
SMRiQ9D4H8. Positions 4-745.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the cullin family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG5647.
GeneTreeiENSGT00760000119212.
HOGENOMiHOG000176713.
HOVERGENiHBG106177.
InParanoidiQ9D4H8.
KOiK03870.
OMAiVMLDYVE.
OrthoDBiEOG7X3QQG.
PhylomeDBiQ9D4H8.
TreeFamiTF101152.

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]
SUPFAMiSSF74788. SSF74788. 1 hit.
SSF75632. SSF75632. 1 hit.
PROSITEiPS01256. CULLIN_1. 1 hit.
PS50069. CULLIN_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9D4H8-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSLKPRVVDF DETWNKLLTT IKAVVMLEYV ERATWNDRFS DIYALCVAYP
60 70 80 90 100
EPLGERLYAE TKIFLESHVR HLYKRVLESE EQVLVMYHRY WEEYSKGADY
110 120 130 140 150
MDCLYRYLNT QYIKKNKLTE ADIQYGYGGV DMNEPLMEIG ELALDMWRKL
160 170 180 190 200
MVEPLQNILI RMLLREIKND RGGEDPNQKV IHGVINSFVH VEQYKKKFPL
210 220 230 240 250
KFYQGIFVSP FLTETGEYYK QEASNLLQES NCSQYMEKVL GRLKDEEIRC
260 270 280 290 300
RKYLHPSSYT KVIHECQQRM VADHLQFLHS ECHSIIQQER KNDMANMYVL
310 320 330 340 350
LRAVSSGLPH MIEELQKHIH DEGLRATSNL TQEHMPTLFV ESVLEVHGKF
360 370 380 390 400
VQLINTVLNG DQHFMSALDK ALTSVVNYRE PKSVCKAPEL LAKYCDNLLK
410 420 430 440 450
KSAKGMTENE VEDKLTSFIT VFKYIDDKDV FQKFYARMLA KRLIHGLSMS
460 470 480 490 500
MDSEEAMINK LKQACGYEFT SKLHRMYTDM SVSADLNNKF NNFIRNQDTV
510 520 530 540 550
IDLGISFQIY VLQAGAWPLT QAPSSTFAIP QELEKSVQMF ELFYSQHFSG
560 570 580 590 600
RKLTWLHYLC TGEVKMNYLG KPYVAMVTTY QMAVLLAFNN SETVSYKELQ
610 620 630 640 650
DSTQMNEKEL TKTIKSLLDV KMINHDSEKE DIDAESSFSL NMSFSSKRTK
660 670 680 690 700
FKITTSMQKD TPQELEQTRS AVDEDRKMYL QAAIVRIMKA RKVLRHNALI
710 720 730 740
QEVISQSRAR FNPSISMIKK CIEVLIDKQY IERSQASADE YSYVA
Length:745
Mass (Da):86,877
Last modified:November 7, 2003 - v2
Checksum:i311C05CC262692E0
GO
Isoform 2 (identifier: Q9D4H8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     664-702: Missing.

Show »
Length:706
Mass (Da):82,271
Checksum:iDDF5F2945896FA3D
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti612 – 6121K → R in BAB30283 (PubMed:16141072).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei664 – 70239Missing in isoform 2. 2 PublicationsVSP_008823Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK016520 mRNA. Translation: BAB30283.1.
AK160597 mRNA. Translation: BAE35903.1.
BC026779 mRNA. Translation: AAH26779.1.
BC027428 mRNA. Translation: AAH27428.1.
BC025902 mRNA. Translation: AAH25902.1.
CCDSiCCDS29032.2. [Q9D4H8-1]
RefSeqiNP_083678.2. NM_029402.3. [Q9D4H8-1]
XP_006526337.1. XM_006526274.2. [Q9D4H8-1]
XP_006526338.1. XM_006526275.2. [Q9D4H8-1]
UniGeneiMm.291707.
Mm.443148.

Genome annotation databases

EnsembliENSMUST00000025073; ENSMUSP00000025073; ENSMUSG00000024231. [Q9D4H8-2]
ENSMUST00000162301; ENSMUSP00000125403; ENSMUSG00000024231. [Q9D4H8-1]
GeneIDi71745.
KEGGimmu:71745.
UCSCiuc008dxz.2. mouse. [Q9D4H8-2]
uc008dya.2. mouse. [Q9D4H8-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK016520 mRNA. Translation: BAB30283.1.
AK160597 mRNA. Translation: BAE35903.1.
BC026779 mRNA. Translation: AAH26779.1.
BC027428 mRNA. Translation: AAH27428.1.
BC025902 mRNA. Translation: AAH25902.1.
CCDSiCCDS29032.2. [Q9D4H8-1]
RefSeqiNP_083678.2. NM_029402.3. [Q9D4H8-1]
XP_006526337.1. XM_006526274.2. [Q9D4H8-1]
XP_006526338.1. XM_006526275.2. [Q9D4H8-1]
UniGeneiMm.291707.
Mm.443148.

3D structure databases

ProteinModelPortaliQ9D4H8.
SMRiQ9D4H8. Positions 4-745.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi214895. 6 interactions.
IntActiQ9D4H8. 7 interactions.
MINTiMINT-4092642.

PTM databases

PhosphoSiteiQ9D4H8.

Proteomic databases

MaxQBiQ9D4H8.
PaxDbiQ9D4H8.
PRIDEiQ9D4H8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000025073; ENSMUSP00000025073; ENSMUSG00000024231. [Q9D4H8-2]
ENSMUST00000162301; ENSMUSP00000125403; ENSMUSG00000024231. [Q9D4H8-1]
GeneIDi71745.
KEGGimmu:71745.
UCSCiuc008dxz.2. mouse. [Q9D4H8-2]
uc008dya.2. mouse. [Q9D4H8-1]

Organism-specific databases

CTDi8453.
MGIiMGI:1918995. Cul2.

Phylogenomic databases

eggNOGiCOG5647.
GeneTreeiENSGT00760000119212.
HOGENOMiHOG000176713.
HOVERGENiHBG106177.
InParanoidiQ9D4H8.
KOiK03870.
OMAiVMLDYVE.
OrthoDBiEOG7X3QQG.
PhylomeDBiQ9D4H8.
TreeFamiTF101152.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiREACT_276107. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
REACT_343568. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

NextBioi334387.
PROiQ9D4H8.
SOURCEiSearch...

Gene expression databases

BgeeiQ9D4H8.
CleanExiMM_CUL2.
ExpressionAtlasiQ9D4H8. baseline and differential.
GenevestigatoriQ9D4H8.

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]
SUPFAMiSSF74788. 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. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Strain: C57BL/6J.
    Tissue: Testis.
  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] (ISOFORMS 1 AND 2).
    Strain: C57BL/6J and Czech II.
    Tissue: Mammary tumor.
  3. "The COP9 signalosome inhibits p27(kip1) degradation and impedes G1-S phase progression via deneddylation of SCF Cul1."
    Yang X., Menon S., Lykke-Andersen K., Tsuge T., Xiao D., Wang X., Rodriguez-Suarez R.J., Zhang H., Wei N.
    Curr. Biol. 12:667-672(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH COPS2.
  4. "Mammalian mediator subunit mMED8 is an Elongin BC-interacting protein that can assemble with Cul2 and Rbx1 to reconstitute a ubiquitin ligase."
    Brower C.S., Sato S., Tomomori-Sato C., Kamura T., Pause A., Stearman R., Klausner R.D., Malik S., Lane W.S., Sorokina I., Roeder R.G., Conaway J.W., Conaway R.C.
    Proc. Natl. Acad. Sci. U.S.A. 99:10353-10358(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MED8.
  5. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
    Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
    Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-393, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Embryonic fibroblast.

Entry informationi

Entry nameiCUL2_MOUSE
AccessioniPrimary (citable) accession number: Q9D4H8
Secondary accession number(s): Q3TUR8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 7, 2003
Last sequence update: November 7, 2003
Last modified: May 27, 2015
This is version 117 of the entry and version 2 of the sequence. [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

External Data

Dasty 3

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 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.