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Q9D4H8 (CUL2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cullin-2

Short name=CUL-2
Gene names
Name:Cul2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length745 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Pathway

Protein modification; protein ubiquitination.

Subunit structure

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. Ref.3 Ref.4

Post-translational modification

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

Sequence similarities

Belongs to the cullin family.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9D4H8-1)

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.
Isoform 2 (identifier: Q9D4H8-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 745745Cullin-2
PRO_0000119791

Amino acid modifications

Modified residue3931N6-acetyllysine Ref.5
Modified residue6611Phosphothreonine By similarity
Cross-link689Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8) By similarity

Natural variations

Alternative sequence664 – 70239Missing in isoform 2.
VSP_008823

Experimental info

Sequence conflict6121K → R in BAB30283. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 7, 2003. Version 2.
Checksum: 311C05CC262692E0

FASTA74586,877
        10         20         30         40         50         60 
MSLKPRVVDF DETWNKLLTT IKAVVMLEYV ERATWNDRFS DIYALCVAYP EPLGERLYAE 

        70         80         90        100        110        120 
TKIFLESHVR HLYKRVLESE EQVLVMYHRY WEEYSKGADY MDCLYRYLNT QYIKKNKLTE 

       130        140        150        160        170        180 
ADIQYGYGGV DMNEPLMEIG ELALDMWRKL MVEPLQNILI RMLLREIKND RGGEDPNQKV 

       190        200        210        220        230        240 
IHGVINSFVH VEQYKKKFPL KFYQGIFVSP FLTETGEYYK QEASNLLQES NCSQYMEKVL 

       250        260        270        280        290        300 
GRLKDEEIRC RKYLHPSSYT KVIHECQQRM VADHLQFLHS ECHSIIQQER KNDMANMYVL 

       310        320        330        340        350        360 
LRAVSSGLPH MIEELQKHIH DEGLRATSNL TQEHMPTLFV ESVLEVHGKF VQLINTVLNG 

       370        380        390        400        410        420 
DQHFMSALDK ALTSVVNYRE PKSVCKAPEL LAKYCDNLLK KSAKGMTENE VEDKLTSFIT 

       430        440        450        460        470        480 
VFKYIDDKDV FQKFYARMLA KRLIHGLSMS MDSEEAMINK LKQACGYEFT SKLHRMYTDM 

       490        500        510        520        530        540 
SVSADLNNKF NNFIRNQDTV IDLGISFQIY VLQAGAWPLT QAPSSTFAIP QELEKSVQMF 

       550        560        570        580        590        600 
ELFYSQHFSG RKLTWLHYLC TGEVKMNYLG KPYVAMVTTY QMAVLLAFNN SETVSYKELQ 

       610        620        630        640        650        660 
DSTQMNEKEL TKTIKSLLDV KMINHDSEKE DIDAESSFSL NMSFSSKRTK FKITTSMQKD 

       670        680        690        700        710        720 
TPQELEQTRS AVDEDRKMYL QAAIVRIMKA RKVLRHNALI QEVISQSRAR FNPSISMIKK 

       730        740 
CIEVLIDKQY IERSQASADE YSYVA 

« Hide

Isoform 2 [UniParc].

Checksum: DDF5F2945896FA3D
Show »

FASTA70682,271

References

« Hide 'large scale' references
[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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_083678.2. NM_029402.3.
XP_006526337.1. XM_006526274.1.
XP_006526338.1. XM_006526275.1.
UniGeneMm.291707.
Mm.443148.

3D structure databases

ProteinModelPortalQ9D4H8.
SMRQ9D4H8. Positions 10-745.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid214895. 4 interactions.
IntActQ9D4H8. 7 interactions.
MINTMINT-4092642.

PTM databases

PhosphoSiteQ9D4H8.

Proteomic databases

PaxDbQ9D4H8.
PRIDEQ9D4H8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000025073; ENSMUSP00000025073; ENSMUSG00000024231. [Q9D4H8-2]
ENSMUST00000162301; ENSMUSP00000125403; ENSMUSG00000024231. [Q9D4H8-1]
GeneID71745.
KEGGmmu:71745.
UCSCuc008dxz.2. mouse. [Q9D4H8-2]
uc008dya.2. mouse. [Q9D4H8-1]

Organism-specific databases

CTD8453.
MGIMGI:1918995. Cul2.

Phylogenomic databases

eggNOGCOG5647.
GeneTreeENSGT00730000110820.
HOGENOMHOG000176713.
HOVERGENHBG106177.
InParanoidQ9D4H8.
KOK03870.
OMAVMLDYVE.
OrthoDBEOG7X3QQG.
PhylomeDBQ9D4H8.
TreeFamTF101152.

Enzyme and pathway databases

UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ9D4H8.
BgeeQ9D4H8.
CleanExMM_CUL2.
GenevestigatorQ9D4H8.

Family and domain databases

Gene3D1.10.10.10. 2 hits.
InterProIPR016157. Cullin_CS.
IPR016158. Cullin_homology.
IPR001373. Cullin_N.
IPR019559. Cullin_neddylation_domain.
IPR016159. Cullin_repeat-like_dom.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamPF00888. Cullin. 1 hit.
PF10557. Cullin_Nedd8. 1 hit.
[Graphical view]
SMARTSM00182. CULLIN. 1 hit.
SM00884. Cullin_Nedd8. 1 hit.
[Graphical view]
SUPFAMSSF74788. SSF74788. 1 hit.
SSF75632. SSF75632. 1 hit.
PROSITEPS01256. CULLIN_1. 1 hit.
PS50069. CULLIN_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio334387.
PROQ9D4H8.
SOURCESearch...

Entry information

Entry nameCUL2_MOUSE
AccessionPrimary (citable) accession number: Q9D4H8
Secondary accession number(s): Q3TUR8
Entry history
Integrated into UniProtKB/Swiss-Prot: November 7, 2003
Last sequence update: November 7, 2003
Last modified: April 16, 2014
This is version 106 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot