Q9D4H8 (CUL2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cullin-2
Short name=CUL-2

Gene names

Name:

Cul2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	745 AA.
Sequence status	Complete.
Protein existence	Evidence 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 By similarity. 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 By similarity. Interacts with COPS2, and MED8. Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, TCEB2 AND CUL2 By similarity. 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.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Coding sequence diversity	Alternative splicing
PTM	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	protein catabolic process Inferred from mutant phenotype PubMed 15601820. Source: MGI protein ubiquitination Inferred from electronic annotation. Source: UniProtKB-UniPathway ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular_component	Cul2-RING ubiquitin ligase complex Inferred from electronic annotation. Source: Compara
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 745	745	Cullin-2		PRO_0000119791
Amino acid modifications
	Modified residue	284	1	Phosphoserine Ref.5
	Modified residue	393	1	N6-acetyllysine By similarity
	Modified residue	394	1	Phosphotyrosine Ref.5
	Modified residue	661	1	Phosphothreonine By similarity
	Cross-link	689		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8) By similarity
Natural variations
	Alternative sequence	664 – 702	39	Missing in isoform 2.		VSP_008823
Experimental info
	Sequence conflict	612	1	K → R in BAB30283. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 7, 2003. Version 2. Checksum: 311C05CC262692E0	FASTA	745	86,877
	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
	Isoform 2 [UniParc]. Checksum: DDF5F2945896FA3D	FASTA	706	82,271
	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 TPQVISQSRA RFNPSISMIK KCIEVLIDKQ YIERSQASAD EYSYVA

References

	« Hide 'large scale' referencesShow '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. , 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]	"Protein phosphorylation and expression profiling by Yin-yang multidimensional liquid chromatography (Yin-yang MDLC) mass spectrometry." Dai J., Jin W.-H., Sheng Q.-H., Shieh C.-H., Wu J.-R., Zeng R. J. Proteome Res. 6:250-262(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284 AND TYR-394, MASS SPECTROMETRY. Tissue: Liver.
+	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.
IPI	IPI00387216. IPI00387217.
RefSeq	NP_083678.2. NM_029402.3.
UniGene	Mm.291707. Mm.443148.
3D structure databases
ProteinModelPortal	Q9D4H8.
SMR	Q9D4H8. Positions 4-745.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9D4H8. 4 interactions.
PTM databases
PhosphoSite	Q9D4H8.
Proteomic databases
PaxDb	Q9D4H8.
PRIDE	Q9D4H8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000025073; ENSMUSP00000025073; ENSMUSG00000024231. ENSMUST00000162301; ENSMUSP00000125403; ENSMUSG00000024231.
GeneID	71745.
KEGG	mmu:71745.
UCSC	uc008dxz.2. mouse.
Organism-specific databases
CTD	8453.
MGI	MGI:1918995. Cul2.
Phylogenomic databases
eggNOG	COG5647.
GeneTree	ENSGT00550000074299.
HOGENOM	HOG000176713.
HOVERGEN	HBG106177.
InParanoid	Q9D4H8.
KO	K03870.
OMA	VMLDYVE.
OrthoDB	EOG4Z0B51.
Enzyme and pathway databases
UniPathway	UPA00143.
Gene expression databases
ArrayExpress	Q9D4H8.
Bgee	Q9D4H8.
CleanEx	MM_CUL2.
Genevestigator	Q9D4H8.
GermOnline	ENSMUSG00000024231. Mus musculus.
Family and domain databases
Gene3D	1.10.10.10. 2 hits.
InterPro	IPR016157. Cullin_CS. IPR016158. Cullin_homology. IPR001373. Cullin_N. IPR019559. Cullin_neddylation_domain. IPR016159. Cullin_repeat-like_dom. IPR011991. WHTH_DNA-bd_dom. [Graphical view]
Pfam	PF00888. Cullin. 1 hit. PF10557. Cullin_Nedd8. 1 hit. [Graphical view]
SMART	SM00182. CULLIN. 1 hit. SM00884. Cullin_Nedd8. 1 hit. [Graphical view]
SUPFAM	SSF75632. Cullin_homology. 1 hit. SSF74788. Cullin_repeat-like. 1 hit.
PROSITE	PS01256. CULLIN_1. 1 hit. PS50069. CULLIN_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	334387.
SOURCE	Search...

Entry information

Entry name

CUL2_MOUSE

Accession

Primary (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:	May 1, 2013
This is version 97 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program