Q7L5N1 (CSN6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
COP9 signalosome complex subunit 6
Short name=SGN6
Short name=Signalosome subunit 6

Alternative name(s):
JAB1-containing signalosome subunit 6
MOV34 homolog
Vpr-interacting protein
Short name=hVIP

Gene names

Name:	COPS6
Synonyms:	CSN6, HVIP

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	327 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. Has some glucocorticoid receptor-responsive activity. Ref.5 Ref.8 Ref.9 Ref.12 Ref.13
Subunit structure	Component of the CSN complex, composed of COPS1/GPS1, COPS2, COPS3, COPS4, COPS5, COP6, COPS7 (COPS7A or COPS7B) and COPS8. In the complex, it probably interacts directly with COPS2, COPS4, COPS5 and COPS7 (COPS7A or COPS7B). Interacts with the translation initiation factor EIF3S6. Interacts weakly with RBX1. Interacts with the HIV-1 protein Vpr. Ref.6 Ref.7 Ref.9 Ref.10 Ref.11
Subcellular location	Nucleus. Cytoplasm. Note: The interaction with HIV-1 Vpr protein possibly leads its translocation to a perinuclear region. Ref.5 Ref.7
Tissue specificity	Widely expressed. Ref.7
Miscellaneous	Although strongly related to metalloprotease proteins, it lacks the JAMM motif that probably constitutes the catalytic center. Its function as protease is therefore unsure.
Sequence similarities	Belongs to the peptidase M67A family. CSN6 subfamily. Contains 1 MPN (JAB/Mov34) domain.
Sequence caution	The sequence AAD03469.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Host-virus interaction
Cellular component	Cytoplasm Nucleus Signalosome
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	cullin deneddylation Inferred from direct assay. Source: UniProtKB interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell signalosome Inferred from direct assay Ref.14. Source: UniProtKB
Molecular function	protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BTBD2	Q9BX70	2	EBI-486838,EBI-710091

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 327	327	COP9 signalosome complex subunit 6		PRO_0000194860
Regions
	Domain	39 – 148	110	MPN
	Region	211 – 327	117	Interaction with Vpr

Sequences

	Sequence		Length	Mass (Da)
	Q7L5N1 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: E33CAC6ADF799A8D	FASTA	327	36,163
	10 20 30 40 50 60 MAAAAAAAAA TNGTGGSSGM EVDAAVVPSV MACGVTGSVS VALHPLVILN ISDHWIRMRS 70 80 90 100 110 120 QEGRPVQVIG ALIGKQEGRN IEVMNSFELL SHTVEEKIII DKEYYYTKEE QFKQVFKELE 130 140 150 160 170 180 FLGWYTTGGP PDPSDIHVHK QVCEIIESPL FLKLNPMTKH TDLPVSVFES VIDIINGEAT 190 200 210 220 230 240 MLFAELTYTL ATEEAERIGV DHVARMTATG SGENSTVAEH LIAQHSAIKM LHSRVKLILE 250 260 270 280 290 300 YVKASEAGEV PFNHEILREA YALCHCLPVL STDKFKTDFY DQCNDVGLMA YLGTITKTCN 310 320 TMNQFVNKFN VLYDRQGIGR RMRGLFF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed: 12690205] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[4]	"Structure of cDNAs encoding human eukaryotic initiation factor 3 subunits. Possible roles in RNA binding and macromolecular assembly." Asano K., Vornlocher H.-P., Richter-Cook N.J., Merrick W.C., Hinnebusch A.G., Hershey J.W.B. J. Biol. Chem. 272:27042-27052(1997) [PubMed: 9341143] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 22-327.
[5]	"A novel protein complex involved in signal transduction possessing similarities to 26S proteasome subunits." Seeger M., Kraft R., Ferrell K., Bech-Otschir D., Dumdey R., Schade R., Gordon C., Naumann M., Dubiel W. FASEB J. 12:469-478(1998) [PubMed: 9535219] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION.
[6]	"Biochemical mechanism of HIV-I Vpr function. Specific interaction with a cellular protein." Zhao L.-J., Mukherjee S., Narayan O. J. Biol. Chem. 269:15577-15582(1994) [PubMed: 8195203] [Abstract] Cited for: INTERACTION WITH HIV-1 VPR.
[7]	"HIV-1 Vpr interacts with a human 34-kDa mov34 homologue, a cellular factor linked to the G2/M phase transition of the mammalian cell cycle." Mahalingam S., Ayyavoo V., Patel M., Kieber-Emmons T., Kao G.D., Muschel R.J., Weiner D.B. Proc. Natl. Acad. Sci. U.S.A. 95:3419-3424(1998) [PubMed: 9520381] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH HUMAN VPR.
[8]	"COP9 signalosome-specific phosphorylation targets p53 to degradation by the ubiquitin system." Bech-Otschir D., Kraft R., Huang X., Henklein P., Kapelari B., Pollmann C., Dubiel W. EMBO J. 20:1630-1639(2001) [PubMed: 11285227] [Abstract] Cited for: FUNCTION.
[9]	"Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome." Lyapina S., Cope G., Shevchenko A., Serino G., Tsuge T., Zhou C., Wolf D.A., Wei N., Shevchenko A., Deshaies R.J. Science 292:1382-1385(2001) [PubMed: 11337588] [Abstract] Cited for: FUNCTION, COMPOSITION OF THE CSN COMPLEX, INTERACTION WITH RBX1.
[10]	"Association of the mammalian proto-oncoprotein Int-6 with the three protein complexes eIF3, COP9 signalosome and 26S proteasome." Hoareau Alves K., Bochard V., Rety S., Jalinot P. FEBS Lett. 527:15-21(2002) [PubMed: 12220626] [Abstract] Cited for: INTERACTION WITH EIF3S6.
[11]	"Carboxyl terminus of hVIP/mov34 is critical for HIV-1-Vpr interaction and glucocorticoid-mediated signaling." Ramanathan M.P., Curley E. III, Su M., Chambers J.A., Weiner D.B. J. Biol. Chem. 277:47854-47860(2002) [PubMed: 12237292] [Abstract] Cited for: INTERACTION WITH VPR.
[12]	"The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage." Groisman R., Polanowska J., Kuraoka I., Sawada J., Saijo M., Drapkin R., Kisselev A.F., Tanaka K., Nakatani Y. Cell 113:357-367(2003) [PubMed: 12732143] [Abstract] Cited for: FUNCTION.
[13]	"Protein kinase CK2 and protein kinase D are associated with the COP9 signalosome." Uhle S., Medalia O., Waldron R., Dumdey R., Henklein P., Bech-Otschir D., Huang X., Berse M., Sperling J., Schade R., Dubiel W. EMBO J. 22:1302-1312(2003) [PubMed: 12628923] [Abstract] Cited for: FUNCTION.
[14]	"Characterization of the human COP9 signalosome complex using affinity purification and mass spectrometry." Fang L., Wang X., Yamoah K., Chen P.L., Pan Z.Q., Huang L. J. Proteome Res. 7:4914-4925(2008) [PubMed: 18850735] [Abstract] Cited for: IDENTIFICATION IN THE CSN COMPLEX.
[15]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	CH236956 Genomic DNA. Translation: EAL23857.1. CH471091 Genomic DNA. Translation: EAW76601.1. BC002520 mRNA. Translation: AAH02520.2. U70735 mRNA. Translation: AAD03469.1. Different initiation.
IPI	IPI00163230.
RefSeq	NP_006824.2. NM_006833.4.
UniGene	Hs.15591.
3D structure databases
ProteinModelPortal	Q7L5N1.
SMR	Q7L5N1. Positions 38-211.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-32655N.
IntAct	Q7L5N1. 119 interactions.
MINT	MINT-5005311.
STRING	Q7L5N1.
Protein family/group databases
MEROPS	M67.972.
PTM databases
PhosphoSite	Q7L5N1.
Polymorphism databases
DMDM	55976470.
Proteomic databases
PeptideAtlas	Q7L5N1.
PRIDE	Q7L5N1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000303904; ENSP00000304102; ENSG00000168090.
GeneID	10980.
KEGG	hsa:10980.
UCSC	uc003usu.1. human.
Organism-specific databases
CTD	10980.
GeneCards	GC07P099686.
H-InvDB	HIX0006906.
HGNC	HGNC:21749. COPS6.
HPA	HPA044315.
neXtProt	NX_Q7L5N1.
PharmGKB	PA134919933.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00530000063075.
HOGENOM	HBG736979.
HOVERGEN	HBG107770.
InParanoid	Q7L5N1.
OMA	IGKQKGR.
OrthoDB	EOG4JDH76.
PhylomeDB	Q7L5N1.
Gene expression databases
ArrayExpress	Q7L5N1.
Bgee	Q7L5N1.
CleanEx	HS_COPS6.
Genevestigator	Q7L5N1.
GermOnline	ENSG00000168090. Homo sapiens.
Family and domain databases
InterPro	IPR000555. Mov34_MPN_PAD1. [Graphical view]
KO	K12179.
Pfam	PF01398. Mov34. 1 hit. [Graphical view]
SMART	SM00232. JAB_MPN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	41718.

Entry information

Entry name

CSN6_HUMAN

Accession

Primary (citable) accession number: Q7L5N1
Secondary accession number(s): A4D2A3, O15387

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 23, 2004
Last sequence update:	July 5, 2004
Last modified:	January 25, 2012
This is version 76 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.