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Protein

COP9 signalosome complex subunit 5

Gene

COPS5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Probable protease subunit 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 the 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. In the complex, it probably acts as the catalytic center that mediates the cleavage of Nedd8 from cullins. It however has no metalloprotease activity by itself and requires the other subunits of the CSN complex. Interacts directly with a large number of proteins that are regulated by the CSN complex, confirming a key role in the complex. Promotes the proteasomal degradation of BRSK2.8 Publications

Miscellaneous

The CSN complex is associated with some 'Lys-63'-specific deubiquitination. Such activity is however not mediated by the core CSN complex but by the BRCC3/BRCC36 component of the BRISC complex.

Cofactori

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi138Zinc; catalyticPROSITE-ProRule annotation1
Metal bindingi140Zinc; catalyticPROSITE-ProRule annotation1
Metal bindingi151Zinc; catalyticPROSITE-ProRule annotation1

GO - Molecular functioni

  • enzyme binding Source: Ensembl
  • macrophage migration inhibitory factor binding Source: Ensembl
  • metal ion binding Source: UniProtKB-KW
  • metalloendopeptidase activity Source: InterPro
  • metallopeptidase activity Source: UniProtKB
  • NEDD8-specific protease activity Source: Reactome
  • thiol-dependent ubiquitin-specific protease activity Source: FlyBase
  • transcription coactivator activity Source: ProtInc
  • translation initiation factor activity Source: ProtInc

GO - Biological processi

  • exosomal secretion Source: FlyBase
  • negative regulation of apoptotic process Source: UniProtKB
  • nucleotide-excision repair, DNA damage recognition Source: Reactome
  • positive regulation of DNA binding transcription factor activity Source: UniProtKB
  • positive regulation of transcription by RNA polymerase II Source: UniProtKB
  • post-translational protein modification Source: Reactome
  • protein deneddylation Source: UniProtKB
  • protein deubiquitination Source: FlyBase
  • regulation of cell cycle Source: Ensembl
  • regulation of IRE1-mediated unfolded protein response Source: ParkinsonsUK-UCL
  • regulation of JNK cascade Source: UniProtKB
  • transcription by RNA polymerase II Source: ProtInc
  • transcription-coupled nucleotide-excision repair Source: Reactome
  • translation Source: ProtInc

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
LigandMetal-binding

Enzyme and pathway databases

ReactomeiR-HSA-5696394 DNA Damage Recognition in GG-NER
R-HSA-6781823 Formation of TC-NER Pre-Incision Complex
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-8951664 Neddylation
SIGNORiQ92905

Protein family/group databases

MEROPSiM67.002

Names & Taxonomyi

Protein namesi
Recommended name:
COP9 signalosome complex subunit 5 (EC:3.4.-.-)
Short name:
SGN5
Short name:
Signalosome subunit 5
Alternative name(s):
Jun activation domain-binding protein 1
Gene namesi
Name:COPS5
Synonyms:CSN5, JAB1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000121022.13
HGNCiHGNC:2240 COPS5
MIMi604850 gene
neXtProtiNX_Q92905

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

Keywords - Cellular componenti

Cell junction, Cytoplasm, Cytoplasmic vesicle, Nucleus, Signalosome, Synapse

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi138H → Q: Abolishes ability to deneddylate cullins, without affecting the 'Lys-63'-specific deubiquitination associated with the COP9 signalosome complex. 1 Publication1

Organism-specific databases

DisGeNETi10987
OpenTargetsiENSG00000121022
PharmGKBiPA26757

Polymorphism and mutation databases

BioMutaiCOPS5
DMDMi55976562

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved2 Publications
ChainiPRO_00001948352 – 334COP9 signalosome complex subunit 5Add BLAST333

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanine2 Publications1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ92905
MaxQBiQ92905
PaxDbiQ92905
PeptideAtlasiQ92905
PRIDEiQ92905

2D gel databases

REPRODUCTION-2DPAGEiIPI00009958

PTM databases

iPTMnetiQ92905
PhosphoSitePlusiQ92905
SwissPalmiQ92905

Expressioni

Gene expression databases

BgeeiENSG00000121022
CleanExiHS_COPS5
ExpressionAtlasiQ92905 baseline and differential
GenevisibleiQ92905 HS

Organism-specific databases

HPAiCAB004242
HPA004845
HPA051531

Interactioni

Subunit structurei

Component of the CSN complex, composed of COPS1/GPS1, COPS2, COPS3, COPS4, COPS5, COPS6, COPS7 (COPS7A or COPS7B), COPS8 and COPS9 isoform 1 (PubMed:26456823). In the complex, it probably interacts directly with COPS1, COPS2, COPS4, COPS6 and COPS7 (COPS7A or COPS7B) and COPS9 isoform 1 (PubMed:26456823). Interacts with COPS9 isoform 2 (PubMed:23776465). The CSN complex interacts with the BRISC complex. Also exists as monomeric form. Interacts with TP53, MIF, JUN, UCHL1, NCOA1, HIF1A, CDKN1B, BCL3, GFER, PGR, LHCGR, SMAD4, SMAD7, ID1, ID3, ITGB2 and TOP2A. Part of a complex consisting of RANBP9, Ran, DYRK1B and COPS5. Interacts with IFIT3. Interacts with BRSK2. Interacts with ZDHHC16 (PubMed:17123647). Interacts with MINDY3 (PubMed:21499297). Interacts with FANK1; regulates the phosphorylation of JUN and the transcriptional activity of AP-1 (PubMed:20978819).21 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi116183, 812 interactors
CORUMiQ92905
DIPiDIP-34546N
IntActiQ92905, 142 interactors
MINTiQ92905
STRINGi9606.ENSP00000350512

Chemistry databases

BindingDBiQ92905

Structurei

Secondary structure

1334
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi6 – 42Combined sources37
Helixi44 – 46Combined sources3
Beta strandi54 – 58Combined sources5
Helixi59 – 71Combined sources13
Turni72 – 74Combined sources3
Beta strandi78 – 86Combined sources9
Beta strandi89 – 97Combined sources9
Helixi104 – 107Combined sources4
Helixi111 – 126Combined sources16
Beta strandi132 – 139Combined sources8
Turni141 – 143Combined sources3
Helixi149 – 161Combined sources13
Beta strandi166 – 170Combined sources5
Beta strandi183 – 188Combined sources6
Turni208 – 210Combined sources3
Helixi211 – 217Combined sources7
Beta strandi220 – 223Combined sources4
Beta strandi225 – 229Combined sources5
Helixi233 – 235Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4D10X-ray3.80E/M1-334[»]
4D18X-ray4.08E/M12-334[»]
4F7OX-ray2.60A/B1-257[»]
4WSNX-ray5.50E/M/U/c/k/s14-334[»]
5JOGX-ray2.46A2-257[»]
5JOHX-ray1.99A2-257[»]
5M5QX-ray2.20A2-257[»]
ProteinModelPortaliQ92905
SMRiQ92905
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini55 – 192MPNPROSITE-ProRule annotationAdd BLAST138

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi138 – 151JAMM motifPROSITE-ProRule annotationAdd BLAST14

Domaini

The JAMM motif is essential for the protease activity of the CSN complex resulting in deneddylation of cullins. It constitutes the catalytic center of the complex (By similarity).By similarity

Sequence similaritiesi

Belongs to the peptidase M67A family. CSN5 subfamily.Curated

Phylogenomic databases

eggNOGiKOG1554 Eukaryota
COG1310 LUCA
GeneTreeiENSGT00550000074850
HOGENOMiHOG000116528
HOVERGENiHBG051137
InParanoidiQ92905
KOiK09613
OMAiKYWVQTL
OrthoDBiEOG091G0AAO
PhylomeDBiQ92905
TreeFamiTF105601

Family and domain databases

InterProiView protein in InterPro
IPR037740 CSN5
IPR000555 JAMM/MPN+_dom
IPR037518 MPN
PANTHERiPTHR10410:SF6 PTHR10410:SF6, 1 hit
PfamiView protein in Pfam
PF01398 JAB, 1 hit
SMARTiView protein in SMART
SM00232 JAB_MPN, 1 hit
PROSITEiView protein in PROSITE
PS50249 MPN, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q92905-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAASGSGMAQ KTWELANNMQ EAQSIDEIYK YDKKQQQEIL AAKPWTKDHH
60 70 80 90 100
YFKYCKISAL ALLKMVMHAR SGGNLEVMGL MLGKVDGETM IIMDSFALPV
110 120 130 140 150
EGTETRVNAQ AAAYEYMAAY IENAKQVGRL ENAIGWYHSH PGYGCWLSGI
160 170 180 190 200
DVSTQMLNQQ FQEPFVAVVI DPTRTISAGK VNLGAFRTYP KGYKPPDEGP
210 220 230 240 250
SEYQTIPLNK IEDFGVHCKQ YYALEVSYFK SSLDRKLLEL LWNKYWVNTL
260 270 280 290 300
SSSSLLTNAD YTTGQVFDLS EKLEQSEAQL GRGSFMLGLE THDRKSEDKL
310 320 330
AKATRDSCKT TIEAIHGLMS QVIKDKLFNQ INIS
Length:334
Mass (Da):37,579
Last modified:January 23, 2007 - v4
Checksum:iB5742F4AAD03A1CF
GO

Sequence cautioni

The sequence AAL82571 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti43 – 45KPW → NLG in AAD03468 (PubMed:9341143).Curated3
Sequence conflicti129R → H in AAB16847 (PubMed:8837781).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U65928 mRNA Translation: AAB16847.1
U70734 mRNA Translation: AAD03468.1
CR541678 mRNA Translation: CAG46479.1
BC001187 mRNA Translation: AAH01187.1
BC001859 mRNA Translation: AAH01859.1
BC007272 mRNA Translation: AAH07272.1
BX648542 mRNA Translation: CAH10375.1
AY078082 mRNA Translation: AAL82571.1 Different initiation.
CCDSiCCDS6198.1
PIRiS71820
RefSeqiNP_006828.2, NM_006837.2
UniGeneiHs.491912

Genome annotation databases

EnsembliENST00000357849; ENSP00000350512; ENSG00000121022
GeneIDi10987
KEGGihsa:10987
UCSCiuc003xxe.4 human

Similar proteinsi

Entry informationi

Entry nameiCSN5_HUMAN
AccessioniPrimary (citable) accession number: Q92905
Secondary accession number(s): O15386
, Q6AW95, Q86WQ4, Q9BQ17
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 23, 2004
Last sequence update: January 23, 2007
Last modified: March 28, 2018
This is version 170 of the entry and version 4 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, Direct protein sequencing, Reference proteome
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Main funding by: National Institutes of Health