P62191 (PRS4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
26S protease regulatory subunit 4
Short name=P26s4

Alternative name(s):
26S proteasome AAA-ATPase subunit RPT2
Proteasome 26S subunit ATPase 1

Gene names

Name:

PSMC1

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	440 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	The 26S protease is involved in the ATP-dependent degradation of ubiquitinated proteins. The regulatory (or ATPase) complex confers ATP dependency and substrate specificity to the 26S complex.
Subunit structure	Interacts with SCA7. Interacts with NGLY1. Interacts with PAAF1. Ref.4 Ref.6 Ref.7
Subcellular location	Cytoplasm. Nucleus.
Sequence similarities	Belongs to the AAA ATPase family.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus Proteasome
Ligand	ATP-binding Nucleotide-binding
PTM	Acetylation Isopeptide bond Lipoprotein Myristate Phosphoprotein Ubl conjugation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest Traceable author statement. Source: Reactome G1/S transition of mitotic cell cycle Traceable author statement. Source: Reactome M/G1 transition of mitotic cell cycle Traceable author statement. Source: Reactome S phase of mitotic cell cycle Traceable author statement. Source: Reactome anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process Traceable author statement. Source: Reactome antigen processing and presentation of peptide antigen via MHC class I Traceable author statement. Source: Reactome apoptotic process Traceable author statement. Source: Reactome mRNA metabolic process Traceable author statement. Source: Reactome negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle Traceable author statement. Source: Reactome positive regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle Traceable author statement. Source: Reactome protein polyubiquitination Traceable author statement. Source: Reactome regulation of apoptotic process Traceable author statement. Source: Reactome regulation of cellular amino acid metabolic process Traceable author statement. Source: Reactome viral reproduction Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome proteasome complex Non-traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATPase activity Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PSMC2	P35998	2	EBI-357598,EBI-359710
PSMC6	P62333	3	EBI-357598,EBI-357669
PSMD2	Q13200	5	EBI-357598,EBI-357648

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed
	Chain	2 – 440	439	26S protease regulatory subunit 4		PRO_0000084677
Regions
	Nucleotide binding	226 – 233	8	ATP Potential
Amino acid modifications
	Modified residue	4	1	Phosphoserine Ref.10
	Modified residue	258	1	N6-acetyllysine Ref.11
	Modified residue	439	1	Phosphotyrosine Ref.5
	Lipidation	2	1	N-myristoyl glycine Ref.8
	Cross-link	237		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.9
Experimental info
	Sequence conflict	19	1	K → E in AAA35484. Ref.1
	Sequence conflict	120	1	H → R in AAH16368. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P62191 [UniParc]. Last modified June 21, 2004. Version 1. Checksum: ACA80782F4F96F49	FASTA	440	49,185
	10 20 30 40 50 60 MGQSQSGGHG PGGGKKDDKD KKKKYEPPVP TRVGKKKKKT KGPDAASKLP LVTPHTQCRL 70 80 90 100 110 120 KLLKLERIKD YLLMEEEFIR NQEQMKPLEE KQEEERSKVD DLRGTPMSVG TLEEIIDDNH 130 140 150 160 170 180 AIVSTSVGSE HYVSILSFVD KDLLEPGCSV LLNHKVHAVI GVLMDDTDPL VTVMKVEKAP 190 200 210 220 230 240 QETYADIGGL DNQIQEIKES VELPLTHPEY YEEMGIKPPK GVILYGPPGT GKTLLAKAVA 250 260 270 280 290 300 NQTSATFLRV VGSELIQKYL GDGPKLVREL FRVAEEHAPS IVFIDEIDAI GTKRYDSNSG 310 320 330 340 350 360 GEREIQRTML ELLNQLDGFD SRGDVKVIMA TNRIETLDPA LIRPGRIDRK IEFPLPDEKT 370 380 390 400 410 420 KKRIFQIHTS RMTLADDVTL DDLIMAKDDL SGADIKAICT EAGLMALRER RMKVTNEDFK 430 440 KSKENVLYKK QEGTPEGLYL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Subunit 4 of the 26 S protease is a member of a novel eukaryotic ATPase family." Dubiel W., Ferrell K., Pratt G., Rechsteiner M.C. J. Biol. Chem. 267:22699-22702(1992) [PubMed: 1429620] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
[2]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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: Bone marrow, Lung and Prostate.
[4]	"Association of ataxin-7 with the proteasome subunit S4 of the 19S regulatory complex." Matilla A., Gorbea C., Einum D.D., Townsend J., Michalik A., van Broeckhoven C., Jensen C.C., Murphy K.J., Ptacek L.J., Fu Y.H. Hum. Mol. Genet. 10:2821-2831(2001) [PubMed: 11734547] [Abstract] Cited for: INTERACTION WITH SCA7.
[5]	"Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry." Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C. Anal. Chem. 76:2763-2772(2004) [PubMed: 15144186] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-439, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[6]	"A complex between peptide:N-glycanase and two proteasome-linked proteins suggests a mechanism for the degradation of misfolded glycoproteins." Katiyar S., Li G., Lennarz W.J. Proc. Natl. Acad. Sci. U.S.A. 101:13774-13779(2004) [PubMed: 15358861] [Abstract] Cited for: INTERACTION WITH NGLY1.
[7]	"Proteasomal ATPase-associated factor 1 negatively regulates proteasome activity by interacting with proteasomal ATPases." Park Y., Hwang Y.-P., Lee J.-S., Seo S.-H., Yoon S.K., Yoon J.-B. Mol. Cell. Biol. 25:3842-3853(2005) [PubMed: 15831487] [Abstract] Cited for: INTERACTION WITH PAAF1.
[8]	"Mass spectrometric characterization of the affinity-purified human 26S proteasome complex." Wang X., Chen C.-F., Baker P.R., Chen P.-L., Kaiser P., Huang L. Biochemistry 46:3553-3565(2007) [PubMed: 17323924] [Abstract] Cited for: MYRISTOYLATION [LARGE SCALE ANALYSIS] AT GLY-2, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[9]	"Tryptic digestion of ubiquitin standards reveals an improved strategy for identifying ubiquitinated proteins by mass spectrometry." Denis N.J., Vasilescu J., Lambert J.-P., Smith J.C., Figeys D. Proteomics 7:868-874(2007) [PubMed: 17370265] [Abstract] Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-237, MASS SPECTROMETRY. Tissue: Mammary cancer.
[10]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[11]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-258, MASS SPECTROMETRY.
[12]	"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	L02426 mRNA. Translation: AAA35484.1. CR457044 mRNA. Translation: CAG33325.1. BC000512 mRNA. Translation: AAH00512.1. BC016368 mRNA. Translation: AAH16368.1. BC073818 mRNA. Translation: AAH73818.1.
IPI	IPI00011126.
PIR	A44468.
RefSeq	NP_002793.2. NM_002802.2.
UniGene	Hs.356654.
3D structure databases
ProteinModelPortal	P62191.
SMR	P62191. Positions 63-432.
ModBase	Search...
Protein-protein interaction databases
IntAct	P62191. 17 interactions.
MINT	MINT-1141832.
STRING	P62191.
PTM databases
PhosphoSite	P62191.
Polymorphism databases
DMDM	49065817.
Proteomic databases
PeptideAtlas	P62191.
PRIDE	P62191.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000261303; ENSP00000261303; ENSG00000100764.
GeneID	5700.
KEGG	hsa:5700.
UCSC	uc001xyf.1. human.
Organism-specific databases
CTD	5700.
GeneCards	GC14P090722.
H-InvDB	HIX0011881. HIX0030744.
HGNC	HGNC:9547. PSMC1.
HPA	HPA000872.
MIM	602706. gene.
neXtProt	NX_P62191.
PharmGKB	PA33892.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG04671.
HOGENOM	HBG724153.
HOVERGEN	HBG000109.
InParanoid	P62191.
OMA	FIRNQER.
OrthoDB	EOG4D7Z5Q.
PhylomeDB	P62191.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction. REACT_111217. Metabolism. REACT_13505. Proteasome mediated degradation of PAK-2p34. REACT_152. Cell Cycle, Mitotic. REACT_1538. Cell Cycle Checkpoints. REACT_383. DNA Replication. REACT_578. Apoptosis. REACT_6185. HIV Infection. REACT_6850. Cdc20:Phospho-APC/C mediated degradation of Cyclin A. REACT_6900. Immune System.
Gene expression databases
ArrayExpress	P62191.
Bgee	P62191.
CleanEx	HS_PSMC1.
Genevestigator	P62191.
GermOnline	ENSG00000100764. Homo sapiens.
Family and domain databases
InterPro	IPR005937. 26S_Psome_P45. IPR003593. ATPase_AAA+_core. IPR003959. ATPase_AAA_core. IPR003960. ATPase_AAA_CS. [Graphical view]
KO	K03062.
Pfam	PF00004. AAA. 1 hit. [Graphical view]
SMART	SM00382. AAA. 1 hit. [Graphical view]
TIGRFAMs	TIGR01242. 26Sp45. 1 hit.
PROSITE	PS00674. AAA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	22146.
SOURCE	Search...

Entry information

Entry name

PRS4_HUMAN

Accession

Primary (citable) accession number: P62191
Secondary accession number(s): P49014 , Q03527, Q6IAW0, Q96AZ3

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 21, 2004
Last sequence update:	June 21, 2004
Last modified:	January 25, 2012
This is version 88 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.