P25789 (PSA4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Proteasome subunit alpha type-4
EC=3.4.25.1

Alternative name(s):
Macropain subunit C9
Multicatalytic endopeptidase complex subunit C9
Proteasome component C9
Proteasome subunit L

Gene names

Name:	PSMA4
Synonyms:	HC9, PSC9

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	261 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity.
Catalytic activity	Cleavage of peptide bonds with very broad specificity.
Subunit structure	The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel. Interaction with HTLV-1 TAX protein favors NFKB1 activation.
Subcellular location	Cytoplasm. Nucleus. Cytoplasm › P-body By similarity. Note: Co-localizes with TRIM5 in the cytoplasmic bodies By similarity.
Induction	Down-regulated by antioxidants BO-653 and probucol. Ref.8
Sequence similarities	Belongs to the peptidase T1A family.

Ontologies

Keywords
Biological process	Host-virus interaction
Cellular component	Cytoplasm Nucleus Proteasome
Coding sequence diversity	Alternative splicing
Molecular function	Hydrolase Protease Threonine protease
PTM	Acetylation Phosphoprotein
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 exogenous peptide antigen via MHC class I, TAP-dependent Traceable author statement. Source: Reactome apoptotic process Traceable author statement. Source: Reactome gene expression 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 small molecule metabolic process Traceable author statement. Source: Reactome viral reproduction Traceable author statement. Source: Reactome virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasmic mRNA processing body Inferred from sequence or structural similarity. Source: UniProtKB cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome proteasome core complex Inferred from sequence or structural similarity. Source: UniProtKB proteasome core complex, alpha-subunit complex Inferred from electronic annotation. Source: InterPro
Molecular_function	threonine-type endopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PSMA1	P25786	3	EBI-359310,EBI-359352
PSMA2	P25787	6	EBI-359310,EBI-603262
PSMA3	P25788	4	EBI-359310,EBI-348380
PSMA7	O14818	6	EBI-359310,EBI-603272

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P25789-1)

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: P25789-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-71: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 261	261	Proteasome subunit alpha type-4		PRO_0000124103
Amino acid modifications
	Modified residue	13	1	Phosphoserine Ref.10 Ref.12
	Modified residue	75	1	Phosphoserine Ref.9
	Modified residue	127	1	N6-acetyllysine Ref.11
	Modified residue	176	1	N6-acetyllysine Ref.11
Natural variations
	Alternative sequence	1 – 71	71	Missing in isoform 2.		VSP_043102

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1992. Version 1. Checksum: 7867422B1B31F3B9	FASTA	261	29,484
	10 20 30 40 50 60 MSRRYDSRTT IFSPEGRLYQ VEYAMEAIGH AGTCLGILAN DGVLLAAERR NIHKLLDEVF 70 80 90 100 110 120 FSEKIYKLNE DMACSVAGIT SDANVLTNEL RLIAQRYLLQ YQEPIPCEQL VTALCDIKQA 130 140 150 160 170 180 YTQFGGKRPF GVSLLYIGWD KHYGFQLYQS DPSGNYGGWK ATCIGNNSAA AVSMLKQDYK 190 200 210 220 230 240 EGEMTLKSAL ALAIKVLNKT MDVSKLSAEK VEIATLTREN GKTVIRVLKQ KEVEQLIKKH 250 260 EEEEAKAERE KKEKEQKEKD K
	Isoform 2 [UniParc]. Checksum: 0F5AC7AC01335F6A	FASTA	190	21,365
	10 20 30 40 50 60 MACSVAGITS DANVLTNELR LIAQRYLLQY QEPIPCEQLV TALCDIKQAY TQFGGKRPFG 70 80 90 100 110 120 VSLLYIGWDK HYGFQLYQSD PSGNYGGWKA TCIGNNSAAA VSMLKQDYKE GEMTLKSALA 130 140 150 160 170 180 LAIKVLNKTM DVSKLSAEKV EIATLTRENG KTVIRVLKQK EVEQLIKKHE EEEAKAEREK 190 KEKEQKEKDK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and sequence analysis of cDNAs for five major subunits of human proteasomes (multi-catalytic proteinase complexes)." Tamura T., Lee D.H., Osaka F., Fujiwara T., Shin S., Chung C.H., Tanaka K., Ichihara A. Biochim. Biophys. Acta 1089:95-102(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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].
[5]	"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). Tissue: Blood, Brain, Lung, Pancreas and Urinary bladder.
[6]	"Human proteasome subunits from 2-dimensional gels identified by partial sequencing." Kristensen P., Johnsen A.H., Uerkvitz W., Tanaka K., Hendil K.B. Biochem. Biophys. Res. Commun. 205:1785-1789(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-39.
[7]	"Effects on NF-kappa B1/p105 processing of the interaction between the HTLV-1 transactivator Tax and the proteasome." Rousset R., Desbois C., Bantignies F., Jalinot P. Nature 381:328-331(1996) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HTLV-1 TAX.
[8]	"Gene expression induced by BO-653, probucol and BHQ in human endothelial cells." Takabe W., Mataki C., Wada Y., Ishii M., Izumi A., Aburatani H., Hamakubo T., Niki E., Kodama T., Noguchi N. J. Atheroscler. Thromb. 7:223-230(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION BY BO-653 AND PROBUCOL.
[9]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-75, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[10]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[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.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-127 AND LYS-176, MASS SPECTROMETRY.
[12]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D00763 mRNA. Translation: BAA00660.1. BT009784 mRNA. Translation: AAP88786.1. AC027228 Genomic DNA. No translation available. CH471136 Genomic DNA. Translation: EAW99163.1. CH471136 Genomic DNA. Translation: EAW99164.1. BC005361 mRNA. Translation: AAH05361.1. BC022445 mRNA. Translation: AAH22445.1. BC022817 mRNA. Translation: AAH22817.2. BC047667 mRNA. Translation: AAH47667.1. BC093069 mRNA. Translation: AAH93069.1.
IPI	IPI00299155. IPI00792218.
PIR	SNHUC9. S15972.
RefSeq	NP_001096137.1. NM_001102667.1. NP_001096138.1. NM_001102668.1. NP_002780.1. NM_002789.4.
UniGene	Hs.251531.
3D structure databases
ProteinModelPortal	P25789.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29365N.
IntAct	P25789. 15 interactions.
MINT	MINT-5002513.
STRING	9606.ENSP00000044462.
Protein family/group databases
MEROPS	T01.973.
PTM databases
PhosphoSite	P25789.
Polymorphism databases
DMDM	130861.
2D gel databases
UCD-2DPAGE	P25789.
Proteomic databases
PaxDb	P25789.
PRIDE	P25789.
Protocols and materials databases
DNASU	5685.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000044462; ENSP00000044462; ENSG00000041357. ENST00000413382; ENSP00000402118; ENSG00000041357. ENST00000559082; ENSP00000453887; ENSG00000041357.
GeneID	5685.
KEGG	hsa:5685.
UCSC	uc002bdu.4. human.
Organism-specific databases
CTD	5685.
GeneCards	GC15P078832.
HGNC	HGNC:9533. PSMA4.
HPA	CAB004973.
MIM	176846. gene.
neXtProt	NX_P25789.
PharmGKB	PA33878.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0638.
HOGENOM	HOG000091085.
HOVERGEN	HBG003005.
InParanoid	P25789.
KO	K02728.
OMA	LVSHLCD.
OrthoDB	EOG49079S.
PhylomeDB	P25789.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction. REACT_111217. Metabolism. REACT_115566. Cell Cycle. REACT_116125. Disease. REACT_13505. Proteasome mediated degradation of PAK-2p34. REACT_21257. Metabolism of RNA. REACT_21300. Mitotic M-M/G1 phases. REACT_383. DNA Replication. REACT_578. Apoptosis. REACT_6850. Cdc20:Phospho-APC/C mediated degradation of Cyclin A. REACT_6900. Immune System. REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	P25789.
Bgee	P25789.
CleanEx	HS_PSMA4.
Genevestigator	P25789.
GermOnline	ENSG00000041357. Homo sapiens.
Family and domain databases
InterPro	IPR000426. Proteasome_asu_N. IPR016050. Proteasome_bsu_CS. IPR023332. Proteasome_suA-type. IPR001353. Proteasome_sua/b. [Graphical view]
Pfam	PF00227. Proteasome. 1 hit. PF10584. Proteasome_A_N. 1 hit. [Graphical view]
SMART	SM00948. Proteasome_A_N. 1 hit. [Graphical view]
PROSITE	PS00388. PROTEASOME_A_1. 1 hit. PS51475. PROTEASOME_A_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	PSMA4. human.
GenomeRNAi	5685.
NextBio	22078.
SOURCE	Search...

Entry information

Entry name

PSA4_HUMAN

Accession

Primary (citable) accession number: P25789
Secondary accession number(s): D3DW86 , Q53XP2, Q567Q5, Q8TBD1

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1992
Last sequence update:	May 1, 1992
Last modified:	May 1, 2013
This is version 141 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.