P25786 (PSA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Proteasome subunit alpha type-1
EC=3.4.25.1

Alternative name(s):
30 kDa prosomal protein
Short name=PROS-30
Macropain subunit C2
Multicatalytic endopeptidase complex subunit C2
Proteasome component C2
Proteasome nu chain

Gene names

Name:	PSMA1
Synonyms:	HC2, NU, PROS30, PSC2

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	263 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. Mediates the lipopolysaccharide-induced signal transduction in the macrophage proteasome By similarity. Might be involved in the anti-inflammatory response of macrophages during the interaction with C.albicans heat-inactivated cells By similarity.
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. Interacts with bacterial lipopolysaccharide (LPS) By similarity. Interacts with NOTCH3. Ref.12
Subcellular location	Cytoplasm. Nucleus.
Induction	Induced in breast cancer tissue (at protein level). Up-regulated in liver tumor tissues. Ref.10 Ref.11 Ref.14
Sequence similarities	Belongs to the peptidase T1A family.

Ontologies

Keywords
Biological process	Immunity
Cellular component	Cytoplasm Nucleus Proteasome
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Hydrolase Protease Threonine protease
PTM	Acetylation Glycoprotein Isopeptide bond 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 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
Cellular_component	centrosome Inferred from direct assay. Source: HPA cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome polysome Traceable author statement PubMed 7681138. Source: ProtInc 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	RNA binding Traceable author statement PubMed 7681138. Source: ProtInc threonine-type endopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PSMA2	P25787	5	EBI-359352,EBI-603262
PSMA3	P25788	3	EBI-359352,EBI-348380
PSMA4	P25789	3	EBI-359352,EBI-359310
PSMA7	O14818	7	EBI-359352,EBI-603272

Alternative products

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

Isoform Short (identifier: P25786-1)

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 Long (identifier: P25786-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MQLSKVK

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 263	263	Proteasome subunit alpha type-1		PRO_0000124060
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine By similarity
	Modified residue	14	1	Phosphoserine Ref.16 Ref.17
	Glycosylation	110	1	O-linked (GlcNAc...) By similarity
	Cross-link	115		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.15
	Cross-link	208		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.15
Natural variations
	Alternative sequence	1	1	M → MQLSKVK in isoform Long.		VSP_005279
	Natural variant	37	1	G → V. Ref.4 Ref.7 Corresponds to variant rs17850016 [ dbSNP | Ensembl ].		VAR_067454
Experimental info
	Sequence conflict	14 – 15	2	SP → TA in AAA92734. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform Short [UniParc]. Last modified May 1, 1992. Version 1. Checksum: 3F159C5BCEFE8DED	FASTA	263	29,556
	10 20 30 40 50 60 MFRNQYDNDV TVWSPQGRIH QIEYAMEAVK QGSATVGLKS KTHAVLVALK RAQSELAAHQ 70 80 90 100 110 120 KKILHVDNHI GISIAGLTAD ARLLCNFMRQ ECLDSRFVFD RPLPVSRLVS LIGSKTQIPT 130 140 150 160 170 180 QRYGRRPYGV GLLIAGYDDM GPHIFQTCPS ANYFDCRAMS IGARSQSART YLERHMSEFM 190 200 210 220 230 240 ECNLNELVKH GLRALRETLP AEQDLTTKNV SIGIVGKDLE FTIYDDDDVS PFLEGLEERP 250 260 QRKAQPAQPA DEPAEKADEP MEH
	Isoform Long [UniParc]. Checksum: DB7435F82890F923	FASTA	269	30,239
	10 20 30 40 50 60 MQLSKVKFRN QYDNDVTVWS PQGRIHQIEY AMEAVKQGSA TVGLKSKTHA VLVALKRAQS 70 80 90 100 110 120 ELAAHQKKIL HVDNHIGISI AGLTADARLL CNFMRQECLD SRFVFDRPLP VSRLVSLIGS 130 140 150 160 170 180 KTQIPTQRYG RRPYGVGLLI AGYDDMGPHI FQTCPSANYF DCRAMSIGAR SQSARTYLER 190 200 210 220 230 240 HMSEFMECNL NELVKHGLRA LRETLPAEQD LTTKNVSIGI VGKDLEFTIY DDDDVSPFLE 250 260 GLEERPQRKA QPAQPADEPA EKADEPMEH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The primary structures of four subunits of the human, high-molecular-weight proteinase, macropain (proteasome), are distinct but homologous." DeMartino G.N., Orth K., McCullough M.L., Lee L.W., Munn T.Z., Moomaw C.R., Dawson P.A., Slaughter C.A. Biochim. Biophys. Acta 1079:29-38(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
[2]	"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 SHORT).
[3]	"Two mRNAs exist for the Hs PROS-30 gene encoding a component of human prosomes." Silva-Pereira I., Bey F., Coux O., Scherrer K. Gene 120:235-242(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
[4]	"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 (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-37.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT).
[6]	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].
[7]	"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] (ISOFORM SHORT), VARIANT VAL-37. Tissue: Bone marrow, Brain, Ovary, Placenta and Prostate.
[8]	Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 4-18; 63-82; 97-107 AND 244-256, MASS SPECTROMETRY. Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[9]	"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 63-82.
[10]	"Comparative proteome analysis of breast cancer and adjacent normal breast tissues in human." Deng S., Xing T., Zhou H., Xiong R., Lu Y., Wen B., Liu S., Yang J. Genomics Proteomics Bioinformatics 4:165-172(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION, MASS SPECTROMETRY.
[11]	"The up-regulation of proteasome subunits and lysosomal proteases in hepatocellular carcinomas of the HBx gene knockin transgenic mice." Cui F., Wang Y., Wang J., Wei K., Hu J., Liu F., Wang H., Zhao X., Zhang X., Yang X. Proteomics 6:498-504(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[12]	"Conserved signal peptide of Notch3 inhibits interaction with proteasome." Zhang Y., Jia L., Lee S.J., Wang M.M. Biochem. Biophys. Res. Commun. 355:245-251(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NOTCH3.
[13]	"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Embryonic kidney.
[14]	"Over-expression of genes and proteins of ubiquitin specific peptidases (USPs) and proteasome subunits (PSs) in breast cancer tissue observed by the methods of RFDD-PCR and proteomics." Deng S., Zhou H., Xiong R., Lu Y., Yan D., Xing T., Dong L., Tang E., Yang H. Breast Cancer Res. Treat. 104:21-30(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION, MASS SPECTROMETRY.
[15]	"Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry." Meierhofer D., Wang X., Huang L., Kaiser P. J. Proteome Res. 7:4566-4576(2008) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-115 AND LYS-208, MASS SPECTROMETRY.
[16]	"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-14, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[17]	"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-14, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[18]	"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	X61969 mRNA. Translation: CAA43961.1. D00759 mRNA. Translation: BAA00656.1. M64992 mRNA. Translation: AAA92734.1. BT006647 mRNA. Translation: AAP35293.1. AK290765 mRNA. Translation: BAF83454.1. CH471064 Genomic DNA. Translation: EAW68479.1. BC002577 mRNA. Translation: AAH02577.1. BC005932 mRNA. Translation: AAH05932.1. BC008472 mRNA. Translation: AAH08472.1. BC009576 mRNA. Translation: AAH09576.1. BC015105 mRNA. Translation: AAH15105.1. BC015356 mRNA. Translation: AAH15356.1. BC022372 mRNA. Translation: AAH22372.1.
IPI	IPI00016832. IPI00472442.
PIR	JC1445.
RefSeq	NP_002777.1. NM_002786.3. NP_683877.1. NM_148976.2.
UniGene	Hs.102798.
3D structure databases
ProteinModelPortal	P25786.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29369N.
IntAct	P25786. 50 interactions.
MINT	MINT-1155600.
STRING	9606.ENSP00000315309.
Protein family/group databases
MEROPS	T01.976.
PTM databases
PhosphoSite	P25786.
Polymorphism databases
DMDM	130848.
2D gel databases
OGP	P25786.
REPRODUCTION-2DPAGE	IPI00016832.
Proteomic databases
PaxDb	P25786.
PRIDE	P25786.
Protocols and materials databases
DNASU	5682.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000396393; ENSP00000379675; ENSG00000129084. ENST00000396394; ENSP00000379676; ENSG00000129084. ENST00000418988; ENSP00000414359; ENSG00000129084.
GeneID	5682.
KEGG	hsa:5682.
UCSC	uc001mlk.3. human. uc001mll.3. human.
Organism-specific databases
CTD	5682.
GeneCards	GC11M014526.
HGNC	HGNC:9530. PSMA1.
HPA	HPA037646.
MIM	602854. gene.
neXtProt	NX_P25786.
PharmGKB	PA33875.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0638.
HOGENOM	HOG000091080.
HOVERGEN	HBG105373.
KO	K02725.
OMA	RTYLERC.
OrthoDB	EOG4S1T7S.
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	P25786.
Bgee	P25786.
CleanEx	HS_PSMA1.
Genevestigator	P25786.
GermOnline	ENSG00000129084. Homo sapiens.
Family and domain databases
InterPro	IPR000426. Proteasome_asu_N. 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	PSMA1. human.
GenomeRNAi	5682.
NextBio	22062.
SOURCE	Search...

Entry information

Entry name

PSA1_HUMAN

Accession

Primary (citable) accession number: P25786
Secondary accession number(s): A8K400, Q53YE8, Q9BRV9

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1992
Last sequence update:	May 1, 1992
Last modified:	May 1, 2013
This is version 155 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.