Reviewed, UniProtKB/Swiss-Prot P25786 (PSA1_HUMAN)

Names and origin

Protein names

Recommended name:
    Proteasome subunit alpha type-1
    EC=3.4.25.1
Alternative name(s):
    Proteasome component C2
    Macropain subunit C2
    Multicatalytic endopeptidase complex subunit C2
    Proteasome nu chain
    30 kDa prosomal protein
    PROS-30

Gene names

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

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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.
Subcellular location	Cytoplasm. Nucleus.
Induction	Induced in breast cancer tissue (at protein level). Up-regulated in liver tumor tissues.
Sequence similarities	Belongs to the peptidase T1A family.

Ontologies

Keywords
Biological process	Immune response
Cellular component	Cytoplasm Nucleus Proteasome
Coding sequence diversity	Alternative splicing
Molecular function	Hydrolase Protease Threonine protease
PTM	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process Inferred from Experiment. Source: Reactome negative regulation of ubiquitin-protein ligase activity during mitotic cell cycle Inferred from Experiment. Source: Reactome positive regulation of ubiquitin-protein ligase activity during mitotic cell cycle Inferred from Experiment. Source: Reactome
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Traceable author statement. Source: ProtInc polysome Traceable author statement. Source: ProtInc proteasome core complex, alpha-subunit complex Inferred from electronic annotation. Source: InterPro
Molecular function	RNA binding Traceable author statement. Source: ProtInc protein binding Ref.11 Inferred from physical interaction. Source: UniProtKB threonine-type endopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PSMA4	P25789	1	EBI-359352,EBI-359310
PSMA7	O14818	3	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 Ref.12
	Modified residue	14	1	Phosphoserine Ref.15
	Cross-link	115		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.14
	Cross-link	208		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.14
Natural variations
	Alternative sequence	1	1	M → MQLSKVK in isoform Long.		VSP_005279
Experimental info
	Sequence conflict	14 – 15	2	SP → TA in AAA92734. Ref.3
	Sequence conflict	37	1	G → V in AAH05932. Ref.6

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. 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: 1888762] [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: 2025653] [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: 1398136] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
[4]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT).
[5]	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].
[6]	"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] (ISOFORM SHORT). Tissue: Bone marrow, Brain, Ovary, Placenta and Prostate.
[7]	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.
[8]	"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: 7811265] [Abstract] Cited for: PROTEIN SEQUENCE OF 63-82.
[9]	"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: 17127214] [Abstract] Cited for: INDUCTION, MASS SPECTROMETRY.
[10]	"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: 16317774] [Abstract] Cited for: INDUCTION.
[11]	"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: 17292860] [Abstract] Cited for: INTERACTION WITH NOTCH3.
[12]	"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: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, MASS SPECTROMETRY.
[13]	"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: 17004105] [Abstract] Cited for: INDUCTION, MASS SPECTROMETRY.
[14]	"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: 18781797] [Abstract] Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-115 AND LYS-208, MASS SPECTROMETRY.
[15]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14, MASS SPECTROMETRY.
[16]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	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. 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. NP_683877.1.
UniGene	Hs.102798 Hs.445711
3D structure databases
SMR	P25786. Positions 4-241.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29369N.
IntAct	P25786. 53 interactions.
STRING	P25786.
Protein family/group databases
MEROPS	T01.976.
PTM databases
PhosphoSite	P25786.
2-D gel databases
Aarhus/Ghent-2DPAGE	2223. IEF.
OGP	P25786.
REPRODUCTION-2DPAGE	IPI00016832.
Proteomic databases
PRIDE	P25786.
Genome annotation databases
Ensembl	ENST00000249924; ENSP00000249924; ENSG00000129084; Homo sapiens. [Genome view] ENST00000396393; ENSP00000379675; ENSG00000129084; Homo sapiens. [Genome view]
GeneID	5682.
UCSC	uc001mlk.1. human. uc001mll.1. human.
Organism-specific databases
CTD	5682.
GeneCards	GC11M014482.
H-InvDB	HIX0009467.
HGNC	HGNC:9530. PSMA1.
MIM	602854. gene.
PharmGKB	PA33875.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG15820.
HOVERGEN	P25786.
OMA	IVGKDME.
OrthoDB	EOG941SXB.
PhylomeDB	P25786.
Enzyme and pathway databases
BRENDA	3.4.25.1. 247.
Reactome	REACT_11045. Signaling by Wnt. REACT_13. Metabolism of amino acids. REACT_13635. Regulation of activated PAK-2p34 by proteasome mediated degradation. 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_9035. APC/C:Cdh1-mediated degradation of Skp2.
Gene expression databases
ArrayExpress	P25786.
Bgee	P25786.
CleanEx	HS_PSMA1.
Genevestigator	P25786.
GermOnline	ENSG00000129084. Homo sapiens.
Family and domain databases
InterPro	IPR000426. Proteasome_asu_CS. IPR001353. Proteasome_sua/b. [Graphical view]
Pfam	PF00227. Proteasome. 1 hit. PF10584. 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 Resources
NextBio	22062.
SOURCE	Search...

Entry information

Entry name

PSA1_HUMAN

Accession

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

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1992
Last sequence update:	May 1, 1992
Last modified:	February 9, 2010
This is version 120 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.