P17980 (PRS6A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
26S protease regulatory subunit 6A

Alternative name(s):
26S proteasome AAA-ATPase subunit RPT5
Proteasome 26S subunit ATPase 3
Proteasome subunit P50
Tat-binding protein 1
Short name=TBP-1

Gene names

Name:	PSMC3
Synonyms:	TBP1

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	439 AA.
Sequence status	Complete.
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 By similarity. In case of HIV-1 infection, suppresses Tat-mediated transactivation.
Subunit structure	May form a heterodimer with a related family member. Interacts with PAAF1. Interacts with HIV-1 Tat. Ref.6 Ref.10
Subcellular location	Cytoplasm Potential. Nucleus Potential. Cytoplasm › P-body By similarity. Note: Co-localizes with TRIM5 in the cytoplasmic bodies By similarity.
Post-translational modification	Sumoylated by UBE2I in response to MEKK1-mediated stimuli. Ref.12
Sequence similarities	Belongs to the AAA ATPase family.
Sequence caution	The sequence AAI07805.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Host-virus interaction
Cellular component	Cytoplasm Nucleus Proteasome
Ligand	ATP-binding Nucleotide-binding
PTM	Acetylation 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 blastocyst development Inferred from electronic annotation. Source: Compara 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 perinuclear region of cytoplasm Inferred from electronic annotation. Source: Compara proteasome accessory complex Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW nucleoside-triphosphatase activity Inferred from electronic annotation. Source: InterPro transcription coactivator activity Traceable author statement Ref.1. Source: ProtInc transcription corepressor activity Traceable author statement Ref.6. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PSMC6	P62333	5	EBI-359720,EBI-357669
PSMD9	O00233	4	EBI-359720,EBI-750973

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 439	439	26S protease regulatory subunit 6A		PRO_0000084698
Regions
	Nucleotide binding	227 – 234	8	ATP Potential
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine Ref.13 Ref.15
	Modified residue	9	1	Phosphoserine Ref.11 Ref.13 Ref.15
Experimental info
	Mutagenesis	233	1	K → H: Loss of function.
	Mutagenesis	289	1	D → A: Loss of function.
	Sequence conflict	356	1	M → T in BAD96205. Ref.5
	Sequence conflict	409	1	R → A in AAA36666. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	P17980 [UniParc]. Last modified May 10, 2002. Version 3. Checksum: 0E443465DDDEBB0B	FASTA	439	49,204
	10 20 30 40 50 60 MNLLPNIESP VTRQEKMATV WDEAEQDGIG EEVLKMSTEE IIQRTRLLDS EIKIMKSEVL 70 80 90 100 110 120 RVTHELQAMK DKIKENSEKI KVNKTLPYLV SNVIELLDVD PNDQEEDGAN IDLDSQRKGK 130 140 150 160 170 180 CAVIKTSTRQ TYFLPVIGLV DAEKLKPGDL VGVNKDSYLI LETLPTEYDS RVKAMEVDER 190 200 210 220 230 240 PTEQYSDIGG LDKQIQELVE AIVLPMNHKE KFENLGIQPP KGVLMYGPPG TGKTLLARAC 250 260 270 280 290 300 AAQTKATFLK LAGPQLVQMF IGDGAKLVRD AFALAKEKAP SIIFIDELDA IGTKRFDSEK 310 320 330 340 350 360 AGDREVQRTM LELLNQLDGF QPNTQVKVIA ATNRVDILDP ALLRSGRLDR KIEFPMPNEE 370 380 390 400 410 420 ARARIMQIHS RKMNVSPDVN YEELARCTDD FNGAQCKAVC VEAGMIALRR GATELTHEDY 430 MEGILEVQAK KKANLQYYA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The type 1 human immunodeficiency virus Tat binding protein is a transcriptional activator belonging to an additional family of evolutionarily conserved genes." Ohana B., Moore P.A., Ruben S.M., Southgate C.D., Green M.R., Rosen C.A. Proc. Natl. Acad. Sci. U.S.A. 90:138-142(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"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].
[3]	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].
[4]	"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]. Tissue: Kidney, Lung and Peripheral nerve.
[5]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 16-439. Tissue: Adipose tissue.
[6]	"A cDNA for a protein that interacts with the human immunodeficiency virus Tat transactivator." Nelbock P., Dillion P.J., Perkins A., Rosen C.A. Science 248:1650-1653(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 36-439, INTERACTION WITH HIV-1 TAT.
[7]	"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] OF 36-439.
[8]	Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 130-144; 156-171; 174-233; 251-266; 277-294; 309-327; 335-344; 351-362; 372-386 AND 398-409, MASS SPECTROMETRY. Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[9]	"Identification, purification, and characterization of a PA700-dependent activator of the proteasome." Demartino G.N., Proske R.J., Moomaw C.R., Strong A.A., Song X., Hisamatsu H., Tanaka K., Slaughter C.A. J. Biol. Chem. 271:3112-3118(1996) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE.
[10]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PAAF1.
[11]	"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-9, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[12]	"Ubc9 fusion-directed SUMOylation identifies constitutive and inducible SUMOylation." Jakobs A., Himstedt F., Funk M., Korn B., Gaestel M., Niedenthal R. Nucleic Acids Res. 35:E109-E109(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION.
[13]	"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: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"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].
[15]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK313518 mRNA. Translation: BAG36298.1. CH471064 Genomic DNA. Translation: EAW67916.1. BC008713 mRNA. Translation: AAH08713.4. BC073165 mRNA. Translation: AAH73165.3. BC106920 mRNA. Translation: AAI06921.1. BC107804 mRNA. Translation: AAI07805.1. Different initiation. AK222485 mRNA. Translation: BAD96205.1. M34079 mRNA. Translation: AAA36666.1. CR456731 mRNA. Translation: CAG33012.1.
IPI	IPI00018398.
PIR	A34832.
RefSeq	NP_002795.2. NM_002804.4.
UniGene	Hs.250758.
3D structure databases
ProteinModelPortal	P17980.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-27555N.
IntAct	P17980. 18 interactions.
MINT	MINT-1149785.
STRING	9606.ENSP00000298852.
PTM databases
PhosphoSite	P17980.
Polymorphism databases
DMDM	20532406.
2D gel databases
REPRODUCTION-2DPAGE	IPI00018398.
Proteomic databases
PaxDb	P17980.
PeptideAtlas	P17980.
PRIDE	P17980.
Protocols and materials databases
DNASU	5702.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000298852; ENSP00000298852; ENSG00000165916.
GeneID	5702.
KEGG	hsa:5702.
UCSC	uc001nfh.2. human.
Organism-specific databases
CTD	5702.
GeneCards	GC11M047440.
HGNC	HGNC:9549. PSMC3.
HPA	HPA006065.
MIM	186852. gene.
neXtProt	NX_P17980.
PharmGKB	PA33894.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1222.
HOVERGEN	HBG000109.
InParanoid	P17980.
KO	K03065.
OMA	GALMYGP.
OrthoDB	EOG46143Z.
PhylomeDB	P17980.
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	P17980.
Bgee	P17980.
CleanEx	HS_PSMC3.
Genevestigator	P17980.
GermOnline	ENSG00000165916. Homo sapiens.
Family and domain databases
InterPro	IPR005937. 26S_Psome_P45. IPR003593. AAA+_ATPase. IPR003959. ATPase_AAA_core. IPR003960. ATPase_AAA_CS. [Graphical view]
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
ChiTaRS	PSMC3. human.
GenomeRNAi	5702.
NextBio	22154.
PMAP-CutDB	P17980.
SOURCE	Search...

Entry information

Entry name

PRS6A_HUMAN

Accession

Primary (citable) accession number: P17980
Secondary accession number(s): B2R8V1 , Q3B757, Q3B865, Q53HU5, Q6GPG8, Q6IBS1, Q96HD3

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	May 10, 2002
Last modified:	May 1, 2013
This is version 145 of the entry and version 3 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.