P62195 (PRS8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
26S protease regulatory subunit 8

Alternative name(s):
26S proteasome AAA-ATPase subunit RPT6
Proteasome 26S subunit ATPase 5
Proteasome subunit p45
Thyroid hormone receptor-interacting protein 1
Short name=TRIP1
p45/SUG

Gene names

Name:	PSMC5
Synonyms:	SUG1

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	406 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, in vitro, with the thyroid hormone receptor (in a thyroid hormone T3-dependent manner) and with retinoid X receptor (RXR) By similarity. Interacts with NDC80. Interacts with PAAF1. Interacts with TRIM5. Ref.7 Ref.8 Ref.9 Ref.13
Subcellular location	Cytoplasm Potential. Nucleus Potential.
Sequence similarities	Belongs to the AAA ATPase family.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus Proteasome
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
PTM	Acetylation
Technical term	3D-structure Complete proteome 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 mRNA metabolic process Traceable author statement. Source: Reactome negative regulation of programmed cell death Non-traceable author statement PubMed 16432160. Source: UniProtKB negative regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: Compara negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle Traceable author statement. Source: Reactome positive regulation of transcription, DNA-dependent Non-traceable author statement PubMed 7870181. Source: UniProtKB 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 transcription from RNA polymerase II promoter Traceable author statement PubMed 7870181. Source: ProtInc viral reproduction Traceable author statement. Source: Reactome
Cellular_component	cytoplasmic vesicle Inferred from direct assay PubMed 15885686. Source: UniProtKB cytosol Traceable author statement. Source: Reactome nuclear proteasome complex Inferred from electronic annotation. Source: Compara nucleoplasm Traceable author statement. Source: Reactome proteasome accessory complex Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATPase activity Traceable author statement PubMed 9464850. Source: UniProtKB transcription cofactor activity Traceable author statement PubMed 7870181. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Camk2a	P11275	4	EBI-357745,EBI-2640645	From a different organism.
Camk2b	P08413	3	EBI-357745,EBI-916155	From a different organism.
ERCC3	P19447	4	EBI-357745,EBI-1183307
PAAF1	Q9BRP4	2	EBI-357745,EBI-1056358
PSMC4	P43686	11	EBI-357745,EBI-743997

Alternative products

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

Isoform 1 (identifier: P62195-1)

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: P62195-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-8: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 406

405

26S protease regulatory subunit 8

PRO_0000084721

Regions

Nucleotide binding

190 – 197

8

ATP Potential

Amino acid modifications

Modified residue

2

1

N-acetylalanine By similarity

Modified residue

222

1

N6-acetyllysine Ref.11

Natural variations

Alternative sequence

1 – 8

8

Missing in isoform 2.

VSP_045441

Natural variant

60

1

R → Q in a colorectal cancer sample; somatic mutation. Ref.15

VAR_035901

Natural variant

258

1

R → W.
Corresponds to variant rs11543211 [ dbSNP | Ensembl ].

VAR_048119

Experimental info

Sequence conflict

61

1

E → R in BAA07919. Ref.1

Sequence conflict

127 – 128

2

LP → ML in AAB88187. Ref.6

Sequence conflict

266

1

D → S in AAC41735. Ref.2

Sequence conflict

272

1

T → Q in AAC41735. Ref.2

Sequence conflict

300

1

I → M in AAC41735. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

406

Helix Strand Turn

Details...

Helix

322 – 333

12

Beta strand

336 – 338

3

Helix

344 – 349

6

Helix

356 – 372

17

Beta strand

376 – 378

3

Helix

380 – 391

12

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 21, 2004. Version 1. Checksum: 29C6410C4A85A7F7	FASTA	406	45,626
	10 20 30 40 50 60 MALDGPEQME LEEGKAGSGL RQYYLSKIEE LQLIVNDKSQ NLRRLQAQRN ELNAKVRLLR 70 80 90 100 110 120 EELQLLQEQG SYVGEVVRAM DKKKVLVKVH PEGKFVVDVD KNIDINDVTP NCRVALRNDS 130 140 150 160 170 180 YTLHKILPNK VDPLVSLMMV EKVPDSTYEM IGGLDKQIKE IKEVIELPVK HPELFEALGI 190 200 210 220 230 240 AQPKGVLLYG PPGTGKTLLA RAVAHHTDCT FIRVSGSELV QKFIGEGARM VRELFVMARE 250 260 270 280 290 300 HAPSIIFMDE IDSIGSSRLE GGSGGDSEVQ RTMLELLNQL DGFEATKNIK VIMATNRIDI 310 320 330 340 350 360 LDSALLRPGR IDRKIEFPPP NEEARLDILK IHSRKMNLTR GINLRKIAEL MPGASGAEVK 370 380 390 400 GVCTEAGMYA LRERRVHVTQ EDFEMAVAKV MQKDSEKNMS IKKLWK
	Isoform 2 [UniParc]. Checksum: 450BB51DA8C9381D	FASTA	398	44,784
	10 20 30 40 50 60 MELEEGKAGS GLRQYYLSKI EELQLIVNDK SQNLRRLQAQ RNELNAKVRL LREELQLLQE 70 80 90 100 110 120 QGSYVGEVVR AMDKKKVLVK VHPEGKFVVD VDKNIDINDV TPNCRVALRN DSYTLHKILP 130 140 150 160 170 180 NKVDPLVSLM MVEKVPDSTY EMIGGLDKQI KEIKEVIELP VKHPELFEAL GIAQPKGVLL 190 200 210 220 230 240 YGPPGTGKTL LARAVAHHTD CTFIRVSGSE LVQKFIGEGA RMVRELFVMA REHAPSIIFM 250 260 270 280 290 300 DEIDSIGSSR LEGGSGGDSE VQRTMLELLN QLDGFEATKN IKVIMATNRI DILDSALLRP 310 320 330 340 350 360 GRIDRKIEFP PPNEEARLDI LKIHSRKMNL TRGINLRKIA ELMPGASGAE VKGVCTEAGM 370 380 390 YALRERRVHV TQEDFEMAVA KVMQKDSEKN MSIKKLWK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning of a new putative ATPase subunit p45 of the human 26S proteasome, a homolog of yeast transcriptional factor Sug1p." Akiyama K., Yokota K., Kagawa S., Shimbara N., Demartino G.N., Slaughter C.A., Noda C., Tanaka K. FEBS Lett. 363:151-156(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Hepatoma.
[2]	"Two classes of proteins dependent on either the presence or absence of thyroid hormone for interaction with the thyroid hormone receptor." Lee J.W., Choi H.-S., Gyuris J., Brent R., Moore D.D. Mol. Endocrinol. 9:243-254(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"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] (ISOFORMS 1 AND 2). Tissue: Skeletal muscle.
[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] (ISOFORM 1). Tissue: Lung carcinoma.
[6]	"Large-scale concatenation cDNA sequencing." Yu W., Andersson B., Worley K.C., Muzny D.M., Ding Y., Liu W., Ricafrente J.Y., Wentland M.A., Lennon G., Gibbs R.A. Genome Res. 7:353-358(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 127-406. Tissue: Brain.
[7]	"HEC binds to the seventh regulatory subunit of the 26 S proteasome and modulates the proteolysis of mitotic cyclins." Chen Y., Sharp Z.D., Lee W.-H. J. Biol. Chem. 272:24081-24087(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NDC80.
[8]	"Hec1p, an evolutionarily conserved coiled-coil protein, modulates chromosome segregation through interaction with SMC proteins." Zheng L., Chen Y., Lee W.-H. Mol. Cell. Biol. 19:5417-5428(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NDC80.
[9]	"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.
[10]	"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.
[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-222, 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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"TRIM5alpha associates with proteasomal subunits in cells while in complex with HIV-1 virions." Lukic Z., Hausmann S., Sebastian S., Rucci J., Sastri J., Robia S.L., Luban J., Campbell E.M. Retrovirology 8:93-93(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TRIM5.
[14]	"Crystal structure of a domain of 26s proteasome regulatory subunit 8 from Homo sapiens. Northeast structural genomics consortium target ID HR3102A." Northeast structural genomics consortium (NESG) Submitted (JAN-2010) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 318-395, STRUCTURE BY NMR OF 320-395.
[15]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] GLN-60.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D44467 mRNA. Translation: BAA07919.1.
L38810 mRNA. Translation: AAC41735.1.
AK290758 mRNA. Translation: BAF83447.1.
AK291878 mRNA. Translation: BAF84567.1.
AC015651 Genomic DNA. No translation available.
CH471109 Genomic DNA. Translation: EAW94270.1.
CH471109 Genomic DNA. Translation: EAW94271.1.
CH471109 Genomic DNA. Translation: EAW94272.1.
BC001932 mRNA. Translation: AAH01932.1.
BC002367 mRNA. Translation: AAH02367.3.
AF035309 mRNA. Translation: AAB88187.1.

IPI

IPI00023919.

PIR

S60343.
S65536.

RefSeq

NP_001186092.1. NM_001199163.1.
NP_002796.4. NM_002805.5.

UniGene

Hs.79387.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2KRK	NMR	-	A	320-395	[»]
3KW6	X-ray	2.10	A	318-395	[»]

ProteinModelPortal

P62195.

ModBase

Search...

Protein-protein interaction databases

IntAct

P62195. 32 interactions.

MINT

MINT-5004394.

STRING

9606.ENSP00000310572.

PTM databases

PhosphoSite

P62195.

Polymorphism databases

DMDM

49065819.

Proteomic databases

PaxDb

P62195.

PRIDE

P62195.

Protocols and materials databases

DNASU

5705.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000310144; ENSP00000310572; ENSG00000087191.
ENST00000375812; ENSP00000364970; ENSG00000087191.
ENST00000580864; ENSP00000462495; ENSG00000087191.
ENST00000581882; ENSP00000463938; ENSG00000087191.

GeneID

5705.

KEGG

hsa:5705.

UCSC

uc002jcb.3. human.

Organism-specific databases

CTD

5705.

GeneCards

GC17P061904.

HGNC

HGNC:9552. PSMC5.

HPA

HPA017871.

MIM

601681. gene.

neXtProt

NX_P62195.

PharmGKB

PA33897.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1222.

HOVERGEN

HBG000109.

InParanoid

P62195.

KO

K03066.

OMA

QNIKVIM.

OrthoDB

EOG4MKNGF.

PhylomeDB

P62195.

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

P62195.

Bgee

P62195.

CleanEx

HS_PSMC5.

Genevestigator

P62195.

GermOnline

ENSG00000087191. 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

PSMC5. human.

EvolutionaryTrace

P62195.

GenomeRNAi

5705.

NextBio

22166.

SOURCE

Search...

Entry information

Entry name

PRS8_HUMAN

Accession

Primary (citable) accession number: P62195
Secondary accession number(s): A8K3Z3 , A8K763, O35051, O43208, P47210, P52915, P52916

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 21, 2004
Last sequence update:	June 21, 2004
Last modified:	May 1, 2013
This is version 99 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.