Q13200 (PSMD2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
26S proteasome non-ATPase regulatory subunit 2

Alternative name(s):
26S proteasome regulatory subunit RPN1
26S proteasome regulatory subunit S2
26S proteasome subunit p97
Protein 55.11
Tumor necrosis factor type 1 receptor-associated protein 2

Gene names

Name:	PSMD2
Synonyms:	TRAP2

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	908 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Acts as a regulatory subunit of the 26 proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins. Binds to the intracellular domain of tumor necrosis factor type 1 receptor. The binding domain of TRAP1 and TRAP2 resides outside the death domain of TNFR1.
Tissue specificity	Found in skeletal muscle, liver, heart, brain, kidney, pancreas, lung and placenta.
Sequence similarities	Belongs to the proteasome subunit S2 family. Contains 7 PC repeats.
Sequence caution	The sequence AAA87705.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Proteasome
Coding sequence diversity	Polymorphism
Domain	Repeat
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 regulation of protein catabolic process Inferred from electronic annotation. Source: InterPro small molecule metabolic process Traceable author statement. Source: Reactome viral reproduction Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome proteasome regulatory particle Traceable author statement Ref.1. Source: ProtInc
Molecular_function	enzyme regulator activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PSMC1	P62191	6	EBI-357648,EBI-357598

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 908	908	26S proteasome non-ATPase regulatory subunit 2		PRO_0000173810
Regions
	Repeat	409 – 442	34	PC 1
	Repeat	443 – 479	37	PC 2
	Repeat	480 – 514	35	PC 3
	Repeat	517 – 551	35	PC 4
	Repeat	560 – 589	30	PC 5
	Repeat	692 – 723	32	PC 6
	Repeat	742 – 757	16	PC 7
	Compositional bias	623 – 641	19	Glu/Lys-rich
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine By similarity
	Modified residue	16	1	Phosphoserine Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.14
	Modified residue	24	1	Phosphothreonine Ref.7 Ref.12
	Modified residue	29	1	Phosphoserine Ref.7
	Modified residue	194	1	Phosphotyrosine Ref.7
	Modified residue	361	1	Phosphoserine Ref.11 Ref.12 Ref.14
Natural variations
	Natural variant	176	1	A → T. Corresponds to variant rs11545172 [ dbSNP | Ensembl ].		VAR_051554
	Natural variant	313	1	E → D. Corresponds to variant rs11545169 [ dbSNP | Ensembl ].		VAR_051555
	Natural variant	724	1	N → Y. Ref.2 Ref.3 Corresponds to variant rs17856236 [ dbSNP | Ensembl ].		VAR_067451
Experimental info
	Sequence conflict	10	1	P → R in CAA60167. Ref.5
	Sequence conflict	21	1	P → S Ref.4
	Sequence conflict	32	1	E → G Ref.4
	Sequence conflict	43	1	Q → L Ref.4
	Sequence conflict	57	1	E → V Ref.4
	Sequence conflict	60	1	V → A in BAA11226. Ref.1
	Sequence conflict	226	1	Y → S in AAA87705. Ref.4
	Sequence conflict	260	1	S → T in CAA60167. Ref.5
	Sequence conflict	281 – 283	3	IFT → SS in AAA87705. Ref.4
	Sequence conflict	415	1	G → A in BAA11226. Ref.1
	Sequence conflict	731	1	M → MGM Ref.4
	Sequence conflict	900 – 908	9	LRKNPNYDL → FGRTPIMISK Ref.3
	Sequence conflict	900 – 908	9	LRKNPNYDL → FGRTPIMISK Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Q13200 [UniParc]. Last modified July 15, 1999. Version 3. Checksum: FAD71E7B26101BE3	FASTA	908	100,200
	10 20 30 40 50 60 MEEGGRDKAP VQPQQSPAAA PGGTDEKPSG KERRDAGDKD KEQELSEEDK QLQDELEMLV 70 80 90 100 110 120 ERLGEKDTSL YRPALEELRR QIRSSTTSMT SVPKPLKFLR PHYGKLKEIY ENMAPGENKR 130 140 150 160 170 180 FAADIISVLA MTMSGERECL KYRLVGSQEE LASWGHEYVR HLAGEVAKEW QELDDAEKVQ 190 200 210 220 230 240 REPLLTLVKE IVPYNMAHNA EHEACDLLME IEQVDMLEKD IDENAYAKVC LYLTSCVNYV 250 260 270 280 290 300 PEPENSALLR CALGVFRKFS RFPEALRLAL MLNDMELVED IFTSCKDVVV QKQMAFMLGR 310 320 330 340 350 360 HGVFLELSED VEEYEDLTEI MSNVQLNSNF LALARELDIM EPKVPDDIYK THLENNRFGG 370 380 390 400 410 420 SGSQVDSARM NLASSFVNGF VNAAFGQDKL LTDDGNKWLY KNKDHGMLSA AASLGMILLW 430 440 450 460 470 480 DVDGGLTQID KYLYSSEDYI KSGALLACGI VNSGVRNECD PALALLSDYV LHNSNTMRLG 490 500 510 520 530 540 SIFGLGLAYA GSNREDVLTL LLPVMGDSKS SMEVAGVTAL ACGMIAVGSC NGDVTSTILQ 550 560 570 580 590 600 TIMEKSETEL KDTYARWLPL GLGLNHLGKG EAIEAILAAL EVVSEPFRSF ANTLVDVCAY 610 620 630 640 650 660 AGSGNVLKVQ QLLHICSEHF DSKEKEEDKD KKEKKDKDKK EAPADMGAHQ GVAVLGIALI 670 680 690 700 710 720 AMGEEIGAEM ALRTFGHLLR YGEPTLRRAV PLALALISVS NPRLNILDTL SKFSHDADPE 730 740 750 760 770 780 VSYNSIFAMG MVGSGTNNAR LAAMLRQLAQ YHAKDPNNLF MVRLAQGLTH LGKGTLTLCP 790 800 810 820 830 840 YHSDRQLMSQ VAVAGLLTVL VSFLDVRNII LGKSHYVLYG LVAAMQPRML VTFDEELRPL 850 860 870 880 890 900 PVSVRVGQAV DVVGQAGKPK TITGFQTHTT PVLLAHGERA ELATEEFLPV TPILEGFVIL RKNPNYDL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning and functional analysis of the p97 subunit of the 26S proteasome, a polypeptide identical to the type-1 tumor-necrosis-factor-receptor-associated protein-2/55.11." Tsurumi C., Shimizu Y., Saeki M., Kato S., DeMartino G.N., Slaughter C.A., Fujimuro M., Yokosawa H., Yamasaki M., Hendil K.B., Toh-e A., Tanahashi N., Tanaka K. Eur. J. Biochem. 239:912-921(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 49-66; 81-85; 91-117; 138-145; 148-158; 182-193; 209-229; 438-441 AND 471-481. Tissue: Fibrosarcoma.
[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], VARIANT TYR-724.
[3]	"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], VARIANT TYR-724. Tissue: Lung, Muscle and Skin.
[4]	"Two-hybrid cloning of a gene encoding TNF receptor-associated protein 2, a protein that interacts with the intracellular domain of the type 1 TNF receptor: identity with subunit 2 of the 26S protease." Dunbar J.D., Song H.Y., Guo D., Wu L.-W., Donner D.B. J. Immunol. 158:4252-4259(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 21-908.
[5]	"A protein related to a proteasomal subunit binds to the intracellular domain of the p55 TNF receptor upstream to its 'death domain'." Boldin M.P., Mett I.L., Wallach D. FEBS Lett. 367:39-44(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 10-908. Tissue: Liver.
[6]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[7]	"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-16; THR-24; SER-29 AND TYR-194, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[8]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[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-16, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16 AND SER-361, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[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-16; THR-24 AND SER-361, 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].
[14]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16 AND SER-361, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D78151 mRNA. Translation: BAA11226.1. BT009736 mRNA. Translation: AAP88738.1. BC002368 mRNA. Translation: AAH02368.1. BC002997 mRNA. Translation: AAH02997.1. BC007897 mRNA. Translation: AAH07897.1. U12596 mRNA. Translation: AAA87705.1. Different initiation. X86446 mRNA. Translation: CAA60167.1.
IPI	IPI00012268.
RefSeq	NP_002799.3. NM_002808.3.
UniGene	Hs.518464.
3D structure databases
ProteinModelPortal	Q13200.
SMR	Q13200. Positions 671-734.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q13200. 24 interactions.
MINT	MINT-1142723.
STRING	9606.ENSP00000310129.
PTM databases
PhosphoSite	Q13200.
Polymorphism databases
DMDM	6174930.
Proteomic databases
PaxDb	Q13200.
PeptideAtlas	Q13200.
PRIDE	Q13200.
Protocols and materials databases
DNASU	5708.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000310118; ENSP00000310129; ENSG00000175166.
GeneID	5708.
KEGG	hsa:5708.
UCSC	uc003fnn.1. human.
Organism-specific databases
CTD	5708.
GeneCards	GC03P184016.
HGNC	HGNC:9559. PSMD2.
HPA	HPA045192.
MIM	606223. gene.
neXtProt	NX_Q13200.
PharmGKB	PA33905.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5110.
HOVERGEN	HBG001842.
InParanoid	Q13200.
KO	K03028.
OMA	IAQGLTH.
OrthoDB	EOG483D3X.
PhylomeDB	Q13200.
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	Q13200.
Bgee	Q13200.
CleanEx	HS_PSMD2.
Genevestigator	Q13200.
GermOnline	ENSG00000175166. Homo sapiens.
Family and domain databases
InterPro	IPR016643. 26S_Psome_Rpn1. IPR002015. APC_proteasome. IPR016024. ARM-type_fold. [Graphical view]
PANTHER	PTHR10943:SF1. PTHR10943:SF1. 1 hit.
Pfam	PF01851. PC_rep. 2 hits. [Graphical view]
PIRSF	PIRSF015965. 26S_Psome_Rpn1. 1 hit.
SUPFAM	SSF48371. ARM-type_fold. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	PSMD2. human.
DrugBank	DB00188. Bortezomib.
GenomeRNAi	5708.
NextBio	22178.
SOURCE	Search...

Entry information

Entry name

PSMD2_HUMAN

Accession

Primary (citable) accession number: Q13200
Secondary accession number(s): Q12932 , Q15321, Q53XQ4, Q96I12

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	July 15, 1999
Last modified:	May 1, 2013
This is version 133 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.