O75832 (PSD10_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
26S proteasome non-ATPase regulatory subunit 10

Alternative name(s):
26S proteasome regulatory subunit p28
Gankyrin
p28(GANK)

Gene names

Name:

PSMD10

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	226 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Acts as a chaperone during the assembly of the 26S proteasome, specifically of the PA700/19S regulatory complex (RC). In the initial step of the base subcomplex assembly is part of an intermediate PSMD10:PSMC4:PSMC5:PAAF1 module which probably assembles with a PSMD5:PSMC2:PSMC1:PSMD2 module. Ref.5 Ref.6 Ref.7 Ref.8 Ref.10 Ref.11 Ref.12 Acts as an proto-oncoprotein by being involved in negative regulation of tumor suppressors RB1 and p53/TP53. Overexpression is leading to phosphorylation of RB1 and proteasomal degradation of RB1. Regulates CDK4-mediated phosphorylation of RB1 by competing with CDKN2A for binding with CDK4. Facilitates binding of MDM2 to p53/TP53 and the mono- and polyubiquitination of p53/TP53 by MDM2 suggesting a function in targeting the TP53:MDM2 complex to the 26S proteasome. Involved in p53-independent apoptosis. Involved in regulation of NF-kappa-B by retaining it in the cytoplasm. Binds to the NF-kappa-B component RELA and accelerates its XPO1/CRM1-mediated nuclear export. Ref.5 Ref.6 Ref.7 Ref.8 Ref.10 Ref.11 Ref.12
Subunit structure	Part of transient complex containing PSMD10, PSMC4, PSMC5 and PAAF1 formed during the assembly of the 26S proteasome. Stays associated throughout the assembly of the PA700/19S RC and is released upon association with the 20S core. Interacts with PSMC4. Interacts with RB1. Interacts with CDK4. Interacts with MDM2. Interacts with RELA. Associates with a CDK4:CCND2 serine/threonine kinase complex. Ref.5 Ref.6 Ref.7 Ref.8 Ref.10 Ref.11
Subcellular location	Cytoplasm. Nucleus Ref.10.
Tissue specificity	Overexpressed in hepatocellular carcinomas. Ref.5
Sequence similarities	Contains 7 ANK repeats.
Caution	Was initially identified as a genuine component of the 26S proteasome.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm Nucleus
Domain	ANK repeat Repeat
Molecular function	Chaperone
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 peptide antigen via MHC class I Traceable author statement. Source: Reactome apoptotic process Traceable author statement. Source: Reactome cytoplasmic sequestering of NF-kappaB Inferred from direct assay Ref.10. Source: UniProtKB mRNA metabolic process Traceable author statement. Source: Reactome negative regulation of DNA damage response, signal transduction by p53 class mediator Inferred from direct assay Ref.8. Source: UniProtKB negative regulation of MAPKKK cascade Inferred from mutant phenotype Ref.12. Source: UniProtKB negative regulation of NF-kappaB transcription factor activity Inferred from direct assay Ref.10. Source: UniProtKB negative regulation of apoptotic process Inferred from direct assay Ref.8. Source: UniProtKB negative regulation of release of cytochrome c from mitochondria Inferred from mutant phenotype Ref.12. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.8. Source: UniProtKB negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle Traceable author statement. Source: Reactome positive regulation of cell growth Inferred from direct assay Ref.5. Source: UniProtKB positive regulation of cyclin-dependent protein kinase activity Inferred from direct assay Ref.6. Source: UniProtKB positive regulation of proteasomal ubiquitin-dependent protein catabolic process Inferred from direct assay Ref.8. Source: UniProtKB positive regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle Traceable author statement. Source: Reactome proteasome regulatory particle assembly Inferred from mutant phenotype Ref.11. Source: UniProtKB protein polyubiquitination Traceable author statement. Source: Reactome regulation of cellular amino acid metabolic process Traceable author statement. Source: Reactome viral reproduction Traceable author statement. Source: Reactome
Cellular component	actin cytoskeleton Inferred from direct assay. Source: HPA cytosol Traceable author statement. Source: Reactome intermediate filament cytoskeleton Inferred from direct assay. Source: HPA nucleoplasm Traceable author statement. Source: Reactome proteasome regulatory particle Traceable author statement. Source: ProtInc
Molecular function	transcription factor binding Inferred from physical interaction Ref.10. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MAGEA4	P43358	5	EBI-752185,EBI-743122
PSMC4	P43686	8	EBI-752185,EBI-743997

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 226

226

26S proteasome non-ATPase regulatory subunit 10

PRO_0000067045

Regions

Repeat

3 – 36

34

ANK 1

Repeat

37 – 69

33

ANK 2

Repeat

70 – 102

33

ANK 3

Repeat

103 – 135

33

ANK 4

Repeat

136 – 168

33

ANK 5

Repeat

169 – 201

33

ANK 6

Repeat

202 – 226

25

ANK 7

Region

1 – 71

71

Interaction with RB1

Region

1 – 37

37

Required for nuclear localization

Region

39 – 226

188

Interaction with RELA

Region

171 – 226

56

Interaction with RB1

Amino acid modifications

Modified residue

1

1

N-acetylmethionine Ref.9

Experimental info

Mutagenesis

182

1

E → A: Abolishes interaction with RB1. Ref.5

Secondary structure

1

.

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226

Helix Strand Turn

Details...

Beta strand

6 – 8

3

Helix

9 – 15

7

Helix

19 – 28

10

Helix

30 – 34

5

Helix

43 – 50

8

Helix

53 – 62

10

Helix

76 – 83

8

Helix

86 – 94

9

Helix

109 – 115

7

Helix

119 – 127

9

Helix

142 – 148

7

Helix

152 – 160

9

Helix

175 – 181

7

Helix

185 – 193

9

Helix

208 – 211

4

Helix

216 – 224

9

Sequences

	Sequence		Length	Mass (Da)
	O75832 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 57158E33146EC7C8	FASTA	226	24,428
	10 20 30 40 50 60 MEGCVSNLMV CNLAYSGKLE ELKESILADK SLATRTDQDS RTALHWACSA GHTEIVEFLL 70 80 90 100 110 120 QLGVPVNDKD DAGWSPLHIA ASAGRDEIVK ALLGKGAQVN AVNQNGCTPL HYAASKNRHE 130 140 150 160 170 180 IAVMLLEGGA NPDAKDHYEA TAMHRAAAKG NLKMIHILLY YKASTNIQDT EGNTPLHLAC 190 200 210 220 DEERVEEAKL LVSQGASIYI ENKEEKTPLQ VAKGGLGLIL KRMVEG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning and functional analysis of p28 (Nas6p) and p40.5 (Nas7p), two novel regulatory subunits of the 26S proteasome." Hori T., Kato S., Saeki M., DeMartino G.N., Slaughter C.A., Takeuchi J., Toh-e A., Tanaka K. Gene 216:113-122(1998) [PubMed: 9714768] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Enhanced expression of a novel tumour marker in the human hepatomas." Higashitsuji H., Fujita J. Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[3]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed: 15772651] [Abstract] 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[5]	"Reduced stability of retinoblastoma protein by gankyrin, an oncogenic ankyrin-repeat protein overexpressed in hepatomas." Higashitsuji H., Itoh K., Nagao T., Dawson S., Nonoguchi K., Kido T., Mayer R.J., Arii S., Fujita J. Nat. Med. 6:96-99(2000) [PubMed: 10613832] [Abstract] Cited for: FUNCTION AS POTENTIAL PROTO-ONCOGENE, INTERACTION WITH RB1, TISSUE SPECIFICITY, MUTAGENESIS OF GLU-182.
[6]	"Novel insights into the INK4-CDK4/6-Rb pathway: counter action of gankyrin against INK4 proteins regulates the CDK4-mediated phosphorylation of Rb." Li J., Tsai M.D. Biochemistry 41:3977-3983(2002) [PubMed: 11900540] [Abstract] Cited for: FUNCTION, INTERACTION WITH CDK4.
[7]	"Gankyrin is an ankyrin-repeat oncoprotein that interacts with CDK4 kinase and the S6 ATPase of the 26 S proteasome." Dawson S., Apcher S., Mee M., Higashitsuji H., Baker R., Uhle S., Dubiel W., Fujita J., Mayer R.J. J. Biol. Chem. 277:10893-10902(2002) [PubMed: 11779854] [Abstract] Cited for: FUNCTION, INTERACTION WITH PSMC4.
[8]	"The oncoprotein gankyrin binds to MDM2/HDM2, enhancing ubiquitylation and degradation of p53." Higashitsuji H., Higashitsuji H., Itoh K., Sakurai T., Nagao T., Sumitomo Y., Masuda T., Dawson S., Shimada Y., Mayer R.J., Fujita J. Cancer Cell 8:75-87(2005) [PubMed: 16023600] [Abstract] Cited for: FUNCTION IN DEGRADATION OF TP53, INTERACTION WITH MDM2.
[9]	"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. Tissue: Embryonic kidney.
[10]	"Oncoprotein p28 GANK binds to RelA and retains NF-kappaB in the cytoplasm through nuclear export." Chen Y., Li H.H., Fu J., Wang X.F., Ren Y.B., Dong L.W., Tang S.H., Liu S.Q., Wu M.C., Wang H.Y. Cell Res. 17:1020-1029(2007) [PubMed: 18040287] [Abstract] Cited for: FUNCTION IN REGULATION OF NF-KAPPA-B, INTERACTION WITH RELY, SUBCELLULAR LOCATION.
[11]	"Assembly pathway of the Mammalian proteasome base subcomplex is mediated by multiple specific chaperones." Kaneko T., Hamazaki J., Iemura S., Sasaki K., Furuyama K., Natsume T., Tanaka K., Murata S. Cell 137:914-925(2009) [PubMed: 19490896] [Abstract] Cited for: FUNCTION AS PROTEASOME CHAPERONE, SUBUNIT.
[12]	"Involvement of the mitochondrial pathway in p53-independent apoptosis induced by p28GANK knockdown in Hep3B cells." Wang J., Wang X.F., Zhang L.G., Xie S.Y., Li Z.L., Li Y.J., Li H.H., Jiao F. Cytogenet. Genome Res. 125:87-97(2009) [PubMed: 19729910] [Abstract] Cited for: FUNCTION IN APOPTOSIS.
[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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]	"Solution structure of the human oncogenic protein gankyrin containing seven ankyrin repeats and analysis of its structure-function relationship." Yuan C., Li J., Mahajan A., Poi M.J., Byeon I.-J., Tsai M.-D. Biochemistry 43:12152-12161(2004) [PubMed: 15379554] [Abstract] Cited for: STRUCTURE BY NMR, DOMAINS ANK REPEATS.
[15]	"The crystal structure of gankyrin, an oncoprotein found in complexes with cyclin-dependent kinase 4, a 19 S proteasomal ATPase regulator, and the tumor suppressors Rb and p53." Krzywda S., Brzozowski A.M., Higashitsuji H., Fujita J., Welchman R., Dawson S., Mayer R.J., Wilkinson A.J. J. Biol. Chem. 279:1541-1545(2004) [PubMed: 14573599] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), DOMAIN ANKYRIN REPEATS.
[16]	"X-ray structure of human gankyrin, the product of a gene linked to hepatocellular carcinoma." Manjasetty B.A., Quedenau C., Sievert V., Bussow K., Niesen F., Delbruck H., Heinemann U. Proteins 55:214-217(2004) [PubMed: 14997555] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 2-226.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB009619 mRNA. Translation: BAA33215.1.
D83197 mRNA. Translation: BAA34594.1.
AL031177 Genomic DNA. Translation: CAA20117.1.
BC011960 mRNA. Translation: AAH11960.1.

IPI

IPI00003565.

RefSeq

NP_002805.1. NM_002814.3.
NP_736606.1. NM_170750.2.

UniGene

Hs.522752.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1QYM	X-ray	2.80	A	2-226	[»]
1TR4	NMR	-	A	1-226	[»]
1UOH	X-ray	2.00	A	1-226	[»]

ProteinModelPortal

O75832.

SMR

O75832. Positions 4-226.

ModBase

Search...

Protein-protein interaction databases

IntAct

O75832. 20 interactions.

STRING

O75832.

PTM databases

PhosphoSite

O75832.

2D gel databases

OGP

O75832.

Proteomic databases

PRIDE

O75832.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000217958; ENSP00000217958; ENSG00000101843.

GeneID

5716.

KEGG

hsa:5716.

NMPDR

fig|9606.3.peg.33217.

UCSC

uc004enp.1. human.

Organism-specific databases

CTD

5716.

GeneCards

GC0XM107327.

H-InvDB

HIX0016981.

HGNC

HGNC:9555. PSMD10.

HPA

CAB010434.
HPA002920.

MIM

603480. gene.

neXtProt

NX_O75832.

PharmGKB

PA33900.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG07027.

HOGENOM

HBG595165.

HOVERGEN

HBG053737.

InParanoid

O75832.

OMA

ATDHFES.

OrthoDB

EOG45490J.

PhylomeDB

O75832.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_13505. Proteasome mediated degradation of PAK-2p34.
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_6900. Immune System.

Gene expression databases

ArrayExpress

O75832.

Bgee

O75832.

CleanEx

HS_PSMD10.

Genevestigator

O75832.

GermOnline

ENSG00000101843. Homo sapiens.

Family and domain databases

InterPro

IPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
[Graphical view]

Gene3D

G3DSA:1.25.40.20. ANK. 2 hits.

KO

K06694.

Pfam

PF00023. Ank. 5 hits.
[Graphical view]

PRINTS

PR01415. ANKYRIN.

SMART

SM00248. ANK. 5 hits.
[Graphical view]

SUPFAM

SSF48403. ANK. 1 hit.

PROSITE

PS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 5 hits.
[Graphical view]

ProtoNet

Search...

Other

NextBio

22206.

SOURCE

Search...

Entry information

Entry name

PSD10_HUMAN

Accession

Primary (citable) accession number: O75832

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2002
Last sequence update:	November 1, 1998
Last modified:	January 25, 2012
This is version 117 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.