Full text data of PSMD10
PSMD10
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
26S proteasome non-ATPase regulatory subunit 10 (26S proteasome regulatory subunit p28; Gankyrin; p28(GANK))
Note: presumably soluble (membrane word is not in UniProt keywords or features)
26S proteasome non-ATPase regulatory subunit 10 (26S proteasome regulatory subunit p28; Gankyrin; p28(GANK))
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
O75832
ID PSD10_HUMAN Reviewed; 226 AA.
AC O75832; Q5U0B2; Q8IZK9;
DT 10-MAY-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1998, sequence version 1.
DT 22-JAN-2014, entry version 137.
DE RecName: Full=26S proteasome non-ATPase regulatory subunit 10;
DE AltName: Full=26S proteasome regulatory subunit p28;
DE AltName: Full=Gankyrin;
DE AltName: Full=p28(GANK);
GN Name=PSMD10;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9714768; DOI=10.1016/S0378-1119(98)00309-6;
RA Hori T., Kato S., Saeki M., DeMartino G.N., Slaughter C.A.,
RA Takeuchi J., Toh-e A., Tanaka K.;
RT "cDNA cloning and functional analysis of p28 (Nas6p) and p40.5
RT (Nas7p), two novel regulatory subunits of the 26S proteasome.";
RL Gene 216:113-122(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RA Higashitsuji H., Fujita J.;
RT "Enhanced expression of a novel tumour marker in the human
RT hepatomas.";
RL Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Liver;
RA Wang H., Fu X., Wu M.;
RT "Involvement of p28-II in hepatocellular carcinoma.";
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Subthalamic nucleus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP FUNCTION AS POTENTIAL PROTO-ONCOGENE, INTERACTION WITH RB1, TISSUE
RP SPECIFICITY, AND MUTAGENESIS OF GLU-182.
RX PubMed=10613832; DOI=10.1038/71600;
RA Higashitsuji H., Itoh K., Nagao T., Dawson S., Nonoguchi K., Kido T.,
RA Mayer R.J., Arii S., Fujita J.;
RT "Reduced stability of retinoblastoma protein by gankyrin, an oncogenic
RT ankyrin-repeat protein overexpressed in hepatomas.";
RL Nat. Med. 6:96-99(2000).
RN [9]
RP FUNCTION, AND INTERACTION WITH CDK4.
RX PubMed=11900540; DOI=10.1021/bi011550s;
RA Li J., Tsai M.D.;
RT "Novel insights into the INK4-CDK4/6-Rb pathway: counter action of
RT gankyrin against INK4 proteins regulates the CDK4-mediated
RT phosphorylation of Rb.";
RL Biochemistry 41:3977-3983(2002).
RN [10]
RP FUNCTION, AND INTERACTION WITH PSMC4.
RX PubMed=11779854; DOI=10.1074/jbc.M107313200;
RA Dawson S., Apcher S., Mee M., Higashitsuji H., Baker R., Uhle S.,
RA Dubiel W., Fujita J., Mayer R.J.;
RT "Gankyrin is an ankyrin-repeat oncoprotein that interacts with CDK4
RT kinase and the S6 ATPase of the 26 S proteasome.";
RL J. Biol. Chem. 277:10893-10902(2002).
RN [11]
RP FUNCTION IN DEGRADATION OF TP53, AND INTERACTION WITH MDM2.
RX PubMed=16023600; DOI=10.1016/j.ccr.2005.06.006;
RA Higashitsuji H., Higashitsuji H., Itoh K., Sakurai T., Nagao T.,
RA Sumitomo Y., Masuda T., Dawson S., Shimada Y., Mayer R.J., Fujita J.;
RT "The oncoprotein gankyrin binds to MDM2/HDM2, enhancing ubiquitylation
RT and degradation of p53.";
RL Cancer Cell 8:75-87(2005).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17323924; DOI=10.1021/bi061994u;
RA Wang X., Chen C.-F., Baker P.R., Chen P.-L., Kaiser P., Huang L.;
RT "Mass spectrometric characterization of the affinity-purified human
RT 26S proteasome complex.";
RL Biochemistry 46:3553-3565(2007).
RN [13]
RP FUNCTION IN REGULATION OF NF-KAPPA-B, INTERACTION WITH RELY, AND
RP SUBCELLULAR LOCATION.
RX PubMed=18040287; DOI=10.1038/cr.2007.99;
RA Chen Y., Li H.H., Fu J., Wang X.F., Ren Y.B., Dong L.W., Tang S.H.,
RA Liu S.Q., Wu M.C., Wang H.Y.;
RT "Oncoprotein p28 GANK binds to RelA and retains NF-kappaB in the
RT cytoplasm through nuclear export.";
RL Cell Res. 17:1020-1029(2007).
RN [14]
RP FUNCTION AS PROTEASOME CHAPERONE, AND SUBUNIT.
RX PubMed=19490896; DOI=10.1016/j.cell.2009.05.008;
RA Kaneko T., Hamazaki J., Iemura S., Sasaki K., Furuyama K., Natsume T.,
RA Tanaka K., Murata S.;
RT "Assembly pathway of the Mammalian proteasome base subcomplex is
RT mediated by multiple specific chaperones.";
RL Cell 137:914-925(2009).
RN [15]
RP FUNCTION IN APOPTOSIS.
RX PubMed=19729910; DOI=10.1159/000227831;
RA Wang J., Wang X.F., Zhang L.G., Xie S.Y., Li Z.L., Li Y.J., Li H.H.,
RA Jiao F.;
RT "Involvement of the mitochondrial pathway in p53-independent apoptosis
RT induced by p28GANK knockdown in Hep3B cells.";
RL Cytogenet. Genome Res. 125:87-97(2009).
RN [16]
RP FUNCTION IN AKT ACTIVATION, INTERACTION WITH ARHGDIA, AND TISSUE
RP SPECIFICITY.
RX PubMed=20628200; DOI=10.1172/JCI42542;
RA Man J.H., Liang B., Gu Y.X., Zhou T., Li A.L., Li T., Jin B.F.,
RA Bai B., Zhang H.Y., Zhang W.N., Li W.H., Gong W.L., Li H.Y.,
RA Zhang X.M.;
RT "Gankyrin plays an essential role in Ras-induced tumorigenesis through
RT regulation of the RhoA/ROCK pathway in mammalian cells.";
RL J. Clin. Invest. 120:2829-2841(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP STRUCTURE BY NMR, AND DOMAINS ANK REPEATS.
RX PubMed=15379554; DOI=10.1021/bi049116o;
RA Yuan C., Li J., Mahajan A., Poi M.J., Byeon I.-J., Tsai M.-D.;
RT "Solution structure of the human oncogenic protein gankyrin containing
RT seven ankyrin repeats and analysis of its structure-function
RT relationship.";
RL Biochemistry 43:12152-12161(2004).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), AND DOMAIN ANK REPEATS.
RX PubMed=14573599; DOI=10.1074/jbc.M310265200;
RA Krzywda S., Brzozowski A.M., Higashitsuji H., Fujita J., Welchman R.,
RA Dawson S., Mayer R.J., Wilkinson A.J.;
RT "The crystal structure of gankyrin, an oncoprotein found in complexes
RT with cyclin-dependent kinase 4, a 19 S proteasomal ATPase regulator,
RT and the tumor suppressors Rb and p53.";
RL J. Biol. Chem. 279:1541-1545(2004).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 2-226.
RX PubMed=14997555; DOI=10.1002/prot.20028;
RA Manjasetty B.A., Quedenau C., Sievert V., Bussow K., Niesen F.,
RA Delbruck H., Heinemann U.;
RT "X-ray structure of human gankyrin, the product of a gene linked to
RT hepatocellular carcinoma.";
RL Proteins 55:214-217(2004).
CC -!- FUNCTION: Acts as a chaperone during the assembly of the 26S
CC proteasome, specifically of the PA700/19S regulatory complex (RC).
CC In the initial step of the base subcomplex assembly is part of an
CC intermediate PSMD10:PSMC4:PSMC5:PAAF1 module which probably
CC assembles with a PSMD5:PSMC2:PSMC1:PSMD2 module. Independently of
CC the proteasome, regulates EGF-induced AKT activation through
CC inhibition of the RHOA/ROCK/PTEN pahway, leading to prolonged AKT
CC activation. Plays an important role in RAS-induced tumorigenesis.
CC -!- FUNCTION: Acts as an proto-oncoprotein by being involved in
CC negative regulation of tumor suppressors RB1 and p53/TP53.
CC Overexpression is leading to phosphorylation of RB1 and
CC proteasomal degradation of RB1. Regulates CDK4-mediated
CC phosphorylation of RB1 by competing with CDKN2A for binding with
CC CDK4. Facilitates binding of MDM2 to p53/TP53 and the mono- and
CC polyubiquitination of p53/TP53 by MDM2 suggesting a function in
CC targeting the TP53:MDM2 complex to the 26S proteasome. Involved in
CC p53-independent apoptosis. Involved in regulation of NF-kappa-B by
CC retaining it in the cytoplasm. Binds to the NF-kappa-B component
CC RELA and accelerates its XPO1/CRM1-mediated nuclear export.
CC -!- SUBUNIT: Part of transient complex containing PSMD10, PSMC4, PSMC5
CC and PAAF1 formed during the assembly of the 26S proteasome. Stays
CC associated throughout the assembly of the PA700/19S RC and is
CC released upon association with the 20S core. Interacts with PSMC4.
CC Interacts with RB1. Interacts with CDK4. Interacts with MDM2.
CC Interacts with RELA. Associates with a CDK4:CCND2 serine/threonine
CC kinase complex. Interacts with ARHGDIA and increases the
CC interaction between ARHGDIA and RHOA, hence promotes ARHGDIA
CC inactivation of RHOA and ROCK.
CC -!- INTERACTION:
CC P43358:MAGEA4; NbExp=5; IntAct=EBI-752185, EBI-743122;
CC P43686:PSMC4; NbExp=8; IntAct=EBI-752185, EBI-743997;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O75832-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75832-2; Sequence=VSP_043043;
CC -!- TISSUE SPECIFICITY: Tends to be up-regulated in cancer cells with
CC RAS mutations, including lung cancers and adenocarconimas (at
CC protein level).
CC -!- SIMILARITY: Contains 7 ANK repeats.
CC -!- CAUTION: Was initially identified as a genuine component of the
CC 26S proteasome.
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DR EMBL; AB009619; BAA33215.1; -; mRNA.
DR EMBL; D83197; BAA34594.1; -; mRNA.
DR EMBL; AY057056; AAL25260.1; -; mRNA.
DR EMBL; AK295996; BAG58771.1; -; mRNA.
DR EMBL; BT019689; AAV38495.1; -; mRNA.
DR EMBL; AL031177; CAA20117.1; -; Genomic_DNA.
DR EMBL; AL031177; CAI43131.1; -; Genomic_DNA.
DR EMBL; BC011960; AAH11960.1; -; mRNA.
DR RefSeq; NP_002805.1; NM_002814.3.
DR RefSeq; NP_736606.1; NM_170750.2.
DR UniGene; Hs.522752; -.
DR PDB; 1QYM; X-ray; 2.80 A; A=2-226.
DR PDB; 1TR4; NMR; -; A=1-226.
DR PDB; 1UOH; X-ray; 2.00 A; A=1-226.
DR PDBsum; 1QYM; -.
DR PDBsum; 1TR4; -.
DR PDBsum; 1UOH; -.
DR ProteinModelPortal; O75832; -.
DR SMR; O75832; 4-226.
DR IntAct; O75832; 21.
DR MINT; MINT-254757; -.
DR STRING; 9606.ENSP00000217958; -.
DR ChEMBL; CHEMBL2331054; -.
DR PhosphoSite; O75832; -.
DR OGP; O75832; -.
DR PaxDb; O75832; -.
DR PRIDE; O75832; -.
DR DNASU; 5716; -.
DR Ensembl; ENST00000217958; ENSP00000217958; ENSG00000101843.
DR Ensembl; ENST00000361815; ENSP00000354906; ENSG00000101843.
DR GeneID; 5716; -.
DR KEGG; hsa:5716; -.
DR UCSC; uc004enp.2; human.
DR CTD; 5716; -.
DR GeneCards; GC0XM107327; -.
DR HGNC; HGNC:9555; PSMD10.
DR HPA; CAB010434; -.
DR HPA; HPA002920; -.
DR MIM; 300880; gene.
DR neXtProt; NX_O75832; -.
DR PharmGKB; PA33900; -.
DR eggNOG; COG0666; -.
DR HOGENOM; HOG000158359; -.
DR HOVERGEN; HBG053737; -.
DR InParanoid; O75832; -.
DR KO; K06694; -.
DR OMA; CSAGHTN; -.
DR OrthoDB; EOG7B5WX7; -.
DR PhylomeDB; O75832; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_13505; Proteasome mediated degradation of PAK-2p34.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_21300; Mitotic M-M/G1 phases.
DR Reactome; REACT_383; DNA Replication.
DR Reactome; REACT_578; Apoptosis.
DR Reactome; REACT_6850; Cdc20:Phospho-APC/C mediated degradation of Cyclin A.
DR Reactome; REACT_6900; Immune System.
DR Reactome; REACT_71; Gene Expression.
DR EvolutionaryTrace; O75832; -.
DR GeneWiki; PSMD10; -.
DR GenomeRNAi; 5716; -.
DR NextBio; 22206; -.
DR PRO; PR:O75832; -.
DR ArrayExpress; O75832; -.
DR Bgee; O75832; -.
DR CleanEx; HS_PSMD10; -.
DR Genevestigator; O75832; -.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0045111; C:intermediate filament cytoskeleton; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005838; C:proteasome regulatory particle; TAS:ProtInc.
DR GO; GO:0031145; P:anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process; TAS:Reactome.
DR GO; GO:0002479; P:antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent; TAS:Reactome.
DR GO; GO:0006915; P:apoptotic process; TAS:Reactome.
DR GO; GO:0007253; P:cytoplasmic sequestering of NF-kappaB; IDA:UniProtKB.
DR GO; GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; TAS:Reactome.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; TAS:Reactome.
DR GO; GO:0010467; P:gene expression; TAS:Reactome.
DR GO; GO:0016071; P:mRNA metabolic process; TAS:Reactome.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; IDA:UniProtKB.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; IMP:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
DR GO; GO:0051436; P:negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle; TAS:Reactome.
DR GO; GO:0030307; P:positive regulation of cell growth; IDA:UniProtKB.
DR GO; GO:0045737; P:positive regulation of cyclin-dependent protein kinase activity; IDA:UniProtKB.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0051437; P:positive regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle; TAS:Reactome.
DR GO; GO:0070682; P:proteasome regulatory particle assembly; IMP:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; TAS:Reactome.
DR GO; GO:0006521; P:regulation of cellular amino acid metabolic process; TAS:Reactome.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR GO; GO:0016032; P:viral process; TAS:Reactome.
DR Gene3D; 1.25.40.20; -; 2.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR020683; Ankyrin_rpt-contain_dom.
DR Pfam; PF00023; Ank; 5.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 5.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 5.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ANK repeat; Apoptosis; Chaperone;
KW Complete proteome; Cytoplasm; Nucleus; Reference proteome; Repeat.
FT CHAIN 1 226 26S proteasome non-ATPase regulatory
FT subunit 10.
FT /FTId=PRO_0000067045.
FT REPEAT 3 36 ANK 1.
FT REPEAT 37 69 ANK 2.
FT REPEAT 70 102 ANK 3.
FT REPEAT 103 135 ANK 4.
FT REPEAT 136 168 ANK 5.
FT REPEAT 169 201 ANK 6.
FT REPEAT 202 226 ANK 7.
FT REGION 1 71 Interaction with RB1.
FT REGION 1 37 Required for nuclear localization.
FT REGION 39 226 Interaction with RELA.
FT REGION 171 226 Interaction with RB1.
FT VAR_SEQ 150 226 GNLKMIHILLYYKASTNIQDTEGNTPLHLACDEERVEEAKL
FT LVSQGASIYIENKEEKTPLQVAKGGLGLILKRMVEG -> D
FT T (in isoform 2).
FT /FTId=VSP_043043.
FT MUTAGEN 182 182 E->A: Abolishes interaction with RB1.
FT CONFLICT 196 196 A -> T (in Ref. 5; AAV38495).
FT STRAND 6 8
FT HELIX 9 15
FT HELIX 19 28
FT HELIX 30 34
FT TURN 38 40
FT HELIX 43 50
FT HELIX 53 62
FT STRAND 71 73
FT HELIX 76 83
FT HELIX 86 94
FT HELIX 109 115
FT HELIX 119 127
FT HELIX 142 148
FT HELIX 152 160
FT HELIX 175 181
FT HELIX 185 193
FT HELIX 208 211
FT HELIX 216 224
SQ SEQUENCE 226 AA; 24428 MW; 57158E33146EC7C8 CRC64;
MEGCVSNLMV CNLAYSGKLE ELKESILADK SLATRTDQDS RTALHWACSA GHTEIVEFLL
QLGVPVNDKD DAGWSPLHIA ASAGRDEIVK ALLGKGAQVN AVNQNGCTPL HYAASKNRHE
IAVMLLEGGA NPDAKDHYEA TAMHRAAAKG NLKMIHILLY YKASTNIQDT EGNTPLHLAC
DEERVEEAKL LVSQGASIYI ENKEEKTPLQ VAKGGLGLIL KRMVEG
//
ID PSD10_HUMAN Reviewed; 226 AA.
AC O75832; Q5U0B2; Q8IZK9;
DT 10-MAY-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1998, sequence version 1.
DT 22-JAN-2014, entry version 137.
DE RecName: Full=26S proteasome non-ATPase regulatory subunit 10;
DE AltName: Full=26S proteasome regulatory subunit p28;
DE AltName: Full=Gankyrin;
DE AltName: Full=p28(GANK);
GN Name=PSMD10;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9714768; DOI=10.1016/S0378-1119(98)00309-6;
RA Hori T., Kato S., Saeki M., DeMartino G.N., Slaughter C.A.,
RA Takeuchi J., Toh-e A., Tanaka K.;
RT "cDNA cloning and functional analysis of p28 (Nas6p) and p40.5
RT (Nas7p), two novel regulatory subunits of the 26S proteasome.";
RL Gene 216:113-122(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RA Higashitsuji H., Fujita J.;
RT "Enhanced expression of a novel tumour marker in the human
RT hepatomas.";
RL Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Liver;
RA Wang H., Fu X., Wu M.;
RT "Involvement of p28-II in hepatocellular carcinoma.";
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Subthalamic nucleus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP FUNCTION AS POTENTIAL PROTO-ONCOGENE, INTERACTION WITH RB1, TISSUE
RP SPECIFICITY, AND MUTAGENESIS OF GLU-182.
RX PubMed=10613832; DOI=10.1038/71600;
RA Higashitsuji H., Itoh K., Nagao T., Dawson S., Nonoguchi K., Kido T.,
RA Mayer R.J., Arii S., Fujita J.;
RT "Reduced stability of retinoblastoma protein by gankyrin, an oncogenic
RT ankyrin-repeat protein overexpressed in hepatomas.";
RL Nat. Med. 6:96-99(2000).
RN [9]
RP FUNCTION, AND INTERACTION WITH CDK4.
RX PubMed=11900540; DOI=10.1021/bi011550s;
RA Li J., Tsai M.D.;
RT "Novel insights into the INK4-CDK4/6-Rb pathway: counter action of
RT gankyrin against INK4 proteins regulates the CDK4-mediated
RT phosphorylation of Rb.";
RL Biochemistry 41:3977-3983(2002).
RN [10]
RP FUNCTION, AND INTERACTION WITH PSMC4.
RX PubMed=11779854; DOI=10.1074/jbc.M107313200;
RA Dawson S., Apcher S., Mee M., Higashitsuji H., Baker R., Uhle S.,
RA Dubiel W., Fujita J., Mayer R.J.;
RT "Gankyrin is an ankyrin-repeat oncoprotein that interacts with CDK4
RT kinase and the S6 ATPase of the 26 S proteasome.";
RL J. Biol. Chem. 277:10893-10902(2002).
RN [11]
RP FUNCTION IN DEGRADATION OF TP53, AND INTERACTION WITH MDM2.
RX PubMed=16023600; DOI=10.1016/j.ccr.2005.06.006;
RA Higashitsuji H., Higashitsuji H., Itoh K., Sakurai T., Nagao T.,
RA Sumitomo Y., Masuda T., Dawson S., Shimada Y., Mayer R.J., Fujita J.;
RT "The oncoprotein gankyrin binds to MDM2/HDM2, enhancing ubiquitylation
RT and degradation of p53.";
RL Cancer Cell 8:75-87(2005).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17323924; DOI=10.1021/bi061994u;
RA Wang X., Chen C.-F., Baker P.R., Chen P.-L., Kaiser P., Huang L.;
RT "Mass spectrometric characterization of the affinity-purified human
RT 26S proteasome complex.";
RL Biochemistry 46:3553-3565(2007).
RN [13]
RP FUNCTION IN REGULATION OF NF-KAPPA-B, INTERACTION WITH RELY, AND
RP SUBCELLULAR LOCATION.
RX PubMed=18040287; DOI=10.1038/cr.2007.99;
RA Chen Y., Li H.H., Fu J., Wang X.F., Ren Y.B., Dong L.W., Tang S.H.,
RA Liu S.Q., Wu M.C., Wang H.Y.;
RT "Oncoprotein p28 GANK binds to RelA and retains NF-kappaB in the
RT cytoplasm through nuclear export.";
RL Cell Res. 17:1020-1029(2007).
RN [14]
RP FUNCTION AS PROTEASOME CHAPERONE, AND SUBUNIT.
RX PubMed=19490896; DOI=10.1016/j.cell.2009.05.008;
RA Kaneko T., Hamazaki J., Iemura S., Sasaki K., Furuyama K., Natsume T.,
RA Tanaka K., Murata S.;
RT "Assembly pathway of the Mammalian proteasome base subcomplex is
RT mediated by multiple specific chaperones.";
RL Cell 137:914-925(2009).
RN [15]
RP FUNCTION IN APOPTOSIS.
RX PubMed=19729910; DOI=10.1159/000227831;
RA Wang J., Wang X.F., Zhang L.G., Xie S.Y., Li Z.L., Li Y.J., Li H.H.,
RA Jiao F.;
RT "Involvement of the mitochondrial pathway in p53-independent apoptosis
RT induced by p28GANK knockdown in Hep3B cells.";
RL Cytogenet. Genome Res. 125:87-97(2009).
RN [16]
RP FUNCTION IN AKT ACTIVATION, INTERACTION WITH ARHGDIA, AND TISSUE
RP SPECIFICITY.
RX PubMed=20628200; DOI=10.1172/JCI42542;
RA Man J.H., Liang B., Gu Y.X., Zhou T., Li A.L., Li T., Jin B.F.,
RA Bai B., Zhang H.Y., Zhang W.N., Li W.H., Gong W.L., Li H.Y.,
RA Zhang X.M.;
RT "Gankyrin plays an essential role in Ras-induced tumorigenesis through
RT regulation of the RhoA/ROCK pathway in mammalian cells.";
RL J. Clin. Invest. 120:2829-2841(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP STRUCTURE BY NMR, AND DOMAINS ANK REPEATS.
RX PubMed=15379554; DOI=10.1021/bi049116o;
RA Yuan C., Li J., Mahajan A., Poi M.J., Byeon I.-J., Tsai M.-D.;
RT "Solution structure of the human oncogenic protein gankyrin containing
RT seven ankyrin repeats and analysis of its structure-function
RT relationship.";
RL Biochemistry 43:12152-12161(2004).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), AND DOMAIN ANK REPEATS.
RX PubMed=14573599; DOI=10.1074/jbc.M310265200;
RA Krzywda S., Brzozowski A.M., Higashitsuji H., Fujita J., Welchman R.,
RA Dawson S., Mayer R.J., Wilkinson A.J.;
RT "The crystal structure of gankyrin, an oncoprotein found in complexes
RT with cyclin-dependent kinase 4, a 19 S proteasomal ATPase regulator,
RT and the tumor suppressors Rb and p53.";
RL J. Biol. Chem. 279:1541-1545(2004).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 2-226.
RX PubMed=14997555; DOI=10.1002/prot.20028;
RA Manjasetty B.A., Quedenau C., Sievert V., Bussow K., Niesen F.,
RA Delbruck H., Heinemann U.;
RT "X-ray structure of human gankyrin, the product of a gene linked to
RT hepatocellular carcinoma.";
RL Proteins 55:214-217(2004).
CC -!- FUNCTION: Acts as a chaperone during the assembly of the 26S
CC proteasome, specifically of the PA700/19S regulatory complex (RC).
CC In the initial step of the base subcomplex assembly is part of an
CC intermediate PSMD10:PSMC4:PSMC5:PAAF1 module which probably
CC assembles with a PSMD5:PSMC2:PSMC1:PSMD2 module. Independently of
CC the proteasome, regulates EGF-induced AKT activation through
CC inhibition of the RHOA/ROCK/PTEN pahway, leading to prolonged AKT
CC activation. Plays an important role in RAS-induced tumorigenesis.
CC -!- FUNCTION: Acts as an proto-oncoprotein by being involved in
CC negative regulation of tumor suppressors RB1 and p53/TP53.
CC Overexpression is leading to phosphorylation of RB1 and
CC proteasomal degradation of RB1. Regulates CDK4-mediated
CC phosphorylation of RB1 by competing with CDKN2A for binding with
CC CDK4. Facilitates binding of MDM2 to p53/TP53 and the mono- and
CC polyubiquitination of p53/TP53 by MDM2 suggesting a function in
CC targeting the TP53:MDM2 complex to the 26S proteasome. Involved in
CC p53-independent apoptosis. Involved in regulation of NF-kappa-B by
CC retaining it in the cytoplasm. Binds to the NF-kappa-B component
CC RELA and accelerates its XPO1/CRM1-mediated nuclear export.
CC -!- SUBUNIT: Part of transient complex containing PSMD10, PSMC4, PSMC5
CC and PAAF1 formed during the assembly of the 26S proteasome. Stays
CC associated throughout the assembly of the PA700/19S RC and is
CC released upon association with the 20S core. Interacts with PSMC4.
CC Interacts with RB1. Interacts with CDK4. Interacts with MDM2.
CC Interacts with RELA. Associates with a CDK4:CCND2 serine/threonine
CC kinase complex. Interacts with ARHGDIA and increases the
CC interaction between ARHGDIA and RHOA, hence promotes ARHGDIA
CC inactivation of RHOA and ROCK.
CC -!- INTERACTION:
CC P43358:MAGEA4; NbExp=5; IntAct=EBI-752185, EBI-743122;
CC P43686:PSMC4; NbExp=8; IntAct=EBI-752185, EBI-743997;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O75832-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75832-2; Sequence=VSP_043043;
CC -!- TISSUE SPECIFICITY: Tends to be up-regulated in cancer cells with
CC RAS mutations, including lung cancers and adenocarconimas (at
CC protein level).
CC -!- SIMILARITY: Contains 7 ANK repeats.
CC -!- CAUTION: Was initially identified as a genuine component of the
CC 26S proteasome.
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DR EMBL; AB009619; BAA33215.1; -; mRNA.
DR EMBL; D83197; BAA34594.1; -; mRNA.
DR EMBL; AY057056; AAL25260.1; -; mRNA.
DR EMBL; AK295996; BAG58771.1; -; mRNA.
DR EMBL; BT019689; AAV38495.1; -; mRNA.
DR EMBL; AL031177; CAA20117.1; -; Genomic_DNA.
DR EMBL; AL031177; CAI43131.1; -; Genomic_DNA.
DR EMBL; BC011960; AAH11960.1; -; mRNA.
DR RefSeq; NP_002805.1; NM_002814.3.
DR RefSeq; NP_736606.1; NM_170750.2.
DR UniGene; Hs.522752; -.
DR PDB; 1QYM; X-ray; 2.80 A; A=2-226.
DR PDB; 1TR4; NMR; -; A=1-226.
DR PDB; 1UOH; X-ray; 2.00 A; A=1-226.
DR PDBsum; 1QYM; -.
DR PDBsum; 1TR4; -.
DR PDBsum; 1UOH; -.
DR ProteinModelPortal; O75832; -.
DR SMR; O75832; 4-226.
DR IntAct; O75832; 21.
DR MINT; MINT-254757; -.
DR STRING; 9606.ENSP00000217958; -.
DR ChEMBL; CHEMBL2331054; -.
DR PhosphoSite; O75832; -.
DR OGP; O75832; -.
DR PaxDb; O75832; -.
DR PRIDE; O75832; -.
DR DNASU; 5716; -.
DR Ensembl; ENST00000217958; ENSP00000217958; ENSG00000101843.
DR Ensembl; ENST00000361815; ENSP00000354906; ENSG00000101843.
DR GeneID; 5716; -.
DR KEGG; hsa:5716; -.
DR UCSC; uc004enp.2; human.
DR CTD; 5716; -.
DR GeneCards; GC0XM107327; -.
DR HGNC; HGNC:9555; PSMD10.
DR HPA; CAB010434; -.
DR HPA; HPA002920; -.
DR MIM; 300880; gene.
DR neXtProt; NX_O75832; -.
DR PharmGKB; PA33900; -.
DR eggNOG; COG0666; -.
DR HOGENOM; HOG000158359; -.
DR HOVERGEN; HBG053737; -.
DR InParanoid; O75832; -.
DR KO; K06694; -.
DR OMA; CSAGHTN; -.
DR OrthoDB; EOG7B5WX7; -.
DR PhylomeDB; O75832; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_13505; Proteasome mediated degradation of PAK-2p34.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_21300; Mitotic M-M/G1 phases.
DR Reactome; REACT_383; DNA Replication.
DR Reactome; REACT_578; Apoptosis.
DR Reactome; REACT_6850; Cdc20:Phospho-APC/C mediated degradation of Cyclin A.
DR Reactome; REACT_6900; Immune System.
DR Reactome; REACT_71; Gene Expression.
DR EvolutionaryTrace; O75832; -.
DR GeneWiki; PSMD10; -.
DR GenomeRNAi; 5716; -.
DR NextBio; 22206; -.
DR PRO; PR:O75832; -.
DR ArrayExpress; O75832; -.
DR Bgee; O75832; -.
DR CleanEx; HS_PSMD10; -.
DR Genevestigator; O75832; -.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0045111; C:intermediate filament cytoskeleton; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005838; C:proteasome regulatory particle; TAS:ProtInc.
DR GO; GO:0031145; P:anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process; TAS:Reactome.
DR GO; GO:0002479; P:antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent; TAS:Reactome.
DR GO; GO:0006915; P:apoptotic process; TAS:Reactome.
DR GO; GO:0007253; P:cytoplasmic sequestering of NF-kappaB; IDA:UniProtKB.
DR GO; GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; TAS:Reactome.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; TAS:Reactome.
DR GO; GO:0010467; P:gene expression; TAS:Reactome.
DR GO; GO:0016071; P:mRNA metabolic process; TAS:Reactome.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; IDA:UniProtKB.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; IMP:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
DR GO; GO:0051436; P:negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle; TAS:Reactome.
DR GO; GO:0030307; P:positive regulation of cell growth; IDA:UniProtKB.
DR GO; GO:0045737; P:positive regulation of cyclin-dependent protein kinase activity; IDA:UniProtKB.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0051437; P:positive regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle; TAS:Reactome.
DR GO; GO:0070682; P:proteasome regulatory particle assembly; IMP:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; TAS:Reactome.
DR GO; GO:0006521; P:regulation of cellular amino acid metabolic process; TAS:Reactome.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR GO; GO:0016032; P:viral process; TAS:Reactome.
DR Gene3D; 1.25.40.20; -; 2.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR020683; Ankyrin_rpt-contain_dom.
DR Pfam; PF00023; Ank; 5.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 5.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 5.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ANK repeat; Apoptosis; Chaperone;
KW Complete proteome; Cytoplasm; Nucleus; Reference proteome; Repeat.
FT CHAIN 1 226 26S proteasome non-ATPase regulatory
FT subunit 10.
FT /FTId=PRO_0000067045.
FT REPEAT 3 36 ANK 1.
FT REPEAT 37 69 ANK 2.
FT REPEAT 70 102 ANK 3.
FT REPEAT 103 135 ANK 4.
FT REPEAT 136 168 ANK 5.
FT REPEAT 169 201 ANK 6.
FT REPEAT 202 226 ANK 7.
FT REGION 1 71 Interaction with RB1.
FT REGION 1 37 Required for nuclear localization.
FT REGION 39 226 Interaction with RELA.
FT REGION 171 226 Interaction with RB1.
FT VAR_SEQ 150 226 GNLKMIHILLYYKASTNIQDTEGNTPLHLACDEERVEEAKL
FT LVSQGASIYIENKEEKTPLQVAKGGLGLILKRMVEG -> D
FT T (in isoform 2).
FT /FTId=VSP_043043.
FT MUTAGEN 182 182 E->A: Abolishes interaction with RB1.
FT CONFLICT 196 196 A -> T (in Ref. 5; AAV38495).
FT STRAND 6 8
FT HELIX 9 15
FT HELIX 19 28
FT HELIX 30 34
FT TURN 38 40
FT HELIX 43 50
FT HELIX 53 62
FT STRAND 71 73
FT HELIX 76 83
FT HELIX 86 94
FT HELIX 109 115
FT HELIX 119 127
FT HELIX 142 148
FT HELIX 152 160
FT HELIX 175 181
FT HELIX 185 193
FT HELIX 208 211
FT HELIX 216 224
SQ SEQUENCE 226 AA; 24428 MW; 57158E33146EC7C8 CRC64;
MEGCVSNLMV CNLAYSGKLE ELKESILADK SLATRTDQDS RTALHWACSA GHTEIVEFLL
QLGVPVNDKD DAGWSPLHIA ASAGRDEIVK ALLGKGAQVN AVNQNGCTPL HYAASKNRHE
IAVMLLEGGA NPDAKDHYEA TAMHRAAAKG NLKMIHILLY YKASTNIQDT EGNTPLHLAC
DEERVEEAKL LVSQGASIYI ENKEEKTPLQ VAKGGLGLIL KRMVEG
//
MIM
300880
*RECORD*
*FIELD* NO
300880
*FIELD* TI
*300880 PROTEASOME 26S SUBUNIT, NON-ATPase, 10; PSMD10
;;p28;;
GANKYRIN;;
p28(GANK)
read more*FIELD* TX
DESCRIPTION
Ubiquitinated proteins are degraded by a 26S ATP-dependent protease. The
protease is composed of a 20S catalytic proteasome and PA700, a 700-kD
regulatory complex (see PSMC1, 602706) that includes PSMD10 (Hori et
al., 1998).
CLONING
Hori et al. (1998) determined the partial protein sequences of bovine
p28 and p40.5 (PSMD13; 603481), 2 components of PA700. By searching a
sequence database, they identified cDNAs encoding the human p28 and
p40.5 homologs, and they cloned the cDNAs from a U937 monocyte cDNA
library. The predicted 226-amino acid human p28 protein contains 5
ankyrin repeats, which are thought to function in protein-protein
interactions. Using computerized homology searches, Hori et al. (1998)
identified Nas6, an S. cerevisiae gene encoding a protein with 38%
identity to p28. Northern blot analysis revealed that p28 was expressed
as a 1.3-kb mRNA in all human tissues tested.
GENE FUNCTION
Hori et al. (1998) found that disruption of yeast Nas6 had no effect on
cell viability.
Man et al. (2010) found that expression of constitutively active mutant
RAS (HRAS; 190020) increased gankyrin mRNA and protein expression and
induced a tumorigenic phenotype in transfected NIH3T3 mouse fibroblasts.
Knockdown of gankyrin reversed RAS-induced transformation and
tumorigenesis. Gankyrin was highly expressed in human lung cancers
expressing RAS with oncogenic mutations, and gankyrin expression was
higher in adenocarcinomas than in squamous carcinomas. Knockdown and
molecular studies performed predominantly with mouse cells revealed that
gankyrin increased interaction between Rhoa (165390) and its inhibitor
Rhogdi (ARHGDIA; 601925), resulting in elevated Akt (see 164730)
activation via the Rhoa-Rock (see 601702)-Pten (601728) pathway.
Knockdown of Rock or deletion of Pten reversed gankyrin-mediated Akt
activation.
Dong et al. (2011) stated that p28(GANK) is highly expressed in human
hepatocellular carcinoma (HCC) cells. Using a reporter gene assay with
HepG2 and HEK293 cells, they found that the growth factors EGF (131530)
and HGF (142409), in addition to RAS, elevated p28(GANK) mRNA and
protein expression in a dose-dependent manner. Molecular and inhibitor
studies revealed that this activation of p28(GANK) occurred through the
PI3 kinase (see 601232)-AKT signaling pathway. In 40 primary HCC
samples, p28(GANK) protein levels correlated with AKT activation.
Beta-catenin (see 116806) and MYC (190080) also activated p28(GANK)
expression, and p28(GANK) increased beta-catenin signaling in a
positive-feedback loop. p28(GNAK) appeared to increase beta-catenin
signaling by releasing it from cytoskeletal sequestration in complex
with E-cadherin (CDH1; 192090).
Zhen et al. (2013) found that gankyrin was highly overexpressed in human
breast cancers and that gankyrin expression correlated strongly with
lymph node metastasis. In cultured human breast cancer cells, knockdown
of gankyrin reduced cell migration and increased cell adhesion, with
formation of large focal adhesions. Expression of constitutively active
RAC1 (602048) reversed the effects of gankyrin knockdown. Overexpression
of gankyrin accelerated focal adhesion turnover and increased cell
migration.
MAPPING
Hartz (2012) mapped the PSMD10 gene to chromosome Xq22.32 based on an
alignment of the PSMD10 sequence (GenBank GENBANK AB009619) with the
genomic sequence (GRCh37).
*FIELD* RF
1. Dong, L.; Yang, G.; Pan, Y.; Chen, Y.; Tan, Y.; Dai, R.; Ren, Y.;
Fu, J.; Wang, H.: The oncoprotein p28(GANK) establishes a positive
feedback loop in beta-catenin signaling. Cell Res. 21: 1248-1261,
2011.
2. Hartz, P. A.: Personal Communication. Baltimore, Md. 9/26/2012.
3. Hori, T.; Kato, S.; Saeki, M.; DeMartino, G. N.; Slaughter, C.
A.; Takeuchi, J.; Toh-e, A.; Tanaka, K.: cDNA cloning and functional
analysis of p28 (Nas6p) and p40.5 (Nas7p), two novel regulatory subunits
of the 26S proteasome. Gene 216: 113-122, 1998.
4. Man, J.-H.; Liang, B.; Gu, Y.-X.; Zhou, T.; Li, A.-L.; Li, T.;
Jin, B.-F.; Bai, B.; Zhang, H.-Y.; Zhang, W.-N.; Li, W.-H.; Gong,
W.-L.; Li, H.-Y.; Zhang, X.-M.: Gankyrin plays an essential role
in Ras-induced tumorigenesis through regulation of the RhoA/ROCK pathway
in mammalian cells. J. Clin. Invest. 120: 2829-2841, 2010.
5. Zhen, C.; Chen, L.; Zhao, Q.; Liang, B.; Gu, Y.-X.; Bai, Z.; Wang,
K.; Xu, X.; Han, Q.; Fang, D.; Wang, S.; Zhou, T.; Xia, Q.; Gong,
W.-I.; Wang, N.; Li, H.-Y.; Jin, B.-F.; Man, J.: Gankyrin promotes
breast cancer cell metastasis by regulating Rac1 activity. Oncogene 32:
3452-3460, 2013.
*FIELD* CN
Patricia A. Hartz - updated: 9/26/2012
*FIELD* CD
Patricia A. Hartz: 9/24/2012
*FIELD* ED
mcolton: 11/26/2013
mgross: 10/10/2012
terry: 9/26/2012
joanna: 9/24/2012
*RECORD*
*FIELD* NO
300880
*FIELD* TI
*300880 PROTEASOME 26S SUBUNIT, NON-ATPase, 10; PSMD10
;;p28;;
GANKYRIN;;
p28(GANK)
read more*FIELD* TX
DESCRIPTION
Ubiquitinated proteins are degraded by a 26S ATP-dependent protease. The
protease is composed of a 20S catalytic proteasome and PA700, a 700-kD
regulatory complex (see PSMC1, 602706) that includes PSMD10 (Hori et
al., 1998).
CLONING
Hori et al. (1998) determined the partial protein sequences of bovine
p28 and p40.5 (PSMD13; 603481), 2 components of PA700. By searching a
sequence database, they identified cDNAs encoding the human p28 and
p40.5 homologs, and they cloned the cDNAs from a U937 monocyte cDNA
library. The predicted 226-amino acid human p28 protein contains 5
ankyrin repeats, which are thought to function in protein-protein
interactions. Using computerized homology searches, Hori et al. (1998)
identified Nas6, an S. cerevisiae gene encoding a protein with 38%
identity to p28. Northern blot analysis revealed that p28 was expressed
as a 1.3-kb mRNA in all human tissues tested.
GENE FUNCTION
Hori et al. (1998) found that disruption of yeast Nas6 had no effect on
cell viability.
Man et al. (2010) found that expression of constitutively active mutant
RAS (HRAS; 190020) increased gankyrin mRNA and protein expression and
induced a tumorigenic phenotype in transfected NIH3T3 mouse fibroblasts.
Knockdown of gankyrin reversed RAS-induced transformation and
tumorigenesis. Gankyrin was highly expressed in human lung cancers
expressing RAS with oncogenic mutations, and gankyrin expression was
higher in adenocarcinomas than in squamous carcinomas. Knockdown and
molecular studies performed predominantly with mouse cells revealed that
gankyrin increased interaction between Rhoa (165390) and its inhibitor
Rhogdi (ARHGDIA; 601925), resulting in elevated Akt (see 164730)
activation via the Rhoa-Rock (see 601702)-Pten (601728) pathway.
Knockdown of Rock or deletion of Pten reversed gankyrin-mediated Akt
activation.
Dong et al. (2011) stated that p28(GANK) is highly expressed in human
hepatocellular carcinoma (HCC) cells. Using a reporter gene assay with
HepG2 and HEK293 cells, they found that the growth factors EGF (131530)
and HGF (142409), in addition to RAS, elevated p28(GANK) mRNA and
protein expression in a dose-dependent manner. Molecular and inhibitor
studies revealed that this activation of p28(GANK) occurred through the
PI3 kinase (see 601232)-AKT signaling pathway. In 40 primary HCC
samples, p28(GANK) protein levels correlated with AKT activation.
Beta-catenin (see 116806) and MYC (190080) also activated p28(GANK)
expression, and p28(GANK) increased beta-catenin signaling in a
positive-feedback loop. p28(GNAK) appeared to increase beta-catenin
signaling by releasing it from cytoskeletal sequestration in complex
with E-cadherin (CDH1; 192090).
Zhen et al. (2013) found that gankyrin was highly overexpressed in human
breast cancers and that gankyrin expression correlated strongly with
lymph node metastasis. In cultured human breast cancer cells, knockdown
of gankyrin reduced cell migration and increased cell adhesion, with
formation of large focal adhesions. Expression of constitutively active
RAC1 (602048) reversed the effects of gankyrin knockdown. Overexpression
of gankyrin accelerated focal adhesion turnover and increased cell
migration.
MAPPING
Hartz (2012) mapped the PSMD10 gene to chromosome Xq22.32 based on an
alignment of the PSMD10 sequence (GenBank GENBANK AB009619) with the
genomic sequence (GRCh37).
*FIELD* RF
1. Dong, L.; Yang, G.; Pan, Y.; Chen, Y.; Tan, Y.; Dai, R.; Ren, Y.;
Fu, J.; Wang, H.: The oncoprotein p28(GANK) establishes a positive
feedback loop in beta-catenin signaling. Cell Res. 21: 1248-1261,
2011.
2. Hartz, P. A.: Personal Communication. Baltimore, Md. 9/26/2012.
3. Hori, T.; Kato, S.; Saeki, M.; DeMartino, G. N.; Slaughter, C.
A.; Takeuchi, J.; Toh-e, A.; Tanaka, K.: cDNA cloning and functional
analysis of p28 (Nas6p) and p40.5 (Nas7p), two novel regulatory subunits
of the 26S proteasome. Gene 216: 113-122, 1998.
4. Man, J.-H.; Liang, B.; Gu, Y.-X.; Zhou, T.; Li, A.-L.; Li, T.;
Jin, B.-F.; Bai, B.; Zhang, H.-Y.; Zhang, W.-N.; Li, W.-H.; Gong,
W.-L.; Li, H.-Y.; Zhang, X.-M.: Gankyrin plays an essential role
in Ras-induced tumorigenesis through regulation of the RhoA/ROCK pathway
in mammalian cells. J. Clin. Invest. 120: 2829-2841, 2010.
5. Zhen, C.; Chen, L.; Zhao, Q.; Liang, B.; Gu, Y.-X.; Bai, Z.; Wang,
K.; Xu, X.; Han, Q.; Fang, D.; Wang, S.; Zhou, T.; Xia, Q.; Gong,
W.-I.; Wang, N.; Li, H.-Y.; Jin, B.-F.; Man, J.: Gankyrin promotes
breast cancer cell metastasis by regulating Rac1 activity. Oncogene 32:
3452-3460, 2013.
*FIELD* CN
Patricia A. Hartz - updated: 9/26/2012
*FIELD* CD
Patricia A. Hartz: 9/24/2012
*FIELD* ED
mcolton: 11/26/2013
mgross: 10/10/2012
terry: 9/26/2012
joanna: 9/24/2012