O00487 (PSDE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
26S proteasome non-ATPase regulatory subunit 14
EC=3.4.19.-

Alternative name(s):
26S proteasome regulatory subunit RPN11
26S proteasome-associated PAD1 homolog 1

Gene names

Name:	PSMD14
Synonyms:	POH1

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

General annotation (Comments)

Function	Metalloprotease component of the 26S proteasome that specifically cleaves 'Lys-63'-linked polyubiquitin chains. The 26S proteasome is involved in the ATP-dependent degradation of ubiquitinated proteins. Plays a role in response to double-strand breaks (DSBs): acts as a regulator of non-homologous end joining (NHEJ) by cleaving 'Lys-63'-linked polyubiquitin, thereby promoting retention of JMJD2A/KDM4A on chromatin and restricting TP53BP1 accumulation. Also involved in homologous recombination repair by promoting RAD51 loading. Ref.1 Ref.8 Ref.12
Subunit structure	Component of the lid subcomplex of the 19S proteasome regulatory particle complex (also named PA700 complex). The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. Interacts with TXNL1. Ref.8 Ref.9 Ref.12
Tissue specificity	Widely expressed. Highest levels in heart and skeletal muscle. Ref.1
Sequence similarities	Belongs to the peptidase M67A family. PSMD14 subfamily. Contains 1 MPN (JAB/Mov34) domain.

Ontologies

Keywords
Biological process	DNA damage DNA repair Ubl conjugation pathway
Cellular component	Proteasome
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	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 double-strand break repair via homologous recombination Inferred from mutant phenotype Ref.12. Source: UniProtKB double-strand break repair via nonhomologous end joining Inferred from mutant phenotype Ref.12. Source: UniProtKB 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 K63-linked deubiquitination Inferred from mutant phenotype Ref.12. Source: UniProtKB 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 proteasomal protein catabolic process Inferred from mutant phenotype PubMed 18162577. Source: UniProtKB 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, lid subcomplex Inferred from mutant phenotype Ref.12. Source: UniProtKB
Molecular_function	endopeptidase activator activity Inferred from mutant phenotype PubMed 18162577. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW metallopeptidase activity Traceable author statement Ref.8. Source: UniProtKB proteasome binding Inferred from direct assay PubMed 18162577. Source: UniProtKB ubiquitin thiolesterase activity Inferred from mutant phenotype Ref.12. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 310	310	26S proteasome non-ATPase regulatory subunit 14		PRO_0000213952
Regions
	Domain	26 – 139	114	MPN
	Motif	113 – 126	14	JAMM motif
Sites
	Metal binding	113	1	Zinc; catalytic Probable
	Metal binding	115	1	Zinc; catalytic Probable
	Metal binding	126	1	Zinc; catalytic By similarity
Amino acid modifications
	Modified residue	150	1	Phosphoserine Ref.7
	Modified residue	224	1	Phosphoserine Ref.6
Experimental info
	Mutagenesis	113 – 115	3	HSH → ASA: Abolishes ubiquitin thiolesterase activity, leading to prevent maintenance of JMJD2A/KDM4A on chromatin. Ref.12

Sequences

	Sequence		Length	Mass (Da)
	O00487 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: 18ACE876C7682039	FASTA	310	34,577
	10 20 30 40 50 60 MDRLLRLGGG MPGLGQGPPT DAPAVDTAEQ VYISSLALLK MLKHGRAGVP MEVMGLMLGE 70 80 90 100 110 120 FVDDYTVRVI DVFAMPQSGT GVSVEAVDPV FQAKMLDMLK QTGRPEMVVG WYHSHPGFGC 130 140 150 160 170 180 WLSGVDINTQ QSFEALSERA VAVVVDPIQS VKGKVVIDAF RLINANMMVL GHEPRQTTSN 190 200 210 220 230 240 LGHLNKPSIQ ALIHGLNRHY YSITINYRKN ELEQKMLLNL HKKSWMEGLT LQDYSEHCKH 250 260 270 280 290 300 NESVVKEMLE LAKNYNKAVE EEDKMTPEQL AIKNVGKQDP KRHLEEHVDV LMTSNIVQCL 310 AAMLDTVVFK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Resistance to diverse drugs and ultraviolet light conferred by overexpression of a novel human 26 S proteasome subunit." Spataro V., Toda T., Craig R., Seeger M., Dubiel W., Harris A.L., Norbury C. J. Biol. Chem. 272:30470-30475(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY. Tissue: Lung.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[5]	Lubec G., Afjehi-Sadat L. Submitted (MAR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 199-208, MASS SPECTROMETRY. Tissue: Brain and Cajal-Retzius cell.
[6]	"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-224, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[7]	"Quantitative phosphoproteome profiling of Wnt3a-mediated signaling network: indicating the involvement of ribonucleoside-diphosphate reductase M2 subunit phosphorylation at residue serine 20 in canonical Wnt signal transduction." Tang L.-Y., Deng N., Wang L.-S., Dai J., Wang Z.-L., Jiang X.-S., Li S.-J., Li L., Sheng Q.-H., Wu D.-Q., Li L., Zeng R. Mol. Cell. Proteomics 6:1952-1967(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-150, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[8]	"K63-specific deubiquitination by two JAMM/MPN+ complexes: BRISC-associated Brcc36 and proteasomal Poh1." Cooper E.M., Cutcliffe C., Kristiansen T.Z., Pandey A., Pickart C.M., Cohen R.E. EMBO J. 28:621-631(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PROBABLE FUNCTION, IDENTIFICATION IN THE PROTEASOME.
[9]	"Thioredoxin Txnl1/TRP32 is a redox-active cofactor of the 26 S proteasome." Andersen K.M., Madsen L., Prag S., Johnsen A.H., Semple C.A., Hendil K.B., Hartmann-Petersen R. J. Biol. Chem. 284:15246-15254(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TXNL1.
[10]	"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[11]	"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].
[12]	"The proteasomal de-ubiquitinating enzyme POH1 promotes the double-strand DNA break response." Butler L.R., Densham R.M., Jia J., Garvin A.J., Stone H.R., Shah V., Weekes D., Festy F., Beesley J., Morris J.R. EMBO J. 31:3918-3934(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IDENTIFICATION IN THE PROTEASOME, MUTAGENESIS OF 113-HIS--HIS-115.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U86782 mRNA. Translation: AAC51866.1. AK055128 mRNA. Translation: BAG51474.1. CH471058 Genomic DNA. Translation: EAX11370.1. BC066336 mRNA. Translation: AAH66336.1.
IPI	IPI00024821.
RefSeq	NP_005796.1. NM_005805.5.
UniGene	Hs.740477.
3D structure databases
ProteinModelPortal	O00487.
ModBase	Search...
Protein-protein interaction databases
IntAct	O00487. 21 interactions.
STRING	9606.ENSP00000386541.
Protein family/group databases
MEROPS	M67.001.
PTM databases
PhosphoSite	O00487.
2D gel databases
OGP	O00487.
REPRODUCTION-2DPAGE	IPI00024821.
Proteomic databases
PaxDb	O00487.
PeptideAtlas	O00487.
PRIDE	O00487.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000409682; ENSP00000386541; ENSG00000115233.
GeneID	10213.
KEGG	hsa:10213.
UCSC	uc002ubu.2. human.
Organism-specific databases
CTD	10213.
GeneCards	GC02P162164.
HGNC	HGNC:16889. PSMD14.
HPA	HPA002114.
MIM	607173. gene.
neXtProt	NX_O00487.
PharmGKB	PA134957776.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1310.
HOGENOM	HOG000183690.
HOVERGEN	HBG053742.
InParanoid	O00487.
KO	K03030.
OMA	MVLGQEP.
OrthoDB	EOG4R23V7.
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	O00487.
Bgee	O00487.
CleanEx	HS_PSMD14.
Genevestigator	O00487.
GermOnline	ENSG00000115233. Homo sapiens.
Family and domain databases
InterPro	IPR000555. JAB1_Mov34_MPN_PAD1. IPR024969. Rpn11/EIF3F_C. [Graphical view]
Pfam	PF01398. JAB. 1 hit. PF13012. MitMem_reg. 1 hit. [Graphical view]
SMART	SM00232. JAB_MPN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	O00487.
ChEMBL	CHEMBL2007629.
GenomeRNAi	10213.
NextBio	38668.
SOURCE	Search...

Entry information

Entry name

PSDE_HUMAN

Accession

Primary (citable) accession number: O00487
Secondary accession number(s): B3KNW2, O00176

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 31, 2004
Last sequence update:	July 1, 1997
Last modified:	May 1, 2013
This is version 114 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.