POH1, PSMD14 (2q24.2), proteosomikompleksin komponentti

https://www.ncbi.nlm.nih.gov/gene/10213

Official Symbol PSMD14

Official Full Name: proteasome 26S subunit, non-ATPase 14

Gene type: protein coding

Also known as  PAD1; POH1; RPN11

Summary: This gene encodes a component of the 26S proteasome. The 26S proteasome is a large multiprotein complex that catalyzes the degradation of ubiquitinated intracellular proteins.

 The encoded protein is a component of the 19S regulatory cap complex of the 26S proteasome and mediates substrate deubiquitination. A pseudogene of this gene is also located on the long arm of chromosome 2. [provided by RefSeq, Feb 2012]

Expression Ubiquitous expression in brain (RPKM 24.9), testis (RPKM 22.1) and 25 other tissues See more Orthologs mouse all

 

Preferred Names

26S proteasome non-ATPase regulatory subunit 14

Names

26S proteasome regulatory subunit rpn11

26S proteasome-associated PAD1 homolog 1

proteasome (prosome, macropain) 26S subunit, non-ATPase, 14

testis tissue sperm-binding protein Li 69n

 https://www.ncbi.nlm.nih.gov/protein/NP_005796.1

ORIGIN      
        1 mdrllrlggg mpglgqgppt dapavdtaeq vyisslallk mlkhgragvp mevmglmlge
       61 fvddytvrvi dvfampqsgt gvsveavdpv fqakmldmlk qtgrpemvvg wyHsHpgfgc
      121 wlsgvDintq qsfealsera vavvvdpiqs vkgkvvidaf rlinanmmvl gheprqttsn
      181 lghlnkpsiq alihglnrhy ysitinyrkn eleqkmllnl hkkswmeglt lqdysehckh
      241 nesvvkemle laknynkave eedkmtpeql aiknvgkqdp krhleehvdv lmtsnivqcl
      301 aamldtvvfk
//

Site            order(E52,H113,H115,S123,D126) 
                     /site_type="other"
                     /note="MPN+ (JAMM) motif" (ehhsd) 
                     /db_xref="CDD:163700"
     Region          113..126
                     /region_name="JAMM motif.
                     {ECO:0000255|PROSITE-ProRule:PRU01182}"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (O00487.1)"
     Site            order(H113,H115,D126)
                     /site_type="other"
                     /note="Zinc-binding site [ion binding]"
                     /db_xref="CDD:163700"

Conserved Domains (1) summary

cd08069
Location:21 → 286

MPN_RPN11_CSN5; Mov34/MPN/PAD-1 family: proteasomal regulatory protein Rpn11 and signalosome complex subunit CSN5

This family contains proteasomal regulatory protein Rpn11 (26S proteasome regulatory subunit rpn11; PAD1; POH1; RPN11; PSMD14; Rpn11 subunit of the 19S-proteasome; regulatory particle number 11) and signalosomal CSN5 (COP9 signalosome complex subunit 5; COP9 complex homolog subunit 5; c-Jun activation domain-binding protein-1; CSN5/JAB1; JAB1). COP9 signalosome (CSN) and the proteasome lid are paralogous complexes and their respective subunits CSN5 and Rpn11 are most closely related between the two complexes, both containing the conserved JAMM (JAB1/MPN/Mov34 metalloenzyme) motif involved in zinc ion coordination and providing the active site for isopeptidase activity. Rpn11 is responsible for substrate deubiquitination during proteasomal degradation. It is essential for maintaining a correct cell cycle and normal mitochondrial morphology and physiology; mutations in Rpn11 cause cell cycle and mitochondrial defects, temperature sensitivity and sensitivity to DNA damaging reagents such as UV. It has been shown that the C-terminal region of Rpn11 is involved in the regulation of the mitochondrial fission and tubulation processes. CSN5, one of the eight subunits of CSN, is critical for nuclear export and the degradation of several tumor suppressor proteins, including p53, p27, and Smad4. Its MPN+ domain is critical for the physical interaction of RUNX3 and Jab1. It has been suggested that the direct interaction of CSN5/JAB1 with p27 provides p27 with a leucine-rich nuclear export signal (NES), which is required for binding to chromosomal region maintenance 1 (CRM1), and facilitates nuclear export. The over-expression of CSN5/JAB1 also has been implicated in cancer initiation and progression, including cancer of the lung, pancreas, mouth, thyroid, and breast, suggesting that the oncogenic activity of CSN5 is associated with the down-regulation of RUNX3.

Related articles in PubMed

1. RPN11 deubiquitinase promotes proliferation and migration of breast cancer cells. Luo G, et al. Mol Med Rep, 2017 Jul. PMID 28535005
2. Knockdown of human deubiquitinase PSMD14 induces cell cycle arrest and senescence. Byrne A, et al. Exp Cell Res, 2010 Jan 15. PMID 19732767
3. Relationship between expression of Pad1 homologue and multidrug resistance of idiopathic nephrotic syndrome. Ma Z, et al. Pediatr Int, 2009 Oct. PMID 19419512
4. The JAMM motif of human deubiquitinase Poh1 is essential for cell viability. Gallery M, et al. Mol Cancer Ther, 2007 Jan. PMID 17237285
5. The 19 S proteasomal subunit POH1 contributes to the regulation of c-Jun ubiquitination, stability, and subcellular localization. Nabhan JF, et al. J Biol Chem, 2006 Jun 9. PMID 16569633

See all (97) citations in PubMed

GeneRIFs: Gene References Into Functions

1. Findings suggest proteasome 26S subunit non-ATPase 14 (PSMD14) as a deubiquitinating enzyme to regulate Snail transcription factor (SNAIL) at the post-translational level and provide a promising therapeutic strategy against tumor metastasis of esophageal cancer.
2. POH1 knockdown induced cell apoptosis through increased expression of p53 and Bim.
3. overexpression of RPN11 in breast cancer tissues was associated with an advanced clinical stage. Patients with tumors with high expression of RPN11 had worse prognosis.
4. Deubiquitylase POH1 stabilizes E2F1 protein through binding to and deubiquitylating E2F1 in liver cancer.
5. The data demonstrated that proteasomal POH1 is a key de-ubiquitinating enzyme that regulates ubiquitin conjugates generated in response to damage and that several aspects of the DNA double-strand break response are regulated by the proteasome.
6. Disorder of POH1 expression is involved in the onset of idiopathic nephrotic syndrome (INS), and confers multidrug resistance in children with INS
7. Down-regulation of PSMD14 results in decreased cell proliferation, cell cycle arrest and senescence. A comparative study with PSMB5, revealed that PSMB5 and PSMD14 have different effects on cell cycle, senescence and associated molecular events.
8. Specificity for K63-linked polyubiquitin is a common property of the JAMM/MPN+ family of deubiquitinating enzymes.
9. Ectopic expression of POH1 in HEK293 cells decreased the level of c-Jun ubiquitination, leading to significant accumulation of the protein and a corresponding increase in AP1-mediated gene expression
10. An intact zinc metalloproteinase motif of Poh1 is essential for cell viability and 26S proteasome function.