USP21 (1q23.3) sentrosominen deubikitinaasi

 https://www.youtube.com/watch?v=iv-u4uOFY7U

16.6. 2019 . Kaksi avainasemasa olevaa deubikitinaasia solusyklissä ovat USP21 ja  OTU-alaryhmän Cezanne. Ne sijaitsevat  molemmat  1q 21-22  tienoossa.  niiden molempien  säätely  rintaasyövässä omaa samankaltaisuutta solusyklioskillaatioissa. Ylläoleva opetusvideo selittää tarkemmin.

USP21 (1q23.3)  Sentrosomaalinen deubikitinaasi, ubikitiinin C terminaalinen hydrolaasi 21

https://www.ncbi.nlm.nih.gov/gene/27005

Also known (before) USP16; USP23

Summary

This gene encodes a member of the C19 peptidase family, also known as family 2 of ubiquitin carboxy-terminal hydrolases. 

The encoded protein cleaves ubiquitin from ubiquitinated proteins for recycling in intracellular protein degradation. 

The encoded protein is also able to release NEDD8, a ubiquitin-like (Ubl)  protein, from NEDD8-conjugated proteins. 

This gene has been referred to as USP16 and USP23 but is now known as USP21. Alternatively spliced transcript variants encoding different isoforms have been found for this gene

Preferred Names

ubiquitin carboxyl-terminal hydrolase 21

Names

NEDD8-specific protease,

deubiquitinating enzyme 21, (DUB 21)

ubiquitin specific protease 21, (USP21)

ubiquitin thioesterase 21,

ubiquitin thiolesterase 21.

ubiquitin-specific processing protease 21,

ubiquitin-specific protease 16. ( old name)

 Related articles about  USP21:

1. Proteome-wide search for functional motifs altered in tumors: Prediction of nuclear export signals inactivated by cancer-related mutations. Prieto G, et al. Sci Rep, 2016 May 12. PMID 27174732, Free PMC Article
2. Ubiquitin-specific protease 21 regulating the K48-linked polyubiquitination of NANOG. Kwon SK, et al. Biochem Biophys Res Commun, 2017 Jan 22. PMID 27956178
3. Ubiquitin specific peptidase 21 regulates interleukin-8 expression, stem-cell like property of human renal cell carcinoma. Peng L, et al. Oncotarget, 2016 Jul 5. PMID 27259257, Free PMC Article
4. Deubiquitination and stabilization of IL-33 by USP21. Tao L, et al. Int J Clin Exp Pathol, 2014. PMID 25197364, Free PMC Article
5. Identification of a novel isopeptidase with dual specificity for ubiquitin- and NEDD8-conjugated proteins. Gong L, et al. J Biol Chem, 2000 May 12. PMID 10799498 

GeneRIFs: Gene References Into Functions

6. Results from computational biology identified a cancer mutation that inactivates the nuclear export signals (NES) of the human deubiquitinase USP21, and leads to the aberrant accumulation of this protein in the nucleus.
7. Data show that ubiquitin variants (Ubvs) that bind to USP2 or USP21 contain a similar core functional epitope, or "hot spot," consisting mainly of positions that are conserved as the wild type sequence, but also some positions that prefer mutant sequences.
8. USP21 binds to the promoter region of IL-8 and mediates transcriptional initiation, which regulates the stem-cell like property of human renal cell carcinoma
9. USP21 interacts with, deubiquitinates and stabilizes BRCA2 to promote efficient RAD51 loading at DNA double-strand breaks.
10. a critical role of p38-mediated USP21 phosphorylation in regulating STING-mediated antiviral functions and identifies p38-USP21 axis as an important pathway that DNA virus adopts to avoid innate immunity responses.
11. USP21 recruits and stabilises Gli1 at the centrosome.
12. USP21 specifically regulates the Lys48-linked polyubiquitination and stability of NANOG
13. Data show that SUMOylated BANP, E5R, and Nac1 (BEN) domain 3 (BEND3) stabilizes NoRC component TTF-1-interacting protein 5 (Tip5)via association with ubiquitin specific protease 21 (USP21) debiquitinase
14. The protein stability of IL-33 is maintained by USP21 through deubiquitination
15. Identification of the E3 deubiquitinase ubiquitin-specific peptidase 21 (USP21) as a positive regulator of the transcription factor GATA3 

Peptide history, structure: (ubiquitin carboxyl-terminal hydrolase 21 isoform c. https://www.ncbi.nlm.nih(2017) .gov/protein/NP_001014443

Conserved Domains (2) summary
cd02674
Location:213 → 556
Peptidase_C19R; .A subfamily of peptidase C19. Peptidase C19 contains ubiquitinyl hydrolases. They are intracellular peptidases that remove ubiquitin molecules from polyubiquinated peptides by cleavage of isopeptide bonds. They hydrolyze bonds involving the carboxyl group of the C-terminal Gly residue of ubiquitin. The purpose of the de-ubiquitination is thought to be editing of the ubiquitin conjugates, which could rescue them from degradation, as well as recycling of the ubiquitin. The ubiquitin/proteasome system is responsible for most protein turnover in the mammalian cell, and with over 50 members, family C19 is one of the largest families of peptidases in the human genome.
pfam00443
Location:212 → 555
UCH; Ubiquitin carboxyl-terminal hydrolase

Go to:

LOCUS NP_001014443 565 aa linear PRI 23-JUN-2018
DEFINITION ubiquitin carboxyl-terminal hydrolase 21 isoform c [Homo sapiens].
•  (2017 ) Ubiquitin-specific protease 21 stabilizes BRCA2 to control DNA repair and tumor growth
• a critical role of p38-mediated USP21 phosphorylation in regulating STING-mediated antiviral functions and identifies p38-USP21 axis as an important pathway that DNA virus adopts to avoid innate immunity responses.
• (2017) Ubiquitin-specific protease 21 regulating  the K48-linked polyubiquitination of NANOG
• (2016) The centrosomal deubiquitylase USP21 regulates Gli1 transcriptional activity and stability 
• (2012) Systematic survey of deubiquitinase localization identifies USP21 as a regulator of centrosome- and microtubule-associated functions 
• (2011) Polyubiquitin binding and cross-reactivity in the USP domain deubiquitinase USP21
• (2010) USP21 plays an important role in the down-regulation  TNFalpha-induced NF-kappaB activation through deubiquitinating RIP1.
• (2000) Identification of a novel isopeptidase with dual  specificity for ubiquitin- and NEDD8-conjugated proteins,
• ##Evidence-Data-END##
  FEATURES Location/Qualifiers
  source 1..565
  /organism="Homo sapiens"
  /db_xref="taxon:9606"
  /chromosome="1"
  /map="1q23.3"
  Protein 1..565
  /product="ubiquitin carboxyl-terminal hydrolase 21 isoform
  c"
  /EC_number="3.4.19.12"
  /note="ubiquitin specific protease 21; ubiquitin
  thiolesterase 21; ubiquitin-specific processing protease
  21; deubiquitinating enzyme 21; ubiquitin
  carboxyl-terminal hydrolase 21; ubiquitin-specific
  protease 16; NEDD8-specific protease; ubiquitin
  thioesterase 21"
  /calculated_mol_wt=62525
  Region 134..152
  /region_name="Nuclear export signal"
  /experiment="experimental evidence, no additional details
  recorded"
  /note="propagated from UniProtKB/Swiss-Prot (Q9UK80.1)"
  Region 212..555
  /region_name="UCH"
  /note="Ubiquitin carboxyl-terminal hydrolase; pfam00443"
  /db_xref="CDD:278850"
  Region 213..556
  /region_name="Peptidase_C19R"
  /note="A subfamily of peptidase C19. Peptidase C19
  contains ubiquitinyl hydrolases. They are intracellular
  peptidases that remove ubiquitin molecules from
  polyubiquinated peptides by cleavage of isopeptide bonds.
  They hydrolyze bonds involving the carboxyl...; cd02674"
  /db_xref="CDD:239139"
  Site order(216,221,518,534)
  /site_type="active"
  /db_xref="CDD:239139"
  CDS 1..565
  /gene="USP21"
  /gene_synonym="USP16; USP23"
  /coded_by="NM_001014443.2:378..2075"
  /note="isoform c is encoded by transcript variant 3"
  /db_xref="CCDS:CCDS30920.1"
  /db_xref="GeneID:27005"
  /db_xref="HGNC:HGNC:12620"
  /db_xref="MIM:604729"
  ORIGIN
  1 mpqasehrlg rtreppvniq prvgsklpfa prarskerrn pasgpnpmlr plpprpglpd
  61 erlkklelgr grtsgprprg plradhgvpl pgsppptval plpsrtnlar sksvssgdlr
  121 pmgialgghr gtgelgaals rlalrpeppt lrrstslrrl ggfpgpptlf sirteppash
  181 gsfhmisars sepfysddkm ahhtlllgsg hvglrnlgnt cflnavlqcl sstrplrdfc
  241 lrrdfrqevp gggraqelte afadvigalw hpdsceavnp trfravfqky vpsfsgysqq
  301 daqeflkllm erlhleinrr grrappilan gpvpspprrg galleepels dddranlmwk
  361 ryleredski vdlfvgqlks clkcqacgyr sttfevfcdl slpipkkgfa ggkvslrdcf
  421 nlftkeeele senapvcdrc rqktrstkkl tvqrfprilv lhlnrfsasr gsikkssvgv
  481 dfplqrlslg dfasdkagsp vyqlyalcnh sgsvhyghyt alcrcqtgwh vyndsrvspv
  541 senqvasseg yvlfyqlmqe pprcl
  //
  Päivitystä. 21.5. 2019 Muistiin USP21, DUB.( useita kohdemolekyylejä! Mm. BRCA2, NANOG, GATA3, IL-33, Gli1, RIP1)