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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''Ubiquitin carboxyl-terminal hydrolase or Ubiquitin specific protease 11''' is an [[enzyme]] that in humans is encoded by the ''USP11'' [[gene]].<ref name="pmid12838346">{{cite journal | vauthors = Puente XS, Sánchez LM, Overall CM, López-Otín C | title = Human and mouse proteases: a comparative genomic approach | journal = Nature Reviews. Genetics | volume = 4 | issue = 7 | pages = 544–58 | date = July 2003 | pmid = 12838346 | pmc =  | doi = 10.1038/nrg1111 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: USP11 ubiquitin specific peptidase 11| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8237| accessdate = }}</ref> USP11 belongs to the Ubiquitin specific proteases family (USPs) which is a sub-family of the Deubiquitinating enzymes (DUBs).USPs are multiple domain proteases and belong to the C19 cysteine proteases sub‒family. Depending on their domain architecture and position there is different homology between the various members. Generally the largest domain is the catalytic domain which harbours the three residue catalytic triad that is included inside conserved motifs (Cys and His boxes). The catalytic domain also contains sequences that are not related with the catalysis function and their role is mostly not clearly understood at present, the length of these sequences varies for each USP and therefore the length of the whole catalytic domain can range from approximately 295 to 850 amino acids.<ref>{{cite journal | vauthors = Nijman SM, Luna-Vargas MP, Velds A, Brummelkamp TR, Dirac AM, Sixma TK, Bernards R | title = A genomic and functional inventory of deubiquitinating enzymes | journal = Cell | volume = 123 | issue = 5 | pages = 773–86 | date = December 2005 | pmid = 16325574 | doi = 10.1016/j.cell.2005.11.007 }}</ref> Particular sequences inside the catalytic domain or at the N‒terminus of some USPs have been characterised as UBL (Ubiquitin like) and DUSP (domain present in ubiquitin‒specific proteases) domains respectively. In some cases, regarding the UBL domains, it has been reported to have a catalysis enhancing function as in the case of USP7.<ref>{{cite journal | vauthors = Faesen AC, Dirac AM, Shanmugham A, Ovaa H, Perrakis A, Sixma TK | title = Mechanism of USP7/HAUSP activation by its C-terminal ubiquitin-like domain and allosteric regulation by GMP-synthetase | journal = Molecular Cell | volume = 44 | issue = 1 | pages = 147–59 | date = October 2011 | pmid = 21981925 | doi = 10.1016/j.molcel.2011.06.034 }}</ref> In addition, a so‒called DU domain module is the combination of a DUSP domain followed by a UBL domain separated by a linker and is found in USP11 as well as in USP15 and USP4.
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
USP11 is 963aa protein with a MW of approximately 109.8 kDa and a pI of ~5.28; it shares significant homology with USP15 and along with USP4 forms the DU subfamily. Nevertheless, alignment of the three USPs confirms that USP15 and USP4 are the closest homologues with the identity reaching ~73 % between their UBL1 domains whereas USP11 is the most distant member with an identity of only ~32.3 % when compared to USP15. An UBL2 domain insertion (285aa) is present within the catalytic domain, which encompasses amino acids 310‒931, and the catalytic triad consists of a cysteine, a histidine and an aspartic acid.
{{GNF_Protein_box
| image = 
| image_source = 
| PDB =
| Name = Ubiquitin specific peptidase 11
| HGNCid = 12609
| Symbol = USP11
| AltSymbols =; UHX1
| OMIM = 300050
| ECnumber = 
| Homologene = 31252
| MGIid = 2384312
| Function = {{GNF_GO|id=GO:0004197 |text = cysteine-type endopeptidase activity}} {{GNF_GO|id=GO:0004221 |text = ubiquitin thiolesterase activity}} {{GNF_GO|id=GO:0008233 |text = peptidase activity}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}}
| Process = {{GNF_GO|id=GO:0006511 |text = ubiquitin-dependent protein catabolic process}} {{GNF_GO|id=GO:0006512 |text = ubiquitin cycle}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 8237
    | Hs_Ensembl = ENSG00000102226
    | Hs_RefseqProtein = NP_004642
    | Hs_RefseqmRNA = NM_004651
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = X
    | Hs_GenLoc_start = 46977258
    | Hs_GenLoc_end = 46992671
    | Hs_Uniprot = P51784
    | Mm_EntrezGene = 236733
    | Mm_Ensembl = ENSMUSG00000031066
    | Mm_RefseqmRNA = NM_145628
    | Mm_RefseqProtein = NP_663603
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = X
    | Mm_GenLoc_start = 19860891
    | Mm_GenLoc_end = 19877498
    | Mm_Uniprot = Q3T9X4
  }}
}}
'''Ubiquitin specific peptidase 11''', also known as '''USP11''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: USP11 ubiquitin specific peptidase 11| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8237| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{PBB_Summary
| section_title =  
| summary_text = Protein ubiquitination controls many intracellular processes, including cell cycle progression, transcriptional activation, and signal transduction. This dynamic process, involving ubiquitin conjugating enzymes and deubiquitinating enzymes, adds and removes ubiquitin. Deubiquitinating enzymes are cysteine proteases that specifically cleave ubiquitin from ubiquitin-conjugated protein substrates. This gene encodes a deubiquitinating enzyme which lies in a gene cluster on chromosome Xp11.23<ref name="entrez">{{cite web | title = Entrez Gene: USP11 ubiquitin specific peptidase 11| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8237| accessdate = }}</ref>
}}


==References==
Protein ubiquitination controls many intracellular processes, including cell cycle progression, transcriptional activation, and signal transduction. This dynamic process, involving ubiquitin conjugating enzymes and deubiquitinating enzymes, adds and removes ubiquitin. Deubiquitinating enzymes are cysteine proteases that specifically cleave ubiquitin from ubiquitin-conjugated protein substrates. This gene encodes a deubiquitinating enzyme which lies in a gene cluster on chromosome Xp11.23<ref name="entrez"/>
{{reflist|2}}
 
==Further reading==
== Interactions ==
{{refbegin | 2}}
 
{{PBB_Further_reading
USP11 has been shown to [[Protein-protein interaction|interact]] with [[RANBP9]].<ref name=pmid12084015>{{cite journal | vauthors = Ideguchi H, Ueda A, Tanaka M, Yang J, Tsuji T, Ohno S, Hagiwara E, Aoki A, Ishigatsubo Y | title = Structural and functional characterization of the USP11 deubiquitinating enzyme, which interacts with the RanGTP-associated protein RanBPM | journal = The Biochemical Journal | volume = 367 | issue = Pt 1 | pages = 87–95 | date = October 2002 | pmid = 12084015 | pmc = 1222860 | doi = 10.1042/BJ20011851 }}</ref>
| citations =  
 
*{{cite journal | author=D'Andrea A, Pellman D |title=Deubiquitinating enzymes: a new class of biological regulators. |journal=Crit. Rev. Biochem. Mol. Biol. |volume=33 |issue= 5 |pages= 337-52 |year= 1999 |pmid= 9827704 |doi= }}
== Model organisms ==
*{{cite journal  | author=Puente XS, Sánchez LM, Overall CM, López-Otín C |title=Human and mouse proteases: a comparative genomic approach. |journal=Nat. Rev. Genet. |volume=4 |issue= 7 |pages= 544-58 |year= 2003 |pmid= 12838346 |doi= 10.1038/nrg1111 }}
 
*{{cite journal  | author=Swanson DA, Freund CL, Ploder L, ''et al.'' |title=A ubiquitin C-terminal hydrolase gene on the proximal short arm of the X chromosome: implications for X-linked retinal disorders. |journal=Hum. Mol. Genet. |volume=5 |issue= 4 |pages= 533-8 |year= 1996 |pmid= 8845848 |doi= }}
[[Model organism]]s have been used in the study of USP11 function. A conditional [[knockout mouse]] line called ''Usp11<sup>tm1(KOMP)Wtsi</sup>'' was generated at the [[Wellcome Trust Sanger Institute]].<ref name="mgp_reference">{{cite journal |title=The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice |author=Gerdin AK |year=2010 |journal=Acta Ophthalmologica|volume=88 |pages=925–7|doi=10.1111/j.1755-3768.2010.4142.x }}</ref> Male and female animals underwent a standardized [[phenotypic screen]]<ref name="IMPCsearch_ref">{{cite web |url=http://www.mousephenotype.org/data/search?q=Usp11#fq=*:*&facet=gene |title=International Mouse Phenotyping Consortium}}</ref> to determine the effects of deletion.<ref name="pmid21677750">{{cite journal | vauthors = Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A | title = A conditional knockout resource for the genome-wide study of mouse gene function | journal = Nature | volume = 474 | issue = 7351 | pages = 337–42 | date = June 2011 | pmid = 21677750 | pmc = 3572410 | doi = 10.1038/nature10163 }}</ref><ref name="mouse_library">{{cite journal | vauthors = Dolgin E | title = Mouse library set to be knockout | journal = Nature | volume = 474 | issue = 7351 | pages = 262–3 | date = June 2011 | pmid = 21677718 | doi = 10.1038/474262a }}</ref><ref name="mouse_for_all_reasons">{{cite journal | vauthors = Collins FS, Rossant J, Wurst W | title = A mouse for all reasons | journal = Cell | volume = 128 | issue = 1 | pages = 9–13 | date = January 2007 | pmid = 17218247 | doi = 10.1016/j.cell.2006.12.018 }}</ref><ref name="pmid23870131">{{cite journal | vauthors = White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP | display-authors = 6 | title = Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes | journal = Cell | volume = 154 | issue = 2 | pages = 452–64 | date = July 2013 | pmid = 23870131 | pmc = 3717207 | doi = 10.1016/j.cell.2013.06.022 }}</ref> Additional screens performed: In-depth immunological phenotyping<ref name="iii_ref">{{cite web |url= http://www.immunophenotyping.org/data/search?keys=Usp11&field_gene_construct_tid=All |title=Infection and Immunity Immunophenotyping (3i) Consortium}}</ref>
*{{cite journal | author=Brandau O, Nyakatura G, Jedele KB, ''et al.'' |title=UHX1 and PCTK1: precise characterisation and localisation within a gene-rich region in Xp11.23 and evaluation as candidate genes for retinal diseases mapped to Xp21.1-p11.2. |journal=Eur. J. Hum. Genet. |volume=6 |issue= 5 |pages= 459-66 |year= 1999 |pmid= 9801870 |doi= 10.1038/sj.ejhg.5200207 }}
{| class="wikitable sortable collapsible collapsed" border="1" cellpadding="2" style="float: left;" |
*{{cite journal | author=Stoddart KL, Jermak C, Nagaraja R, ''et al.'' |title=Physical map covering a 2 Mb region in human xp11.3 distal to DX6849. |journal=Gene |volume=227 |issue= 1 |pages= 111-6 |year= 1999 |pmid= 9931462 |doi= }}
|+ ''Usp11'' knockout mouse phenotype
*{{cite journal  | author=Thiselton DL, McDowall J, Brandau O, ''et al.'' |title=An integrated, functionally annotated gene map of the DXS8026-ELK1 interval on human Xp11.3-Xp11.23: potential hotspot for neurogenetic disorders. |journal=Genomics |volume=79 |issue= 4 |pages= 560-72 |year= 2002 |pmid= 11944989 |doi= 10.1006/geno.2002.6733 }}
|-
*{{cite journal  | author=Ideguchi H, Ueda A, Tanaka M, ''et al.'' |title=Structural and functional characterization of the USP11 deubiquitinating enzyme, which interacts with the RanGTP-associated protein RanBPM. |journal=Biochem. J. |volume=367 |issue= Pt 1 |pages= 87-95 |year= 2003 |pmid= 12084015 |doi= 10.1042/BJ20011851 }}
! Characteristic!! Phenotype
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
|-
*{{cite journal  | author=Angelats C, Wang XW, Jermiin LS, ''et al.'' |title=Isolation and characterization of the mouse ubiquitin-specific protease Usp15. |journal=Mamm. Genome |volume=14 |issue= 1 |pages= 31-46 |year= 2003 |pmid= 12532266 |doi= 10.1007/s00335-002-3035-0 }}
| colspan=2; style="text-align: center;" | All data available at.<ref name="IMPCsearch_ref"/><ref name="iii_ref" />
*{{cite journal  | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
|-
*{{cite journal  | author=Bouwmeester T, Bauch A, Ruffner H, ''et al.'' |title=A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. |journal=Nat. Cell Biol. |volume=6 |issue= 2 |pages= 97-105 |year= 2004 |pmid= 14743216 |doi= 10.1038/ncb1086 }}
| Insulin || bgcolor="#488ED3"|Normal
*{{cite journal  | author=Schoenfeld AR, Apgar S, Dolios G, ''et al.'' |title=BRCA2 is ubiquitinated in vivo and interacts with USP11, a deubiquitinating enzyme that exhibits prosurvival function in the cellular response to DNA damage. |journal=Mol. Cell. Biol. |volume=24 |issue= 17 |pages= 7444-55 |year= 2004 |pmid= 15314155 |doi= 10.1128/MCB.24.17.7444-7455.2004 }}
 
*{{cite journal | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
|-
*{{cite journal | author=Ross MT, Grafham DV, Coffey AJ, ''et al.'' |title=The DNA sequence of the human X chromosome. |journal=Nature |volume=434 |issue= 7031 |pages= 325-37 |year= 2005 |pmid= 15772651 |doi= 10.1038/nature03440 }}
| Homozygous viability at P14 || bgcolor="#488ED3"|Normal
*{{cite journal | author=Ewing RM, Chu P, Elisma F, ''et al.'' |title=Large-scale mapping of human protein-protein interactions by mass spectrometry. |journal=Mol. Syst. Biol. |volume=3 |issue=  |pages= 89 |year= 2007 |pmid= 17353931 |doi= 10.1038/msb4100134 }}
 
}}
|-
| Homozygous Fertility || bgcolor="#488ED3"|Normal
 
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| Neurological assessment || bgcolor="#488ED3"|Normal
 
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| Grip strength || bgcolor="#488ED3"|Normal
 
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| [[Dysmorphology]] || bgcolor="#488ED3"|Normal
 
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| [[Indirect calorimetry]] || bgcolor="#488ED3"|Normal
 
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| [[Glucose tolerance test]] || bgcolor="#488ED3"|Normal
 
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| [[Auditory brainstem response]] || bgcolor="#488ED3"|Normal
 
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| [[Dual-energy X-ray absorptiometry|DEXA]] || bgcolor="#488ED3"|Normal
 
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| [[Radiography]] || bgcolor="#488ED3"|Normal
 
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| Eye morphology || bgcolor="#488ED3"|Normal
 
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| [[Clinical chemistry]] || bgcolor="#488ED3"|Normal
 
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| ''[[Haematology]]'' 16 Weeks || bgcolor="#488ED3"|Normal
 
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| Peripheral blood leukocytes 16 Weeks || bgcolor="#488ED3"|Normal
 
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{{clear|left}}
 
== References ==
{{reflist|32em}}
 
== Further reading ==
{{refbegin|32em}}
* {{cite journal | vauthors = D'Andrea A, Pellman D | title = Deubiquitinating enzymes: a new class of biological regulators | journal = Critical Reviews in Biochemistry and Molecular Biology | volume = 33 | issue = 5 | pages = 337–52 | year = 1999 | pmid = 9827704 | doi = 10.1080/10409239891204251 }}
* {{cite journal | vauthors = Swanson DA, Freund CL, Ploder L, McInnes RR, Valle D | title = A ubiquitin C-terminal hydrolase gene on the proximal short arm of the X chromosome: implications for X-linked retinal disorders | journal = Human Molecular Genetics | volume = 5 | issue = 4 | pages = 533–8 | date = April 1996 | pmid = 8845848 | doi = 10.1093/hmg/5.4.533 }}
* {{cite journal | vauthors = Brandau O, Nyakatura G, Jedele KB, Platzer M, Achatz H, Ross M, Murken J, Rosenthal A, Meindl A | title = UHX1 and PCTK1: precise characterisation and localisation within a gene-rich region in Xp11.23 and evaluation as candidate genes for retinal diseases mapped to Xp21.1-p11.2 | journal = European Journal of Human Genetics | volume = 6 | issue = 5 | pages = 459–66 | year = 1999 | pmid = 9801870 | doi = 10.1038/sj.ejhg.5200207 }}
* {{cite journal | vauthors = Stoddart KL, Jermak C, Nagaraja R, Schlessinger D, Bech-Hansen NT | title = Physical map covering a 2 Mb region in human xp11.3 distal to DX6849 | journal = Gene | volume = 227 | issue = 1 | pages = 111–6 | date = February 1999 | pmid = 9931462 | doi = 10.1016/S0378-1119(98)00564-2 }}
* {{cite journal | vauthors = Thiselton DL, McDowall J, Brandau O, Ramser J, d'Esposito F, Bhattacharya SS, Ross MT, Hardcastle AJ, Meindl A | title = An integrated, functionally annotated gene map of the DXS8026-ELK1 interval on human Xp11.3-Xp11.23: potential hotspot for neurogenetic disorders | journal = Genomics | volume = 79 | issue = 4 | pages = 560–72 | date = April 2002 | pmid = 11944989 | doi = 10.1006/geno.2002.6733 }}
* {{cite journal | vauthors = Ideguchi H, Ueda A, Tanaka M, Yang J, Tsuji T, Ohno S, Hagiwara E, Aoki A, Ishigatsubo Y | title = Structural and functional characterization of the USP11 deubiquitinating enzyme, which interacts with the RanGTP-associated protein RanBPM | journal = The Biochemical Journal | volume = 367 | issue = Pt 1 | pages = 87–95 | date = October 2002 | pmid = 12084015 | pmc = 1222860 | doi = 10.1042/BJ20011851 }}
* {{cite journal | vauthors = Angelats C, Wang XW, Jermiin LS, Copeland NG, Jenkins NA, Baker RT | title = Isolation and characterization of the mouse ubiquitin-specific protease Usp15 | journal = Mammalian Genome | volume = 14 | issue = 1 | pages = 31–46 | date = January 2003 | pmid = 12532266 | doi = 10.1007/s00335-002-3035-0 }}
* {{cite journal | vauthors = Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G | title = A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway | journal = Nature Cell Biology | volume = 6 | issue = 2 | pages = 97–105 | date = February 2004 | pmid = 14743216 | doi = 10.1038/ncb1086 }}
* {{cite journal | vauthors = Schoenfeld AR, Apgar S, Dolios G, Wang R, Aaronson SA | title = BRCA2 is ubiquitinated in vivo and interacts with USP11, a deubiquitinating enzyme that exhibits prosurvival function in the cellular response to DNA damage | journal = Molecular and Cellular Biology | volume = 24 | issue = 17 | pages = 7444–55 | date = September 2004 | pmid = 15314155 | pmc = 506974 | doi = 10.1128/MCB.24.17.7444-7455.2004 }}
* {{cite journal | vauthors = Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D | title = Large-scale mapping of human protein-protein interactions by mass spectrometry | journal = Molecular Systems Biology | volume = 3 | issue = 1 | pages = 89 | year = 2007 | pmid = 17353931 | pmc = 1847948 | doi = 10.1038/msb4100134 }}
{{refend}}
{{refend}}
{{protein-stub}}
{{WikiDoc Sources}}

Latest revision as of 10:11, 20 March 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

n/a

n/a

Ensembl

n/a

n/a

UniProt

n/a

n/a

RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Ubiquitin carboxyl-terminal hydrolase or Ubiquitin specific protease 11 is an enzyme that in humans is encoded by the USP11 gene.[1][2] USP11 belongs to the Ubiquitin specific proteases family (USPs) which is a sub-family of the Deubiquitinating enzymes (DUBs).USPs are multiple domain proteases and belong to the C19 cysteine proteases sub‒family. Depending on their domain architecture and position there is different homology between the various members. Generally the largest domain is the catalytic domain which harbours the three residue catalytic triad that is included inside conserved motifs (Cys and His boxes). The catalytic domain also contains sequences that are not related with the catalysis function and their role is mostly not clearly understood at present, the length of these sequences varies for each USP and therefore the length of the whole catalytic domain can range from approximately 295 to 850 amino acids.[3] Particular sequences inside the catalytic domain or at the N‒terminus of some USPs have been characterised as UBL (Ubiquitin like) and DUSP (domain present in ubiquitin‒specific proteases) domains respectively. In some cases, regarding the UBL domains, it has been reported to have a catalysis enhancing function as in the case of USP7.[4] In addition, a so‒called DU domain module is the combination of a DUSP domain followed by a UBL domain separated by a linker and is found in USP11 as well as in USP15 and USP4.

USP11 is 963aa protein with a MW of approximately 109.8 kDa and a pI of ~5.28; it shares significant homology with USP15 and along with USP4 forms the DU subfamily. Nevertheless, alignment of the three USPs confirms that USP15 and USP4 are the closest homologues with the identity reaching ~73 % between their UBL1 domains whereas USP11 is the most distant member with an identity of only ~32.3 % when compared to USP15. An UBL2 domain insertion (285aa) is present within the catalytic domain, which encompasses amino acids 310‒931, and the catalytic triad consists of a cysteine, a histidine and an aspartic acid.

Function

Protein ubiquitination controls many intracellular processes, including cell cycle progression, transcriptional activation, and signal transduction. This dynamic process, involving ubiquitin conjugating enzymes and deubiquitinating enzymes, adds and removes ubiquitin. Deubiquitinating enzymes are cysteine proteases that specifically cleave ubiquitin from ubiquitin-conjugated protein substrates. This gene encodes a deubiquitinating enzyme which lies in a gene cluster on chromosome Xp11.23[2]

Interactions

USP11 has been shown to interact with RANBP9.[5]

Model organisms

Model organisms have been used in the study of USP11 function. A conditional knockout mouse line called Usp11tm1(KOMP)Wtsi was generated at the Wellcome Trust Sanger Institute.[6] Male and female animals underwent a standardized phenotypic screen[7] to determine the effects of deletion.[8][9][10][11] Additional screens performed: In-depth immunological phenotyping[12]

References

  1. ↑ Puente XS, Sánchez LM, Overall CM, López-Otín C (July 2003). "Human and mouse proteases: a comparative genomic approach". Nature Reviews. Genetics. 4 (7): 544–58. doi:10.1038/nrg1111. PMID 12838346.
  2. ↑ 2.0 2.1 "Entrez Gene: USP11 ubiquitin specific peptidase 11".
  3. ↑ Nijman SM, Luna-Vargas MP, Velds A, Brummelkamp TR, Dirac AM, Sixma TK, Bernards R (December 2005). "A genomic and functional inventory of deubiquitinating enzymes". Cell. 123 (5): 773–86. doi:10.1016/j.cell.2005.11.007. PMID 16325574.
  4. ↑ Faesen AC, Dirac AM, Shanmugham A, Ovaa H, Perrakis A, Sixma TK (October 2011). "Mechanism of USP7/HAUSP activation by its C-terminal ubiquitin-like domain and allosteric regulation by GMP-synthetase". Molecular Cell. 44 (1): 147–59. doi:10.1016/j.molcel.2011.06.034. PMID 21981925.
  5. ↑ Ideguchi H, Ueda A, Tanaka M, Yang J, Tsuji T, Ohno S, Hagiwara E, Aoki A, Ishigatsubo Y (October 2002). "Structural and functional characterization of the USP11 deubiquitinating enzyme, which interacts with the RanGTP-associated protein RanBPM". The Biochemical Journal. 367 (Pt 1): 87–95. doi:10.1042/BJ20011851. PMC 1222860. PMID 12084015.
  6. ↑ Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  7. ↑ 7.0 7.1 "International Mouse Phenotyping Consortium".
  8. ↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  9. ↑ Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  10. ↑ Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  11. ↑ White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, et al. (July 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
  12. ↑ 12.0 12.1 "Infection and Immunity Immunophenotyping (3i) Consortium".

Further reading

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