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'''NLRP11''', short for [[NOD-like receptor]] family [[pyrin domain]] containing 11, is an [[intracellular]] protein of mammals. It is also known as NALP11, PYPAF6, NOD17, PAN10, and CLR19.6, and is one of 14 pyrin domain containing members of the NOD-like receptor family of [[cytoplasm]]ic receptors.<ref name="pmid12563287">{{cite journal |vauthors=Tschopp J, Martinon F, Burns K |title=NALPs: a novel protein family involved in inflammation |journal=Nat. Rev. Mol. Cell Biol. |volume=4 |issue=2 |pages=95–104 |date=February 2003 |pmid=12563287 |doi=10.1038/nrm1019 |s2cid=31417018 }}</ref> The function of NLRP11 is currently unknown.
NLRP11, short for NOD-like receptor family pyrin domain containing 11, is an intracellular protein of mammals. NLRP11 is an intracellular [[protein]] encoded in humans by the ''NLRP'' gene located on the long arm of human [[chromosome]] 19q13.42. NLRP11 belongs to the NALP subfamily, part of a large subfamily of [[Caterpiller family|caterpiller]]. It is also known as NALP11, PYPAF6, NOD17, PAN10, and CLR19.6

Being a member of the [[NOD-like receptor protein (NLRP)]] gene family, it encodes a protein with an N-terminal pyrin death (PYD) domain and nucleoside triphosphate hydrolase ([[NACHT domain|NACHT]]) domain and a C-terminal leucine-rich repeats (LRR) region.This gene regulates caspases in the proinflammatory signal transduction pathway. Based on studies of other members of the NLRP gene family with similar domain structures, it is predicted to form part of the multiprotein inflammasome complex.<ref name=":0">{{Cite web |title=NLRP11 NLR family pyrin domain containing 11 [Homo sapiens (human)] - Gene - NCBI |url=https://www.ncbi.nlm.nih.gov/gene/204801 |access-date=2023-02-21 |website=www.ncbi.nlm.nih.gov}}</ref>,<ref name=":1">{{Cite journal |last=Tschopp |first=Jürg |last2=Martinon |first2=Fabio |last3=Burns |first3=Kimberly |date=2003-02 |title=NALPs: a novel protein family involved in inflammation |url=https://www.nature.com/articles/nrm1019 |journal=Nature Reviews Molecular Cell Biology |language=en |volume=4 |issue=2 |pages=95–104 |doi=10.1038/nrm1019 |issn=1471-0080}}</ref>

NLRP11 is expressed mainly in immune cells, B cells, myeloid cells, and B cell lymphoma cell lines. NLRP11 is involved in the regulation of inflammatory responses in human cells.<ref>{{Cite journal |last=Ellwanger |first=Kornelia |last2=Becker |first2=Emily |last3=Kienes |first3=Ioannis |last4=Sowa |first4=Anna |last5=Postma |first5=Yvonne |last6=Gloria |first6=Yamel Cardona |last7=Weber |first7=Alexander N. R. |last8=Kufer |first8=Thomas A. |date=2018-02-23 |title=The NLR family pyrin domain–containing 11 protein contributes to the regulation of inflammatory signaling |url=https://www.jbc.org/article/S0021-9258(17)47578-8/abstract |journal=Journal of Biological Chemistry |language=English |volume=293 |issue=8 |pages=2701–2710 |doi=10.1074/jbc.RA117.000152 |issn=0021-9258 |pmc=PMC5827450 |pmid=29301940}}</ref>

NALPs family controls cytokines, inflammatory responses, NF-κB activation, and likely cell death and survival.<ref>{{Cite journal |last=Harton |first=Jonathan A. |last2=Linhoff |first2=Michael W. |last3=Zhang |first3=Jinghua |last4=Ting |first4=Jenny P.-Y. |date=2002-10-15 |title=Cutting Edge: CATERPILLER: A Large Family of Mammalian Genes Containing CARD, Pyrin, Nucleotide-Binding, and Leucine-Rich Repeat Domains |url=https://doi.org/10.4049/jimmunol.169.8.4088 |journal=The Journal of Immunology |volume=169 |issue=8 |pages=4088–4093 |doi=10.4049/jimmunol.169.8.4088 |issn=0022-1767}}</ref>

=== Structure: ===
This gene encodes a protein with an N-terminal pyrin death (PYD) domain and nucleoside triphosphate hydrolase (NACHT) domain, and a C-terminal leucine-rich repeats (LRR) region. It contains a total of 14 LRRs and 1033 amino acids.<ref name=":0" /><ref name=":1" />

=== Evolution: ===
NLRP11 is a primate-specific gene and is not found in mice A study on the evolution of mammalian reproduction-related NLRPs found that NLRP11 is part of a family cluster of genes that duplicated before the divergence of mammals.<ref>{{Cite journal |last=Tian |first=Xin |last2=Pascal |first2=Géraldine |last3=Monget |first3=Philippe |date=2009-08-14 |title=Evolution and functional divergence of NLRPgenes in mammalian reproductive systems |url=https://doi.org/10.1186/1471-2148-9-202 |journal=BMC Evolutionary Biology |volume=9 |issue=1 |pages=202 |doi=10.1186/1471-2148-9-202 |issn=1471-2148 |pmc=PMC2735741 |pmid=19682372}}</ref>

=== Function: ===
Bacterial lipopolysaccharide (LPS) is an endotoxin that can lead to lethal infection sepsis by activating innate immune responses. Cytoplasmic LPS(cLPS) induces the assembly of an inflammasome that contains [[Caspase|caspases]]-4/5 in humans or [[Caspase 11|caspase-11]] in mice NLRP11 serves as a pattern recognition receptor for cLPS and can result in [[Caspase 4|caspase-4]] inflammasome activation.<ref>{{Cite journal |last=Rojas-Lopez |first=Maricarmen |last2=Zajac |first2=Amanda S. |last3=Wood |first3=Thomas E. |last4=Miller |first4=Kelly A. |last5=Gil-Marqués |first5=María Luisa |last6=Hachey |first6=Austin C. |last7=Kharbanda |first7=Vritti |last8=Egger |first8=Keith T. |last9=Goldberg |first9=Marcia B. |date=2022-06-15 |title=Pattern Recognition Receptor for Bacterial Lipopolysaccharide in the Cytosol of Human Macrophages |url=https://www.biorxiv.org/content/10.1101/2021.10.22.465470v4 |language=en |pages=2021.10.22.465470 |doi=10.1101/2021.10.22.465470}}</ref>

There is also a novel role of NLRP11 in the regulation of inflammatory responses in human cells. In primates, NLRP11 also serves as a conserved negative regulator of TLR signaling. NLRP11 acts as a negative regulator of type I IFN and virus-induced apoptosis by disrupting the [[Mitochondrial antiviral-signaling protein (MAVS)]] signalosome activity. ATP-dependent RNA helicase [[DDX3X]] is a novel binding partner of NLRP11.NLRP11 suppressed the positive effect of DDX3X on [[NLRP3 inflammasome|NLRP3]] inflammasome-mediated caspase-1 activation. Research also suggested that there might be a role of NLRP11 function in innate immunity. NLRP11 and DDX3X might become promising targets for the modulation of innate immune responses.<ref>{{Cite journal |last=Kienes |first=Ioannis |last2=Bauer |first2=Sarah |last3=Gottschild |first3=Clarissa |last4=Mirza |first4=Nora |last5=Pfannstiel |first5=Jens |last6=Schröder |first6=Martina |last7=Kufer |first7=Thomas A. |date=2021 |title=DDX3X Links NLRP11 to the Regulation of Type I Interferon Responses and NLRP3 Inflammasome Activation |url=https://www.frontiersin.org/articles/10.3389/fimmu.2021.653883 |journal=Frontiers in Immunology |volume=12 |doi=10.3389/fimmu.2021.653883 |issn=1664-3224 |pmc=PMC8158815 |pmid=34054816}}</ref>

Upon viral infection, Type I IFN activates NLRP11, and upon activation, it translocates to mitochondria to interact with MAVS. NLRP11 degrades TRAF6 using MAVS to attenuate the production of type I IFNs and virus-induced apoptosis. NLRP11 acts as a negative regulator of type I IFN and virus-induced apoptosis via disrupting the activity of MAVS signalosome.<ref>{{Cite journal |last=Qin |first=Yunfei |last2=Su |first2=Zexiong |last3=Wu |first3=Yaoxing |last4=Wu |first4=Chenglei |last5=Jin |first5=Shouheng |last6=Xie |first6=Weihong |last7=Jiang |first7=Wei |last8=Zhou |first8=Rongbin |last9=Cui |first9=Jun |date=2017-12 |title=NLRP 11 disrupts MAVS signalosome to inhibit type I interferon signaling and virus‐induced apoptosis |url=https://onlinelibrary.wiley.com/doi/10.15252/embr.201744480 |journal=EMBO reports |language=en |volume=18 |issue=12 |pages=2160–2171 |doi=10.15252/embr.201744480 |issn=1469-221X}}</ref>

In human macrophages, NLRP11 is an indispensable component of the NLRP3 inflammasome. The most studied inflammasome sensor molecule of the NLR family is NLRP3, and it contains an amino­terminal PYRIN (PYD) domain, a nucleotide-binding NACHT domain, and a carboxy­terminal leucine-rich repeat (LRR) domain. The ATP binding is required for NLRP3 activation, NACHT domain of NLRP3 contains ATPase activity, and mutation of this site reduces ATP binding, caspase-1 activation, IL-1 production, cell death, macromolecular complex formation, and its association with ASC.

There is an interaction between NLRP11, NLRP3, and ASC. NLRP3 inflammasome activation is inhibited by specific deletion of NLRP11, which leads to inhibition of ASC polymerization, caspase-1 activation, and subsequent cytokine release. NLRP3 mutations that cause [[cryopyrin-associated periodic syndrome (CAPS)]] also require NLRP11 for inflammasome responses. The complex biology of [[inflammasome]] regulation is being explored, and the role of NLRP11 in diseases is partially understood.<ref>{{Cite web |title= |url=https://doi.org/10.1073/pnas.06114961047}}</ref><ref>{{Cite journal |last=Gangopadhyay |first=Anu |last2=Devi |first2=Savita |last3=Tenguria |first3=Shivendra |last4=Carriere |first4=Jessica |last5=Nguyen |first5=Huyen |last6=Jäger |first6=Elisabeth |last7=Khatri |first7=Hemisha |last8=Chu |first8=Lan H. |last9=Ratsimandresy |first9=Rojo A. |last10=Dorfleutner |first10=Andrea |last11=Stehlik |first11=Christian |date=2022-06 |title=NLRP3 licenses NLRP11 for inflammasome activation in human macrophages |url=https://www.nature.com/articles/s41590-022-01220-3 |journal=Nature Immunology |language=en |volume=23 |issue=6 |pages=892–903 |doi=10.1038/s41590-022-01220-3 |issn=1529-2916 |pmc=PMC9174058 |pmid=35624206}}</ref>


==References==
==References==

Revision as of 17:27, 21 February 2023

NLRP11
Identifiers
AliasesNLRP11, CLR19.6, NALP11, NOD17, PAN10, PYPAF6, PYPAF7, NLR family, pyrin domain containing 11, NLR family pyrin domain containing 11
External IDsOMIM: 609664 HomoloGene: 64817 GeneCards: NLRP11
Orthologs
SpeciesHumanMouse
Entrez

204801

n/a

Ensembl

ENSG00000179873

n/a

UniProt

P59045

n/a

RefSeq (mRNA)

NM_145007
NM_001297743

n/a

RefSeq (protein)

NP_001284672
NP_659444

n/a

Location (UCSC)Chr 19: 55.79 – 55.84 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

NLRP11, short for NOD-like receptor family pyrin domain containing 11, is an intracellular protein of mammals. NLRP11 is an intracellular protein encoded in humans by the NLRP gene located on the long arm of human chromosome 19q13.42. NLRP11 belongs to the NALP subfamily, part of a large subfamily of caterpiller. It is also known as NALP11, PYPAF6, NOD17, PAN10, and CLR19.6

Being a member of the NOD-like receptor protein (NLRP) gene family, it encodes a protein with an N-terminal pyrin death (PYD) domain and nucleoside triphosphate hydrolase (NACHT) domain and a C-terminal leucine-rich repeats (LRR) region.This gene regulates caspases in the proinflammatory signal transduction pathway. Based on studies of other members of the NLRP gene family with similar domain structures, it is predicted to form part of the multiprotein inflammasome complex.[3],[4]

NLRP11 is expressed mainly in immune cells, B cells, myeloid cells, and B cell lymphoma cell lines. NLRP11 is involved in the regulation of inflammatory responses in human cells.[5]

NALPs family controls cytokines, inflammatory responses, NF-κB activation, and likely cell death and survival.[6]

Structure:

This gene encodes a protein with an N-terminal pyrin death (PYD) domain and nucleoside triphosphate hydrolase (NACHT) domain, and a C-terminal leucine-rich repeats (LRR) region. It contains a total of 14 LRRs and 1033 amino acids.[3][4]

Evolution:

NLRP11 is a primate-specific gene and is not found in mice A study on the evolution of mammalian reproduction-related NLRPs found that NLRP11 is part of a family cluster of genes that duplicated before the divergence of mammals.[7]

Function:

Bacterial lipopolysaccharide (LPS) is an endotoxin that can lead to lethal infection sepsis by activating innate immune responses. Cytoplasmic LPS(cLPS) induces the assembly of an inflammasome that contains caspases-4/5 in humans or caspase-11 in mice NLRP11 serves as a pattern recognition receptor for cLPS and can result in caspase-4 inflammasome activation.[8]

There is also a novel role of NLRP11 in the regulation of inflammatory responses in human cells. In primates, NLRP11 also serves as a conserved negative regulator of TLR signaling. NLRP11 acts as a negative regulator of type I IFN and virus-induced apoptosis by disrupting the Mitochondrial antiviral-signaling protein (MAVS) signalosome activity. ATP-dependent RNA helicase DDX3X is a novel binding partner of NLRP11.NLRP11 suppressed the positive effect of DDX3X on NLRP3 inflammasome-mediated caspase-1 activation. Research also suggested that there might be a role of NLRP11 function in innate immunity. NLRP11 and DDX3X might become promising targets for the modulation of innate immune responses.[9]

Upon viral infection, Type I IFN activates NLRP11, and upon activation, it translocates to mitochondria to interact with MAVS. NLRP11 degrades TRAF6 using MAVS to attenuate the production of type I IFNs and virus-induced apoptosis. NLRP11 acts as a negative regulator of type I IFN and virus-induced apoptosis via disrupting the activity of MAVS signalosome.[10]

In human macrophages, NLRP11 is an indispensable component of the NLRP3 inflammasome. The most studied inflammasome sensor molecule of the NLR family is NLRP3, and it contains an amino­terminal PYRIN (PYD) domain, a nucleotide-binding NACHT domain, and a carboxy­terminal leucine-rich repeat (LRR) domain. The ATP binding is required for NLRP3 activation, NACHT domain of NLRP3 contains ATPase activity, and mutation of this site reduces ATP binding, caspase-1 activation, IL-1 production, cell death, macromolecular complex formation, and its association with ASC.

There is an interaction between NLRP11, NLRP3, and ASC. NLRP3 inflammasome activation is inhibited by specific deletion of NLRP11, which leads to inhibition of ASC polymerization, caspase-1 activation, and subsequent cytokine release. NLRP3 mutations that cause cryopyrin-associated periodic syndrome (CAPS) also require NLRP11 for inflammasome responses. The complex biology of inflammasome regulation is being explored, and the role of NLRP11 in diseases is partially understood.[11][12]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000179873 – Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ a b "NLRP11 NLR family pyrin domain containing 11 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-02-21.
  4. ^ a b Tschopp, Jürg; Martinon, Fabio; Burns, Kimberly (2003-02). "NALPs: a novel protein family involved in inflammation". Nature Reviews Molecular Cell Biology. 4 (2): 95–104. doi:10.1038/nrm1019. ISSN 1471-0080. {{cite journal}}: Check date values in: |date= (help)
  5. ^ Ellwanger, Kornelia; Becker, Emily; Kienes, Ioannis; Sowa, Anna; Postma, Yvonne; Gloria, Yamel Cardona; Weber, Alexander N. R.; Kufer, Thomas A. (2018-02-23). "The NLR family pyrin domain–containing 11 protein contributes to the regulation of inflammatory signaling". Journal of Biological Chemistry. 293 (8): 2701–2710. doi:10.1074/jbc.RA117.000152. ISSN 0021-9258. PMC 5827450. PMID 29301940.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  6. ^ Harton, Jonathan A.; Linhoff, Michael W.; Zhang, Jinghua; Ting, Jenny P.-Y. (2002-10-15). "Cutting Edge: CATERPILLER: A Large Family of Mammalian Genes Containing CARD, Pyrin, Nucleotide-Binding, and Leucine-Rich Repeat Domains". The Journal of Immunology. 169 (8): 4088–4093. doi:10.4049/jimmunol.169.8.4088. ISSN 0022-1767.
  7. ^ Tian, Xin; Pascal, Géraldine; Monget, Philippe (2009-08-14). "Evolution and functional divergence of NLRPgenes in mammalian reproductive systems". BMC Evolutionary Biology. 9 (1): 202. doi:10.1186/1471-2148-9-202. ISSN 1471-2148. PMC 2735741. PMID 19682372.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  8. ^ Rojas-Lopez, Maricarmen; Zajac, Amanda S.; Wood, Thomas E.; Miller, Kelly A.; Gil-Marqués, María Luisa; Hachey, Austin C.; Kharbanda, Vritti; Egger, Keith T.; Goldberg, Marcia B. (2022-06-15). "Pattern Recognition Receptor for Bacterial Lipopolysaccharide in the Cytosol of Human Macrophages": 2021.10.22.465470. doi:10.1101/2021.10.22.465470. {{cite journal}}: Cite journal requires |journal= (help)
  9. ^ Kienes, Ioannis; Bauer, Sarah; Gottschild, Clarissa; Mirza, Nora; Pfannstiel, Jens; Schröder, Martina; Kufer, Thomas A. (2021). "DDX3X Links NLRP11 to the Regulation of Type I Interferon Responses and NLRP3 Inflammasome Activation". Frontiers in Immunology. 12. doi:10.3389/fimmu.2021.653883. ISSN 1664-3224. PMC 8158815. PMID 34054816.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  10. ^ Qin, Yunfei; Su, Zexiong; Wu, Yaoxing; Wu, Chenglei; Jin, Shouheng; Xie, Weihong; Jiang, Wei; Zhou, Rongbin; Cui, Jun (2017-12). "NLRP 11 disrupts MAVS signalosome to inhibit type I interferon signaling and virus‐induced apoptosis". EMBO reports. 18 (12): 2160–2171. doi:10.15252/embr.201744480. ISSN 1469-221X. {{cite journal}}: Check date values in: |date= (help)
  11. ^ https://doi.org/10.1073/pnas.06114961047. {{cite web}}: Missing or empty |title= (help)
  12. ^ Gangopadhyay, Anu; Devi, Savita; Tenguria, Shivendra; Carriere, Jessica; Nguyen, Huyen; Jäger, Elisabeth; Khatri, Hemisha; Chu, Lan H.; Ratsimandresy, Rojo A.; Dorfleutner, Andrea; Stehlik, Christian (2022-06). "NLRP3 licenses NLRP11 for inflammasome activation in human macrophages". Nature Immunology. 23 (6): 892–903. doi:10.1038/s41590-022-01220-3. ISSN 1529-2916. PMC 9174058. PMID 35624206. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)

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