TRIM21: Difference between revisions

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{{Infobox_gene}}
{{Infobox_gene}}
'''Tripartite motif-containing protein 21''' also known as '''E3 ubiquitin-protein ligase TRIM21''' is a [[protein]] that in humans is encoded by the ''TRIM21'' [[gene]].<ref name="pmid8094596">{{cite journal |vauthors=Frank MB, Itoh K, Fujisaku A, Pontarotti P, Mattei MG, Neas BR | title = The mapping of the human 52-kD Ro/SSA autoantigen gene to human chromosome 11, and its polymorphisms | journal = Am J Hum Genet | volume = 52 | issue = 1 | pages = 183–91 |date=Mar 1993 | pmid = 8094596 | pmc = 1682114 | doi =  }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: TRIM21 tripartite motif-containing 21| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6737| accessdate = }}</ref> Alternatively spliced transcript variants for this gene have been described but the full-length nature of only one has been determined. It is expressed in most human tissues.<ref name="pmid21045130"/>
'''Tripartite motif-containing protein 21''' also known as '''E3 ubiquitin-protein ligase TRIM21''' is a [[protein]] that in humans is encoded by the ''TRIM21'' [[gene]].<ref name="pmid8094596">{{cite journal | vauthors = Frank MB, Itoh K, Fujisaku A, Pontarotti P, Mattei MG, Neas BR | title = The mapping of the human 52-kD Ro/SSA autoantigen gene to human chromosome 11, and its polymorphisms | journal = American Journal of Human Genetics | volume = 52 | issue = 1 | pages = 183–91 | date = January 1993 | pmid = 8094596 | pmc = 1682114 | doi =  }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: TRIM21 tripartite motif-containing 21| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6737| access-date = }}</ref> Alternatively spliced transcript variants for this gene have been described but the full-length nature of only one has been determined. It is expressed in most human tissues.<ref name="pmid21045130"/>


== Structure ==
== Structure ==
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== Function ==
== Function ==


TRIM21 is an intracellular antibody effector in the [[intracellular antibody-mediated proteolysis]] pathway. It recognizes [[Fc-domain|Fc domain]]<ref name="pmid17400754">{{cite journal | vauthors = James LC, Keeble AH, Khan Z, Rhodes DA, Trowsdale J | title = Structural basis for PRYSPRY-mediated tripartite motif (TRIM) protein function | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 15 | pages = 6200–5 | year = 2007 | pmid = 17400754 | pmc = 1851072 | doi = 10.1073/pnas.0609174104 }}</ref> and binds to [[immunoglobulin G]] as well as [[immunoglobulin M]] on antibody marked non-enveloped virions which have infected the cell. Either by [[Ubiquitin|autoubiquitination]] or by ubiquitination of a cofactor, it is then responsible for directing the virions to the [[proteasome]]. TRIM21 itself is not degraded in the proteasome unlike both the viral capsid and the bound antibody.<ref name="pmid21045130">{{cite journal | vauthors = Mallery DL, McEwan WA, Bidgood SR, Towers GJ, Johnson CM, James LC | title = Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21) | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 46 | pages = 19985–90 | year = 2010 | pmid = 21045130 | pmc = 2993423 | doi = 10.1073/pnas.1014074107 }}</ref>
TRIM21 is an intracellular antibody effector in the [[intracellular antibody-mediated proteolysis]] pathway. It recognizes [[Fc-domain|Fc domain]]<ref name="pmid17400754">{{cite journal | vauthors = James LC, Keeble AH, Khan Z, Rhodes DA, Trowsdale J | title = Structural basis for PRYSPRY-mediated tripartite motif (TRIM) protein function | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 15 | pages = 6200–5 | date = April 2007 | pmid = 17400754 | pmc = 1851072 | doi = 10.1073/pnas.0609174104 }}</ref> and binds to [[immunoglobulin G]] as well as [[immunoglobulin M]] on antibody marked non-enveloped virions which have infected the cell. Either by [[Ubiquitin|autoubiquitination]] or by ubiquitination of a cofactor, it is then responsible for directing the virions to the [[proteasome]]. TRIM21 itself is not degraded in the proteasome unlike both the viral capsid and the bound antibody.<ref name="pmid21045130">{{cite journal | vauthors = Mallery DL, McEwan WA, Bidgood SR, Towers GJ, Johnson CM, James LC | title = Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21) | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 46 | pages = 19985–90 | date = November 2010 | pmid = 21045130 | pmc = 2993423 | doi = 10.1073/pnas.1014074107 }}</ref>


TRIM21 is part of the RoSSA ribonucleoprotein, which includes a single polypeptide and one of four small RNA molecules. The RoSSA particle localizes to both the cytoplasm and the nucleus.<ref name="entrez"/>
TRIM21 is part of the RoSSA ribonucleoprotein, which includes a single polypeptide and one of four small RNA molecules. The RoSSA particle localizes to both the cytoplasm and the nucleus.<ref name="entrez"/>
Line 14: Line 14:
== Clinical significance ==
== Clinical significance ==


RoSSA interacts with autoantigens in patients with [[Sjögren's syndrome]] and [[systemic lupus erythematosus]].<ref name="entrez"/>
RoSSA interacts with autoantigens in patients with [[Sjögren's syndrome]] and [[systemic lupus erythematosus]].<ref name="entrez"/> In addition, the inability for lupus-prone macrophages to degrade immune complexes in the lysosome results in the leakage of autoantibodies into the cytosol that can bind to TRIM21 and enhance NF-κB signaling.<ref>{{cite journal | vauthors = Monteith AJ, Kang S, Scott E, Hillman K, Rajfur Z, Jacobson K, Costello MJ, Vilen BJ | title = Defects in lysosomal maturation facilitate the activation of innate sensors in systemic lupus erythematosus | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 113 | issue = 15 | pages = E2142-51 | date = April 2016 | pmid = 27035940 | doi = 10.1073/pnas.1513943113 }}</ref>


TRIM21 can be used to knockout specific proteins with their corresponding antibodies, a method known as Trim-Away. In this assay, TRIM21 and  antibodies are delivered into cells through [[electroporation]], and the targeted protein is degraded within a few minutes.<ref>{{cite journal | vauthors = Clift D, McEwan WA, Labzin LI, Konieczny V, Mogessie B, James LC, Schuh M | title = A Method for the Acute and Rapid Degradation of Endogenous Proteins | journal=Cell | doi=10.1016/j.cell.2017.10.033 | }}</ref>  
TRIM21 can be used to knockout specific proteins with their corresponding antibodies, a method known as Trim-Away. In this assay, TRIM21 and  antibodies are delivered into cells through [[electroporation]], and the targeted protein is degraded within a few minutes.<ref>{{cite journal | vauthors = Clift D, McEwan WA, Labzin LI, Konieczny V, Mogessie B, James LC, Schuh M | title = A Method for the Acute and Rapid Degradation of Endogenous Proteins | journal = Cell | volume = 171 | issue = 7 | pages = 1692–1706.e18 | date = December 2017 | pmid = 29153837 | doi = 10.1016/j.cell.2017.10.033 }}</ref>  


==References==
== References ==
{{reflist}}
{{reflist}}
{{Clear}}
{{Clear}}


==Further reading==
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
*{{cite journal | author=Jones SK |title=Ultraviolet radiation (UVR) induces cell-surface Ro/SSA antigen expression by human keratinocytes in vitro: a possible mechanism for the UVR induction of cutaneous lupus lesions |journal=Br. J. Dermatol. |volume=126 |issue= 6 |pages= 546–553 |year= 1992 |pmid= 1610705 |doi=10.1111/j.1365-2133.1992.tb00098.x }}
* {{cite journal | vauthors = Jones SK | title = Ultraviolet radiation (UVR) induces cell-surface Ro/SSA antigen expression by human keratinocytes in vitro: a possible mechanism for the UVR induction of cutaneous lupus lesions | journal = The British Journal of Dermatology | volume = 126 | issue = 6 | pages = 546–53 | date = June 1992 | pmid = 1610705 | doi = 10.1111/j.1365-2133.1992.tb00098.x }}
*{{cite journal |vauthors=Itoh K, Itoh Y, Frank MB |title=Protein heterogeneity in the human Ro/SSA ribonucleoproteins. The 52- and 60-kD Ro/SSA autoantigens are encoded by separate genes |journal=J. Clin. Invest. |volume=87 |issue= 1 |pages= 177–186 |year= 1991 |pmid= 1985094 |doi=10.1172/JCI114968 | pmc=295020  }}
* {{cite journal | vauthors = Itoh K, Itoh Y, Frank MB | title = Protein heterogeneity in the human Ro/SSA ribonucleoproteins. The 52- and 60-kD Ro/SSA autoantigens are encoded by separate genes | journal = The Journal of Clinical Investigation | volume = 87 | issue = 1 | pages = 177–86 | date = January 1991 | pmid = 1985094 | pmc = 295020 | doi = 10.1172/JCI114968 }}
*{{cite journal |vauthors=Chan EK, Hamel JC, Buyon JP, Tan EM |title=Molecular definition and sequence motifs of the 52-kD component of human SS-A/Ro autoantigen |journal=J. Clin. Invest. |volume=87 |issue= 1 |pages= 68–76 |year= 1991 |pmid= 1985112 |doi=10.1172/JCI115003 | pmc=294993  }}
* {{cite journal | vauthors = Chan EK, Hamel JC, Buyon JP, Tan EM | title = Molecular definition and sequence motifs of the 52-kD component of human SS-A/Ro autoantigen | journal = The Journal of Clinical Investigation | volume = 87 | issue = 1 | pages = 68–76 | date = January 1991 | pmid = 1985112 | pmc = 294993 | doi = 10.1172/JCI115003 }}
*{{cite journal | author=Miyagawa S |title=SSA/Ro antigen expression in simian virus 40-transformed human keratinocytes |journal=J. Invest. Dermatol. |volume=90 |issue= 3 |pages= 342–345 |year= 1988 |pmid= 2450143 |doi=10.1111/1523-1747.ep12456308 |name-list-format=vanc| author2=Okada N  | author3=Inagaki Y  | display-authors=3  | last4=Kitano  | first4=Yukio  | last5=Ueki  | first5=Hiroaki  | last6=Sakamoto  | first6=Kuniki  | last7=Steinberg  | first7=Mark L.  }}
* {{cite journal | vauthors = Miyagawa S, Okada N, Inagaki Y, Kitano Y, Ueki H, Sakamoto K, Steinberg ML | title = SSA/Ro antigen expression in simian virus 40-transformed human keratinocytes | journal = The Journal of Investigative Dermatology | volume = 90 | issue = 3 | pages = 342–5 | date = March 1988 | pmid = 2450143 | doi = 10.1111/1523-1747.ep12456308 }}
*{{cite journal  | author=Chan EK |title=52-kD SS-A/Ro: genomic structure and identification of an alternatively spliced transcript encoding a novel leucine zipper-minus autoantigen expressed in fetal and adult heart |journal=J. Exp. Med. |volume=182 |issue= 4 |pages= 983–992 |year= 1995 |pmid= 7561701 |doi=10.1084/jem.182.4.983  | pmc=2192297  |name-list-format=vanc| author2=Di Donato F  | author3=Hamel JC  | display-authors=3  | last4=Tseng  | first4=CE  | last5=Buyon  | first5=JP }}
* {{cite journal | vauthors = Chan EK, Di Donato F, Hamel JC, Tseng CE, Buyon JP | title = 52-kD SS-A/Ro: genomic structure and identification of an alternatively spliced transcript encoding a novel leucine zipper-minus autoantigen expressed in fetal and adult heart | journal = The Journal of Experimental Medicine | volume = 182 | issue = 4 | pages = 983–92 | date = October 1995 | pmid = 7561701 | pmc = 2192297 | doi = 10.1084/jem.182.4.983 }}
*{{cite journal |vauthors=Tsugu H, Horowitz R, Gibson N, Frank MB |title=The location of a disease-associated polymorphism and genomic structure of the human 52-kDa Ro/SSA locus (SSA1) |journal=Genomics |volume=24 |issue= 3 |pages= 541–548 |year= 1995 |pmid= 7713506 |doi= 10.1006/geno.1994.1664 }}
* {{cite journal | vauthors = Tsugu H, Horowitz R, Gibson N, Frank MB | title = The location of a disease-associated polymorphism and genomic structure of the human 52-kDa Ro/SSA locus (SSA1) | journal = Genomics | volume = 24 | issue = 3 | pages = 541–8 | date = December 1994 | pmid = 7713506 | doi = 10.1006/geno.1994.1664 }}
*{{cite journal |vauthors=Frank MB, McCubbin VR, Heldermon C |title=Expression and DNA binding of the human 52 kDa Ro/SSA autoantigen |journal=Biochem. J. |volume=305 |issue= 2|pages= 359–62 |year= 1995 |pmid= 7832745 |doi= | pmc=1136368  }}
* {{cite journal | vauthors = Frank MB, McCubbin VR, Heldermon C | title = Expression and DNA binding of the human 52 kDa Ro/SSA autoantigen | journal = The Biochemical Journal | volume = 305 ( Pt 2) | issue = 2 | pages = 359–62 | date = January 1995 | pmid = 7832745 | pmc = 1136368 | doi =  }}
*{{cite journal |vauthors=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides |journal=Gene |volume=138 |issue= 1–2 |pages= 171–174 |year= 1994 |pmid= 8125298 |doi=10.1016/0378-1119(94)90802-8  }}
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1-2 | pages = 171–4 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
*{{cite journal |vauthors=Keech CL, Gordon TP, McCluskey J |title=Structural differences between the human and mouse 52-kD Ro autoantigens associated with poorly conserved autoantibody activity across species |journal=Clin. Exp. Immunol. |volume=104 |issue= 2 |pages= 255–263 |year= 1996 |pmid= 8625517 |doi=10.1046/j.1365-2249.1996.16726.x  | pmc=2200432  }}
* {{cite journal | vauthors = Keech CL, Gordon TP, McCluskey J | title = Structural differences between the human and mouse 52-kD Ro autoantigens associated with poorly conserved autoantibody activity across species | journal = Clinical and Experimental Immunology | volume = 104 | issue = 2 | pages = 255–63 | date = May 1996 | pmid = 8625517 | pmc = 2200432 | doi = 10.1046/j.1365-2249.1996.16726.x }}
*{{cite journal |vauthors=Igarashi T, Itoh Y, Fukunaga Y, Yamamoto M |title=Stress-induced cell surface expression and antigenic alteration of the Ro/SSA autoantigen |journal=Autoimmunity |volume=22 |issue= 1 |pages= 33–42 |year= 1996 |pmid= 8882420 |doi=10.3109/08916939508995297  }}
* {{cite journal | vauthors = Igarashi T, Itoh Y, Fukunaga Y, Yamamoto M | title = Stress-induced cell surface expression and antigenic alteration of the Ro/SSA autoantigen | journal = Autoimmunity | volume = 22 | issue = 1 | pages = 33–42 | year = 1996 | pmid = 8882420 | doi = 10.3109/08916939508995297 }}
*{{cite journal | author=Suzuki Y |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library |journal=Gene |volume=200 |issue= 1–2 |pages= 149–156 |year= 1997 |pmid= 9373149 |doi=10.1016/S0378-1119(97)00411-3  |name-list-format=vanc| author2=Yoshitomo-Nakagawa K  | author3=Maruyama K  | display-authors=3  | last4=Suyama  | first4=A  | last5=Sugano  | first5=S  }}
* {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1-2 | pages = 149–56 | date = October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
*{{cite journal | author=Bepler G |title=A 1.4-Mb high-resolution physical map and contig of chromosome segment 11p15.5 and genes in the LOH11A metastasis suppressor region |journal=Genomics |volume=55 |issue= 2 |pages= 164–175 |year= 1999 |pmid= 9933563 |doi= 10.1006/geno.1998.5659  |name-list-format=vanc| author2=O'briant KC  | author3=Kim YC  | display-authors=3  | last4=Schreiber  | first4=G  | last5=Pitterle  | first5=DM }}
* {{cite journal | vauthors = Bepler G, O'briant KC, Kim YC, Schreiber G, Pitterle DM | title = A 1.4-Mb high-resolution physical map and contig of chromosome segment 11p15.5 and genes in the LOH11A metastasis suppressor region | journal = Genomics | volume = 55 | issue = 2 | pages = 164–75 | date = January 1999 | pmid = 9933563 | doi = 10.1006/geno.1998.5659 }}
*{{cite journal  | author=Tseng CE |title=mRNA and protein expression of SSA/Ro and SSB/La in human fetal cardiac myocytes cultured using a novel application of the Langendorff procedure |journal=Pediatr. Res. |volume=45 |issue= 2 |pages= 260–269 |year= 1999 |pmid= 10022600 |doi=10.1203/00006450-199902000-00018  |name-list-format=vanc| author2=Miranda E  | author3=Di Donato F  | display-authors=3 | last4=Boutjdir  | first4=Mohamed  | last5=Rashbaum  | first5=William  | last6=Chan  | first6=Edward K. L.  | last7=Buyon  | first7=Jill P.  }}
* {{cite journal | vauthors = Tseng CE, Miranda E, Di Donato F, Boutjdir M, Rashbaum W, Chan EK, Buyon JP | title = mRNA and protein expression of SSA/Ro and SSB/La in human fetal cardiac myocytes cultured using a novel application of the Langendorff procedure | journal = Pediatric Research | volume = 45 | issue = 2 | pages = 260–9 | date = February 1999 | pmid = 10022600 | doi = 10.1203/00006450-199902000-00018 }}
*{{cite journal  | author=Fabini G |title=Analysis of the molecular composition of Ro ribonucleoprotein complexes. Identification of novel Y RNA-binding proteins |journal=Eur. J. Biochem. |volume=267 |issue= 9 |pages= 2778–2789 |year= 2000 |pmid= 10785401 |doi=10.1046/j.1432-1327.2000.01298.x  |name-list-format=vanc| author2=Rutjes SA  | author3=Zimmermann C  | display-authors=3  | last4=Pruijn  | first4=Ger J. M.  | last5=Steiner  | first5=Gunter  }}
* {{cite journal | vauthors = Fabini G, Rutjes SA, Zimmermann C, Pruijn GJ, Steiner G | title = Analysis of the molecular composition of Ro ribonucleoprotein complexes. Identification of novel Y RNA-binding proteins | journal = European Journal of Biochemistry | volume = 267 | issue = 9 | pages = 2778–89 | date = May 2000 | pmid = 10785401 | doi = 10.1046/j.1432-1327.2000.01298.x }}
*{{cite journal  | author=Kurien BT |title=Autoantibody to the leucine zipper region of 52 kDa Ro/SSA binds native 60 kDa Ro/SSA: identification of a tertiary epitope with components from 60 kDa Ro/SSA and 52 kDa Ro/SSA |journal=Scand. J. Immunol. |volume=53 |issue= 3 |pages= 268–276 |year= 2001 |pmid= 11251884 |doi=10.1046/j.1365-3083.2001.00870.x  |name-list-format=vanc| author2=Chambers TL  | author3=Thomas PY  | display-authors=3  | last4=Frank  | first4=M. B.  | last5=Scofield  | first5=R. H.  }}
* {{cite journal | vauthors = Kurien BT, Chambers TL, Thomas PY, Frank MB, Scofield RH | title = Autoantibody to the leucine zipper region of 52 kDa Ro/SSA binds native 60 kDa Ro/SSA: identification of a tertiary epitope with components from 60 kDa Ro/SSA and 52 kDa Ro/SSA | journal = Scandinavian Journal of Immunology | volume = 53 | issue = 3 | pages = 268–76 | date = March 2001 | pmid = 11251884 | doi = 10.1046/j.1365-3083.2001.00870.x }}
*{{cite journal  | author=Reymond A |title=The tripartite motif family identifies cell compartments |journal=EMBO J. |volume=20 |issue= 9 |pages= 2140–2151 |year= 2001 |pmid= 11331580 |doi= 10.1093/emboj/20.9.2140  | pmc=125245  |name-list-format=vanc| author2=Meroni G  | author3=Fantozzi A  | display-authors=3  | last4=Merla  | first4=G  | last5=Cairo  | first5=S  | last6=Luzi  | first6=L  | last7=Riganelli  | first7=D  | last8=Zanaria  | first8=E  | last9=Messali  | first9=S }}
* {{cite journal | vauthors = Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L, Riganelli D, Zanaria E, Messali S, Cainarca S, Guffanti A, Minucci S, Pelicci PG, Ballabio A | title = The tripartite motif family identifies cell compartments | journal = The EMBO Journal | volume = 20 | issue = 9 | pages = 2140–51 | date = May 2001 | pmid = 11331580 | pmc = 125245 | doi = 10.1093/emboj/20.9.2140 }}
*{{cite journal  | author=Di Donato F |title=Interaction between 52 kDa SSA/Ro and deubiquitinating enzyme UnpEL: a clue to function |journal=Int. J. Biochem. Cell Biol. |volume=33 |issue= 9 |pages= 924–934 |year= 2001 |pmid= 11461834 |doi=10.1016/S1357-2725(01)00055-3  |name-list-format=vanc| author2=Chan EK  | author3=Askanase AD  | display-authors=3  | last4=Miranda-Carus  | first4=Maria-Eugenia  | last5=Buyon  | first5=Jill P  }}
* {{cite journal | vauthors = Di Donato F, Chan EK, Askanase AD, Miranda-Carus M, Buyon JP | title = Interaction between 52 kDa SSA/Ro and deubiquitinating enzyme UnpEL: a clue to function | journal = The International Journal of Biochemistry & Cell Biology | volume = 33 | issue = 9 | pages = 924–34 | date = September 2001 | pmid = 11461834 | doi = 10.1016/S1357-2725(01)00055-3 }}
*{{cite journal  |vauthors=Fukuda-Kamitani T, Kamitani T |title=Ubiquitination of Ro52 autoantigen |journal=Biochem. Biophys. Res. Commun. |volume=295 |issue= 4 |pages= 774–778 |year= 2002 |pmid= 12127959 |doi=10.1016/S0006-291X(02)00750-7  }}
* {{cite journal | vauthors = Fukuda-Kamitani T, Kamitani T | title = Ubiquitination of Ro52 autoantigen | journal = Biochemical and Biophysical Research Communications | volume = 295 | issue = 4 | pages = 774–8 | date = July 2002 | pmid = 12127959 | doi = 10.1016/S0006-291X(02)00750-7 }}
*{{cite journal  | author=Strausberg RL |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= 16899–16903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899  | pmc=139241  |name-list-format=vanc| author2=Feingold EA  | author3=Grouse LH  | display-authors=3  | last4=Derge  | first4=JG  | last5=Klausner  | first5=RD  | last6=Collins  | first6=FS  | last7=Wagner  | first7=L  | last8=Shenmen  | first8=CM  | last9=Schuler  | first9=GD }}
{{refend}}
{{refend}}
{{PDB Gallery|geneid=6737}}
{{PDB Gallery|geneid=6737}}

Latest revision as of 21:34, 3 January 2019

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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

Tripartite motif-containing protein 21 also known as E3 ubiquitin-protein ligase TRIM21 is a protein that in humans is encoded by the TRIM21 gene.[1][2] Alternatively spliced transcript variants for this gene have been described but the full-length nature of only one has been determined. It is expressed in most human tissues.[3]

Structure

TRIM21 is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING finger domain, a B-box type 1 and a B-box type 2 zinc finger, and a coiled coil region.[2]

Function

TRIM21 is an intracellular antibody effector in the intracellular antibody-mediated proteolysis pathway. It recognizes Fc domain[4] and binds to immunoglobulin G as well as immunoglobulin M on antibody marked non-enveloped virions which have infected the cell. Either by autoubiquitination or by ubiquitination of a cofactor, it is then responsible for directing the virions to the proteasome. TRIM21 itself is not degraded in the proteasome unlike both the viral capsid and the bound antibody.[3]

TRIM21 is part of the RoSSA ribonucleoprotein, which includes a single polypeptide and one of four small RNA molecules. The RoSSA particle localizes to both the cytoplasm and the nucleus.[2]

Clinical significance

RoSSA interacts with autoantigens in patients with Sjögren's syndrome and systemic lupus erythematosus.[2] In addition, the inability for lupus-prone macrophages to degrade immune complexes in the lysosome results in the leakage of autoantibodies into the cytosol that can bind to TRIM21 and enhance NF-κB signaling.[5]

TRIM21 can be used to knockout specific proteins with their corresponding antibodies, a method known as Trim-Away. In this assay, TRIM21 and antibodies are delivered into cells through electroporation, and the targeted protein is degraded within a few minutes.[6]

References

  1. ↑ Frank MB, Itoh K, Fujisaku A, Pontarotti P, Mattei MG, Neas BR (January 1993). "The mapping of the human 52-kD Ro/SSA autoantigen gene to human chromosome 11, and its polymorphisms". American Journal of Human Genetics. 52 (1): 183–91. PMC 1682114. PMID 8094596.
  2. ↑ 2.0 2.1 2.2 2.3 "Entrez Gene: TRIM21 tripartite motif-containing 21".
  3. ↑ 3.0 3.1 Mallery DL, McEwan WA, Bidgood SR, Towers GJ, Johnson CM, James LC (November 2010). "Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21)". Proceedings of the National Academy of Sciences of the United States of America. 107 (46): 19985–90. doi:10.1073/pnas.1014074107. PMC 2993423. PMID 21045130.
  4. ↑ James LC, Keeble AH, Khan Z, Rhodes DA, Trowsdale J (April 2007). "Structural basis for PRYSPRY-mediated tripartite motif (TRIM) protein function". Proceedings of the National Academy of Sciences of the United States of America. 104 (15): 6200–5. doi:10.1073/pnas.0609174104. PMC 1851072. PMID 17400754.
  5. ↑ Monteith AJ, Kang S, Scott E, Hillman K, Rajfur Z, Jacobson K, Costello MJ, Vilen BJ (April 2016). "Defects in lysosomal maturation facilitate the activation of innate sensors in systemic lupus erythematosus". Proceedings of the National Academy of Sciences of the United States of America. 113 (15): E2142–51. doi:10.1073/pnas.1513943113. PMID 27035940.
  6. ↑ Clift D, McEwan WA, Labzin LI, Konieczny V, Mogessie B, James LC, Schuh M (December 2017). "A Method for the Acute and Rapid Degradation of Endogenous Proteins". Cell. 171 (7): 1692–1706.e18. doi:10.1016/j.cell.2017.10.033. PMID 29153837.

Further reading

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