TRIM21
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| Location (UCSC) | Chr 11: 4.38 – 4.39 Mb | Chr 7: 102.21 – 102.21 Mb | |||||||
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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.[5][6] 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.[7]
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.[6]
Function
TRIM21 is an intracellular antibody effector in the
Fc domain[8] and binds to immunoglobulin G, immunoglobulin A[9] and 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.[7]
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.[6]
Clinical significance
RoSSA interacts with autoantigens in patients with
systemic lupus erythematosus.[6] 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.[10]
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.[11]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000132109 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030966 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 8094596.
- ^ a b c d "Entrez Gene: TRIM21 tripartite motif-containing 21".
- ^ PMID 21045130.
- PMID 17400754.
- PMID 25169018.
- PMID 27035940.
- PMID 29153837.
Further reading
- Jones SK (June 1992). "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". The British Journal of Dermatology. 126 (6): 546–53. S2CID 24542694.
- Itoh K, Itoh Y, Frank MB (January 1991). "Protein heterogeneity in the human Ro/SSA ribonucleoproteins. The 52- and 60-kD Ro/SSA autoantigens are encoded by separate genes". The Journal of Clinical Investigation. 87 (1): 177–86. PMID 1985094.
- Chan EK, Hamel JC, Buyon JP, Tan EM (January 1991). "Molecular definition and sequence motifs of the 52-kD component of human SS-A/Ro autoantigen". The Journal of Clinical Investigation. 87 (1): 68–76. PMID 1985112.
- Miyagawa S, Okada N, Inagaki Y, Kitano Y, Ueki H, Sakamoto K, Steinberg ML (March 1988). "SSA/Ro antigen expression in simian virus 40-transformed human keratinocytes". The Journal of Investigative Dermatology. 90 (3): 342–5. PMID 2450143.
- Chan EK, Di Donato F, Hamel JC, Tseng CE, Buyon JP (October 1995). "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". The Journal of Experimental Medicine. 182 (4): 983–92. PMID 7561701.
- Tsugu H, Horowitz R, Gibson N, Frank MB (December 1994). "The location of a disease-associated polymorphism and genomic structure of the human 52-kDa Ro/SSA locus (SSA1)". Genomics. 24 (3): 541–8. PMID 7713506.
- Frank MB, McCubbin VR, Heldermon C (January 1995). "Expression and DNA binding of the human 52 kDa Ro/SSA autoantigen". The Biochemical Journal. 305 (2): 359–62. PMID 7832745.
- Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. PMID 8125298.
- Keech CL, Gordon TP, McCluskey J (May 1996). "Structural differences between the human and mouse 52-kD Ro autoantigens associated with poorly conserved autoantibody activity across species". Clinical and Experimental Immunology. 104 (2): 255–63. PMID 8625517.
- Igarashi T, Itoh Y, Fukunaga Y, Yamamoto M (1996). "Stress-induced cell surface expression and antigenic alteration of the Ro/SSA autoantigen". Autoimmunity. 22 (1): 33–42. PMID 8882420.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. PMID 9373149.
- Bepler G, O'briant KC, Kim YC, Schreiber G, Pitterle DM (January 1999). "A 1.4-Mb high-resolution physical map and contig of chromosome segment 11p15.5 and genes in the LOH11A metastasis suppressor region". Genomics. 55 (2): 164–75. PMID 9933563.
- Tseng CE, Miranda E, Di Donato F, Boutjdir M, Rashbaum W, Chan EK, Buyon JP (February 1999). "mRNA and protein expression of SSA/Ro and SSB/La in human fetal cardiac myocytes cultured using a novel application of the Langendorff procedure". Pediatric Research. 45 (2): 260–9. PMID 10022600.
- Fabini G, Rutjes SA, Zimmermann C, Pruijn GJ, Steiner G (May 2000). "Analysis of the molecular composition of Ro ribonucleoprotein complexes. Identification of novel Y RNA-binding proteins". European Journal of Biochemistry. 267 (9): 2778–89. PMID 10785401.
- Kurien BT, Chambers TL, Thomas PY, Frank MB, Scofield RH (March 2001). "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". Scandinavian Journal of Immunology. 53 (3): 268–76. S2CID 7923255.
- 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 (May 2001). "The tripartite motif family identifies cell compartments". The EMBO Journal. 20 (9): 2140–51. PMID 11331580.
- Di Donato F, Chan EK, Askanase AD, Miranda-Carus M, Buyon JP (September 2001). "Interaction between 52 kDa SSA/Ro and deubiquitinating enzyme UnpEL: a clue to function". The International Journal of Biochemistry & Cell Biology. 33 (9): 924–34. PMID 11461834.
- Fukuda-Kamitani T, Kamitani T (July 2002). "Ubiquitination of Ro52 autoantigen". Biochemical and Biophysical Research Communications. 295 (4): 774–8. PMID 12127959.
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