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Aliases for TRIM21 Gene

Aliases for TRIM21 Gene

  • Tripartite Motif Containing 21 2 3 5
  • Sjogren Syndrome Antigen A1 (52kDa, Ribonucleoprotein Autoantigen SS-A/Ro) 2 3
  • 52 KDa Ribonucleoprotein Autoantigen Ro/SS-A 3 4
  • Tripartite Motif-Containing Protein 21 3 4
  • Sjoegren Syndrome Type A Antigen 3 4
  • Tripartite Motif-Containing 21 2 3
  • RING Finger Protein 81 3 4
  • 52 KDa Ro Protein 3 4
  • Ro(SS-A) 3 4
  • RNF81 3 4
  • SSA1 3 4
  • RO52 3 4
  • SS-A 3 4
  • Sicca Syndrome Antigen A 3
  • EC 6.3.2.- 4
  • Ro/SSA 3
  • SSA 3

External Ids for TRIM21 Gene

Previous HGNC Symbols for TRIM21 Gene

  • SSA1

Previous GeneCards Identifiers for TRIM21 Gene

  • GC11M004363
  • GC11M004064

Summaries for TRIM21 Gene

Entrez Gene Summary for TRIM21 Gene

  • This gene encodes a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The encoded protein 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. RoSSA interacts with autoantigens in patients with Sjogren syndrome and systemic lupus erythematosus. Alternatively spliced transcript variants for this gene have been described but the full-length nature of only one has been determined. [provided by RefSeq, Jul 2008]

GeneCards Summary for TRIM21 Gene

TRIM21 (Tripartite Motif Containing 21) is a Protein Coding gene. Diseases associated with TRIM21 include myelofibrosis with myeloid metaplasia, somatic and thrombocythemia 1. Among its related pathways are Immune System and Interferon gamma signaling. GO annotations related to this gene include identical protein binding and ligase activity. An important paralog of this gene is TRIM58.

UniProtKB/Swiss-Prot for TRIM21 Gene

  • E3 ubiquitin-protein ligase whose activity is dependent on E2 enzymes, UBE2D1, UBE2D2, UBE2E1 and UBE2E2. Forms a ubiquitin ligase complex in cooperation with the E2 UBE2D2 that is used not only for the ubiquitination of USP4 and IKBKB but also for its self-ubiquitination. Component of cullin-RING-based SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes such as SCF(SKP2)-like complexes. A TRIM21-containing SCF(SKP2)-like complex is shown to mediate ubiquitination of CDKN1B (Thr-187 phosphorylated-form), thereby promoting its degradation by the proteasome. Monoubiquitinates IKBKB that will negatively regulates Tax-induced NF-kappa-B signaling. Negatively regulates IFN-beta production post-pathogen recognition by polyubiquitin-mediated degradation of IRF3. Mediates the ubiquitin-mediated proteasomal degradation of IgG1 heavy chain, which is linked to the VCP-mediated ER-associated degradation (ERAD) pathway. Promotes IRF8 ubiquitination, which enhanced the ability of IRF8 to stimulate cytokine genes transcription in macrophages. Plays a role in the regulation of the cell cycle progression. Enhances the decapping activity of DCP2. Exists as a ribonucleoprotein particle present in all mammalian cells studied and composed of a single polypeptide and one of four small RNA molecules. At least two isoforms are present in nucleated and red blood cells, and tissue specific differences in RO/SSA proteins have been identified. The common feature of these proteins is their ability to bind HY RNAs.2. Involved in the regulation of innate immunity and the inflammatory response in response to IFNG/IFN-gamma. Organizes autophagic machinery by serving as a platform for the assembly of ULK1, Beclin 1/BECN1 and ATG8 family members and recognizes specific autophagy targets, thus coordinating target recognition with assembly of the autophagic apparatus and initiation of autophagy. Acts as an autophagy receptor for the degradation of IRF3, hence attenuating type I interferon (IFN)-dependent immune responses (PubMed:26347139).

Gene Wiki entry for TRIM21 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for TRIM21 Gene

Genomics for TRIM21 Gene

Regulatory Elements for TRIM21 Gene

Promoters for TRIM21 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around TRIM21 on UCSC Golden Path with GeneCards custom track

Genomic Location for TRIM21 Gene

Chromosome:
11
Start:
4,384,897 bp from pter
End:
4,393,712 bp from pter
Size:
8,816 bases
Orientation:
Minus strand

Genomic View for TRIM21 Gene

Genes around TRIM21 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TRIM21 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TRIM21 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TRIM21 Gene

Proteins for TRIM21 Gene

  • Protein details for TRIM21 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P19474-RO52_HUMAN
    Recommended name:
    E3 ubiquitin-protein ligase TRIM21
    Protein Accession:
    P19474
    Secondary Accessions:
    • Q5XPV5
    • Q96RF8

    Protein attributes for TRIM21 Gene

    Size:
    475 amino acids
    Molecular mass:
    54170 Da
    Quaternary structure:
    • Homotrimer (PubMed:17156811) (PubMed:26347139). Interacts (via C-terminus) with IRF8 (via C-terminus) (By similarity). Component of a SCF(SKP2)-like complex containing CUL1, SKP1, TRIM21 and SKP2. Interacts with CALR, CUL1, FBXW11, HSPA5, IKBKB, IRF3, SKP1 and VCP. Interacts with SKP2; the interaction with SKP2 does not depend on an intact F-box domain. Interacts (via N-terminus and C-terminus) with DCP2 (via N-terminus and C-terminus). Interacts with ULK1, BECN1 and with ATG8 family members, including GABARAP, GABARAPL1, GABARAPL2 and MAP1LC3C/LC3C. Interacts with TRIM21 and SQSTM1/sequestosome 1. Interacts with IRF3 (PubMed:26347139).

    Three dimensional structures from OCA and Proteopedia for TRIM21 Gene

    Alternative splice isoforms for TRIM21 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TRIM21 Gene

Proteomics data for TRIM21 Gene at MOPED

Post-translational modifications for TRIM21 Gene

  • Autoubiquitinated; does not lead to its proteasomal degradation. Deubiquitinated by USP4; leading to its stabilization.
  • Ubiquitination at Lys 260
  • Modification sites at PhosphoSitePlus

Other Protein References for TRIM21 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for TRIM21 (TRIM21)

No data available for DME Specific Peptides for TRIM21 Gene

Domains & Families for TRIM21 Gene

Gene Families for TRIM21 Gene

Suggested Antigen Peptide Sequences for TRIM21 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P19474

UniProtKB/Swiss-Prot:

RO52_HUMAN :
  • The coiled-coil is necessary for the cytoplasmic localization. The B30.2/SPRY domain is necessary for the cytoplasmic localization, the interaction with IRF3 and for the IRF3-driven interferon beta promoter activity. The RING-type zinc finger is necessary for ubiquitination and for the IRF3-driven interferon beta promoter activity. Interacts with SKP2 and CUL1 in a RING finger-independent manner.
  • Belongs to the TRIM/RBCC family.
  • Contains 1 B box-type zinc finger.
Domain:
  • The coiled-coil is necessary for the cytoplasmic localization. The B30.2/SPRY domain is necessary for the cytoplasmic localization, the interaction with IRF3 and for the IRF3-driven interferon beta promoter activity. The RING-type zinc finger is necessary for ubiquitination and for the IRF3-driven interferon beta promoter activity. Interacts with SKP2 and CUL1 in a RING finger-independent manner.
  • Contains 1 B30.2/SPRY domain.
Family:
  • Belongs to the TRIM/RBCC family.
Similarity:
  • Contains 1 B box-type zinc finger.
  • Contains 1 RING-type zinc finger.
genes like me logo Genes that share domains with TRIM21: view

Function for TRIM21 Gene

Molecular function for TRIM21 Gene

UniProtKB/Swiss-Prot Function:
E3 ubiquitin-protein ligase whose activity is dependent on E2 enzymes, UBE2D1, UBE2D2, UBE2E1 and UBE2E2. Forms a ubiquitin ligase complex in cooperation with the E2 UBE2D2 that is used not only for the ubiquitination of USP4 and IKBKB but also for its self-ubiquitination. Component of cullin-RING-based SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes such as SCF(SKP2)-like complexes. A TRIM21-containing SCF(SKP2)-like complex is shown to mediate ubiquitination of CDKN1B (Thr-187 phosphorylated-form), thereby promoting its degradation by the proteasome. Monoubiquitinates IKBKB that will negatively regulates Tax-induced NF-kappa-B signaling. Negatively regulates IFN-beta production post-pathogen recognition by polyubiquitin-mediated degradation of IRF3. Mediates the ubiquitin-mediated proteasomal degradation of IgG1 heavy chain, which is linked to the VCP-mediated ER-associated degradation (ERAD) pathway. Promotes IRF8 ubiquitination, which enhanced the ability of IRF8 to stimulate cytokine genes transcription in macrophages. Plays a role in the regulation of the cell cycle progression. Enhances the decapping activity of DCP2. Exists as a ribonucleoprotein particle present in all mammalian cells studied and composed of a single polypeptide and one of four small RNA molecules. At least two isoforms are present in nucleated and red blood cells, and tissue specific differences in RO/SSA proteins have been identified. The common feature of these proteins is their ability to bind HY RNAs.2. Involved in the regulation of innate immunity and the inflammatory response in response to IFNG/IFN-gamma. Organizes autophagic machinery by serving as a platform for the assembly of ULK1, Beclin 1/BECN1 and ATG8 family members and recognizes specific autophagy targets, thus coordinating target recognition with assembly of the autophagic apparatus and initiation of autophagy. Acts as an autophagy receptor for the degradation of IRF3, hence attenuating type I interferon (IFN)-dependent immune responses (PubMed:26347139).
UniProtKB/Swiss-Prot Induction:
Up-regulated by isoform 2 of XBP1. Up-regulated by IFNG/interferon-gamma, with a peak after 2-4 hours of treatment in monocytes/macrophages.

Enzyme Numbers (IUBMB) for TRIM21 Gene

Gene Ontology (GO) - Molecular Function for TRIM21 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016874 ligase activity IEA --
genes like me logo Genes that share ontologies with TRIM21: view
genes like me logo Genes that share phenotypes with TRIM21: view

Animal Models for TRIM21 Gene

MGI Knock Outs for TRIM21:

Animal Model Products

  • Taconic Biosciences Mouse Models for TRIM21

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for TRIM21 Gene

Localization for TRIM21 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TRIM21 Gene

Cytoplasm. Cytoplasmic vesicle, autophagosome. Nucleus. Cytoplasm, P-body. Note=Enters the nucleus upon exposure to nitric oxide. Localizes to small dot- or rod-like structures in the cytoplasm, called cytoplasmic bodies (P-body) that are located underneath the plasma membrane and also diffusely in the cytoplasm and are highly motil in cells. Cytoplasmic bodies are located along the microtubules and do not share the same cytoplasmic bodies with TRIM5. Colocalizes with DCP2 in P-body.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for TRIM21 Gene COMPARTMENTS Subcellular localization image for TRIM21 gene
Compartment Confidence
cytosol 5
nucleus 5
vacuole 3
endoplasmic reticulum 1

Gene Ontology (GO) - Cellular Components for TRIM21 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol TAS --
GO:0031410 cytoplasmic vesicle IEA --
genes like me logo Genes that share ontologies with TRIM21: view

Pathways & Interactions for TRIM21 Gene

genes like me logo Genes that share pathways with TRIM21: view

Pathways by source for TRIM21 Gene

UniProtKB/Swiss-Prot P19474-RO52_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

SIGNOR curated interactions for TRIM21 Gene

Inactivates:

Gene Ontology (GO) - Biological Process for TRIM21 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000209 protein polyubiquitination TAS --
GO:0019221 cytokine-mediated signaling pathway TAS --
GO:0032897 negative regulation of viral transcription IDA 18248090
GO:0046598 positive regulation of viral entry into host cell IEA --
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity IDA 23077300
genes like me logo Genes that share ontologies with TRIM21: view

Drugs & Compounds for TRIM21 Gene

(3) Drugs for TRIM21 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(2) Additional Compounds for TRIM21 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with TRIM21: view

Transcripts for TRIM21 Gene

mRNA/cDNA for TRIM21 Gene

Unigene Clusters for TRIM21 Gene

Tripartite motif containing 21:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for TRIM21 Gene

No ASD Table

Relevant External Links for TRIM21 Gene

GeneLoc Exon Structure for
TRIM21
ECgene alternative splicing isoforms for
TRIM21

Expression for TRIM21 Gene

mRNA expression in normal human tissues for TRIM21 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for TRIM21 Gene

This gene is overexpressed in Whole Blood (x9.0).

Protein differential expression in normal tissues from HIPED for TRIM21 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (11.5), Lymph node (11.0), Heart (9.4), and Monocytes (6.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for TRIM21 Gene



SOURCE GeneReport for Unigene cluster for TRIM21 Gene Hs.532357

mRNA Expression by UniProt/SwissProt for TRIM21 Gene

P19474-RO52_HUMAN
Tissue specificity: Isoform 1 and isoform 2 are expressed in fetal and adult heart and fetal lung.
genes like me logo Genes that share expression patterns with TRIM21: view

Protein tissue co-expression partners for TRIM21 Gene

- Elite partner

Primer Products

In Situ Assay Products

Orthologs for TRIM21 Gene

This gene was present in the common ancestor of chordates.

Orthologs for TRIM21 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia TRIM21 36
  • 100 (a)
OneToOne
TRIM21 35
  • 99.51 (n)
  • 100 (a)
cow
(Bos Taurus)
Mammalia TRIM21 35
  • 83.76 (n)
  • 77.56 (a)
TRIM21 36
  • 71 (a)
OneToOne
dog
(Canis familiaris)
Mammalia TRIM21 36
  • 76 (a)
OneToOne
TRIM21 35
  • 83.01 (n)
  • 76.03 (a)
mouse
(Mus musculus)
Mammalia Trim21 16
Trim21 36
  • 70 (a)
OneToOne
Trim21 35
  • 77.54 (n)
  • 70.65 (a)
rat
(Rattus norvegicus)
Mammalia Trim21 35
  • 77.61 (n)
  • 70.82 (a)
chicken
(Gallus gallus)
Aves -- 36
  • 36 (a)
OneToMany
lizard
(Anolis carolinensis)
Reptilia -- 36
  • 40 (a)
OneToMany
Species with no ortholog for TRIM21:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • oppossum (Monodelphis domestica)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)
  • zebrafish (Danio rerio)

Evolution for TRIM21 Gene

ENSEMBL:
Gene Tree for TRIM21 (if available)
TreeFam:
Gene Tree for TRIM21 (if available)

Paralogs for TRIM21 Gene

genes like me logo Genes that share paralogs with TRIM21: view

Variants for TRIM21 Gene

Sequence variations from dbSNP and Humsavar for TRIM21 Gene

SNP ID Clin Chr 11 pos Sequence Context AA Info Type
rs1042302 - 4,390,256(-) TCTGT(C/G)CTGTG reference, missense
rs2975162 - 4,390,124(+) CTCTC(C/T)ATGCA reference, missense
rs2554934 - 4,388,344(+) TAGCT(C/T)TGAGA intron-variant, reference, missense
rs58403334 - 4,390,148(+) CCCCT(G/T)TGTGC reference, missense
rs760217 -- 4,388,905(+) CCTGT(C/T)CCCAC intron-variant

Structural Variations from Database of Genomic Variants (DGV) for TRIM21 Gene

Variant ID Type Subtype PubMed ID
essv17026 CNV CNV 17122850
nsv428248 CNV Gain+Loss 18775914
dgv338e1 CNV Complex 17122850
nsv832054 CNV Gain 17160897
nsv469800 CNV Complex 16826518
dgv1021n71 CNV Gain 21882294
nsv896908 CNV Gain 21882294
nsv896911 CNV Gain 21882294

Variation tolerance for TRIM21 Gene

Residual Variation Intolerance Score: 61.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.88; 18.39% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for TRIM21 Gene

HapMap Linkage Disequilibrium report
TRIM21
Human Gene Mutation Database (HGMD)
TRIM21

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TRIM21 Gene

Disorders for TRIM21 Gene

MalaCards: The human disease database

(25) MalaCards diseases for TRIM21 Gene - From: OMIM, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
myelofibrosis with myeloid metaplasia, somatic
  • myelofibrosis, somatic
thrombocythemia 1
  • thrombocythemia, somatic
sjogren's syndrome
  • sicca syndrome
rheumatic disease
  • rheumatic diseases
cutaneous lupus erythematosus
  • lupus erythematosus, cutaneous
- elite association - COSMIC cancer census association via MalaCards

Relevant External Links for TRIM21

Genetic Association Database (GAD)
TRIM21
Human Genome Epidemiology (HuGE) Navigator
TRIM21
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
TRIM21
genes like me logo Genes that share disorders with TRIM21: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TRIM21 Gene

Publications for TRIM21 Gene

  1. Autoantigen Ro52 is an E3 ubiquitin ligase. (PMID: 16297862) Wada K. … Kamitani T. (Biochem. Biophys. Res. Commun. 2006) 3 4 23 67
  2. rs660 polymorphism in Ro52 (SSA1; TRIM21) is a marker for age-dependent tolerance induction and efficiency of alloimmunization in sickle cell disease. (PMID: 19201475) Tatari-Calderone Z. … Vukmanovic S. (Mol. Immunol. 2009) 3 23
  3. Ro52 functionally interacts with IgG1 and regulates its quality control via the ERAD system. (PMID: 18022694) Takahata M. … Hatakeyama S. (Mol. Immunol. 2008) 3 23
  4. Interferon-alpha induces up-regulation and nuclear translocation of the Ro52 autoantigen as detected by a panel of novel Ro52-specific monoclonal antibodies. (PMID: 18071879) Strandberg L. … Wahren-Herlenius M. (J. Clin. Immunol. 2008) 3 23
  5. SSA/Ro52 autoantigen interacts with Dcp2 to enhance its decapping activity. (PMID: 18361920) Yamochi T. … Morimoto C. (Biochem. Biophys. Res. Commun. 2008) 3 23

Products for TRIM21 Gene

Sources for TRIM21 Gene

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