Human Gene TRIM21 (ENST00000254436.8) Description and Page Index
  Description: Homo sapiens tripartite motif containing 21 (TRIM21), mRNA. (from RefSeq NM_003141)
RefSeq Summary (NM_003141): 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].
Gencode Transcript: ENST00000254436.8
Gencode Gene: ENSG00000132109.10
Transcript (Including UTRs)
   Position: hg38 chr11:4,384,897-4,393,702 Size: 8,806 Total Exon Count: 7 Strand: -
Coding Region
   Position: hg38 chr11:4,385,285-4,390,409 Size: 5,125 Coding Exon Count: 6 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated at UCSC: 2019-09-04

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr11:4,384,897-4,393,702)mRNA (may differ from genome)Protein (475 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=E3 ubiquitin-protein ligase TRIM21; EC=6.3.2.-; AltName: Full=52 kDa Ro protein; AltName: Full=52 kDa ribonucleoprotein autoantigen Ro/SS-A; AltName: Full=RING finger protein 81; AltName: Full=Ro(SS-A); AltName: Full=Sjoegren syndrome type A antigen; Short=SS-A; AltName: Full=Tripartite motif-containing protein 21;
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.
PATHWAY: Protein modification; protein ubiquitination.
SUBUNIT: 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).
INTERACTION: Q13107-1:USP4; NbExp=3; IntAct=EBI-81290, EBI-723305;
SUBCELLULAR LOCATION: Cytoplasm. 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.
TISSUE SPECIFICITY: Isoform 1 and isoform 2 are expressed in fetal and adult heart and fetal lung.
INDUCTION: Up-regulated by isoform 2 of XBP1.
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.
PTM: Autoubiquitinated; does not lead to its proteasomal degradation. Deubiquitinated by USP4; leading to its stabilization.
SIMILARITY: Belongs to the TRIM/RBCC family.
SIMILARITY: Contains 1 B box-type zinc finger.
SIMILARITY: Contains 1 B30.2/SPRY domain.
SIMILARITY: Contains 1 RING-type zinc finger.

-  MalaCards Disease Associations
  MalaCards Gene Search: TRIM21
Diseases sorted by gene-association score: sjogren's syndrome (40), heart block, congenital (30), subacute cutaneous lupus erythematosus (27), idiopathic inflammatory myopathy (26), rheumatic disease (23), lupus erythematosus (21), cutaneous lupus erythematosus (19), systemic lupus erythematosus (18), transient neonatal thrombocytopenia (15), transient neonatal neutropenia (15), salivary gland disease (12), phototoxic dermatitis (11), xerophthalmia (10), third-degree atrioventricular block (9), photoparoxysmal response 1 (9), adie pupil (8), neonatal lupus erythematosus (8), hyperglobulinemic purpura (7), lacrimal apparatus disease (7), hypersensitivity reaction type ii disease (7), hypersensitivity reaction disease (7), lymphoid interstitial pneumonia (7), lactocele (6), facial hemiatrophy (6), diffuse scleroderma (6), chilblain lupus (5), heart conduction disease (5), diffuse infiltrative lymphocytosis syndrome (5), sialadenitis (5), exanthem (5), pericardium disease (5), punctate epithelial keratoconjunctivitis (4), cogan syndrome (4), myositis (3), immune system disease (1), collagen disease (1), leukoencephalopathy with vanishing white matter (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 30.29 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 393.45 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -24.50119-0.206 Picture PostScript Text
3' UTR -78.10388-0.201 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001870 - B30.2/SPRY
IPR003879 - Butyrophylin
IPR008985 - ConA-like_lec_gl_sf
IPR006574 - PRY
IPR018355 - SPla/RYanodine_receptor_subgr
IPR003877 - SPRY_rcpt
IPR000315 - Znf_B-box
IPR020457 - Znf_B-box_chordata
IPR018957 - Znf_C3HC4_RING-type
IPR001841 - Znf_RING
IPR017907 - Znf_RING_CS

Pfam Domains:
PF00622 - SPRY domain
PF00643 - B-box zinc finger
PF00097 - Zinc finger, C3HC4 type (RING finger)

Protein Data Bank (PDB) 3-D Structure
MuPIT help

- X-ray

ModBase Predicted Comparative 3D Structure on P19474
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologGenome BrowserNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl WormBase 
Protein SequenceProtein Sequence  Protein Sequence 
AlignmentAlignment  Alignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003677 DNA binding
GO:0003723 RNA binding
GO:0004842 ubiquitin-protein transferase activity
GO:0005515 protein binding
GO:0008270 zinc ion binding
GO:0016740 transferase activity
GO:0042802 identical protein binding
GO:0046872 metal ion binding

Biological Process:
GO:0000209 protein polyubiquitination
GO:0006513 protein monoubiquitination
GO:0007049 cell cycle
GO:0010508 positive regulation of autophagy
GO:0016567 protein ubiquitination
GO:0031648 protein destabilization
GO:0032088 negative regulation of NF-kappaB transcription factor activity
GO:0032479 regulation of type I interferon production
GO:0032897 negative regulation of viral transcription
GO:0034341 response to interferon-gamma
GO:0045087 innate immune response
GO:0045787 positive regulation of cell cycle
GO:0046598 positive regulation of viral entry into host cell
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051865 protein autoubiquitination
GO:0060333 interferon-gamma-mediated signaling pathway
GO:0070206 protein trimerization
GO:0090086 negative regulation of protein deubiquitination
GO:1902187 negative regulation of viral release from host cell

Cellular Component:
GO:0000932 P-body
GO:0005622 intracellular
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005776 autophagosome
GO:0005829 cytosol
GO:0031410 cytoplasmic vesicle
GO:1990904 ribonucleoprotein complex
GO:0019005 SCF ubiquitin ligase complex

-  Descriptions from all associated GenBank mRNAs
  BC010861 - Homo sapiens tripartite motif-containing 21, mRNA (cDNA clone MGC:9233 IMAGE:3900540), complete cds.
AK225564 - Homo sapiens mRNA for 52kD Ro/SSA autoantigen variant, clone: LNF00719.
M62800 - Human 52-kD SS-A/Ro autoantigen mRNA, complete cds.
M34551 - Human 52-kD ribonucleoprotein Ro/SSA mRNA, complete cds.
JD279809 - Sequence 260833 from Patent EP1572962.
JD382826 - Sequence 363850 from Patent EP1572962.
JD110858 - Sequence 91882 from Patent EP1572962.
JD299989 - Sequence 281013 from Patent EP1572962.
JD056302 - Sequence 37326 from Patent EP1572962.
JD056301 - Sequence 37325 from Patent EP1572962.
JD437875 - Sequence 418899 from Patent EP1572962.
AY742713 - Homo sapiens Sjogren syndrome antigen A1 mRNA, complete cds.
KJ901052 - Synthetic construct Homo sapiens clone ccsbBroadEn_10446 TRIM21 gene, encodes complete protein.
EU446706 - Synthetic construct Homo sapiens clone IMAGE:100070204; IMAGE:100011915; FLH257294.01L tripartite motif-containing 21 (TRIM21) gene, encodes complete protein.
AB527770 - Synthetic construct DNA, clone: pF1KB5826, Homo sapiens TRIM21 gene for tripartite motif-containing 21, without stop codon, in Flexi system.
CU679827 - Synthetic construct Homo sapiens gateway clone IMAGE:100017343 5' read TRIM21 mRNA.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa05322 - Systemic lupus erythematosus

Reactome (by CSHL, EBI, and GO)

Protein P19474 (Reactome details) participates in the following event(s):

R-HSA-3134946 DDX41 ubiquitination by TRIM21
R-HSA-983157 Interaction of E3 with substrate and E2-Ub complex
R-HSA-983147 Release of E3 from polyubiquitinated substrate
R-HSA-983140 Transfer of Ub from E2 to substrate and release of E2
R-HSA-3134975 Regulation of innate immune responses to cytosolic DNA
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-877300 Interferon gamma signaling
R-HSA-1834949 Cytosolic sensors of pathogen-associated DNA
R-HSA-983169 Class I MHC mediated antigen processing & presentation
R-HSA-913531 Interferon Signaling
R-HSA-168249 Innate Immune System
R-HSA-1280218 Adaptive Immune System
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-168256 Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: NM_003141, P19474, Q5XPV5, Q96RF8, RNF81, RO52, RO52_HUMAN, SSA1, uc001lyy.1, uc001lyy.2, uc001lyy.3
UCSC ID: uc001lyy.3
RefSeq Accession: NM_003141
Protein: P19474 (aka RO52_HUMAN)
CCDS: CCDS44525.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.