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Protein

E3 ubiquitin-protein ligase TRIM21

Gene

TRIM21

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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).10 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri16 – 55RING-typePROSITE-ProRule annotationAdd BLAST40
Zinc fingeri92 – 123B box-typePROSITE-ProRule annotationAdd BLAST32

GO - Molecular functioni

  • DNA binding Source: UniProtKB-KW
  • identical protein binding Source: IntAct
  • RNA binding Source: UniProtKB-KW
  • ubiquitin-protein transferase activity Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

Keywordsi

Molecular functionDNA-binding, Ribonucleoprotein, RNA-binding, Transferase
Biological processCell cycle, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-1834941 STING mediated induction of host immune responses
R-HSA-3134975 Regulation of innate immune responses to cytosolic DNA
R-HSA-877300 Interferon gamma signaling
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SIGNORiP19474
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase TRIM21 (EC:2.3.2.27)
Alternative name(s):
52 kDa Ro protein
52 kDa ribonucleoprotein autoantigen Ro/SS-A
RING finger protein 81
RING-type E3 ubiquitin transferase TRIM21Curated
Ro(SS-A)
Sjoegren syndrome type A antigen
Short name:
SS-A
Tripartite motif-containing protein 21
Gene namesi
Name:TRIM21
Synonyms:RNF81, RO52, SSA1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000132109.9
HGNCiHGNC:11312 TRIM21
MIMi109092 gene
neXtProtiNX_P19474

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoplasmic vesicle, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi16C → A: Loss of E3 ubiquitin-protein ligase activity. Does not inhibit NF-kappa-B-induced gene expression. 3 Publications1

Organism-specific databases

DisGeNETi6737
OpenTargetsiENSG00000132109
PharmGKBiPA36136

Polymorphism and mutation databases

BioMutaiTRIM21
DMDMi133250

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000561151 – 475E3 ubiquitin-protein ligase TRIM21Add BLAST475

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei266PhosphoserineCombined sources1

Post-translational modificationi

Autoubiquitinated; does not lead to its proteasomal degradation. Deubiquitinated by USP4; leading to its stabilization.5 Publications

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP19474
MaxQBiP19474
PaxDbiP19474
PeptideAtlasiP19474
PRIDEiP19474
ProteomicsDBi53666
53667 [P19474-2]

PTM databases

iPTMnetiP19474
PhosphoSitePlusiP19474

Expressioni

Tissue specificityi

Isoform 1 and isoform 2 are expressed in fetal and adult heart and fetal lung.

Inductioni

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.1 Publication

Gene expression databases

BgeeiENSG00000132109 Expressed in 148 organ(s), highest expression level in leukocyte
CleanExiHS_TRIM21
ExpressionAtlasiP19474 baseline and differential
GenevisibleiP19474 HS

Organism-specific databases

HPAiCAB004566
HPA005673

Interactioni

Subunit structurei

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).By similarity9 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112615, 99 interactors
IntActiP19474, 58 interactors
MINTiP19474
STRINGi9606.ENSP00000254436

Structurei

Secondary structure

1475
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP19474
SMRiP19474
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP19474

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini268 – 465B30.2/SPRYPROSITE-ProRule annotationAdd BLAST198

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili128 – 238Sequence analysisAdd BLAST111

Domaini

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.1 Publication

Sequence similaritiesi

Belongs to the TRIM/RBCC family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri16 – 55RING-typePROSITE-ProRule annotationAdd BLAST40
Zinc fingeri92 – 123B box-typePROSITE-ProRule annotationAdd BLAST32

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

eggNOGiKOG2177 Eukaryota
ENOG4111G04 LUCA
GeneTreeiENSGT00760000118893
HOGENOMiHOG000234133
HOVERGENiHBG001357
InParanoidiP19474
KOiK10651
OMAiCWVCSQS
OrthoDBiEOG091G05W2
PhylomeDBiP19474
TreeFamiTF338674

Family and domain databases

CDDicd00021 BBOX, 1 hit
cd12900 SPRY_PRY_TRIM21, 1 hit
Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR001870 B30.2/SPRY
IPR003879 Butyrophylin_SPRY
IPR013320 ConA-like_dom_sf
IPR006574 PRY
IPR035831 PRY/SPRY_TRIM21
IPR003877 SPRY_dom
IPR003613 Ubox_domain
IPR000315 Znf_B-box
IPR020457 Znf_B-box_chordata
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
PfamiView protein in Pfam
PF13765 PRY, 1 hit
PF00622 SPRY, 1 hit
PF00643 zf-B_box, 1 hit
PRINTSiPR01406 BBOXZNFINGER
PR01407 BUTYPHLNCDUF
SMARTiView protein in SMART
SM00336 BBOX, 1 hit
SM00589 PRY, 1 hit
SM00184 RING, 1 hit
SM00449 SPRY, 1 hit
SM00504 Ubox, 1 hit
SUPFAMiSSF49899 SSF49899, 1 hit
PROSITEiView protein in PROSITE
PS50188 B302_SPRY, 1 hit
PS50119 ZF_BBOX, 1 hit
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.iShow all

Isoform 1 (identifier: P19474-1) [UniParc]FASTAAdd to basket
Also known as: Ro52alpha, 52alpha

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MASAARLTMM WEEVTCPICL DPFVEPVSIE CGHSFCQECI SQVGKGGGSV
60 70 80 90 100
CPVCRQRFLL KNLRPNRQLA NMVNNLKEIS QEAREGTQGE RCAVHGERLH
110 120 130 140 150
LFCEKDGKAL CWVCAQSRKH RDHAMVPLEE AAQEYQEKLQ VALGELRRKQ
160 170 180 190 200
ELAEKLEVEI AIKRADWKKT VETQKSRIHA EFVQQKNFLV EEEQRQLQEL
210 220 230 240 250
EKDEREQLRI LGEKEAKLAQ QSQALQELIS ELDRRCHSSA LELLQEVIIV
260 270 280 290 300
LERSESWNLK DLDITSPELR SVCHVPGLKK MLRTCAVHIT LDPDTANPWL
310 320 330 340 350
ILSEDRRQVR LGDTQQSIPG NEERFDSYPM VLGAQHFHSG KHYWEVDVTG
360 370 380 390 400
KEAWDLGVCR DSVRRKGHFL LSSKSGFWTI WLWNKQKYEA GTYPQTPLHL
410 420 430 440 450
QVPPCQVGIF LDYEAGMVSF YNITDHGSLI YSFSECAFTG PLRPFFSPGF
460 470
NDGGKNTAPL TLCPLNIGSQ GSTDY
Length:475
Mass (Da):54,170
Last modified:February 1, 1991 - v1
Checksum:iDDFF2944AFC629FB
GO
Isoform 2 (identifier: P19474-2) [UniParc]FASTAAdd to basket
Also known as: Ro52beta, 52beta

The sequence of this isoform differs from the canonical sequence as follows:
     169-245: Missing.

Note: No experimental confirmation available.
Show »
Length:398
Mass (Da):45,057
Checksum:i552986C67B78356F
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YDP8H0YDP8_HUMAN
E3 ubiquitin-protein ligase TRIM21
TRIM21
90Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti10M → T in AAU89982 (Ref. 6) Curated1
Sequence conflicti189L → P in AAU89982 (Ref. 6) Curated1
Sequence conflicti216A → T in AAU89982 (Ref. 6) Curated1
Sequence conflicti262L → V in AAU89982 (Ref. 6) Curated1
Sequence conflicti313D → V in AAU89982 (Ref. 6) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01374952P → A1 PublicationCorresponds to variant dbSNP:rs1042302Ensembl.1
Natural variantiVAR_06182188Q → K. Corresponds to variant dbSNP:rs58403334Ensembl.1
Natural variantiVAR_01375096G → R1 PublicationCorresponds to variant dbSNP:rs2975162Ensembl.1
Natural variantiVAR_013751231E → K. Corresponds to variant dbSNP:rs2554934Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_039627169 – 245Missing in isoform 2. CuratedAdd BLAST77

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M34551 mRNA Translation: AAA36581.1
U01882 Genomic DNA Translation: AAB87094.1
M62800 mRNA Translation: AAA36651.1
U13658, U13657 Genomic DNA Translation: AAA79867.1
AF391283 Genomic DNA Translation: AAK76432.1
AY742713 mRNA Translation: AAU89982.1
AC009758 Genomic DNA No translation available.
BC010861 mRNA Translation: AAH10861.1
CCDSiCCDS44525.1 [P19474-1]
PIRiA55642 A37241
RefSeqiNP_003132.2, NM_003141.3 [P19474-1]
UniGeneiHs.532357

Genome annotation databases

EnsembliENST00000254436; ENSP00000254436; ENSG00000132109 [P19474-1]
GeneIDi6737
KEGGihsa:6737
UCSCiuc001lyy.2 human [P19474-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M34551 mRNA Translation: AAA36581.1
U01882 Genomic DNA Translation: AAB87094.1
M62800 mRNA Translation: AAA36651.1
U13658, U13657 Genomic DNA Translation: AAA79867.1
AF391283 Genomic DNA Translation: AAK76432.1
AY742713 mRNA Translation: AAU89982.1
AC009758 Genomic DNA No translation available.
BC010861 mRNA Translation: AAH10861.1
CCDSiCCDS44525.1 [P19474-1]
PIRiA55642 A37241
RefSeqiNP_003132.2, NM_003141.3 [P19474-1]
UniGeneiHs.532357

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2IWGX-ray2.35B/E287-465[»]
5JPXNMR-A86-130[»]
5OLMX-ray1.95A/B1-129[»]
ProteinModelPortaliP19474
SMRiP19474
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112615, 99 interactors
IntActiP19474, 58 interactors
MINTiP19474
STRINGi9606.ENSP00000254436

PTM databases

iPTMnetiP19474
PhosphoSitePlusiP19474

Polymorphism and mutation databases

BioMutaiTRIM21
DMDMi133250

Proteomic databases

EPDiP19474
MaxQBiP19474
PaxDbiP19474
PeptideAtlasiP19474
PRIDEiP19474
ProteomicsDBi53666
53667 [P19474-2]

Protocols and materials databases

DNASUi6737
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000254436; ENSP00000254436; ENSG00000132109 [P19474-1]
GeneIDi6737
KEGGihsa:6737
UCSCiuc001lyy.2 human [P19474-1]

Organism-specific databases

CTDi6737
DisGeNETi6737
EuPathDBiHostDB:ENSG00000132109.9
GeneCardsiTRIM21
HGNCiHGNC:11312 TRIM21
HPAiCAB004566
HPA005673
MIMi109092 gene
neXtProtiNX_P19474
OpenTargetsiENSG00000132109
PharmGKBiPA36136
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2177 Eukaryota
ENOG4111G04 LUCA
GeneTreeiENSGT00760000118893
HOGENOMiHOG000234133
HOVERGENiHBG001357
InParanoidiP19474
KOiK10651
OMAiCWVCSQS
OrthoDBiEOG091G05W2
PhylomeDBiP19474
TreeFamiTF338674

Enzyme and pathway databases

UniPathwayi
UPA00143

ReactomeiR-HSA-1834941 STING mediated induction of host immune responses
R-HSA-3134975 Regulation of innate immune responses to cytosolic DNA
R-HSA-877300 Interferon gamma signaling
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SIGNORiP19474

Miscellaneous databases

EvolutionaryTraceiP19474
GeneWikiiTRIM21
GenomeRNAii6737
PROiPR:P19474
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000132109 Expressed in 148 organ(s), highest expression level in leukocyte
CleanExiHS_TRIM21
ExpressionAtlasiP19474 baseline and differential
GenevisibleiP19474 HS

Family and domain databases

CDDicd00021 BBOX, 1 hit
cd12900 SPRY_PRY_TRIM21, 1 hit
Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR001870 B30.2/SPRY
IPR003879 Butyrophylin_SPRY
IPR013320 ConA-like_dom_sf
IPR006574 PRY
IPR035831 PRY/SPRY_TRIM21
IPR003877 SPRY_dom
IPR003613 Ubox_domain
IPR000315 Znf_B-box
IPR020457 Znf_B-box_chordata
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
PfamiView protein in Pfam
PF13765 PRY, 1 hit
PF00622 SPRY, 1 hit
PF00643 zf-B_box, 1 hit
PRINTSiPR01406 BBOXZNFINGER
PR01407 BUTYPHLNCDUF
SMARTiView protein in SMART
SM00336 BBOX, 1 hit
SM00589 PRY, 1 hit
SM00184 RING, 1 hit
SM00449 SPRY, 1 hit
SM00504 Ubox, 1 hit
SUPFAMiSSF49899 SSF49899, 1 hit
PROSITEiView protein in PROSITE
PS50188 B302_SPRY, 1 hit
PS50119 ZF_BBOX, 1 hit
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiRO52_HUMAN
AccessioniPrimary (citable) accession number: P19474
Secondary accession number(s): Q5XPV5, Q96RF8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: February 1, 1991
Last modified: September 12, 2018
This is version 206 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health

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