DegronMD - P19474(TRIM21)

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, PubMed:16297862, PubMed:16316627, PubMed:16472766, PubMed:16880511, PubMed:18022694, PubMed:18361920, PubMed:18641315, PubMed:18845142, PubMed:19675099). Represses the innate antiviral response by facilitating the formation of the NMI-IFI35 complex through 'Lys-63'-linked ubiquitination of NMI (PubMed:26342464). {ECO:0000269|PubMed:16297862, ECO:0000269|PubMed:16316627, ECO:0000269|PubMed:16472766, ECO:0000269|PubMed:16880511, ECO:0000269|PubMed:18022694, ECO:0000269|PubMed:18361920, ECO:0000269|PubMed:18641315, ECO:0000269|PubMed:18845142, ECO:0000269|PubMed:19675099, ECO:0000269|PubMed:26342464, ECO:0000269|PubMed:26347139}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.A165S	TCGA-76-6656	GBM	TCGA	KSRIHAE	LIG_APCC_ABBAyCdc20_2	175:181	Mutation rewiring degron network	0.0556
p.A165S	DO13671	GBM	ICGC	KSRIHAE	LIG_APCC_ABBAyCdc20_2	175:181	Mutation rewiring degron network	0.0556
p.A165S	DO35192	PACA	ICGC	KSRIHAE	LIG_APCC_ABBAyCdc20_2	175:181	Mutation rewiring degron network	0.0556
p.A180T	TCGA-AX-A2H7	UCEC	TCGA	KSRIHAE	LIG_APCC_ABBAyCdc20_2	175:181	Mutation altering degron motif	0.6028
p.A180T	DO41044	UCEC	ICGC	KSRIHAE	LIG_APCC_ABBAyCdc20_2	175:181	Mutation altering degron motif	0.6028
p.N187S	TCGA-BR-6452	STAD	TCGA	KSRIHAE	LIG_APCC_ABBAyCdc20_2	175:181	Mutation rewiring degron network	0.1667
p.N187S	DO38404	STAD	ICGC	KSRIHAE	LIG_APCC_ABBAyCdc20_2	175:181	Mutation rewiring degron network	0.1667
p.T170A	TCGA-D1-A103	UCEC	TCGA	KSRIHAE	LIG_APCC_ABBAyCdc20_2	175:181	Mutation rewiring degron network	0.1944
p.T170A	DO42312	UCEC	ICGC	KSRIHAE	LIG_APCC_ABBAyCdc20_2	175:181	Mutation rewiring degron network	0.1944
p.F188Y	TCGA-DI-A1BU	UCEC	TCGA	KSRIHAE	LIG_APCC_ABBAyCdc20_2	175:181	Mutation rewiring degron network	0.1389
p.F188Y	DO42023	UCEC	ICGC	KSRIHAE	LIG_APCC_ABBAyCdc20_2	175:181	Mutation rewiring degron network	0.1389
p.V190I	TCGA-HU-A4GU	STAD	TCGA	KSRIHAE	LIG_APCC_ABBAyCdc20_2	175:181	Mutation rewiring degron network	0.0833
p.V190I	DO47849	STAD	ICGC	KSRIHAE	LIG_APCC_ABBAyCdc20_2	175:181	Mutation rewiring degron network	0.0833
p.S176F	TCGA-RP-A693	SKCM	TCGA	KSRIHAE	LIG_APCC_ABBAyCdc20_2	175:181	Mutation altering degron motif	0.6871
p.S176F	DO51268	SKCM	ICGC	KSRIHAE	LIG_APCC_ABBAyCdc20_2	175:181	Mutation altering degron motif	0.6871
p.K175N	DO222884	COCA	ICGC	KSRIHAE	LIG_APCC_ABBAyCdc20_2	175:181	Mutation altering degron motif	0.6918
p.A165E	DO234256	ESAD	ICGC	KSRIHAE	LIG_APCC_ABBAyCdc20_2	175:181	Mutation rewiring degron network	0.0556
p.T173K	DO229032	LICA	ICGC	KSRIHAE	LIG_APCC_ABBAyCdc20_2	175:181	Mutation rewiring degron network	0.2778
p.H179N	DO229031	LICA	ICGC	KSRIHAE	LIG_APCC_ABBAyCdc20_2	175:181	Mutation altering degron motif	0.7423

DegronMD: protein-targeted degradation, mutation and drug response to degrons

TRIM21

UniProt ID: P19474

Entrez ID: 6737

Protein name: E3 ubiquitin-protein ligase TRIM21 (EC 2.3.2.27) (52 kDa Ro protein) (52 kDa ribonucleoprotein autoantigen Ro/SS-A) (RING finger protein 81) (RING-type E3 ubiquitin transferase TRIM21) (Ro(SS-A)) (Sjoegren syndrome type A antigen) (SS-A) (Tripartite motif-containing protein 21)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for TRIM21 in