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Protein

E3 ubiquitin-protein ligase TRIM56

Gene

TRIM56

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

Functioni

E3 ubiquitin-protein ligase that plays a key role in innate antiviral immunity (PubMed:21289118). In response to pathogen- and host-derived double-stranded DNA (dsDNA), targets TMEM173/STING to 'Lys-63'-linked ubiquitination, thereby promoting its homodimerization, a step required for the production of type I interferon IFN-beta (By similarity). Independently of its E3 ubiquitin ligase activity, positive regulator of TLR3 signaling. Potentiates extracellular double stranded RNA (dsRNA)-induced expression of IFNB1 and interferon-stimulated genes ISG15, IFIT1/ISG56, CXCL10, OASL and CCL5/RANTES. Promotes establishment of an antiviral state by TLR3 ligand and TLR3-mediated chemokine induction following infection by hepatitis C virus (PubMed:22948160).By similarity2 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.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri21 – 60RING-typePROSITE-ProRule annotationAdd BLAST40
Zinc fingeri98 – 149B box-type 1PROSITE-ProRule annotationAdd BLAST52
Zinc fingeri164 – 205B box-type 2PROSITE-ProRule annotationAdd BLAST42

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processAntiviral defense, Immunity, Innate immunity, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-3134975 Regulation of innate immune responses to cytosolic DNA

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase TRIM56 (EC:2.3.2.27)
Alternative name(s):
RING finger protein 109
RING-type E3 ubiquitin transferase TRIM56Curated
Tripartite motif-containing protein 56
Gene namesi
Name:TRIM56
Synonyms:RNF109
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000169871.12
HGNCiHGNC:19028 TRIM56
MIMi616996 gene
neXtProtiNX_Q9BRZ2

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi21C → A: Complete loss of autoubiquitination. Complete loss of autoubiquitination, loss of antiviral activity against yellow fever virus and human coronavirus virus OC43, but normal induction of interferon-beta following Sendai virus infection; when associated with A-24. 1 Publication1
Mutagenesisi24C → A: Complete loss of autoubiquitination, loss of antiviral activity against yellow fever virus and human coronavirus virus OC43, but normal induction of interferon-beta following Sendia virus infection; when associated with A-24. 1 Publication1

Organism-specific databases

DisGeNETi81844
OpenTargetsiENSG00000169871
PharmGKBiPA134958549

Polymorphism and mutation databases

BioMutaiTRIM56
DMDMi56749788

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000562881 – 755E3 ubiquitin-protein ligase TRIM56Add BLAST755

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei418PhosphothreonineCombined sources1
Modified residuei442PhosphothreonineCombined sources1
Modified residuei475PhosphoserineCombined sources1

Post-translational modificationi

Autoubiquitinated.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9BRZ2
MaxQBiQ9BRZ2
PaxDbiQ9BRZ2
PeptideAtlasiQ9BRZ2
PRIDEiQ9BRZ2

PTM databases

iPTMnetiQ9BRZ2
PhosphoSitePlusiQ9BRZ2

Expressioni

Tissue specificityi

Widely expressed (at protein level).1 Publication

Inductioni

Up-regulated by IFN-alpha.1 Publication

Gene expression databases

BgeeiENSG00000169871
CleanExiHS_TRIM56
ExpressionAtlasiQ9BRZ2 baseline and differential
GenevisibleiQ9BRZ2 HS

Organism-specific databases

HPAiHPA024358

Interactioni

Subunit structurei

Homooligomer. Interacts with TMEM173/STING (By similarity). Interacts with TICAM1 (PubMed:22948160).By similarity1 Publication

Protein-protein interaction databases

BioGridi123596, 25 interactors
IntActiQ9BRZ2, 20 interactors
STRINGi9606.ENSP00000305161

Structurei

Secondary structure

1755
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni22 – 24Combined sources3
Helixi42 – 48Combined sources7
Beta strandi57 – 59Combined sources3
Beta strandi66 – 69Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5JW7X-ray2.85B1-93[»]
ProteinModelPortaliQ9BRZ2
SMRiQ9BRZ2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili216 – 314Sequence analysisAdd BLAST99

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi302 – 309Poly-Ala8
Compositional biasi459 – 464Poly-Lys6

Sequence similaritiesi

Belongs to the TRIM/RBCC family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri21 – 60RING-typePROSITE-ProRule annotationAdd BLAST40
Zinc fingeri98 – 149B box-type 1PROSITE-ProRule annotationAdd BLAST52
Zinc fingeri164 – 205B box-type 2PROSITE-ProRule annotationAdd BLAST42

Keywords - Domaini

Coiled coil, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410ITEJ Eukaryota
ENOG410YNG0 LUCA
GeneTreeiENSGT00890000139359
HOGENOMiHOG000154679
HOVERGENiHBG079280
InParanoidiQ9BRZ2
KOiK12026
OMAiAYHGLEK
OrthoDBiEOG091G03B5
PhylomeDBiQ9BRZ2
TreeFamiTF338323

Family and domain databases

CDDicd00021 BBOX, 1 hit
Gene3Di2.120.10.30, 1 hit
3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR011042 6-blade_b-propeller_TolB-like
IPR027370 Znf-RING_LisH
IPR000315 Znf_B-box
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
PfamiView protein in Pfam
PF00643 zf-B_box, 1 hit
PF13445 zf-RING_UBOX, 1 hit
SMARTiView protein in SMART
SM00336 BBOX, 1 hit
SM00184 RING, 1 hit
PROSITEiView protein in PROSITE
PS50119 ZF_BBOX, 1 hit
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9BRZ2-1) [UniParc]FASTAAdd to basket

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
MVSHGSSPSL LEALSSDFLA CKICLEQLRA PKTLPCLHTY CQDCLAQLAD
60 70 80 90 100
GGRVRCPECR ETVPVPPEGV ASFKTNFFVN GLLDLVKARA CGDLRAGKPA
110 120 130 140 150
CALCPLVGGT STGGPATARC LDCADDLCQA CADGHRCTRQ THTHRVVDLV
160 170 180 190 200
GYRAGWYDEE ARERQAAQCP QHPGEALRFL CQPCSQLLCR ECRLDPHLDH
210 220 230 240 250
PCLPLAEAVR ARRPGLEGLL AGVDNNLVEL EAARRVEKEA LARLREQAAR
260 270 280 290 300
VGTQVEEAAE GVLRALLAQK QEVLGQLRAH VEAAEEAARE RLAELEGREQ
310 320 330 340 350
VARAAAAFAR RVLSLGREAE ILSLEGAIAQ RLRQLQGCPW APGPAPCLLP
360 370 380 390 400
QLELHPGLLD KNCHLLRLSF EEQQPQKDGG KDGAGTQGGE ESQSRREDEP
410 420 430 440 450
KTERQGGVQP QAGDGAQTPK EEKAQTTREE GAQTLEEDRA QTPHEDGGPQ
460 470 480 490 500
PHRGGRPNKK KKFKGRLKSI SREPSPALGP NLDGSGLLPR PIFYCSFPTR
510 520 530 540 550
MPGDKRSPRI TGLCPFGPRE ILVADEQNRA LKRFSLNGDY KGTVPVPEGC
560 570 580 590 600
SPCSVAALQS AVAFSASARL YLINPNGEVQ WRRALSLSQA SHAVAALPSG
610 620 630 640 650
DRVAVSVAGH VEVYNMEGSL ATRFIPGGKA SRGLRALVFL TTSPQGHFVG
660 670 680 690 700
SDWQQNSVVI CDGLGQVVGE YKGPGLHGCQ PGSVSVDKKG YIFLTLREVN
710 720 730 740 750
KVVILDPKGS LLGDFLTAYH GLEKPRVTTM VDGRYLVVSL SNGTIHIFRV

RSPDS
Length:755
Mass (Da):81,488
Last modified:December 21, 2004 - v3
Checksum:iCF72D0C8EC9F69E7
GO
Isoform 2 (identifier: Q9BRZ2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     273-308: VLGQLRAHVEAAEEAARERLAELEGREQVARAAAAF → NHLNPGGGSCSELRSHHCTPAWVTRMKLHLKKKKKK
     309-755: Missing.

Note: No experimental confirmation available.
Show »
Length:308
Mass (Da):33,550
Checksum:iEB69C6B0CE90A126
GO
Isoform 3 (identifier: Q9BRZ2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     259-269: AEGVLRALLAQ → CLLRTESCKAE
     270-755: Missing.

Show »
Length:269
Mass (Da):29,185
Checksum:iCA973592F7F41BB4
GO

Sequence cautioni

The sequence AAH11882 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAC11500 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti230L → P in AK092927 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_029109259 – 269AEGVLRALLAQ → CLLRTESCKAE in isoform 3. 1 PublicationAdd BLAST11
Alternative sequenceiVSP_029110270 – 755Missing in isoform 3. 1 PublicationAdd BLAST486
Alternative sequenceiVSP_029111273 – 308VLGQL…AAAAF → NHLNPGGGSCSELRSHHCTP AWVTRMKLHLKKKKKK in isoform 2. 1 PublicationAdd BLAST36
Alternative sequenceiVSP_029112309 – 755Missing in isoform 2. 1 PublicationAdd BLAST447

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK075255 mRNA Translation: BAC11500.1 Different initiation.
AK092927 mRNA No translation available.
AC105446 Genomic DNA No translation available.
BC005847 mRNA Translation: AAH05847.3
BC011882 mRNA Translation: AAH11882.1 Different initiation.
BC048194 mRNA Translation: AAH48194.1
AL512757 mRNA Translation: CAC21676.1
CCDSiCCDS43625.1 [Q9BRZ2-1]
RefSeqiNP_112223.1, NM_030961.2 [Q9BRZ2-1]
XP_011514891.1, XM_011516589.2 [Q9BRZ2-1]
UniGeneiHs.521092
Hs.593351

Genome annotation databases

EnsembliENST00000306085; ENSP00000305161; ENSG00000169871 [Q9BRZ2-1]
GeneIDi81844
KEGGihsa:81844
UCSCiuc003uxq.4 human [Q9BRZ2-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiTRI56_HUMAN
AccessioniPrimary (citable) accession number: Q9BRZ2
Secondary accession number(s): Q6PJS5
, Q86VT6, Q8N2H8, Q8NAC0, Q9H031
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 21, 2004
Last sequence update: December 21, 2004
Last modified: May 23, 2018
This is version 145 of the entry and version 3 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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