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Protein

E3 ubiquitin-protein ligase TRIM63

Gene

TRIM63

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

E3 ubiquitin ligase. Mediates the ubiquitination and subsequent proteasomal degradation of CKM, GMEB1 and HIBADH. Regulates the proteasomal degradation of muscle proteins under amino acid starvation, where muscle protein is catabolized to provide other organs with amino acids. Inhibits de novo skeletal muscle protein synthesis under amino acid starvation. Regulates proteasomal degradation of cardiac troponin I/TNNI3 and probably of other sarcomeric-associated proteins. May play a role in striated muscle atrophy and hypertrophy by regulating an anti-hypertrophic PKC-mediated signaling pathway. May regulate the organization of myofibrils through TTN in muscle cells.2 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 fingeri23 – 79RING-typePROSITE-ProRule annotationAdd BLAST57
Zinc fingeri117 – 159B box-typePROSITE-ProRule annotationAdd BLAST43

GO - Molecular functioni

  • signal transducer activity Source: UniProtKB
  • titin binding Source: UniProtKB
  • ubiquitin-protein transferase activity Source: Ensembl
  • zinc ion binding Source: InterPro

GO - Biological processi

Keywordsi

Molecular functionMuscle protein, Transferase
Biological processUbl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SIGNORiQ969Q1.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase TRIM63 (EC:2.3.2.27)
Alternative name(s):
Iris RING finger protein
Muscle-specific RING finger protein 1
Short name:
MuRF-1
Short name:
MuRF1
RING finger protein 28
RING-type E3 ubiquitin transferase TRIM63Curated
Striated muscle RING zinc finger protein
Tripartite motif-containing protein 63
Gene namesi
Name:TRIM63
Synonyms:IRF, MURF1, RNF28, SMRZ
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:16007. TRIM63.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • M band Source: UniProtKB-SubCell
  • microtubule Source: UniProtKB
  • nucleus Source: UniProtKB-SubCell
  • Z disc Source: UniProtKB-SubCell

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi39C → A: Loss of SUMO2-binding. 1 Publication1
Mutagenesisi41H → A: Loss of SUMO2-binding. 1 Publication1
Mutagenesisi44C → A: Loss of SUMO2-binding. 1 Publication1
Mutagenesisi47C → A: Loss of SUMO2-binding. 1 Publication1

Organism-specific databases

DisGeNETi84676.
OpenTargetsiENSG00000158022.
PharmGKBiPA34431.

Polymorphism and mutation databases

BioMutaiTRIM63.
DMDMi21362898.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000562901 – 353E3 ubiquitin-protein ligase TRIM63Add BLAST353

Proteomic databases

MaxQBiQ969Q1.
PaxDbiQ969Q1.
PeptideAtlasiQ969Q1.
PRIDEiQ969Q1.

PTM databases

iPTMnetiQ969Q1.
PhosphoSitePlusiQ969Q1.

Expressioni

Tissue specificityi

Muscle specific. Selectively expressed in heart and skeletal muscle. Also expressed in the iris.4 Publications

Developmental stagei

Expressed throughout all developmental stages.1 Publication

Gene expression databases

BgeeiENSG00000158022.
CleanExiHS_TRIM63.
GenevisibleiQ969Q1. HS.

Interactioni

Subunit structurei

Homodimer. Homooligomer and heterooligomer. Interacts with SUMO2, titin/TTN and GMEB1. Interacts with TRIM54 and probably with TRIM55 and TNNI3. Forms a ternary complex with RACK1 and PRKCE (By similarity). Interacts with CKM.By similarity5 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • titin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi124195. 92 interactors.
IntActiQ969Q1. 37 interactors.
MINTiMINT-6492114.
STRINGi9606.ENSP00000363390.

Structurei

Secondary structure

1353
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi123 – 125Combined sources3
Beta strandi132 – 134Combined sources3
Turni135 – 138Combined sources4
Beta strandi139 – 141Combined sources3
Helixi143 – 148Combined sources6
Turni150 – 153Combined sources4
Beta strandi156 – 158Combined sources3
Turni159 – 161Combined sources3
Helixi214 – 267Combined sources54

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2D8UNMR-A119-169[»]
3DDTX-ray1.90A/B/C117-161[»]
4M3LX-ray2.10A/B/C/D214-271[»]
ProteinModelPortaliQ969Q1.
SMRiQ969Q1.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ969Q1.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini267 – 325COSPROSITE-ProRule annotationAdd BLAST59

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni74 – 218Interaction with TTN1 PublicationAdd BLAST145

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili207 – 269Sequence analysisAdd BLAST63

Domaini

The RING-type zinc finger mediates interaction with SUMO2 and localization to the nucleus. Also required for the E3 ubiquitin ligase activity (By similarity).By similarity
The B box-type zinc finger mediates homodimerization.3 Publications

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri23 – 79RING-typePROSITE-ProRule annotationAdd BLAST57
Zinc fingeri117 – 159B box-typePROSITE-ProRule annotationAdd BLAST43

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

eggNOGiENOG410ITEN. Eukaryota.
ENOG4110918. LUCA.
GeneTreeiENSGT00760000118878.
HOGENOMiHOG000231156.
HOVERGENiHBG071242.
InParanoidiQ969Q1.
KOiK10655.
OMAiSHPMCKE.
OrthoDBiEOG091G071N.
PhylomeDBiQ969Q1.
TreeFamiTF331669.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiView protein in InterPro
IPR017903. COS_domain.
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
PS51262. COS. 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

Isoform 1 (identifier: Q969Q1-1) [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
MDYKSSLIQD GNPMENLEKQ LICPICLEMF TKPVVILPCQ HNLCRKCAND
60 70 80 90 100
IFQAANPYWT SRGSSVSMSG GRFRCPTCRH EVIMDRHGVY GLQRNLLVEN
110 120 130 140 150
IIDIYKQECS SRPLQKGSHP MCKEHEDEKI NIYCLTCEVP TCSMCKVFGI
160 170 180 190 200
HKACEVAPLQ SVFQGQKTEL NNCISMLVAG NDRVQTIITQ LEDSRRVTKE
210 220 230 240 250
NSHQVKEELS QKFDTLYAIL DEKKSELLQR ITQEQEKKLS FIEALIQQYQ
260 270 280 290 300
EQLDKSTKLV ETAIQSLDEP GGATFLLTAK QLIKSIVEAS KGCQLGKTEQ
310 320 330 340 350
GFENMDFFTL DLEHIADALR AIDFGTDEEE EEFIEEEDQE EEESTEGKEE

GHQ
Length:353
Mass (Da):40,248
Last modified:December 1, 2001 - v1
Checksum:i9BE4B1505039BC86
GO
Isoform 2 (identifier: Q969Q1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     104-131: Missing.

Note: No experimental confirmation available.
Show »
Length:325
Mass (Da):36,950
Checksum:iB03213D38E2063B0
GO

Sequence cautioni

The sequence AAK52497 differs from that shown. Sequencing errors.Curated
The sequence AAK52497 differs from that shown. Reason: Frameshift at several positions.Curated
The sequence CAC33173 differs from that shown. Reason: Erroneous initiation.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0740925S → L Rare variant; found in a patient with hypertrophic cardiomyopathy; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs762015648Ensembl.1
Natural variantiVAR_07409361S → R1 Publication1
Natural variantiVAR_07409473F → S Rare variant; found in a patient with hypertrophic cardiomyopathy; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs758754060Ensembl.1
Natural variantiVAR_07409586R → C Rare variant; found in a patient with hypertrophic cardiomyopathy; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs529429430Ensembl.1
Natural variantiVAR_07409686R → H Rare variant; found in a patient with hypertrophic cardiomyopathy; unknown pathological significance. 1 Publication1
Natural variantiVAR_074097101I → F Rare variant; found in a patient with hypertrophic cardiomyopathy; unknown pathological significance. 1 Publication1
Natural variantiVAR_074098126E → D1 PublicationCorresponds to variant dbSNP:rs142601731Ensembl.1
Natural variantiVAR_074099232T → M Rare variant; found in a patient with hypertrophic cardiomyopathy; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs376414719Ensembl.1
Natural variantiVAR_020116237K → E2 PublicationsCorresponds to variant dbSNP:rs2275950Ensembl.1
Natural variantiVAR_074100254D → N1 Publication1
Natural variantiVAR_074101305M → I1 Publication1
Natural variantiVAR_074102318A → D Rare variant; found in a patient with hypertrophic cardiomyopathy; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs201397530Ensembl.1
Natural variantiVAR_074103321A → D1 Publication1
Natural variantiVAR_074104351G → R1 PublicationCorresponds to variant dbSNP:rs202001619Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_055443104 – 131Missing in isoform 2. 1 PublicationAdd BLAST28

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ291713 mRNA. Translation: CAC33173.1. Different initiation.
AF353673 mRNA. Translation: AAK39519.1.
AJ276484 mRNA. Translation: CAC81706.1.
AF361946 mRNA. Translation: AAK52497.1. Sequence problems.
AK056942 mRNA. Translation: BAB71318.1.
AK297820 mRNA. Translation: BAG60157.1.
AL391650 Genomic DNA. Translation: CAI17133.1.
BC080529 mRNA. Translation: AAH80529.1.
CCDSiCCDS273.1. [Q969Q1-1]
RefSeqiNP_115977.2. NM_032588.3. [Q969Q1-1]
UniGeneiHs.279709.

Genome annotation databases

EnsembliENST00000374272; ENSP00000363390; ENSG00000158022. [Q969Q1-1]
GeneIDi84676.
KEGGihsa:84676.
UCSCiuc001bli.3. human. [Q969Q1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTRI63_HUMAN
AccessioniPrimary (citable) accession number: Q969Q1
Secondary accession number(s): B4DN95
, Q5T2I1, Q96BD3, Q96KD9, Q9BYV4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 6, 2002
Last sequence update: December 1, 2001
Last modified: August 30, 2017
This is version 155 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

Caution

It is uncertain whether Met-1 or Met-14 is the initiator.Curated
Variant Arg-351 is erroneously reported as Trp-351 in PubMed:24865491.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references