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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

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)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri23 – 7957RING-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri117 – 15943B box-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

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

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ligase, Muscle protein

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Metal-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:6.3.2.-)
Alternative name(s):
Iris RING finger protein
Muscle-specific RING finger protein 1
Short name:
MuRF-1
Short name:
MuRF1
RING finger protein 28
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
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi39 – 391C → A: Loss of SUMO2-binding. 1 Publication
Mutagenesisi41 – 411H → A: Loss of SUMO2-binding. 1 Publication
Mutagenesisi44 – 441C → A: Loss of SUMO2-binding. 1 Publication
Mutagenesisi47 – 471C → A: Loss of SUMO2-binding. 1 Publication

Organism-specific databases

PharmGKBiPA34431.

Polymorphism and mutation databases

BioMutaiTRIM63.
DMDMi21362898.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 353353E3 ubiquitin-protein ligase TRIM63PRO_0000056290Add
BLAST

Proteomic databases

PaxDbiQ969Q1.
PeptideAtlasiQ969Q1.
PRIDEiQ969Q1.

PTM databases

iPTMnetiQ969Q1.
PhosphoSiteiQ969Q1.

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

WithEntry#Exp.IntActNotes
CCAR1Q8IX122EBI-5661333,EBI-356265
EEF1GP266412EBI-5661333,EBI-351467
GFM1Q96RP92EBI-5661333,EBI-2255048
MRPL41Q8IXM32EBI-5661333,EBI-912501
MYOZ1Q9NP982EBI-5661333,EBI-744402
TTNQ8WZ423EBI-5661333,EBI-681210

GO - Molecular functioni

  • titin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi124195. 90 interactions.
IntActiQ969Q1. 37 interactions.
MINTiMINT-6492114.
STRINGi9606.ENSP00000363390.

Structurei

Secondary structure

1
353
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi123 – 1253Combined sources
Beta strandi132 – 1343Combined sources
Turni135 – 1384Combined sources
Beta strandi139 – 1413Combined sources
Helixi143 – 1486Combined sources
Turni150 – 1534Combined sources
Beta strandi156 – 1583Combined sources
Turni159 – 1613Combined sources
Helixi214 – 26754Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2D8UNMR-A119-169[»]
3DDTX-ray1.90A/B/C117-161[»]
4M3LX-ray2.10A/B/C/D214-271[»]
ProteinModelPortaliQ969Q1.
SMRiQ969Q1. Positions 5-107, 117-161, 214-270.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ969Q1.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini267 – 32559COSPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni74 – 218145Interaction with TTNAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili207 – 26963Sequence analysisAdd
BLAST

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

Sequence similaritiesi

Contains 1 B box-type zinc finger.PROSITE-ProRule annotation
Contains 1 COS domain.PROSITE-ProRule annotation
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri23 – 7957RING-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri117 – 15943B box-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

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

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
4.10.45.10. 1 hit.
InterProiIPR017903. COS_domain.
IPR027370. Znf-RING_LisH.
IPR000315. Znf_B-box.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamiPF00643. zf-B_box. 1 hit.
PF13445. zf-RING_UBOX. 1 hit.
[Graphical view]
SMARTiSM00336. BBOX. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]
PROSITEiPS51262. COS. 1 hit.
PS50119. ZF_BBOX. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti5 – 51S → L Rare variant; found in a patient with hypertrophic cardiomyopathy; unknown pathological significance. 1 Publication
Corresponds to variant rs762015648 [ dbSNP | Ensembl ].
VAR_074092
Natural varianti61 – 611S → R.1 Publication
VAR_074093
Natural varianti73 – 731F → S Rare variant; found in a patient with hypertrophic cardiomyopathy; unknown pathological significance. 1 Publication
Corresponds to variant rs758754060 [ dbSNP | Ensembl ].
VAR_074094
Natural varianti86 – 861R → C Rare variant; found in a patient with hypertrophic cardiomyopathy; unknown pathological significance. 1 Publication
Corresponds to variant rs529429430 [ dbSNP | Ensembl ].
VAR_074095
Natural varianti86 – 861R → H Rare variant; found in a patient with hypertrophic cardiomyopathy; unknown pathological significance. 1 Publication
VAR_074096
Natural varianti101 – 1011I → F Rare variant; found in a patient with hypertrophic cardiomyopathy; unknown pathological significance. 1 Publication
VAR_074097
Natural varianti126 – 1261E → D.1 Publication
Corresponds to variant rs142601731 [ dbSNP | Ensembl ].
VAR_074098
Natural varianti232 – 2321T → M Rare variant; found in a patient with hypertrophic cardiomyopathy; unknown pathological significance. 1 Publication
Corresponds to variant rs376414719 [ dbSNP | Ensembl ].
VAR_074099
Natural varianti237 – 2371K → E.2 Publications
Corresponds to variant rs2275950 [ dbSNP | Ensembl ].
VAR_020116
Natural varianti254 – 2541D → N.1 Publication
VAR_074100
Natural varianti305 – 3051M → I.1 Publication
VAR_074101
Natural varianti318 – 3181A → D Rare variant; found in a patient with hypertrophic cardiomyopathy; unknown pathological significance. 1 Publication
Corresponds to variant rs201397530 [ dbSNP | Ensembl ].
VAR_074102
Natural varianti321 – 3211A → D.1 Publication
VAR_074103
Natural varianti351 – 3511G → R.1 Publication
Corresponds to variant rs202001619 [ dbSNP | Ensembl ].
VAR_074104

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei104 – 13128Missing in isoform 2. 1 PublicationVSP_055443Add
BLAST

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

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2D8UNMR-A119-169[»]
3DDTX-ray1.90A/B/C117-161[»]
4M3LX-ray2.10A/B/C/D214-271[»]
ProteinModelPortaliQ969Q1.
SMRiQ969Q1. Positions 5-107, 117-161, 214-270.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124195. 90 interactions.
IntActiQ969Q1. 37 interactions.
MINTiMINT-6492114.
STRINGi9606.ENSP00000363390.

PTM databases

iPTMnetiQ969Q1.
PhosphoSiteiQ969Q1.

Polymorphism and mutation databases

BioMutaiTRIM63.
DMDMi21362898.

Proteomic databases

PaxDbiQ969Q1.
PeptideAtlasiQ969Q1.
PRIDEiQ969Q1.

Protocols and materials databases

DNASUi84676.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi84676.
GeneCardsiTRIM63.
HGNCiHGNC:16007. TRIM63.
MIMi606131. gene.
neXtProtiNX_Q969Q1.
PharmGKBiPA34431.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiTRIM63. human.
EvolutionaryTraceiQ969Q1.
GeneWikiiTRIM63.
GenomeRNAii84676.
PROiQ969Q1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000158022.
CleanExiHS_TRIM63.
GenevisibleiQ969Q1. HS.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
4.10.45.10. 1 hit.
InterProiIPR017903. COS_domain.
IPR027370. Znf-RING_LisH.
IPR000315. Znf_B-box.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamiPF00643. zf-B_box. 1 hit.
PF13445. zf-RING_UBOX. 1 hit.
[Graphical view]
SMARTiSM00336. BBOX. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]
PROSITEiPS51262. COS. 1 hit.
PS50119. ZF_BBOX. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTRI63_HUMAN
AccessioniPrimary (citable) accession number: Q969Q1
Secondary accession number(s): B4DN95
, Q5T2I1, Q96BD3, Q96KD9, Q9BYV4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 6, 2002
Last sequence update: December 1, 2001
Last modified: September 7, 2016
This is version 146 of the entry and version 1 of the sequence. [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
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.