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Q969Q1 (TRI63_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:TRIM63
Synonyms:IRF, MURF1, RNF28, SMRZ
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length353 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.9 Ref.11

Pathway

Protein modification; protein ubiquitination.

Subunit structure

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 GNB2L1 and PRKCE By similarity. Interacts with CKM. Ref.1 Ref.4 Ref.9 Ref.11 Ref.13

Subcellular location

Cytoplasm. Nucleus By similarity. CytoplasmmyofibrilsarcomereM line. CytoplasmmyofibrilsarcomereZ line. Note: Colocalizes with TNNI3 in myocytes By similarity. Localizes to the M- and Z-lines in skeletal muscle. Ref.1 Ref.4 Ref.9 Ref.10

Tissue specificity

Muscle specific. Selectively expressed in heart and skeletal muscle. Also expressed in the iris. Ref.1 Ref.2 Ref.4 Ref.8

Developmental stage

Expressed throughout all developmental stages. Ref.1

Domain

The RING-type zinc finger mediates interaction with SUMO2 and localization to the nucleus. Also required for the E3 ubiquitin ligase activity By similarity. Ref.4 Ref.9 Ref.13

The B box-type zinc finger mediates homodimerization. Ref.4 Ref.9 Ref.13

Sequence similarities

Contains 1 B box-type zinc finger.

Contains 1 COS domain.

Contains 1 RING-type zinc finger.

Caution

It is uncertain whether Met-1 or Met-14 is the initiator.

Sequence caution

The sequence AAK52497.1 differs from that shown. Reason: Frameshift at several positions.

The sequence AAK52497.1 differs from that shown. Reason: Sequencing errors.

The sequence CAC33173.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processUbl conjugation pathway
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   DomainCoiled coil
Zinc-finger
   LigandMetal-binding
Zinc
   Molecular functionLigase
Muscle protein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processmuscle contraction

Inferred from electronic annotation. Source: Ensembl

proteasome-mediated ubiquitin-dependent protein catabolic process

Inferred from electronic annotation. Source: Ensembl

regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

response to electrical stimulus involved in regulation of muscle adaptation

Inferred from sequence or structural similarity. Source: UniProtKB

response to glucocorticoid

Inferred from electronic annotation. Source: Ensembl

response to interleukin-1

Inferred from electronic annotation. Source: Ensembl

signal transduction

Non-traceable author statement Ref.1. Source: UniProtKB

skeletal muscle atrophy

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentM band

Inferred from electronic annotation. Source: UniProtKB-SubCell

Z disc

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from direct assay Ref.9. Source: UniProtKB

microtubule

Non-traceable author statement Ref.1. Source: UniProtKB

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionprotein binding

Inferred from physical interaction PubMed 18157088PubMed 23414517. Source: IntAct

signal transducer activity

Non-traceable author statement Ref.1. Source: UniProtKB

titin binding

Inferred from direct assay Ref.9. Source: UniProtKB

ubiquitin-protein transferase activity

Inferred from electronic annotation. Source: Ensembl

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 353353E3 ubiquitin-protein ligase TRIM63
PRO_0000056290

Regions

Domain267 – 32559COS
Zinc finger23 – 7957RING-type
Zinc finger117 – 15943B box-type
Region74 – 218145Interaction with TTN
Coiled coil207 – 26963 Potential

Natural variations

Natural variant2371K → E. Ref.1 Ref.7
Corresponds to variant rs2275950 [ dbSNP | Ensembl ].
VAR_020116

Experimental info

Mutagenesis391C → A: Loss of SUMO2-binding. Ref.4
Mutagenesis411H → A: Loss of SUMO2-binding. Ref.4
Mutagenesis441C → A: Loss of SUMO2-binding. Ref.4
Mutagenesis471C → A: Loss of SUMO2-binding. Ref.4

Secondary structure

............... 353
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q969Q1 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: 9BE4B1505039BC86

FASTA35340,248
        10         20         30         40         50         60 
MDYKSSLIQD GNPMENLEKQ LICPICLEMF TKPVVILPCQ HNLCRKCAND IFQAANPYWT 

        70         80         90        100        110        120 
SRGSSVSMSG GRFRCPTCRH EVIMDRHGVY GLQRNLLVEN IIDIYKQECS SRPLQKGSHP 

       130        140        150        160        170        180 
MCKEHEDEKI NIYCLTCEVP TCSMCKVFGI HKACEVAPLQ SVFQGQKTEL NNCISMLVAG 

       190        200        210        220        230        240 
NDRVQTIITQ LEDSRRVTKE NSHQVKEELS QKFDTLYAIL DEKKSELLQR ITQEQEKKLS 

       250        260        270        280        290        300 
FIEALIQQYQ EQLDKSTKLV ETAIQSLDEP GGATFLLTAK QLIKSIVEAS KGCQLGKTEQ 

       310        320        330        340        350 
GFENMDFFTL DLEHIADALR AIDFGTDEEE EEFIEEEDQE EEESTEGKEE GHQ 

« Hide

References

« Hide 'large scale' references
[1]"Identification of muscle specific ring finger proteins as potential regulators of the titin kinase domain."
Centner T., Yano J., Kimura E., McElhinny A.S., Pelin K., Witt C.C., Bang M.-L., Trombitas K., Granzier H., Gregorio C.C., Sorimachi H., Labeit S.
J. Mol. Biol. 306:717-726(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLU-237, INTERACTION WITH TTN; TRIM54 AND TRIM55, SUBUNIT, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION.
[2]"Expressed sequence tag analysis of adult human iris for the NEIBank project: steroid-response factors and similarities with retinal pigment epithelium."
Wistow G., Bernstein S.L., Ray S., Wyatt M.K., Behal A., Touchman J.W., Bouffard G., Smith D., Peterson K.
Mol. Vis. 8:185-195(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Tissue: Iris.
[3]"Characterisation of MURF2, a new muscle-specific RING finger protein of the RBCC family that associates with microtubules."
Stanchi F.
Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Skeletal muscle.
[4]"A novel human striated muscle RING zinc finger protein, SMRZ, interacts with SMT3b via its RING domain."
Dai K.-S., Liew C.-C.
J. Biol. Chem. 276:23992-23999(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PRELIMINARY NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH SUMO2, MUTAGENESIS OF CYS-39; HIS-41; CYS-44 AND CYS-47, DOMAIN.
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Skeletal muscle.
[6]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLU-237.
Tissue: Skin.
[8]"Identification of ubiquitin ligases required for skeletal muscle atrophy."
Bodine S.C., Latres E., Baumhueter S., Lai V.K.-M., Nunez L., Clarke B.A., Poueymirou W.T., Panaro F.J., Na E., Dharmarajan K., Pan Z.-Q., Valenzuela D.M., DeChiara T.M., Stitt T.N., Yancopoulos G.D., Glass D.J.
Science 294:1704-1708(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[9]"Muscle-specific RING finger-1 interacts with titin to regulate sarcomeric M-line and thick filament structure and may have nuclear functions via its interaction with glucocorticoid modulatory element binding protein-1."
McElhinny A.S., Kakinuma K., Sorimachi H., Labeit S., Gregorio C.C.
J. Cell Biol. 157:125-136(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, DOMAIN, FUNCTION, INTERACTION WITH GMEB1.
[10]"MuRF1-dependent regulation of systemic carbohydrate metabolism as revealed from transgenic mouse studies."
Hirner S., Krohne C., Schuster A., Hoffmann S., Witt S., Erber R., Sticht C., Gasch A., Labeit S., Labeit D.
J. Mol. Biol. 379:666-677(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[11]"Muscle RING-finger protein-1 (MuRF1) as a connector of muscle energy metabolism and protein synthesis."
Koyama S., Hata S., Witt C.C., Ono Y., Lerche S., Ojima K., Chiba T., Doi N., Kitamura F., Tanaka K., Abe K., Witt S.H., Rybin V., Gasch A., Franz T., Labeit S., Sorimachi H.
J. Mol. Biol. 376:1224-1236(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CKM, FUNCTION.
[12]"Solution structure of the B-box domain of the human tripartite motif-containing 63 protein."
RIKEN structural genomics initiative (RSGI)
Submitted (JUN-2006) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 119-169.
[13]"Structural analysis of B-Box 2 from MuRF1: identification of a novel self-association pattern in a RING-like fold."
Mrosek M., Meier S., Ucurum-Fotiadis Z., von Castelmur E., Hedbom E., Lustig A., Grzesiek S., Labeit D., Labeit S., Mayans O.
Biochemistry 47:10722-10730(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 117-161 IN COMPLEX WITH ZINC IONS, DOMAIN, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
AL391650 Genomic DNA. Translation: CAI17133.1.
BC080529 mRNA. Translation: AAH80529.1.
CCDSCCDS273.1.
RefSeqNP_115977.2. NM_032588.3.
UniGeneHs.279709.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2D8UNMR-A119-169[»]
3DDTX-ray1.90A/B/C117-161[»]
4M3LX-ray2.10A/B/C/D214-271[»]
ProteinModelPortalQ969Q1.
SMRQ969Q1. Positions 16-78, 117-161, 214-270.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid124195. 66 interactions.
IntActQ969Q1. 37 interactions.
MINTMINT-6492114.
STRING9606.ENSP00000363390.

PTM databases

PhosphoSiteQ969Q1.

Polymorphism databases

DMDM21362898.

Proteomic databases

PaxDbQ969Q1.
PRIDEQ969Q1.

Protocols and materials databases

DNASU84676.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000374272; ENSP00000363390; ENSG00000158022.
GeneID84676.
KEGGhsa:84676.
UCSCuc001bli.2. human.

Organism-specific databases

CTD84676.
GeneCardsGC01M026377.
HGNCHGNC:16007. TRIM63.
MIM606131. gene.
neXtProtNX_Q969Q1.
PharmGKBPA34431.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG310224.
HOGENOMHOG000231156.
HOVERGENHBG071242.
InParanoidQ969Q1.
KOK10655.
OMADGNPMEN.
OrthoDBEOG7VDXPK.
PhylomeDBQ969Q1.
TreeFamTF331669.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
UniPathwayUPA00143.

Gene expression databases

BgeeQ969Q1.
CleanExHS_TRIM63.
GenevestigatorQ969Q1.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
4.10.45.10. 1 hit.
InterProIPR017903. COS_domain.
IPR000315. Znf_B-box.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamPF00643. zf-B_box. 1 hit.
[Graphical view]
SMARTSM00336. BBOX. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]
PROSITEPS51262. COS. 1 hit.
PS50119. ZF_BBOX. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTRIM63. human.
EvolutionaryTraceQ969Q1.
GeneWikiTRIM63.
GenomeRNAi84676.
NextBio74699.
PROQ969Q1.
SOURCESearch...

Entry information

Entry nameTRI63_HUMAN
AccessionPrimary (citable) accession number: Q969Q1
Secondary accession number(s): Q5T2I1 expand/collapse secondary AC list , Q96BD3, Q96KD9, Q9BYV4
Entry history
Integrated into UniProtKB/Swiss-Prot: June 6, 2002
Last sequence update: December 1, 2001
Last modified: July 9, 2014
This is version 127 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM