Q969Q1 (TRI63_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	TRIM63
Synonyms:	IRF, MURF1, RNF28, SMRZ

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	353 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Cytoplasm › myofibril › sarcomere › M line. Cytoplasm › myofibril › sarcomere › Z 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 process	Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Domain	Coiled coil Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase Muscle protein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	muscle contraction Inferred from electronic annotation. Source: Compara proteasomal ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: Compara response to glucocorticoid stimulus Inferred from electronic annotation. Source: Compara response to interleukin-1 Inferred from electronic annotation. Source: Compara skeletal muscle atrophy Inferred from electronic annotation. Source: Compara
Cellular_component	M 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_function	signal transducer activity Non-traceable author statement Ref.1. Source: UniProtKB titin binding Inferred from direct assay Ref.9. Source: UniProtKB ubiquitin-protein ligase activity Inferred from electronic annotation. Source: Compara zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 353

353

E3 ubiquitin-protein ligase TRIM63

PRO_0000056290

Regions

Domain

267 – 325

59

COS

Zinc finger

23 – 79

57

RING-type

Zinc finger

117 – 159

43

B box-type

Region

74 – 218

145

Interaction with TTN

Coiled coil

207 – 269

63

Potential

Natural variations

Natural variant

237

1

K → E. Ref.1 Ref.7
Corresponds to variant rs2275950 [ dbSNP | Ensembl ].

VAR_020116

Experimental info

Mutagenesis

39

1

C → A: Loss of SUMO2-binding. Ref.4

Mutagenesis

41

1

H → A: Loss of SUMO2-binding. Ref.4

Mutagenesis

44

1

C → A: Loss of SUMO2-binding. Ref.4

Mutagenesis

47

1

C → A: Loss of SUMO2-binding. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

353

Helix Strand Turn

Details...

Beta strand

123 – 125

3

Beta strand

132 – 134

3

Turn

135 – 138

4

Beta strand

139 – 141

3

Helix

143 – 148

6

Turn

150 – 153

4

Beta strand

156 – 158

3

Turn

159 – 161

3

Sequences

	Sequence		Length	Mass (Da)
	Q969Q1 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 9BE4B1505039BC86	FASTA	353	40,248
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.

IPI

IPI00000309.

RefSeq

NP_115977.2. NM_032588.3.

UniGene

Hs.279709.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2D8U	NMR	-	A	119-169	[»]
3DDT	X-ray	1.90	A/B/C	117-161	[»]

ProteinModelPortal

Q969Q1.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q969Q1. 7 interactions.

MINT

MINT-6492114.

STRING

9606.ENSP00000363390.

PTM databases

PhosphoSite

Q969Q1.

Polymorphism databases

DMDM

21362898.

Proteomic databases

PaxDb

Q969Q1.

PRIDE

Q969Q1.

Protocols and materials databases

DNASU

84676.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000374272; ENSP00000363390; ENSG00000158022.

GeneID

84676.

KEGG

hsa:84676.

UCSC

uc001bli.1. human.

Organism-specific databases

CTD

84676.

GeneCards

GC01M026377.

HGNC

HGNC:16007. TRIM63.

MIM

606131. gene.

neXtProt

NX_Q969Q1.

PharmGKB

PA34431.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG310224.

HOGENOM

HOG000231156.

HOVERGEN

HBG071242.

InParanoid

Q969Q1.

KO

K10655.

OMA

FDTLYAI.

OrthoDB

EOG457571.

PhylomeDB

Q969Q1.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

UniPathway

UPA00143.

Gene expression databases

Bgee

Q969Q1.

CleanEx

HS_TRIM63.

Genevestigator

Q969Q1.

GermOnline

ENSG00000158022. Homo sapiens.

Family and domain databases

Gene3D

3.30.40.10. 1 hit.

InterPro

IPR017903. COS_domain.
IPR000315. Znf_B-box.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]

Pfam

PF00643. zf-B_box. 1 hit.
[Graphical view]

SMART

SM00336. BBOX. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]

PROSITE

PS51262. COS. 1 hit.
PS50119. ZF_BBOX. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

TRIM63. human.

EvolutionaryTrace

Q969Q1.

GenomeRNAi

84676.

NextBio

74699.

SOURCE

Search...

Entry information

Entry name

TRI63_HUMAN

Accession

Primary (citable) accession number: Q969Q1
Secondary accession number(s): Q5T2I1 , Q96BD3, Q96KD9, Q9BYV4

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 6, 2002
Last sequence update:	December 1, 2001
Last modified:	May 1, 2013
This is version 116 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.