Q8N668 (COMD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
COMM domain-containing protein 1

Alternative name(s):
Protein Murr1

Gene names

Name:	COMMD1
Synonyms:	C2orf5, MURR1

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	190 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Promotes ubiquitination of NF-kappa-B subunit RELA and its subsequent proteasomal degradation. Down-regulates NF-kappa-B activity. Down-regulates SOD1 activity by interfering with its homodimerization. Plays a role in copper ion homeostasis. Can bind one copper ion per monomer. May function to facilitate biliary copper excretion within hepatocytes. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13 Ref.14
Subunit structure	Monomer and homodimer. Interacts (via COMM domain) with COMMD2, COMMD3, COMMD4, COMMD5, COMMD6, COMMD7, COMMD8 and COMMD10 (via COMM domain). Identified in a complex with an E3 ubiquitin ligase complex composed of TCEB1/elongin C, CUL2, SOCS1 and RBX1. Interacts directly with SOCS1 and CUL2. Interacts directly the N-terminal region of ATP7B. Interacts with CCS, CDKN2A, RELA and NFKBIB. Identified in a complex with NF-kappa-B. Interacts with CLU. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.14 Ref.15
Subcellular location	Nucleus. Cytoplasm. Note: Shuttles between nucleus and cytosol. Detected in perinuclear foci that may be aggresomes containing misfolded, ubiquitinated proteins. Ref.8 Ref.9 Ref.12 Ref.15
Tissue specificity	Ubiquitous. Highest expression in the liver, with lower expression in brain, lung, placenta, pancreas, small intestine, heart, skeletal muscle, kidney and placenta. Ref.5 Ref.8 Ref.9
Post-translational modification	Ubiquitinated; undergoes both 'Lys-63'- and 'Lys-48'-linked polyubiquitination. Ubiquitinated by XIAP, leading to its proteasomal degradation. Ref.7 Ref.12 Ref.15
Sequence similarities	Contains 1 COMM domain.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Ligand	Copper Metal-binding
PTM	Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	copper ion homeostasis Inferred from direct assay Ref.7. Source: UniProtKB negative regulation of NF-kappaB transcription factor activity Inferred from direct assay Ref.8. Source: UniProtKB positive regulation of protein ubiquitination Inferred from direct assay Ref.11. Source: UniProtKB regulation of proteasomal ubiquitin-dependent protein catabolic process Inferred from mutant phenotype Ref.11. Source: UniProtKB
Cellular_component	Cul2-RING ubiquitin ligase complex Inferred from direct assay Ref.11. Source: UniProtKB cell junction Inferred from direct assay. Source: HPA cytoplasm Inferred from direct assay Ref.7. Source: UniProtKB nucleolus Inferred from direct assay. Source: HPA
Molecular_function	copper ion binding Inferred from direct assay Ref.10. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-1550112,EBI-1550112
COMMD3	Q9UBI1	3	EBI-1550112,EBI-714979
COMMD4	Q9H0A8	2	EBI-1550112,EBI-1550064
COMMD6	Q7Z4G1	2	EBI-1550112,EBI-1550081
NFKBIA	P25963	3	EBI-1550112,EBI-307386
REL	Q04864	3	EBI-1550112,EBI-307352
RELA	Q04206	7	EBI-1550112,EBI-73886
RELB	Q01201	2	EBI-1550112,EBI-357837
SCNN1D	P51172	3	EBI-1550112,EBI-2547114

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 190

190

COMM domain-containing protein 1

PRO_0000077384

Regions

Domain

118 – 186

69

COMM

Sites

Metal binding

101

1

Copper Potential

Metal binding

110

1

Copper Potential

Metal binding

134

1

Copper Potential

Experimental info

Mutagenesis

110

1

M → A: Reduces copper-induced fluorescence change. Ref.10

Mutagenesis

134

1

H → A: Reduces copper-induced fluorescence change. Ref.10

Secondary structure

1

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190

Helix Strand Turn

Details...

Beta strand

3 – 5

3

Helix

9 – 13

5

Helix

15 – 18

4

Beta strand

23 – 25

3

Helix

32 – 39

8

Beta strand

41 – 43

3

Helix

48 – 52

5

Turn

53 – 55

3

Helix

59 – 62

4

Turn

63 – 65

3

Turn

69 – 71

3

Turn

73 – 75

3

Helix

76 – 79

4

Beta strand

82 – 84

3

Helix

88 – 94

7

Turn

95 – 101

7

Beta strand

102 – 106

5

Sequences

	Sequence		Length	Mass (Da)
	Q8N668 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: 9C810AECA67011DC	FASTA	190	21,178
	10 20 30 40 50 60 MAAGELEGGK PLSGLLNALA QDTFHGYPGI TEELLRSQLY PEVPPEEFRP FLAKMRGILK 70 80 90 100 110 120 SIASADMDFN QLEAFLTAQT KKQGGITSDQ AAVISKFWKS HKTKIRESLM NQSRWNSGLR 130 140 150 160 170 180 GLSWRVDGKS QSRHSAQIHT PVAIIELELG KYGQESEFLC LEFDEVKVNQ ILKTLSEVEE 190 SISTLISQPN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The canine copper toxicosis gene MURR1 does not cause non-Wilsonian hepatic copper toxicosis." Mueller T., van de Sluis B.A.J., Zhernakova A., van Binsbergen E., Janecke A.R., Bavdekar A., Pandit A., Weirich-Schwaiger H., Witt H., Ellemunter H., Deutsch J., Denk H., Mueller W., Sternlieb I., Tanner M.S., Wijmenga C. J. Hepatol. 38:164-168(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Analysis of the human homologue of the canine copper toxicosis gene MURR1 in Wilson disease patients." Stuehler B., Reichert J., Stremmel W., Schaefer M. J. Mol. Med. 82:629-634(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Comparative analyses of gene imprinting and CpG island methylation around mouse Murr1 and human syntenic region identify the 5'-portion of U2af1-rs1 CpG island as an imprinting control region." Zhang Z., Yatsuki H., Wang Y., Joh K., Nabetani A., Hatada I., Soejima H., Iwasaka T., Mukai T. Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Kidney.
[4]	"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]. Tissue: Ovary and Skin.
[5]	"Identification of a new copper metabolism gene by positional cloning in a purebred dog population." van De Sluis B.A.J., Rothuizen J., Pearson P.L., van Oost B.A., Wijmenga C. Hum. Mol. Genet. 11:165-173(2002) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[6]	"The copper toxicosis gene product Murr1 directly interacts with the Wilson disease protein." Tao T.Y., Liu F., Klomp L., Wijmenga C., Gitlin J.D. J. Biol. Chem. 278:41593-41596(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ATP7B.
[7]	"A novel role for XIAP in copper homeostasis through regulation of MURR1." Burstein E., Ganesh L., Dick R.D., van De Sluis B., Wilkinson J.C., Klomp L.W., Wijmenga C., Brewer G.J., Nabel G.J., Duckett C.S. EMBO J. 23:244-254(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, UBIQUITINATION, INTERACTION WITH XIAP.
[8]	"COMMD proteins, a novel family of structural and functional homologs of MURR1." Burstein E., Hoberg J.E., Wilkinson A.S., Rumble J.M., Csomos R.A., Komarck C.M., Maine G.N., Wilkinson J.C., Mayo M.W., Duckett C.S. J. Biol. Chem. 280:22222-22232(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH RELA; COMMD2; COMMD3; COMMD4; COMMD5; COMMD6; COMMD7; COMMD8 AND COMMD10, IDENTIFICATION IN A COMPLEX WITH NF-KAPPA-B, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[9]	"Characterization of COMMD protein-protein interactions in NF-kappaB signalling." de Bie P., van de Sluis B., Burstein E., Duran K.J., Berger R., Duckett C.S., Wijmenga C., Klomp L.W. Biochem. J. 398:63-71(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH COMMD6 AND NFKBIB, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[10]	"Characterization and copper binding properties of human COMMD1 (MURR1)." Narindrasorasak S., Kulkarni P., Deschamps P., She Y.M., Sarkar B. Biochemistry 46:3116-3128(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, MASS SPECTROMETRY, MUTAGENESIS OF MET-110 AND HIS-134, COPPER-BINDING.
[11]	"COMMD1 promotes the ubiquitination of NF-kappaB subunits through a cullin-containing ubiquitin ligase." Maine G.N., Mao X., Komarck C.M., Burstein E. EMBO J. 26:436-447(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, INTERACTION WITH SOCS1 AND CUL2, IDENTIFICATION IN AN E3 UBIQUITIN LIGASE COMPLEX COMPOSED OF TCEB1/ELONGIN C; CUL2; SOCS1 AND RBX1.
[12]	"Tumor suppressor ARF promotes non-classic proteasome-independent polyubiquitination of COMMD1." Huang Y., Wu M., Li H.Y. J. Biol. Chem. 283:11453-11460(2008) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION, SUBCELLULAR LOCATION, INTERACTION WITH CDKN2A.
[13]	"Nucleolar targeting of RelA(p65) is regulated by COMMD1-dependent ubiquitination." Thoms H.C., Loveridge C.J., Simpson J., Clipson A., Reinhardt K., Dunlop M.G., Stark L.A. Cancer Res. 70:139-149(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[14]	"Cu,Zn superoxide dismutase maturation and activity are regulated by COMMD1." Vonk W.I., Wijmenga C., Berger R., van de Sluis B., Klomp L.W. J. Biol. Chem. 285:28991-29000(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CCS.
[15]	"Clusterin facilitates COMMD1 and I-kappaB degradation to enhance NF-kappaB activity in prostate cancer cells." Zoubeidi A., Ettinger S., Beraldi E., Hadaschik B., Zardan A., Klomp L.W., Nelson C.C., Rennie P.S., Gleave M.E. Mol. Cancer Res. 8:119-130(2010) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, UBIQUITINATION, PROTEASOMAL DEGRADATION, INTERACTION WITH CLU.
[16]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]	"Solution structure of the COMMD1 N-terminal domain." Sommerhalter M., Zhang Y., Rosenzweig A.C. J. Mol. Biol. 365:715-721(2007) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 1-108.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB178811 mRNA. Translation: BAD18972.1.
BC009266 mRNA. Translation: AAH09266.2.
BC022046 mRNA. Translation: AAH22046.1.

IPI

IPI00171117.

RefSeq

NP_689729.1. NM_152516.2.

UniGene

Hs.468702.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2H2M	NMR	-	A	1-108	[»]

ProteinModelPortal

Q8N668.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q8N668. 21 interactions.

MINT

MINT-4140741.

STRING

9606.ENSP00000308236.

PTM databases

PhosphoSite

Q8N668.

Polymorphism databases

DMDM

51316026.

Proteomic databases

PaxDb

Q8N668.

PRIDE

Q8N668.

Protocols and materials databases

DNASU

150684.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000311832; ENSP00000308236; ENSG00000173163.

GeneID

150684.

KEGG

hsa:150684.

UCSC

uc002sbp.3. human.

Organism-specific databases

CTD

150684.

GeneCards

GC02P062115.

HGNC

HGNC:23024. COMMD1.

HPA

HPA034633.

MIM

607238. gene.

neXtProt

NX_Q8N668.

PharmGKB

PA134891368.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG46398.

HOGENOM

HOG000236295.

HOVERGEN

HBG051067.

InParanoid

Q8N668.

OMA

LLAQSRW.

OrthoDB

EOG4JM7QR.

PhylomeDB

Q8N668.

Gene expression databases

ArrayExpress

Q8N668.

Bgee

Q8N668.

CleanEx

HS_COMMD1.

Genevestigator

Q8N668.

GermOnline

ENSG00000173163. Homo sapiens.

Family and domain databases

InterPro

IPR017920. COMM.
IPR009886. HCaRG.
[Graphical view]

Pfam

PF07258. HCaRG. 1 hit.
[Graphical view]

PROSITE

PS51269. COMM. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

COMMD1. human.

EvolutionaryTrace

Q8N668.

GenomeRNAi

150684.

NextBio

86500.

SOURCE

Search...

Entry information

Entry name

COMD1_HUMAN

Accession

Primary (citable) accession number: Q8N668
Secondary accession number(s): Q96GS0

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 16, 2004
Last sequence update:	October 1, 2002
Last modified:	May 1, 2013
This is version 83 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.