ID COMD1_HUMAN Reviewed; 190 AA. AC Q8N668; Q96GS0; DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2002, sequence version 1. DT 06-MAR-2013, entry version 81. DE RecName: Full=COMM domain-containing protein 1; DE AltName: Full=Protein Murr1; GN Name=COMMD1; Synonyms=C2orf5, MURR1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=12547404; DOI=10.1016/S0168-8278(02)00356-2; RA Mueller T., van de Sluis B.A.J., Zhernakova A., van Binsbergen E., RA Janecke A.R., Bavdekar A., Pandit A., Weirich-Schwaiger H., Witt H., RA Ellemunter H., Deutsch J., Denk H., Mueller W., Sternlieb I., RA Tanner M.S., Wijmenga C.; RT "The canine copper toxicosis gene MURR1 does not cause non-Wilsonian RT hepatic copper toxicosis."; RL J. Hepatol. 38:164-168(2003). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=15205742; DOI=10.1007/s00109-004-0557-9; RA Stuehler B., Reichert J., Stremmel W., Schaefer M.; RT "Analysis of the human homologue of the canine copper toxicosis gene RT MURR1 in Wilson disease patients."; RL J. Mol. Med. 82:629-634(2004). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Kidney; RA Zhang Z., Yatsuki H., Wang Y., Joh K., Nabetani A., Hatada I., RA Soejima H., Iwasaka T., Mukai T.; RT "Comparative analyses of gene imprinting and CpG island methylation RT around mouse Murr1 and human syntenic region identify the 5'-portion RT of U2af1-rs1 CpG island as an imprinting control region."; RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Ovary, and Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP TISSUE SPECIFICITY. RX PubMed=11809725; DOI=10.1093/hmg/11.2.165; RA van De Sluis B.A.J., Rothuizen J., Pearson P.L., van Oost B.A., RA Wijmenga C.; RT "Identification of a new copper metabolism gene by positional cloning RT in a purebred dog population."; RL Hum. Mol. Genet. 11:165-173(2002). RN [6] RP INTERACTION WITH ATP7B. RX PubMed=12968035; DOI=10.1074/jbc.C300391200; RA Tao T.Y., Liu F., Klomp L., Wijmenga C., Gitlin J.D.; RT "The copper toxicosis gene product Murr1 directly interacts with the RT Wilson disease protein."; RL J. Biol. Chem. 278:41593-41596(2003). RN [7] RP FUNCTION, UBIQUITINATION, AND INTERACTION WITH XIAP. RX PubMed=14685266; DOI=10.1038/sj.emboj.7600031; RA Burstein E., Ganesh L., Dick R.D., van De Sluis B., Wilkinson J.C., RA Klomp L.W., Wijmenga C., Brewer G.J., Nabel G.J., Duckett C.S.; RT "A novel role for XIAP in copper homeostasis through regulation of RT MURR1."; RL EMBO J. 23:244-254(2004). RN [8] RP FUNCTION, INTERACTION WITH RELA; COMMD2; COMMD3; COMMD4; COMMD5; RP COMMD6; COMMD7; COMMD8 AND COMMD10, IDENTIFICATION IN A COMPLEX WITH RP NF-KAPPA-B, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=15799966; DOI=10.1074/jbc.M501928200; RA Burstein E., Hoberg J.E., Wilkinson A.S., Rumble J.M., Csomos R.A., RA Komarck C.M., Maine G.N., Wilkinson J.C., Mayo M.W., Duckett C.S.; RT "COMMD proteins, a novel family of structural and functional homologs RT of MURR1."; RL J. Biol. Chem. 280:22222-22232(2005). RN [9] RP FUNCTION, INTERACTION WITH COMMD6 AND NFKBIB, SUBCELLULAR LOCATION, RP AND TISSUE SPECIFICITY. RX PubMed=16573520; DOI=10.1042/BJ20051664; RA de Bie P., van de Sluis B., Burstein E., Duran K.J., Berger R., RA Duckett C.S., Wijmenga C., Klomp L.W.; RT "Characterization of COMMD protein-protein interactions in NF-kappaB RT signalling."; RL Biochem. J. 398:63-71(2006). RN [10] RP FUNCTION, SUBUNIT, MASS SPECTROMETRY, MUTAGENESIS OF MET-110 AND RP HIS-134, AND COPPER-BINDING. RX PubMed=17309234; DOI=10.1021/bi0620656; RA Narindrasorasak S., Kulkarni P., Deschamps P., She Y.M., Sarkar B.; RT "Characterization and copper binding properties of human COMMD1 RT (MURR1)."; RL Biochemistry 46:3116-3128(2007). RN [11] RP FUNCTION, SUBUNIT, INTERACTION WITH SOCS1 AND CUL2, AND IDENTIFICATION RP IN AN E3 UBIQUITIN LIGASE COMPLEX COMPOSED OF TCEB1/ELONGIN C; CUL2; RP SOCS1 AND RBX1. RX PubMed=17183367; DOI=10.1038/sj.emboj.7601489; RA Maine G.N., Mao X., Komarck C.M., Burstein E.; RT "COMMD1 promotes the ubiquitination of NF-kappaB subunits through a RT cullin-containing ubiquitin ligase."; RL EMBO J. 26:436-447(2007). RN [12] RP UBIQUITINATION, SUBCELLULAR LOCATION, AND INTERACTION WITH CDKN2A. RX PubMed=18305112; DOI=10.1074/jbc.M708544200; RA Huang Y., Wu M., Li H.Y.; RT "Tumor suppressor ARF promotes non-classic proteasome-independent RT polyubiquitination of COMMD1."; RL J. Biol. Chem. 283:11453-11460(2008). RN [13] RP FUNCTION. RX PubMed=20048074; DOI=10.1158/0008-5472.CAN-09-1397; RA Thoms H.C., Loveridge C.J., Simpson J., Clipson A., Reinhardt K., RA Dunlop M.G., Stark L.A.; RT "Nucleolar targeting of RelA(p65) is regulated by COMMD1-dependent RT ubiquitination."; RL Cancer Res. 70:139-149(2010). RN [14] RP FUNCTION, AND INTERACTION WITH CCS. RX PubMed=20595380; DOI=10.1074/jbc.M110.101477; RA Vonk W.I., Wijmenga C., Berger R., van de Sluis B., Klomp L.W.; RT "Cu,Zn superoxide dismutase maturation and activity are regulated by RT COMMD1."; RL J. Biol. Chem. 285:28991-29000(2010). RN [15] RP SUBCELLULAR LOCATION, UBIQUITINATION, PROTEASOMAL DEGRADATION, AND RP INTERACTION WITH CLU. RX PubMed=20068069; DOI=10.1158/1541-7786.MCR-09-0277; RA Zoubeidi A., Ettinger S., Beraldi E., Hadaschik B., Zardan A., RA Klomp L.W., Nelson C.C., Rennie P.S., Gleave M.E.; RT "Clusterin facilitates COMMD1 and I-kappaB degradation to enhance NF- RT kappaB activity in prostate cancer cells."; RL Mol. Cancer Res. 8:119-130(2010). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [17] RP STRUCTURE BY NMR OF 1-108. RX PubMed=17097678; DOI=10.1016/j.jmb.2006.10.030; RA Sommerhalter M., Zhang Y., Rosenzweig A.C.; RT "Solution structure of the COMMD1 N-terminal domain."; RL J. Mol. Biol. 365:715-721(2007). CC -!- FUNCTION: Promotes ubiquitination of NF-kappa-B subunit RELA and CC its subsequent proteasomal degradation. Down-regulates NF-kappa-B CC activity. Down-regulates SOD1 activity by interfering with its CC homodimerization. Plays a role in copper ion homeostasis. Can bind CC one copper ion per monomer. May function to facilitate biliary CC copper excretion within hepatocytes. CC -!- SUBUNIT: Monomer and homodimer. Interacts (via COMM domain) with CC COMMD2, COMMD3, COMMD4, COMMD5, COMMD6, COMMD7, COMMD8 and COMMD10 CC (via COMM domain). Identified in a complex with an E3 ubiquitin CC ligase complex composed of TCEB1/elongin C, CUL2, SOCS1 and RBX1. CC Interacts directly with SOCS1 and CUL2. Interacts directly the N- CC terminal region of ATP7B. Interacts with CCS, CDKN2A, RELA and CC NFKBIB. Identified in a complex with NF-kappa-B. Interacts with CC CLU. CC -!- INTERACTION: CC Self; NbExp=2; IntAct=EBI-1550112, EBI-1550112; CC Q9UBI1:COMMD3; NbExp=3; IntAct=EBI-1550112, EBI-714979; CC Q9H0A8:COMMD4; NbExp=2; IntAct=EBI-1550112, EBI-1550064; CC Q7Z4G1:COMMD6; NbExp=2; IntAct=EBI-1550112, EBI-1550081; CC P25963:NFKBIA; NbExp=3; IntAct=EBI-1550112, EBI-307386; CC Q04864:REL; NbExp=3; IntAct=EBI-1550112, EBI-307352; CC Q04206:RELA; NbExp=7; IntAct=EBI-1550112, EBI-73886; CC Q01201:RELB; NbExp=2; IntAct=EBI-1550112, EBI-357837; CC P51172:SCNN1D; NbExp=3; IntAct=EBI-1550112, EBI-2547114; CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Shuttles between CC nucleus and cytosol. Detected in perinuclear foci that may be CC aggresomes containing misfolded, ubiquitinated proteins. CC -!- TISSUE SPECIFICITY: Ubiquitous. Highest expression in the liver, CC with lower expression in brain, lung, placenta, pancreas, small CC intestine, heart, skeletal muscle, kidney and placenta. CC -!- PTM: Ubiquitinated; undergoes both 'Lys-63'- and 'Lys-48'-linked CC polyubiquitination. Ubiquitinated by XIAP, leading to its CC proteasomal degradation. CC -!- SIMILARITY: Contains 1 COMM domain. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB178811; BAD18972.1; -; mRNA. DR EMBL; BC009266; AAH09266.2; -; mRNA. DR EMBL; BC022046; AAH22046.1; -; mRNA. DR IPI; IPI00171117; -. DR RefSeq; NP_689729.1; NM_152516.2. DR UniGene; Hs.468702; -. DR PDB; 2H2M; NMR; -; A=1-108. DR PDBsum; 2H2M; -. DR ProteinModelPortal; Q8N668; -. DR SMR; Q8N668; 1-108. DR IntAct; Q8N668; 21. DR MINT; MINT-4140741; -. DR STRING; Q8N668; -. DR PhosphoSite; Q8N668; -. DR DMDM; 51316026; -. DR PaxDb; Q8N668; -. DR PRIDE; Q8N668; -. DR DNASU; 150684; -. DR Ensembl; ENST00000311832; ENSP00000308236; ENSG00000173163. DR GeneID; 150684; -. DR KEGG; hsa:150684; -. DR UCSC; uc002sbp.3; human. DR CTD; 150684; -. DR GeneCards; GC02P062115; -. DR HGNC; HGNC:23024; COMMD1. DR HPA; HPA034633; -. DR MIM; 607238; gene. DR neXtProt; NX_Q8N668; -. DR PharmGKB; PA134891368; -. DR eggNOG; NOG46398; -. DR HOGENOM; HOG000236295; -. DR HOVERGEN; HBG051067; -. DR InParanoid; Q8N668; -. DR OMA; LLAQSRW; -. DR OrthoDB; EOG4JM7QR; -. DR PhylomeDB; Q8N668; -. DR ChiTaRS; COMMD1; human. DR EvolutionaryTrace; Q8N668; -. DR GenomeRNAi; 150684; -. DR NextBio; 86500; -. DR ArrayExpress; Q8N668; -. DR Bgee; Q8N668; -. DR CleanEx; HS_COMMD1; -. DR Genevestigator; Q8N668; -. DR GermOnline; ENSG00000173163; Homo sapiens. DR GO; GO:0030054; C:cell junction; IDA:HPA. DR GO; GO:0031462; C:Cul2-RING ubiquitin ligase complex; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005507; F:copper ion binding; IDA:UniProtKB. DR GO; GO:0055070; P:copper ion homeostasis; IDA:UniProtKB. DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:UniProtKB. DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:UniProtKB. DR GO; GO:0032434; P:regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB. DR InterPro; IPR017920; COMM. DR InterPro; IPR009886; HCaRG. DR Pfam; PF07258; HCaRG; 1. DR PROSITE; PS51269; COMM; 1. PE 1: Evidence at protein level; KW 3D-structure; Complete proteome; Copper; Cytoplasm; Metal-binding; KW Nucleus; Reference proteome; Ubl conjugation; Ubl conjugation pathway. FT CHAIN 1 190 COMM domain-containing protein 1. FT /FTId=PRO_0000077384. FT DOMAIN 118 186 COMM. FT METAL 101 101 Copper (Potential). FT METAL 110 110 Copper (Potential). FT METAL 134 134 Copper (Potential). FT MUTAGEN 110 110 M->A: Reduces copper-induced fluorescence FT change. FT MUTAGEN 134 134 H->A: Reduces copper-induced fluorescence FT change. FT STRAND 3 5 FT HELIX 9 13 FT HELIX 15 18 FT STRAND 23 25 FT HELIX 32 39 FT STRAND 41 43 FT HELIX 48 52 FT TURN 53 55 FT HELIX 59 62 FT TURN 63 65 FT TURN 69 71 FT TURN 73 75 FT HELIX 76 79 FT STRAND 82 84 FT HELIX 88 94 FT TURN 95 101 FT STRAND 102 106 SQ SEQUENCE 190 AA; 21178 MW; 9C810AECA67011DC CRC64; MAAGELEGGK PLSGLLNALA QDTFHGYPGI TEELLRSQLY PEVPPEEFRP FLAKMRGILK SIASADMDFN QLEAFLTAQT KKQGGITSDQ AAVISKFWKS HKTKIRESLM NQSRWNSGLR GLSWRVDGKS QSRHSAQIHT PVAIIELELG KYGQESEFLC LEFDEVKVNQ ILKTLSEVEE SISTLISQPN //