COMD1_HUMAN
ID COMD1_HUMAN Reviewed; 190 AA.
AC Q8N668; B4DFQ4; Q96GS0;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 158.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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., Tanner M.S.,
RA 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] (ISOFORM 1).
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 MURR1
RT in Wilson disease patients.";
RL J. Mol. Med. 82:629-634(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
RA Zhang Z., Yatsuki H., Wang Y., Joh K., Nabetani A., Hatada I., Soejima H.,
RA Iwasaka T., Mukai T.;
RT "Comparative analyses of gene imprinting and CpG island methylation around
RT mouse Murr1 and human syntenic region identify the 5'-portion of U2af1-rs1
RT 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] (ISOFORM 2).
RC TISSUE=Amygdala;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
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 in a
RT purebred dog population.";
RL Hum. Mol. Genet. 11:165-173(2002).
RN [8]
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 Wilson
RT disease protein.";
RL J. Biol. Chem. 278:41593-41596(2003).
RN [9]
RP UBIQUITINATION BY 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 MURR1.";
RL EMBO J. 23:244-254(2004).
RN [10]
RP FUNCTION, AND INTERACTION WITH SCNN1D.
RX PubMed=14645214; DOI=10.1074/jbc.m311155200;
RA Biasio W., Chang T., McIntosh C.J., McDonald F.J.;
RT "Identification of Murr1 as a regulator of the human delta epithelial
RT sodium channel.";
RL J. Biol. Chem. 279:5429-5434(2004).
RN [11]
RP FUNCTION, INTERACTION WITH RELA; REL; RELB; NFKB1; NFKB2; COMMD2; COMMD3;
RP COMMD4; COMMD5; COMMD6; COMMD7; COMMD8 AND COMMD10, SUBCELLULAR LOCATION,
RP 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 of
RT MURR1.";
RL J. Biol. Chem. 280:22222-22232(2005).
RN [12]
RP INTERACTION WITH COMMD6 AND NFKBIB, SUBCELLULAR LOCATION, AND TISSUE
RP 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 [13]
RP FUNCTION, SUBUNIT, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF
RP MET-110 AND 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 (MURR1).";
RL Biochemistry 46:3116-3128(2007).
RN [14]
RP FUNCTION, SUBUNIT, INTERACTION WITH SOCS1 AND CUL2, AND IDENTIFICATION IN
RP AN E3 UBIQUITIN LIGASE COMPLEX COMPOSED OF TCEB1/ELONGIN C; CUL2; SOCS1 AND
RP 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 cullin-
RT containing ubiquitin ligase.";
RL EMBO J. 26:436-447(2007).
RN [15]
RP INTERACTION WITH ATP7B.
RX PubMed=17919502; DOI=10.1053/j.gastro.2007.07.020;
RA de Bie P., van de Sluis B., Burstein E., van de Berghe P.V., Muller P.,
RA Berger R., Gitlin J.D., Wijmenga C., Klomp L.W.;
RT "Distinct Wilson's disease mutations in ATP7B are associated with enhanced
RT binding to COMMD1 and reduced stability of ATP7B.";
RL Gastroenterology 133:1316-1326(2007).
RN [16]
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 [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [18]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18940794; DOI=10.1074/jbc.m804766200;
RA Burkhead J.L., Morgan C.T., Shinde U., Haddock G., Lutsenko S.;
RT "COMMD1 forms oligomeric complexes targeted to the endocytic membranes via
RT specific interactions with phosphatidylinositol 4,5-bisphosphate.";
RL J. Biol. Chem. 284:696-707(2009).
RN [19]
RP FUNCTION, AND INTERACTION WITH SGK1 AND AKT1.
RX PubMed=20237237; DOI=10.1152/ajprenal.00257.2009;
RA Ke Y., Butt A.G., Swart M., Liu Y.F., McDonald F.J.;
RT "COMMD1 downregulates the epithelial sodium channel through Nedd4-2.";
RL Am. J. Physiol. 298:F1445-F1456(2010).
RN [20]
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 [21]
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 [22]
RP FUNCTION, INTERACTION WITH HIF1A, AND TISSUE SPECIFICITY.
RX PubMed=20458141; DOI=10.1172/jci40583;
RA van de Sluis B., Mao X., Zhai Y., Groot A.J., Vermeulen J.F.,
RA van der Wall E., van Diest P.J., Hofker M.H., Wijmenga C., Klomp L.W.,
RA Cho K.R., Fearon E.R., Vooijs M., Burstein E.;
RT "COMMD1 disrupts HIF-1alpha/beta dimerization and inhibits human tumor cell
RT invasion.";
RL J. Clin. Invest. 120:2119-2130(2010).
RN [23]
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., Klomp L.W.,
RA Nelson C.C., Rennie P.S., Gleave M.E.;
RT "Clusterin facilitates COMMD1 and I-kappaB degradation to enhance NF-kappaB
RT activity in prostate cancer cells.";
RL Mol. Cancer Res. 8:119-130(2010).
RN [24]
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., Buerckstuemmer T.,
RA 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 [25]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21741370; DOI=10.1016/j.bbrc.2011.06.149;
RA Chang T., Ke Y., Ly K., McDonald F.J.;
RT "COMMD1 regulates the delta epithelial sodium channel (deltaENaC) through
RT trafficking and ubiquitination.";
RL Biochem. Biophys. Res. Commun. 411:506-511(2011).
RN [26]
RP FUNCTION, INTERACTION WITH CUL1; CUL2; CUL3; CUL4A; CUL4B; CUL5 AND CUL7,
RP AND SUBCELLULAR LOCATION.
RX PubMed=21778237; DOI=10.1074/jbc.m111.278408;
RA Mao X., Gluck N., Chen B., Starokadomskyy P., Li H., Maine G.N.,
RA Burstein E.;
RT "COMMD1 (copper metabolism MURR1 domain-containing protein 1) regulates
RT Cullin RING ligases by preventing CAND1 (Cullin-associated Nedd8-
RT dissociated protein 1) binding.";
RL J. Biol. Chem. 286:32355-32365(2011).
RN [27]
RP FUNCTION, INTERACTION WITH CFTR, AND SUBCELLULAR LOCATION.
RX PubMed=21483833; DOI=10.1371/journal.pone.0018334;
RA Drevillon L., Tanguy G., Hinzpeter A., Arous N., de Becdelievre A.,
RA Aissat A., Tarze A., Goossens M., Fanen P.;
RT "COMMD1-mediated ubiquitination regulates CFTR trafficking.";
RL PLoS ONE 6:E18334-E18334(2011).
RN [28]
RP INTERACTION WITH ATP7A.
RX PubMed=21667063; DOI=10.1007/s00018-011-0743-1;
RA Vonk W.I., de Bie P., Wichers C.G., van den Berghe P.V., van der Plaats R.,
RA Berger R., Wijmenga C., Klomp L.W., van de Sluis B.;
RT "The copper-transporting capacity of ATP7A mutants associated with Menkes
RT disease is ameliorated by COMMD1 as a result of improved protein
RT expression.";
RL Cell. Mol. Life Sci. 69:149-163(2012).
RN [29]
RP FUNCTION, AND INTERACTION WITH SLC12A2.
RX PubMed=23515529; DOI=10.1152/ajpcell.00394.2012;
RA Smith L., Litman P., Liedtke C.M.;
RT "COMMD1 interacts with the COOH terminus of NKCC1 in Calu-3 airway
RT epithelial cells to modulate NKCC1 ubiquitination.";
RL Am. J. Physiol. 305:C133-C146(2013).
RN [30]
RP INTERACTION WITH SCNN1B.
RX PubMed=23637203; DOI=10.1152/ajprenal.00158.2013;
RA Liu Y.F., Swart M., Ke Y., Ly K., McDonald F.J.;
RT "Functional interaction of COMMD3 and COMMD9 with the epithelial sodium
RT channel.";
RL Am. J. Physiol. 305:F80-F89(2013).
RN [31]
RP INTERACTION WITH CCDC22; CUL2 AND TCEB1.
RX PubMed=23563313; DOI=10.1172/jci66466;
RA Starokadomskyy P., Gluck N., Li H., Chen B., Wallis M., Maine G.N., Mao X.,
RA Zaidi I.W., Hein M.Y., McDonald F.J., Lenzner S., Zecha A., Ropers H.H.,
RA Kuss A.W., McGaughran J., Gecz J., Burstein E.;
RT "CCDC22 deficiency in humans blunts activation of proinflammatory NF-kappaB
RT signaling.";
RL J. Clin. Invest. 123:2244-2256(2013).
RN [32]
RP ACETYLATION BY EP300, AND INTERACTION WITH RELA.
RX PubMed=25074812; DOI=10.1242/jcs.149328;
RA O'Hara A., Simpson J., Morin P., Loveridge C.J., Williams A.C., Novo S.M.,
RA Stark L.A.;
RT "p300-mediated acetylation of COMMD1 regulates its stability, and the
RT ubiquitylation and nucleolar translocation of the RelA NF-kappaB subunit.";
RL J. Cell Sci. 127:3659-3665(2014).
RN [33]
RP FUNCTION, IDENTIFICATION IN THE CCC COMPLEX, SUBCELLULAR LOCATION, AND
RP SUBUNIT.
RX PubMed=25355947; DOI=10.1091/mbc.e14-06-1073;
RA Phillips-Krawczak C.A., Singla A., Starokadomskyy P., Deng Z.,
RA Osborne D.G., Li H., Dick C.J., Gomez T.S., Koenecke M., Zhang J.S.,
RA Dai H., Sifuentes-Dominguez L.F., Geng L.N., Kaufmann S.H., Hein M.Y.,
RA Wallis M., McGaughran J., Gecz J., van de Sluis B., Billadeau D.D.,
RA Burstein E.;
RT "COMMD1 is linked to the WASH complex and regulates endosomal trafficking
RT of the copper transporter ATP7A.";
RL Mol. Biol. Cell 26:91-103(2015).
RN [34]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [35]
RP INTERACTION WITH CCDC22 AND VSP35L.
RX PubMed=28892079; DOI=10.1038/ncb3610;
RA McNally K.E., Faulkner R., Steinberg F., Gallon M., Ghai R., Pim D.,
RA Langton P., Pearson N., Danson C.M., Naegele H., Morris L.L., Singla A.,
RA Overlee B.L., Heesom K.J., Sessions R., Banks L., Collins B.M., Berger I.,
RA Billadeau D.D., Burstein E., Cullen P.J.;
RT "Retriever is a multiprotein complex for retromer-independent endosomal
RT cargo recycling.";
RL Nat. Cell Biol. 19:1214-1225(2017).
RN [36]
RP FUNCTION, INTERACTION WITH FAM107A, AND SUBCELLULAR LOCATION.
RX PubMed=28604741; DOI=10.1038/onc.2017.181;
RA Mu P., Akashi T., Lu F., Kishida S., Kadomatsu K.;
RT "A novel nuclear complex of DRR1, F-actin and COMMD1 involved in NF-kappaB
RT degradation and cell growth suppression in neuroblastoma.";
RL Oncogene 36:5745-5756(2017).
RN [37]
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: Proposed scaffold protein that is implicated in diverse
CC physiological processes and whose function may be in part linked to its
CC ability to regulate ubiquitination of specific cellular proteins. Can
CC modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes by
CC displacing CAND1; in vitro promotes CRL E3 activity and dissociates
CC CAND1 from CUL1 and CUL2 (PubMed:21778237). Promotes ubiquitination of
CC NF-kappa-B subunit RELA and its subsequent proteasomal degradation.
CC Down-regulates NF-kappa-B activity (PubMed:15799966, PubMed:17183367,
CC PubMed:20048074). Involved in the regulation of membrane expression and
CC ubiquitination of SLC12A2 (PubMed:23515529). Modulates Na(+) transport
CC in epithelial cells by regulation of apical cell surface expression of
CC amiloride-sensitive sodium channel (ENaC) subunits and by promoting
CC their ubiquitination presumably involving NEDD4L. Promotes the
CC localization of SCNN1D to recycling endosomes (PubMed:14645214,
CC PubMed:20237237, PubMed:21741370). Promotes CFTR cell surface
CC expression through regulation of its ubiquitination (PubMed:21483833).
CC Down-regulates SOD1 activity by interfering with its homodimerization
CC (PubMed:20595380). Plays a role in copper ion homeostasis. Involved in
CC copper-dependent ATP7A trafficking between the trans-Golgi network and
CC vesicles in the cell periphery; the function is proposed to depend on
CC its association within the CCC complex and cooperation with the WASH
CC complex on early endosomes (PubMed:25355947). Can bind one copper ion
CC per monomer (PubMed:17309234). May function to facilitate biliary
CC copper excretion within hepatocytes. Binds to phosphatidylinositol 4,5-
CC bisphosphate (PtdIns(4,5)P2) (PubMed:18940794). Involved in the
CC regulation of HIF1A-mediated transcription; competes with ARNT/Hif-1-
CC beta for binding to HIF1A resulting in decreased DNA binding and
CC impaired transcriptional activation by HIF-1 (PubMed:20458141).
CC Negatively regulates neuroblastoma G1/S phase cell cycle progression
CC and cell proliferation by stimulating ubiquitination of NF-kappa-B
CC subunit RELA and NF-kappa-B degradation in a FAM107A- and actin-
CC dependent manner (PubMed:28604741). {ECO:0000269|PubMed:14645214,
CC ECO:0000269|PubMed:14685266, ECO:0000269|PubMed:15799966,
CC ECO:0000269|PubMed:16573520, ECO:0000269|PubMed:17183367,
CC ECO:0000269|PubMed:17309234, ECO:0000269|PubMed:20048074,
CC ECO:0000269|PubMed:20237237, ECO:0000269|PubMed:20458141,
CC ECO:0000269|PubMed:20595380, ECO:0000269|PubMed:21483833,
CC ECO:0000269|PubMed:21741370, ECO:0000269|PubMed:21778237,
CC ECO:0000269|PubMed:23515529, ECO:0000269|PubMed:25355947,
CC ECO:0000269|PubMed:28604741}.
CC -!- SUBUNIT: Monomer, homodimer. Can form heterodimers with other COMM
CC domain-containing proteins but only certain combinations may exist in
CC vivo (PubMed:23563313). Interacts (via COMM domain) with COMMD2,
CC COMMD3, COMMD4, COMMD5, COMMD6, COMMD7, COMMD8 and COMMD10 (via COMM
CC domain). Identified in a complex with an E3 ubiquitin ligase complex
CC composed of TCEB1/elongin C, CUL2, SOCS1 and RBX1; in the complex
CC interacts directly with SOCS1 and CUL2. Interacts directly with ATP7B
CC (via the N-terminal region). Interacts with CCS, CDKN2A, RELA, REL,
CC RELB, NFKB1/p105, NFKB2/p100, NFKBIB, SCNN1D, SCNN1B, CFTR, CLU, SGK1,
CC AKT1, CUL1, CUL2, CUL3, CUL4A, CUL4B, CUL5, CUL7, HIF1A. Identified in
CC a complex with NF-kappa-B. Interacts directly with SLC12A2. Interacts
CC with CCDC22 and CCDC93; proposed to be a component of the CCC
CC (COMMD/CCDC22/CCDC93) complex which contains at least COMMD1 (and
CC possibly other COMM domain-containing proteins), CCDC22, CCDC93
CC (PubMed:25355947, PubMed:28892079). Interacts with VPS35L; the
CC interaction associates CCC complex with retriever complex
CC (PubMed:28892079, PubMed:25355947). Interacts with ATP7A
CC (PubMed:21667063). Interacts with FAM107A; this interaction stabilizes
CC COMMD1 in the nucleus (PubMed:28604741). {ECO:0000269|PubMed:12547404,
CC ECO:0000269|PubMed:12968035, ECO:0000269|PubMed:14645214,
CC ECO:0000269|PubMed:14685266, ECO:0000269|PubMed:15799966,
CC ECO:0000269|PubMed:16573520, ECO:0000269|PubMed:17183367,
CC ECO:0000269|PubMed:17309234, ECO:0000269|PubMed:17919502,
CC ECO:0000269|PubMed:18305112, ECO:0000269|PubMed:20068069,
CC ECO:0000269|PubMed:20237237, ECO:0000269|PubMed:20458141,
CC ECO:0000269|PubMed:20595380, ECO:0000269|PubMed:21667063,
CC ECO:0000269|PubMed:21778237, ECO:0000269|PubMed:23515529,
CC ECO:0000269|PubMed:23563313, ECO:0000269|PubMed:23637203,
CC ECO:0000269|PubMed:25355947, ECO:0000269|PubMed:28604741,
CC ECO:0000269|PubMed:28892079, ECO:0000305|PubMed:23563313,
CC ECO:0000305|PubMed:25355947}.
CC -!- INTERACTION:
CC Q8N668; P35670: ATP7B; NbExp=10; IntAct=EBI-1550112, EBI-11668501;
CC Q8N668; O60826: CCDC22; NbExp=25; IntAct=EBI-1550112, EBI-3943153;
CC Q8N668; Q567U6: CCDC93; NbExp=10; IntAct=EBI-1550112, EBI-1104769;
CC Q8N668; Q8N668: COMMD1; NbExp=2; IntAct=EBI-1550112, EBI-1550112;
CC Q8N668; Q9Y6G5: COMMD10; NbExp=2; IntAct=EBI-1550112, EBI-1550310;
CC Q8N668; Q86X83: COMMD2; NbExp=2; IntAct=EBI-1550112, EBI-1550220;
CC Q8N668; Q9UBI1: COMMD3; NbExp=6; IntAct=EBI-1550112, EBI-714979;
CC Q8N668; Q9H0A8: COMMD4; NbExp=4; IntAct=EBI-1550112, EBI-1550064;
CC Q8N668; Q9GZQ3: COMMD5; NbExp=2; IntAct=EBI-1550112, EBI-1550256;
CC Q8N668; Q7Z4G1: COMMD6; NbExp=20; IntAct=EBI-1550112, EBI-1550081;
CC Q8N668; Q9NX08: COMMD8; NbExp=3; IntAct=EBI-1550112, EBI-725694;
CC Q8N668; Q13617: CUL2; NbExp=6; IntAct=EBI-1550112, EBI-456179;
CC Q8N668; Q15369: ELOC; NbExp=2; IntAct=EBI-1550112, EBI-301231;
CC Q8N668; P26583: HMGB2; NbExp=3; IntAct=EBI-1550112, EBI-1057009;
CC Q8N668; P25963: NFKBIA; NbExp=3; IntAct=EBI-1550112, EBI-307386;
CC Q8N668; Q04864: REL; NbExp=3; IntAct=EBI-1550112, EBI-307352;
CC Q8N668; Q04206: RELA; NbExp=7; IntAct=EBI-1550112, EBI-73886;
CC Q8N668; Q01201: RELB; NbExp=2; IntAct=EBI-1550112, EBI-357837;
CC Q8N668; P51172: SCNN1D; NbExp=3; IntAct=EBI-1550112, EBI-2547114;
CC Q8N668; O15524: SOCS1; NbExp=3; IntAct=EBI-1550112, EBI-968198;
CC Q8N668; Q8IYN2: TCEAL8; NbExp=3; IntAct=EBI-1550112, EBI-2116184;
CC Q8N668; Q96BW1: UPRT; NbExp=3; IntAct=EBI-1550112, EBI-742943;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21778237,
CC ECO:0000269|PubMed:28604741}. Cytoplasm {ECO:0000269|PubMed:21778237}.
CC Endosome membrane {ECO:0000269|PubMed:18940794}. Cytoplasmic vesicle
CC {ECO:0000269|PubMed:18940794}. Early endosome
CC {ECO:0000269|PubMed:21483833, ECO:0000269|PubMed:25355947}. Recycling
CC endosome {ECO:0000269|PubMed:21483833, ECO:0000269|PubMed:21741370}.
CC Note=Shuttles between nucleus and cytosol. Detected in perinuclear foci
CC that may be aggresomes containing misfolded, ubiquitinated proteins.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8N668-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8N668-2; Sequence=VSP_055532;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highest expression in the liver, with
CC lower expression in brain, lung, placenta, pancreas, small intestine,
CC heart, skeletal muscle, kidney and placenta. Down-regulated in cancer
CC tissues. {ECO:0000269|PubMed:11809725, ECO:0000269|PubMed:15799966,
CC ECO:0000269|PubMed:16573520, ECO:0000269|PubMed:20458141}.
CC -!- PTM: Acetylated by EP300 ina stimuli-specific manner; protecting it
CC from XIAP-mediated proteasomal degradation and required for interaction
CC with RElA in response to stress. {ECO:0000269|PubMed:25074812}.
CC -!- PTM: Ubiquitinated; undergoes both 'Lys-63'- and 'Lys-48'-linked
CC polyubiquitination. Ubiquitinated by XIAP, leading to its proteasomal
CC degradation. {ECO:0000269|PubMed:14685266, ECO:0000269|PubMed:18305112,
CC ECO:0000269|PubMed:20068069}.
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DR EMBL; AB178811; BAD18972.1; -; mRNA.
DR EMBL; AK294203; BAG57515.1; -; mRNA.
DR EMBL; AC018462; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC107081; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC116652; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC009266; AAH09266.2; -; mRNA.
DR EMBL; BC022046; AAH22046.1; -; mRNA.
DR CCDS; CCDS1869.1; -. [Q8N668-1]
DR RefSeq; NP_689729.1; NM_152516.3. [Q8N668-1]
DR PDB; 2H2M; NMR; -; A=1-108.
DR PDBsum; 2H2M; -.
DR AlphaFoldDB; Q8N668; -.
DR BMRB; Q8N668; -.
DR SMR; Q8N668; -.
DR BioGRID; 127317; 105.
DR CORUM; Q8N668; -.
DR IntAct; Q8N668; 59.
DR MINT; Q8N668; -.
DR STRING; 9606.ENSP00000308236; -.
DR iPTMnet; Q8N668; -.
DR PhosphoSitePlus; Q8N668; -.
DR BioMuta; COMMD1; -.
DR DMDM; 51316026; -.
DR EPD; Q8N668; -.
DR jPOST; Q8N668; -.
DR MassIVE; Q8N668; -.
DR MaxQB; Q8N668; -.
DR PaxDb; Q8N668; -.
DR PeptideAtlas; Q8N668; -.
DR PRIDE; Q8N668; -.
DR ProteomicsDB; 4066; -.
DR ProteomicsDB; 72135; -. [Q8N668-1]
DR Antibodypedia; 30711; 449 antibodies from 32 providers.
DR DNASU; 150684; -.
DR Ensembl; ENST00000311832.6; ENSP00000308236.5; ENSG00000173163.11. [Q8N668-1]
DR GeneID; 150684; -.
DR KEGG; hsa:150684; -.
DR MANE-Select; ENST00000311832.6; ENSP00000308236.5; NM_152516.4; NP_689729.1.
DR UCSC; uc002sbp.4; human. [Q8N668-1]
DR CTD; 150684; -.
DR DisGeNET; 150684; -.
DR GeneCards; COMMD1; -.
DR HGNC; HGNC:23024; COMMD1.
DR HPA; ENSG00000173163; Low tissue specificity.
DR MIM; 607238; gene.
DR neXtProt; NX_Q8N668; -.
DR OpenTargets; ENSG00000173163; -.
DR PharmGKB; PA134891368; -.
DR VEuPathDB; HostDB:ENSG00000173163; -.
DR eggNOG; ENOG502RXN6; Eukaryota.
DR GeneTree; ENSGT00390000012029; -.
DR HOGENOM; CLU_126878_0_0_1; -.
DR InParanoid; Q8N668; -.
DR OMA; SWRIDIK; -.
DR OrthoDB; 1323631at2759; -.
DR PhylomeDB; Q8N668; -.
DR TreeFam; TF332823; -.
DR PathwayCommons; Q8N668; -.
DR Reactome; R-HSA-8951664; Neddylation.
DR SignaLink; Q8N668; -.
DR BioGRID-ORCS; 150684; 10 hits in 1076 CRISPR screens.
DR ChiTaRS; COMMD1; human.
DR EvolutionaryTrace; Q8N668; -.
DR GeneWiki; COMMD1; -.
DR GenomeRNAi; 150684; -.
DR Pharos; Q8N668; Tbio.
DR PRO; PR:Q8N668; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q8N668; protein.
DR Bgee; ENSG00000173163; Expressed in left ventricle myocardium and 184 other tissues.
DR ExpressionAtlas; Q8N668; baseline and differential.
DR Genevisible; Q8N668; HS.
DR GO; GO:0031462; C:Cul2-RING ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; IBA:GO_Central.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB.
DR GO; GO:0005507; F:copper ion binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0070300; F:phosphatidic acid binding; IDA:UniProtKB.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:UniProtKB.
DR GO; GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; IDA:UniProtKB.
DR GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; IDA:UniProtKB.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0019871; F:sodium channel inhibitor activity; IDA:MGI.
DR GO; GO:0055070; P:copper ion homeostasis; IDA:UniProtKB.
DR GO; GO:0006893; P:Golgi to plasma membrane transport; IMP:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:2000009; P:negative regulation of protein localization to cell surface; IDA:UniProtKB.
DR GO; GO:1902306; P:negative regulation of sodium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0006289; P:nucleotide-excision repair; IMP:CACAO.
DR GO; GO:0048227; P:plasma membrane to endosome transport; IDA:UniProtKB.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0032434; P:regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR CDD; cd04749; Commd1_MURR1; 1.
DR InterPro; IPR017920; COMM.
DR InterPro; IPR033776; COMMD1_N.
DR InterPro; IPR037351; Murr1.
DR PANTHER; PTHR21199; PTHR21199; 1.
DR Pfam; PF07258; COMM_domain; 1.
DR Pfam; PF17221; COMMD1_N; 1.
DR PROSITE; PS51269; COMM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Copper; Cytoplasm;
KW Cytoplasmic vesicle; Endosome; Lipid-binding; Membrane; Metal-binding;
KW Nucleus; Protein transport; Reference proteome; Transcription;
KW Transcription regulation; Transport; Ubl conjugation;
KW Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..190
FT /note="COMM domain-containing protein 1"
FT /id="PRO_0000077384"
FT DOMAIN 118..186
FT /note="COMM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00602"
FT REGION 2..123
FT /note="Sufficient for interaction with SLC12A2"
FT /evidence="ECO:0000269|PubMed:23515529"
FT REGION 125..190
FT /note="Required for binding to PtdIns(4,5)P2"
FT /evidence="ECO:0000269|PubMed:18940794"
FT BINDING 101
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000255"
FT BINDING 110
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000255"
FT BINDING 134
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000255"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT VAR_SEQ 155..190
FT /note="ESEFLCLEFDEVKVNQILKTLSEVEESISTLISQPN -> VHCNQ (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055532"
FT MUTAGEN 110
FT /note="M->A: Reduces copper-induced fluorescence change."
FT /evidence="ECO:0000269|PubMed:17309234"
FT MUTAGEN 134
FT /note="H->A: Reduces copper-induced fluorescence change."
FT /evidence="ECO:0000269|PubMed:17309234"
FT STRAND 3..5
FT /evidence="ECO:0007829|PDB:2H2M"
FT HELIX 9..13
FT /evidence="ECO:0007829|PDB:2H2M"
FT HELIX 15..18
FT /evidence="ECO:0007829|PDB:2H2M"
FT STRAND 23..25
FT /evidence="ECO:0007829|PDB:2H2M"
FT HELIX 32..39
FT /evidence="ECO:0007829|PDB:2H2M"
FT STRAND 41..43
FT /evidence="ECO:0007829|PDB:2H2M"
FT HELIX 48..52
FT /evidence="ECO:0007829|PDB:2H2M"
FT TURN 53..55
FT /evidence="ECO:0007829|PDB:2H2M"
FT HELIX 59..62
FT /evidence="ECO:0007829|PDB:2H2M"
FT TURN 63..65
FT /evidence="ECO:0007829|PDB:2H2M"
FT TURN 69..71
FT /evidence="ECO:0007829|PDB:2H2M"
FT TURN 73..75
FT /evidence="ECO:0007829|PDB:2H2M"
FT HELIX 76..79
FT /evidence="ECO:0007829|PDB:2H2M"
FT STRAND 82..84
FT /evidence="ECO:0007829|PDB:2H2M"
FT HELIX 88..94
FT /evidence="ECO:0007829|PDB:2H2M"
FT TURN 95..101
FT /evidence="ECO:0007829|PDB:2H2M"
FT STRAND 102..106
FT /evidence="ECO:0007829|PDB:2H2M"
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
