COMD6_HUMAN
ID COMD6_HUMAN Reviewed; 85 AA.
AC Q7Z4G1; A6NF28; B7ZLN0; Q5TBK4;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=COMM domain-containing protein 6;
GN Name=COMMD6; ORFNames=MSTP076;
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), FUNCTION, INTERACTION WITH COMMD1;
RP RELA; RELB AND NFKB1, 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Aorta;
RA Qin B.M., Sheng H., Liu Y.Q., Zhao B., Liu B., Wang X.Y., Zhang Q.,
RA Song L., Gao Y., Zhang C.L., Ye J., Ji X.J., Liu B.H., Lu H., Xu H.S.,
RA Chen J.Z., Cai M.Q., Zheng W.Y., Teng C.Y., Liu Q., Yu L.T., Lin J.,
RA Gong Q., Zhang A.M., Gao R.L., Hui R.T.;
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [5]
RP FUNCTION, INTERACTION WITH COMMD1, SUBUNIT, MUTAGENESIS OF TRP-24 AND
RP PRO-41, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND ALTERNATIVE SPLICING
RP (ISOFORM 2).
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 [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [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 [7]
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 [8]
RP FUNCTION, INTERACTION WITH CUL4A, 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 [9]
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 [10]
RP INTERACTION WITH CCDC22.
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 [11]
RP INTERACTION WITH CCDC93.
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).
CC -!- FUNCTION: May modulate activity of cullin-RING E3 ubiquitin ligase
CC (CRL) complexes (PubMed:21778237). Down-regulates activation of NF-
CC kappa-B. Inhibits TNF-induced NFKB1 activation.
CC {ECO:0000269|PubMed:15799966, ECO:0000269|PubMed:16573520,
CC ECO:0000305|PubMed:21778237}.
CC -!- SUBUNIT: Homodimer. Can only homodimerize with isoform 1. Interacts
CC directly with COMMD1 (via COMM domain). Interacts with RELA, RELB,
CC NFKB1/p105. Does not interact with NFKBIB. Interacts with CCDC22,
CC CCDC93, SCNN1B, CUL4A. {ECO:0000269|PubMed:15799966,
CC ECO:0000269|PubMed:16573520, ECO:0000269|PubMed:21778237,
CC ECO:0000269|PubMed:23563313, ECO:0000269|PubMed:23637203,
CC ECO:0000269|PubMed:25355947}.
CC -!- INTERACTION:
CC Q7Z4G1; O60826: CCDC22; NbExp=7; IntAct=EBI-1550081, EBI-3943153;
CC Q7Z4G1; Q567U6: CCDC93; NbExp=3; IntAct=EBI-1550081, EBI-1104769;
CC Q7Z4G1; Q8N668: COMMD1; NbExp=20; IntAct=EBI-1550081, EBI-1550112;
CC Q7Z4G1; Q9P000: COMMD9; NbExp=4; IntAct=EBI-1550081, EBI-1550510;
CC Q7Z4G1; P17066: HSPA6; NbExp=3; IntAct=EBI-1550081, EBI-355106;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16573520,
CC ECO:0000269|PubMed:21778237}. Cytoplasm {ECO:0000269|PubMed:16573520}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q7Z4G1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7Z4G1-2; Sequence=VSP_026593;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Expressed in brain, heart, skeletal
CC muscle, lung, pancreas, liver, kidney, small intestine and placenta.
CC {ECO:0000269|PubMed:15799966, ECO:0000269|PubMed:16573520}.
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DR EMBL; AY542161; AAS22243.1; -; mRNA.
DR EMBL; AF169971; AAQ13599.1; -; mRNA.
DR EMBL; AL137244; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC117391; AAI17392.1; -; mRNA.
DR EMBL; BC143912; AAI43913.1; -; mRNA.
DR EMBL; BC171758; AAI71758.1; -; mRNA.
DR CCDS; CCDS9451.1; -. [Q7Z4G1-1]
DR CCDS; CCDS9452.1; -. [Q7Z4G1-2]
DR RefSeq; NP_987091.1; NM_203495.3. [Q7Z4G1-1]
DR RefSeq; NP_987093.1; NM_203497.3. [Q7Z4G1-2]
DR AlphaFoldDB; Q7Z4G1; -.
DR SMR; Q7Z4G1; -.
DR BioGRID; 128071; 40.
DR CORUM; Q7Z4G1; -.
DR IntAct; Q7Z4G1; 29.
DR GlyGen; Q7Z4G1; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q7Z4G1; -.
DR MetOSite; Q7Z4G1; -.
DR PhosphoSitePlus; Q7Z4G1; -.
DR BioMuta; COMMD6; -.
DR DMDM; 51315937; -.
DR EPD; Q7Z4G1; -.
DR jPOST; Q7Z4G1; -.
DR MassIVE; Q7Z4G1; -.
DR MaxQB; Q7Z4G1; -.
DR PeptideAtlas; Q7Z4G1; -.
DR PRIDE; Q7Z4G1; -.
DR ProteomicsDB; 69174; -. [Q7Z4G1-1]
DR ProteomicsDB; 69175; -. [Q7Z4G1-2]
DR Antibodypedia; 71333; 29 antibodies from 6 providers.
DR DNASU; 170622; -.
DR Ensembl; ENST00000355801.4; ENSP00000348054.4; ENSG00000188243.14. [Q7Z4G1-2]
DR Ensembl; ENST00000377615.7; ENSP00000366841.3; ENSG00000188243.14. [Q7Z4G1-1]
DR Ensembl; ENST00000682242.1; ENSP00000506987.1; ENSG00000188243.14. [Q7Z4G1-1]
DR GeneID; 170622; -.
DR KEGG; hsa:170622; -.
DR MANE-Select; ENST00000682242.1; ENSP00000506987.1; NM_203495.4; NP_987091.1.
DR UCSC; uc001vjn.3; human. [Q7Z4G1-1]
DR CTD; 170622; -.
DR DisGeNET; 170622; -.
DR GeneCards; COMMD6; -.
DR HGNC; HGNC:24015; COMMD6.
DR HPA; ENSG00000188243; Low tissue specificity.
DR MIM; 612377; gene.
DR neXtProt; NX_Q7Z4G1; -.
DR OpenTargets; ENSG00000188243; -.
DR PharmGKB; PA134906013; -.
DR VEuPathDB; HostDB:ENSG00000188243; -.
DR GeneTree; ENSGT00390000018369; -.
DR HOGENOM; CLU_139245_1_0_1; -.
DR InParanoid; Q7Z4G1; -.
DR OMA; IADHAGH; -.
DR OrthoDB; 1516873at2759; -.
DR PhylomeDB; Q7Z4G1; -.
DR PathwayCommons; Q7Z4G1; -.
DR Reactome; R-HSA-8951664; Neddylation.
DR SignaLink; Q7Z4G1; -.
DR BioGRID-ORCS; 170622; 26 hits in 1082 CRISPR screens.
DR ChiTaRS; COMMD6; human.
DR GenomeRNAi; 170622; -.
DR Pharos; Q7Z4G1; Tbio.
DR PRO; PR:Q7Z4G1; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q7Z4G1; protein.
DR Bgee; ENSG00000188243; Expressed in upper arm skin and 184 other tissues.
DR ExpressionAtlas; Q7Z4G1; baseline and differential.
DR Genevisible; Q7Z4G1; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0051059; F:NF-kappaB binding; IPI:MGI.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:MGI.
DR InterPro; IPR017920; COMM.
DR Pfam; PF07258; COMM_domain; 1.
DR PROSITE; PS51269; COMM; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cytoplasm; Nucleus; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation pathway.
FT CHAIN 1..85
FT /note="COMM domain-containing protein 6"
FT /id="PRO_0000077398"
FT DOMAIN 18..85
FT /note="COMM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00602"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT VAR_SEQ 69
FT /note="Q -> QPQLLATSSLLSAS (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_026593"
FT VARIANT 52
FT /note="H -> N (in dbSNP:rs1063485)"
FT /id="VAR_048813"
FT MUTAGEN 24
FT /note="W->A: Does not abolish homodimerization and
FT interaction with COMMD1. Does not abolish repression of
FT TNF-induced NFKB1 activation. Abolishes repression of TNF-
FT induced NFKB1 activation; when associated with A-41."
FT /evidence="ECO:0000269|PubMed:16573520"
FT MUTAGEN 41
FT /note="P->A: Does not abolish homodimerization and
FT interaction with COMMD1. Does not abolish repression of
FT TNF-induced NFKB1 activation. Abolishes repression of TNF-
FT induced NFKB1 activation; when associated with A-24."
FT /evidence="ECO:0000269|PubMed:16573520"
SQ SEQUENCE 85 AA; 9638 MW; FBF29F240EA8756B CRC64;
MEASSEPPLD AKSDVTNQLV DFQWKLGMAV SSDTCRSLKY PYVAVMLKVA DHSGQVKTKC
FEMTIPQFQN FYRQFKEIAA VIETV
