COMD4_HUMAN
ID COMD4_HUMAN Reviewed; 199 AA.
AC Q9H0A8; B2RBN4; H3BUL2; Q7L637; Q9NX43;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=COMM domain-containing protein 4;
GN Name=COMMD4;
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=Testis;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Prostate;
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=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Cervix, and Mammary gland;
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 [8]
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 [9]
RP FUNCTION, INTERACTION WITH CUL2; CUL3; CUL4A; CUL5 AND CUL7, AND
RP 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 [10]
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 [11]
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 [12]
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).
RN [13]
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).
CC -!- FUNCTION: May modulate activity of cullin-RING E3 ubiquitin ligase
CC (CRL) complexes (PubMed:21778237). Down-regulates activation of NF-
CC kappa-B. {ECO:0000269|PubMed:15799966, ECO:0000305|PubMed:21778237}.
CC -!- SUBUNIT: Interacts (via COMM domain) with COMMD1 (via COMM domain).
CC Interacts with RELA, RELB, NFKB1/p105. Interacts with CCDC22, CCDC93,
CC SCNN1B, CUL2, CUL3, CUL4A, CUL5, CUL7. {ECO:0000269|PubMed:15799966,
CC ECO:0000269|PubMed:21778237, ECO:0000269|PubMed:23563313,
CC ECO:0000269|PubMed:23637203, ECO:0000269|PubMed:25355947}.
CC -!- INTERACTION:
CC Q9H0A8; O60826: CCDC22; NbExp=6; IntAct=EBI-1550064, EBI-3943153;
CC Q9H0A8; Q567U6: CCDC93; NbExp=2; IntAct=EBI-1550064, EBI-1104769;
CC Q9H0A8; Q8N668: COMMD1; NbExp=4; IntAct=EBI-1550064, EBI-1550112;
CC Q9H0A8; Q9NX08: COMMD8; NbExp=9; IntAct=EBI-1550064, EBI-725694;
CC Q9H0A8; Q5VU43-11: PDE4DIP; NbExp=4; IntAct=EBI-1550064, EBI-10769071;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21778237}. Nucleus
CC {ECO:0000269|PubMed:21778237}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9H0A8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H0A8-2; Sequence=VSP_011394;
CC Name=3;
CC IsoId=Q9H0A8-3; Sequence=VSP_055664;
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:15799966}.
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DR EMBL; AY542160; AAS22242.1; -; mRNA.
DR EMBL; AL136872; CAB66806.1; -; mRNA.
DR EMBL; CR533452; CAG38483.1; -; mRNA.
DR EMBL; AK000459; BAA91178.1; -; mRNA.
DR EMBL; AK314740; BAG37281.1; -; mRNA.
DR EMBL; AC068338; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471136; EAW99263.1; -; Genomic_DNA.
DR EMBL; BC000837; AAH00837.2; -; mRNA.
DR EMBL; BC068998; AAH68998.1; -; mRNA.
DR CCDS; CCDS10277.1; -. [Q9H0A8-1]
DR CCDS; CCDS66834.1; -. [Q9H0A8-2]
DR CCDS; CCDS66835.1; -. [Q9H0A8-3]
DR RefSeq; NP_001271306.1; NM_001284377.1. [Q9H0A8-2]
DR RefSeq; NP_001271307.1; NM_001284378.1. [Q9H0A8-3]
DR RefSeq; NP_060298.2; NM_017828.4. [Q9H0A8-1]
DR AlphaFoldDB; Q9H0A8; -.
DR SMR; Q9H0A8; -.
DR BioGRID; 120279; 90.
DR CORUM; Q9H0A8; -.
DR IntAct; Q9H0A8; 34.
DR MINT; Q9H0A8; -.
DR STRING; 9606.ENSP00000267935; -.
DR iPTMnet; Q9H0A8; -.
DR PhosphoSitePlus; Q9H0A8; -.
DR BioMuta; COMMD4; -.
DR DMDM; 51316094; -.
DR EPD; Q9H0A8; -.
DR jPOST; Q9H0A8; -.
DR MassIVE; Q9H0A8; -.
DR MaxQB; Q9H0A8; -.
DR PaxDb; Q9H0A8; -.
DR PeptideAtlas; Q9H0A8; -.
DR PRIDE; Q9H0A8; -.
DR ProteomicsDB; 42963; -.
DR ProteomicsDB; 80236; -. [Q9H0A8-1]
DR ProteomicsDB; 80237; -. [Q9H0A8-2]
DR Antibodypedia; 55565; 102 antibodies from 17 providers.
DR DNASU; 54939; -.
DR Ensembl; ENST00000267935.13; ENSP00000267935.8; ENSG00000140365.16. [Q9H0A8-1]
DR Ensembl; ENST00000338995.10; ENSP00000340867.6; ENSG00000140365.16. [Q9H0A8-2]
DR Ensembl; ENST00000480484.5; ENSP00000433662.1; ENSG00000140365.16. [Q9H0A8-1]
DR Ensembl; ENST00000567195.5; ENSP00000457693.1; ENSG00000140365.16. [Q9H0A8-3]
DR GeneID; 54939; -.
DR KEGG; hsa:54939; -.
DR MANE-Select; ENST00000267935.13; ENSP00000267935.8; NM_017828.5; NP_060298.2.
DR UCSC; uc002azy.5; human. [Q9H0A8-1]
DR CTD; 54939; -.
DR DisGeNET; 54939; -.
DR GeneCards; COMMD4; -.
DR HGNC; HGNC:26027; COMMD4.
DR HPA; ENSG00000140365; Low tissue specificity.
DR MIM; 616701; gene.
DR neXtProt; NX_Q9H0A8; -.
DR OpenTargets; ENSG00000140365; -.
DR PharmGKB; PA134993083; -.
DR VEuPathDB; HostDB:ENSG00000140365; -.
DR eggNOG; ENOG502QSP3; Eukaryota.
DR GeneTree; ENSGT00390000015516; -.
DR HOGENOM; CLU_095496_1_0_1; -.
DR InParanoid; Q9H0A8; -.
DR OMA; TAVACIN; -.
DR OrthoDB; 1505629at2759; -.
DR PhylomeDB; Q9H0A8; -.
DR TreeFam; TF317482; -.
DR PathwayCommons; Q9H0A8; -.
DR Reactome; R-HSA-8951664; Neddylation.
DR SignaLink; Q9H0A8; -.
DR BioGRID-ORCS; 54939; 37 hits in 1077 CRISPR screens.
DR ChiTaRS; COMMD4; human.
DR GeneWiki; COMMD4; -.
DR GenomeRNAi; 54939; -.
DR Pharos; Q9H0A8; Tbio.
DR PRO; PR:Q9H0A8; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q9H0A8; protein.
DR Bgee; ENSG00000140365; Expressed in left testis and 198 other tissues.
DR ExpressionAtlas; Q9H0A8; baseline and differential.
DR Genevisible; Q9H0A8; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:LIFEdb.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR CDD; cd04752; Commd4; 1.
DR InterPro; IPR017920; COMM.
DR InterPro; IPR037356; Commd4.
DR Pfam; PF07258; COMM_domain; 1.
DR PROSITE; PS51269; COMM; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Nucleus; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation pathway.
FT CHAIN 1..199
FT /note="COMM domain-containing protein 4"
FT /id="PRO_0000077393"
FT DOMAIN 130..199
FT /note="COMM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00602"
FT VAR_SEQ 101..186
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_055664"
FT VAR_SEQ 128..187
FT /note="MNRLAGVGWRVDYTLSSSLLQSVEEPMVHLRLEVAAAPGTPAQPVAMSLSAD
FT KFQVLLAE -> K (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_011394"
SQ SEQUENCE 199 AA; 21764 MW; 7B7B85234E3FB59B CRC64;
MRFRFCGDLD CPDWVLAEIS TLAKMSSVKL RLLCSQVLKE LLGQGIDYEK ILKLTADAKF
ESGDVKATVA VLSFILSSAA KHSVDGESLS SELQQLGLPK EHAASLCRCY EEKQSPLQKH
LRVCSLRMNR LAGVGWRVDY TLSSSLLQSV EEPMVHLRLE VAAAPGTPAQ PVAMSLSADK
FQVLLAELKQ AQTLMSSLG
