ID COMD2_HUMAN Reviewed; 199 AA.
AC Q86X83; Q561V4; Q9H3L5; Q9Y5V1;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 27-MAR-2024, entry version 152.
DE RecName: Full=COMM domain-containing protein 2;
GN Name=COMMD2; ORFNames=HSPC042, My004;
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; NFKB1 AND NFKB2, TISSUE SPECIFICITY, AND VARIANT LEU-113.
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=Fetal brain;
RA Mao Y.M., Xie Y., Zhou Z.X.;
RL Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LEU-113.
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT cells.";
RL Genome Res. 10:1546-1560(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP LEU-113.
RC TISSUE=Liver;
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 CUL3; CUL4B; CUL5 AND CUL7, AND SUBCELLULAR
RP 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 [6]
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 [7]
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 [8]
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 [9]
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 [10]
RP INTERACTION WITH CCDC22.
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).
CC -!- FUNCTION: May modulate activity of cullin-RING E3 ubiquitin ligase
CC (CRL) complexes (PubMed:21778237). May down-regulate activation of NF-
CC kappa-B (PubMed:15799966). {ECO:0000269|PubMed:15799966,
CC ECO:0000305|PubMed:21778237}.
CC -!- SUBUNIT: Interacts (via COMM domain) with COMMD1 (via COMM domain)
CC (PubMed:15799966). Interacts with RELA, RELB, NFKB1/p105, NFKB2/p100.
CC Interacts with CCDC22, CCDC93, SCNN1B, CUL3, CUL4B, CUL5, CUL7
CC (PubMed:28892079, PubMed:15799966, PubMed:21778237, PubMed:23563313,
CC PubMed:23637203, PubMed:25355947). {ECO:0000269|PubMed:15799966,
CC ECO:0000269|PubMed:21778237, ECO:0000269|PubMed:23563313,
CC ECO:0000269|PubMed:23637203, ECO:0000269|PubMed:25355947,
CC ECO:0000269|PubMed:28892079}.
CC -!- INTERACTION:
CC Q86X83; O60826: CCDC22; NbExp=9; IntAct=EBI-1550220, EBI-3943153;
CC Q86X83; Q567U6: CCDC93; NbExp=3; IntAct=EBI-1550220, EBI-1104769;
CC Q86X83; Q8N668: COMMD1; NbExp=5; IntAct=EBI-1550220, EBI-1550112;
CC Q86X83; Q9UBI1: COMMD3; NbExp=8; IntAct=EBI-1550220, EBI-714979;
CC Q86X83; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-1550220, EBI-5235340;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21778237}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q86X83-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86X83-2; Sequence=VSP_055533;
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:15799966}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD39913.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AY542158; AAS22240.1; -; mRNA.
DR EMBL; AF059618; AAG43117.1; -; mRNA.
DR EMBL; AF125096; AAD39913.1; ALT_FRAME; mRNA.
DR EMBL; BC046131; AAH46131.1; -; mRNA.
DR EMBL; BC093077; AAH93077.1; -; mRNA.
DR CCDS; CCDS3145.1; -. [Q86X83-1]
DR RefSeq; NP_057178.2; NM_016094.3. [Q86X83-1]
DR PDB; 8F2R; EM; 3.12 A; B=1-199.
DR PDB; 8F2U; EM; 3.53 A; B=1-199.
DR PDBsum; 8F2R; -.
DR PDBsum; 8F2U; -.
DR AlphaFoldDB; Q86X83; -.
DR EMDB; EMD-28825; -.
DR EMDB; EMD-28827; -.
DR SMR; Q86X83; -.
DR BioGRID; 119309; 89.
DR ComplexPortal; CPX-2211; Commander complex.
DR CORUM; Q86X83; -.
DR IntAct; Q86X83; 35.
DR STRING; 9606.ENSP00000419475; -.
DR GlyGen; Q86X83; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q86X83; -.
DR PhosphoSitePlus; Q86X83; -.
DR BioMuta; COMMD2; -.
DR DMDM; 116241310; -.
DR EPD; Q86X83; -.
DR jPOST; Q86X83; -.
DR MassIVE; Q86X83; -.
DR MaxQB; Q86X83; -.
DR PaxDb; 9606-ENSP00000419475; -.
DR PeptideAtlas; Q86X83; -.
DR ProteomicsDB; 70254; -. [Q86X83-1]
DR Pumba; Q86X83; -.
DR TopDownProteomics; Q86X83-1; -. [Q86X83-1]
DR Antibodypedia; 48056; 56 antibodies from 15 providers.
DR DNASU; 51122; -.
DR Ensembl; ENST00000473414.6; ENSP00000419475.1; ENSG00000114744.9. [Q86X83-1]
DR GeneID; 51122; -.
DR KEGG; hsa:51122; -.
DR MANE-Select; ENST00000473414.6; ENSP00000419475.1; NM_016094.4; NP_057178.2.
DR UCSC; uc003exj.2; human. [Q86X83-1]
DR AGR; HGNC:24993; -.
DR CTD; 51122; -.
DR DisGeNET; 51122; -.
DR GeneCards; COMMD2; -.
DR HGNC; HGNC:24993; COMMD2.
DR HPA; ENSG00000114744; Low tissue specificity.
DR MIM; 616699; gene.
DR neXtProt; NX_Q86X83; -.
DR OpenTargets; ENSG00000114744; -.
DR PharmGKB; PA134923363; -.
DR VEuPathDB; HostDB:ENSG00000114744; -.
DR eggNOG; ENOG502QU0W; Eukaryota.
DR GeneTree; ENSGT00390000008489; -.
DR InParanoid; Q86X83; -.
DR OMA; NGDHNTQ; -.
DR OrthoDB; 51546at2759; -.
DR PhylomeDB; Q86X83; -.
DR TreeFam; TF323519; -.
DR PathwayCommons; Q86X83; -.
DR Reactome; R-HSA-8951664; Neddylation.
DR SignaLink; Q86X83; -.
DR BioGRID-ORCS; 51122; 48 hits in 1173 CRISPR screens.
DR ChiTaRS; COMMD2; human.
DR GenomeRNAi; 51122; -.
DR Pharos; Q86X83; Tdark.
DR PRO; PR:Q86X83; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q86X83; Protein.
DR Bgee; ENSG00000114744; Expressed in secondary oocyte and 193 other cell types or tissues.
DR ExpressionAtlas; Q86X83; baseline and differential.
DR Genevisible; Q86X83; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR CDD; cd04750; Commd2; 1.
DR InterPro; IPR017920; COMM.
DR InterPro; IPR037354; Commd2.
DR PANTHER; PTHR15857; COMM DOMAIN CONTAINING PROTEIN 2; 1.
DR PANTHER; PTHR15857:SF0; COMM DOMAIN-CONTAINING PROTEIN 2; 1.
DR Pfam; PF07258; COMM_domain; 1.
DR PROSITE; PS51269; COMM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation pathway.
FT CHAIN 1..199
FT /note="COMM domain-containing protein 2"
FT /id="PRO_0000077386"
FT DOMAIN 123..190
FT /note="COMM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00602"
FT VAR_SEQ 166..199
FT /note="QTDPATLLHLVQQLEQALEEMKTNHCRRVVRNIK -> GLQA (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_055533"
FT VARIANT 113
FT /note="I -> L (in dbSNP:rs9843784)"
FT /evidence="ECO:0000269|PubMed:11042152,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:15799966"
FT /id="VAR_028010"
FT VARIANT 177
FT /note="Q -> H (in dbSNP:rs1546732)"
FT /id="VAR_028011"
FT CONFLICT 199
FT /note="K -> Q (in Ref. 3; AAD39913)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 199 AA; 22745 MW; ECB4B7C26FCEA0F2 CRC64;
MLLELSEEHK EHLAFLPQVD SAVVAEFGRI AVEFLRRGAN PKIYEGAARK LNVSSDTVQH
GVEGLTYLLT ESSKLMISEL DFQDSVFVLG FSEELNKLLL QLYLDNRKEI RTILSELAPS
LPSYHNLEWR LDVQLASRSL RQQIKPAVTI KLHLNQNGDH NTKVLQTDPA TLLHLVQQLE
QALEEMKTNH CRRVVRNIK
//
