ID   COMD5_HUMAN             Reviewed;         224 AA.
AC   Q9GZQ3; D3DWN7; Q9NVN6; Q9UHX5;
DT   16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2001, sequence version 1.
DT   07-APR-2021, entry version 142.
DE   RecName: Full=COMM domain-containing protein 5;
DE   AltName: Full=Hypertension-related calcium-regulated gene protein;
DE            Short=HCaRG;
GN   Name=COMMD5; ORFNames=HT002;
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], AND TISSUE SPECIFICITY.
RC   TISSUE=Parathyroid;
RX   PubMed=10918053; DOI=10.1074/jbc.m001352200;
RA   Solban N., Jia H.-P., Richard S., Tremblay S., Devlin A.M., Peng J.,
RA   Gossard F., Guo D.-F., Morel G., Hamet P., Lewanczuk R., Tremblay J.;
RT   "HCaRG, a novel calcium-regulated gene coding for a nuclear protein, is
RT   potentially involved in the regulation of cell proliferation.";
RL   J. Biol. Chem. 275:32234-32243(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-6.
RC   TISSUE=Hypothalamus;
RX   PubMed=10931946; DOI=10.1073/pnas.160270997;
RA   Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA   Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W.,
RA   Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J.,
RA   Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z.,
RA   Chen M.-D., Chen J.-L.;
RT   "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis
RT   and full-length cDNA cloning.";
RL   Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [4]
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   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Skin, and Uterus;
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   [6]
RP   FUNCTION, INTERACTION WITH COMMD1; RELA; RELB AND NFKB1, AND TISSUE
RP   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   [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 CUL2; CUL3; CUL4A; CUL4B 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   [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).
RN   [12]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP   METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [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). Negatively regulates cell
CC       proliferation. Negatively regulates cell cycle G2/M phase transition
CC       probably by transactivating p21/CDKN1A through the p53/TP53-independent
CC       signaling pathway. Involved in kidney proximal tubule morphogenesis (By
CC       similarity). Down-regulates activation of NF-kappa-B (PubMed:15799966).
CC       {ECO:0000250|UniProtKB:Q9ERR2, ECO:0000269|PubMed:15799966,
CC       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, CUL4B, 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       Q9GZQ3; O60826: CCDC22; NbExp=6; IntAct=EBI-1550256, EBI-3943153;
CC       Q9GZQ3; Q8N668: COMMD1; NbExp=2; IntAct=EBI-1550256, EBI-1550112;
CC       Q9GZQ3; Q9Y6G5: COMMD10; NbExp=7; IntAct=EBI-1550256, EBI-1550310;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21778237}. Nucleus
CC       {ECO:0000269|PubMed:21778237}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in heart, stomach, jejunum,
CC       kidney, liver, and adrenal gland. Expression was generally higher in
CC       adult organs than in fetal tissues, particularly in heart, kidney, and
CC       liver. {ECO:0000269|PubMed:10918053, ECO:0000269|PubMed:15799966}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAF14877.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; AF290195; AAG09915.1; -; mRNA.
DR   EMBL; AF113540; AAF14877.1; ALT_FRAME; mRNA.
DR   EMBL; AK001477; BAA91714.1; -; mRNA.
DR   EMBL; AK023070; BAB14389.1; -; mRNA.
DR   EMBL; CH471162; EAW82033.1; -; Genomic_DNA.
DR   EMBL; CH471162; EAW82034.1; -; Genomic_DNA.
DR   EMBL; CH471162; EAW82035.1; -; Genomic_DNA.
DR   EMBL; CH471162; EAW82036.1; -; Genomic_DNA.
DR   EMBL; CH471162; EAW82037.1; -; Genomic_DNA.
DR   EMBL; BC002672; AAH02672.1; -; mRNA.
DR   EMBL; BC003055; AAH03055.1; -; mRNA.
DR   EMBL; BC065729; AAH65729.1; -; mRNA.
DR   CCDS; CCDS6436.1; -.
DR   RefSeq; NP_001074472.1; NM_001081003.2.
DR   RefSeq; NP_001074473.1; NM_001081004.2.
DR   RefSeq; NP_001274166.1; NM_001287237.1.
DR   RefSeq; NP_054785.2; NM_014066.3.
DR   SMR; Q9GZQ3; -.
DR   BioGRID; 118812; 22.
DR   CORUM; Q9GZQ3; -.
DR   IntAct; Q9GZQ3; 17.
DR   STRING; 9606.ENSP00000394331; -.
DR   iPTMnet; Q9GZQ3; -.
DR   PhosphoSitePlus; Q9GZQ3; -.
DR   BioMuta; COMMD5; -.
DR   DMDM; 51316093; -.
DR   EPD; Q9GZQ3; -.
DR   jPOST; Q9GZQ3; -.
DR   MassIVE; Q9GZQ3; -.
DR   MaxQB; Q9GZQ3; -.
DR   PaxDb; Q9GZQ3; -.
DR   PeptideAtlas; Q9GZQ3; -.
DR   PRIDE; Q9GZQ3; -.
DR   ProteomicsDB; 80111; -.
DR   Antibodypedia; 28668; 42 antibodies.
DR   DNASU; 28991; -.
DR   Ensembl; ENST00000305103; ENSP00000304544; ENSG00000170619.
DR   Ensembl; ENST00000402718; ENSP00000385793; ENSG00000170619.
DR   Ensembl; ENST00000450361; ENSP00000394331; ENSG00000170619.
DR   Ensembl; ENST00000543949; ENSP00000445840; ENSG00000170619.
DR   GeneID; 28991; -.
DR   KEGG; hsa:28991; -.
DR   UCSC; uc003zem.4; human.
DR   CTD; 28991; -.
DR   DisGeNET; 28991; -.
DR   GeneCards; COMMD5; -.
DR   HGNC; HGNC:17902; COMMD5.
DR   HPA; ENSG00000170619; Low tissue specificity.
DR   MIM; 608216; gene.
DR   neXtProt; NX_Q9GZQ3; -.
DR   OpenTargets; ENSG00000170619; -.
DR   PharmGKB; PA134873412; -.
DR   VEuPathDB; HostDB:ENSG00000170619.9; -.
DR   eggNOG; ENOG502RCJ6; Eukaryota.
DR   GeneTree; ENSGT00390000013770; -.
DR   InParanoid; Q9GZQ3; -.
DR   OMA; DCQEAVQ; -.
DR   OrthoDB; 1318335at2759; -.
DR   PhylomeDB; Q9GZQ3; -.
DR   TreeFam; TF323880; -.
DR   PathwayCommons; Q9GZQ3; -.
DR   Reactome; R-HSA-8951664; Neddylation.
DR   SIGNOR; Q9GZQ3; -.
DR   BioGRID-ORCS; 28991; 18 hits in 967 CRISPR screens.
DR   ChiTaRS; COMMD5; human.
DR   GenomeRNAi; 28991; -.
DR   Pharos; Q9GZQ3; Tbio.
DR   PRO; PR:Q9GZQ3; -.
DR   Proteomes; UP000005640; Chromosome 8.
DR   RNAct; Q9GZQ3; protein.
DR   Bgee; ENSG00000170619; Expressed in vagina and 193 other tissues.
DR   ExpressionAtlas; Q9GZQ3; baseline and differential.
DR   Genevisible; Q9GZQ3; HS.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   InterPro; IPR017920; COMM.
DR   InterPro; IPR037357; COMMD5.
DR   PANTHER; PTHR15666; PTHR15666; 1.
DR   Pfam; PF07258; COMM_domain; 1.
DR   PROSITE; PS51269; COMM; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Cytoplasm; Nucleus; Reference proteome; Transcription;
KW   Transcription regulation; Ubl conjugation pathway.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0007744|PubMed:25944712"
FT   CHAIN           2..224
FT                   /note="COMM domain-containing protein 5"
FT                   /id="PRO_0000077395"
FT   DOMAIN          151..215
FT                   /note="COMM"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00602"
FT   MOD_RES         2
FT                   /note="N-acetylserine"
FT                   /evidence="ECO:0007744|PubMed:25944712"
FT   VARIANT         6
FT                   /note="A -> T (in dbSNP:rs1209879)"
FT                   /evidence="ECO:0000269|PubMed:10931946"
FT                   /id="VAR_020130"
FT   VARIANT         69
FT                   /note="Q -> H (in dbSNP:rs421427)"
FT                   /id="VAR_048812"
FT   CONFLICT        108
FT                   /note="T -> I (in Ref. 3; BAA91714)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   224 AA;  24670 MW;  C4CC0563B9FA3240 CRC64;
     MSAVGAATPY LHHPGDSHSG RVSFLGAQLP PEVAAMARLL GDLDRSTFRK LLKFVVSSLQ
     GEDCREAVQR LGVSANLPEE QLGALLAGMH TLLQQALRLP PTSLKPDTFR DQLQELCIPQ
     DLVGDLASVV FGSQRPLLDS VAQQQGAWLP HVADFRWRVD VAISTSALAR SLQPSVLMQL
     KLSDGSAYRF EVPTAKFQEL RYSVALVLKE MADLEKRCER RLQD
//