CIDEA_MOUSE
ID CIDEA_MOUSE Reviewed; 217 AA.
AC O70302; Q4V9X2;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Cell death activator CIDE-A;
DE AltName: Full=Cell death-inducing DFFA-like effector A;
GN Name=Cidea;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION IN APOPTOSIS.
RX PubMed=9564035; DOI=10.1093/emboj/17.9.2526;
RA Inohara N., Koseki T., Chen S., Wu X., Nunez G.;
RT "CIDE, a novel family of cell death activators with homology to the 45 kDa
RT subunit of the DNA fragmentation factor.";
RL EMBO J. 17:2526-2533(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=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 [5]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=12910269; DOI=10.1038/ng1225;
RA Zhou Z., Yon Toh S., Chen Z., Guo K., Ng C.P., Ponniah S., Lin S.C.,
RA Hong W., Li P.;
RT "Cidea-deficient mice have lean phenotype and are resistant to obesity.";
RL Nat. Genet. 35:49-56(2003).
RN [6]
RP FUNCTION, INDUCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=18509062; DOI=10.1073/pnas.0802063105;
RA Puri V., Ranjit S., Konda S., Nicoloro S.M., Straubhaar J., Chawla A.,
RA Chouinard M., Lin C., Burkart A., Corvera S., Perugini R.A., Czech M.P.;
RT "Cidea is associated with lipid droplets and insulin sensitivity in
RT humans.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:7833-7838(2008).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22144693; DOI=10.1083/jcb.201104142;
RA Gong J., Sun Z., Wu L., Xu W., Schieber N., Xu D., Shui G., Yang H.,
RA Parton R.G., Li P.;
RT "Fsp27 promotes lipid droplet growth by lipid exchange and transfer at
RT lipid droplet contact sites.";
RL J. Cell Biol. 195:953-963(2011).
RN [8]
RP FUNCTION AS A CEBPB COACTIVATOR, INTERACTION WITH CEBPB, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE,
RP AND MUTAGENESIS OF LYS-23 AND LYS-24.
RX PubMed=22245780; DOI=10.1038/nm.2614;
RA Wang W., Lv N., Zhang S., Shui G., Qian H., Zhang J., Chen Y., Ye J.,
RA Xie Y., Shen Y., Wenk M.R., Li P.;
RT "Cidea is an essential transcriptional coactivator regulating mammary gland
RT secretion of milk lipids.";
RL Nat. Med. 18:235-243(2012).
CC -!- FUNCTION: Binds to lipid droplets and regulates their enlargement,
CC thereby restricting lipolysis and favoring storage. At focal contact
CC sites between lipid droplets, promotes directional net neutral lipid
CC transfer from the smaller to larger lipid droplets. The transfer
CC direction may be driven by the internal pressure difference between the
CC contacting lipid droplet pair and occurs at a lower rate than that
CC promoted by CIDEC. Acts as a CEBPB coactivator in mammary epithelial
CC cells to control the expression of a subset of CEBPB downstream target
CC genes, including ID2, IGF1, PRLR, SOCS1, SOCS3, XDH, but not casein. By
CC interacting with CEBPB, strengthens the association of CEBPB with the
CC XDH promoter, increases histone acetylation and dissociates HDAC1 from
CC the promoter. When overexpressed, induces apoptosis. The physiological
CC significance of its role in apoptosis is unclear.
CC {ECO:0000269|PubMed:18509062, ECO:0000269|PubMed:22144693,
CC ECO:0000269|PubMed:22245780, ECO:0000269|PubMed:9564035}.
CC -!- SUBUNIT: Interacts with CIDEC (By similarity). Directly interacts with
CC CEBPB. {ECO:0000250, ECO:0000269|PubMed:22245780}.
CC -!- INTERACTION:
CC O70302; Q9Y478: PRKAB1; Xeno; NbExp=4; IntAct=EBI-7927848, EBI-719769;
CC -!- SUBCELLULAR LOCATION: Lipid droplet. Nucleus. Note=Enriched at lipid
CC droplet contact sites. Using a GFP-tagged construct, has been shown to
CC localize to mitochondria, where it could interact with UCP1 and hence
CC inhibit UCP1 uncoupling activity (PubMed:12910269). These data could
CC not be confirmed (PubMed:22245780, PubMed:18509062).
CC {ECO:0000269|PubMed:12910269, ECO:0000269|PubMed:18509062,
CC ECO:0000269|PubMed:22245780}.
CC -!- TISSUE SPECIFICITY: Highly expressed in brown adipose tissue and, at
CC lower levels, in white adipose tissue (at protein level). Expressed in
CC mammary gland during pregnancy and lactation, in epithelial cells, but
CC not in the surrounding adipose tissue. Secreted into milk via milk fat
CC globules. Undetectable in undifferentiated preadipocytes.
CC {ECO:0000269|PubMed:12910269, ECO:0000269|PubMed:18509062,
CC ECO:0000269|PubMed:22245780}.
CC -!- DEVELOPMENTAL STAGE: Expressed at 15 dpc in the interscapular region of
CC the embryo, that could correspond to the developing brown adipose
CC tissue. Expression continues in the interscapular region at 18 dpc and
CC postnatally. In mammary glands, begins to be highly expressed at day
CC 14.5 of pregnancy. Expression is maintained at high levels throughout
CC lactation and declines during post-lactational involution.
CC {ECO:0000269|PubMed:22245780}.
CC -!- INDUCTION: Up-regulated under conditions that enhance triacylglycerol
CC deposition, including rosiglitazone treatment and high-fat diet. This
CC up-regulation is mediated by PPARG. {ECO:0000269|PubMed:18509062}.
CC -!- DISRUPTION PHENOTYPE: Mutant animals appear normal and fertile and
CC produce the expected Mendelian ratio of heterozygous and homozygous
CC descendents. They are lean and resistant to diet-induced obesity and
CC diabetes. They exhibit higher metabolic rate, lipolysis in brown
CC adipose tissue and core body temperature when subjected to cold
CC treatment. Mutant females are unable to properly feed their pups who
CC die within 3 days postpartum due to severely reduced milk lipids.
CC {ECO:0000269|PubMed:12910269, ECO:0000269|PubMed:22245780}.
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DR EMBL; AF041376; AAC34985.1; -; mRNA.
DR EMBL; AC154125; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466528; EDL09649.1; -; Genomic_DNA.
DR EMBL; CH466528; EDL09650.1; -; Genomic_DNA.
DR EMBL; BC096649; AAH96649.1; -; mRNA.
DR CCDS; CCDS37846.1; -.
DR RefSeq; NP_031728.2; NM_007702.2.
DR AlphaFoldDB; O70302; -.
DR BioGRID; 198712; 3.
DR IntAct; O70302; 7.
DR MINT; O70302; -.
DR STRING; 10090.ENSMUSP00000025404; -.
DR PaxDb; O70302; -.
DR PRIDE; O70302; -.
DR ProteomicsDB; 279081; -.
DR Antibodypedia; 6758; 318 antibodies from 35 providers.
DR DNASU; 12683; -.
DR Ensembl; ENSMUST00000025404; ENSMUSP00000025404; ENSMUSG00000024526.
DR GeneID; 12683; -.
DR KEGG; mmu:12683; -.
DR UCSC; uc012beh.1; mouse.
DR CTD; 1149; -.
DR MGI; MGI:1270845; Cidea.
DR VEuPathDB; HostDB:ENSMUSG00000024526; -.
DR eggNOG; ENOG502RG9M; Eukaryota.
DR GeneTree; ENSGT00390000018596; -.
DR HOGENOM; CLU_090011_2_0_1; -.
DR InParanoid; O70302; -.
DR OMA; KCMGAKS; -.
DR OrthoDB; 1421916at2759; -.
DR PhylomeDB; O70302; -.
DR TreeFam; TF334321; -.
DR Reactome; R-MMU-8964572; Lipid particle organization.
DR BioGRID-ORCS; 12683; 3 hits in 73 CRISPR screens.
DR PRO; PR:O70302; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; O70302; protein.
DR Bgee; ENSMUSG00000024526; Expressed in aorta tunica adventitia and 119 other tissues.
DR Genevisible; O70302; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005811; C:lipid droplet; ISO:MGI.
DR GO; GO:0005740; C:mitochondrial envelope; IDA:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0070417; P:cellular response to cold; IDA:MGI.
DR GO; GO:0006629; P:lipid metabolic process; IMP:MGI.
DR GO; GO:0019915; P:lipid storage; IMP:BHF-UCL.
DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR GO; GO:0001818; P:negative regulation of cytokine production; ISO:MGI.
DR GO; GO:1900118; P:negative regulation of execution phase of apoptosis; IDA:BHF-UCL.
DR GO; GO:0050995; P:negative regulation of lipid catabolic process; IMP:BHF-UCL.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; ISO:MGI.
DR GO; GO:0010890; P:positive regulation of sequestering of triglyceride; IDA:BHF-UCL.
DR GO; GO:1902510; P:regulation of apoptotic DNA fragmentation; IDA:BHF-UCL.
DR GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:0035634; P:response to stilbenoid; IEP:UniProtKB.
DR GO; GO:0001659; P:temperature homeostasis; IMP:BHF-UCL.
DR InterPro; IPR032936; CIDE-A.
DR InterPro; IPR003508; CIDE-N_dom.
DR PANTHER; PTHR12306:SF8; PTHR12306:SF8; 1.
DR Pfam; PF02017; CIDE-N; 1.
DR SMART; SM00266; CAD; 1.
DR PROSITE; PS51135; CIDE_N; 1.
PE 1: Evidence at protein level;
KW Activator; Apoptosis; Lipid droplet; Nucleus; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN 1..217
FT /note="Cell death activator CIDE-A"
FT /id="PRO_0000144719"
FT DOMAIN 33..110
FT /note="CIDE-N"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00447"
FT MUTAGEN 23
FT /note="K->A: Sustantial reduction in nuclear localization
FT and loss of XDH induction; when associated with A-24."
FT /evidence="ECO:0000269|PubMed:22245780"
FT MUTAGEN 23
FT /note="K->R: Increased nuclear localization."
FT /evidence="ECO:0000269|PubMed:22245780"
FT MUTAGEN 24
FT /note="K->A: Sustantial reduction in nuclear localization
FT and loss of XDH induction; when associated with A-23."
FT /evidence="ECO:0000269|PubMed:22245780"
FT CONFLICT 165
FT /note="S -> R (in Ref. 1; AAC34985)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 217 AA; 24669 MW; C9E406895CFD4CBA CRC64;
METARDYAGA LIRPLTFMGL QTKKVLLTPL IHPARPFRVS NHDRSSRRGV MASSLQELIS
KTLDVLVITT GLVTLVLEED GTVVDTEEFF QTLRDNTHFM ILEKGQKWTP GSKYVPVCKQ
PKKSGIARVT FDLYRLNPKD FLGCLNVKAT MYEMYSVSYD IRCTSFKAVL RNLLRFMSYA
AQMTGQFLVY AGTYMLRVLG DTEEQPSPKP STKGWFM
