O70302 (CIDEA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cell death activator CIDE-A

Alternative name(s):
Cell death-inducing DFFA-like effector A

Gene names

Name:

Cidea

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	217 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Binds to lipid droplets and regulates their enlargement, thereby restricting lipolysis and favoring storage. At focal contact sites between lipid droplets, promotes directional net neutral lipid transfer from the smaller to larger lipid droplets. The transfer direction may be driven by the internal pressure difference between the contacting lipid droplet pair and occurs at a lower rate than that promoted by CIDEC. Acts as a CEBPB coactivator in mammary epithelial cells to control the expression of a subset of CEBPB downstream target genes, including ID2, IGF1, PRLR, SOCS1, SOCS3, XDH, but not casein. By interacting with CEBPB, strengthens the association of CEBPB with the XDH promoter, increases histone acetylation and dissociates HDAC1 from the promoter. When overexpressed, induces apoptosis. The physiological significance of its role in apoptosis is unclear. Ref.1 Ref.6 Ref.7 Ref.8
Subunit structure	Interacts with CIDEC By similarity. Directly interacts with CEBPB. Ref.8
Subcellular location	Lipid droplet. Nucleus. Note: Enriched at lipid droplet contact sites. Using a GFP-tagged construct, has been shown to localize to mitonchondria, where it could interact with UCP1 and hence inhibit UCP1 uncoupling activity (Ref.5). These data could not be confirmed (Ref.8, Ref.6). Ref.5 Ref.6 Ref.7 Ref.8
Tissue specificity	Highly expressed in brown adipose tissue and, at lower levels, in white adipose tissue (at protein level). Expressed in mammary gland during pregnancy and lactation, in epithelial cells, but not in the surrounding adipose tissue. Secreted into milk via milk fat globules. Undetectable in undifferentiated preadipocytes. Ref.5 Ref.6 Ref.8
Developmental stage	Expressed at 15 dpc in the interscapular region of the embryo, that could correspond to the developing brown adipose tissue. Expression continues in the interscapular region at 18 dpc and postnatally. In mammary glands, begins to be highly expressed at day 14.5 of pregnancy. Expression is maintained at high levels throughout lactation and declines during post-lactational involution. Ref.8
Induction	Up-regulated under conditions that enhance triacylglycerol deposition, including rosiglitazone treatment and high-fat diet. This up-regulation is mediated by PPARG. Ref.6
Disruption phenotype	Mutant animals appear normal and fertile and produce the expected Mendelian ratio of heterozygous and homozygous descendents. They are lean and resistant to diet-induced obesity and diabetes. They exhibit higher metabolic rate, lipolysis in brown adipose tissue and core body temperature when subjected to cold treatment. Mutant females are unable to properly feed their pups who die within 3 days postpartum due to severely reduced milk lipids. Ref.5 Ref.8
Sequence similarities	Contains 1 CIDE-N domain.

Ontologies

Keywords
Biological process	Apoptosis Transcription Transcription regulation
Cellular component	Lipid droplet Nucleus
Molecular function	Activator
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic DNA fragmentation Inferred from direct assay Ref.1. Source: BHF-UCL lipid metabolic process Inferred from mutant phenotype Ref.5. Source: MGI lipid storage Inferred from mutant phenotype Ref.5. Source: BHF-UCL negative regulation of apoptotic process Inferred from direct assay PubMed 17080483. Source: BHF-UCL negative regulation of cytokine secretion Inferred from electronic annotation. Source: Compara negative regulation of lipid catabolic process Inferred from mutant phenotype Ref.5. Source: BHF-UCL negative regulation of transforming growth factor beta receptor signaling pathway Inferred from direct assay PubMed 17080483. Source: BHF-UCL negative regulation of tumor necrosis factor production Inferred from electronic annotation. Source: Compara positive regulation of sequestering of triglyceride Inferred from direct assay Ref.6. Source: BHF-UCL regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW response to stilbenoid Inferred from expression pattern PubMed 17086191. Source: UniProtKB temperature homeostasis Inferred from mutant phenotype Ref.5. Source: BHF-UCL transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	lipid particle Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrial envelope Inferred from direct assay Ref.5. Source: MGI nucleus Inferred from direct assay PubMed 17080483. Source: BHF-UCL
Molecular_function	protein homodimerization activity Inferred from direct assay PubMed 17080483. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 217	217	Cell death activator CIDE-A		PRO_0000144719
Regions
	Domain	33 – 110	78	CIDE-N
Experimental info
	Mutagenesis	23	1	K → A: Sustantial reduction in nuclear localization and loss of XDH induction; when associated with A-24. Ref.8
	Mutagenesis	23	1	K → R: Increased nuclear localization. Ref.8
	Mutagenesis	24	1	K → A: Sustantial reduction in nuclear localization and loss of XDH induction; when associated with A-23. Ref.8
	Sequence conflict	165	1	S → R in AAC34985. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O70302 [UniParc]. Last modified October 3, 2012. Version 2. Checksum: C9E406895CFD4CBA	FASTA	217	24,669
	10 20 30 40 50 60 METARDYAGA LIRPLTFMGL QTKKVLLTPL IHPARPFRVS NHDRSSRRGV MASSLQELIS 70 80 90 100 110 120 KTLDVLVITT GLVTLVLEED GTVVDTEEFF QTLRDNTHFM ILEKGQKWTP GSKYVPVCKQ 130 140 150 160 170 180 PKKSGIARVT FDLYRLNPKD FLGCLNVKAT MYEMYSVSYD IRCTSFKAVL RNLLRFMSYA 190 200 210 AQMTGQFLVY AGTYMLRVLG DTEEQPSPKP STKGWFM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"CIDE, a novel family of cell death activators with homology to the 45 kDa subunit of the DNA fragmentation factor." Inohara N., Koseki T., Chen S., Wu X., Nunez G. EMBO J. 17:2526-2533(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION IN APOPTOSIS.
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[3]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Mammary gland.
[5]	"Cidea-deficient mice have lean phenotype and are resistant to obesity." Zhou Z., Yon Toh S., Chen Z., Guo K., Ng C.P., Ponniah S., Lin S.C., Hong W., Li P. Nat. Genet. 35:49-56(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
[6]	"Cidea is associated with lipid droplets and insulin sensitivity in humans." Puri V., Ranjit S., Konda S., Nicoloro S.M., Straubhaar J., Chawla A., Chouinard M., Lin C., Burkart A., Corvera S., Perugini R.A., Czech M.P. Proc. Natl. Acad. Sci. U.S.A. 105:7833-7838(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INDUCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[7]	"Fsp27 promotes lipid droplet growth by lipid exchange and transfer at lipid droplet contact sites." Gong J., Sun Z., Wu L., Xu W., Schieber N., Xu D., Shui G., Yang H., Parton R.G., Li P. J. Cell Biol. 195:953-963(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[8]	"Cidea is an essential transcriptional coactivator regulating mammary gland secretion of milk lipids." Wang W., Lv N., Zhang S., Shui G., Qian H., Zhang J., Chen Y., Ye J., Xie Y., Shen Y., Wenk M.R., Li P. Nat. Med. 18:235-243(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS A CEBPB COACTIVATOR, INTERACTION WITH CEBPB, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, MUTAGENESIS OF LYS-23 AND LYS-24.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF041376 mRNA. Translation: AAC34985.1. AC154125 Genomic DNA. No translation available. CH466528 Genomic DNA. Translation: EDL09649.1. CH466528 Genomic DNA. Translation: EDL09650.1. BC096649 mRNA. Translation: AAH96649.1.
IPI	IPI00117225. IPI00881744.
RefSeq	NP_031728.2. NM_007702.2.
UniGene	Mm.449.
3D structure databases
ProteinModelPortal	O70302.
SMR	O70302. Positions 33-110.
ModBase	Search...
Protein-protein interaction databases
STRING	10090.ENSMUSP00000025404.
PTM databases
PhosphoSite	O70302.
Proteomic databases
PaxDb	O70302.
PRIDE	O70302.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000025404; ENSMUSP00000025404; ENSMUSG00000024526.
GeneID	12683.
KEGG	mmu:12683.
Organism-specific databases
CTD	1149.
MGI	MGI:1270845. Cidea.
Phylogenomic databases
eggNOG	NOG43753.
GeneTree	ENSGT00390000018596.
HOGENOM	HOG000029211.
HOVERGEN	HBG050961.
InParanoid	O70302.
OMA	YRLNPKD.
OrthoDB	EOG437RFP.
Gene expression databases
Genevestigator	O70302.
GermOnline	ENSMUSG00000024526. Mus musculus.
Family and domain databases
InterPro	IPR003508. CAD. [Graphical view]
Pfam	PF02017. CIDE-N. 1 hit. [Graphical view]
SMART	SM00266. CAD. 1 hit. [Graphical view]
PROSITE	PS51135. CIDE_N. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	281928.
SOURCE	Search...

Entry information

Entry name

CIDEA_MOUSE

Accession

Primary (citable) accession number: O70302
Secondary accession number(s): Q4V9X2

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	October 3, 2012
Last modified:	May 1, 2013
This is version 78 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program