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O70302

- CIDEA_MOUSE

UniProt

O70302 - CIDEA_MOUSE

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Protein

Cell death activator CIDE-A

Gene

Cidea

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.4 Publications

GO - Molecular functioni

  1. protein homodimerization activity Source: BHF-UCL

GO - Biological processi

  1. apoptotic process Source: UniProtKB-KW
  2. cell death Source: BHF-UCL
  3. lipid metabolic process Source: MGI
  4. lipid storage Source: BHF-UCL
  5. negative regulation of cytokine secretion Source: Ensembl
  6. negative regulation of execution phase of apoptosis Source: BHF-UCL
  7. negative regulation of lipid catabolic process Source: BHF-UCL
  8. negative regulation of transforming growth factor beta receptor signaling pathway Source: BHF-UCL
  9. negative regulation of tumor necrosis factor production Source: Ensembl
  10. positive regulation of sequestering of triglyceride Source: BHF-UCL
  11. regulation of apoptotic DNA fragmentation Source: BHF-UCL
  12. regulation of transcription, DNA-templated Source: UniProtKB-KW
  13. response to stilbenoid Source: UniProtKB
  14. temperature homeostasis Source: BHF-UCL
  15. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Apoptosis, Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
Cell death activator CIDE-A
Alternative name(s):
Cell death-inducing DFFA-like effector A
Gene namesi
Name:Cidea
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 18

Organism-specific databases

MGIiMGI:1270845. Cidea.

Subcellular locationi

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 (PubMed:12910269). These data could not be confirmed (PubMed:22245780, PubMed:18509062).3 Publications

GO - Cellular componenti

  1. cytoplasm Source: BHF-UCL
  2. lipid particle Source: UniProtKB-KW
  3. mitochondrial envelope Source: MGI
  4. mitochondrion Source: MGI
  5. nucleus Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Lipid droplet, Nucleus

Pathology & Biotechi

Disruption phenotypei

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.2 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi23 – 231K → A: Sustantial reduction in nuclear localization and loss of XDH induction; when associated with A-24. 1 Publication
Mutagenesisi23 – 231K → R: Increased nuclear localization. 1 Publication
Mutagenesisi24 – 241K → A: Sustantial reduction in nuclear localization and loss of XDH induction; when associated with A-23. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 217217Cell death activator CIDE-APRO_0000144719Add
BLAST

Proteomic databases

PaxDbiO70302.
PRIDEiO70302.

PTM databases

PhosphoSiteiO70302.

Expressioni

Tissue specificityi

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.3 Publications

Developmental stagei

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.1 Publication

Inductioni

Up-regulated under conditions that enhance triacylglycerol deposition, including rosiglitazone treatment and high-fat diet. This up-regulation is mediated by PPARG.1 Publication

Gene expression databases

GenevestigatoriO70302.

Interactioni

Subunit structurei

Interacts with CIDEC (By similarity). Directly interacts with CEBPB.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
PRKAB1Q9Y4784EBI-7927848,EBI-719769From a different organism.

Protein-protein interaction databases

IntActiO70302. 7 interactions.
STRINGi10090.ENSMUSP00000025404.

Structurei

3D structure databases

ProteinModelPortaliO70302.
SMRiO70302. Positions 33-110.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini33 – 11078CIDE-NPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 CIDE-N domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG43753.
GeneTreeiENSGT00390000018596.
HOGENOMiHOG000029211.
HOVERGENiHBG050961.
InParanoidiO70302.
OMAiAQITGQF.
OrthoDBiEOG7K3TN6.
TreeFamiTF334321.

Family and domain databases

InterProiIPR003508. CIDE-N_dom.
[Graphical view]
PfamiPF02017. CIDE-N. 1 hit.
[Graphical view]
SMARTiSM00266. CAD. 1 hit.
[Graphical view]
PROSITEiPS51135. CIDE_N. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O70302-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
METARDYAGA LIRPLTFMGL QTKKVLLTPL IHPARPFRVS NHDRSSRRGV
60 70 80 90 100
MASSLQELIS KTLDVLVITT GLVTLVLEED GTVVDTEEFF QTLRDNTHFM
110 120 130 140 150
ILEKGQKWTP GSKYVPVCKQ PKKSGIARVT FDLYRLNPKD FLGCLNVKAT
160 170 180 190 200
MYEMYSVSYD IRCTSFKAVL RNLLRFMSYA AQMTGQFLVY AGTYMLRVLG
210
DTEEQPSPKP STKGWFM
Length:217
Mass (Da):24,669
Last modified:October 3, 2012 - v2
Checksum:iC9E406895CFD4CBA
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti165 – 1651S → R in AAC34985. (PubMed:9564035)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS37846.1.
RefSeqiNP_031728.2. NM_007702.2.
UniGeneiMm.449.

Genome annotation databases

EnsembliENSMUST00000025404; ENSMUSP00000025404; ENSMUSG00000024526.
GeneIDi12683.
KEGGimmu:12683.
UCSCiuc012beh.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS37846.1.
RefSeqi NP_031728.2. NM_007702.2.
UniGenei Mm.449.

3D structure databases

ProteinModelPortali O70302.
SMRi O70302. Positions 33-110.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi O70302. 7 interactions.
STRINGi 10090.ENSMUSP00000025404.

PTM databases

PhosphoSitei O70302.

Proteomic databases

PaxDbi O70302.
PRIDEi O70302.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000025404 ; ENSMUSP00000025404 ; ENSMUSG00000024526 .
GeneIDi 12683.
KEGGi mmu:12683.
UCSCi uc012beh.1. mouse.

Organism-specific databases

CTDi 1149.
MGIi MGI:1270845. Cidea.

Phylogenomic databases

eggNOGi NOG43753.
GeneTreei ENSGT00390000018596.
HOGENOMi HOG000029211.
HOVERGENi HBG050961.
InParanoidi O70302.
OMAi AQITGQF.
OrthoDBi EOG7K3TN6.
TreeFami TF334321.

Miscellaneous databases

NextBioi 281928.
PROi O70302.
SOURCEi Search...

Gene expression databases

Genevestigatori O70302.

Family and domain databases

InterProi IPR003508. CIDE-N_dom.
[Graphical view ]
Pfami PF02017. CIDE-N. 1 hit.
[Graphical view ]
SMARTi SM00266. CAD. 1 hit.
[Graphical view ]
PROSITEi PS51135. CIDE_N. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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.

Entry informationi

Entry nameiCIDEA_MOUSE
AccessioniPrimary (citable) accession number: O70302
Secondary accession number(s): Q4V9X2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: October 3, 2012
Last modified: October 29, 2014
This is version 91 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3