CISD2_MOUSE
ID CISD2_MOUSE Reviewed; 135 AA.
AC Q9CQB5; Q9D0Y0;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=CDGSH iron-sulfur domain-containing protein 2;
DE AltName: Full=MitoNEET-related 1 protein;
DE Short=Miner1;
DE AltName: Full=Nervous system overexpressed protein 70;
GN Name=Cisd2; Synonyms=Cdgsh2, Noxp70, Zcd2;
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 TISSUE SPECIFICITY.
RC STRAIN=129/Sv;
RX PubMed=17029606; DOI=10.1111/j.1471-4159.2006.04093.x;
RA Boucquey M.F.A., De Plaen E., Locker M., Poliard A., Mouillet-Richard S.,
RA Boon T., Kellermann O.;
RT "Noxp20 and Noxp70, two new markers of early neuronal differentiation,
RT detected in teratocarcinoma-derived neuroectodermic precursor cells.";
RL J. Neurochem. 99:657-669(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cerebellum;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N-3; TISSUE=Mammary tumor;
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 [4]
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19451219; DOI=10.1101/gad.1779509;
RA Chen Y.F., Kao C.H., Chen Y.T., Wang C.H., Wu C.Y., Tsai C.Y., Liu F.C.,
RA Yang C.W., Wei Y.H., Hsu M.T., Tsai S.F., Tsai T.F.;
RT "Cisd2 deficiency drives premature aging and causes mitochondria-mediated
RT defects in mice.";
RL Genes Dev. 23:1183-1194(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Regulator of autophagy that contributes to antagonize BECN1-
CC mediated cellular autophagy at the endoplasmic reticulum. Participates
CC in the interaction of BCL2 with BECN1 and is required for BCL2-mediated
CC depression of endoplasmic reticulum Ca(2+) stores during autophagy.
CC Contributes to BIK-initiated autophagy, while it is not involved in
CC BIK-dependent activation of caspases. Involved in life span control,
CC probably via its function as regulator of autophagy (By similarity).
CC {ECO:0000250, ECO:0000269|PubMed:19451219}.
CC -!- COFACTOR:
CC Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135; Evidence={ECO:0000250};
CC Note=Binds 1 [2Fe-2S] cluster. {ECO:0000250};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Redox potential:
CC E is 0 +/- 10 mV for 2Fe-2S at pH 7.5.;
CC -!- SUBUNIT: Homodimer. Interacts with BCL2; the interaction is direct and
CC disrupted by BIK interaction with BCL2. Interacts with BCL2L1.
CC Interacts with ITPR1 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:19451219}; Single-pass membrane protein
CC {ECO:0000269|PubMed:19451219}. Mitochondrion outer membrane
CC {ECO:0000269|PubMed:19451219}; Single-pass membrane protein
CC {ECO:0000269|PubMed:19451219}. Note=According to PubMed:19451219, it
CC mainly localizes to the mitochondrion outer membrane and localizes only
CC at low level to the endoplasmic reticulum. However, inverse results are
CC observed in human cells.
CC -!- TISSUE SPECIFICITY: Brain. {ECO:0000269|PubMed:17029606}.
CC -!- INDUCTION: Expression decreases in an age-dependent manner.
CC {ECO:0000269|PubMed:19451219}.
CC -!- DISRUPTION PHENOTYPE: Premature aging associated with a shortened life
CC span, probably caused by mitochondrial degeneration and autophagy. 8
CC week old mice begin to acquire a set of aged appearance phenomena
CC remarkably similar to those of premature aging syndrome, including
CC prominent eyes and protruding ears. Ocular abnormalities are observed:
CC mice develop opaque eyes and blindness, which is accompanied by cornea
CC damage at 20 week old. The opacity of the cornea is due to debris
CC deposition in the scar tissue outside the cornea. In addition, corneal
CC neovascularization is observed, possibly impairing vision. An early
CC depigmentation in the fur at around 48 week old is also observed;
CC furthermore, hair follicle atrophy and a decreased hair density is
CC detected. A decrease in the hair regrowth rate is also observed.
CC Additionally, the skin of 48-week-old mice exhibits a phenotype with a
CC noticeably thickened dermis, an expanded surface, and a significant
CC decrease in subcutaneous adipose tissue and muscle. The trabeculae of
CC the femur are noticeably thinner and dual energy X-ray absorptiometer
CC (DEXA) detects a decrease in femur density after 8 week old. Mice also
CC display a significant lordokyphosis phenotype after 12 week old;
CC leading to a decrease in mean thoracic volume and thence pulmonary
CC function abnormalities. Muscle degeneration is detectable at 3 week old
CC with a progressive degeneration of muscle fibers and the magnitude of
CC the degeneration exacerbated with age. {ECO:0000269|PubMed:19451219}.
CC -!- SIMILARITY: Belongs to the CISD protein family. CISD2 subfamily.
CC {ECO:0000305}.
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DR EMBL; AM162549; CAJ44265.1; -; mRNA.
DR EMBL; AK003486; BAB22814.1; -; mRNA.
DR EMBL; AK004257; BAB23237.1; -; mRNA.
DR EMBL; AK005184; BAB23868.1; -; mRNA.
DR EMBL; BC058279; AAH58279.1; -; mRNA.
DR CCDS; CCDS17856.1; -.
DR RefSeq; NP_080178.1; NM_025902.3.
DR RefSeq; XP_006501981.1; XM_006501918.3.
DR AlphaFoldDB; Q9CQB5; -.
DR SMR; Q9CQB5; -.
DR BioGRID; 211870; 2.
DR STRING; 10090.ENSMUSP00000029815; -.
DR iPTMnet; Q9CQB5; -.
DR PhosphoSitePlus; Q9CQB5; -.
DR SwissPalm; Q9CQB5; -.
DR EPD; Q9CQB5; -.
DR jPOST; Q9CQB5; -.
DR MaxQB; Q9CQB5; -.
DR PaxDb; Q9CQB5; -.
DR PeptideAtlas; Q9CQB5; -.
DR PRIDE; Q9CQB5; -.
DR ProteomicsDB; 281626; -.
DR Antibodypedia; 2500; 175 antibodies from 30 providers.
DR DNASU; 67006; -.
DR Ensembl; ENSMUST00000029815; ENSMUSP00000029815; ENSMUSG00000028165.
DR GeneID; 67006; -.
DR KEGG; mmu:67006; -.
DR UCSC; uc008rlk.2; mouse.
DR CTD; 493856; -.
DR MGI; MGI:1914256; Cisd2.
DR VEuPathDB; HostDB:ENSMUSG00000028165; -.
DR eggNOG; KOG3461; Eukaryota.
DR GeneTree; ENSGT00940000156660; -.
DR HOGENOM; CLU_132293_1_0_1; -.
DR InParanoid; Q9CQB5; -.
DR OMA; PKCDGSH; -.
DR OrthoDB; 1393750at2759; -.
DR PhylomeDB; Q9CQB5; -.
DR TreeFam; TF324661; -.
DR BioGRID-ORCS; 67006; 5 hits in 71 CRISPR screens.
DR ChiTaRS; Cisd2; mouse.
DR PRO; PR:Q9CQB5; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q9CQB5; protein.
DR Bgee; ENSMUSG00000028165; Expressed in interventricular septum and 224 other tissues.
DR ExpressionAtlas; Q9CQB5; baseline and differential.
DR Genevisible; Q9CQB5; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0097038; C:perinuclear endoplasmic reticulum; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0000422; P:autophagy of mitochondrion; IMP:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; ISO:MGI.
DR Gene3D; 3.40.5.90; -; 1.
DR InterPro; IPR045131; CISD1/2.
DR InterPro; IPR018967; FeS-contain_CDGSH-typ.
DR InterPro; IPR019610; FeS-contain_mitoNEET_N.
DR InterPro; IPR042216; MitoNEET_CISD.
DR PANTHER; PTHR13680; PTHR13680; 1.
DR Pfam; PF10660; MitoNEET_N; 1.
DR Pfam; PF09360; zf-CDGSH; 1.
DR SMART; SM00704; ZnF_CDGSH; 1.
PE 1: Evidence at protein level;
KW 2Fe-2S; Autophagy; Endoplasmic reticulum; Iron; Iron-sulfur; Membrane;
KW Metal-binding; Mitochondrion; Mitochondrion outer membrane;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..135
FT /note="CDGSH iron-sulfur domain-containing protein 2"
FT /id="PRO_0000316006"
FT TOPO_DOM 1..37
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 38..60
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 61..135
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT BINDING 99
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000250"
FT BINDING 101
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000250"
FT BINDING 110
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000250"
FT BINDING 114
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000250"
FT CONFLICT 61
FT /note="P -> A (in Ref. 2; BAB23237)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 135 AA; 15242 MW; A46C87D9C6F73EF0 CRC64;
MVLDSVARIV KVQLPAYLKQ LPVPDSITGF ARLTVSDWLR LLPFLGVLAL LGYLAVRPFF
PKKKQQKDSL INLKIQKENP KVVNEINIED LCLTKAAYCR CWRSKTFPAC DGSHNKHNEL
TGDNVGPLIL KKKEV
