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Q8N5K1

- CISD2_HUMAN

UniProt

Q8N5K1 - CISD2_HUMAN

Protein

CDGSH iron-sulfur domain-containing protein 2

Gene

CISD2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. Functioni

    Regulator of autophagy that contributes to antagonize BECN1-mediated cellular autophagy at the endoplasmic reticulum. Participates in the interaction of BCL2 with BECN1 and is required for BCL2-mediated depression of endoplasmic reticulum Ca2+ stores during autophagy. Contributes to BIK-initiated autophagy, while it is not involved in BIK-dependent activation of caspases. Involved in life span control, probably via its function as regulator of autophagy.2 Publications

    Cofactori

    Binds 1 2Fe-2S cluster.1 Publication

    Redox potential

    E is 0 +/- 10 mV for 2Fe-2S at pH 7.5.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi99 – 991Iron-sulfur (2Fe-2S)
    Metal bindingi101 – 1011Iron-sulfur (2Fe-2S)
    Metal bindingi110 – 1101Iron-sulfur (2Fe-2S)
    Metal bindingi114 – 1141Iron-sulfur (2Fe-2S); via pros nitrogen

    GO - Molecular functioni

    1. 2 iron, 2 sulfur cluster binding Source: UniProtKB
    2. metal ion binding Source: UniProtKB-KW
    3. poly(A) RNA binding Source: UniProtKB
    4. protein binding Source: UniProtKB
    5. protein homodimerization activity Source: UniProtKB

    GO - Biological processi

    1. mitochondrion degradation Source: Ensembl
    2. multicellular organismal aging Source: UniProtKB
    3. regulation of autophagy Source: UniProtKB

    Keywords - Biological processi

    Autophagy

    Keywords - Ligandi

    2Fe-2S, Iron, Iron-sulfur, Metal-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    CDGSH iron-sulfur domain-containing protein 2
    Alternative name(s):
    Endoplasmic reticulum intermembrane small protein
    MitoNEET-related 1 protein
    Short name:
    Miner1
    Nutrient-deprivation autophagy factor-1
    Short name:
    NAF-1
    Gene namesi
    Name:CISD2
    Synonyms:CDGSH2, ERIS, ZCD2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 4

    Organism-specific databases

    HGNCiHGNC:24212. CISD2.

    Subcellular locationi

    Endoplasmic reticulum membrane; Single-pass membrane protein. Mitochondrion outer membrane; Single-pass membrane protein
    Note: According to PubMed:20010695, it mainly localizes to the endoplasmic reticulum. However, experiments in mouse showed that it mainly localizes to the mitochondrion outer membrane.

    GO - Cellular componenti

    1. endoplasmic reticulum Source: HPA
    2. endoplasmic reticulum membrane Source: UniProtKB
    3. integral component of membrane Source: UniProtKB-KW
    4. membrane Source: UniProtKB
    5. mitochondrial outer membrane Source: UniProtKB
    6. protein complex Source: LIFEdb

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Mitochondrion, Mitochondrion outer membrane

    Pathology & Biotechi

    Involvement in diseasei

    Wolfram syndrome 2 (WFS2) [MIM:604928]: A rare disorder characterized by juvenile-onset insulin-dependent diabetes mellitus with optic atrophy. Other manifestations include diabetes insipidus, sensorineural deafness, dementia, psychiatric illnesses. WFS2 patients additionally show a strong bleeding tendency and gastrointestinal ulceration. Diabetes insipidus may be absent.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi92 – 921C → S: Has the same optical signature of the native protein and improves yields of purified protein and a decreased tendency to aggregate. 1 Publication
    Mutagenesisi99 – 991C → S: Impairs interaction with BCL2; when associated with S-101; S-110 and Q-114. 1 Publication
    Mutagenesisi101 – 1011C → S: Impairs interaction with BCL2; when associated with S-99; S-110 and Q-114. 1 Publication
    Mutagenesisi110 – 1101C → S: Impairs interaction with BCL2; when associated with S-99; S-101 and Q-114. 1 Publication
    Mutagenesisi114 – 1141H → Q: Impairs interaction with BCL2; when associated with S-99; S-101 and S-110. 1 Publication

    Keywords - Diseasei

    Deafness, Diabetes mellitus

    Organism-specific databases

    MIMi604928. phenotype.
    Orphaneti3463. Wolfram syndrome.
    PharmGKBiPA162382300.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 135135CDGSH iron-sulfur domain-containing protein 2PRO_0000316005Add
    BLAST

    Proteomic databases

    MaxQBiQ8N5K1.
    PaxDbiQ8N5K1.
    PeptideAtlasiQ8N5K1.
    PRIDEiQ8N5K1.

    PTM databases

    PhosphoSiteiQ8N5K1.

    Expressioni

    Tissue specificityi

    Testis, small intestine, kidney, lung, brain, heart, pancreas and platelets.1 Publication

    Gene expression databases

    ArrayExpressiQ8N5K1.
    BgeeiQ8N5K1.
    CleanExiHS_CISD2.
    GenevestigatoriQ8N5K1.

    Organism-specific databases

    HPAiHPA015914.

    Interactioni

    Subunit structurei

    Homodimer. Interacts with BCL2; the interaction is direct and disrupted by BIK interaction with BCL2. Interacts with BCL2L1. Interacts with ITPR1.2 Publications

    Protein-protein interaction databases

    BioGridi138922. 7 interactions.
    MINTiMINT-4722106.
    STRINGi9606.ENSP00000273986.

    Structurei

    Secondary structure

    1
    135
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi73 – 753
    Beta strandi79 – 879
    Helixi88 – 903
    Beta strandi93 – 986
    Beta strandi100 – 1023
    Turni105 – 1084
    Helixi113 – 1219
    Beta strandi125 – 1317

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3FNVX-ray2.10A/B57-135[»]
    ProteinModelPortaliQ8N5K1.
    SMRiQ8N5K1. Positions 68-135.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ8N5K1.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 3737LumenalSequence AnalysisAdd
    BLAST
    Topological domaini61 – 13575CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei38 – 6023HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the CISD protein family. CISD2 subfamily.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG236423.
    HOGENOMiHOG000242301.
    HOVERGENiHBG052444.
    InParanoidiQ8N5K1.
    OMAiLCLTKAY.
    OrthoDBiEOG7GQXZ6.
    PhylomeDBiQ8N5K1.
    TreeFamiTF324661.

    Family and domain databases

    InterProiIPR018967. FeS-contain_CDGSH-typ.
    IPR006622. FeS-contain_CDGSH-typ_subfam.
    IPR019610. FeS-contain_mitoNEET_N.
    [Graphical view]
    PfamiPF10660. MitoNEET_N. 1 hit.
    PF09360. zf-CDGSH. 1 hit.
    [Graphical view]
    SMARTiSM00704. ZnF_CDGSH. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q8N5K1-1 [UniParc]FASTAAdd to Basket

    « Hide

    MVLESVARIV KVQLPAYLKR LPVPESITGF ARLTVSEWLR LLPFLGVLAL    50
    LGYLAVRPFL PKKKQQKDSL INLKIQKENP KVVNEINIED LCLTKAAYCR 100
    CWRSKTFPAC DGSHNKHNEL TGDNVGPLIL KKKEV 135
    Length:135
    Mass (Da):15,278
    Last modified:October 1, 2002 - v1
    Checksum:i44AD1817D6C536D6
    GO

    Sequence cautioni

    The sequence CAD97935.1 differs from that shown. Reason: Erroneous initiation.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AK292134 mRNA. Translation: BAF84823.1.
    BX537971 mRNA. Translation: CAD97935.1. Different initiation.
    CH471057 Genomic DNA. Translation: EAX06148.1.
    BC032300 mRNA. Translation: AAH32300.1.
    CCDSiCCDS34040.1.
    RefSeqiNP_001008389.1. NM_001008388.4.
    UniGeneiHs.444955.
    Hs.745013.

    Genome annotation databases

    EnsembliENST00000273986; ENSP00000273986; ENSG00000145354.
    GeneIDi493856.
    KEGGihsa:493856.
    UCSCiuc003hwt.4. human.

    Polymorphism databases

    DMDMi74729013.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AK292134 mRNA. Translation: BAF84823.1 .
    BX537971 mRNA. Translation: CAD97935.1 . Different initiation.
    CH471057 Genomic DNA. Translation: EAX06148.1 .
    BC032300 mRNA. Translation: AAH32300.1 .
    CCDSi CCDS34040.1.
    RefSeqi NP_001008389.1. NM_001008388.4.
    UniGenei Hs.444955.
    Hs.745013.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3FNV X-ray 2.10 A/B 57-135 [» ]
    ProteinModelPortali Q8N5K1.
    SMRi Q8N5K1. Positions 68-135.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 138922. 7 interactions.
    MINTi MINT-4722106.
    STRINGi 9606.ENSP00000273986.

    PTM databases

    PhosphoSitei Q8N5K1.

    Polymorphism databases

    DMDMi 74729013.

    Proteomic databases

    MaxQBi Q8N5K1.
    PaxDbi Q8N5K1.
    PeptideAtlasi Q8N5K1.
    PRIDEi Q8N5K1.

    Protocols and materials databases

    DNASUi 493856.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000273986 ; ENSP00000273986 ; ENSG00000145354 .
    GeneIDi 493856.
    KEGGi hsa:493856.
    UCSCi uc003hwt.4. human.

    Organism-specific databases

    CTDi 493856.
    GeneCardsi GC04P103790.
    HGNCi HGNC:24212. CISD2.
    HPAi HPA015914.
    MIMi 604928. phenotype.
    611507. gene.
    neXtProti NX_Q8N5K1.
    Orphaneti 3463. Wolfram syndrome.
    PharmGKBi PA162382300.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG236423.
    HOGENOMi HOG000242301.
    HOVERGENi HBG052444.
    InParanoidi Q8N5K1.
    OMAi LCLTKAY.
    OrthoDBi EOG7GQXZ6.
    PhylomeDBi Q8N5K1.
    TreeFami TF324661.

    Miscellaneous databases

    ChiTaRSi CISD2. human.
    EvolutionaryTracei Q8N5K1.
    GenomeRNAii 493856.
    NextBioi 111774.
    PROi Q8N5K1.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8N5K1.
    Bgeei Q8N5K1.
    CleanExi HS_CISD2.
    Genevestigatori Q8N5K1.

    Family and domain databases

    InterProi IPR018967. FeS-contain_CDGSH-typ.
    IPR006622. FeS-contain_CDGSH-typ_subfam.
    IPR019610. FeS-contain_mitoNEET_N.
    [Graphical view ]
    Pfami PF10660. MitoNEET_N. 1 hit.
    PF09360. zf-CDGSH. 1 hit.
    [Graphical view ]
    SMARTi SM00704. ZnF_CDGSH. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2."
      Amr S., Heisey C., Zhang M., Xia X.J., Shows K.H., Ajlouni K., Pandya A., Satin L.S., El-Shanti H., Shiang R.
      Am. J. Hum. Genet. 81:673-683(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INVOLVEMENT IN WFS2.
    2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Synovium.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Retina.
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "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].
      Tissue: Cervix.
    6. Bienvenut W.V.
      Submitted (JUN-2005) to UniProtKB
      Cited for: PROTEIN SEQUENCE OF 21-32; 82-95 AND 117-131, IDENTIFICATION BY MASS SPECTROMETRY.
      Tissue: B-cell lymphoma.
    7. "MitoNEET is an iron-containing outer mitochondrial membrane protein that regulates oxidative capacity."
      Wiley S.E., Murphy A.N., Ross S.A., van der Geer P., Dixon J.E.
      Proc. Natl. Acad. Sci. U.S.A. 104:5318-5323(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: COFACTOR, SUBCELLULAR LOCATION.
    8. "Antagonism of Beclin 1-dependent autophagy by BCL-2 at the endoplasmic reticulum requires NAF-1."
      Chang N.C., Nguyen M., Germain M., Shore G.C.
      EMBO J. 29:606-618(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH BCL2; BCL2L1 AND ITPR1, MUTAGENESIS OF CYS-99; CYS-101; CYS-110 AND HIS-114.
    9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    10. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    11. "Crystal structure of Miner1: The redox-active 2Fe-2S protein causative in Wolfram Syndrome 2."
      Conlan A.R., Axelrod H.L., Cohen A.E., Abresch E.C., Zuris J., Yee D., Nechushtai R., Jennings P.A., Paddock M.L.
      J. Mol. Biol. 392:143-153(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 57-135 OF MUTANT CYS-92 IN COMPLEX WITH 2FE-2S, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF CYS-92.

    Entry informationi

    Entry nameiCISD2_HUMAN
    AccessioniPrimary (citable) accession number: Q8N5K1
    Secondary accession number(s): Q7Z3D5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 15, 2008
    Last sequence update: October 1, 2002
    Last modified: October 1, 2014
    This is version 92 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Caution

    Although initially thought (PubMed:17846994) to be a zinc-finger protein, it was later shown (PubMed:17376863) that it binds 1 2Fe-2S cluster instead.2 Publications

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 4
      Human chromosome 4: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3