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Q8N5K1

- CISD2_HUMAN

UniProt

Q8N5K1 - CISD2_HUMAN

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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

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 homodimerization activity Source: UniProtKB

GO - Biological processi

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

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
Complete GO annotation...

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

BgeeiQ8N5K1.
CleanExiHS_CISD2.
ExpressionAtlasiQ8N5K1. baseline and differential.
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. 13 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[»]
4OO7X-ray1.65A/B68-135[»]
4OOAX-ray1.58A/B/C/D/E/F68-135[»]
ProteinModelPortaliQ8N5K1.
SMRiQ8N5K1. Positions 69-135.
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.
GeneTreeiENSGT00390000001233.
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

        10         20         30         40         50
MVLESVARIV KVQLPAYLKR LPVPESITGF ARLTVSEWLR LLPFLGVLAL
60 70 80 90 100
LGYLAVRPFL PKKKQQKDSL INLKIQKENP KVVNEINIED LCLTKAAYCR
110 120 130
CWRSKTFPAC DGSHNKHNEL TGDNVGPLIL KKKEV
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 [» ]
4OO7 X-ray 1.65 A/B 68-135 [» ]
4OOA X-ray 1.58 A/B/C/D/E/F 68-135 [» ]
ProteinModelPortali Q8N5K1.
SMRi Q8N5K1. Positions 69-135.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 138922. 13 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.
GeneTreei ENSGT00390000001233.
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

Bgeei Q8N5K1.
CleanExi HS_CISD2.
ExpressionAtlasi Q8N5K1. baseline and differential.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 93 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