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Q8N5K1 (CISD2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 88. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:CISD2
Synonyms:CDGSH2, ERIS, ZCD2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length135 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.8

Cofactor

Binds 1 2Fe-2S cluster. Ref.7

Subunit structure

Homodimer. Interacts with BCL2; the interaction is direct and disrupted by BIK interaction with BCL2. Interacts with BCL2L1. Interacts with ITPR1. Ref.8

Subcellular location

Endoplasmic reticulum membrane; Single-pass membrane protein. Mitochondrion outer membrane; Single-pass membrane protein. Note: According to Ref.8, it mainly localizes to the endoplasmic reticulum. However, experiments in mouse showed that it mainly localizes to the mitochondrion outer membrane. Ref.1 Ref.7 Ref.8

Tissue specificity

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

Involvement in disease

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1

Sequence similarities

Belongs to the CISD protein family. CISD2 subfamily.

Caution

Although initially thought (Ref.1) to be a zinc-finger protein, it was later shown (Ref.7) that it binds 1 2Fe-2S cluster instead.

Biophysicochemical properties

Redox potential:

E is 0 +/- 10 mV for 2Fe-2S at pH 7.5. Ref.11

Sequence caution

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 135135CDGSH iron-sulfur domain-containing protein 2
PRO_0000316005

Regions

Topological domain1 – 3737Lumenal Potential
Transmembrane38 – 6023Helical; Potential
Topological domain61 – 13575Cytoplasmic Potential

Sites

Metal binding991Iron-sulfur (2Fe-2S)
Metal binding1011Iron-sulfur (2Fe-2S)
Metal binding1101Iron-sulfur (2Fe-2S)
Metal binding1141Iron-sulfur (2Fe-2S); via pros nitrogen

Experimental info

Mutagenesis921C → S: Has the same optical signature of the native protein and improves yields of purified protein and a decreased tendency to aggregate. Ref.11
Mutagenesis991C → S: Impairs interaction with BCL2; when associated with S-101; S-110 and Q-114. Ref.8
Mutagenesis1011C → S: Impairs interaction with BCL2; when associated with S-99; S-110 and Q-114. Ref.8
Mutagenesis1101C → S: Impairs interaction with BCL2; when associated with S-99; S-101 and Q-114. Ref.8
Mutagenesis1141H → Q: Impairs interaction with BCL2; when associated with S-99; S-101 and S-110. Ref.8

Secondary structure

................ 135
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q8N5K1 [UniParc].

Last modified October 1, 2002. Version 1.
Checksum: 44AD1817D6C536D6

FASTA13515,278
        10         20         30         40         50         60 
MVLESVARIV KVQLPAYLKR LPVPESITGF ARLTVSEWLR LLPFLGVLAL LGYLAVRPFL 

        70         80         90        100        110        120 
PKKKQQKDSL INLKIQKENP KVVNEINIED LCLTKAAYCR CWRSKTFPAC DGSHNKHNEL 

       130 
TGDNVGPLIL KKKEV 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Retina.
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK292134 mRNA. Translation: BAF84823.1.
BX537971 mRNA. Translation: CAD97935.1. Different initiation.
CH471057 Genomic DNA. Translation: EAX06148.1.
BC032300 mRNA. Translation: AAH32300.1.
RefSeqNP_001008389.1. NM_001008388.4.
UniGeneHs.444955.
Hs.745013.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3FNVX-ray2.10A/B57-135[»]
ProteinModelPortalQ8N5K1.
SMRQ8N5K1. Positions 68-135.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid138922. 7 interactions.
MINTMINT-4722106.
STRING9606.ENSP00000273986.

PTM databases

PhosphoSiteQ8N5K1.

Polymorphism databases

DMDM74729013.

Proteomic databases

PaxDbQ8N5K1.
PeptideAtlasQ8N5K1.
PRIDEQ8N5K1.

Protocols and materials databases

DNASU493856.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000273986; ENSP00000273986; ENSG00000145354.
GeneID493856.
KEGGhsa:493856.
UCSCuc003hwt.4. human.

Organism-specific databases

CTD493856.
GeneCardsGC04P103790.
HGNCHGNC:24212. CISD2.
HPAHPA015914.
MIM604928. phenotype.
611507. gene.
neXtProtNX_Q8N5K1.
Orphanet3463. Wolfram syndrome.
PharmGKBPA162382300.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG236423.
HOGENOMHOG000242301.
HOVERGENHBG052444.
InParanoidQ8N5K1.
OMAPVCDKSH.
OrthoDBEOG7GQXZ6.
PhylomeDBQ8N5K1.
TreeFamTF324661.

Gene expression databases

ArrayExpressQ8N5K1.
BgeeQ8N5K1.
CleanExHS_CISD2.
GenevestigatorQ8N5K1.

Family and domain databases

InterProIPR018967. FeS-contain_CDGSH-typ.
IPR006622. FeS-contain_CDGSH-typ_subfam.
IPR019610. FeS-contain_mitoNEET_N.
[Graphical view]
PfamPF10660. MitoNEET_N. 1 hit.
PF09360. zf-CDGSH. 1 hit.
[Graphical view]
SMARTSM00704. ZnF_CDGSH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCISD2. human.
EvolutionaryTraceQ8N5K1.
GenomeRNAi493856.
NextBio111774.
PROQ8N5K1.
SOURCESearch...

Entry information

Entry nameCISD2_HUMAN
AccessionPrimary (citable) accession number: Q8N5K1
Secondary accession number(s): Q7Z3D5
Entry history
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: October 1, 2002
Last modified: April 16, 2014
This is version 88 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM