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Protein

CDGSH iron-sulfur domain-containing protein 2

Gene

CISD2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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

Cofactori

[2Fe-2S] cluster1 PublicationNote: 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)DescriptionActionsGraphical viewLength
Metal bindingi99Iron-sulfur (2Fe-2S)1
Metal bindingi101Iron-sulfur (2Fe-2S)1
Metal bindingi110Iron-sulfur (2Fe-2S)1
Metal bindingi114Iron-sulfur (2Fe-2S); via pros nitrogen1

GO - Molecular functioni

GO - Biological processi

  • autophagy of mitochondrion Source: Ensembl
  • multicellular organism aging Source: UniProtKB
  • regulation of autophagy Source: UniProtKB

Keywordsi

Biological processAutophagy
Ligand2Fe-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
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000145354.9
HGNCiHGNC:24212 CISD2
MIMi611507 gene
neXtProtiNX_Q8N5K1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini2 – 37LumenalSequence analysisAdd BLAST36
Transmembranei38 – 60HelicalSequence analysisAdd BLAST23
Topological domaini61 – 135CytoplasmicSequence analysisAdd BLAST75

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Involvement in diseasei

Wolfram syndrome 2 (WFS2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:604928

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi92C → S: Has the same optical signature of the native protein and improves yields of purified protein and a decreased tendency to aggregate. 1 Publication1
Mutagenesisi99C → S: Impairs interaction with BCL2; when associated with S-101; S-110 and Q-114. 1 Publication1
Mutagenesisi101C → S: Impairs interaction with BCL2; when associated with S-99; S-110 and Q-114. 1 Publication1
Mutagenesisi110C → S: Impairs interaction with BCL2; when associated with S-99; S-101 and Q-114. 1 Publication1
Mutagenesisi114H → Q: Impairs interaction with BCL2; when associated with S-99; S-101 and S-110. 1 Publication1

Keywords - Diseasei

Deafness, Diabetes mellitus

Organism-specific databases

DisGeNETi493856
MalaCardsiCISD2
MIMi604928 phenotype
OpenTargetsiENSG00000145354
Orphaneti3463 Wolfram syndrome
PharmGKBiPA162382300

Polymorphism and mutation databases

BioMutaiCISD2
DMDMi74729013

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00003160052 – 135CDGSH iron-sulfur domain-containing protein 2Add BLAST134

Proteomic databases

EPDiQ8N5K1
MaxQBiQ8N5K1
PaxDbiQ8N5K1
PeptideAtlasiQ8N5K1
PRIDEiQ8N5K1
ProteomicsDBi72071
TopDownProteomicsiQ8N5K1

PTM databases

iPTMnetiQ8N5K1
PhosphoSitePlusiQ8N5K1

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000145354 Expressed in 205 organ(s), highest expression level in pancreas
CleanExiHS_CISD2
ExpressionAtlasiQ8N5K1 baseline and differential
GenevisibleiQ8N5K1 HS

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi138922, 43 interactors
IntActiQ8N5K1, 53 interactors
STRINGi9606.ENSP00000273986

Structurei

Secondary structure

1135
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ8N5K1
SMRiQ8N5K1
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8N5K1

Family & Domainsi

Sequence similaritiesi

Belongs to the CISD protein family. CISD2 subfamily.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3461 Eukaryota
ENOG41122II LUCA
GeneTreeiENSGT00390000001233
HOGENOMiHOG000242301
HOVERGENiHBG052444
InParanoidiQ8N5K1
OMAiTGYLAFC
PhylomeDBiQ8N5K1
TreeFamiTF324661

Family and domain databases

InterProiView protein in InterPro
IPR018967 FeS-contain_CDGSH-typ
IPR019610 FeS-contain_mitoNEET_N
PfamiView protein in Pfam
PF10660 MitoNEET_N, 1 hit
PF09360 zf-CDGSH, 1 hit
SMARTiView protein in SMART
SM00704 ZnF_CDGSH, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RCF4D6RCF4_HUMAN
CDGSH iron-sulfur domain-containing...
CISD2
145Annotation score:
I3L1N9I3L1N9_HUMAN
CDGSH iron-sulfur domain-containing...
CISD2
47Annotation score:
A0A2R8Y540A0A2R8Y540_HUMAN
CDGSH iron-sulfur domain-containing...
CISD2
40Annotation score:
A0A2R8Y4Y3A0A2R8Y4Y3_HUMAN
CDGSH iron-sulfur domain-containing...
CISD2
50Annotation score:

Sequence cautioni

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

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.5 human

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3FNVX-ray2.10A/B57-135[»]
4OO7X-ray1.65A/B68-135[»]
4OOAX-ray1.58A/B/C/D/E/F68-135[»]
ProteinModelPortaliQ8N5K1
SMRiQ8N5K1
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi138922, 43 interactors
IntActiQ8N5K1, 53 interactors
STRINGi9606.ENSP00000273986

PTM databases

iPTMnetiQ8N5K1
PhosphoSitePlusiQ8N5K1

Polymorphism and mutation databases

BioMutaiCISD2
DMDMi74729013

Proteomic databases

EPDiQ8N5K1
MaxQBiQ8N5K1
PaxDbiQ8N5K1
PeptideAtlasiQ8N5K1
PRIDEiQ8N5K1
ProteomicsDBi72071
TopDownProteomicsiQ8N5K1

Protocols and materials databases

DNASUi493856
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000273986; ENSP00000273986; ENSG00000145354
GeneIDi493856
KEGGihsa:493856
UCSCiuc003hwt.5 human

Organism-specific databases

CTDi493856
DisGeNETi493856
EuPathDBiHostDB:ENSG00000145354.9
GeneCardsiCISD2
HGNCiHGNC:24212 CISD2
HPAiHPA015914
MalaCardsiCISD2
MIMi604928 phenotype
611507 gene
neXtProtiNX_Q8N5K1
OpenTargetsiENSG00000145354
Orphaneti3463 Wolfram syndrome
PharmGKBiPA162382300
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3461 Eukaryota
ENOG41122II LUCA
GeneTreeiENSGT00390000001233
HOGENOMiHOG000242301
HOVERGENiHBG052444
InParanoidiQ8N5K1
OMAiTGYLAFC
PhylomeDBiQ8N5K1
TreeFamiTF324661

Miscellaneous databases

ChiTaRSiCISD2 human
EvolutionaryTraceiQ8N5K1
GenomeRNAii493856
PROiPR:Q8N5K1
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000145354 Expressed in 205 organ(s), highest expression level in pancreas
CleanExiHS_CISD2
ExpressionAtlasiQ8N5K1 baseline and differential
GenevisibleiQ8N5K1 HS

Family and domain databases

InterProiView protein in InterPro
IPR018967 FeS-contain_CDGSH-typ
IPR019610 FeS-contain_mitoNEET_N
PfamiView protein in Pfam
PF10660 MitoNEET_N, 1 hit
PF09360 zf-CDGSH, 1 hit
SMARTiView protein in SMART
SM00704 ZnF_CDGSH, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCISD2_HUMAN
AccessioniPrimary (citable) accession number: Q8N5K1
Secondary accession number(s): Q7Z3D5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: October 1, 2002
Last modified: October 10, 2018
This is version 126 of the entry and version 1 of the sequence. See 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

Keywords - Technical termi

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

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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