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Protein

CDGSH iron-sulfur domain-containing protein 2

Gene

CISD2

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

[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)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

  • 2 iron, 2 sulfur cluster binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • poly(A) RNA binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

  • mitophagy Source: Ensembl
  • multicellular organism aging Source: UniProtKB
  • 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
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:24212. CISD2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini2 – 3736LumenalSequence analysisAdd
BLAST
Transmembranei38 – 6023HelicalSequence analysisAdd
BLAST
Topological domaini61 – 13575CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • endoplasmic reticulum Source: HPA
  • endoplasmic reticulum membrane Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: UniProtKB
  • mitochondrial outer membrane Source: UniProtKB
  • 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)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)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

MalaCardsiCISD2.
MIMi604928. phenotype.
Orphaneti3463. Wolfram syndrome.
PharmGKBiPA162382300.

Polymorphism and mutation databases

BioMutaiCISD2.
DMDMi74729013.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedCombined sources
Chaini2 – 135134CDGSH iron-sulfur domain-containing protein 2PRO_0000316005Add
BLAST

Proteomic databases

EPDiQ8N5K1.
MaxQBiQ8N5K1.
PaxDbiQ8N5K1.
PeptideAtlasiQ8N5K1.
PRIDEiQ8N5K1.
TopDownProteomicsiQ8N5K1.

PTM databases

iPTMnetiQ8N5K1.
PhosphoSiteiQ8N5K1.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000145354.
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 homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi138922. 34 interactions.
IntActiQ8N5K1. 3 interactions.
MINTiMINT-4722106.
STRINGi9606.ENSP00000273986.

Structurei

Secondary structure

1
135
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni75 – 784Combined sources
Beta strandi79 – 879Combined sources
Helixi88 – 903Combined sources
Beta strandi93 – 986Combined sources
Beta strandi100 – 1023Combined sources
Turni105 – 1084Combined sources
Helixi113 – 1219Combined sources
Beta strandi128 – 1314Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.

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.
OMAiHGEHNKL.
PhylomeDBiQ8N5K1.
TreeFamiTF324661.

Family and domain databases

InterProiIPR018967. FeS-contain_CDGSH-typ.
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.

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

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 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.

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
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...

Protein-protein interaction databases

BioGridi138922. 34 interactions.
IntActiQ8N5K1. 3 interactions.
MINTiMINT-4722106.
STRINGi9606.ENSP00000273986.

PTM databases

iPTMnetiQ8N5K1.
PhosphoSiteiQ8N5K1.

Polymorphism and mutation databases

BioMutaiCISD2.
DMDMi74729013.

Proteomic databases

EPDiQ8N5K1.
MaxQBiQ8N5K1.
PaxDbiQ8N5K1.
PeptideAtlasiQ8N5K1.
PRIDEiQ8N5K1.
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.
GeneCardsiCISD2.
HGNCiHGNC:24212. CISD2.
HPAiHPA015914.
MalaCardsiCISD2.
MIMi604928. phenotype.
611507. gene.
neXtProtiNX_Q8N5K1.
Orphaneti3463. Wolfram syndrome.
PharmGKBiPA162382300.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3461. Eukaryota.
ENOG41122II. LUCA.
GeneTreeiENSGT00390000001233.
HOGENOMiHOG000242301.
HOVERGENiHBG052444.
InParanoidiQ8N5K1.
OMAiHGEHNKL.
PhylomeDBiQ8N5K1.
TreeFamiTF324661.

Miscellaneous databases

ChiTaRSiCISD2. human.
EvolutionaryTraceiQ8N5K1.
GenomeRNAii493856.
PROiQ8N5K1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000145354.
CleanExiHS_CISD2.
ExpressionAtlasiQ8N5K1. baseline and differential.
GenevisibleiQ8N5K1. HS.

Family and domain databases

InterProiIPR018967. FeS-contain_CDGSH-typ.
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]
ProtoNetiSearch...

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: September 7, 2016
This is version 110 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.