Q9NZ45 (CISD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
CDGSH iron-sulfur domain-containing protein 1

Alternative name(s):
MitoNEET

Gene names

Name:	CISD1
Synonyms:	C10orf70, ZCD1
ORF Names:	MDS029

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	108 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays a key role in regulating maximal capacity for electron transport and oxidative phosphorylation By similarity. May be involved in Fe-S cluster shuttling and/or in redox reactions. Ref.6 Ref.11
Cofactor	Binds 1 2Fe-2S cluster per subunit. The 2Fe-2S cluster is redox-active and pH labile and is significantly less stable at pH 4.5 as compared with pH 7.0. Ref.6 Ref.7 Ref.10 Ref.11 Ref.12
Subunit structure	Homodimer. Ref.10 Ref.11 Ref.12
Subcellular location	Mitochondrion outer membrane; Single-pass type III membrane protein Ref.1 Ref.7 Ref.10 Ref.12.
Tissue specificity	Expression is reduced in cells derived from cystic fibrosis patients. Ref.1
Induction	Expression is down-regulated by glibenclamide and 5-[(4-carboxyphenyl)methylene]-2-thioxo-3-(3-trifluoromethyl)phenyl-4-thiazolidinone (CFTR(inh)172), and up-regulated by cAMP/isoproterenol/IBMX, components that inhibit and stimulate chloride transport activity respectively. Ref.1
Miscellaneous	Binds pioglitazone, an anti-diabetes drug. Binding increases the stability of the 2Fe-2S cluster.
Sequence similarities	Belongs to the CISD protein family.
Biophysicochemical properties	Redox potential: E is 0 +/- 10 mV for 2Fe-2S at pH 7.5. Ref.8

Ontologies

Keywords
Cellular component	Membrane Mitochondrion Mitochondrion outer membrane
Domain	Signal-anchor Transmembrane Transmembrane helix
Ligand	2Fe-2S Iron Iron-sulfur Metal-binding
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	regulation of cellular respiration Inferred from electronic annotation. Source: Compara
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial outer membrane Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	2 iron, 2 sulfur cluster binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 108

108

CDGSH iron-sulfur domain-containing protein 1

PRO_0000089803

Regions

Transmembrane

14 – 31

18

Helical; Signal-anchor for type III membrane protein; Potential

Topological domain

32 – 108

77

Cytoplasmic Potential

Sites

Metal binding

72

1

Iron-sulfur (2Fe-2S)

Metal binding

74

1

Iron-sulfur (2Fe-2S)

Metal binding

83

1

Iron-sulfur (2Fe-2S)

Metal binding

87

1

Iron-sulfur (2Fe-2S); via pros nitrogen

Amino acid modifications

Modified residue

104

1

N6-acetyllysine By similarity

Experimental info

Mutagenesis

72

1

C → S: Abolishes absorption in the 300-500 nm range. Ref.6

Mutagenesis

74

1

C → S: Abolishes absorption in the 300-500 nm range. Ref.6

Mutagenesis

83

1

C → S: Abolishes absorption in the 300-500 nm range. Ref.6

Mutagenesis

84

1

D → N: Does not affect absorption in the 300-500 nm range. Ref.6

Mutagenesis

87

1

H → C: Affects absorption in the 300-500 nm range but it is not reduced. Increased stability of the 2Fe-2S cluster at low pH. Ref.6

Mutagenesis

87

1

H → Q: Abolishes absorption in the 300-500 nm range. Ref.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

108

Helix Strand Turn

Details...

Beta strand

47 – 49

3

Beta strand

53 – 66

14

Beta strand

68 – 71

4

Beta strand

73 – 75

3

Turn

78 – 81

4

Helix

86 – 94

9

Beta strand

98 – 104

7

Sequences

	Sequence		Length	Mass (Da)
	Q9NZ45 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 2E47000F0635CBB7	FASTA	108	12,199
	10 20 30 40 50 60 MSLTSSSSVR VEWIAAVTIA AGTAAIGYLA YKRFYVKDHR NKAMINLHIQ KDNPKIVHAF 70 80 90 100 DMEDLGDKAV YCRCWRSKKF PFCDGAHTKH NEETGDNVGP LIIKKKET

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"CISD1 codifies a mitochondrial protein upregulated by the CFTR channel." Taminelli G.L., Sotomayor V., Valdivieso A.G., Teiber M.L., Marin M.C., Santa-Coloma T.A. Biochem. Biophys. Res. Commun. 365:856-862(2008) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION.
[2]	"Novel genes expressed in hematopoietic stem/progenitor cells from myelodysplastic syndrome patients." Zhao M., Gu J., Li N., Peng Y., Han Z., Chen Z. Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Hematopoietic stem cell.
[3]	"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: Spleen.
[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. , 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: Bone marrow, Brain and Lung.
[6]	"The outer mitochondrial membrane protein mitoNEET contains a novel redox-active 2Fe-2S cluster." Wiley S.E., Paddock M.L., Abresch E.C., Gross L., van der Geer P., Nechushtai R., Murphy A.N., Jennings P.A., Dixon J.E. J. Biol. Chem. 282:23745-23749(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, COFACTOR, MUTAGENESIS OF CYS-72; CYS-74; CYS-83; ASP-84 AND HIS-87.
[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: SUBCELLULAR LOCATION, COFACTOR.
[8]	"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: BIOPHYSICOCHEMICAL PROPERTIES.
[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]	"Crystallographic studies of human MitoNEET." Hou X., Liu R., Ross S., Smart E.J., Zhu H., Gong W. J. Biol. Chem. 282:33242-33246(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 33-108, COFACTOR, SUBUNIT, SUBCELLULAR LOCATION.
[11]	"MitoNEET is a uniquely folded 2Fe 2S outer mitochondrial membrane protein stabilized by pioglitazone." Paddock M.L., Wiley S.E., Axelrod H.L., Cohen A.E., Roy M., Abresch E.C., Capraro D., Murphy A.N., Nechushtai R., Dixon J.E., Jennings P.A. Proc. Natl. Acad. Sci. U.S.A. 104:14342-14347(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 33-108, FUNCTION, COFACTOR, SUBUNIT.
[12]	"Crystal structure of human mitoNEET reveals distinct groups of iron sulfur proteins." Lin J., Zhou T., Ye K., Wang J. Proc. Natl. Acad. Sci. U.S.A. 104:14640-14645(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.81 ANGSTROMS) OF 32-108, COFACTOR, SUBUNIT, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY960578 mRNA. Translation: AAY32336.1.
AF220049 mRNA. Translation: AAF67642.1.
AK312017 mRNA. Translation: BAG34955.1.
CH471083 Genomic DNA. Translation: EAW54163.1.
BC005962 mRNA. Translation: AAH05962.1.
BC007043 mRNA. Translation: AAH07043.1.
BC008474 mRNA. Translation: AAH08474.1.
BC059168 mRNA. Translation: AAH59168.1.

IPI

IPI00020510.

RefSeq

NP_060934.1. NM_018464.4.

UniGene

Hs.370102.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2QD0	X-ray	1.81	A/B	32-108	[»]
2QH7	X-ray	1.50	A/B	33-108	[»]
2R13	X-ray	1.80	A	33-108	[»]
3EW0	X-ray	1.40	A/B	33-108	[»]
3LPQ	X-ray	1.70	A/B	33-107	[»]
3REE	X-ray	1.76	A	32-108	[»]
4EZF	X-ray	1.19	A/B	33-108	[»]
4F1E	X-ray	2.40	A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R	33-108	[»]
4F28	X-ray	1.55	A/B	33-108	[»]
4F2C	X-ray	1.35	A/B	33-108	[»]

ProteinModelPortal

Q9NZ45.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-46446N.

IntAct

Q9NZ45. 2 interactions.

STRING

9606.ENSP00000363041.

PTM databases

PhosphoSite

Q9NZ45.

Polymorphism databases

DMDM

25453105.

Proteomic databases

PaxDb

Q9NZ45.

PeptideAtlas

Q9NZ45.

PRIDE

Q9NZ45.

Protocols and materials databases

DNASU

55847.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000333926; ENSP00000363041; ENSG00000122873.

GeneID

55847.

KEGG

hsa:55847.

UCSC

uc001jkc.4. human.

Organism-specific databases

CTD

55847.

GeneCards

GC10P060028.

H-InvDB

HIX0201471.

HGNC

HGNC:30880. CISD1.

HPA

CAB045965.

MIM

611932. gene.

neXtProt

NX_Q9NZ45.

PharmGKB

PA162382289.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG236423.

HOGENOM

HOG000242301.

HOVERGEN

HBG052444.

InParanoid

Q9NZ45.

OMA

MVNLHIQ.

OrthoDB

EOG4001KW.

PhylomeDB

Q9NZ45.

Gene expression databases

Bgee

Q9NZ45.

CleanEx

HS_CISD1.

Genevestigator

Q9NZ45.

GermOnline

ENSG00000122873. Homo sapiens.

Family and domain databases

InterPro

IPR018967. FeS-contain_CDGSH-typ.
IPR006622. FeS-contain_CDGSH-typ_subfam.
IPR019610. FeS-contain_mitoNEET_N.
[Graphical view]

Pfam

PF10660. MitoNEET_N. 1 hit.
PF09360. zf-CDGSH. 1 hit.
[Graphical view]

SMART

SM00704. ZnF_CDGSH. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q9NZ45.

ChEMBL

CHEMBL1795168.

ChiTaRS

CISD1. human.

EvolutionaryTrace

Q9NZ45.

GenomeRNAi

55847.

NextBio

61099.

SOURCE

Search...

Entry information

Entry name

CISD1_HUMAN

Accession

Primary (citable) accession number: Q9NZ45
Secondary accession number(s): Q1X902

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 25, 2002
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 105 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.