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Protein

Iron-sulfur cluster assembly enzyme ISCU, mitochondrial

Gene

ISCU

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Scaffold protein for the de novo synthesis of iron-sulfur (Fe-S) clusters within mitochondria, which is required for maturation of both mitochondrial and cytoplasmic [2Fe-2S] and [4Fe-4S] proteins (PubMed:11060020). First, a [2Fe-2S] cluster is transiently assembled on the scaffold protein ISCU. In a second step, the cluster is released from ISCU, transferred to a glutaredoxin GLRX5, followed by the formation of mitochondrial [2Fe-2S] proteins, the synthesis of [4Fe-4S] clusters and their target-specific insertion into the recipient apoproteins. Cluster assembly on ISCU depends on the function of the cysteine desulfurase complex NFS1-LYRM4/ISD11, which serves as the sulfur donor for cluster synthesis, the iron-binding protein frataxin as the putative iron donor, and the electron transfer chain comprised of ferredoxin reductase and ferredoxin, which receive their electrons from NADH (By similarity).By similarity1 Publication

GO - Molecular functioni

  • 2 iron, 2 sulfur cluster binding Source: GO_Central
  • 4 iron, 4 sulfur cluster binding Source: GO_Central
  • ferrous iron binding Source: GO_Central
  • iron ion binding Source: UniProtKB
  • iron-sulfur transferase activity Source: GO_Central
  • protein complex scaffold Source: HGNC

GO - Biological processi

  • [2Fe-2S] cluster assembly Source: GO_Central
  • cellular iron ion homeostasis Source: GO_Central
  • iron-sulfur cluster assembly Source: UniProtKB
  • nitrogen fixation Source: UniProtKB
  • protein maturation by iron-sulfur cluster transfer Source: GO_Central
  • small molecule metabolic process Source: Reactome
Complete GO annotation...

Keywords - Ligandi

Iron, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000136003-MONOMER.
ReactomeiR-HSA-1362409. Mitochondrial iron-sulfur cluster biogenesis.
SIGNORiQ9H1K1.

Names & Taxonomyi

Protein namesi
Recommended name:
Iron-sulfur cluster assembly enzyme ISCU, mitochondrial
Alternative name(s):
NifU-like N-terminal domain-containing protein
NifU-like protein
Gene namesi
Name:ISCU
Synonyms:NIFUN
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:29882. ISCU.

Subcellular locationi

Isoform 1 :
  • Mitochondrion 1 Publication
Isoform 2 :
  • Cytoplasm
  • Nucleus 1 Publication

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: HGNC
  • mitochondrial matrix Source: GO_Central
  • mitochondrion Source: UniProtKB
  • nucleus Source: HGNC
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Nucleus

Pathology & Biotechi

Involvement in diseasei

Myopathy with exercise intolerance Swedish type (MEIS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAutosomal recessive metabolic disease characterized by lifelong severe exercise intolerance, in which minor exertion causes fatigue of active muscles, shortness of breath, and cardiac palpitations in association with lactic acidosis. The biochemical phenotype is characterized by a deficiency in mitochondrial iron-sulfur proteins and impaired muscle oxidative metabolism.
See also OMIM:255125

Organism-specific databases

DisGeNETi23479.
MalaCardsiISCU.
MIMi255125. phenotype.
OpenTargetsiENSG00000136003.
Orphaneti43115. Hereditary myopathy with lactic acidosis due to ISCU deficiency.
PharmGKBiPA162392328.

Polymorphism and mutation databases

BioMutaiISCU.
DMDMi313104118.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 34MitochondrionSequence analysisAdd BLAST34
ChainiPRO_000001969235 – 167Iron-sulfur cluster assembly enzyme ISCU, mitochondrialAdd BLAST133

Proteomic databases

EPDiQ9H1K1.
MaxQBiQ9H1K1.
PaxDbiQ9H1K1.
PeptideAtlasiQ9H1K1.
PRIDEiQ9H1K1.
TopDownProteomicsiQ9H1K1-1. [Q9H1K1-1]

PTM databases

iPTMnetiQ9H1K1.
PhosphoSitePlusiQ9H1K1.

Expressioni

Tissue specificityi

Detected in heart, liver, skeletal muscle, brain, pancreas, kidney, lung and placenta.2 Publications

Gene expression databases

BgeeiENSG00000136003.
CleanExiHS_ISCU.
ExpressionAtlasiQ9H1K1. baseline and differential.
GenevisibleiQ9H1K1. HS.

Organism-specific databases

HPAiCAB006329.
HPA038602.
HPA057592.

Interactioni

Subunit structurei

Binds NFS1 (PubMed:11060020). Interacts with HSCB (PubMed:20668094). Interacts with GLRX5 (PubMed:26100117).3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AGTRAPQ6RW133EBI-1047335,EBI-741181
BANPQ8N9N53EBI-1047335,EBI-744695
CCDC172P0C7W63EBI-1047335,EBI-2548868
FAM9BQ8IZU03EBI-1047335,EBI-10175124
GOLGA2Q083793EBI-1047335,EBI-618309
HPRT1P004923EBI-1047335,EBI-748210
IKZF1Q134223EBI-1047335,EBI-745305
KRT40Q6A1623EBI-1047335,EBI-10171697
LNX1Q8TBB13EBI-1047335,EBI-739832
MID2Q9UJV3-23EBI-1047335,EBI-10172526
NECAB2H3BTW23EBI-1047335,EBI-10172876
NUP62P371985EBI-1047335,EBI-347978

GO - Molecular functioni

  • protein complex scaffold Source: HGNC

Protein-protein interaction databases

BioGridi117038. 19 interactors.
IntActiQ9H1K1. 20 interactors.
MINTiMINT-3066312.
STRINGi9606.ENSP00000310623.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5KZ5electron microscopy14.30a/b/c/d/e/f/g/h/i/j/k/l50-167[»]
ProteinModelPortaliQ9H1K1.
SMRiQ9H1K1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the NifU family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG3361. Eukaryota.
COG0822. LUCA.
GeneTreeiENSGT00390000015813.
HOGENOMiHOG000069228.
HOVERGENiHBG052621.
InParanoidiQ9H1K1.
OMAiMDHFTNP.
OrthoDBiEOG091G0RA2.
PhylomeDBiQ9H1K1.
TreeFamiTF105422.

Family and domain databases

CDDicd06664. IscU_like. 1 hit.
InterProiIPR011339. ISC_FeS_clus_asmbl_IscU.
IPR002871. NIF_FeS_clus_asmbl_NifU_N.
[Graphical view]
PfamiPF01592. NifU_N. 1 hit.
[Graphical view]
TIGRFAMsiTIGR01999. iscU. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9H1K1-1) [UniParc]FASTAAdd to basket
Also known as: ISCU2

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAAAGAFRLR RAASALLLRS PRLPARELSA PARLYHKKVV DHYENPRNVG
60 70 80 90 100
SLDKTSKNVG TGLVGAPACG DVMKLQIQVD EKGKIVDARF KTFGCGSAIA
110 120 130 140 150
SSSLATEWVK GKTVEEALTI KNTDIAKELC LPPVKLHCSM LAEDAIKAAL
160
ADYKLKQEPK KGEAEKK
Length:167
Mass (Da):17,999
Last modified:November 30, 2010 - v2
Checksum:i0166D3EC9F1EEB47
GO
Isoform 2 (identifier: Q9H1K1-2) [UniParc]FASTAAdd to basket
Also known as: ISCU1

The sequence of this isoform differs from the canonical sequence as follows:
     1-38: MAAAGAFRLRRAASALLLRSPRLPARELSAPARLYHKK → MVLIDMSVDLSTQ

Show »
Length:142
Mass (Da):15,263
Checksum:iEE72CEDC86CD6FF0
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti7F → G in AAG37428 (PubMed:11060020).Curated1
Sequence conflicti7F → G in AAH11906 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06072812A → V.Combined sources2 PublicationsCorresponds to variant rs2287555dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0134921 – 38MAAAG…LYHKK → MVLIDMSVDLSTQ in isoform 2. 1 PublicationAdd BLAST38

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY009127 mRNA. Translation: AAG37427.1.
AY009128 mRNA. Translation: AAG37428.1.
AC008119 Genomic DNA. No translation available.
BC011906 mRNA. Translation: AAH11906.1.
BC061903 mRNA. Translation: AAH61903.1.
U47101 mRNA. Translation: AAC50885.1.
CCDSiCCDS44966.1. [Q9H1K1-1]
CCDS9118.1. [Q9H1K1-2]
RefSeqiNP_001306971.1. NM_001320042.1.
NP_055116.1. NM_014301.4. [Q9H1K1-2]
NP_998760.1. NM_213595.3. [Q9H1K1-1]
UniGeneiHs.615131.

Genome annotation databases

EnsembliENST00000311893; ENSP00000310623; ENSG00000136003. [Q9H1K1-1]
ENST00000392807; ENSP00000376554; ENSG00000136003. [Q9H1K1-2]
GeneIDi23479.
KEGGihsa:23479.
UCSCiuc001tnc.5. human. [Q9H1K1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY009127 mRNA. Translation: AAG37427.1.
AY009128 mRNA. Translation: AAG37428.1.
AC008119 Genomic DNA. No translation available.
BC011906 mRNA. Translation: AAH11906.1.
BC061903 mRNA. Translation: AAH61903.1.
U47101 mRNA. Translation: AAC50885.1.
CCDSiCCDS44966.1. [Q9H1K1-1]
CCDS9118.1. [Q9H1K1-2]
RefSeqiNP_001306971.1. NM_001320042.1.
NP_055116.1. NM_014301.4. [Q9H1K1-2]
NP_998760.1. NM_213595.3. [Q9H1K1-1]
UniGeneiHs.615131.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5KZ5electron microscopy14.30a/b/c/d/e/f/g/h/i/j/k/l50-167[»]
ProteinModelPortaliQ9H1K1.
SMRiQ9H1K1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117038. 19 interactors.
IntActiQ9H1K1. 20 interactors.
MINTiMINT-3066312.
STRINGi9606.ENSP00000310623.

PTM databases

iPTMnetiQ9H1K1.
PhosphoSitePlusiQ9H1K1.

Polymorphism and mutation databases

BioMutaiISCU.
DMDMi313104118.

Proteomic databases

EPDiQ9H1K1.
MaxQBiQ9H1K1.
PaxDbiQ9H1K1.
PeptideAtlasiQ9H1K1.
PRIDEiQ9H1K1.
TopDownProteomicsiQ9H1K1-1. [Q9H1K1-1]

Protocols and materials databases

DNASUi23479.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000311893; ENSP00000310623; ENSG00000136003. [Q9H1K1-1]
ENST00000392807; ENSP00000376554; ENSG00000136003. [Q9H1K1-2]
GeneIDi23479.
KEGGihsa:23479.
UCSCiuc001tnc.5. human. [Q9H1K1-1]

Organism-specific databases

CTDi23479.
DisGeNETi23479.
GeneCardsiISCU.
GeneReviewsiISCU.
HGNCiHGNC:29882. ISCU.
HPAiCAB006329.
HPA038602.
HPA057592.
MalaCardsiISCU.
MIMi255125. phenotype.
611911. gene.
neXtProtiNX_Q9H1K1.
OpenTargetsiENSG00000136003.
Orphaneti43115. Hereditary myopathy with lactic acidosis due to ISCU deficiency.
PharmGKBiPA162392328.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3361. Eukaryota.
COG0822. LUCA.
GeneTreeiENSGT00390000015813.
HOGENOMiHOG000069228.
HOVERGENiHBG052621.
InParanoidiQ9H1K1.
OMAiMDHFTNP.
OrthoDBiEOG091G0RA2.
PhylomeDBiQ9H1K1.
TreeFamiTF105422.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000136003-MONOMER.
ReactomeiR-HSA-1362409. Mitochondrial iron-sulfur cluster biogenesis.
SIGNORiQ9H1K1.

Miscellaneous databases

ChiTaRSiISCU. human.
GeneWikiiISCU.
GenomeRNAii23479.
PROiQ9H1K1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000136003.
CleanExiHS_ISCU.
ExpressionAtlasiQ9H1K1. baseline and differential.
GenevisibleiQ9H1K1. HS.

Family and domain databases

CDDicd06664. IscU_like. 1 hit.
InterProiIPR011339. ISC_FeS_clus_asmbl_IscU.
IPR002871. NIF_FeS_clus_asmbl_NifU_N.
[Graphical view]
PfamiPF01592. NifU_N. 1 hit.
[Graphical view]
TIGRFAMsiTIGR01999. iscU. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiISCU_HUMAN
AccessioniPrimary (citable) accession number: Q9H1K1
Secondary accession number(s): Q6P713, Q99617, Q9H1K2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 26, 2005
Last sequence update: November 30, 2010
Last modified: November 30, 2016
This is version 138 of the entry and version 2 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.