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Protein

Iron-sulfur cluster assembly enzyme ISCU, mitochondrial

Gene

ISCU

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

GO - Biological processi

Keywordsi

LigandIron, Metal-binding

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000136003.15
HGNCiHGNC:29882 ISCU
MIMi611911 gene
neXtProtiNX_Q9H1K1

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

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
GeneReviewsiISCU
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). Interacts with HSPA9 (PubMed:26702583).4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • protein-containing complex scaffold activity Source: HGNC

Protein-protein interaction databases

BioGridi117038, 20 interactors
DIPiDIP-39616N
IntActiQ9H1K1, 26 interactors
MINTiQ9H1K1
STRINGi9606.ENSP00000310623

Structurei

Secondary structure

1167
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni41 – 44Combined sources4
Beta strandi47 – 50Combined sources4
Beta strandi54 – 65Combined sources12
Turni67 – 69Combined sources3
Beta strandi72 – 79Combined sources8
Beta strandi83 – 94Combined sources12
Helixi96 – 108Combined sources13
Turni109 – 111Combined sources3
Helixi114 – 118Combined sources5
Helixi122 – 129Combined sources8
Turni134 – 136Combined sources3
Helixi137 – 156Combined sources20

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[»]
5WKPX-ray3.15D/H38-167[»]
5WLWX-ray3.32D/H38-167[»]
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
KOiK22068
OMAiSMVTEMV
OrthoDBiEOG091G0RA2
PhylomeDBiQ9H1K1
TreeFamiTF105422

Family and domain databases

CDDicd06664 IscU_like, 1 hit
InterProiView protein in InterPro
IPR011339 ISC_FeS_clus_asmbl_IscU
IPR002871 NIF_FeS_clus_asmbl_NifU_N
PANTHERiPTHR10093 PTHR10093, 1 hit
PfamiView protein in Pfam
PF01592 NifU_N, 1 hit
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 → VCombined sources2 PublicationsCorresponds to variant dbSNP:rs2287555Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiISCU_HUMAN
AccessioniPrimary (citable) accession number: Q9H1K1
Secondary accession number(s): Q6P713, Q99617, Q9H1K2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 26, 2005
Last sequence update: November 30, 2010
Last modified: May 23, 2018
This is version 150 of the entry and version 2 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, Reference proteome

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