Q9H1K1 (ISCU_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Iron-sulfur cluster assembly enzyme ISCU, mitochondrial

Alternative name(s):
NifU-like N-terminal domain-containing protein
NifU-like protein

Gene names

Name:	ISCU
Synonyms:	NIFUN

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	167 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in the assembly or repair of the [Fe-S] clusters present in iron-sulfur proteins. Binds iron. Ref.1
Subunit structure	Binds NFS1. Interacts with HSCB. Ref.1 Ref.6
Subcellular location	Isoform 1: Mitochondrion Ref.1. Isoform 2: Cytoplasm. Nucleus Ref.1.
Tissue specificity	Detected in heart, liver, skeletal muscle, brain, pancreas, kidney, lung and placenta. Ref.1 Ref.4
Involvement in disease	Myopathy with exercise intolerance Swedish type (MEIS) [MIM:255125]: Autosomal 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5
Sequence similarities	Belongs to the NifU family.

Ontologies

Keywords
Cellular component	Cytoplasm Mitochondrion Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transit peptide
Ligand	Iron Metal-binding
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	iron-sulfur cluster assembly Traceable author statement Ref.1. Source: UniProtKB nitrogen fixation Traceable author statement Ref.4. Source: UniProtKB
Cellular_component	cytosol Inferred from direct assay PubMed 16527810. Source: HGNC mitochondrion Inferred from direct assay Ref.1. Source: UniProtKB nucleus Traceable author statement PubMed 16527810. Source: HGNC
Molecular_function	iron ion binding Traceable author statement Ref.1. Source: UniProtKB iron-sulfur cluster binding Inferred from electronic annotation. Source: InterPro protein complex scaffold Inferred from direct assay PubMed 16527810. Source: HGNC
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9H1K1-1)

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.

Isoform 2 (identifier: Q9H1K1-2)

Also known as: ISCU1;

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 34	34	Mitochondrion Potential
	Chain	35 – 167	133	Iron-sulfur cluster assembly enzyme ISCU, mitochondrial		PRO_0000019692
Amino acid modifications
	Modified residue	14	1	Phosphoserine Ref.7
Natural variations
	Alternative sequence	1 – 38	38	MAAAG…LYHKK → MVLIDMSVDLSTQ in isoform 2.		VSP_013492
	Natural variant	12	1	A → V. Ref.1 Ref.3 Ref.7 Ref.9 Corresponds to variant rs2287555 [ dbSNP | Ensembl ].		VAR_060728
Experimental info
	Sequence conflict	7	1	F → G in AAG37428. Ref.1
	Sequence conflict	7	1	F → G in AAH11906. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (ISCU2) [UniParc]. Last modified November 30, 2010. Version 2. Checksum: 0166D3EC9F1EEB47	FASTA	167	17,999
	10 20 30 40 50 60 MAAAGAFRLR RAASALLLRS PRLPARELSA PARLYHKKVV DHYENPRNVG SLDKTSKNVG 70 80 90 100 110 120 TGLVGAPACG DVMKLQIQVD EKGKIVDARF KTFGCGSAIA SSSLATEWVK GKTVEEALTI 130 140 150 160 KNTDIAKELC LPPVKLHCSM LAEDAIKAAL ADYKLKQEPK KGEAEKK
	Isoform 2 (ISCU1) [UniParc]. Checksum: EE72CEDC86CD6FF0	FASTA	142	15,263
	10 20 30 40 50 60 MVLIDMSVDL STQVVDHYEN PRNVGSLDKT SKNVGTGLVG APACGDVMKL QIQVDEKGKI 70 80 90 100 110 120 VDARFKTFGC GSAIASSSLA TEWVKGKTVE EALTIKNTDI AKELCLPPVK LHCSMLAEDA 130 140 IKAALADYKL KQEPKKGEAE KK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Distinct iron-sulfur cluster assembly complexes exist in the cytosol and mitochondria of human cells." Tong W.-H., Rouault T. EMBO J. 19:5692-5700(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH NFS1, TISSUE SPECIFICITY, VARIANT VAL-12.
[2]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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] (ISOFORM 1), VARIANT VAL-12. Tissue: Brain.
[4]	"A modular domain of NifU, a nitrogen fixation cluster protein, is highly conserved in evolution." Hwang D.M., Dempsey A., Tan K.-T., Liew C.-C. J. Mol. Evol. 43:536-540(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 47-167, TISSUE SPECIFICITY. Tissue: Heart.
[5]	"Splice mutation in the iron-sulfur cluster scaffold protein ISCU causes myopathy with exercise intolerance." Mochel F., Knight M.A., Tong W.-H., Hernandez D., Ayyad K., Taivassalo T., Andersen P.M., Singleton A., Rouault T.A., Fischbeck K.H., Haller R.G. Am. J. Hum. Genet. 82:652-660(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN MEIS.
[6]	"Characterization of the human HSC20, an unusual DnaJ type III protein, involved in iron-sulfur cluster biogenesis." Uhrigshardt H., Singh A., Kovtunovych G., Ghosh M., Rouault T.A. Hum. Mol. Genet. 19:3816-3834(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HSCB.
[7]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14, VARIANT [LARGE SCALE ANALYSIS] VAL-12, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"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].
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] VAL-12, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00022240. IPI00164885.
RefSeq	NP_055116.1. NM_014301.3. NP_998760.1. NM_213595.2.
UniGene	Hs.615131.
3D structure databases
ProteinModelPortal	Q9H1K1.
SMR	Q9H1K1. Positions 44-162.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9H1K1. 1 interaction.
MINT	MINT-3066312.
STRING	9606.ENSP00000310623.
PTM databases
PhosphoSite	Q9H1K1.
Polymorphism databases
DMDM	62900736.
Proteomic databases
PaxDb	Q9H1K1.
PRIDE	Q9H1K1.
Protocols and materials databases
DNASU	23479.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000311893; ENSP00000310623; ENSG00000136003. ENST00000392807; ENSP00000376554; ENSG00000136003.
GeneID	23479.
KEGG	hsa:23479.
UCSC	uc001tnc.4. human. uc010sxc.2. human.
Organism-specific databases
CTD	23479.
GeneCards	GC12P108956.
HGNC	HGNC:29882. ISCU.
HPA	CAB006329.
MIM	255125. phenotype. 611911. gene.
neXtProt	NX_Q9H1K1.
Orphanet	43115. Aconitase deficiency.
PharmGKB	PA162392328.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0822.
HOGENOM	HOG000069228.
HOVERGEN	HBG052621.
InParanoid	Q9H1K1.
OMA	PIKMHCS.
OrthoDB	EOG4SJ5G2.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	Q9H1K1.
Bgee	Q9H1K1.
CleanEx	HS_ISCU.
Genevestigator	Q9H1K1.
GermOnline	ENSG00000136003. Homo sapiens.
Family and domain databases
InterPro	IPR011339. ISC_FeS_clus_asmbl_IscU. IPR002871. NIF_FeS_clus_asmbl_NifU_N. [Graphical view]
Pfam	PF01592. NifU_N. 1 hit. [Graphical view]
TIGRFAMs	TIGR01999. iscU. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	ISCU. human.
GenomeRNAi	23479.
NextBio	45827.
SOURCE	Search...

Entry information

Entry name

ISCU_HUMAN

Accession

Primary (citable) accession number: Q9H1K1
Secondary accession number(s): Q6P713, Q99617, Q9H1K2

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 26, 2005
Last sequence update:	November 30, 2010
Last modified:	May 1, 2013
This is version 102 of the entry and version 2 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.