Q9UMS0 (NFU1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
NFU1 iron-sulfur cluster scaffold homolog, mitochondrial

Alternative name(s):
HIRA-interacting protein 5

Gene names

Name:	NFU1
Synonyms:	HIRIP5
ORF Names:	CGI-33

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	254 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	Iron-sulfur cluster scaffold protein which can assemble [4Fe-2S] clusters and deliver them to target proteins. Ref.3
Subunit structure	Interacts with HIRA and EPM2A/laforin. Ref.2
Subcellular location	Mitochondrion. Cytoplasm › cytosol Ref.2 Ref.3 Ref.9.
Tissue specificity	Ubiquitous. Expression in adult lung is weak compared to fetal lung. Ref.2
Developmental stage	Expressed in embryo and adult. Ref.2
Involvement in disease	Multiple mitochondrial dysfunctions syndrome 1 (MMDS1) [MIM:605711]: A severe disorder of systemic energy metabolism, resulting in weakness, respiratory failure, lack of neurologic development, lactic acidosis, hyperglycinemia and early death. Some patients show failure to thrive, pulmonary hypertension, hypotonia and irritability. Biochemical features include severe combined deficiency of the 2-oxoacid dehydrogenases, defective lipoic acid synthesis and reduction in activity of mitochondrial respiratory chain complexes. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.12
Sequence similarities	Belongs to the NifU family.
Sequence caution	The sequence AAD27742.1 differs from that shown. Reason: Frameshift at positions 5, 16, 115 and 117. The sequence AAY14828.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence BAG36716.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence CAB53015.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Cellular component	Cytoplasm Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Transit peptide
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	iron-sulfur cluster assembly Inferred from direct assay Ref.3. Source: UniProtKB
Cellular_component	centrosome Inferred from direct assay. Source: HPA cytosol Inferred from direct assay Ref.3Ref.2. Source: UniProtKB mitochondrion Inferred from direct assay Ref.3. Source: UniProtKB nucleus Inferred from direct assay Ref.3. Source: UniProtKB
Molecular_function	4 iron, 4 sulfur cluster binding Inferred from direct assay Ref.3. Source: UniProtKB iron ion binding Inferred from direct assay Ref.3. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ORF	Q9Q2G4	3	EBI-725252,EBI-6248094	From a different organism.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9UMS0-1)

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: Q9UMS0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-141: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q9UMS0-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-24: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 9

9

Mitochondrion Potential

Chain

10 – 254

245

NFU1 iron-sulfur cluster scaffold homolog, mitochondrial

PRO_0000166191

Regions

Region

173 – 241

69

NifU

Natural variations

Alternative sequence

1 – 141

141

Missing in isoform 2.

VSP_041224

Alternative sequence

1 – 24

24

Missing in isoform 3.

VSP_041225

Natural variant

25

1

M → K. Ref.2 Ref.5
Corresponds to variant rs4453725 [ dbSNP | Ensembl ].

VAR_044429

Natural variant

208

1

G → C in MMDS1. Ref.12

VAR_066639

Experimental info

Sequence conflict

158

1

S → P in AAD27742. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

254

Helix Strand Turn

Details...

Beta strand

62 – 64

3

Beta strand

71 – 75

5

Beta strand

80 – 83

4

Beta strand

86 – 88

3

Helix

93 – 96

4

Helix

98 – 103

6

Beta strand

109 – 115

7

Beta strand

118 – 125

8

Helix

130 – 147

18

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 2, 2008. Version 2. Checksum: E84B7F47A4A282CF	FASTA	254	28,463
	10 20 30 40 50 60 MAATARRGWG AAAVAAGLRR RFCHMLKNPY TIKKQPLHQF VQRPLFPLPA AFYHPVRYMF 70 80 90 100 110 120 IQTQDTPNPN SLKFIPGKPV LETRTMDFPT PAAAFRSPLA RQLFRIEGVK SVFFGPDFIT 130 140 150 160 170 180 VTKENEELDW NLLKPDIYAT IMDFFASGLP LVTEETPSGE AGSEEDDEVV AMIKELLDTR 190 200 210 220 230 240 IRPTVQEDGG DVIYKGFEDG IVQLKLQGSC TSCPSSIITL KNGIQNMLQF YIPEVEGVEQ 250 VMDDESDEKE ANSP
	Isoform 2 [UniParc]. Checksum: C46A36AEC7E4C515	FASTA	113	12,347
	10 20 30 40 50 60 MDFFASGLPL VTEETPSGEA GSEEDDEVVA MIKELLDTRI RPTVQEDGGD VIYKGFEDGI 70 80 90 100 110 VQLKLQGSCT SCPSSIITLK NGIQNMLQFY IPEVEGVEQV MDDESDEKEA NSP
	Isoform 3 [UniParc]. Checksum: 2B953543B3A68DCC	FASTA	230	25,924
	10 20 30 40 50 60 MLKNPYTIKK QPLHQFVQRP LFPLPAAFYH PVRYMFIQTQ DTPNPNSLKF IPGKPVLETR 70 80 90 100 110 120 TMDFPTPAAA FRSPLARQLF RIEGVKSVFF GPDFITVTKE NEELDWNLLK PDIYATIMDF 130 140 150 160 170 180 FASGLPLVTE ETPSGEAGSE EDDEVVAMIK ELLDTRIRPT VQEDGGDVIY KGFEDGIVQL 190 200 210 220 230 KLQGSCTSCP SSIITLKNGI QNMLQFYIPE VEGVEQVMDD ESDEKEANSP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of human and mouse HIRA-interacting protein-5 (HIRIP5), two mammalian representatives in a family of phylogenetically conserved proteins with a role in the biogenesis of Fe/S proteins." Lorain S., Lecluse Y., Scamps C., Mattei M.-G., Lipinski M. Biochim. Biophys. Acta 1517:376-383(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). Tissue: Myeloid leukemia cell.
[2]	"The Lafora disease gene product laforin interacts with HIRIP5, a phylogenetically conserved protein containing a NifU-like domain." Ganesh S., Tsurutani N., Suzuki T., Ueda K., Agarwala K.L., Osada H., Delgado-Escueta A.V., Yamakawa K. Hum. Mol. Genet. 12:2359-2368(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH EPM2A, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, VARIANT LYS-25. Tissue: Brain.
[3]	"Subcellular compartmentalization of human Nfu, an iron-sulfur cluster scaffold protein, and its ability to assemble a [4Fe-4S] cluster." Tong W.-H., Jameson G.N.L., Huynh B.H., Rouault T.A. Proc. Natl. Acad. Sci. U.S.A. 100:9762-9767(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), FUNCTION, SUBCELLULAR LOCATION.
[4]	"Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics." Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C. Genome Res. 10:703-713(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[5]	"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] (ISOFORMS 1 AND 2), VARIANT LYS-25. Tissue: Skeletal muscle.
[6]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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). Tissue: Cerebellum.
[9]	"Mutations in iron-sulfur cluster scaffold genes NFU1 and BOLA3 cause a fatal deficiency of multiple respiratory chain and 2-oxoacid dehydrogenase enzymes." Cameron J.M., Janer A., Levandovskiy V., Mackay N., Rouault T.A., Tong W.H., Ogilvie I., Shoubridge E.A., Robinson B.H. Am. J. Hum. Genet. 89:486-495(2011) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INVOLVEMENT IN MMDS1.
[10]	"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].
[11]	"Solution NMR structure of NFU1 iron-sulfur cluster scaffold homolog from Homo sapiens, Northeast structural genomics consortium (NESG) target HR2876B." Northeast structural genomics consortium (NESG) Submitted (AUG-2012) to the PDB data bank Cited for: STRUCTURE BY NMR OF 59-155.
[12]	"A fatal mitochondrial disease is associated with defective NFU1 function in the maturation of a subset of mitochondrial Fe-S proteins." Navarro-Sastre A., Tort F., Stehling O., Uzarska M.A., Arranz J.A., Del Toro M., Labayru M.T., Landa J., Font A., Garcia-Villoria J., Merinero B., Ugarte M., Gutierrez-Solana L.G., Campistol J., Garcia-Cazorla A., Vaquerizo J., Riudor E., Briones P. , Elpeleg O., Ribes A., Lill R. Am. J. Hum. Genet. 89:656-667(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MMDS1 CYS-208.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AJ132584 mRNA. Translation: CAB53015.1. Different initiation.
AY335194 mRNA. Translation: AAQ73784.1.
AY286306 mRNA. Translation: AAP92372.1.
AY286307 mRNA. Translation: AAP92373.1.
AF132967 mRNA. Translation: AAD27742.1. Frameshift.
AK314004 mRNA. Translation: BAG36716.1. Different initiation.
AK300700 mRNA. Translation: BAG62381.1.
DB304061 mRNA. No translation available.
AC114772 Genomic DNA. Translation: AAY14828.1. Sequence problems.
CH471053 Genomic DNA. Translation: EAW99849.1.
CH471053 Genomic DNA. Translation: EAW99850.1.
BC113692 mRNA. Translation: AAI13693.1.
BC113694 mRNA. Translation: AAI13695.1.

IPI

IPI00160021.
IPI00455153.
IPI00472265.

RefSeq

NP_001002755.1. NM_001002755.2.
NP_001002756.1. NM_001002756.2.
NP_056515.2. NM_015700.3.

UniGene

Hs.430439.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2LTM	NMR	-	A	59-155	[»]

ProteinModelPortal

Q9UMS0.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UMS0. 4 interactions.

MINT

MINT-1388264.

STRING

9606.ENSP00000387219.

Polymorphism databases

DMDM

205371805.

Proteomic databases

PaxDb

Q9UMS0.

PRIDE

Q9UMS0.

Protocols and materials databases

DNASU

27247.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000303698; ENSP00000306965; ENSG00000169599.
ENST00000394305; ENSP00000377842; ENSG00000169599.
ENST00000410022; ENSP00000387219; ENSG00000169599.
ENST00000462320; ENSP00000418598; ENSG00000169599.

GeneID

27247.

KEGG

hsa:27247.

UCSC

uc002sfj.3. human.

Organism-specific databases

CTD

27247.

GeneCards

GC02M069622.

HGNC

HGNC:16287. NFU1.

HPA

HPA035825.

MIM

605711. phenotype.
608100. gene.

neXtProt

NX_Q9UMS0.

Orphanet

293838. Fatal infantile encephalopathy-pulmonary hypertension syndrome.
289573. Fatal multiple mitochondrial dysfunction syndrome.

PharmGKB

PA162397454.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0694.

HOVERGEN

HBG054438.

InParanoid

Q9UMS0.

OMA

GAIMEHF.

OrthoDB

EOG4TB4C3.

Gene expression databases

ArrayExpress

Q9UMS0.

Bgee

Q9UMS0.

CleanEx

HS_NFU1.

Genevestigator

Q9UMS0.

GermOnline

ENSG00000169599. Homo sapiens.

Family and domain databases

Gene3D

3.30.1370.70. 1 hit.

InterPro

IPR017065. HIRA-interacting_protein_5.
IPR014824. NIF_FeS_clus_asmbl_NifU-like_N.
IPR001075. NIF_FeS_clus_asmbl_NifU_C.
[Graphical view]

Pfam

PF08712. Nfu_N. 1 hit.
PF01106. NifU. 1 hit.
[Graphical view]

PIRSF

PIRSF036773. HIRIP5. 1 hit.

ProDom

PD002830. NIF_FeS_clus_asmbl_NifU_C. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00932. Nfu_N. 1 hit.
[Graphical view]

SUPFAM

SSF110836. NIF_FeS_clus_asmbl_NifU-like_N. 1 hit.

ProtoNet

Search...

Other

ChiTaRS

NFU1. human.

GenomeRNAi

27247.

NextBio

50161.

SOURCE

Search...

Entry information

Entry name

NFU1_HUMAN

Accession

Primary (citable) accession number: Q9UMS0
Secondary accession number(s): B4DUL9 , Q53QE5, Q6VNZ8, Q7Z5B1, Q7Z5B2, Q9Y322

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 2002
Last sequence update:	September 2, 2008
Last modified:	May 1, 2013
This is version 103 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.