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Q9UHB4 (NDOR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 108. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
NADPH-dependent diflavin oxidoreductase 1

EC=1.6.-.-
Alternative name(s):
NADPH-dependent FMN and FAD-containing oxidoreductase
Novel reductase 1
Gene names
Name:NDOR1
Synonyms:NR1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length597 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Component of the cytosolic iron-sulfur (Fe-S) protein assembly (CIA) machinery. Required for the maturation of extramitochondrial Fe-S proteins By similarity. Part of an electron transfer chain functioning in an early step of cytosolic Fe-S biogenesis. Transfers electrons from NADPH to the Fe/S cluster of CIAPIN1. Ref.1 Ref.7 Ref.9

Cofactor

FMN. Ref.1 Ref.9

FAD. Ref.1 Ref.9

Subunit structure

Interacts with CIAPIN1. Interacts with DCPS. Ref.6 Ref.7 Ref.9

Subcellular location

Cytoplasmperinuclear region. Note: Concentrated in perinuclear structure. Ref.1 Ref.2

Tissue specificity

Low expression in brain, heart, kidney, pancreas, prostate and skeletal muscle. Highest levels in the placenta. Expressed in cancer cell lines including promyelocytic leukemia, HeLaS3, chronic myelagenous leukemia, lymphoblastic leukemia, Burkitt's lymphoma, colorectal adenocarcinoma, lung carcinoma, and melanoma G-361. Ref.2

Miscellaneous

Overexpression enhanced cytotoxicity of menadione, and consequently induced cell death, coexpression with DCPS reduced this toxicity.

Sequence similarities

Belongs to the NADPH-dependent diflavin oxidoreductase NDOR1 family.

In the C-terminal section; belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.

Contains 1 FAD-binding FR-type domain.

Contains 1 flavodoxin-like domain.

Biophysicochemical properties

Kinetic parameters:

KM=21 µM for cytochrome c Ref.1

Vmax=1.2 µmol/min/µg enzyme for cytochrome c reduction

pH dependence:

Optimum pH is about 8.0.

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandFAD
Flavoprotein
FMN
NADP
   Molecular functionOxidoreductase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell death

Inferred from direct assay Ref.6. Source: UniProtKB

cellular response to menadione

Inferred from direct assay Ref.6. Source: UniProtKB

iron-sulfur cluster assembly

Inferred from electronic annotation. Source: UniProtKB-HAMAP

oxidation-reduction process

Inferred from direct assay Ref.1PubMed 12631275Ref.10. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasm

Inferred from direct assay. Source: HPA

cytosol

Inferred from direct assay Ref.6. Source: UniProtKB

intermediate filament cytoskeleton

Inferred from direct assay. Source: HPA

nucleus

Inferred from direct assay. Source: HPA

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-HAMAP

   Molecular_functionFMN binding

Inferred from electronic annotation. Source: UniProtKB-HAMAP

NADP binding

Inferred from electronic annotation. Source: UniProtKB-HAMAP

NADPH-hemoprotein reductase activity

Inferred from electronic annotation. Source: InterPro

flavin adenine dinucleotide binding

Inferred from electronic annotation. Source: UniProtKB-HAMAP

iron ion binding

Inferred from electronic annotation. Source: InterPro

oxidoreductase activity

Inferred from direct assay Ref.1PubMed 12631275Ref.10. Source: UniProtKB

oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9UHB4-1)

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: Q9UHB4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     518-518: Q → QPPALFSALQ
Isoform 3 (identifier: Q9UHB4-3)

The sequence of this isoform differs from the canonical sequence as follows:
     138-171: Missing.
     543-597: GAYFYLAGNAKSMPADVSEALMSIFQEEGGLCSPDAAAYLARLQQTRRFQTETWA → ATPSPCQRTSRKP
Note: No experimental confirmation available.
Isoform 4 (identifier: Q9UHB4-4)

The sequence of this isoform differs from the canonical sequence as follows:
     392-398: Missing.
Note: Gene prediction based on EST data.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 597597NADPH-dependent diflavin oxidoreductase 1 HAMAP-Rule MF_03178
PRO_0000319539

Regions

Domain6 – 150145Flavodoxin-like
Domain206 – 447242FAD-binding FR-type
Nucleotide binding12 – 165FMN HAMAP-Rule MF_03178
Nucleotide binding96 – 10510FMN HAMAP-Rule MF_03178
Nucleotide binding242 – 25312FAD By similarity
Nucleotide binding379 – 38911FAD By similarity
Nucleotide binding454 – 47219NADP By similarity
Nucleotide binding543 – 55917NADP By similarity
Compositional bias158 – 1614Poly-Pro HAMAP-Rule MF_03178

Sites

Binding site1321FMN

Natural variations

Alternative sequence138 – 17134Missing in isoform 3.
VSP_046313
Alternative sequence392 – 3987Missing in isoform 4.
VSP_053807
Alternative sequence5181Q → QPPALFSALQ in isoform 2.
VSP_031487
Alternative sequence543 – 59755GAYFY…TETWA → ATPSPCQRTSRKP in isoform 3.
VSP_046314
Natural variant5221V → I in allele NDOR1*1; shows a decrease in affinity for NADPH and a reduction in ferricyanide reductase activity. Ref.5 Ref.10
Corresponds to variant rs62587579 [ dbSNP | Ensembl ].
VAR_039010

Secondary structure

................................. 597
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: 0D1340D7280A4D8F

FASTA59766,763
        10         20         30         40         50         60 
MPSPQLLVLF GSQTGTAQDV SERLGREARR RRLGCRVQAL DSYPVVNLIN EPLVIFVCAT 

        70         80         90        100        110        120 
TGQGDPPDNM KNFWRFIFRK NLPSTALCQM DFAVLGLGDS SYAKFNFVAK KLHRRLLQLG 

       130        140        150        160        170        180 
GSALLPVCLG DDQHELGPDA AVDPWLRDLW DRVLGLYPPP PGLTEIPPGV PLPSKFTLLF 

       190        200        210        220        230        240 
LQEAPSTGSE GQRVAHPGSQ EPPSESKPFL APMISNQRVT GPSHFQDVRL IEFDILGSGI 

       250        260        270        280        290        300 
SFAAGDVVLI QPSNSAAHVQ RFCQVLGLDP DQLFMLQPRE PDVSSPTRLP QPCSMRHLVS 

       310        320        330        340        350        360 
HYLDIASVPR RSFFELLACL SLHELEREKL LEFSSAQGQE ELFEYCNRPR RTILEVLCDF 

       370        380        390        400        410        420 
PHTAAAIPPD YLLDLIPVIR PRAFSIASSL LTHPSRLQIL VAVVQFQTRL KEPRRGLCSS 

       430        440        450        460        470        480 
WLASLDPGQG PVRVPLWVRP GSLAFPETPD TPVIMVGPGT GVAPFRAAIQ ERVAQGQTGN 

       490        500        510        520        530        540 
FLFFGCRWRD QDFYWEAEWQ ELEKRDCLTL IPAFSREQEQ KVYVQHRLRE LGSLVWELLD 

       550        560        570        580        590 
RQGAYFYLAG NAKSMPADVS EALMSIFQEE GGLCSPDAAA YLARLQQTRR FQTETWA 

« Hide

Isoform 2 [UniParc].

Checksum: 82F727F05E64E5DA
Show »

FASTA60667,688
Isoform 3 [UniParc].

Checksum: 3070040C37E92223
Show »

FASTA52158,455
Isoform 4 [UniParc].

Checksum: 769AB27A3A4A2379
Show »

FASTA59065,943

References

« Hide 'large scale' references
[1]"Cloning and characterization of a novel human dual flavin reductase."
Paine M.J., Garner A.P., Powell D., Sibbald J., Sales M., Pratt N., Smith T., Tew D.G., Wolf C.R.
J. Biol. Chem. 275:1471-1478(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION.
[2]"Coordinate expression of NADPH-dependent flavin reductase, Fre-1, and Hint-related 7meGMP-directed hydrolase, DCS-1."
Kwasnicka D.A., Krakowiak A., Thacker C., Brenner C., Vincent S.R.
J. Biol. Chem. 278:39051-39058(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Brain.
[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. expand/collapse author list , 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 3).
Tissue: Hippocampus and Umbilical vein endothelial cell.
[4]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
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] (ISOFORM 1), VARIANT ILE-522.
Tissue: Brain and Skin.
[6]"Role of a novel dual flavin reductase (NR1) and an associated histidine triad protein (DCS-1) in menadione-induced cytotoxicity."
Kwasnicka-Crawford D.A., Vincent S.R.
Biochem. Biophys. Res. Commun. 336:565-571(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DCPS, CYTOTOXICITY.
[7]"Tah18 transfers electrons to Dre2 in cytosolic iron-sulfur protein biogenesis."
Netz D.J., Stumpfig M., Dore C., Muhlenhoff U., Pierik A.J., Lill R.
Nat. Chem. Biol. 6:758-765(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CIAPIN1.
[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]"Molecular view of an electron transfer process essential for iron-sulfur protein biogenesis."
Banci L., Bertini I., Calderone V., Ciofi-Baffoni S., Giachetti A., Jaiswal D., Mikolajczyk M., Piccioli M., Winkelmann J.
Proc. Natl. Acad. Sci. U.S.A. 110:7136-7141(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-161 IN COMPLEX WITH FMN, FUNCTION, COFACTOR, INTERACTION WITH CIAPIN1.
[10]"Identification of a functionally impaired allele of human novel oxidoreductase 1 (NDOR1), NDOR1*1."
Finn R.D., Wilkie M., Smith G., Paine M.J.
Pharmacogenet. Genomics 15:381-386(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ILE-522, CHARACTERIZATION OF VARIANT ILE-522.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF199509 mRNA. Translation: AAF25205.1.
AY077845 mRNA. Translation: AAL77754.1.
AK074403 mRNA. No translation available.
AK290026 mRNA. Translation: BAF82715.1.
AL929554, BX255925 Genomic DNA. Translation: CAH72886.2.
BX255925, AL929554 Genomic DNA. Translation: CAM24151.1.
BC015735 mRNA. Translation: AAH15735.1.
BC093782 mRNA. Translation: AAH93782.1.
BC111943 mRNA. Translation: AAI11944.1.
RefSeqNP_001137498.1. NM_001144026.2.
NP_001137499.1. NM_001144027.2.
NP_001137500.1. NM_001144028.2.
NP_055249.1. NM_014434.3.
UniGeneHs.512564.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4H2DX-ray1.80A/B1-161[»]
ProteinModelPortalQ9UHB4.
SMRQ9UHB4. Positions 3-597.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid118038. 6 interactions.
STRING9606.ENSP00000360576.

PTM databases

PhosphoSiteQ9UHB4.

Polymorphism databases

DMDM74735011.

Proteomic databases

PaxDbQ9UHB4.
PRIDEQ9UHB4.

Protocols and materials databases

DNASU27158.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000344894; ENSP00000343344; ENSG00000188566. [Q9UHB4-1]
ENST00000371521; ENSP00000360576; ENSG00000188566. [Q9UHB4-2]
ENST00000427047; ENSP00000394309; ENSG00000188566. [Q9UHB4-3]
ENST00000458322; ENSP00000389905; ENSG00000188566.
GeneID27158.
KEGGhsa:27158.
UCSCuc004clw.3. human. [Q9UHB4-1]

Organism-specific databases

CTD27158.
GeneCardsGC09P140100.
HGNCHGNC:29838. NDOR1.
HPAHPA024504.
MIM606073. gene.
neXtProtNX_Q9UHB4.
PharmGKBPA134885020.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0369.
HOGENOMHOG000173033.
HOVERGENHBG104950.
OMAGPSHFQD.
OrthoDBEOG7QG44B.
PhylomeDBQ9UHB4.
TreeFamTF105716.

Enzyme and pathway databases

BRENDA1.5.1.30. 2681.
ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressQ9UHB4.
BgeeQ9UHB4.
CleanExHS_NDOR1.
GenevestigatorQ9UHB4.

Family and domain databases

Gene3D1.20.990.10. 1 hit.
HAMAPMF_03178. NDOR1.
InterProIPR003097. FAD-binding_1.
IPR017927. Fd_Rdtase_FAD-bd.
IPR001094. Flavdoxin.
IPR008254. Flavodoxin/NO_synth.
IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase.
IPR023173. NADPH_Cyt_P450_Rdtase_dom3.
IPR028879. NDOR1.
IPR001433. OxRdtase_FAD/NAD-bd.
IPR017938. Riboflavin_synthase-like_b-brl.
[Graphical view]
PfamPF00667. FAD_binding_1. 1 hit.
PF00258. Flavodoxin_1. 1 hit.
PF00175. NAD_binding_1. 1 hit.
[Graphical view]
PRINTSPR00369. FLAVODOXIN.
PR00371. FPNCR.
SUPFAMSSF63380. SSF63380. 1 hit.
PROSITEPS51384. FAD_FR. 1 hit.
PS50902. FLAVODOXIN_LIKE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNDOR1. human.
GeneWikiNDOR1.
GenomeRNAi27158.
NextBio49931.
PROQ9UHB4.
SOURCESearch...

Entry information

Entry nameNDOR1_HUMAN
AccessionPrimary (citable) accession number: Q9UHB4
Secondary accession number(s): D3YTG6 expand/collapse secondary AC list , D3YTH9, Q5VSG4, Q86US9, Q96BC6
Entry history
Integrated into UniProtKB/Swiss-Prot: February 26, 2008
Last sequence update: May 1, 2000
Last modified: April 16, 2014
This is version 108 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM