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Protein

NADPH-dependent diflavin oxidoreductase 1

Gene

NDOR1

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

Functioni

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.UniRule annotation3 Publications

Cofactori

Protein has several cofactor binding sites:

Kineticsi

  1. KM=21 µM for cytochrome c1 Publication
  1. Vmax=1.2 µmol/min/µg enzyme for cytochrome c reduction1 Publication

pH dependencei

Optimum pH is about 8.0.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei132FMNUniRule annotation1 Publication1
Binding sitei350FADUniRule annotation1
Binding sitei460NADPUniRule annotation1
Binding sitei558NADPUniRule annotation1
Binding sitei596FADUniRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi12 – 17FMNUniRule annotation1 Publication6
Nucleotide bindingi59 – 62FMNUniRule annotation1 Publication4
Nucleotide bindingi97 – 106FMNUniRule annotation1 Publication10
Nucleotide bindingi382 – 385FADUniRule annotation4
Nucleotide bindingi416 – 419FADUniRule annotation4
Nucleotide bindingi515 – 516NADPUniRule annotation2
Nucleotide bindingi521 – 525NADPUniRule annotation5

GO - Molecular functioni

  • flavin adenine dinucleotide binding Source: UniProtKB
  • FMN binding Source: UniProtKB
  • NADP binding Source: UniProtKB
  • NADPH-hemoprotein reductase activity Source: InterPro
  • oxidoreductase activity Source: UniProtKB

GO - Biological processi

  • cell death Source: UniProtKB
  • cellular response to menadione Source: UniProtKB
  • iron-sulfur cluster assembly Source: UniProtKB-HAMAP
  • oxidation-reduction process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

FAD, Flavoprotein, FMN, NADP

Enzyme and pathway databases

BioCyciZFISH:G66-32560-MONOMER.
BRENDAi1.5.1.30. 2681.
ReactomeiR-HSA-2564830. Cytosolic iron-sulfur cluster assembly.

Names & Taxonomyi

Protein namesi
Recommended name:
NADPH-dependent diflavin oxidoreductase 1UniRule annotation (EC:1.18.1.-UniRule annotation)
Alternative name(s):
NADPH-dependent FMN and FAD-containing oxidoreductaseUniRule annotation
Novel reductase 1
Gene namesi
Name:NDOR1UniRule annotation
Synonyms:NR1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:29838. NDOR1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: UniProtKB
  • intermediate filament cytoskeleton Source: HPA
  • nucleus Source: HPA
  • perinuclear region of cytoplasm Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

OpenTargetsiENSG00000188566.
ENSG00000283590.
PharmGKBiPA134885020.

Polymorphism and mutation databases

BioMutaiNDOR1.
DMDMi74735011.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003195391 – 597NADPH-dependent diflavin oxidoreductase 1Add BLAST597

Proteomic databases

EPDiQ9UHB4.
PaxDbiQ9UHB4.
PeptideAtlasiQ9UHB4.
PRIDEiQ9UHB4.

PTM databases

iPTMnetiQ9UHB4.
PhosphoSitePlusiQ9UHB4.

Expressioni

Tissue specificityi

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-361.1 Publication

Gene expression databases

BgeeiENSG00000188566.
CleanExiHS_NDOR1.
GenevisibleiQ9UHB4. HS.

Organism-specific databases

HPAiHPA024504.

Interactioni

Subunit structurei

Interacts with CIAPIN1. Interacts with DCPS.UniRule annotation3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CIAPIN1Q6FI815EBI-10249760,EBI-750511
EFHC2Q5JST63EBI-10249760,EBI-2349927
MTUS2Q5JR593EBI-10249760,EBI-742948
TCF4P158843EBI-10249760,EBI-533224
TCHPQ9BT925EBI-10249760,EBI-740781

Protein-protein interaction databases

BioGridi118038. 11 interactors.
IntActiQ9UHB4. 15 interactors.
STRINGi9606.ENSP00000360576.

Structurei

Secondary structure

1597
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi5 – 11Combined sources7
Beta strandi13 – 15Combined sources3
Helixi16 – 30Combined sources15
Beta strandi34 – 39Combined sources6
Turni40 – 42Combined sources3
Helixi45 – 50Combined sources6
Beta strandi52 – 59Combined sources8
Helixi62 – 64Combined sources3
Helixi68 – 70Combined sources3
Helixi71 – 77Combined sources7
Turni84 – 89Combined sources6
Beta strandi91 – 98Combined sources8
Beta strandi102 – 104Combined sources3
Helixi107 – 118Combined sources12
Beta strandi122 – 125Combined sources4
Beta strandi128 – 131Combined sources4
Turni135 – 138Combined sources4
Helixi139 – 156Combined sources18

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4H2DX-ray1.80A/B1-161[»]
ProteinModelPortaliQ9UHB4.
SMRiQ9UHB4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini6 – 150Flavodoxin-likeUniRule annotationAdd BLAST145
Domaini206 – 447FAD-binding FR-typeUniRule annotationAdd BLAST242

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi158 – 161Poly-Pro4

Sequence similaritiesi

Belongs to the NADPH-dependent diflavin oxidoreductase NDOR1 family.UniRule annotation
In the N-terminal section; belongs to the flavodoxin family.UniRule annotation
In the C-terminal section; belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.UniRule annotation
Contains 1 FAD-binding FR-type domain.UniRule annotation
Contains 1 flavodoxin-like domain.UniRule annotation

Phylogenomic databases

eggNOGiKOG1159. Eukaryota.
COG0369. LUCA.
GeneTreeiENSGT00860000133885.
HOGENOMiHOG000173033.
HOVERGENiHBG104950.
InParanoidiQ9UHB4.
OMAiAIPPDYL.
OrthoDBiEOG091G0GP1.
PhylomeDBiQ9UHB4.
TreeFamiTF105716.

Family and domain databases

Gene3Di1.20.990.10. 1 hit.
3.40.50.360. 1 hit.
HAMAPiMF_03178. NDOR1. 1 hit.
InterProiIPR003097. FAD-binding_1.
IPR017927. Fd_Rdtase_FAD-bd.
IPR001094. Flavdoxin-like.
IPR008254. Flavodoxin/NO_synth.
IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase.
IPR029039. Flavoprotein-like_dom.
IPR023173. NADPH_Cyt_P450_Rdtase_dom3.
IPR028879. NDOR1.
IPR001433. OxRdtase_FAD/NAD-bd.
IPR017938. Riboflavin_synthase-like_b-brl.
[Graphical view]
PfamiPF00667. FAD_binding_1. 1 hit.
PF00258. Flavodoxin_1. 1 hit.
PF00175. NAD_binding_1. 1 hit.
[Graphical view]
PRINTSiPR00369. FLAVODOXIN.
PR00371. FPNCR.
SUPFAMiSSF52218. SSF52218. 1 hit.
SSF63380. SSF63380. 1 hit.
PROSITEiPS51384. FAD_FR. 1 hit.
PS50902. FLAVODOXIN_LIKE. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9UHB4-1) [UniParc]FASTAAdd to basket

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
MPSPQLLVLF GSQTGTAQDV SERLGREARR RRLGCRVQAL DSYPVVNLIN
60 70 80 90 100
EPLVIFVCAT TGQGDPPDNM KNFWRFIFRK NLPSTALCQM DFAVLGLGDS
110 120 130 140 150
SYAKFNFVAK KLHRRLLQLG GSALLPVCLG DDQHELGPDA AVDPWLRDLW
160 170 180 190 200
DRVLGLYPPP PGLTEIPPGV PLPSKFTLLF LQEAPSTGSE GQRVAHPGSQ
210 220 230 240 250
EPPSESKPFL APMISNQRVT GPSHFQDVRL IEFDILGSGI SFAAGDVVLI
260 270 280 290 300
QPSNSAAHVQ RFCQVLGLDP DQLFMLQPRE PDVSSPTRLP QPCSMRHLVS
310 320 330 340 350
HYLDIASVPR RSFFELLACL SLHELEREKL LEFSSAQGQE ELFEYCNRPR
360 370 380 390 400
RTILEVLCDF PHTAAAIPPD YLLDLIPVIR PRAFSIASSL LTHPSRLQIL
410 420 430 440 450
VAVVQFQTRL KEPRRGLCSS WLASLDPGQG PVRVPLWVRP GSLAFPETPD
460 470 480 490 500
TPVIMVGPGT GVAPFRAAIQ ERVAQGQTGN FLFFGCRWRD QDFYWEAEWQ
510 520 530 540 550
ELEKRDCLTL IPAFSREQEQ KVYVQHRLRE LGSLVWELLD RQGAYFYLAG
560 570 580 590
NAKSMPADVS EALMSIFQEE GGLCSPDAAA YLARLQQTRR FQTETWA
Length:597
Mass (Da):66,763
Last modified:May 1, 2000 - v1
Checksum:i0D1340D7280A4D8F
GO
Isoform 2 (identifier: Q9UHB4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     518-518: Q → QPPALFSALQ

Show »
Length:606
Mass (Da):67,688
Checksum:i82F727F05E64E5DA
GO
Isoform 3 (identifier: Q9UHB4-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     138-171: Missing.
     543-597: GAYFYLAGNAKSMPADVSEALMSIFQEEGGLCSPDAAAYLARLQQTRRFQTETWA → ATPSPCQRTSRKP

Note: No experimental confirmation available.
Show »
Length:521
Mass (Da):58,455
Checksum:i3070040C37E92223
GO
Isoform 4 (identifier: Q9UHB4-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     392-398: Missing.

Note: Gene prediction based on EST data.
Show »
Length:590
Mass (Da):65,943
Checksum:i769AB27A3A4A2379
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_039010522V → I in allele NDOR1*1; shows a decrease in affinity for NADPH and a reduction in ferricyanide reductase activity. 2 PublicationsCorresponds to variant rs62587579dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_046313138 – 171Missing in isoform 3. 1 PublicationAdd BLAST34
Alternative sequenceiVSP_053807392 – 398Missing in isoform 4. Curated7
Alternative sequenceiVSP_031487518Q → QPPALFSALQ in isoform 2. 1 Publication1
Alternative sequenceiVSP_046314543 – 597GAYFY…TETWA → ATPSPCQRTSRKP in isoform 3. 1 PublicationAdd BLAST55

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS48061.1. [Q9UHB4-2]
CCDS48062.1. [Q9UHB4-4]
CCDS48063.1. [Q9UHB4-3]
CCDS7036.1. [Q9UHB4-1]
RefSeqiNP_001137498.1. NM_001144026.2. [Q9UHB4-2]
NP_001137499.1. NM_001144027.2. [Q9UHB4-3]
NP_001137500.1. NM_001144028.2. [Q9UHB4-4]
NP_055249.1. NM_014434.3. [Q9UHB4-1]
UniGeneiHs.512564.

Genome annotation databases

EnsembliENST00000344894; ENSP00000343344; ENSG00000283590. [Q9UHB4-1]
ENST00000371521; ENSP00000360576; ENSG00000188566. [Q9UHB4-2]
ENST00000427047; ENSP00000394309; ENSG00000188566. [Q9UHB4-3]
ENST00000458322; ENSP00000389905; ENSG00000188566. [Q9UHB4-4]
GeneIDi27158.
KEGGihsa:27158.
UCSCiuc004clw.4. human. [Q9UHB4-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS48061.1. [Q9UHB4-2]
CCDS48062.1. [Q9UHB4-4]
CCDS48063.1. [Q9UHB4-3]
CCDS7036.1. [Q9UHB4-1]
RefSeqiNP_001137498.1. NM_001144026.2. [Q9UHB4-2]
NP_001137499.1. NM_001144027.2. [Q9UHB4-3]
NP_001137500.1. NM_001144028.2. [Q9UHB4-4]
NP_055249.1. NM_014434.3. [Q9UHB4-1]
UniGeneiHs.512564.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4H2DX-ray1.80A/B1-161[»]
ProteinModelPortaliQ9UHB4.
SMRiQ9UHB4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118038. 11 interactors.
IntActiQ9UHB4. 15 interactors.
STRINGi9606.ENSP00000360576.

PTM databases

iPTMnetiQ9UHB4.
PhosphoSitePlusiQ9UHB4.

Polymorphism and mutation databases

BioMutaiNDOR1.
DMDMi74735011.

Proteomic databases

EPDiQ9UHB4.
PaxDbiQ9UHB4.
PeptideAtlasiQ9UHB4.
PRIDEiQ9UHB4.

Protocols and materials databases

DNASUi27158.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000344894; ENSP00000343344; ENSG00000283590. [Q9UHB4-1]
ENST00000371521; ENSP00000360576; ENSG00000188566. [Q9UHB4-2]
ENST00000427047; ENSP00000394309; ENSG00000188566. [Q9UHB4-3]
ENST00000458322; ENSP00000389905; ENSG00000188566. [Q9UHB4-4]
GeneIDi27158.
KEGGihsa:27158.
UCSCiuc004clw.4. human. [Q9UHB4-1]

Organism-specific databases

CTDi27158.
GeneCardsiNDOR1.
HGNCiHGNC:29838. NDOR1.
HPAiHPA024504.
MIMi606073. gene.
neXtProtiNX_Q9UHB4.
OpenTargetsiENSG00000188566.
ENSG00000283590.
PharmGKBiPA134885020.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1159. Eukaryota.
COG0369. LUCA.
GeneTreeiENSGT00860000133885.
HOGENOMiHOG000173033.
HOVERGENiHBG104950.
InParanoidiQ9UHB4.
OMAiAIPPDYL.
OrthoDBiEOG091G0GP1.
PhylomeDBiQ9UHB4.
TreeFamiTF105716.

Enzyme and pathway databases

BioCyciZFISH:G66-32560-MONOMER.
BRENDAi1.5.1.30. 2681.
ReactomeiR-HSA-2564830. Cytosolic iron-sulfur cluster assembly.

Miscellaneous databases

ChiTaRSiNDOR1. human.
GeneWikiiNDOR1.
GenomeRNAii27158.
PROiQ9UHB4.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000188566.
CleanExiHS_NDOR1.
GenevisibleiQ9UHB4. HS.

Family and domain databases

Gene3Di1.20.990.10. 1 hit.
3.40.50.360. 1 hit.
HAMAPiMF_03178. NDOR1. 1 hit.
InterProiIPR003097. FAD-binding_1.
IPR017927. Fd_Rdtase_FAD-bd.
IPR001094. Flavdoxin-like.
IPR008254. Flavodoxin/NO_synth.
IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase.
IPR029039. Flavoprotein-like_dom.
IPR023173. NADPH_Cyt_P450_Rdtase_dom3.
IPR028879. NDOR1.
IPR001433. OxRdtase_FAD/NAD-bd.
IPR017938. Riboflavin_synthase-like_b-brl.
[Graphical view]
PfamiPF00667. FAD_binding_1. 1 hit.
PF00258. Flavodoxin_1. 1 hit.
PF00175. NAD_binding_1. 1 hit.
[Graphical view]
PRINTSiPR00369. FLAVODOXIN.
PR00371. FPNCR.
SUPFAMiSSF52218. SSF52218. 1 hit.
SSF63380. SSF63380. 1 hit.
PROSITEiPS51384. FAD_FR. 1 hit.
PS50902. FLAVODOXIN_LIKE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNDOR1_HUMAN
AccessioniPrimary (citable) accession number: Q9UHB4
Secondary accession number(s): D3YTG6
, D3YTH9, Q5VSG4, Q86US9, Q96BC6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 26, 2008
Last sequence update: May 1, 2000
Last modified: November 30, 2016
This is version 133 of the entry and version 1 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

Miscellaneous

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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: 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.