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Protein

Dihydroorotate dehydrogenase (quinone), mitochondrial

Gene

DHODH

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

Functioni

Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.

Miscellaneous

The identification of DHODH defects as the cause of postaxial acrofacial dysostosis (POADS) was obtained via exome sequencing (PubMed:19915526), demonstrating that this method is a powerful tool for identifying genes underlying rare Mendelian disorders. Exome sequencing consists of targeted resequencing of all protein-coding subsequences, which requires around 5% as much sequencing as a whole human genome.1 Publication

Catalytic activityi

(S)-dihydroorotate + a quinone = orotate + a quinol.1 Publication

Cofactori

FMN1 PublicationNote: Binds 1 FMN per subunit.1 Publication

Pathwayi: UMP biosynthesis via de novo pathway

This protein is involved in step 1 of the subpathway that synthesizes orotate from (S)-dihydroorotate (quinone route).
Proteins known to be involved in this subpathway in this organism are:
  1. Dihydroorotate dehydrogenase (quinone), mitochondrial (DHODH), Dihydroorotate dehydrogenase (quinone), mitochondrial (pyrD), Dihydroorotate dehydrogenase (quinone), mitochondrial (DHODH)
This subpathway is part of the pathway UMP biosynthesis via de novo pathway, which is itself part of Pyrimidine metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes orotate from (S)-dihydroorotate (quinone route), the pathway UMP biosynthesis via de novo pathway and in Pyrimidine metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei99Substrate1
Binding sitei119FMN2 Publications1
Binding sitei180FMN2 Publications1
Binding sitei211FMN2 Publications1
Active sitei214Nucleophile1
Binding sitei254FMN2 Publications1
Binding sitei282FMN; via carbonyl oxygen2 Publications1
Binding sitei305FMN; via amide nitrogen2 Publications1
Binding sitei334FMN; via amide nitrogen2 Publications1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi95 – 99FMN2 Publications5
Nucleotide bindingi355 – 356FMN2 Publications2

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase
Biological processPyrimidine biosynthesis
LigandFlavoprotein, FMN

Enzyme and pathway databases

BRENDAi1.3.5.2 2681
1.3.98.1 2681
ReactomeiR-HSA-500753 Pyrimidine biosynthesis
SABIO-RKiQ02127
UniPathwayi
UPA00070;UER00946

Names & Taxonomyi

Protein namesi
Recommended name:
Dihydroorotate dehydrogenase (quinone), mitochondrial (EC:1.3.5.2)
Short name:
DHOdehase
Alternative name(s):
Dihydroorotate oxidase
Gene namesi
Name:DHODH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000102967.11
HGNCiHGNC:2867 DHODH
MIMi126064 gene
neXtProtiNX_Q02127

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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 10Mitochondrial matrixBy similarity10
Transmembranei11 – 30HelicalBy similarityAdd BLAST20
Topological domaini31 – 395Mitochondrial intermembraneBy similarityAdd BLAST365

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion inner membrane

Pathology & Biotechi

Involvement in diseasei

Postaxial acrofacial dysostosis (POADS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionPOADS is characterized by severe micrognathia, cleft lip and/or palate, hypoplasia or aplasia of the posterior elements of the limbs, coloboma of the eyelids and supernumerary nipples. POADS is a very rare disorder: only 2 multiplex families, each consisting of 2 affected siblings born to unaffected, nonconsanguineous parents, have been described among a total of around 30 reported cases.
See also OMIM:263750
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06241219G → E in POADS. 1 PublicationCorresponds to variant dbSNP:rs267606765EnsemblClinVar.1
Natural variantiVAR_062413135R → C in POADS. 1 PublicationCorresponds to variant dbSNP:rs201230446EnsemblClinVar.1
Natural variantiVAR_062414152G → R in POADS. 1 PublicationCorresponds to variant dbSNP:rs267606766EnsemblClinVar.1
Natural variantiVAR_062415199R → C in POADS. 1 PublicationCorresponds to variant dbSNP:rs267606769EnsemblClinVar.1
Natural variantiVAR_062416202G → A in POADS. 1 PublicationCorresponds to variant dbSNP:rs267606767EnsemblClinVar.1
Natural variantiVAR_062417202G → D in POADS. 1 PublicationCorresponds to variant dbSNP:rs267606767EnsemblClinVar.1
Natural variantiVAR_062418244R → W in POADS. 1 PublicationCorresponds to variant dbSNP:rs267606768EnsemblClinVar.1
Natural variantiVAR_062419284T → I in POADS. 1 Publication1
Natural variantiVAR_062420346R → W in POADS. 1 PublicationCorresponds to variant dbSNP:rs201947120EnsemblClinVar.1
Natural variantiVAR_062421392D → G in POADS. 1 PublicationCorresponds to variant dbSNP:rs779076692Ensembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi1723
MalaCardsiDHODH
MIMi263750 phenotype
OpenTargetsiENSG00000102967
Orphaneti246 Postaxial acrofacial dysostosis
PharmGKBiPA27327

Chemistry databases

ChEMBLiCHEMBL1966
DrugBankiDB07561 (2Z)-2-cyano-N-(3'-ethoxybiphenyl-4-yl)-3-hydroxybut-2-enamide
DB08172 (2Z)-N-(3-chloro-2'-methoxybiphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide
DB08169 (2Z)-N-biphenyl-4-yl-2-cyano-3-cyclopropyl-3-hydroxyprop-2-enamide
DB07443 (2Z)-N-biphenyl-4-yl-2-cyano-3-hydroxybut-2-enamide
DB07976 3-{[(3-FLUORO-3'-METHOXYBIPHENYL-4-YL)AMINO]CARBONYL}THIOPHENE-2-CARBOXYLIC ACID
DB03805 Antiproliferative Agent A771726
DB01117 Atovaquone
DB03480 Brequinar Analog
DB04147 Lauryl Dimethylamine-N-Oxide
DB01097 Leflunomide
DB02262 Orotic Acid
DB03247 Riboflavin Monophosphate
DB05125 SC12267
DB08880 Teriflunomide
GuidetoPHARMACOLOGYi2604

Polymorphism and mutation databases

BioMutaiDHODH
DMDMi56405372

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000298841 – 395Dihydroorotate dehydrogenase (quinone), mitochondrialAdd BLAST395
Transit peptidei1 – 10Mitochondrion; not cleavedBy similarity10

Post-translational modificationi

The uncleaved transit peptide is required for mitochondrial targeting and proper membrane integration.

Proteomic databases

EPDiQ02127
MaxQBiQ02127
PaxDbiQ02127
PeptideAtlasiQ02127
PRIDEiQ02127
ProteomicsDBi58051
TopDownProteomicsiQ02127

PTM databases

iPTMnetiQ02127
PhosphoSitePlusiQ02127

Expressioni

Gene expression databases

BgeeiENSG00000102967 Expressed in 124 organ(s), highest expression level in right lobe of liver
CleanExiHS_DHODH
ExpressionAtlasiQ02127 baseline and differential
GenevisibleiQ02127 HS

Organism-specific databases

HPAiHPA010123
HPA011942

Interactioni

Subunit structurei

Monomer.2 Publications

Protein-protein interaction databases

BioGridi108068, 16 interactors
IntActiQ02127, 4 interactors
STRINGi9606.ENSP00000219240

Chemistry databases

BindingDBiQ02127

Structurei

Secondary structure

1395
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ02127
SMRiQ02127
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ02127

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni144 – 148Substrate binding5
Regioni211 – 216Substrate binding6
Regioni283 – 284Substrate binding2

Sequence similaritiesi

Keywords - Domaini

Transit peptide, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1436 Eukaryota
COG0167 LUCA
GeneTreeiENSGT00500000044924
HOGENOMiHOG000225103
HOVERGENiHBG006898
InParanoidiQ02127
KOiK00254
OMAiLQNAMGF
OrthoDBiEOG091G07JK
PhylomeDBiQ02127
TreeFamiTF105973

Family and domain databases

CDDicd04738 DHOD_2_like, 1 hit
Gene3Di3.20.20.70, 1 hit
InterProiView protein in InterPro
IPR013785 Aldolase_TIM
IPR005720 Dihydroorotate_DH
IPR005719 Dihydroorotate_DH_2
IPR001295 Dihydroorotate_DH_CS
PfamiView protein in Pfam
PF01180 DHO_dh, 1 hit
TIGRFAMsiTIGR01036 pyrD_sub2, 1 hit
PROSITEiView protein in PROSITE
PS00911 DHODEHASE_1, 1 hit
PS00912 DHODEHASE_2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All

Q02127-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAWRHLKKRA QDAVIILGGG GLLFASYLMA TGDERFYAEH LMPTLQGLLD
60 70 80 90 100
PESAHRLAVR FTSLGLLPRA RFQDSDMLEV RVLGHKFRNP VGIAAGFDKH
110 120 130 140 150
GEAVDGLYKM GFGFVEIGSV TPKPQEGNPR PRVFRLPEDQ AVINRYGFNS
160 170 180 190 200
HGLSVVEHRL RARQQKQAKL TEDGLPLGVN LGKNKTSVDA AEDYAEGVRV
210 220 230 240 250
LGPLADYLVV NVSSPNTAGL RSLQGKAELR RLLTKVLQER DGLRRVHRPA
260 270 280 290 300
VLVKIAPDLT SQDKEDIASV VKELGIDGLI VTNTTVSRPA GLQGALRSET
310 320 330 340 350
GGLSGKPLRD LSTQTIREMY ALTQGRVPII GVGGVSSGQD ALEKIRAGAS
360 370 380 390
LVQLYTALTF WGPPVVGKVK RELEALLKEQ GFGGVTDAIG ADHRR
Length:395
Mass (Da):42,867
Last modified:December 7, 2004 - v3
Checksum:i072C3169E78C6440
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
I3NI32I3NI32_HUMAN
Dihydroorotate dehydrogenase (quino...
DHODH
393Annotation score:
I3L449I3L449_HUMAN
Dihydroorotate dehydrogenase (quino...
DHODH
193Annotation score:
J3QRQ3J3QRQ3_HUMAN
Dihydroorotate dehydrogenase (quino...
DHODH
144Annotation score:
J3QRJ4J3QRJ4_HUMAN
Dihydroorotate dehydrogenase (quino...
DHODH
76Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1 – 2MA → KLP in AAA50163 (PubMed:1446837).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0220947K → Q2 PublicationsCorresponds to variant dbSNP:rs3213422EnsemblClinVar.1
Natural variantiVAR_06241219G → E in POADS. 1 PublicationCorresponds to variant dbSNP:rs267606765EnsemblClinVar.1
Natural variantiVAR_062413135R → C in POADS. 1 PublicationCorresponds to variant dbSNP:rs201230446EnsemblClinVar.1
Natural variantiVAR_062414152G → R in POADS. 1 PublicationCorresponds to variant dbSNP:rs267606766EnsemblClinVar.1
Natural variantiVAR_062415199R → C in POADS. 1 PublicationCorresponds to variant dbSNP:rs267606769EnsemblClinVar.1
Natural variantiVAR_062416202G → A in POADS. 1 PublicationCorresponds to variant dbSNP:rs267606767EnsemblClinVar.1
Natural variantiVAR_062417202G → D in POADS. 1 PublicationCorresponds to variant dbSNP:rs267606767EnsemblClinVar.1
Natural variantiVAR_062418244R → W in POADS. 1 PublicationCorresponds to variant dbSNP:rs267606768EnsemblClinVar.1
Natural variantiVAR_062419284T → I in POADS. 1 Publication1
Natural variantiVAR_062420346R → W in POADS. 1 PublicationCorresponds to variant dbSNP:rs201947120EnsemblClinVar.1
Natural variantiVAR_062421392D → G in POADS. 1 PublicationCorresponds to variant dbSNP:rs779076692Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M94065 mRNA Translation: AAA50163.1
AK292293 mRNA Translation: BAF84982.1
BC065245 mRNA Translation: AAH65245.1
CCDSiCCDS42192.1
PIRiPC1219
RefSeqiNP_001352.2, NM_001361.4
UniGeneiHs.654427

Genome annotation databases

EnsembliENST00000219240; ENSP00000219240; ENSG00000102967
GeneIDi1723
KEGGihsa:1723
UCSCiuc002fbp.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M94065 mRNA Translation: AAA50163.1
AK292293 mRNA Translation: BAF84982.1
BC065245 mRNA Translation: AAH65245.1
CCDSiCCDS42192.1
PIRiPC1219
RefSeqiNP_001352.2, NM_001361.4
UniGeneiHs.654427

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1D3GX-ray1.60A29-395[»]
1D3HX-ray1.80A29-395[»]
2B0MX-ray2.00A29-395[»]
2BXVX-ray2.15A29-395[»]
2FPTX-ray2.40A29-395[»]
2FPVX-ray1.80A29-395[»]
2FPYX-ray2.00A29-395[»]
2FQIX-ray1.95A29-395[»]
2PRHX-ray2.40A29-395[»]
2PRLX-ray2.10A29-395[»]
2PRMX-ray3.00A29-395[»]
2WV8X-ray1.90A31-395[»]
3F1QX-ray2.00A29-395[»]
3FJ6X-ray1.80A29-395[»]
3FJLX-ray1.90A29-395[»]
3G0UX-ray2.00A29-395[»]
3G0XX-ray1.80A29-395[»]
3KVJX-ray1.94A29-395[»]
3KVKX-ray2.05A29-395[»]
3KVLX-ray1.85A29-395[»]
3KVMX-ray2.00A29-395[»]
3U2OX-ray2.18A1-395[»]
3W7RX-ray1.68A29-395[»]
3ZWSX-ray1.60A29-395[»]
3ZWTX-ray1.55A29-395[»]
4IGHX-ray1.30A32-395[»]
4JGDX-ray2.05A29-395[»]
4JS3X-ray2.00A29-395[»]
4JTSX-ray2.21A29-395[»]
4JTTX-ray2.10A29-395[»]
4JTUX-ray1.90A29-395[»]
4LS0X-ray2.07A29-395[»]
4LS1X-ray2.20A29-395[»]
4LS2X-ray2.27A29-395[»]
4OQVX-ray1.23A32-395[»]
4RK8X-ray2.22A29-395[»]
4RKAX-ray2.71A29-395[»]
4RLIX-ray2.50A29-395[»]
4RR4X-ray2.38A29-395[»]
4YLWX-ray1.79A29-395[»]
4ZL1X-ray1.86A29-395[»]
4ZMGX-ray1.90A29-395[»]
5H2ZX-ray1.58A29-395[»]
5H73X-ray1.58A29-395[»]
5HINX-ray1.60A29-395[»]
5HQEX-ray1.62A29-395[»]
5K9CX-ray1.66A29-395[»]
5K9DX-ray1.70A29-395[»]
5MUTX-ray1.75A31-395[»]
5MVCX-ray1.85A29-395[»]
5MVDX-ray1.95A33-395[»]
5TCENMR-A32-65[»]
6CJFX-ray1.63A/B32-395[»]
6CJGX-ray2.85A32-395[»]
6ET4X-ray1.70A29-395[»]
6FMDX-ray1.58A1-395[»]
ProteinModelPortaliQ02127
SMRiQ02127
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108068, 16 interactors
IntActiQ02127, 4 interactors
STRINGi9606.ENSP00000219240

Chemistry databases

BindingDBiQ02127
ChEMBLiCHEMBL1966
DrugBankiDB07561 (2Z)-2-cyano-N-(3'-ethoxybiphenyl-4-yl)-3-hydroxybut-2-enamide
DB08172 (2Z)-N-(3-chloro-2'-methoxybiphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide
DB08169 (2Z)-N-biphenyl-4-yl-2-cyano-3-cyclopropyl-3-hydroxyprop-2-enamide
DB07443 (2Z)-N-biphenyl-4-yl-2-cyano-3-hydroxybut-2-enamide
DB07976 3-{[(3-FLUORO-3'-METHOXYBIPHENYL-4-YL)AMINO]CARBONYL}THIOPHENE-2-CARBOXYLIC ACID
DB03805 Antiproliferative Agent A771726
DB01117 Atovaquone
DB03480 Brequinar Analog
DB04147 Lauryl Dimethylamine-N-Oxide
DB01097 Leflunomide
DB02262 Orotic Acid
DB03247 Riboflavin Monophosphate
DB05125 SC12267
DB08880 Teriflunomide
GuidetoPHARMACOLOGYi2604

PTM databases

iPTMnetiQ02127
PhosphoSitePlusiQ02127

Polymorphism and mutation databases

BioMutaiDHODH
DMDMi56405372

Proteomic databases

EPDiQ02127
MaxQBiQ02127
PaxDbiQ02127
PeptideAtlasiQ02127
PRIDEiQ02127
ProteomicsDBi58051
TopDownProteomicsiQ02127

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000219240; ENSP00000219240; ENSG00000102967
GeneIDi1723
KEGGihsa:1723
UCSCiuc002fbp.4 human

Organism-specific databases

CTDi1723
DisGeNETi1723
EuPathDBiHostDB:ENSG00000102967.11
GeneCardsiDHODH
HGNCiHGNC:2867 DHODH
HPAiHPA010123
HPA011942
MalaCardsiDHODH
MIMi126064 gene
263750 phenotype
neXtProtiNX_Q02127
OpenTargetsiENSG00000102967
Orphaneti246 Postaxial acrofacial dysostosis
PharmGKBiPA27327
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1436 Eukaryota
COG0167 LUCA
GeneTreeiENSGT00500000044924
HOGENOMiHOG000225103
HOVERGENiHBG006898
InParanoidiQ02127
KOiK00254
OMAiLQNAMGF
OrthoDBiEOG091G07JK
PhylomeDBiQ02127
TreeFamiTF105973

Enzyme and pathway databases

UniPathwayi
UPA00070;UER00946

BRENDAi1.3.5.2 2681
1.3.98.1 2681
ReactomeiR-HSA-500753 Pyrimidine biosynthesis
SABIO-RKiQ02127

Miscellaneous databases

ChiTaRSiDHODH human
EvolutionaryTraceiQ02127
GenomeRNAii1723
PROiPR:Q02127
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000102967 Expressed in 124 organ(s), highest expression level in right lobe of liver
CleanExiHS_DHODH
ExpressionAtlasiQ02127 baseline and differential
GenevisibleiQ02127 HS

Family and domain databases

CDDicd04738 DHOD_2_like, 1 hit
Gene3Di3.20.20.70, 1 hit
InterProiView protein in InterPro
IPR013785 Aldolase_TIM
IPR005720 Dihydroorotate_DH
IPR005719 Dihydroorotate_DH_2
IPR001295 Dihydroorotate_DH_CS
PfamiView protein in Pfam
PF01180 DHO_dh, 1 hit
TIGRFAMsiTIGR01036 pyrD_sub2, 1 hit
PROSITEiView protein in PROSITE
PS00911 DHODEHASE_1, 1 hit
PS00912 DHODEHASE_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPYRD_HUMAN
AccessioniPrimary (citable) accession number: Q02127
Secondary accession number(s): A8K8C8, Q6P176
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: December 7, 2004
Last modified: October 10, 2018
This is version 192 of the entry and version 3 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

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. SIMILARITY comments
    Index of protein domains and families
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  6. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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