Dihydroorotate dehydrogenase, mitochondrial precursor

Names and origin

Protein names

Recommended name:
    Dihydroorotate dehydrogenase, mitochondrial
      Short name=DHOdehase
    EC=1.3.3.1
Alternative name(s):
    Dihydroorotate oxidase

Gene names

Name:

DHODH

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Hide | Top

Protein attributes

Sequence length	395 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

Hide | Top

General annotation (Comments)

Catalytic activity	(S)-dihydroorotate + O₂ = orotate + H₂O₂. Ref.5
Cofactor	Binds 1 FAD per subunit.
Pathway	Pyrimidine metabolism; UMP biosynthesis via de novo pathway; UMP from HCO(3)(-): step 4/6.
Subcellular location	Mitochondrion inner membrane.
Sequence similarities	Belongs to the dihydroorotate dehydrogenase family.

Hide | Top

Ontologies

Keywords
Biological process	Pyrimidine biosynthesis
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Coding sequence diversity	Polymorphism
Domain	Transit peptide
Ligand	FAD Flavoprotein
Molecular function	Oxidoreductase
Technical term	3D-structure
Gene Ontology (GO)
Biological process	'de novo' pyrimidine base biosynthetic process Non-traceable author statement. Source: UniProtKB UMP biosynthetic process Inferred from electronic annotation. Source: InterPro oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrial inner membrane Non-traceable author statement. Source: UniProtKB
Molecular function	dihydroorotate oxidase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Hide | Top

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 9

9

Mitochondrion Potential

Chain

10 – 395

386

Dihydroorotate dehydrogenase, mitochondrial

PRO_0000029884

Sites

Active site

214

1

Nucleophile

Natural variations

Natural variant

7

1

K → Q: dbSNP rs3213422. Ref.1 Ref.3

VAR_022094

Experimental info

Sequence conflict

1 – 2

2

MA → KLP Ref.1

Secondary structure

1

.

395

Helix Strand Turn

Details...

Hide | Top

Sequences

Sequence

Length

Mass (Da)

Tools

Q02127-1 [UniParc].

Last modified December 7, 2004. Version 3.
Checksum: 072C3169E78C6440
Show »

FASTA

395

42,867

        10         20         30         40         50         60 
MAWRHLKKRA QDAVIILGGG GLLFASYLMA TGDERFYAEH LMPTLQGLLD PESAHRLAVR 

        70         80         90        100        110        120 
FTSLGLLPRA RFQDSDMLEV RVLGHKFRNP VGIAAGFDKH GEAVDGLYKM GFGFVEIGSV 

       130        140        150        160        170        180 
TPKPQEGNPR PRVFRLPEDQ AVINRYGFNS HGLSVVEHRL RARQQKQAKL TEDGLPLGVN 

       190        200        210        220        230        240 
LGKNKTSVDA AEDYAEGVRV LGPLADYLVV NVSSPNTAGL RSLQGKAELR RLLTKVLQER 

       250        260        270        280        290        300 
DGLRRVHRPA VLVKIAPDLT SQDKEDIASV VKELGIDGLI VTNTTVSRPA GLQGALRSET 

       310        320        330        340        350        360 
GGLSGKPLRD LSTQTIREMY ALTQGRVPII GVGGVSSGQD ALEKIRAGAS LVQLYTALTF 

       370        380        390 
WGPPVVGKVK RELEALLKEQ GFGGVTDAIG ADHRR

« Hide

Hide | Top

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and sequencing of a human cDNA coding for dihydroorotate dehydrogenase by complementation of the corresponding yeast mutant." Minet M., Dufour M.E., Lacroute F. Gene 121:393-396(1992) [PubMed: 1446837] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLN-7.
[2]	"Recombinant human dihydroorotate dehydrogenase: expression, purification, and characterization of a catalytically functional truncated enzyme." Copeland R.A., Davis J.P., Dowling R.L., Lombardo D., Murphy K.B., Patterson T.A. Arch. Biochem. Biophys. 323:79-86(1995) [PubMed: 7487077] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION.
[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. Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-7. Tissue: Testis.
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin.
[5]	"Functional expression of a fragment of human dihydroorotate dehydrogenase by means of the baculovirus expression vector system, and kinetic investigation of the purified recombinant enzyme." Knecht W., Bergjohann U., Gonski S., Kirschbaum B., Loffler M. Eur. J. Biochem. 240:292-301(1996) [PubMed: 8925840] [Abstract] Cited for: ENZYME ACTIVITY.
[6]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[7]	"Structures of human dihydroorotate dehydrogenase in complex with antiproliferative agents." Liu S., Neidhardt E.A., Grossman T.H., Ocain T., Clardy J. Structure 8:25-33(2000) [PubMed: 10673429] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 29-395.
+	Additional computationally mapped references.

Hide | Top

Cross-references

Sequence databases

M94065 mRNA. Translation: AAA50163.1.
AK292293 mRNA. Translation: BAF84982.1.
BC065245 mRNA. Translation: AAH65245.1.

IPI

IPI00024462.

PIR

PC1219.

RefSeq

NP_001352.2.

UniGene

Hs.654427

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1D3G	X-ray	1.60	A	29-395	[»]
1D3H	X-ray	1.80	A	29-395	[»]
2B0M	X-ray	2.00	A	29-395	[»]
2BXV	X-ray	2.15	A	29-395	[»]
2FPT	X-ray	2.40	A	29-395	[»]
2FPV	X-ray	1.80	A	29-395	[»]
2FPY	X-ray	2.00	A	29-395	[»]
2FQI	X-ray	1.95	A	29-395	[»]
2PRH	X-ray	2.40	A	29-395	[»]
2PRL	X-ray	2.10	A	29-395	[»]
2PRM	X-ray	3.00	A	29-395	[»]

ModBase

Search...

Proteomic databases

PRIDE

Q02127.

Genome annotation databases

Ensembl

ENSG00000102967. Homo sapiens. [Contig view]

GeneID

1723.

KEGG

hsa:1723.

Organism-specific databases

GeneCards

GC16P070600.

H-InvDB

HIX0013221.

HGNC

HGNC:2867. DHODH.

HPA

HPA010123.
HPA011942.

MIM

126064. gene.

PharmGKB

PA27327.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q02127.

HOVERGEN

Q02127.

OMA

Q02127. AALNRMG.

Enzyme and pathway databases

BRENDA

1.3.3.1. 247.

Reactome

REACT_1698. Nucleotide metabolism.

Gene expression databases

ArrayExpress

Q02127.

Bgee

Q02127.

CleanEx

HS_DHODH.

GermOnline

ENSG00000102967. Homo sapiens.

Family and domain databases

InterPro

IPR013785. Aldolase_TIM.
IPR012135. Dihydroorotate_DH_1_2.
IPR005719. Dihydroorotate_DH_2.
IPR001295. Dihydroorotate_DH_CS.
[Graphical view]

Gene3D

G3DSA:3.20.20.70. Aldolase_TIM. 1 hit.

Pfam

PF01180. DHO_dh. 1 hit.
[Graphical view]

PIRSF

PIRSF000164. DHO_oxidase. 1 hit.

TIGRFAMs

TIGR01036. pyrD_sub2. 1 hit.

PROSITE

PS00911. DHODEHASE_1. 1 hit.
PS00912. DHODEHASE_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB01117. Atovaquone.
DB01097. Leflunomide.

NextBio

6971.

SOURCE

Search...

Hide | Top

Entry information

Entry name

PYRD_HUMAN

Accession

Primary (citable) accession number: Q02127
Secondary accession number(s): A8K8C8, Q6P176

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	December 7, 2004
Last modified:	June 16, 2009
This is version 100 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Hide | Top