UniProt functional annotation for Q02127



	UniProt functional annotation for Q02127

UniProt code: Q02127.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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

Catalytic activity: Reaction=(S)-dihydroorotate + a quinone = a quinol + orotate; Xref=Rhea:RHEA:30187, ChEBI:CHEBI:24646, ChEBI:CHEBI:30839, ChEBI:CHEBI:30864, ChEBI:CHEBI:132124; EC=1.3.5.2; Evidence={ECO:0000269|PubMed:8925840};

Cofactor: Name=FMN; Xref=ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:10673429}; Note=Binds 1 FMN per subunit. {ECO:0000269|PubMed:10673429};

Pathway: Pyrimidine metabolism; UMP biosynthesis via de novo pathway; orotate from (S)-dihydroorotate (quinone route): step 1/1.

Subunit: Monomer. {ECO:0000269|PubMed:10673429, ECO:0000269|PubMed:16480261}.

Subcellular location: Mitochondrion inner membrane {ECO:0000269|PubMed:10727948}; Single-pass membrane protein {ECO:0000269|PubMed:10727948}.

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

Disease: Postaxial acrofacial dysostosis (POADS) [MIM:263750]: POADS 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. {ECO:0000269|PubMed:19915526}. Note=The disease is caused by variants affecting the gene represented in this entry.

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. {ECO:0000305|PubMed:19915526}.

Similarity: Belongs to the dihydroorotate dehydrogenase family. Type 2 subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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


Catalytic activity:		Reaction=(S)-dihydroorotate + a quinone = a quinol + orotate; Xref=Rhea:RHEA:30187, ChEBI:CHEBI:24646, ChEBI:CHEBI:30839, ChEBI:CHEBI:30864, ChEBI:CHEBI:132124; EC=1.3.5.2; Evidence={ECO:0000269\|PubMed:8925840};
Cofactor:		Name=FMN; Xref=ChEBI:CHEBI:58210; Evidence={ECO:0000269\|PubMed:10673429}; Note=Binds 1 FMN per subunit. {ECO:0000269\|PubMed:10673429};
Pathway:		Pyrimidine metabolism; UMP biosynthesis via de novo pathway; orotate from (S)-dihydroorotate (quinone route): step 1/1.
Subunit:		Monomer. {ECO:0000269\|PubMed:10673429, ECO:0000269\|PubMed:16480261}.
Subcellular location:		Mitochondrion inner membrane {ECO:0000269\|PubMed:10727948}; Single-pass membrane protein {ECO:0000269\|PubMed:10727948}.
Ptm:		The uncleaved transit peptide is required for mitochondrial targeting and proper membrane integration.
Disease:		Postaxial acrofacial dysostosis (POADS) [MIM:263750]: POADS 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. {ECO:0000269\|PubMed:19915526}. Note=The disease is caused by variants affecting the gene represented in this entry.
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. {ECO:0000305\|PubMed:19915526}.
Similarity:		Belongs to the dihydroorotate dehydrogenase family. Type 2 subfamily. {ECO:0000305}.