UROD

ウロポルフィリノーゲン脱炭酸酵素 uroporphyrinogen decarboxylase

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/06/26 06:51:10」(JST)

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Uroporphyrinogen decarboxylase
PDB rendering based on 1jph.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1JPH, 1JPI, 1JPK, 1R3Q, 1R3R, 1R3S, 1R3T, 1R3V, 1R3W, 1R3Y, 1URO, 2Q6Z, 2Q71, 3GVQ, 3GVR, 3GVV, 3GVW, 3GW0, 3GW3
Identifiers
Symbols	UROD ; PCT; UPD
External IDs	OMIM: 613521 MGI: 98916 HomoloGene: 320 ChEMBL: 1681619 GeneCards: UROD Gene
EC number	4.1.1.37
Gene ontology Molecular function • uroporphyrinogen decarboxylase activity Cellular component • nucleus • nucleolus • cytoplasm • cytosol • microtubule cytoskeleton Biological process • porphyrin-containing compound metabolic process • protoporphyrinogen IX biosynthetic process • heme biosynthetic process • small molecule metabolic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7389	22275
Ensembl	ENSG00000126088	ENSMUSG00000028684
UniProt	P06132	P70697
RefSeq (mRNA)	NM_000374	NM_009478
RefSeq (protein)	NP_000365	NP_033504
Location (UCSC)	Chr 1: 45.48 – 45.48 Mb	Chr 4: 116.99 – 116.99 Mb
PubMed search	[1]	[2]

Uroporphyrinogen decarboxylase, also known as UROD, is an enzyme that in humans is encoded by the UROD gene.

Function

This gene encodes the fifth enzyme of the heme biosynthetic pathway. This enzyme is responsible for catalyzing the conversion of uroporphyrinogen to coproporphyrinogen through the removal of four carboxymethyl side chains.

Uroporphyrinogen III decarboxylase (UroD) is a homodimeric enzyme (EC 4.1.1.37, PDB 1URO) that catalyzes the fifth step in heme biosynthesis: the elimination of carboxyl groups from the four acetate side chains of uroporphyrinogen III to yield coproporphyrinogen III.

Clinical significance

Mutations and deficiency in this enzyme are known to cause familial porphyria cutanea tarda and hepatoerythropoietic porphyria.

Mechanism

At low substrate concentrations, the reaction is believed to follow an ordered route, with the sequential removal of CO₂ from the D, A, B, and C rings, whereas at higher substrate/enzyme levels a random route seems to be operative. The enzyme functions as a dimer in solution, and both the enzymes from human and tobacco have been crystallized and solved at good resolutions.

The reaction catalyzed by UroD

UroD is regarded as an unusual decarboxylase, since it performs decarboxylations without the intervention of any cofactors, unlike the vast majority of decarboxylases. Its mechanism has recently been proposed to proceed through substrate protonation by an arginine residue. A 2008 report demonstrated that the uncatalyzed rate for UroD's reaction is 10⁻¹⁹ s⁻¹, so at pH 10 the rate acceleration of UroD relative to the uncatalyzed rate, catalytic proficiency, is the largest for any enzyme known, 6 x 10²⁴ M⁻¹.

Proposed reaction mechanism of uroporphyrinogen III decarboxyklase

References

Further reading

• Elder GH, Lee GB, Tovey JA (1978). "Decreased activity of hepatic uroporphyrinogen decarboxylase in sporadic porphyria cutanea tarda.". N. Engl. J. Med. 299 (6): 274–8. doi:10.1056/NEJM197808102990603. PMID 661926. 
• de Verneuil H, Bourgeois F, de Rooij F, et al. (1992). "Characterization of a new mutation (R292G) and a deletion at the human uroporphyrinogen decarboxylase locus in two patients with hepatoerythropoietic porphyria.". Hum. Genet. 89 (5): 548–52. PMID 1634232. 
• Romana M, Grandchamp B, Dubart A, et al. (1991). "Identification of a new mutation responsible for hepatoerythropoietic porphyria.". Eur. J. Clin. Invest. 21 (2): 225–9. doi:10.1111/j.1365-2362.1991.tb01814.x. PMID 1905636. 
• Garey JR, Harrison LM, Franklin KF, et al. (1990). "Uroporphyrinogen decarboxylase: a splice site mutation causes the deletion of exon 6 in multiple families with porphyria cutanea tarda.". J. Clin. Invest. 86 (5): 1416–22. doi:10.1172/JCI114856. PMC 296884. PMID 2243121. 
• Garey JR, Hansen JL, Harrison LM, et al. (1989). "A point mutation in the coding region of uroporphyrinogen decarboxylase associated with familial porphyria cutanea tarda.". Blood 73 (4): 892–5. PMID 2920211. 
• Roméo PH, Raich N, Dubart A, et al. (1986). "Molecular cloning and nucleotide sequence of a complete human uroporphyrinogen decarboxylase cDNA.". J. Biol. Chem. 261 (21): 9825–31. PMID 3015909. 
• Dubart A, Mattei MG, Raich N, et al. (1986). "Assignment of human uroporphyrinogen decarboxylase (URO-D) to the p34 band of chromosome 1.". Hum. Genet. 73 (3): 277–9. doi:10.1007/BF00401245. PMID 3460962. 
• Romana M, Dubart A, Beaupain D, et al. (1987). "Structure of the gene for human uroporphyrinogen decarboxylase.". Nucleic Acids Res. 15 (18): 7343–56. doi:10.1093/nar/15.18.7343. PMC 306252. PMID 3658695. 
• de Verneuil H, Grandchamp B, Beaumont C, et al. (1986). "Uroporphyrinogen decarboxylase structural mutant (Gly281----Glu) in a case of porphyria.". Science 234 (4777): 732–4. doi:10.1126/science.3775362. PMID 3775362. 
• Roberts AG, Elder GH, De Salamanca RE, et al. (1995). "A mutation (G281E) of the human uroporphyrinogen decarboxylase gene causes both hepatoerythropoietic porphyria and overt familial porphyria cutanea tarda: biochemical and genetic studies on Spanish patients.". J. Invest. Dermatol. 104 (4): 500–2. doi:10.1111/1523-1747.ep12605953. PMID 7706766. 
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. 
• Meguro K, Fujita H, Ishida N, et al. (1994). "Molecular defects of uroporphyrinogen decarboxylase in a patient with mild hepatoerythropoietic porphyria". J. Invest. Dermatol. 102 (5): 681–5. doi:10.1111/1523-1747.ep12374134. PMID 8176248. 
• Moran-Jimenez MJ, Ged C, Romana M, et al. (1996). "Uroporphyrinogen decarboxylase: complete human gene sequence and molecular study of three families with hepatoerythropoietic porphyria". Am. J. Hum. Genet. 58 (4): 712–21. PMC 1914669. PMID 8644733. 
• McManus JF, Begley CG, Sassa S, Ratnaike S (1996). "Five new mutations in the uroporphyrinogen decarboxylase gene identified in families with cutaneous porphyria". Blood 88 (9): 3589–600. PMID 8896428. 
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. 
• Whitby FG, Phillips JD, Kushner JP, Hill CP (1998). "Crystal structure of human uroporphyrinogen decarboxylase". EMBO J. 17 (9): 2463–71. doi:10.1093/emboj/17.9.2463. PMC 1170588. PMID 9564029. 
• Mendez M, Sorkin L, Rossetti MV, et al. (1998). "Familial porphyria cutanea tarda: characterization of seven novel uroporphyrinogen decarboxylase mutations and frequency of common hemochromatosis alleles". Am. J. Hum. Genet. 63 (5): 1363–75. doi:10.1086/302119. PMC 1377546. PMID 9792863. 
• Wang H, Long Q, Marty SD, et al. (1998). "A zebrafish model for hepatoerythropoietic porphyria". Nat. Genet. 20 (3): 239–43. doi:10.1038/3041. PMID 9806541. 
• McManus JF, Begley CG, Sassa S, Ratnaike S (1999). "Three new mutations in the uroporphyrinogen decarboxylase gene in familial porphyria cutanea tarda. Mutation in brief no. 237. Online". Hum. Mutat. 13 (5): 412. doi:10.1002/(SICI)1098-1004(1999)13:5<412::AID-HUMU13>3.0.CO;2-N. PMID 10338097. 
• Christiansen L, Ged C, Hombrados I, et al. (1999). "Screening for mutations in the uroporphyrinogen decarboxylase gene using denaturing gradient gel electrophoresis. Identification and characterization of six novel mutations associated with familial PCT". Hum. Mutat. 14 (3): 222–32. doi:10.1002/(SICI)1098-1004(1999)14:3<222::AID-HUMU5>3.0.CO;2-V. PMID 10477430. 

Heme synthesis—note that some reactions occur in the cytoplasm and some in the mitochondrion (yellow)

UpToDate Contents

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• 1. 晩発性皮膚ポルフィリン症および肝骨髄性ポルフィリン症 porphyria cutanea tarda and hepatoerythropoietic porphyria
• 2. 晩発性皮膚ポルフィリン症とC型肝炎ウイルス感染 porphyria cutanea tarda and hepatitis c virus infection
• 3. 緊急時のオピオイド離脱 opioid withdrawal in the emergency setting
• 4. ポルフィリン症：概要 porphyrias an overview
• 5. C型肝炎ウイルス感染の肝外症状 extrahepatic manifestations of hepatitis c virus infection

English Journal

• Familial porphyria cutanea tarda in Spain: characterization of eight novel mutations in the UROD gene and haplotype analysis of the common p.G281E mutation.

• Gómez-Abecia S, Morán-Jiménez MJ, Ruiz-Casares E, Henriques-Gil N, García-Pastor I, Garrido-Astray MC, Enríquez de Salamanca R, Méndez M.SourceCentro de Investigación, Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain.
• Gene.Gene.2013 Jun 10;522(1):89-95. doi: 10.1016/j.gene.2013.03.074. Epub 2013 Mar 29.
• Porphyria cutanea tarda (PCT) results from decreased activity of uroporphyrinogen decarboxylase (UROD) in the liver. Deficiency in this enzyme results in accumulation of highly carboxylated porphyrins responsible for the disease. PCT usually occurs in adulthood and is characterized by cutaneous phot
• PMID 23545314

• A possible strategy against head and neck cancer: in silico investigation of three-in-one inhibitors.

• Tsou YA, Chen KC, Chang SS, Wen YR, Chen CY.Sourcea Laboratory of Computational and Systems Biology , China Medical University , Taichung , 40402 , Taiwan.
• Journal of biomolecular structure & dynamics.J Biomol Struct Dyn.2012 Nov 12. [Epub ahead of print]
• Overexpression of epidermal growth factor receptor (EGFR), Her2, and uroporphyrinogen decarboxylase (UROD) occurs in a variety of malignant tumor tissues. UROD has potential to modulate tumor response of radiotherapy for head and neck cancer, and EGFR and Her2 are common drug targets for the treatme
• PMID 23140436

• Molecular analysis of the UROD gene in 17 Argentinean patients with familial porphyria cutanea tarda: characterization of four novel mutations.

• Méndez M, Rossetti MV, Gómez-Abecia S, Morán-Jiménez MJ, Parera V, Batlle A, Enríquez de Salamanca R.SourceCentro de Investigación, Instituto de Investigación Hospital 12 de Octubre, Universidad Complutense de Madrid, Spain. mmendez@h12o.es
• Molecular genetics and metabolism.Mol Genet Metab.2012 Apr;105(4):629-33. doi: 10.1016/j.ymgme.2012.02.002. Epub 2012 Feb 8.
• Porphyria cutanea tarda (PCT) is caused by decreased activity of uroporphyrinogen decarboxylase (UROD) in the liver. The disease usually occurs in adulthood and is characterized by cutaneous photosensitivity, hyperpigmentation, skin fragility and hypertrichosis, due to the accumulation of porphyrins
• PMID 22382040

Japanese Journal

• 色素関係 ウロポルフィリノーゲン脱炭酸酵素(UROD) (広範囲 血液・尿化学検査,免疫学的検査(第7版・1)その数値をどう読むか) -- (生化学的検査(1))

• 近藤 雅雄
• 日本臨床 67(-), 787-789, 2009-12
• NAID 40016874615

• 蒸すを用いた赤ワインとジエトキシカルボニルジヒドロコリジン(DDC)によるウロポルフィリノーゲンデカルボキシラーゼ(UROD)活性への影響

• 網中 雅仁,中村 磐男,大江 敏江,田中 利明,工藤 吉郎
• 産業衛生学雑誌 = Journal of occupational health 39, S182, 1997-04-01
• NAID 10010998369

• 『アンナ・カレーニナ』における「内的関係」 : 「赤い袋」と「小さな髭もじゃの男」について

• 佐藤 雄亮
• ロシア語ロシア文学研究 (27), 41-52, 1995-09-01
• В <<Анне Карениной>> автор очень упорно описывает красный мешочек Анны, как будто мешочек имеет какое-то особенное значение. Эта деталь появвляется неоднократно уже в 1-ой части, при этом …
• NAID 110001248540

Related Links

• UROD Gene - GeneCards | DCUP Protein | DCUP Antibody

Complete information for UROD gene (Protein Coding), Uroporphyrinogen Decarboxylase, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium ... Familial ...

• Развлекательно-публицистический портал Urod.ru

Электрическая почта — urod@urod.ru Сообщить об ошибке — support@urod.ru rss - Читать новости в RSS Disclaimer: Все права на публикуемые аудио, видео, графические и текстовые материалы ...

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★リンクテーブル★

リンク元	「ウロポルフィリノーゲン脱炭酸酵素」「uroporphyrinogen decarboxylase」
拡張検索	「UROD deficiency」

「ウロポルフィリノーゲン脱炭酸酵素」

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英

uroporphyrinogen decarboxylase, UROD

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ウロポルフィリノーゲンデカルボキシラーゼ

「uroporphyrinogen decarboxylase」

　　[★] ウロポルフィリノーゲン脱炭酸酵素 UROD

「UROD deficiency」

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同

uroporphyrinogen decarboxylase