UROD

UROD
Dostupne strukture PDB Pretraga ortologa: PDBe RCSB Spisak PDB ID kodova 1JPH, 1JPI, 1JPK, 1R3Q, 1R3R, 1R3S, 1R3T, 1R3V, 1R3W, 1R3Y, 1URO, 2Q6Z, 2Q71, 3GVQ, 3GVR, 3GVV, 3GVW, 3GW0, 3GW3
Identifikatori
Aliasi	UROD
Vanjski ID-jevi	OMIM: 613521 MGI: 98916 HomoloGene: 320 GeneCards: UROD
Lokacija gena (čovjek) Hrom. Hromosom 1 (čovjek) Bend 1p34.1 Početak 45,010,950 bp Kraj 45,015,575 bp
Lokacija gena (miš) Hrom. Hromosom 4 (miš) Bend 4 D1|4 53.41 cM Početak 116,847,162 bp Kraj 116,851,610 bp
Obrazac RNK ekspresije Više referentnih podataka o ekspresiji
Ontologija gena Molekularna funkcija • GO:0001948, GO:0016582 vezivanje za proteine • lyase activity • uroporphyrinogen decarboxylase activity • carboxy-lyase activity Ćelijska komponenta • nukleoplazma • citoplazma • citosol Biološki proces • protoporphyrinogen IX biosynthetic process • porphyrin-containing compound biosynthetic process • heme biosynthetic process • heme metabolic process Izvori:Amigo / QuickGO
Ortolozi
Vrste	Čovjek	Miš
Entrez	7389	22275
Ensembl	ENSG00000126088	ENSMUSG00000028684
UniProt	P06132	P70697
RefSeq (mRNK)	NM_000374	NM_009478
RefSeq (bjelančevina)	NP_000365	NP_033504
Lokacija (UCSC)	Chr 1: 45.01 – 45.02 Mb	Chr 4: 116.85 – 116.85 Mb
PubMed pretraga
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

Uroporpfirinogen III dekarboksilaza (uroporfirinogen dekarboksilaza ili UROD) jest enzim (EC 4.1.1.37) koji je kod ljudi kodiran genom UROD sa hromosoma 1.

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 367 aminokiselina, a molekulska težina 40.787 Da.

• C: Cistein
• D: Asparaginska kiselina
• E: Glutaminska kiselina
• F: Fenilalanin
• G: Glicin
• H: Histidin
• I: Izoleucin
• K: Lizin
• L: Leucin
• M: Metionin
• N: Asparagin
• P: Prolin
• Q: Glutamin
• R: Arginin
• S: Serin
• T: Treonin
• V: Valin
• W: Triptofan
• Y: Tirozin

10		20		30		40		50
MEANGLGPQG		FPELKNDTFL		RAAWGEETDY		TPVWCMRQAG		RYLPEFRETR
AAQDFFSTCR		SPEACCELTL		QPLRRFPLDA		AIIFSDILVV		PQALGMEVTM
VPGKGPSFPE		PLREEQDLER		LRDPEVVASE		LGYVFQAITL		TRQRLAGRVP
LIGFAGAPWT		LMTYMVEGGG		SSTMAQAKRW		LYQRPQASHQ		LLRILTDALV
PYLVGQVVAG		AQALQLFESH		AGHLGPQLFN		KFALPYIRDV		AKQVKARLRE
AGLAPVPMII		FAKDGHFALE		ELAQAGYEVV		GLDWTVAPKK		ARECVGKTVT
LQGNLDPCAL		YASEEEIGQL		VKQMLDDFGP		HRYIANLGHG		LYPDMDPEHV
GAFVDAVHKH		SRLLRQN

Funkcija

Uroporfirinogen III dekarboksilaza je homodimerni enzim (PDB 1URO) koji katalizuje peti korak u heme biosintezi, što odgovara eliminaciji karboksil grupa sa četiri acetatne strane lanci uroporfirinogen III daju koproporfirinogen III:

uroporfirinogen III $\rightleftharpoons$ koproporfirinogen III + 4 CO₂

Mehanizam

Pri niskim koncentracijama supstrata, vjeruje se da reakcija slijedi uređeni put, sa sekvencnim uklanjanjem CO₂ iz D, A, B i C prstenova, dok se pri višim razinama supstrata/enzima izgleda da je operativna nasumična ruta. Enzim u rastvoru funkcionira kao dimer, a i enzimi čovjeka i duhana su kristalizirani i riješeni u dobrim rezolucijama.

Reakcija koju je katalizirao UROD

UROD se smatra neobičnom dekarboksilazom, jer vrši dekarboksilaciju bez intervencije bilo kakvih kofaktora, za razliku od velike većine dekarboksilaza. Nedavno je predloženo da se njegov mehanizam odvija kroz protonaciju supstrata pomoću argininskih ostatka.

Klinički značaj

Poznato je da mutacije i nedostatak ovog enzima uzrokuju porodičnu porphyria cutanea tarda i hepatoeritropoetsku porfiriju.

Izvještaj iz 2008. pokazao je da je nekatalizirana brzina UroD-ove reakcije 10⁻¹⁹ s⁻¹, tako da je pri pH 10 ubrzanje UroD u odnosu na nekataliziranu brzinu, tj. stručnost, veća negop za bilo koji poznati enzim, 6 x 10²⁴ M⁻¹.

Predloženi mehanizam reakcije uroporfirinogen III dekarboksilaze

Sinteza hema: — neke reakcije dešavaju u citoplazmi, a neke u mitohondrijama (žuto)

Dopunska literatura

• 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. doi:10.1007/bf00219182. hdl:1765/58484. PMID 1634232. S2CID 31811381.
• 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. S2CID 22358220.
• 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. doi:10.1182/blood.V73.4.892.892. 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. doi:10.1016/S0021-9258(18)67589-1. 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. S2CID 34478515.
• 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. Bibcode:1986Sci...234..732D. 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. doi:10.1182/blood.V88.9.3589.bloodjournal8893589. 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. S2CID 28379777.
• 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): 412–413. 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.

Vanjski linkovi

• P06132