ID DCUP_HUMAN Reviewed; 367 AA. AC P06132; A8K762; Q16863; Q16883; Q53YB8; Q53ZP6; Q6IB28; Q9BUZ0; DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 2. DT 27-MAR-2024, entry version 237. DE RecName: Full=Uroporphyrinogen decarboxylase {ECO:0000305}; DE Short=UPD; DE Short=URO-D; DE EC=4.1.1.37 {ECO:0000269|PubMed:11069625, ECO:0000269|PubMed:14633982, ECO:0000269|PubMed:21668429}; GN Name=UROD {ECO:0000312|HGNC:HGNC:12591}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 2-21; 37-65; 101-123; RP 175-251; 259-322; 325-344 AND 346-367. RX PubMed=3015909; DOI=10.1016/s0021-9258(18)67589-1; RA Romeo P.-H., Raich N., Dubart A., Beaupain D., Pryor M., Kushner J.P., RA Cohen-Solal M., Goossens M.; RT "Molecular cloning and nucleotide sequence of a complete human RT uroporphyrinogen decarboxylase cDNA."; RL J. Biol. Chem. 261:9825-9831(1986). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HEP LEU-62; LEU-77; GLU-281 RP AND CYS-311. RX PubMed=8644733; RA Moran-Jimenez M.J., Ged C., Romana M., de Salamanca R.E., Taieb A., RA Topi G., D'Alessandro L., de Verneuil H.; RT "Uroporphyrinogen decarboxylase: complete human gene sequence and molecular RT study of three families with hepatoerythropoietic porphyria."; RL Am. J. Hum. Genet. 58:712-721(1996). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Mendez M.; RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LEU-77. RA Martinez di Montemuros F., Fiorelli G., Cappellini M.D.; RT "Uroporphyrinogen decarboxylase (UROD) cDNA sequence from Italian RT population."; RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-77. RA Martinez di Montemuros F., Cappellini M.D.; RT "Molecular characterization of UROD gene in Italian patients with familial RT porphyria cutanea tarda (f-PCT)."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-303. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., RA LaBaer J.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Skeletal muscle; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-303. RC TISSUE=Lymph; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [13] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-7. RX PubMed=3658695; DOI=10.1093/nar/15.18.7343; RA Romana M., Dubart A., Beaupain D., Chabret C., Goossens M., Romeo P.-H.; RT "Structure of the gene for human uroporphyrinogen decarboxylase."; RL Nucleic Acids Res. 15:7343-7356(1987). RN [14] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 95-258, AND INVOLVEMENT IN FPCT. RX PubMed=2243121; DOI=10.1172/jci114856; RA Garey J.R., Harrison L.M., Franklin K.F., Metcalf K.M., Radisky E.S., RA Kushner J.P.; RT "Uroporphyrinogen decarboxylase: a splice site mutation causes the deletion RT of exon 6 in multiple families with porphyria cutanea tarda."; RL J. Clin. Invest. 86:1416-1422(1990). RN [15] RP CRYSTALLIZATION, IDENTIFICATION BY MASS SPECTROMETRY, AND SUBUNIT. RX PubMed=9194196; DOI=10.1002/pro.5560060624; RA Phillips J.D., Whitby F.G., Kushner J.P., Hill C.P.; RT "Characterization and crystallization of human uroporphyrinogen RT decarboxylase."; RL Protein Sci. 6:1343-1346(1997). RN [16] RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=18004775; DOI=10.1002/prot.21755; RA Cunha L., Kuti M., Bishop D.F., Mezei M., Zeng L., Zhou M.M., Desnick R.J.; RT "Human uroporphyrinogen III synthase: NMR-based mapping of the active RT site."; RL Proteins 71:855-873(2008). RN [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [19] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [20] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [21] RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS), AND SUBUNIT. RX PubMed=9564029; DOI=10.1093/emboj/17.9.2463; RA Whitby F.G., Phillips J.D., Kushner J.P., Hill C.P.; RT "Crystal structure of human uroporphyrinogen decarboxylase."; RL EMBO J. 17:2463-2471(1998). RN [22] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF VARIANTS FPCT ASP-156; LEU-232 AND RP THR-260, FUNCTION, CATALYTIC ACTIVITY, PATHWAY, VARIANTS FPCT GLU-25; RP SER-80; GLN-134; ASP-156; ARG-165; LYS-167; PRO-193; LEU-232; GLN-253 AND RP THR-260, AND CHARACTERIZATION OF VARIANTS FPCT GLU-25; SER-80; GLN-134; RP ASP-156; ARG-165; LYS-167; PRO-193; LEU-232; GLN-253 AND THR-260. RX PubMed=11719352; DOI=10.1182/blood.v98.12.3179; RA Phillips J.D., Parker T.L., Schubert H.L., Whitby F.G., Hill C.P., RA Kushner J.P.; RT "Functional consequences of naturally occurring mutations in human RT uroporphyrinogen decarboxylase."; RL Blood 98:3179-3185(2001). RN [23] RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF WILD-TYPE AND MUTANTS ASN-86; RP GLU-86; GLY-86 AND PHE-164 IN COMPLEX WITH SUBSTRATE ANALOGS, FUNCTION, RP CATALYTIC ACTIVITY, PATHWAY, MUTAGENESIS OF ASP-86 AND TYR-164, AND RP REACTION MECHANISM. RX PubMed=14633982; DOI=10.1093/emboj/cdg606; RA Phillips J.D., Whitby F.G., Kushner J.P., Hill C.P.; RT "Structural basis for tetrapyrrole coordination by uroporphyrinogen RT decarboxylase."; RL EMBO J. 22:6225-6233(2003). RN [24] RP VARIANT HEP GLU-281. RX PubMed=3775362; DOI=10.1126/science.3775362; RA de Verneuil H., Grandchamp B., Beaumont C., Picat C., Nordmann Y.; RT "Uroporphyrinogen decarboxylase structural mutant (Gly-281-->Glu) in a case RT of porphyria."; RL Science 234:732-734(1986). RN [25] RP VARIANT FPCT VAL-281. RX PubMed=2920211; RA Garey J.R., Hansen J.L., Harrison L.M., Kennedy J.B., Kushner J.P.; RT "A point mutation in the coding region of uroporphyrinogen decarboxylase RT associated with familial porphyria cutanea tarda."; RL Blood 73:892-895(1989). RN [26] RP VARIANT HEP LYS-167. RX PubMed=1905636; DOI=10.1111/j.1365-2362.1991.tb01814.x; RA Romana M., Grandchamp B., Dubart A., Amselem S., Chabret C., Nordmann Y., RA Goossens M., Romeo P.-H.; RT "Identification of a new mutation responsible for hepatoerythropoietic RT porphyria."; RL Eur. J. Clin. Invest. 21:225-229(1991). RN [27] RP VARIANT HEP GLY-292. RX PubMed=1634232; DOI=10.1007/bf00219182; RA de Verneuil H., Bourgeois F., de Rooij F.W.M., Siersema P.D., RA Wilson J.H.P., Grandchamp B., Nordmann Y.; RT "Characterization of a new mutation (R292G) and a deletion at the human RT uroporphyrinogen decarboxylase locus in two patients with RT hepatoerythropoietic porphyria."; RL Hum. Genet. 89:548-552(1992). RN [28] RP VARIANTS HEP GLN-134 AND PRO-220. RX PubMed=8176248; DOI=10.1111/1523-1747.ep12374134; RA Meguro K., Fujita H., Ishida N., Akagi R., Kurihara T., Galbraith R.A., RA Kappas A., Zabriskie J.B., Toback A.C., Harber L.C., Sassa S.; RT "Molecular defects of uroporphyrinogen decarboxylase in a patient with mild RT hepatoerythropoietic porphyria."; RL J. Invest. Dermatol. 102:681-685(1994). RN [29] RP VARIANT FPCT GLU-281. RX PubMed=7706766; DOI=10.1111/1523-1747.ep12605953; RA Roberts A.G., Elder G.H., de Salamanca R.E., Herrero C., Lecha M., RA Mascaro J.M.; RT "A mutation 'G281E' of the human uroporphyrinogen decarboxylase gene causes RT both hepatoerythropoietic porphyria and overt familial porphyria cutanea RT tarda: biochemical and genetic studies on Spanish patients."; RL J. Invest. Dermatol. 104:500-502(1995). RN [30] RP VARIANT HEP GLY-80, AND VARIANTS FPCT GLN-253; ARG-318 AND THR-334. RX PubMed=8896428; RA McManus J.F., Begley C.G., Sassa S., Ratnaike S.; RT "Five new mutations in the uroporphyrinogen decarboxylase gene identified RT in families with cutaneous porphyria."; RL Blood 88:3589-3600(1996). RN [31] RP VARIANTS FPCT ARG-165; PHE-195; LYS-304 AND HIS-332. RX PubMed=9792863; DOI=10.1086/302119; RA Mendez M., Sorkin L., Rossetti M.V., Astrin K.H., Batlle A.M.C., RA Parera V.E., Aizencang G.I., Desnick R.J.; RT "Familial porphyria cutanea tarda: characterization of seven novel RT uroporphyrinogen decarboxylase mutations and frequency of common RT hemochromatosis alleles."; RL Am. J. Hum. Genet. 63:1363-1375(1998). RN [32] RP VARIANT FPCT GLN-134. RX PubMed=10338097; RX DOI=10.1002/(sici)1098-1004(1999)13:5<412::aid-humu13>3.0.co;2-n; RA McManus J.F., Begley C.G., Sassa S., Ratnaike S.; RT "Three new mutations in the uroporphyrinogen decarboxylase gene in familial RT porphyria cutanea tarda."; RL Hum. Mutat. 13:412-412(1999). RN [33] RP VARIANTS FPCT LEU-229 AND THR-324. RX PubMed=10477430; RX DOI=10.1002/(sici)1098-1004(1999)14:3<222::aid-humu5>3.0.co;2-v; RA Christiansen L., Ged C., Hombrados I., Broens-Poulsen J., Fontanellas A., RA de Verneuil H., Hoerder M., Petersen N.E.; RT "Screening for mutations in the uroporphyrinogen decarboxylase gene using RT denaturing gradient gel electrophoresis. Identification and RT characterization of six novel mutations associated with familial PCT."; RL Hum. Mutat. 14:222-232(1999). RN [34] RP VARIANTS FPCT SER-80; GLN-134; PRO-144; GLN-216; LYS-218; VAL-281; ARG-282; RP SER-303 AND ARG-318, FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND RP CHARACTERIZATION OF VARIANTS FPCT PRO-144 AND LYS-218. RX PubMed=11069625; DOI=10.1046/j.1523-1747.2000.00148.x; RA Brady J.J., Jackson H.A., Roberts A.G., Morgan R.R., Whatley S.D., RA Rowlands G.L., Darby C., Shudell E., Watson R., Paiker J., Worwood M.W., RA Elder G.H.; RT "Co-inheritance of mutations in the uroporphyrinogen decarboxylase and RT hemochromatosis genes accelerates the onset of porphyria cutanea tarda."; RL J. Invest. Dermatol. 115:868-874(2000). RN [35] RP VARIANTS FPCT GLN-142; GLN-161; PHE-219 AND SER-235. RX PubMed=11295834; DOI=10.1002/humu.35; RA Cappellini M.D., Martinez Di Montemuros F., Tavazzi D., Fargion S., RA Pizzuti A., Comino A., Cainelli T., Fiorelli G.; RT "Seven novel point mutations in the uroporphyrinogen decarboxylase (UROD) RT gene in patients with familial porphyria cutanea tarda (f-PCT)."; RL Hum. Mutat. 17:350-350(2001). RN [36] RP VARIANT HEP LEU-46, FUNCTION, AND CHARACTERIZATION OF VARIANT HEP LEU-46. RX PubMed=12071824; DOI=10.1001/archderm.138.7.957; RA Ged C., Ozalla D., Herrero C., Lecha M., Mendez M., de Verneuil H., RA Mascaro J.M.; RT "Description of a new mutation in hepatoerythropoietic porphyria and RT prenatal exclusion of a homozygous fetus."; RL Arch. Dermatol. 138:957-960(2002). RN [37] RP VARIANT HEP LEU-46. RX PubMed=15491440; DOI=10.1111/j.1365-2133.2004.06101.x; RA Armstrong D.K.B., Sharpe P.C., Chambers C.R., Whatley S.D., Roberts A.G., RA Elder G.H.; RT "Hepatoerythropoietic porphyria: a missense mutation in the UROD gene is RT associated with mild disease and an unusual porphyrin excretion pattern."; RL Br. J. Dermatol. 151:920-923(2004). RN [38] RP VARIANT HEP ARG-168, AND CHARACTERIZATION OF VARIANT HEP ARG-168. RX PubMed=17240319; DOI=10.1016/j.trsl.2006.08.006; RA Phillips J.D., Whitby F.G., Stadtmueller B.M., Edwards C.Q., Hill C.P., RA Kushner J.P.; RT "Two novel uroporphyrinogen decarboxylase (URO-D) mutations causing RT hepatoerythropoietic porphyria (HEP)."; RL Transl. Res. 149:85-91(2007). RN [39] RP VARIANT HEP ASP-170, FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND RP CHARACTERIZATION OF VARIANT HEP ASP-170. RX PubMed=21668429; DOI=10.1111/j.1365-2133.2011.10453.x; RA To-Figueras J., Phillips J., Gonzalez-Lopez J.M., Badenas C., Madrigal I., RA Gonzalez-Romaris E.M., Ramos C., Aguirre J.M., Herrero C.; RT "Hepatoerythropoietic porphyria due to a novel mutation in the RT uroporphyrinogen decarboxylase gene."; RL Br. J. Dermatol. 165:499-505(2011). CC -!- FUNCTION: Catalyzes the sequential decarboxylation of the four acetate CC side chains of uroporphyrinogen to form coproporphyrinogen and CC participates in the fifth step in the heme biosynthetic pathway CC (PubMed:14633982, PubMed:11069625, PubMed:21668429, PubMed:11719352, CC PubMed:18004775). Isomer I or isomer III of uroporphyrinogen may serve CC as substrate, but only coproporphyrinogen III can ultimately be CC converted to heme (PubMed:14633982, PubMed:11069625, PubMed:21668429, CC PubMed:11719352). In vitro also decarboxylates pentacarboxylate CC porphyrinogen I (PubMed:12071824). {ECO:0000269|PubMed:11069625, CC ECO:0000269|PubMed:11719352, ECO:0000269|PubMed:12071824, CC ECO:0000269|PubMed:14633982, ECO:0000269|PubMed:18004775, CC ECO:0000269|PubMed:21668429}. CC -!- CATALYTIC ACTIVITY: CC Reaction=4 H(+) + uroporphyrinogen III = 4 CO2 + coproporphyrinogen CC III; Xref=Rhea:RHEA:19865, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, CC ChEBI:CHEBI:57308, ChEBI:CHEBI:57309; EC=4.1.1.37; CC Evidence={ECO:0000269|PubMed:11069625, ECO:0000269|PubMed:14633982, CC ECO:0000269|PubMed:18004775, ECO:0000269|PubMed:21668429}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19866; CC Evidence={ECO:0000305|PubMed:11069625, ECO:0000305|PubMed:14633982, CC ECO:0000305|PubMed:21668429}; CC -!- CATALYTIC ACTIVITY: CC Reaction=4 H(+) + uroporphyrinogen I = 4 CO2 + coproporphyrinogen I; CC Xref=Rhea:RHEA:31239, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, CC ChEBI:CHEBI:62626, ChEBI:CHEBI:62631; CC Evidence={ECO:0000269|PubMed:11719352, ECO:0000269|PubMed:14633982, CC ECO:0000269|PubMed:21668429}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31240; CC Evidence={ECO:0000305|PubMed:11719352, ECO:0000305|PubMed:14633982, CC ECO:0000305|PubMed:21668429}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC pH dependence: CC Optimum pH is 6.8. {ECO:0000269|PubMed:18004775}; CC -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX CC biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 4/4. CC {ECO:0000269|PubMed:11069625, ECO:0000269|PubMed:11719352, CC ECO:0000269|PubMed:14633982, ECO:0000269|PubMed:21668429}. CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:14633982, CC ECO:0000269|PubMed:9194196, ECO:0000269|PubMed:9564029}. CC -!- INTERACTION: CC P06132; Q96KN1: LRATD2; NbExp=7; IntAct=EBI-2871776, EBI-9057780; CC P06132; P46019: PHKA2; NbExp=3; IntAct=EBI-2871776, EBI-1642846; CC P06132; C9JJ79: PILRA; NbExp=5; IntAct=EBI-2871776, EBI-12117156; CC P06132; Q96PN8: TSSK3; NbExp=3; IntAct=EBI-2871776, EBI-3918381; CC -!- SUBCELLULAR LOCATION: Cytoplasm. CC -!- DISEASE: Familial porphyria cutanea tarda (FPCT) [MIM:176100]: A form CC of porphyria. Porphyrias are inherited defects in the biosynthesis of CC heme, resulting in the accumulation and increased excretion of CC porphyrins or porphyrin precursors. They are classified as CC erythropoietic or hepatic, depending on whether the enzyme deficiency CC occurs in red blood cells or in the liver. Familial porphyria cutanea CC tarda is an autosomal dominant disorder characterized by light- CC sensitive dermatitis, with onset in later life. It is associated with CC the excretion of large amounts of uroporphyrin in the urine. Iron CC overload is often present in association with varying degrees of liver CC damage. {ECO:0000269|PubMed:10338097, ECO:0000269|PubMed:10477430, CC ECO:0000269|PubMed:11069625, ECO:0000269|PubMed:11295834, CC ECO:0000269|PubMed:11719352, ECO:0000269|PubMed:2243121, CC ECO:0000269|PubMed:2920211, ECO:0000269|PubMed:7706766, CC ECO:0000269|PubMed:8896428, ECO:0000269|PubMed:9792863}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Hepatoerythropoietic porphyria (HEP) [MIM:176100]: A form of CC porphyria. Porphyrias are inherited defects in the biosynthesis of CC heme, resulting in the accumulation and increased excretion of CC porphyrins or porphyrin precursors. They are classified as CC erythropoietic or hepatic, depending on whether the enzyme deficiency CC occurs in red blood cells or in the liver. HEP is a cutaneous porphyria CC that presents in infancy. It is characterized biochemically by CC excessive excretion of acetate-substituted porphyrins and accumulation CC of protoporphyrin in erythrocytes. Uroporphyrinogen decarboxylase CC levels are very low in erythrocytes and cultured skin fibroblasts. CC {ECO:0000269|PubMed:12071824, ECO:0000269|PubMed:15491440, CC ECO:0000269|PubMed:1634232, ECO:0000269|PubMed:17240319, CC ECO:0000269|PubMed:1905636, ECO:0000269|PubMed:21668429, CC ECO:0000269|PubMed:3775362, ECO:0000269|PubMed:8176248, CC ECO:0000269|PubMed:8644733, ECO:0000269|PubMed:8896428}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the uroporphyrinogen decarboxylase family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Uroporphyrinogen III decarboxylase CC entry; CC URL="https://en.wikipedia.org/wiki/Uroporphyrinogen_III_decarboxylase"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M14016; AAA61258.1; -; mRNA. DR EMBL; X89267; CAA61540.1; -; Genomic_DNA. DR EMBL; AF047383; AAC03563.1; -; Genomic_DNA. DR EMBL; AF104421; AAD04571.1; -; mRNA. DR EMBL; AF104422; AAD04572.1; -; mRNA. DR EMBL; AF104423; AAD04573.1; -; mRNA. DR EMBL; AF104424; AAD04574.1; -; mRNA. DR EMBL; AF104425; AAD04575.1; -; mRNA. DR EMBL; AF104426; AAD04576.1; -; mRNA. DR EMBL; AF104427; AAD04577.1; -; mRNA. DR EMBL; AF104428; AAD04578.1; -; mRNA. DR EMBL; AF104429; AAD04579.1; -; mRNA. DR EMBL; AF104430; AAD04580.1; -; mRNA. DR EMBL; AF104431; AAD04581.1; -; mRNA. DR EMBL; AF104432; AAD04582.1; -; mRNA. DR EMBL; AF104433; AAD04583.1; -; mRNA. DR EMBL; AF104434; AAD04584.1; -; mRNA. DR EMBL; AF104435; AAD04585.1; -; mRNA. DR EMBL; AF104436; AAD04586.1; -; mRNA. DR EMBL; AF104437; AAD04587.1; -; mRNA. DR EMBL; AF104438; AAD04588.1; -; mRNA. DR EMBL; AF104439; AAD04589.1; -; mRNA. DR EMBL; AF104440; AAD04590.1; -; mRNA. DR EMBL; AY292986; AAP44118.1; -; Genomic_DNA. DR EMBL; BT006737; AAP35383.1; -; mRNA. DR EMBL; CR456976; CAG33257.1; -; mRNA. DR EMBL; CR542057; CAG46854.1; -; mRNA. DR EMBL; AK291877; BAF84566.1; -; mRNA. DR EMBL; AL359473; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471059; EAX07007.1; -; Genomic_DNA. DR EMBL; BC001778; AAH01778.1; -; mRNA. DR EMBL; U30787; AAC50482.1; -; Genomic_DNA. DR EMBL; M60891; AAB59456.1; -; Genomic_DNA. DR CCDS; CCDS518.1; -. DR PIR; A24411; A24411. DR PIR; G02786; G02786. DR RefSeq; NP_000365.3; NM_000374.4. DR PDB; 1JPH; X-ray; 2.10 A; A=1-367. DR PDB; 1JPI; X-ray; 2.30 A; A=1-367. DR PDB; 1JPK; X-ray; 2.20 A; A=1-367. DR PDB; 1R3Q; X-ray; 1.70 A; A=1-367. DR PDB; 1R3R; X-ray; 1.85 A; A=1-367. DR PDB; 1R3S; X-ray; 1.65 A; A=1-367. DR PDB; 1R3T; X-ray; 1.70 A; A=1-367. DR PDB; 1R3V; X-ray; 1.90 A; A=1-367. DR PDB; 1R3W; X-ray; 1.70 A; A=1-367. DR PDB; 1R3Y; X-ray; 1.75 A; A=1-367. DR PDB; 1URO; X-ray; 1.80 A; A=1-367. DR PDB; 2Q6Z; X-ray; 2.00 A; A=11-366. DR PDB; 2Q71; X-ray; 1.90 A; A=11-366. DR PDB; 3GVQ; X-ray; 2.10 A; A=1-367. DR PDB; 3GVR; X-ray; 2.20 A; A=1-367. DR PDB; 3GVV; X-ray; 2.80 A; A=1-367. DR PDB; 3GVW; X-ray; 2.80 A; A=1-367. DR PDB; 3GW0; X-ray; 2.00 A; A=1-367. DR PDB; 3GW3; X-ray; 1.70 A; A=1-367. DR PDBsum; 1JPH; -. DR PDBsum; 1JPI; -. DR PDBsum; 1JPK; -. DR PDBsum; 1R3Q; -. DR PDBsum; 1R3R; -. DR PDBsum; 1R3S; -. DR PDBsum; 1R3T; -. DR PDBsum; 1R3V; -. DR PDBsum; 1R3W; -. DR PDBsum; 1R3Y; -. DR PDBsum; 1URO; -. DR PDBsum; 2Q6Z; -. DR PDBsum; 2Q71; -. DR PDBsum; 3GVQ; -. DR PDBsum; 3GVR; -. DR PDBsum; 3GVV; -. DR PDBsum; 3GVW; -. DR PDBsum; 3GW0; -. DR PDBsum; 3GW3; -. DR AlphaFoldDB; P06132; -. DR SMR; P06132; -. DR BioGRID; 113235; 40. DR IntAct; P06132; 16. DR MINT; P06132; -. DR STRING; 9606.ENSP00000246337; -. DR ChEMBL; CHEMBL1681619; -. DR DrugBank; DB03727; Coproporphyrin I. DR DrugBank; DB04461; Coproporphyrinogen III. DR GlyGen; P06132; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P06132; -. DR MetOSite; P06132; -. DR PhosphoSitePlus; P06132; -. DR BioMuta; UROD; -. DR DMDM; 2507533; -. DR OGP; P06132; -. DR EPD; P06132; -. DR jPOST; P06132; -. DR MassIVE; P06132; -. DR MaxQB; P06132; -. DR PaxDb; 9606-ENSP00000246337; -. DR PeptideAtlas; P06132; -. DR ProteomicsDB; 51870; -. DR Pumba; P06132; -. DR TopDownProteomics; P06132; -. DR Antibodypedia; 18538; 274 antibodies from 32 providers. DR DNASU; 7389; -. DR Ensembl; ENST00000246337.9; ENSP00000246337.4; ENSG00000126088.14. DR GeneID; 7389; -. DR KEGG; hsa:7389; -. DR MANE-Select; ENST00000246337.9; ENSP00000246337.4; NM_000374.5; NP_000365.3. DR UCSC; uc001cna.3; human. DR AGR; HGNC:12591; -. DR CTD; 7389; -. DR DisGeNET; 7389; -. DR GeneCards; UROD; -. DR GeneReviews; UROD; -. DR HGNC; HGNC:12591; UROD. DR HPA; ENSG00000126088; Low tissue specificity. DR MalaCards; UROD; -. DR MIM; 176100; phenotype. DR MIM; 613521; gene. DR neXtProt; NX_P06132; -. DR OpenTargets; ENSG00000126088; -. DR Orphanet; 443062; Familial porphyria cutanea tarda. DR Orphanet; 95159; Hepatoerythropoietic porphyria. DR PharmGKB; PA37221; -. DR VEuPathDB; HostDB:ENSG00000126088; -. DR eggNOG; KOG2872; Eukaryota. DR GeneTree; ENSGT00390000018302; -. DR HOGENOM; CLU_040933_0_0_1; -. DR InParanoid; P06132; -. DR OMA; LWLMRQA; -. DR OrthoDB; 34606at2759; -. DR PhylomeDB; P06132; -. DR TreeFam; TF300744; -. DR BioCyc; MetaCyc:HS04993-MONOMER; -. DR BRENDA; 4.1.1.37; 2681. DR PathwayCommons; P06132; -. DR Reactome; R-HSA-189451; Heme biosynthesis. DR SignaLink; P06132; -. DR UniPathway; UPA00251; UER00321. DR BioGRID-ORCS; 7389; 556 hits in 1169 CRISPR screens. DR ChiTaRS; UROD; human. DR EvolutionaryTrace; P06132; -. DR GeneWiki; Uroporphyrinogen_III_decarboxylase; -. DR GenomeRNAi; 7389; -. DR Pharos; P06132; Tbio. DR PRO; PR:P06132; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P06132; Protein. DR Bgee; ENSG00000126088; Expressed in trabecular bone tissue and 206 other cell types or tissues. DR ExpressionAtlas; P06132; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0004853; F:uroporphyrinogen decarboxylase activity; IDA:UniProtKB. DR GO; GO:0006784; P:heme A biosynthetic process; IEA:Ensembl. DR GO; GO:0006785; P:heme B biosynthetic process; IEA:Ensembl. DR GO; GO:0006783; P:heme biosynthetic process; IBA:GO_Central. DR GO; GO:0048034; P:heme O biosynthetic process; IEA:Ensembl. DR GO; GO:0006787; P:porphyrin-containing compound catabolic process; IDA:UniProtKB. DR GO; GO:0006778; P:porphyrin-containing compound metabolic process; IDA:UniProtKB. DR GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:UniProtKB-UniPathway. DR CDD; cd00717; URO-D; 1. DR DisProt; DP00308; -. DR Gene3D; 3.20.20.210; -; 1. DR HAMAP; MF_00218; URO_D; 1. DR InterPro; IPR038071; UROD/MetE-like_sf. DR InterPro; IPR006361; Uroporphyrinogen_deCO2ase_HemE. DR InterPro; IPR000257; Uroporphyrinogen_deCOase. DR NCBIfam; TIGR01464; hemE; 1. DR PANTHER; PTHR21091; METHYLTETRAHYDROFOLATE:HOMOCYSTEINE METHYLTRANSFERASE RELATED; 1. DR PANTHER; PTHR21091:SF169; UROPORPHYRINOGEN DECARBOXYLASE; 1. DR Pfam; PF01208; URO-D; 1. DR SUPFAM; SSF51726; UROD/MetE-like; 1. DR PROSITE; PS00906; UROD_1; 1. DR PROSITE; PS00907; UROD_2; 1. DR Genevisible; P06132; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cytoplasm; Decarboxylase; KW Direct protein sequencing; Disease variant; Heme biosynthesis; Lyase; KW Porphyrin biosynthesis; Reference proteome. FT CHAIN 1..367 FT /note="Uroporphyrinogen decarboxylase" FT /id="PRO_0000187569" FT BINDING 37..41 FT /ligand="substrate" FT BINDING 55 FT /ligand="substrate" FT BINDING 85 FT /ligand="substrate" FT BINDING 86 FT /ligand="substrate" FT BINDING 164 FT /ligand="substrate" FT BINDING 219 FT /ligand="substrate" FT BINDING 339 FT /ligand="substrate" FT SITE 86 FT /note="Transition state stabilizer" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378" FT VARIANT 15 FT /note="K -> E (in dbSNP:rs11541959)" FT /id="VAR_060683" FT VARIANT 25 FT /note="G -> E (in FPCT; insoluble protein; FT dbSNP:rs764268015)" FT /evidence="ECO:0000269|PubMed:11719352" FT /id="VAR_022567" FT VARIANT 46 FT /note="F -> L (in HEP; mild phenotype; strong decrease of FT activity; dbSNP:rs769378741)" FT /evidence="ECO:0000269|PubMed:12071824, FT ECO:0000269|PubMed:15491440" FT /id="VAR_022568" FT VARIANT 62 FT /note="P -> L (in HEP; dbSNP:rs121918060)" FT /evidence="ECO:0000269|PubMed:8644733" FT /id="VAR_009103" FT VARIANT 77 FT /note="P -> L (in dbSNP:rs1131147)" FT /evidence="ECO:0000269|PubMed:8644733, ECO:0000269|Ref.4, FT ECO:0000269|Ref.5" FT /id="VAR_067457" FT VARIANT 80 FT /note="A -> G (in HEP; dbSNP:rs776907084)" FT /evidence="ECO:0000269|PubMed:8896428" FT /id="VAR_007910" FT VARIANT 80 FT /note="A -> S (in FPCT; decrease of activity; FT dbSNP:rs376921379)" FT /evidence="ECO:0000269|PubMed:11069625, FT ECO:0000269|PubMed:11719352" FT /id="VAR_022569" FT VARIANT 106 FT /note="P -> L (in dbSNP:rs11541962)" FT /id="VAR_060684" FT VARIANT 113 FT /note="R -> T (in dbSNP:rs11541963)" FT /id="VAR_060685" FT VARIANT 134 FT /note="V -> Q (in FPCT and HEP; nearly normal activity; FT requires 2 nucleotide substitutions)" FT /evidence="ECO:0000269|PubMed:10338097, FT ECO:0000269|PubMed:11069625, ECO:0000269|PubMed:11719352, FT ECO:0000269|PubMed:8176248" FT /id="VAR_009104" FT VARIANT 142 FT /note="R -> Q (in FPCT; dbSNP:rs1182234844)" FT /evidence="ECO:0000269|PubMed:11295834" FT /id="VAR_010985" FT VARIANT 144 FT /note="R -> P (in FPCT; decrease of activity)" FT /evidence="ECO:0000269|PubMed:11069625" FT /id="VAR_022570" FT VARIANT 156 FT /note="G -> D (in FPCT; decrease of activity; FT dbSNP:rs762617943)" FT /evidence="ECO:0000269|PubMed:11719352" FT /id="VAR_022571" FT VARIANT 161 FT /note="L -> Q (in FPCT)" FT /evidence="ECO:0000269|PubMed:11295834" FT /id="VAR_010986" FT VARIANT 165 FT /note="M -> R (in FPCT; activity < 2%; dbSNP:rs121918063)" FT /evidence="ECO:0000269|PubMed:11719352, FT ECO:0000269|PubMed:9792863" FT /id="VAR_007911" FT VARIANT 167 FT /note="E -> K (in HEP and FPCT; nearly normal activity; FT dbSNP:rs121918058)" FT /evidence="ECO:0000269|PubMed:11719352, FT ECO:0000269|PubMed:1905636" FT /id="VAR_007714" FT VARIANT 168 FT /note="G -> R (in HEP; relative activity of 65% of FT wild-type towards uroporphyrinogen III)" FT /evidence="ECO:0000269|PubMed:17240319" FT /id="VAR_065558" FT VARIANT 170 FT /note="G -> D (in HEP; relative activity of 17% and 60% of FT wild-type towards uroporphyrinogen I and III respectively)" FT /evidence="ECO:0000269|PubMed:21668429" FT /id="VAR_065559" FT VARIANT 193 FT /note="R -> P (in FPCT; insoluble protein; FT dbSNP:rs143823335)" FT /evidence="ECO:0000269|PubMed:11719352" FT /id="VAR_022572" FT VARIANT 195 FT /note="L -> F (in FPCT; dbSNP:rs121918064)" FT /evidence="ECO:0000269|PubMed:9792863" FT /id="VAR_007912" FT VARIANT 216 FT /note="L -> Q (in FPCT)" FT /evidence="ECO:0000269|PubMed:11069625" FT /id="VAR_022573" FT VARIANT 218 FT /note="E -> K (in FPCT; significant decrease of activity)" FT /evidence="ECO:0000269|PubMed:11069625" FT /id="VAR_022574" FT VARIANT 219 FT /note="S -> F (in FPCT; dbSNP:rs982293378)" FT /evidence="ECO:0000269|PubMed:11295834" FT /id="VAR_010987" FT VARIANT 220 FT /note="H -> P (in HEP; mild form)" FT /evidence="ECO:0000269|PubMed:8176248" FT /id="VAR_009105" FT VARIANT 229 FT /note="F -> L (in FPCT)" FT /evidence="ECO:0000269|PubMed:10477430" FT /id="VAR_009106" FT VARIANT 232 FT /note="F -> L (in FPCT; decrease of activity)" FT /evidence="ECO:0000269|PubMed:11719352" FT /id="VAR_022575" FT VARIANT 235 FT /note="P -> S (in FPCT; dbSNP:rs141312224)" FT /evidence="ECO:0000269|PubMed:11295834" FT /id="VAR_010988" FT VARIANT 253 FT /note="L -> Q (in FPCT; decrease of activity; FT dbSNP:rs36033115)" FT /evidence="ECO:0000269|PubMed:11719352, FT ECO:0000269|PubMed:8896428" FT /id="VAR_007913" FT VARIANT 260 FT /note="I -> T (in FPCT; decrease of activity; FT dbSNP:rs1483459837)" FT /evidence="ECO:0000269|PubMed:11719352" FT /id="VAR_022576" FT VARIANT 281 FT /note="G -> E (in FPCT and HEP; dbSNP:rs121918057)" FT /evidence="ECO:0000269|PubMed:3775362, FT ECO:0000269|PubMed:7706766, ECO:0000269|PubMed:8644733" FT /id="VAR_007715" FT VARIANT 281 FT /note="G -> V (in FPCT; dbSNP:rs121918057)" FT /evidence="ECO:0000269|PubMed:11069625, FT ECO:0000269|PubMed:2920211" FT /id="VAR_007716" FT VARIANT 282 FT /note="L -> R (in FPCT)" FT /evidence="ECO:0000269|PubMed:11069625" FT /id="VAR_022577" FT VARIANT 292 FT /note="R -> G (in HEP; dbSNP:rs121918059)" FT /evidence="ECO:0000269|PubMed:1634232" FT /id="VAR_007717" FT VARIANT 303 FT /note="G -> S (in FPCT; dbSNP:rs964670864)" FT /evidence="ECO:0000269|PubMed:11069625" FT /id="VAR_022578" FT VARIANT 303 FT /note="G -> V (in dbSNP:rs17849533)" FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.6" FT /id="VAR_060686" FT VARIANT 304 FT /note="N -> K (in FPCT; dbSNP:rs121918065)" FT /evidence="ECO:0000269|PubMed:9792863" FT /id="VAR_007914" FT VARIANT 311 FT /note="Y -> C (in HEP; dbSNP:rs121918061)" FT /evidence="ECO:0000269|PubMed:8644733" FT /id="VAR_009107" FT VARIANT 318 FT /note="G -> R (in FPCT; dbSNP:rs116233118)" FT /evidence="ECO:0000269|PubMed:11069625, FT ECO:0000269|PubMed:8896428" FT /id="VAR_007915" FT VARIANT 324 FT /note="M -> T (in FPCT; dbSNP:rs763746230)" FT /evidence="ECO:0000269|PubMed:10477430" FT /id="VAR_009108" FT VARIANT 332 FT /note="R -> H (in FPCT; dbSNP:rs121918066)" FT /evidence="ECO:0000269|PubMed:9792863" FT /id="VAR_007916" FT VARIANT 334 FT /note="I -> T (in FPCT)" FT /evidence="ECO:0000269|PubMed:8896428" FT /id="VAR_007917" FT MUTAGEN 86 FT /note="D->E: 5-10% of wild-type activity." FT /evidence="ECO:0000269|PubMed:14633982" FT MUTAGEN 86 FT /note="D->G: Very low activity. Binds substrate with FT similar geometry as wild-type." FT /evidence="ECO:0000269|PubMed:14633982" FT MUTAGEN 86 FT /note="D->N: No activity. Unable to bind substrate." FT /evidence="ECO:0000269|PubMed:14633982" FT MUTAGEN 164 FT /note="Y->F: 25-30% of wild-type activity." FT /evidence="ECO:0000269|PubMed:14633982" FT CONFLICT 103 FT /note="G -> S (in Ref. 1; AAA61258 and 14; AAB59456)" FT /evidence="ECO:0000305" FT CONFLICT 120 FT /note="R -> A (in Ref. 1; AAA61258 and 14; AAB59456)" FT /evidence="ECO:0000305" FT CONFLICT 212..214 FT /note="Missing (in Ref. 14; AAB59456)" FT /evidence="ECO:0000305" FT HELIX 18..24 FT /evidence="ECO:0007829|PDB:1R3S" FT STRAND 38..40 FT /evidence="ECO:0007829|PDB:1R3S" FT HELIX 44..51 FT /evidence="ECO:0007829|PDB:1R3S" FT HELIX 55..59 FT /evidence="ECO:0007829|PDB:1R3S" FT HELIX 62..75 FT /evidence="ECO:0007829|PDB:1R3S" FT HELIX 89..93 FT /evidence="ECO:0007829|PDB:1R3S" FT STRAND 99..101 FT /evidence="ECO:0007829|PDB:1R3S" FT TURN 102..104 FT /evidence="ECO:0007829|PDB:1R3S" FT STRAND 105..107 FT /evidence="ECO:0007829|PDB:1R3S" FT HELIX 115..120 FT /evidence="ECO:0007829|PDB:1R3S" FT HELIX 124..126 FT /evidence="ECO:0007829|PDB:1R3S" FT HELIX 127..130 FT /evidence="ECO:0007829|PDB:1R3S" FT HELIX 132..145 FT /evidence="ECO:0007829|PDB:1R3S" FT STRAND 151..156 FT /evidence="ECO:0007829|PDB:1R3S" FT HELIX 158..167 FT /evidence="ECO:0007829|PDB:1R3S" FT HELIX 175..183 FT /evidence="ECO:0007829|PDB:1R3S" FT HELIX 185..208 FT /evidence="ECO:0007829|PDB:1R3S" FT STRAND 212..218 FT /evidence="ECO:0007829|PDB:1R3S" FT HELIX 221..223 FT /evidence="ECO:0007829|PDB:1R3S" FT HELIX 226..232 FT /evidence="ECO:0007829|PDB:1R3S" FT HELIX 234..250 FT /evidence="ECO:0007829|PDB:1R3S" FT STRAND 258..262 FT /evidence="ECO:0007829|PDB:1R3S" FT HELIX 266..268 FT /evidence="ECO:0007829|PDB:1R3S" FT HELIX 269..272 FT /evidence="ECO:0007829|PDB:1R3S" FT TURN 273..276 FT /evidence="ECO:0007829|PDB:3GVV" FT STRAND 278..281 FT /evidence="ECO:0007829|PDB:1R3S" FT HELIX 288..295 FT /evidence="ECO:0007829|PDB:1R3S" FT STRAND 297..305 FT /evidence="ECO:0007829|PDB:1R3S" FT HELIX 307..311 FT /evidence="ECO:0007829|PDB:1R3S" FT HELIX 314..328 FT /evidence="ECO:0007829|PDB:1R3S" FT STRAND 330..339 FT /evidence="ECO:0007829|PDB:1R3S" FT HELIX 347..365 FT /evidence="ECO:0007829|PDB:1R3S" SQ SEQUENCE 367 AA; 40787 MW; 840510B36CFC3856 CRC64; 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 //