ID HEM3_HUMAN Reviewed; 361 AA. AC P08397; A8K2L0; G3V1P4; G5EA58; P08396; Q16012; DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 2. DT 09-DEC-2015, entry version 190. DE RecName: Full=Porphobilinogen deaminase; DE Short=PBG-D; DE EC=2.5.1.61; DE AltName: Full=Hydroxymethylbilane synthase; DE Short=HMBS; DE AltName: Full=Pre-uroporphyrinogen synthase; GN Name=HMBS; Synonyms=PBGD, UPS; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=2875434; DOI=10.1093/nar/14.15.5955; RA Raich N., Romeo P.-H., Dubart A., Beaupain D., Cohen-Solal M., RA Goossens M.; RT "Molecular cloning and complete primary sequence of human erythrocyte RT porphobilinogen deaminase."; RL Nucleic Acids Res. 14:5955-5968(1986). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=3816774; DOI=10.1111/j.1432-1033.1987.tb10548.x; RA Grandchamp B., de Verneuil H., Beaumont C., Chretien S., Walter O., RA Nordmann Y.; RT "Tissue-specific expression of porphobilinogen deaminase. Two RT isoenzymes from a single gene."; RL Eur. J. Biochem. 162:105-110(1987). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=7916736; DOI=10.1006/geno.1993.1005; RA Yoo H.-W., Warner C.A., Chen C.-H., Desnick R.J.; RT "Hydroxymethylbilane synthase: complete genomic sequence and RT amplifiable polymorphisms in the human gene."; RL Genomics 15:21-29(1993). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4). RC TISSUE=Colon; 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S., RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., RA Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain, and Lung; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 30-53, AND TISSUE SPECIFICITY. RX PubMed=3422427; DOI=10.1073/pnas.85.1.6; RA Chretien S., Dubart A., Beaupain D., Raich N., Grandchamp B., Rosa J., RA Goossens M., Romeo P.-H.; RT "Alternative transcription and splicing of the human porphobilinogen RT deaminase gene result either in tissue-specific or in housekeeping RT expression."; RL Proc. Natl. Acad. Sci. U.S.A. 85:6-10(1988). RN [9] RP PROTEIN SEQUENCE OF 18-36 (ISOFORM 2). RX PubMed=2609111; RA Lannfelt L., Wetterberg L., Lilius L., Thunell S., Joernvall H., RA Pavlu B., Wielburski A., Gellerfors P.; RT "Porphobilinogen deaminase in human erythrocytes: purification of two RT forms with apparent molecular weights of 40 kDa and 42 kDa."; RL Scand. J. Clin. Lab. Invest. 49:677-684(1989). RN [10] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], 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., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [11] 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., RA Buerckstuemmer T., 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 [12] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], 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., RA Meinnel T., 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 [13] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], 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., RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., RA Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N- RT terminal acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [15] RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS). RX PubMed=19207107; DOI=10.1042/BJ20082077; RA Gill R., Kolstoe S.E., Mohammed F., Al D-Bass A., Mosely J.E., RA Sarwar M., Cooper J.B., Wood S.P., Shoolingin-Jordan P.M.; RT "Structure of human porphobilinogen deaminase at 2.8 A: the molecular RT basis of acute intermittent porphyria."; RL Biochem. J. 420:17-25(2009). RN [16] RP X-RAY CRYSTALLOGRAPHY (2.18 ANGSTROMS), AND PROSTHETIC GROUP AT RP CYS-261. RX PubMed=18936296; DOI=10.1096/fj.08-115469; RA Song G., Li Y., Cheng C., Zhao Y., Gao A., Zhang R., Joachimiak A., RA Shaw N., Liu Z.J.; RT "Structural insight into acute intermittent porphyria."; RL FASEB J. 23:396-404(2009). RN [17] RP VARIANTS AIP GLN-167 AND GLN-173. RX PubMed=2243128; DOI=10.1172/JCI114869; RA Delfau M.H., Picat C., de Rooij F.W.M., Hamer K., Bogard M., RA Wilson J.H.P., Deybach J.-C., Nordmann Y., Grandchamp B.; RT "Two different point G to A mutations in exon 10 of the RT porphobilinogen deaminase gene are responsible for acute intermittent RT porphyria."; RL J. Clin. Invest. 86:1511-1516(1990). RN [18] RP VARIANTS AIP GLN-149 AND ARG-245. RX PubMed=1714233; RA Delfau M.H., Picat C., de Rooij F.W.M., Voortman G., Deybach J.-C., RA Nordmann Y., Grandchamp B.; RT "Molecular heterogeneity of acute intermittent porphyria: RT identification of four additional mutations resulting in the CRIM- RT negative subtype of the disease."; RL Am. J. Hum. Genet. 49:421-428(1991). RN [19] RP VARIANT AIP TRP-167. RX PubMed=1496994; RA Gu X.-F., de Rooij F.W.M., Voortman G., Te Velde K., Nordmann Y., RA Grandchamp B.; RT "High frequency of mutations in exon 10 of the porphobilinogen RT deaminase gene in patients with a CRIM-positive subtype of acute RT intermittent porphyria."; RL Am. J. Hum. Genet. 51:660-665(1992). RN [20] RP VARIANTS AIP LYS-34; GLN-167; ARG-177 AND ASN-256. RX PubMed=1427766; DOI=10.1007/BF00210738; RA Mgone C.S., Lanyon W.G., Moore M.R., Connor J.M.; RT "Detection of seven point mutations in the porphobilinogen deaminase RT gene in patients with acute intermittent porphyria, by direct RT sequencing of in vitro amplified cDNA."; RL Hum. Genet. 90:12-16(1992). RN [21] RP VARIANTS AIP TRP-167 AND GLN-173. RX PubMed=1301948; DOI=10.1002/humu.1380010508; RA Kauppinen R., Peltonen L., Pihlaja H., Mustajoki P.; RT "CRIM-positive mutations of acute intermittent porphyria in Finland."; RL Hum. Mutat. 1:392-396(1992). RN [22] RP VARIANTS AIP ARG-247; THR-252 AND VAL-252. RX PubMed=8262523; DOI=10.1007/BF00420949; RA Mgone C.S., Lanyon W.G., Moore M.R., Louie G.V., Connor J.M.; RT "Detection of a high mutation frequency in exon 12 of the RT porphobilinogen deaminase gene in patients with acute intermittent RT porphyria."; RL Hum. Genet. 92:619-622(1993). RN [23] RP VARIANT AIP HIS-26. RX PubMed=8401516; DOI=10.1093/hmg/2.8.1315; RA Llewellyn D.H., Whatley S.D., Elder G.H.; RT "Acute intermittent porphyria caused by an arginine to histidine RT substitution (R26H) in the cofactor-binding cleft of porphobilinogen RT deaminase."; RL Hum. Mol. Genet. 2:1315-1316(1993). RN [24] RP VARIANT AIP ARG-111. RX PubMed=8268934; DOI=10.1093/hmg/2.10.1735; RA Gu X.-F., de Rooij F.W.M., de Baar E., Bruyland M., Lissens W., RA Nordmann Y., Grandchamp B.; RT "Two novel mutations of the porphobilinogen deaminase gene in acute RT intermittent porphyria."; RL Hum. Mol. Genet. 2:1735-1736(1993). RN [25] RP VARIANTS AIP THR-31; SER-55; LEU-149; LYS-223 AND LYS-250. RX PubMed=8270254; DOI=10.1007/BF00218912; RA Gu X.-F., de Rooij F.W.M., Voortman G., Te Velde K., Deybach J.-C., RA Nordmann Y., Grandchamp B.; RT "Detection of eleven mutations causing acute intermittent porphyria RT using denaturing gradient gel electrophoresis."; RL Hum. Genet. 93:47-52(1994). RN [26] RP VARIANT AIP TRP-201. RX PubMed=8270256; DOI=10.1007/BF00218914; RA Lundin G., Wedell A., Thunell S., Anvret M.; RT "Two new mutations in the porphobilinogen deaminase gene and a RT screening method using PCR amplification of specific alleles."; RL Hum. Genet. 93:59-62(1994). RN [27] RP VARIANTS AIP GLN-116; TRP-173; ARG-177; ILE-269 AND ARG-274. RX PubMed=8081367; DOI=10.1093/hmg/3.5.809; RA Mgone C.S., Lanyon W.G., Moore M.R., Louie G.V., Connor J.M.; RT "Identification of five novel mutations in the porphobilinogen RT deaminase gene."; RL Hum. Mol. Genet. 3:809-811(1994). RN [28] RP REVIEW ON AIP VARIANTS. RX PubMed=7866402; DOI=10.1002/humu.1380040403; RA Astrin K.N., Desnick R.J.; RT "Molecular basis of acute intermittent porphyria: mutations and RT polymorphisms in the human hydroxymethylbilane synthase gene."; RL Hum. Mutat. 4:243-252(1994). RN [29] RP VARIANTS AIP PHE-93; TRP-116; TRP-201 AND PHE-247. RX PubMed=7962538; DOI=10.1172/JCI117543; RA Chen C.-H., Astrin K.H., Lee G., Anderson K.E., Desnick R.J.; RT "Acute intermittent porphyria: identification and expression of exonic RT mutations in the hydroxymethylbilane synthase gene. An initiation RT codon missense mutation in the housekeeping transcript causes 'variant RT acute intermittent porphyria' with normal expression of the erythroid- RT specific enzyme."; RL J. Clin. Invest. 94:1927-1937(1994). RN [30] RP VARIANTS AIP. RX PubMed=7757070; DOI=10.1093/hmg/4.2.215; RA Kauppinen R., Mustajoki S., Pihlaja H., Peltonen L., Mustajoki P.; RT "Acute intermittent porphyria in Finland: 19 mutations in the RT porphobilinogen deaminase gene."; RL Hum. Mol. Genet. 4:215-222(1995). RN [31] RP VARIANTS AIP LEU-119 AND ALA-250. RX PubMed=8825929; DOI=10.1136/jmg.32.12.979; RA Lundin G., Hashemi J., Floderus Y., Thunell S., Sagen E., Laegreid A., RA Wassif W., Peters T., Anvret M.; RT "Four mutations in the porphobilinogen deaminase gene in patients with RT acute intermittent porphyria."; RL J. Med. Genet. 32:979-981(1995). RN [32] RP VARIANTS AIP. RX PubMed=9199558; DOI=10.1086/515455; RA Puy H., Deybach J.-C., Lamoril J., Robreau A.-M., Da Silva V., RA Gouya L., Grandchamp B., Nordmann Y.; RT "Molecular epidemiology and diagnosis of PBG deaminase gene defects in RT acute intermittent porphyria."; RL Am. J. Hum. Genet. 60:1373-1383(1997). RN [33] RP VARIANTS AIP TRP-116; LEU-119; GLN-167; TRP-167; TRP-173; TRP-201 AND RP ASP-216. RX PubMed=9225970; DOI=10.1007/s004390050466; RA Lundin G., Lee J.-S., Thunell S., Anvret M.; RT "Genetic investigation of the porphobilinogen deaminase gene in RT Swedish acute intermittent porphyria families."; RL Hum. Genet. 100:63-66(1997). RN [34] RP VARIANTS AIP MET-222 AND PRO-278. RX PubMed=9654202; DOI=10.1007/s004390050737; RA Mustajoki S., Pihlaja H., Ahola H., Petersen N.E., Mustajoki P., RA Kauppinen R.; RT "Three splicing defects, an insertion, and two missense mutations RT responsible for acute intermittent porphyria."; RL Hum. Genet. 102:541-548(1998). RN [35] RP VARIANT AIP CYS-22. RX PubMed=9463797; DOI=10.1159/000022777; RA Ong P.M., Lanyon W.G., Hift R.J., Halkett J., Cramp C.E., Moore M.R., RA Connor J.M.; RT "Identification of two novel mutations in the hydroxymethylbilane RT synthase gene in three patients from two unrelated families with acute RT intermittent porphyria."; RL Hum. Hered. 48:24-29(1998). RN [36] RP VARIANTS AIP PRO-34; ARG-111; TRP-173; TRP-201; 329-LEU--GLN-332 DEL RP AND SER-335. RX PubMed=10494093; RX DOI=10.1002/(SICI)1096-8628(19991008)86:4<366::AID-AJMG11>3.0.CO;2-#; RA De Siervi A., Rossetti M.V., Parera V.E., Astrin K.H., Aizencang G.I., RA Glass I.A., Batlle A.M.C., Desnick R.J.; RT "Identification and characterization of hydroxymethylbilane synthase RT mutations causing acute intermittent porphyria: evidence for an RT ancestral founder of the common G111R mutation."; RL Am. J. Med. Genet. 86:366-375(1999). RN [37] RP VARIANTS AIP CYS-22; CYS-26; HIS-26; PRO-31; SER-42; ASN-61; ARG-85; RP GLY-90; ARG-111; GLN-173; TRP-173; ARG-177; CYS-195; ASP-219; ARG-247 RP AND ILE-269. RX PubMed=10453740; DOI=10.1007/s004390050995; RA Whatley S.D., Woolf J.R., Elder G.H.; RT "Comparison of complementary and genomic DNA sequencing for the RT detection of mutations in the HMBS gene in British patients with acute RT intermittent porphyria: identification of 25 novel mutations."; RL Hum. Genet. 104:505-510(1999). RN [38] RP VARIANT AIP ALA-152 DEL. RX PubMed=10502788; RX DOI=10.1002/(SICI)1098-1004(199910)14:4<355::AID-HUMU19>3.0.CO;2-T; RA De Siervi A., Mendez M., Parera V.E., Varela L., Batlle A.M.C., RA Rossetti M.V.; RT "Acute intermittent porphyria: characterization of two novel mutations RT in the porphobilinogen deaminase gene, one amino acid deletion (453- RT 455delAGC) and one splicing acceptor site mutation (IVS8-1G>T)."; RL Hum. Mutat. 14:355-355(1999). RN [39] RP VARIANTS AIP CYS-26 AND LEU-202. RX PubMed=10657149; DOI=10.1006/mcpr.1999.0276; RA Gross U., Puy H., Doss M., Robreau A.-M., Nordmann Y., Doss M.O., RA Deybach J.-C.; RT "New mutations of the hydroxymethylbilane synthase gene in German RT patients with acute intermittent porphyria."; RL Mol. Cell. Probes 13:443-447(1999). RN [40] RP VARIANTS AIP ARG-111; TRP-116; TRP-167; TRP-173 AND VAL-212, AND RP CHARACTERIZATION OF VARIANT AIP VAL-212. RX PubMed=10602775; RA Solis C., Lopez-Echaniz I., Sefarty-Graneda D., Astrin K.H., RA Desnick R.J.; RT "Identification and expression of mutations in the hydroxymethylbilane RT synthase gene causing acute intermittent porphyria (AIP)."; RL Mol. Med. 5:664-671(1999). RN [41] RP VARIANTS AIP PRO-78; GLY-80; ARG-111 AND TRP-173. RX PubMed=11399210; DOI=10.1097/00125817-200009000-00004; RA Ramdall R.B., Cunha L., Astrin K.H., Katz D.R., Anderson K.E., RA Glucksman M., Bottomley S.S., Desnick R.J.; RT "Acute intermittent porphyria: novel missense mutations in the human RT hydroxymethylbilane synthase gene."; RL Genet. Med. 2:290-295(2000). RN [42] RP VARIANTS AIP TRP-116 AND GLY-270. RX PubMed=11030413; DOI=10.1007/s004390000323; RA Robreau-Fraolini A.M., Puy H., Aquaron C., Bogard C., Traore M., RA Nordmann Y., Aquaron R., Deybach J.-C.; RT "Porphobilinogen deaminase gene in African and Afro-Caribbean ethnic RT groups: mutations causing acute intermittent porphyria and specific RT intragenic polymorphisms."; RL Hum. Genet. 107:150-159(2000). RN [43] RP VARIANT AIP LEU-217. RX PubMed=10782018; DOI=10.1159/000022924; RA Schneider-Yin X., Bogard C., Rufenacht U.B., Puy H., Nordmann Y., RA Minder E.I., Deybach J.-C.; RT "Identification of a prevalent nonsense mutation (W283X) and two novel RT mutations in the porphobilinogen deaminase gene of Swiss patients with RT acute intermittent porphyria."; RL Hum. Hered. 50:247-250(2000). RN [44] RP VARIANTS AIP MET-35; ARG-111 AND GLY-281 DEL. RX PubMed=11013452; RX DOI=10.1002/1098-1004(200010)16:4<373::AID-HUMU14>3.0.CO;2-A; RA De Siervi A., Weiss Cadiz D.E., Parera V.E., Batlle A.M.C., RA Rossetti M.V.; RT "Identification and characterization of two novel mutations that RT produce acute intermittent porphyria: a 3-base deletion (841- RT 843delGGA) and a missense mutation (T35M)."; RL Hum. Mutat. 16:373-373(2000). RN [45] RP ERRATUM, AND VARIANT AIP ASN-99. RA Martinez di Montemuros F., Di Pierro E., Fiorelli G., Cappellini M.D.; RL Hum. Genet. 109:241-241(2001). RN [46] RP VARIANTS AIP ILE-18; PHE-96; HIS-99; GLY-122; PRO-254 AND TYR-261. RX PubMed=12406973; RA Kauppinen R., von und zu Fraunberg M.; RT "Molecular and biochemical studies of acute intermittent porphyria in RT 196 patients and their families."; RL Clin. Chem. 48:1891-1900(2002). RN [47] RP VARIANTS AIP CYS-26; HIS-26; VAL-86; PRO-92; GLY-99; ARG-111; THR-113; RP GLN-173; ASN-178; GLN-225; GLY-225; TYR-256; ASP-260 AND PRO-343. RX PubMed=12372055; DOI=10.1034/j.1399-0004.2002.620406.x; RA Floderus Y., Shoolingin-Jordan P.M., Harper P.; RT "Acute intermittent porphyria in Sweden. Molecular, functional and RT clinical consequences of some new mutations found in the RT porphobilinogen deaminase gene."; RL Clin. Genet. 62:288-297(2002). RN [48] RP VARIANTS AIP HIS-26; TYR-61; VAL-93 DEL; ARG-111; GLN-173 AND ASP-335. RX PubMed=11857754; DOI=10.1002/humu.9020; RA Gregor A., Schneider-Yin X., Szlendak U., Wettstein A., Lipniacka A., RA Ruefenacht U.B., Minder E.I.; RT "Molecular study of the hydroxymethylbilane synthase gene (HMBS) among RT Polish patients with acute intermittent porphyria."; RL Hum. Mutat. 19:310-310(2002). RN [49] RP CHARACTERIZATION OF VARIANTS AIP GLY-99; GLN-149; GLN-167 AND GLN-173. RX PubMed=12773194; DOI=10.1042/BST0310731; RA Shoolingin-Jordan P.M., Al-Dbass A., McNeill L.A., Sarwar M., RA Butler D.; RT "Human porphobilinogen deaminase mutations in the investigation of the RT mechanism of dipyrromethane cofactor assembly and tetrapyrrole RT formation."; RL Biochem. Soc. Trans. 31:731-735(2003). RN [50] RP VARIANTS AIP GLU-215 AND PRO-238. RX PubMed=14757946; DOI=10.1155/2003/384971; RA Tjensvoll K., Bruland O., Floderus Y., Skadberg O., Sandberg S., RA Apold J.; RT "Haplotype analysis of Norwegian and Swedish patients with acute RT intermittent porphyria (AIP): Extreme haplotype heterogeneity for the RT mutation R116W."; RL Dis. Markers 19:41-46(2003). RN [51] RP VARIANTS AIP ARG-34; SER-236 AND PRO-244. RX PubMed=14669009; DOI=10.1007/s00439-003-1059-5; RA Gouya L., Puy H., Robreau A.-M., Lyoumi S., Lamoril J., Da Silva V., RA Grandchamp B., Deybach J.-C.; RT "Modulation of penetrance by the wild-type allele in dominantly RT inherited erythropoietic protoporphyria and acute hepatic RT porphyrias."; RL Hum. Genet. 114:256-262(2004). RN [52] RP VARIANT AIP PRO-81. RX PubMed=14970743; DOI=10.1023/B:BOLI.0000016613.75677.05; RA Hessels J., Voortman G., van der Wagen A., van der Elzen C., RA Scheffer H., Zuijderhoudt F.M.J.; RT "Homozygous acute intermittent porphyria in a 7-year-old boy with RT massive excretions of porphyrins and porphyrin precursors."; RL J. Inherit. Metab. Dis. 27:19-27(2004). RN [53] RP VARIANTS AIP ARG-111 AND GLN-173. RX PubMed=15669678; DOI=10.1023/B:BOLI.0000042936.20691.ad; RA Schneider-Yin X., Hergersberg M., Schuurmans M.M., Gregor A., RA Minder E.I.; RT "Mutation hotspots in the human porphobilinogen deaminase gene: RT recurrent mutations G111R and R173Q occurring at CpG motifs."; RL J. Inherit. Metab. Dis. 27:625-631(2004). RN [54] RP VARIANTS AIP HIS-26; TRP-173; CYS-195; ARG-247 AND ALA-250, AND RP CHARACTERIZATION OF VARIANTS AIP HIS-26; TRP-173; CYS-195; ARG-247 AND RP ALA-250. RX PubMed=16211556; DOI=10.1002/humu.9381; RA Pischik E., Mehtaelae S., Kauppinen R.; RT "Nine mutations including three novel mutations among Russian patients RT with acute intermittent porphyria."; RL Hum. Mutat. 26:496-496(2005). RN [55] RP VARIANTS AIP ILE-59 AND MET-215, AND CHARACTERIZATION OF VARIANTS AIP RP ILE-59 AND MET-215. RX PubMed=18406650; DOI=10.1016/j.ymgme.2008.03.001; RA Schneider-Yin X., Ulbrichova D., Mamet R., Martasek P., Marohnic C.C., RA Goren A., Minder E.I., Schoenfeld N.; RT "Characterization of two missense variants in the hydroxymethylbilane RT synthase gene in the Israeli population, which differ in their RT associations with acute intermittent porphyria."; RL Mol. Genet. Metab. 94:343-346(2008). RN [56] RP VARIANT AIP PRO-32, AND CHARACTERIZATION OF VARIANTS AIP PRO-32 AND RP ASN-178. RX PubMed=19138865; DOI=10.1016/j.bcmd.2008.11.001; RA Ulbrichova D., Schneider-Yin X., Mamet R., Saudek V., Martasek P., RA Minder E.I., Schoenfeld N.; RT "Correlation between biochemical findings, structural and enzymatic RT abnormalities in mutated HMBS identified in six Israeli families with RT acute intermittent porphyria."; RL Blood Cells Mol. Dis. 42:167-173(2009). RN [57] RP VARIANTS AIP CYS-26; HIS-26; GLN-173; LYS-204 AND ASP-250, AND RP CHARACTERIZATION OF VARIANTS AIP CYS-26; HIS-26; GLN-173; LYS-204 AND RP ASP-250. RX PubMed=19292878; DOI=10.1111/j.1742-4658.2009.06946.x; RA Ulbrichova D., Hrdinka M., Saudek V., Martasek P.; RT "Acute intermittent porphyria--impact of mutations found in the RT hydroxymethylbilane synthase gene on biochemical and enzymatic protein RT properties."; RL FEBS J. 276:2106-2115(2009). RN [58] RP BIOPHYSICOCHEMICAL PROPERTIES, VARIANT ASN-132, CHARACTERIZATION OF RP VARIANTS AIP TRP-116; TRP-167; TRP-173 AND GLU-215, AND RP CHARACTERIZATION OF VARIANT ASN-132. RX PubMed=23815679; DOI=10.1042/BSR20130045; RA Bustad H.J., Vorland M., Ronneseth E., Sandberg S., Martinez A., RA Toska K.; RT "Conformational stability and activity analysis of two RT hydroxymethylbilane synthase mutants, K132N and V215E, with different RT phenotypic association with acute intermittent porphyria."; RL Biosci. Rep. 33:0-0(2013). RN [59] RP VARIANTS AIP ARG-111 AND PRO-338. RX PubMed=25703257; DOI=10.1111/ahg.12102; RA Gonzaga A.D., de Amorim L.M., Fonseca A.B., Nogueira T.L., RA Pereira O.M., Nagai M.A., de Oliveira Barretto O.C., Ribeiro G.S.; RT "Hydroxymethylbilane synthase gene mutations and polymorphisms in RT Brazilian families with acute intermittent porphyria."; RL Ann. Hum. Genet. 79:162-172(2015). RN [60] RP VARIANT AIP PRO-330. RX PubMed=25870942; DOI=10.1016/j.gene.2015.04.027; RA Yang J., Wang H., Yin K., Hua B., Zhu T., Zhao Y., Guo S., Yu X., RA Wu W., Zhou Z.; RT "A novel mutation in the porphobilinogen deaminase gene in an extended RT Chinese family with acute intermittent porphyria."; RL Gene 565:288-290(2015). CC -!- FUNCTION: Tetrapolymerization of the monopyrrole PBG into the CC hydroxymethylbilane pre-uroporphyrinogen in several discrete CC steps. CC -!- CATALYTIC ACTIVITY: 4 porphobilinogen + H(2)O = CC hydroxymethylbilane + 4 NH(3). CC -!- COFACTOR: CC Name=dipyrromethane; Xref=ChEBI:CHEBI:60342; CC Note=Binds 1 dipyrromethane group covalently.; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=48 uM for porphobilinogen {ECO:0000269|PubMed:23815679}; CC Vmax=1261 nmol/h/mg enzyme (at 37 degrees Celsius) CC {ECO:0000269|PubMed:23815679}; CC Temperature dependence: CC Displays high thermal stability. The half-denaturation CC temperature (Tm) is about 74 degrees Celsius. CC {ECO:0000269|PubMed:23815679}; CC -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin- CC IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: CC step 2/4. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=Non-erythropoietic; CC IsoId=P08397-1; Sequence=Displayed; CC Name=2; Synonyms=Erythrocyte; CC IsoId=P08397-2; Sequence=VSP_002067; CC Name=3; CC IsoId=P08397-3; Sequence=VSP_047294; CC Note=No experimental confirmation available.; CC Name=4; CC IsoId=P08397-4; Sequence=VSP_002067, VSP_047294; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Isoform 1 is ubiquitously expressed. Isoform 2 CC is found only in erythroid cells. {ECO:0000269|PubMed:3422427}. CC -!- DISEASE: Acute intermittent porphyria (AIP) [MIM:176000]: A form CC of porphyria. Porphyrias are inherited defects in the biosynthesis CC of 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 CC deficiency occurs in red blood cells or in the liver. AIP is an CC autosomal dominant form of hepatic porphyria characterized by CC attacks of gastrointestinal disturbances, abdominal colic, with CC neurological dysfunctions, hypertension, tachycardia and CC peripheral neuropathy. Most attacks are precipitated by drugs, CC alcohol, caloric deprivation, infections, or endocrine factors. CC {ECO:0000269|PubMed:10453740, ECO:0000269|PubMed:10494093, CC ECO:0000269|PubMed:10502788, ECO:0000269|PubMed:10602775, CC ECO:0000269|PubMed:10657149, ECO:0000269|PubMed:10782018, CC ECO:0000269|PubMed:11013452, ECO:0000269|PubMed:11030413, CC ECO:0000269|PubMed:11399210, ECO:0000269|PubMed:11857754, CC ECO:0000269|PubMed:12372055, ECO:0000269|PubMed:12406973, CC ECO:0000269|PubMed:12773194, ECO:0000269|PubMed:1301948, CC ECO:0000269|PubMed:1427766, ECO:0000269|PubMed:14669009, CC ECO:0000269|PubMed:14757946, ECO:0000269|PubMed:1496994, CC ECO:0000269|PubMed:14970743, ECO:0000269|PubMed:15669678, CC ECO:0000269|PubMed:16211556, ECO:0000269|PubMed:1714233, CC ECO:0000269|PubMed:18406650, ECO:0000269|PubMed:19138865, CC ECO:0000269|PubMed:19292878, ECO:0000269|PubMed:2243128, CC ECO:0000269|PubMed:23815679, ECO:0000269|PubMed:25703257, CC ECO:0000269|PubMed:25870942, ECO:0000269|PubMed:7757070, CC ECO:0000269|PubMed:7962538, ECO:0000269|PubMed:8081367, CC ECO:0000269|PubMed:8262523, ECO:0000269|PubMed:8268934, CC ECO:0000269|PubMed:8270254, ECO:0000269|PubMed:8270256, CC ECO:0000269|PubMed:8401516, ECO:0000269|PubMed:8825929, CC ECO:0000269|PubMed:9199558, ECO:0000269|PubMed:9225970, CC ECO:0000269|PubMed:9463797, ECO:0000269|PubMed:9654202, CC ECO:0000269|Ref.45}. Note=The disease is caused by mutations CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: The porphobilinogen subunits are added to the CC dipyrromethane group. CC -!- SIMILARITY: Belongs to the HMBS family. {ECO:0000305}. 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; X04217; CAA27801.1; -; mRNA. DR EMBL; X04808; CAA28499.1; -; mRNA. DR EMBL; M95623; AAA60029.1; -; Genomic_DNA. DR EMBL; M95623; AAA60030.1; -; Genomic_DNA. DR EMBL; AK000628; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AK131072; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AK290275; BAF82964.1; -; mRNA. DR EMBL; AP003391; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP003392; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471065; EAW67447.1; -; Genomic_DNA. DR EMBL; CH471065; EAW67449.1; -; Genomic_DNA. DR EMBL; CH471065; EAW67450.1; -; Genomic_DNA. DR EMBL; BC000520; AAH00520.1; -; mRNA. DR EMBL; BC008149; AAH08149.1; -; mRNA. DR EMBL; BC019323; AAH19323.1; -; mRNA. DR EMBL; X68018; CAA48156.1; -; Genomic_DNA. DR EMBL; S60381; AAC60602.1; -; Genomic_DNA. DR CCDS; CCDS41726.1; -. [P08397-2] DR CCDS; CCDS58186.1; -. [P08397-3] DR CCDS; CCDS58187.1; -. [P08397-4] DR CCDS; CCDS8409.1; -. [P08397-1] DR PIR; A45012; IBHUN. DR RefSeq; NP_000181.2; NM_000190.3. [P08397-1] DR RefSeq; NP_001019553.1; NM_001024382.1. [P08397-2] DR RefSeq; NP_001245137.1; NM_001258208.1. [P08397-3] DR RefSeq; NP_001245138.1; NM_001258209.1. [P08397-4] DR RefSeq; XP_005271588.1; XM_005271531.1. [P08397-2] DR RefSeq; XP_005271589.1; XM_005271532.1. [P08397-2] DR UniGene; Hs.82609; -. DR PDB; 3ECR; X-ray; 2.18 A; A/B=1-361. DR PDB; 3EQ1; X-ray; 2.80 A; A/B=1-361. DR PDBsum; 3ECR; -. DR PDBsum; 3EQ1; -. DR ProteinModelPortal; P08397; -. DR SMR; P08397; 18-356. DR BioGrid; 109388; 11. DR IntAct; P08397; 2. DR STRING; 9606.ENSP00000278715; -. DR PhosphoSite; P08397; -. DR BioMuta; HMBS; -. DR DMDM; 1170217; -. DR MaxQB; P08397; -. DR PaxDb; P08397; -. DR PRIDE; P08397; -. DR DNASU; 3145; -. DR Ensembl; ENST00000278715; ENSP00000278715; ENSG00000256269. [P08397-1] DR Ensembl; ENST00000392841; ENSP00000376584; ENSG00000256269. [P08397-2] DR Ensembl; ENST00000442944; ENSP00000392041; ENSG00000256269. [P08397-2] DR Ensembl; ENST00000537841; ENSP00000444730; ENSG00000256269. [P08397-2] DR Ensembl; ENST00000542729; ENSP00000443058; ENSG00000256269. [P08397-4] DR Ensembl; ENST00000544387; ENSP00000438424; ENSG00000256269. [P08397-3] DR Ensembl; ENST00000627066; ENSP00000486176; ENSG00000281702. [P08397-1] DR Ensembl; ENST00000627967; ENSP00000487456; ENSG00000281702. [P08397-2] DR Ensembl; ENST00000628117; ENSP00000486199; ENSG00000281702. [P08397-2] DR Ensembl; ENST00000629150; ENSP00000486742; ENSG00000281702. [P08397-3] DR Ensembl; ENST00000630574; ENSP00000486658; ENSG00000281702. [P08397-4] DR Ensembl; ENST00000630689; ENSP00000486979; ENSG00000281702. [P08397-2] DR GeneID; 3145; -. DR KEGG; hsa:3145; -. DR UCSC; uc001puz.1; human. [P08397-1] DR UCSC; uc001pva.1; human. DR UCSC; uc001pve.2; human. DR CTD; 3145; -. DR GeneCards; HMBS; -. DR GeneReviews; HMBS; -. DR HGNC; HGNC:4982; HMBS. DR HPA; HPA006114; -. DR HPA; HPA050659; -. DR MalaCards; HMBS; -. DR MIM; 176000; phenotype. DR MIM; 609806; gene. DR neXtProt; NX_P08397; -. DR Orphanet; 79276; Acute intermittent porphyria. DR PharmGKB; PA29317; -. DR eggNOG; KOG2892; Eukaryota. DR eggNOG; COG0181; LUCA. DR GeneTree; ENSGT00390000009083; -. DR HOGENOM; HOG000228587; -. DR HOVERGEN; HBG000967; -. DR InParanoid; P08397; -. DR KO; K01749; -. DR OMA; GAHTLMG; -. DR PhylomeDB; P08397; -. DR TreeFam; TF105389; -. DR BioCyc; MetaCyc:HS07607-MONOMER; -. DR BRENDA; 2.5.1.61; 2681. DR Reactome; R-HSA-189451; Heme biosynthesis. DR UniPathway; UPA00251; UER00319. DR EvolutionaryTrace; P08397; -. DR GeneWiki; Porphobilinogen_deaminase; -. DR GenomeRNAi; 3145; -. DR NextBio; 12464; -. DR PRO; PR:P08397; -. DR Proteomes; UP000005640; Chromosome 11. DR Bgee; P08397; -. DR CleanEx; HS_HMBS; -. DR ExpressionAtlas; P08397; baseline and differential. DR Genevisible; P08397; HS. DR GO; GO:0030424; C:axon; IEA:Ensembl. DR GO; GO:0000793; C:condensed chromosome; IEA:Ensembl. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IEA:Ensembl. DR GO; GO:0043176; F:amine binding; IEA:Ensembl. DR GO; GO:0031406; F:carboxylic acid binding; IEA:Ensembl. DR GO; GO:0050662; F:coenzyme binding; IEA:Ensembl. DR GO; GO:0004418; F:hydroxymethylbilane synthase activity; IDA:UniProtKB. DR GO; GO:0004852; F:uroporphyrinogen-III synthase activity; IEA:Ensembl. DR GO; GO:0048708; P:astrocyte differentiation; IEA:Ensembl. DR GO; GO:0071418; P:cellular response to amine stimulus; IEA:Ensembl. DR GO; GO:0071236; P:cellular response to antibiotic; IEA:Ensembl. DR GO; GO:0071243; P:cellular response to arsenic-containing substance; IEA:Ensembl. DR GO; GO:0071345; P:cellular response to cytokine stimulus; IEA:Ensembl. DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl. DR GO; GO:0071284; P:cellular response to lead ion; IEA:Ensembl. DR GO; GO:0006783; P:heme biosynthetic process; IC:UniProtKB. DR GO; GO:0031100; P:organ regeneration; IEA:Ensembl. DR GO; GO:0018160; P:peptidyl-pyrromethane cofactor linkage; IEA:InterPro. DR GO; GO:0006778; P:porphyrin-containing compound metabolic process; TAS:Reactome. DR GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:UniProtKB-UniPathway. DR GO; GO:0043200; P:response to amino acid; IEA:Ensembl. DR GO; GO:0009743; P:response to carbohydrate; IEA:Ensembl. DR GO; GO:0032025; P:response to cobalt ion; IEA:Ensembl. DR GO; GO:0042493; P:response to drug; IEA:Ensembl. DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0051597; P:response to methylmercury; IEA:Ensembl. DR GO; GO:0033273; P:response to vitamin; IEA:Ensembl. DR GO; GO:0010043; P:response to zinc ion; IEA:Ensembl. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. DR Gene3D; 3.30.160.40; -; 1. DR HAMAP; MF_00260; Porphobil_deam; 1. DR InterPro; IPR000860; HemC. DR InterPro; IPR022419; Porphobilin_deaminase_cofac_BS. DR InterPro; IPR022417; Porphobilin_deaminase_N. DR InterPro; IPR022418; Porphobilinogen_deaminase_C. DR PANTHER; PTHR11557; PTHR11557; 2. DR Pfam; PF01379; Porphobil_deam; 1. DR Pfam; PF03900; Porphobil_deamC; 1. DR PIRSF; PIRSF001438; 4pyrrol_synth_OHMeBilane_synth; 1. DR PRINTS; PR00151; PORPHBDMNASE. DR SUPFAM; SSF54782; SSF54782; 2. DR TIGRFAMs; TIGR00212; hemC; 1. DR PROSITE; PS00533; PORPHOBILINOGEN_DEAM; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Complete proteome; KW Cytoplasm; Direct protein sequencing; Disease mutation; KW Heme biosynthesis; Porphyrin biosynthesis; Reference proteome; KW Transferase. FT INIT_MET 1 1 Removed. {ECO:0000244|PubMed:19413330, FT ECO:0000244|PubMed:22223895, FT ECO:0000244|PubMed:22814378}. FT CHAIN 2 361 Porphobilinogen deaminase. FT /FTId=PRO_0000143034. FT MOD_RES 2 2 N-acetylserine. FT {ECO:0000244|PubMed:19413330, FT ECO:0000244|PubMed:22223895, FT ECO:0000244|PubMed:22814378}. FT MOD_RES 74 74 N6-acetyllysine. FT {ECO:0000250|UniProtKB:P22907}. FT MOD_RES 261 261 S-(dipyrrolylmethanemethyl)cysteine. FT VAR_SEQ 1 17 Missing (in isoform 2 and isoform 4). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:2875434}. FT /FTId=VSP_002067. FT VAR_SEQ 218 257 Missing (in isoform 3 and isoform 4). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_047294. FT VARIANT 18 18 M -> I (in AIP). FT {ECO:0000269|PubMed:12406973}. FT /FTId=VAR_025558. FT VARIANT 22 22 R -> C (in AIP). FT {ECO:0000269|PubMed:10453740, FT ECO:0000269|PubMed:9463797}. FT /FTId=VAR_003638. FT VARIANT 24 24 G -> S (in AIP). FT /FTId=VAR_011001. FT VARIANT 26 26 R -> C (in AIP; less than 1% of wild-type FT deaminase activity). FT {ECO:0000269|PubMed:10453740, FT ECO:0000269|PubMed:10657149, FT ECO:0000269|PubMed:12372055, FT ECO:0000269|PubMed:19292878}. FT /FTId=VAR_011002. FT VARIANT 26 26 R -> H (in AIP; severe decrease in FT deaminase activity). FT {ECO:0000269|PubMed:10453740, FT ECO:0000269|PubMed:11857754, FT ECO:0000269|PubMed:12372055, FT ECO:0000269|PubMed:16211556, FT ECO:0000269|PubMed:19292878, FT ECO:0000269|PubMed:8401516}. FT /FTId=VAR_003639. FT VARIANT 28 28 S -> N (in AIP). FT /FTId=VAR_011003. FT VARIANT 31 31 A -> P (in AIP). FT {ECO:0000269|PubMed:10453740}. FT /FTId=VAR_011004. FT VARIANT 31 31 A -> T (in AIP). FT {ECO:0000269|PubMed:8270254}. FT /FTId=VAR_003640. FT VARIANT 32 32 R -> P (in AIP; results in less than 1% FT of wild-type deaminase activity). FT {ECO:0000269|PubMed:19138865}. FT /FTId=VAR_074151. FT VARIANT 34 34 Q -> K (in AIP). FT {ECO:0000269|PubMed:1427766}. FT /FTId=VAR_003641. FT VARIANT 34 34 Q -> P (in AIP; less than 3% of FT activity). {ECO:0000269|PubMed:10494093}. FT /FTId=VAR_011005. FT VARIANT 34 34 Q -> R (in AIP). FT {ECO:0000269|PubMed:14669009}. FT /FTId=VAR_025559. FT VARIANT 35 35 T -> M (in AIP). FT {ECO:0000269|PubMed:11013452}. FT /FTId=VAR_011006. FT VARIANT 42 42 L -> S (in AIP). FT {ECO:0000269|PubMed:10453740}. FT /FTId=VAR_011007. FT VARIANT 55 55 A -> S (in AIP). FT {ECO:0000269|PubMed:8270254}. FT /FTId=VAR_003642. FT VARIANT 59 59 T -> I (in AIP; unknown pathological FT significance; has 80% of wild-type FT deaminase activity). FT {ECO:0000269|PubMed:18406650}. FT /FTId=VAR_074152. FT VARIANT 61 61 D -> N (in AIP). FT {ECO:0000269|PubMed:10453740}. FT /FTId=VAR_011008. FT VARIANT 61 61 D -> Y (in AIP). FT {ECO:0000269|PubMed:11857754}. FT /FTId=VAR_025560. FT VARIANT 78 78 T -> P (in AIP). FT {ECO:0000269|PubMed:11399210}. FT /FTId=VAR_025561. FT VARIANT 80 80 E -> G (in AIP). FT {ECO:0000269|PubMed:11399210}. FT /FTId=VAR_025562. FT VARIANT 81 81 L -> P (in AIP). FT {ECO:0000269|PubMed:14970743}. FT /FTId=VAR_025563. FT VARIANT 85 85 L -> R (in AIP). FT {ECO:0000269|PubMed:10453740}. FT /FTId=VAR_011009. FT VARIANT 86 86 E -> V (in AIP). FT {ECO:0000269|PubMed:12372055}. FT /FTId=VAR_025564. FT VARIANT 90 90 V -> G (in AIP). FT {ECO:0000269|PubMed:10453740}. FT /FTId=VAR_011010. FT VARIANT 92 92 L -> P (in AIP). FT {ECO:0000269|PubMed:12372055}. FT /FTId=VAR_025565. FT VARIANT 93 93 V -> F (in AIP; loss of activity). FT {ECO:0000269|PubMed:7962538}. FT /FTId=VAR_003643. FT VARIANT 93 93 Missing (in AIP). FT {ECO:0000269|PubMed:11857754}. FT /FTId=VAR_025566. FT VARIANT 96 96 S -> F (in AIP). FT {ECO:0000269|PubMed:12406973}. FT /FTId=VAR_025567. FT VARIANT 98 98 K -> R (in AIP). FT /FTId=VAR_003644. FT VARIANT 99 99 D -> G (in AIP; complete loss of FT deaminase activity). FT {ECO:0000269|PubMed:12372055, FT ECO:0000269|PubMed:12773194}. FT /FTId=VAR_025568. FT VARIANT 99 99 D -> H (in AIP). FT {ECO:0000269|PubMed:12406973}. FT /FTId=VAR_025569. FT VARIANT 99 99 D -> N (in AIP). {ECO:0000269|Ref.45}. FT /FTId=VAR_025570. FT VARIANT 111 111 G -> R (in AIP). FT {ECO:0000269|PubMed:10453740, FT ECO:0000269|PubMed:10494093, FT ECO:0000269|PubMed:10602775, FT ECO:0000269|PubMed:11013452, FT ECO:0000269|PubMed:11399210, FT ECO:0000269|PubMed:11857754, FT ECO:0000269|PubMed:12372055, FT ECO:0000269|PubMed:15669678, FT ECO:0000269|PubMed:25703257, FT ECO:0000269|PubMed:8268934}. FT /FTId=VAR_003645. FT VARIANT 113 113 I -> T (in AIP). FT {ECO:0000269|PubMed:12372055}. FT /FTId=VAR_025571. FT VARIANT 116 116 R -> Q (in AIP). FT {ECO:0000269|PubMed:8081367}. FT /FTId=VAR_003646. FT VARIANT 116 116 R -> W (in AIP; loss of activity; affects FT protein conformation; lower thermal FT stability than wild-type enzyme). FT {ECO:0000269|PubMed:10602775, FT ECO:0000269|PubMed:11030413, FT ECO:0000269|PubMed:23815679, FT ECO:0000269|PubMed:7962538, FT ECO:0000269|PubMed:9225970}. FT /FTId=VAR_003647. FT VARIANT 119 119 P -> L (in AIP). FT {ECO:0000269|PubMed:8825929, FT ECO:0000269|PubMed:9225970}. FT /FTId=VAR_003648. FT VARIANT 122 122 A -> G (in AIP). FT {ECO:0000269|PubMed:12406973}. FT /FTId=VAR_025572. FT VARIANT 124 124 V -> D (in AIP). FT /FTId=VAR_011011. FT VARIANT 132 132 K -> N (found in a patient with unclear FT porphyria-related biochemical findings FT and abdominal pain; unknown pathological FT significance; does not affect activity; FT does not affect Vmax; does not affect KM; FT does not affect thermal stability; FT dbSNP:rs551209435). FT {ECO:0000269|PubMed:23815679}. FT /FTId=VAR_073714. FT VARIANT 149 149 R -> L (in AIP). FT {ECO:0000269|PubMed:8270254}. FT /FTId=VAR_003649. FT VARIANT 149 149 R -> Q (in AIP; loss of deaminase FT activity). {ECO:0000269|PubMed:12773194, FT ECO:0000269|PubMed:1714233}. FT /FTId=VAR_003650. FT VARIANT 152 152 Missing (in AIP). FT {ECO:0000269|PubMed:10502788}. FT /FTId=VAR_009223. FT VARIANT 167 167 R -> Q (in AIP; decreased deaminase FT activity due to defective enzyme- FT intermediate complexes turnover and FT regeneration of free enzyme molecules). FT {ECO:0000269|PubMed:12773194, FT ECO:0000269|PubMed:1427766, FT ECO:0000269|PubMed:2243128, FT ECO:0000269|PubMed:9225970}. FT /FTId=VAR_003651. FT VARIANT 167 167 R -> W (in AIP; results in less than 5% FT of wild-type activity; 2-fold decrease of FT Vmax; 33-fold increase of KM). FT {ECO:0000269|PubMed:10602775, FT ECO:0000269|PubMed:1301948, FT ECO:0000269|PubMed:1496994, FT ECO:0000269|PubMed:23815679, FT ECO:0000269|PubMed:9225970}. FT /FTId=VAR_003652. FT VARIANT 173 173 R -> Q (in AIP; less than 1% of wild-type FT activity). {ECO:0000269|PubMed:10453740, FT ECO:0000269|PubMed:11857754, FT ECO:0000269|PubMed:12372055, FT ECO:0000269|PubMed:12773194, FT ECO:0000269|PubMed:1301948, FT ECO:0000269|PubMed:15669678, FT ECO:0000269|PubMed:19292878, FT ECO:0000269|PubMed:2243128}. FT /FTId=VAR_003653. FT VARIANT 173 173 R -> W (in AIP; 1% of wild-type activity; FT lower thermal stability than wild-type FT enzyme). {ECO:0000269|PubMed:10453740, FT ECO:0000269|PubMed:10494093, FT ECO:0000269|PubMed:10602775, FT ECO:0000269|PubMed:11399210, FT ECO:0000269|PubMed:16211556, FT ECO:0000269|PubMed:23815679, FT ECO:0000269|PubMed:8081367, FT ECO:0000269|PubMed:9225970}. FT /FTId=VAR_003654. FT VARIANT 177 177 L -> R (in AIP). FT {ECO:0000269|PubMed:10453740, FT ECO:0000269|PubMed:1427766, FT ECO:0000269|PubMed:8081367}. FT /FTId=VAR_003655. FT VARIANT 178 178 D -> N (in AIP; unknown pathological FT significance; has 80% of wild-type FT deaminase activity). FT {ECO:0000269|PubMed:12372055, FT ECO:0000269|PubMed:19138865}. FT /FTId=VAR_011012. FT VARIANT 195 195 R -> C (in AIP; severe decrease of FT deaminase activity; dbSNP:rs34413634). FT {ECO:0000269|PubMed:10453740, FT ECO:0000269|PubMed:16211556}. FT /FTId=VAR_003656. FT VARIANT 201 201 R -> W (in AIP; residual activity). FT {ECO:0000269|PubMed:10494093, FT ECO:0000269|PubMed:7962538, FT ECO:0000269|PubMed:8270256, FT ECO:0000269|PubMed:9225970}. FT /FTId=VAR_003657. FT VARIANT 202 202 V -> L (in AIP). FT {ECO:0000269|PubMed:10657149}. FT /FTId=VAR_011013. FT VARIANT 204 204 Q -> K (in AIP; 46% wild-type deaminase FT activity; decreased enzyme stability). FT {ECO:0000269|PubMed:19292878}. FT /FTId=VAR_074153. FT VARIANT 209 209 E -> K (in AIP). FT /FTId=VAR_011014. FT VARIANT 212 212 M -> V (in AIP; <2% residual activity). FT {ECO:0000269|PubMed:10602775}. FT /FTId=VAR_025573. FT VARIANT 215 215 V -> E (in AIP; unknown pathological FT significance; results in 30% of wild-type FT activity; 3-fold decrease of Vmax; normal FT KM; affects protein conformation). FT {ECO:0000269|PubMed:14757946, FT ECO:0000269|PubMed:23815679}. FT /FTId=VAR_073715. FT VARIANT 215 215 V -> M (in AIP; 19% of wild-type FT deaminase activity). FT {ECO:0000269|PubMed:18406650}. FT /FTId=VAR_074154. FT VARIANT 216 216 G -> D (in AIP). FT {ECO:0000269|PubMed:9225970}. FT /FTId=VAR_011015. FT VARIANT 217 217 Q -> H (in AIP). FT /FTId=VAR_011016. FT VARIANT 217 217 Q -> L (in AIP). FT {ECO:0000269|PubMed:10782018}. FT /FTId=VAR_011017. FT VARIANT 219 219 A -> D (in AIP). FT {ECO:0000269|PubMed:10453740}. FT /FTId=VAR_011018. FT VARIANT 222 222 V -> M (in AIP). FT {ECO:0000269|PubMed:9654202}. FT /FTId=VAR_003658. FT VARIANT 223 223 E -> K (in AIP). FT {ECO:0000269|PubMed:8270254}. FT /FTId=VAR_003659. FT VARIANT 225 225 R -> G (in AIP). FT {ECO:0000269|PubMed:12372055}. FT /FTId=VAR_003660. FT VARIANT 225 225 R -> Q (in AIP). FT {ECO:0000269|PubMed:12372055}. FT /FTId=VAR_025574. FT VARIANT 236 236 G -> S (in AIP). FT {ECO:0000269|PubMed:14669009}. FT /FTId=VAR_025575. FT VARIANT 238 238 L -> P (in AIP; unknown pathological FT significance). FT {ECO:0000269|PubMed:14757946}. FT /FTId=VAR_073716. FT VARIANT 238 238 L -> R (in AIP). FT /FTId=VAR_003661. FT VARIANT 244 244 L -> P (in AIP). FT {ECO:0000269|PubMed:14669009}. FT /FTId=VAR_025576. FT VARIANT 245 245 L -> R (in AIP). FT {ECO:0000269|PubMed:1714233}. FT /FTId=VAR_003662. FT VARIANT 247 247 C -> F (in AIP; residual activity). FT {ECO:0000269|PubMed:7962538}. FT /FTId=VAR_003663. FT VARIANT 247 247 C -> R (in AIP; severe decrease of FT deaminase activity). FT {ECO:0000269|PubMed:10453740, FT ECO:0000269|PubMed:16211556, FT ECO:0000269|PubMed:8262523}. FT /FTId=VAR_003664. FT VARIANT 248 248 I -> IETLLRCI (in AIP). FT /FTId=VAR_011019. FT VARIANT 250 250 E -> A (in AIP; severe decrease of FT deaminase activity). FT {ECO:0000269|PubMed:16211556, FT ECO:0000269|PubMed:8825929}. FT /FTId=VAR_003665. FT VARIANT 250 250 E -> D (in AIP; less than 1% of wild-type FT deaminase activity). FT {ECO:0000269|PubMed:19292878}. FT /FTId=VAR_074155. FT VARIANT 250 250 E -> K (in AIP). FT {ECO:0000269|PubMed:8270254}. FT /FTId=VAR_003666. FT VARIANT 250 250 E -> Q (in AIP). FT /FTId=VAR_011020. FT VARIANT 250 250 E -> V (in AIP). FT /FTId=VAR_011021. FT VARIANT 252 252 A -> T (in AIP). FT {ECO:0000269|PubMed:8262523}. FT /FTId=VAR_003667. FT VARIANT 252 252 A -> V (in AIP). FT {ECO:0000269|PubMed:8262523}. FT /FTId=VAR_003668. FT VARIANT 254 254 L -> P (in AIP). FT {ECO:0000269|PubMed:12406973}. FT /FTId=VAR_025577. FT VARIANT 256 256 H -> N (in AIP). FT {ECO:0000269|PubMed:1427766}. FT /FTId=VAR_003669. FT VARIANT 256 256 H -> Y (in AIP). FT {ECO:0000269|PubMed:12372055}. FT /FTId=VAR_011022. FT VARIANT 260 260 G -> D (in AIP). FT {ECO:0000269|PubMed:12372055}. FT /FTId=VAR_025578. FT VARIANT 261 261 C -> Y (in AIP). FT {ECO:0000269|PubMed:12406973}. FT /FTId=VAR_025579. FT VARIANT 267 267 V -> M (in AIP). FT /FTId=VAR_011023. FT VARIANT 269 269 T -> I (in AIP). FT {ECO:0000269|PubMed:10453740, FT ECO:0000269|PubMed:8081367}. FT /FTId=VAR_003670. FT VARIANT 270 270 A -> D (in AIP). FT /FTId=VAR_011024. FT VARIANT 270 270 A -> G (in AIP). FT {ECO:0000269|PubMed:11030413}. FT /FTId=VAR_011025. FT VARIANT 274 274 G -> R (in AIP). FT {ECO:0000269|PubMed:8081367}. FT /FTId=VAR_003671. FT VARIANT 278 278 L -> P (in AIP). FT {ECO:0000269|PubMed:9654202}. FT /FTId=VAR_003672. FT VARIANT 280 280 G -> R (in AIP). FT /FTId=VAR_003673. FT VARIANT 281 281 Missing (in AIP). FT {ECO:0000269|PubMed:11013452}. FT /FTId=VAR_011026. FT VARIANT 329 332 Missing (in AIP). FT {ECO:0000269|PubMed:10494093}. FT /FTId=VAR_011027. FT VARIANT 330 330 A -> P (in AIP). FT {ECO:0000269|PubMed:25870942}. FT /FTId=VAR_074156. FT VARIANT 335 335 G -> D (in AIP). FT {ECO:0000269|PubMed:11857754}. FT /FTId=VAR_011028. FT VARIANT 335 335 G -> S (in AIP; less than 3% of FT activity). {ECO:0000269|PubMed:10494093}. FT /FTId=VAR_011029. FT VARIANT 338 338 L -> P (in AIP). FT {ECO:0000269|PubMed:25703257}. FT /FTId=VAR_074157. FT VARIANT 343 343 L -> P (in AIP). FT {ECO:0000269|PubMed:12372055}. FT /FTId=VAR_025580. FT CONFLICT 177 177 L -> M (in Ref. 3; AAA60029/AAA60030). FT {ECO:0000305}. FT CONFLICT 210 210 E -> K (in Ref. 2; CAA28499). FT {ECO:0000305}. FT CONFLICT 349 349 N -> T (in Ref. 1; CAA27801). FT {ECO:0000305}. FT STRAND 20 28 {ECO:0000244|PDB:3ECR}. FT HELIX 29 45 {ECO:0000244|PDB:3ECR}. FT STRAND 49 56 {ECO:0000244|PDB:3ECR}. FT HELIX 78 86 {ECO:0000244|PDB:3ECR}. FT STRAND 91 96 {ECO:0000244|PDB:3ECR}. FT HELIX 97 99 {ECO:0000244|PDB:3ECR}. FT STRAND 108 113 {ECO:0000244|PDB:3ECR}. FT STRAND 121 125 {ECO:0000244|PDB:3ECR}. FT HELIX 127 129 {ECO:0000244|PDB:3EQ1}. FT TURN 134 136 {ECO:0000244|PDB:3ECR}. FT STRAND 142 144 {ECO:0000244|PDB:3ECR}. FT HELIX 148 157 {ECO:0000244|PDB:3ECR}. FT STRAND 161 164 {ECO:0000244|PDB:3ECR}. FT HELIX 170 179 {ECO:0000244|PDB:3ECR}. FT STRAND 180 182 {ECO:0000244|PDB:3ECR}. FT STRAND 184 189 {ECO:0000244|PDB:3ECR}. FT HELIX 190 195 {ECO:0000244|PDB:3ECR}. FT HELIX 199 201 {ECO:0000244|PDB:3ECR}. FT TURN 208 210 {ECO:0000244|PDB:3ECR}. FT TURN 215 218 {ECO:0000244|PDB:3ECR}. FT STRAND 220 225 {ECO:0000244|PDB:3ECR}. FT HELIX 229 236 {ECO:0000244|PDB:3ECR}. FT HELIX 241 257 {ECO:0000244|PDB:3ECR}. FT STRAND 263 272 {ECO:0000244|PDB:3ECR}. FT STRAND 275 283 {ECO:0000244|PDB:3ECR}. FT STRAND 289 298 {ECO:0000244|PDB:3ECR}. FT HELIX 325 344 {ECO:0000244|PDB:3ECR}. FT HELIX 347 353 {ECO:0000244|PDB:3ECR}. SQ SEQUENCE 361 AA; 39330 MW; 8F2F6F4150F1AD7E CRC64; MSGNGNAAAT AEENSPKMRV IRVGTRKSQL ARIQTDSVVA TLKASYPGLQ FEIIAMSTTG DKILDTALSK IGEKSLFTKE LEHALEKNEV DLVVHSLKDL PTVLPPGFTI GAICKRENPH DAVVFHPKFV GKTLETLPEK SVVGTSSLRR AAQLQRKFPH LEFRSIRGNL NTRLRKLDEQ QEFSAIILAT AGLQRMGWHN RVGQILHPEE CMYAVGQGAL GVEVRAKDQD ILDLVGVLHD PETLLRCIAE RAFLRHLEGG CSVPVAVHTA MKDGQLYLTG GVWSLDGSDS IQETMQATIH VPAQHEDGPE DDPQLVGITA RNIPRGPQLA AQNLGISLAN LLLSKGAKNI LDVARQLNDA H //