HEM3_HUMAN
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 03-AUG-2022, entry version 236.
DE RecName: Full=Porphobilinogen deaminase {ECO:0000305|PubMed:2875434};
DE Short=PBG-D;
DE EC=2.5.1.61 {ECO:0000269|PubMed:18936296, ECO:0000269|PubMed:19138865, ECO:0000269|PubMed:23815679};
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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., 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 isoenzymes
RT 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 amplifiable
RT 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., 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 [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., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., 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., 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 (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 project:
RT 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; DOI=10.3109/00365518909091544;
RA Lannfelt L., Wetterberg L., Lilius L., Thunell S., Joernvall H., Pavlu B.,
RA Wielburski A., Gellerfors P.;
RT "Porphobilinogen deaminase in human erythrocytes: purification of two forms
RT 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 SPECTROMETRY
RP [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 [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., 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 [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15; SER-69 AND SER-147, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
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., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [16]
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., Sarwar M.,
RA Cooper J.B., Wood S.P., Shoolingin-Jordan P.M.;
RT "Structure of human porphobilinogen deaminase at 2.8 A: the molecular basis
RT of acute intermittent porphyria.";
RL Biochem. J. 420:17-25(2009).
RN [17] {ECO:0007744|PDB:3ECR}
RP X-RAY CRYSTALLOGRAPHY (2.18 ANGSTROMS), PROSTHETIC GROUP AT CYS-261,
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT,
RP COFACTOR, AND MUTAGENESIS OF ARG-26; GLN-34; HIS-120 AND ARG-195.
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 [18]
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., Wilson J.H.P.,
RA Deybach J.-C., Nordmann Y., Grandchamp B.;
RT "Two different point G to A mutations in exon 10 of the porphobilinogen
RT deaminase gene are responsible for acute intermittent porphyria.";
RL J. Clin. Invest. 86:1511-1516(1990).
RN [19]
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: identification of
RT four additional mutations resulting in the CRIM-negative subtype of the
RT disease.";
RL Am. J. Hum. Genet. 49:421-428(1991).
RN [20]
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 deaminase
RT gene in patients with a CRIM-positive subtype of acute intermittent
RT porphyria.";
RL Am. J. Hum. Genet. 51:660-665(1992).
RN [21]
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 gene
RT in patients with acute intermittent porphyria, by direct sequencing of in
RT vitro amplified cDNA.";
RL Hum. Genet. 90:12-16(1992).
RN [22]
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 [23]
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 porphobilinogen
RT deaminase gene in patients with acute intermittent porphyria.";
RL Hum. Genet. 92:619-622(1993).
RN [24]
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 [25]
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 [26]
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 using
RT denaturing gradient gel electrophoresis.";
RL Hum. Genet. 93:47-52(1994).
RN [27]
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 screening
RT method using PCR amplification of specific alleles.";
RL Hum. Genet. 93:59-62(1994).
RN [28]
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 deaminase
RT gene.";
RL Hum. Mol. Genet. 3:809-811(1994).
RN [29]
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 [30]
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 codon
RT missense mutation in the housekeeping transcript causes 'variant acute
RT intermittent porphyria' with normal expression of the erythroid-specific
RT enzyme.";
RL J. Clin. Invest. 94:1927-1937(1994).
RN [31]
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 [32]
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 [33]
RP VARIANTS AIP.
RX PubMed=9199558; DOI=10.1086/515455;
RA Puy H., Deybach J.-C., Lamoril J., Robreau A.-M., Da Silva V., Gouya L.,
RA 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 [34]
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 Swedish
RT acute intermittent porphyria families.";
RL Hum. Genet. 100:63-66(1997).
RN [35]
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 [36]
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 synthase
RT gene in three patients from two unrelated families with acute intermittent
RT porphyria.";
RL Hum. Hered. 48:24-29(1998).
RN [37]
RP VARIANTS AIP PRO-34; ARG-111; TRP-173; TRP-201; 329-LEU--GLN-332 DEL AND
RP 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 ancestral
RT founder of the common G111R mutation.";
RL Am. J. Med. Genet. 86:366-375(1999).
RN [38]
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 AND
RP 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 detection
RT of mutations in the HMBS gene in British patients with acute intermittent
RT porphyria: identification of 25 novel mutations.";
RL Hum. Genet. 104:505-510(1999).
RN [39]
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 in
RT the porphobilinogen deaminase gene, one amino acid deletion (453-455delAGC)
RT and one splicing acceptor site mutation (IVS8-1G>T).";
RL Hum. Mutat. 14:355-355(1999).
RN [40]
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 patients
RT with acute intermittent porphyria.";
RL Mol. Cell. Probes 13:443-447(1999).
RN [41]
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; DOI=10.1007/bf03401985;
RA Solis C., Lopez-Echaniz I., Sefarty-Graneda D., Astrin K.H., 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 [42]
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 [43]
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 [44]
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 [45]
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., Rossetti M.V.;
RT "Identification and characterization of two novel mutations that produce
RT acute intermittent porphyria: a 3-base deletion (841-843delGGA) and a
RT missense mutation (T35M).";
RL Hum. Mutat. 16:373-373(2000).
RN [46]
RP ERRATUM OF PUBMED:11013452, 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 [47]
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 196
RT patients and their families.";
RL Clin. Chem. 48:1891-1900(2002).
RN [48]
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 clinical
RT consequences of some new mutations found in the porphobilinogen deaminase
RT gene.";
RL Clin. Genet. 62:288-297(2002).
RN [49]
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 [50]
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., Butler D.;
RT "Human porphobilinogen deaminase mutations in the investigation of the
RT mechanism of dipyrromethane cofactor assembly and tetrapyrrole formation.";
RL Biochem. Soc. Trans. 31:731-735(2003).
RN [51]
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., 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 [52]
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 inherited
RT erythropoietic protoporphyria and acute hepatic porphyrias.";
RL Hum. Genet. 114:256-262(2004).
RN [53]
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., Scheffer H.,
RA Zuijderhoudt F.M.J.;
RT "Homozygous acute intermittent porphyria in a 7-year-old boy with massive
RT excretions of porphyrins and porphyrin precursors.";
RL J. Inherit. Metab. Dis. 27:19-27(2004).
RN [54]
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., Minder E.I.;
RT "Mutation hotspots in the human porphobilinogen deaminase gene: recurrent
RT mutations G111R and R173Q occurring at CpG motifs.";
RL J. Inherit. Metab. Dis. 27:625-631(2004).
RN [55]
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 with
RT acute intermittent porphyria.";
RL Hum. Mutat. 26:496-496(2005).
RN [56]
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 associations
RT with acute intermittent porphyria.";
RL Mol. Genet. Metab. 94:343-346(2008).
RN [57]
RP VARIANT AIP PRO-32, CHARACTERIZATION OF VARIANTS AIP PRO-32 AND ASN-178,
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
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 acute
RT intermittent porphyria.";
RL Blood Cells Mol. Dis. 42:167-173(2009).
RN [58]
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 [59]
RP VARIANT ASN-132, CHARACTERIZATION OF VARIANTS AIP TRP-116; TRP-167; TRP-173
RP AND GLU-215, CHARACTERIZATION OF VARIANT ASN-132, FUNCTION, CATALYTIC
RP ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=23815679; DOI=10.1042/bsr20130045;
RA Bustad H.J., Vorland M., Ronneseth E., Sandberg S., Martinez A., Toska K.;
RT "Conformational stability and activity analysis of two hydroxymethylbilane
RT synthase mutants, K132N and V215E, with different phenotypic association
RT with acute intermittent porphyria.";
RL Biosci. Rep. 33:0-0(2013).
RN [60]
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., Pereira O.M.,
RA Nagai M.A., de Oliveira Barretto O.C., Ribeiro G.S.;
RT "Hydroxymethylbilane synthase gene mutations and polymorphisms in Brazilian
RT families with acute intermittent porphyria.";
RL Ann. Hum. Genet. 79:162-172(2015).
RN [61]
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., Wu W.,
RA 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: As part of the heme biosynthetic pathway, catalyzes the
CC sequential polymerization of four molecules of porphobilinogen to form
CC hydroxymethylbilane, also known as preuroporphyrinogen
CC (PubMed:18936296, PubMed:19138865, PubMed:23815679). Catalysis begins
CC with the assembly of the dipyrromethane cofactor by the apoenzyme from
CC two molecules of porphobilinogen or from preuroporphyrinogen. The
CC covalently linked cofactor acts as a primer, around which the
CC tetrapyrrole product is assembled. In the last step of catalysis, the
CC product, preuroporphyrinogen, is released, leaving the cofactor bound
CC to the holodeaminase intact (PubMed:18936296).
CC {ECO:0000269|PubMed:18936296, ECO:0000269|PubMed:19138865,
CC ECO:0000269|PubMed:23815679}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + 4 porphobilinogen = hydroxymethylbilane + 4 NH4(+);
CC Xref=Rhea:RHEA:13185, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:57845, ChEBI:CHEBI:58126; EC=2.5.1.61;
CC Evidence={ECO:0000269|PubMed:18936296, ECO:0000269|PubMed:19138865,
CC ECO:0000269|PubMed:23815679};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13186;
CC Evidence={ECO:0000269|PubMed:19138865};
CC -!- COFACTOR:
CC Name=dipyrromethane; Xref=ChEBI:CHEBI:60342;
CC Note=Binds 1 dipyrromethane group covalently.
CC {ECO:0000269|PubMed:18936296};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=48 uM for porphobilinogen {ECO:0000269|PubMed:23815679};
CC KM=15.3 uM for porphobilinogen (at pH 8.0 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:18936296};
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 temperature
CC (Tm) is about 74 degrees Celsius. {ECO:0000269|PubMed:23815679};
CC -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX
CC biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 2/4.
CC {ECO:0000269|PubMed:19138865}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:18936296}.
CC -!- INTERACTION:
CC P08397; P42858: HTT; NbExp=3; IntAct=EBI-9090148, EBI-466029;
CC P08397; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-9090148, EBI-79165;
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 Name=4;
CC IsoId=P08397-4; Sequence=VSP_002067, VSP_047294;
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Is ubiquitously expressed.
CC {ECO:0000269|PubMed:3422427}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Is found only in erythroid cells.
CC {ECO:0000269|PubMed:3422427}.
CC -!- DISEASE: Acute intermittent porphyria (AIP) [MIM:176000]: 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. AIP is an autosomal dominant
CC form of hepatic porphyria characterized by attacks of gastrointestinal
CC disturbances, abdominal colic, with neurological dysfunctions,
CC hypertension, tachycardia and peripheral neuropathy. Most attacks are
CC precipitated by drugs, alcohol, caloric deprivation, infections, or
CC endocrine factors. {ECO:0000269|PubMed:10453740,
CC ECO:0000269|PubMed:10494093, ECO:0000269|PubMed:10502788,
CC ECO:0000269|PubMed:10602775, ECO:0000269|PubMed:10657149,
CC ECO:0000269|PubMed:10782018, ECO:0000269|PubMed:11013452,
CC ECO:0000269|PubMed:11030413, ECO:0000269|PubMed:11399210,
CC ECO:0000269|PubMed:11857754, ECO:0000269|PubMed:12372055,
CC ECO:0000269|PubMed:12406973, ECO:0000269|PubMed:12773194,
CC ECO:0000269|PubMed:1301948, ECO:0000269|PubMed:1427766,
CC ECO:0000269|PubMed:14669009, ECO:0000269|PubMed:14757946,
CC ECO:0000269|PubMed:1496994, ECO:0000269|PubMed:14970743,
CC ECO:0000269|PubMed:15669678, ECO:0000269|PubMed:16211556,
CC ECO:0000269|PubMed:1714233, ECO:0000269|PubMed:18406650,
CC ECO:0000269|PubMed:19138865, ECO:0000269|PubMed:19292878,
CC ECO:0000269|PubMed:2243128, ECO:0000269|PubMed:23815679,
CC ECO:0000269|PubMed:25703257, ECO:0000269|PubMed:25870942,
CC ECO:0000269|PubMed:7757070, ECO:0000269|PubMed:7962538,
CC ECO:0000269|PubMed:8081367, ECO:0000269|PubMed:8262523,
CC ECO:0000269|PubMed:8268934, ECO:0000269|PubMed:8270254,
CC ECO:0000269|PubMed:8270256, ECO:0000269|PubMed:8401516,
CC ECO:0000269|PubMed:8825929, ECO:0000269|PubMed:9199558,
CC ECO:0000269|PubMed:9225970, ECO:0000269|PubMed:9463797,
CC ECO:0000269|PubMed:9654202, ECO:0000269|Ref.46}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the HMBS family. {ECO:0000305}.
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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 RefSeq; XP_016873118.1; XM_017017629.1. [P08397-2]
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 PDB; 5M6R; X-ray; 2.73 A; A/B=1-361.
DR PDB; 5M7F; X-ray; 2.78 A; A/B=18-361.
DR PDB; 7AAJ; X-ray; 1.80 A; A/B=1-361.
DR PDB; 7AAK; X-ray; 1.70 A; A/B=1-361.
DR PDB; 7CCX; X-ray; 1.84 A; A/C=1-361.
DR PDB; 7CCY; X-ray; 2.40 A; A/C=1-361.
DR PDB; 7CCZ; X-ray; 1.79 A; A/B=1-361.
DR PDB; 7CD0; X-ray; 2.31 A; A/B=1-361.
DR PDBsum; 3ECR; -.
DR PDBsum; 3EQ1; -.
DR PDBsum; 5M6R; -.
DR PDBsum; 5M7F; -.
DR PDBsum; 7AAJ; -.
DR PDBsum; 7AAK; -.
DR PDBsum; 7CCX; -.
DR PDBsum; 7CCY; -.
DR PDBsum; 7CCZ; -.
DR PDBsum; 7CD0; -.
DR AlphaFoldDB; P08397; -.
DR SMR; P08397; -.
DR BioGRID; 109388; 29.
DR IntAct; P08397; 8.
DR STRING; 9606.ENSP00000278715; -.
DR BindingDB; P08397; -.
DR ChEMBL; CHEMBL3988601; -.
DR CarbonylDB; P08397; -.
DR GlyGen; P08397; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P08397; -.
DR PhosphoSitePlus; P08397; -.
DR BioMuta; HMBS; -.
DR DMDM; 1170217; -.
DR EPD; P08397; -.
DR jPOST; P08397; -.
DR MassIVE; P08397; -.
DR MaxQB; P08397; -.
DR PaxDb; P08397; -.
DR PeptideAtlas; P08397; -.
DR PRIDE; P08397; -.
DR ProteomicsDB; 32397; -.
DR ProteomicsDB; 34147; -.
DR ProteomicsDB; 52108; -. [P08397-1]
DR ProteomicsDB; 52109; -. [P08397-2]
DR Antibodypedia; 54687; 418 antibodies from 35 providers.
DR DNASU; 3145; -.
DR Ensembl; ENST00000392841.1; ENSP00000376584.1; ENSG00000256269.11. [P08397-2]
DR Ensembl; ENST00000537841.5; ENSP00000444730.1; ENSG00000256269.11. [P08397-2]
DR Ensembl; ENST00000542729.5; ENSP00000443058.1; ENSG00000256269.11. [P08397-4]
DR Ensembl; ENST00000544387.5; ENSP00000438424.1; ENSG00000256269.11. [P08397-3]
DR Ensembl; ENST00000648374.1; ENSP00000497255.1; ENSG00000256269.11. [P08397-2]
DR Ensembl; ENST00000652429.1; ENSP00000498786.1; ENSG00000256269.11. [P08397-1]
DR GeneID; 3145; -.
DR KEGG; hsa:3145; -.
DR MANE-Select; ENST00000652429.1; ENSP00000498786.1; NM_000190.4; NP_000181.2.
DR UCSC; uc001puz.2; human. [P08397-1]
DR CTD; 3145; -.
DR DisGeNET; 3145; -.
DR GeneCards; HMBS; -.
DR GeneReviews; HMBS; -.
DR HGNC; HGNC:4982; HMBS.
DR HPA; ENSG00000256269; Tissue enriched (bone).
DR MalaCards; HMBS; -.
DR MIM; 176000; phenotype.
DR MIM; 609806; gene.
DR neXtProt; NX_P08397; -.
DR OpenTargets; ENSG00000256269; -.
DR Orphanet; 79276; Acute intermittent porphyria.
DR PharmGKB; PA29317; -.
DR VEuPathDB; HostDB:ENSG00000256269; -.
DR eggNOG; KOG2892; Eukaryota.
DR GeneTree; ENSGT00390000009083; -.
DR InParanoid; P08397; -.
DR OMA; LWQANHI; -.
DR OrthoDB; 1189095at2759; -.
DR PhylomeDB; P08397; -.
DR TreeFam; TF105389; -.
DR BioCyc; MetaCyc:HS07607-MON; -.
DR BRENDA; 2.5.1.61; 2681.
DR PathwayCommons; P08397; -.
DR Reactome; R-HSA-189451; Heme biosynthesis.
DR SABIO-RK; P08397; -.
DR SignaLink; P08397; -.
DR UniPathway; UPA00251; UER00319.
DR BioGRID-ORCS; 3145; 78 hits in 1080 CRISPR screens.
DR ChiTaRS; HMBS; human.
DR EvolutionaryTrace; P08397; -.
DR GeneWiki; Porphobilinogen_deaminase; -.
DR GenomeRNAi; 3145; -.
DR Pharos; P08397; Tbio.
DR PRO; PR:P08397; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P08397; protein.
DR Bgee; ENSG00000256269; Expressed in trabecular bone tissue and 191 other tissues.
DR ExpressionAtlas; P08397; baseline and differential.
DR Genevisible; P08397; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0004418; F:hydroxymethylbilane synthase activity; IDA:UniProtKB.
DR GO; GO:0006783; P:heme biosynthetic process; IDA:UniProtKB.
DR GO; GO:0018160; P:peptidyl-pyrromethane cofactor linkage; IEA:InterPro.
DR GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:UniProtKB-UniPathway.
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 InterPro; IPR036803; Porphobilinogen_deaminase_C_sf.
DR PANTHER; PTHR11557; PTHR11557; 1.
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; 1.
DR TIGRFAMs; TIGR00212; hemC; 1.
DR PROSITE; PS00533; PORPHOBILINOGEN_DEAM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm;
KW Direct protein sequencing; Disease variant; Heme biosynthesis;
KW Phosphoprotein; Porphyrin biosynthesis; Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT CHAIN 2..361
FT /note="Porphobilinogen deaminase"
FT /id="PRO_0000143034"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT MOD_RES 15
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 69
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 74
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P22907"
FT MOD_RES 147
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 261
FT /note="S-(dipyrrolylmethanemethyl)cysteine"
FT /evidence="ECO:0000269|PubMed:18936296"
FT VAR_SEQ 1..17
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:2875434"
FT /id="VSP_002067"
FT VAR_SEQ 218..257
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_047294"
FT VARIANT 18
FT /note="M -> I (in AIP)"
FT /evidence="ECO:0000269|PubMed:12406973"
FT /id="VAR_025558"
FT VARIANT 22
FT /note="R -> C (in AIP; dbSNP:rs189159450)"
FT /evidence="ECO:0000269|PubMed:10453740,
FT ECO:0000269|PubMed:9463797"
FT /id="VAR_003638"
FT VARIANT 24
FT /note="G -> S (in AIP)"
FT /id="VAR_011001"
FT VARIANT 26
FT /note="R -> C (in AIP; less than 1% of wild-type deaminase
FT activity; dbSNP:rs998842815)"
FT /evidence="ECO:0000269|PubMed:10453740,
FT ECO:0000269|PubMed:10657149, ECO:0000269|PubMed:12372055,
FT ECO:0000269|PubMed:19292878"
FT /id="VAR_011002"
FT VARIANT 26
FT /note="R -> H (in AIP; severe decrease in deaminase
FT activity; dbSNP:rs118204103)"
FT /evidence="ECO:0000269|PubMed:10453740,
FT ECO:0000269|PubMed:11857754, ECO:0000269|PubMed:12372055,
FT ECO:0000269|PubMed:16211556, ECO:0000269|PubMed:19292878,
FT ECO:0000269|PubMed:8401516"
FT /id="VAR_003639"
FT VARIANT 28
FT /note="S -> N (in AIP)"
FT /id="VAR_011003"
FT VARIANT 31
FT /note="A -> P (in AIP)"
FT /evidence="ECO:0000269|PubMed:10453740"
FT /id="VAR_011004"
FT VARIANT 31
FT /note="A -> T (in AIP; dbSNP:rs118204104)"
FT /evidence="ECO:0000269|PubMed:8270254"
FT /id="VAR_003640"
FT VARIANT 32
FT /note="R -> P (in AIP; loss of hydroxymethylbilane synthase
FT activity; results in less than 1% of wild-type deaminase
FT activity)"
FT /evidence="ECO:0000269|PubMed:19138865"
FT /id="VAR_074151"
FT VARIANT 34
FT /note="Q -> K (in AIP; dbSNP:rs118204105)"
FT /evidence="ECO:0000269|PubMed:1427766"
FT /id="VAR_003641"
FT VARIANT 34
FT /note="Q -> P (in AIP; less than 3% of activity)"
FT /evidence="ECO:0000269|PubMed:10494093"
FT /id="VAR_011005"
FT VARIANT 34
FT /note="Q -> R (in AIP)"
FT /evidence="ECO:0000269|PubMed:14669009"
FT /id="VAR_025559"
FT VARIANT 35
FT /note="T -> M (in AIP; dbSNP:rs974712040)"
FT /evidence="ECO:0000269|PubMed:11013452"
FT /id="VAR_011006"
FT VARIANT 42
FT /note="L -> S (in AIP)"
FT /evidence="ECO:0000269|PubMed:10453740"
FT /id="VAR_011007"
FT VARIANT 55
FT /note="A -> S (in AIP; dbSNP:rs118204106)"
FT /evidence="ECO:0000269|PubMed:8270254"
FT /id="VAR_003642"
FT VARIANT 59
FT /note="T -> I (in AIP; unknown pathological significance;
FT has 80% of wild-type deaminase activity;
FT dbSNP:rs761004837)"
FT /evidence="ECO:0000269|PubMed:18406650"
FT /id="VAR_074152"
FT VARIANT 61
FT /note="D -> N (in AIP)"
FT /evidence="ECO:0000269|PubMed:10453740"
FT /id="VAR_011008"
FT VARIANT 61
FT /note="D -> Y (in AIP)"
FT /evidence="ECO:0000269|PubMed:11857754"
FT /id="VAR_025560"
FT VARIANT 78
FT /note="T -> P (in AIP)"
FT /evidence="ECO:0000269|PubMed:11399210"
FT /id="VAR_025561"
FT VARIANT 80
FT /note="E -> G (in AIP)"
FT /evidence="ECO:0000269|PubMed:11399210"
FT /id="VAR_025562"
FT VARIANT 81
FT /note="L -> P (in AIP; dbSNP:rs118204119)"
FT /evidence="ECO:0000269|PubMed:14970743"
FT /id="VAR_025563"
FT VARIANT 85
FT /note="L -> R (in AIP)"
FT /evidence="ECO:0000269|PubMed:10453740"
FT /id="VAR_011009"
FT VARIANT 86
FT /note="E -> V (in AIP; dbSNP:rs150763621)"
FT /evidence="ECO:0000269|PubMed:12372055"
FT /id="VAR_025564"
FT VARIANT 90
FT /note="V -> G (in AIP)"
FT /evidence="ECO:0000269|PubMed:10453740"
FT /id="VAR_011010"
FT VARIANT 92
FT /note="L -> P (in AIP)"
FT /evidence="ECO:0000269|PubMed:12372055"
FT /id="VAR_025565"
FT VARIANT 93
FT /note="V -> F (in AIP; loss of activity)"
FT /evidence="ECO:0000269|PubMed:7962538"
FT /id="VAR_003643"
FT VARIANT 93
FT /note="Missing (in AIP)"
FT /evidence="ECO:0000269|PubMed:11857754"
FT /id="VAR_025566"
FT VARIANT 96
FT /note="S -> F (in AIP)"
FT /evidence="ECO:0000269|PubMed:12406973"
FT /id="VAR_025567"
FT VARIANT 98
FT /note="K -> R (in AIP)"
FT /id="VAR_003644"
FT VARIANT 99
FT /note="D -> G (in AIP; complete loss of deaminase
FT activity)"
FT /evidence="ECO:0000269|PubMed:12372055,
FT ECO:0000269|PubMed:12773194"
FT /id="VAR_025568"
FT VARIANT 99
FT /note="D -> H (in AIP)"
FT /evidence="ECO:0000269|PubMed:12406973"
FT /id="VAR_025569"
FT VARIANT 99
FT /note="D -> N (in AIP)"
FT /evidence="ECO:0000269|Ref.46"
FT /id="VAR_025570"
FT VARIANT 111
FT /note="G -> R (in AIP; dbSNP:rs118204107)"
FT /evidence="ECO:0000269|PubMed:10453740,
FT ECO:0000269|PubMed:10494093, ECO:0000269|PubMed:10602775,
FT ECO:0000269|PubMed:11013452, ECO:0000269|PubMed:11399210,
FT ECO:0000269|PubMed:11857754, ECO:0000269|PubMed:12372055,
FT ECO:0000269|PubMed:15669678, ECO:0000269|PubMed:25703257,
FT ECO:0000269|PubMed:8268934"
FT /id="VAR_003645"
FT VARIANT 113
FT /note="I -> T (in AIP)"
FT /evidence="ECO:0000269|PubMed:12372055"
FT /id="VAR_025571"
FT VARIANT 116
FT /note="R -> Q (in AIP; dbSNP:rs1165046276)"
FT /evidence="ECO:0000269|PubMed:8081367"
FT /id="VAR_003646"
FT VARIANT 116
FT /note="R -> W (in AIP; loss of hydroxymethylbilane synthase
FT activity; affects protein conformation; lower thermal
FT stability than wild-type enzyme; dbSNP:rs118204094)"
FT /evidence="ECO:0000269|PubMed:10602775,
FT ECO:0000269|PubMed:11030413, ECO:0000269|PubMed:23815679,
FT ECO:0000269|PubMed:7962538, ECO:0000269|PubMed:9225970"
FT /id="VAR_003647"
FT VARIANT 119
FT /note="P -> L (in AIP)"
FT /evidence="ECO:0000269|PubMed:8825929,
FT ECO:0000269|PubMed:9225970"
FT /id="VAR_003648"
FT VARIANT 122
FT /note="A -> G (in AIP)"
FT /evidence="ECO:0000269|PubMed:12406973"
FT /id="VAR_025572"
FT VARIANT 124
FT /note="V -> D (in AIP)"
FT /id="VAR_011011"
FT VARIANT 132
FT /note="K -> N (found in a patient with unclear porphyria-
FT related biochemical findings and abdominal pain; unknown
FT pathological significance; does not affect
FT hydroxymethylbilane synthase activity; does not affect
FT Vmax; does not affect KM; does not affect thermal
FT stability; dbSNP:rs551209435)"
FT /evidence="ECO:0000269|PubMed:23815679"
FT /id="VAR_073714"
FT VARIANT 149
FT /note="R -> L (in AIP)"
FT /evidence="ECO:0000269|PubMed:8270254"
FT /id="VAR_003649"
FT VARIANT 149
FT /note="R -> Q (in AIP; loss of deaminase activity;
FT dbSNP:rs118204098)"
FT /evidence="ECO:0000269|PubMed:12773194,
FT ECO:0000269|PubMed:1714233"
FT /id="VAR_003650"
FT VARIANT 152
FT /note="Missing (in AIP)"
FT /evidence="ECO:0000269|PubMed:10502788"
FT /id="VAR_009223"
FT VARIANT 167
FT /note="R -> Q (in AIP; decreased deaminase activity due to
FT defective enzyme-intermediate complexes turnover and
FT regeneration of free enzyme molecules; dbSNP:rs118204095)"
FT /evidence="ECO:0000269|PubMed:12773194,
FT ECO:0000269|PubMed:1427766, ECO:0000269|PubMed:2243128,
FT ECO:0000269|PubMed:9225970"
FT /id="VAR_003651"
FT VARIANT 167
FT /note="R -> W (in AIP; decreased hydroxymethylbilane
FT synthase activity; results in less than 5% of wild-type
FT activity; 2-fold decrease of Vmax; 33-fold increase of KM;
FT dbSNP:rs118204101)"
FT /evidence="ECO:0000269|PubMed:10602775,
FT ECO:0000269|PubMed:1301948, ECO:0000269|PubMed:1496994,
FT ECO:0000269|PubMed:23815679, ECO:0000269|PubMed:9225970"
FT /id="VAR_003652"
FT VARIANT 173
FT /note="R -> Q (in AIP; less than 1% of wild-type activity;
FT dbSNP:rs118204096)"
FT /evidence="ECO:0000269|PubMed:10453740,
FT ECO:0000269|PubMed:11857754, ECO:0000269|PubMed:12372055,
FT ECO:0000269|PubMed:12773194, ECO:0000269|PubMed:1301948,
FT ECO:0000269|PubMed:15669678, ECO:0000269|PubMed:19292878,
FT ECO:0000269|PubMed:2243128"
FT /id="VAR_003653"
FT VARIANT 173
FT /note="R -> W (in AIP; loss of hydroxymethylbilane synthase
FT activity; 1% of wild-type activity; lower thermal stability
FT than wild-type enzyme; dbSNP:rs575222284)"
FT /evidence="ECO:0000269|PubMed:10453740,
FT ECO:0000269|PubMed:10494093, ECO:0000269|PubMed:10602775,
FT ECO:0000269|PubMed:11399210, ECO:0000269|PubMed:16211556,
FT ECO:0000269|PubMed:23815679, ECO:0000269|PubMed:8081367,
FT ECO:0000269|PubMed:9225970"
FT /id="VAR_003654"
FT VARIANT 177
FT /note="L -> R (in AIP; dbSNP:rs118204108)"
FT /evidence="ECO:0000269|PubMed:10453740,
FT ECO:0000269|PubMed:1427766, ECO:0000269|PubMed:8081367"
FT /id="VAR_003655"
FT VARIANT 178
FT /note="D -> N (in AIP; unknown pathological significance;
FT decreased hydroxymethylbilane synthase activity; has 80% of
FT wild-type deaminase activity; dbSNP:rs536814318)"
FT /evidence="ECO:0000269|PubMed:12372055,
FT ECO:0000269|PubMed:19138865"
FT /id="VAR_011012"
FT VARIANT 195
FT /note="R -> C (in AIP; severe decrease of deaminase
FT activity; dbSNP:rs34413634)"
FT /evidence="ECO:0000269|PubMed:10453740,
FT ECO:0000269|PubMed:16211556"
FT /id="VAR_003656"
FT VARIANT 201
FT /note="R -> W (in AIP; residual activity;
FT dbSNP:rs118204109)"
FT /evidence="ECO:0000269|PubMed:10494093,
FT ECO:0000269|PubMed:7962538, ECO:0000269|PubMed:8270256,
FT ECO:0000269|PubMed:9225970"
FT /id="VAR_003657"
FT VARIANT 202
FT /note="V -> L (in AIP; dbSNP:rs914335144)"
FT /evidence="ECO:0000269|PubMed:10657149"
FT /id="VAR_011013"
FT VARIANT 204
FT /note="Q -> K (in AIP; 46% wild-type deaminase activity;
FT decreased enzyme stability)"
FT /evidence="ECO:0000269|PubMed:19292878"
FT /id="VAR_074153"
FT VARIANT 209
FT /note="E -> K (in AIP; dbSNP:rs1007859875)"
FT /id="VAR_011014"
FT VARIANT 212
FT /note="M -> V (in AIP; <2% residual activity;
FT dbSNP:rs772471000)"
FT /evidence="ECO:0000269|PubMed:10602775"
FT /id="VAR_025573"
FT VARIANT 215
FT /note="V -> E (in AIP; unknown pathological significance;
FT decreased hydroxymethylbilane synthase activity; results in
FT 30% of wild-type activity; 3-fold decrease of Vmax; normal
FT KM; affects protein conformation; dbSNP:rs1205219549)"
FT /evidence="ECO:0000269|PubMed:14757946,
FT ECO:0000269|PubMed:23815679"
FT /id="VAR_073715"
FT VARIANT 215
FT /note="V -> M (in AIP; 19% of wild-type deaminase
FT activity)"
FT /evidence="ECO:0000269|PubMed:18406650"
FT /id="VAR_074154"
FT VARIANT 216
FT /note="G -> D (in AIP; dbSNP:rs118204116)"
FT /evidence="ECO:0000269|PubMed:9225970"
FT /id="VAR_011015"
FT VARIANT 217
FT /note="Q -> H (in AIP)"
FT /id="VAR_011016"
FT VARIANT 217
FT /note="Q -> L (in AIP)"
FT /evidence="ECO:0000269|PubMed:10782018"
FT /id="VAR_011017"
FT VARIANT 219
FT /note="A -> D (in AIP)"
FT /evidence="ECO:0000269|PubMed:10453740"
FT /id="VAR_011018"
FT VARIANT 222
FT /note="V -> M (in AIP; dbSNP:rs1261947877)"
FT /evidence="ECO:0000269|PubMed:9654202"
FT /id="VAR_003658"
FT VARIANT 223
FT /note="E -> K (in AIP; dbSNP:rs118204110)"
FT /evidence="ECO:0000269|PubMed:8270254"
FT /id="VAR_003659"
FT VARIANT 225
FT /note="R -> G (in AIP)"
FT /evidence="ECO:0000269|PubMed:12372055"
FT /id="VAR_003660"
FT VARIANT 225
FT /note="R -> Q (in AIP; dbSNP:rs142459647)"
FT /evidence="ECO:0000269|PubMed:12372055"
FT /id="VAR_025574"
FT VARIANT 236
FT /note="G -> S (in AIP)"
FT /evidence="ECO:0000269|PubMed:14669009"
FT /id="VAR_025575"
FT VARIANT 238
FT /note="L -> P (in AIP; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:14757946"
FT /id="VAR_073716"
FT VARIANT 238
FT /note="L -> R (in AIP)"
FT /id="VAR_003661"
FT VARIANT 244
FT /note="L -> P (in AIP)"
FT /evidence="ECO:0000269|PubMed:14669009"
FT /id="VAR_025576"
FT VARIANT 245
FT /note="L -> R (in AIP; dbSNP:rs118204099)"
FT /evidence="ECO:0000269|PubMed:1714233"
FT /id="VAR_003662"
FT VARIANT 247
FT /note="C -> F (in AIP; residual activity)"
FT /evidence="ECO:0000269|PubMed:7962538"
FT /id="VAR_003663"
FT VARIANT 247
FT /note="C -> R (in AIP; severe decrease of deaminase
FT activity; dbSNP:rs118204111)"
FT /evidence="ECO:0000269|PubMed:10453740,
FT ECO:0000269|PubMed:16211556, ECO:0000269|PubMed:8262523"
FT /id="VAR_003664"
FT VARIANT 248
FT /note="I -> IETLLRCI (in AIP)"
FT /id="VAR_011019"
FT VARIANT 250
FT /note="E -> A (in AIP; severe decrease of deaminase
FT activity)"
FT /evidence="ECO:0000269|PubMed:16211556,
FT ECO:0000269|PubMed:8825929"
FT /id="VAR_003665"
FT VARIANT 250
FT /note="E -> D (in AIP; less than 1% of wild-type deaminase
FT activity)"
FT /evidence="ECO:0000269|PubMed:19292878"
FT /id="VAR_074155"
FT VARIANT 250
FT /note="E -> K (in AIP; dbSNP:rs118204112)"
FT /evidence="ECO:0000269|PubMed:8270254"
FT /id="VAR_003666"
FT VARIANT 250
FT /note="E -> Q (in AIP)"
FT /id="VAR_011020"
FT VARIANT 250
FT /note="E -> V (in AIP)"
FT /id="VAR_011021"
FT VARIANT 252
FT /note="A -> T (in AIP; dbSNP:rs118204113)"
FT /evidence="ECO:0000269|PubMed:8262523"
FT /id="VAR_003667"
FT VARIANT 252
FT /note="A -> V (in AIP; dbSNP:rs118204114)"
FT /evidence="ECO:0000269|PubMed:8262523"
FT /id="VAR_003668"
FT VARIANT 254
FT /note="L -> P (in AIP)"
FT /evidence="ECO:0000269|PubMed:12406973"
FT /id="VAR_025577"
FT VARIANT 256
FT /note="H -> N (in AIP; dbSNP:rs118204115)"
FT /evidence="ECO:0000269|PubMed:1427766"
FT /id="VAR_003669"
FT VARIANT 256
FT /note="H -> Y (in AIP)"
FT /evidence="ECO:0000269|PubMed:12372055"
FT /id="VAR_011022"
FT VARIANT 260
FT /note="G -> D (in AIP; dbSNP:rs990831395)"
FT /evidence="ECO:0000269|PubMed:12372055"
FT /id="VAR_025578"
FT VARIANT 261
FT /note="C -> Y (in AIP; dbSNP:rs1334178100)"
FT /evidence="ECO:0000269|PubMed:12406973"
FT /id="VAR_025579"
FT VARIANT 267
FT /note="V -> M (in AIP; dbSNP:rs1057521126)"
FT /id="VAR_011023"
FT VARIANT 269
FT /note="T -> I (in AIP)"
FT /evidence="ECO:0000269|PubMed:10453740,
FT ECO:0000269|PubMed:8081367"
FT /id="VAR_003670"
FT VARIANT 270
FT /note="A -> D (in AIP)"
FT /id="VAR_011024"
FT VARIANT 270
FT /note="A -> G (in AIP)"
FT /evidence="ECO:0000269|PubMed:11030413"
FT /id="VAR_011025"
FT VARIANT 274
FT /note="G -> R (in AIP)"
FT /evidence="ECO:0000269|PubMed:8081367"
FT /id="VAR_003671"
FT VARIANT 278
FT /note="L -> P (in AIP)"
FT /evidence="ECO:0000269|PubMed:9654202"
FT /id="VAR_003672"
FT VARIANT 280
FT /note="G -> R (in AIP)"
FT /id="VAR_003673"
FT VARIANT 281
FT /note="Missing (in AIP)"
FT /evidence="ECO:0000269|PubMed:11013452"
FT /id="VAR_011026"
FT VARIANT 329..332
FT /note="Missing (in AIP)"
FT /evidence="ECO:0000269|PubMed:10494093"
FT /id="VAR_011027"
FT VARIANT 330
FT /note="A -> P (in AIP)"
FT /evidence="ECO:0000269|PubMed:25870942"
FT /id="VAR_074156"
FT VARIANT 335
FT /note="G -> D (in AIP)"
FT /evidence="ECO:0000269|PubMed:11857754"
FT /id="VAR_011028"
FT VARIANT 335
FT /note="G -> S (in AIP; less than 3% of activity)"
FT /evidence="ECO:0000269|PubMed:10494093"
FT /id="VAR_011029"
FT VARIANT 338
FT /note="L -> P (in AIP)"
FT /evidence="ECO:0000269|PubMed:25703257"
FT /id="VAR_074157"
FT VARIANT 343
FT /note="L -> P (in AIP)"
FT /evidence="ECO:0000269|PubMed:12372055"
FT /id="VAR_025580"
FT MUTAGEN 26
FT /note="R->A: Loss of hydroxymethylbilane synthase
FT activity."
FT /evidence="ECO:0000269|PubMed:18936296"
FT MUTAGEN 34
FT /note="Q->A: Loss of hydroxymethylbilane synthase
FT activity."
FT /evidence="ECO:0000269|PubMed:18936296"
FT MUTAGEN 120
FT /note="H->A: Decreased hydroxymethylbilane synthase
FT activity."
FT /evidence="ECO:0000269|PubMed:18936296"
FT MUTAGEN 120
FT /note="H->P: Loss of hydroxymethylbilane synthase
FT activity."
FT /evidence="ECO:0000269|PubMed:18936296"
FT MUTAGEN 195
FT /note="R->A: Loss of hydroxymethylbilane synthase
FT activity."
FT /evidence="ECO:0000269|PubMed:18936296"
FT CONFLICT 177
FT /note="L -> M (in Ref. 3; AAA60029/AAA60030)"
FT /evidence="ECO:0000305"
FT CONFLICT 210
FT /note="E -> K (in Ref. 2; CAA28499)"
FT /evidence="ECO:0000305"
FT CONFLICT 349
FT /note="N -> T (in Ref. 1; CAA27801)"
FT /evidence="ECO:0000305"
FT STRAND 21..25
FT /evidence="ECO:0007829|PDB:7AAK"
FT HELIX 29..45
FT /evidence="ECO:0007829|PDB:7AAK"
FT STRAND 51..55
FT /evidence="ECO:0007829|PDB:7AAK"
FT STRAND 58..60
FT /evidence="ECO:0007829|PDB:5M6R"
FT HELIX 61..66
FT /evidence="ECO:0007829|PDB:7AAK"
FT HELIX 68..70
FT /evidence="ECO:0007829|PDB:5M6R"
FT HELIX 73..86
FT /evidence="ECO:0007829|PDB:7AAK"
FT STRAND 91..96
FT /evidence="ECO:0007829|PDB:7AAK"
FT HELIX 97..99
FT /evidence="ECO:0007829|PDB:7AAK"
FT STRAND 108..113
FT /evidence="ECO:0007829|PDB:7AAK"
FT STRAND 120..125
FT /evidence="ECO:0007829|PDB:7AAK"
FT HELIX 127..129
FT /evidence="ECO:0007829|PDB:7AAK"
FT HELIX 134..136
FT /evidence="ECO:0007829|PDB:7AAK"
FT STRAND 142..144
FT /evidence="ECO:0007829|PDB:7AAK"
FT HELIX 148..157
FT /evidence="ECO:0007829|PDB:7AAK"
FT STRAND 161..164
FT /evidence="ECO:0007829|PDB:7AAK"
FT HELIX 170..179
FT /evidence="ECO:0007829|PDB:7AAK"
FT STRAND 180..182
FT /evidence="ECO:0007829|PDB:7AAJ"
FT STRAND 184..189
FT /evidence="ECO:0007829|PDB:7AAK"
FT HELIX 190..195
FT /evidence="ECO:0007829|PDB:7AAK"
FT HELIX 199..201
FT /evidence="ECO:0007829|PDB:7AAK"
FT TURN 208..210
FT /evidence="ECO:0007829|PDB:7AAK"
FT TURN 215..218
FT /evidence="ECO:0007829|PDB:7AAK"
FT STRAND 220..225
FT /evidence="ECO:0007829|PDB:7AAK"
FT HELIX 229..235
FT /evidence="ECO:0007829|PDB:7AAK"
FT HELIX 236..238
FT /evidence="ECO:0007829|PDB:7AAK"
FT HELIX 241..257
FT /evidence="ECO:0007829|PDB:7AAK"
FT STRAND 261..272
FT /evidence="ECO:0007829|PDB:7AAK"
FT STRAND 275..283
FT /evidence="ECO:0007829|PDB:7AAK"
FT STRAND 287..298
FT /evidence="ECO:0007829|PDB:7AAK"
FT HELIX 325..344
FT /evidence="ECO:0007829|PDB:7AAK"
FT HELIX 347..358
FT /evidence="ECO:0007829|PDB:7AAK"
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
