HEM4_HUMAN
ID HEM4_HUMAN Reviewed; 265 AA.
AC P10746; B2RC13; D3DRF7; Q9H2T1;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=Uroporphyrinogen-III synthase;
DE Short=UROIIIS;
DE Short=UROS;
DE EC=4.2.1.75;
DE AltName: Full=Hydroxymethylbilane hydrolyase [cyclizing];
DE AltName: Full=Uroporphyrinogen-III cosynthase;
GN Name=UROS;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=3174619; DOI=10.1073/pnas.85.19.7049;
RA Tsai S.-F., Bishop D.F., Desnick R.J.;
RT "Human uroporphyrinogen III synthase: molecular cloning, nucleotide
RT sequence, and expression of a full-length cDNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:7049-7053(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=11112350; DOI=10.1006/geno.2000.6373;
RA Aizencang G., Solis C., Bishop D.F., Warner C., Desnick R.J.;
RT "Human uroporphyrinogen-III synthase: genomic organization, alternative
RT promoters, and erythroid-specific expression.";
RL Genomics 70:223-231(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [7]
RP REVIEW ON VARIANTS.
RX PubMed=8829650;
RX DOI=10.1002/(sici)1098-1004(1996)7:3<187::aid-humu1>3.0.co;2-8;
RA Xu W., Astrin K.H., Desnick R.J.;
RT "Molecular basis of congenital erythropoietic porphyria: mutations in the
RT human uroporphyrinogen III synthase gene.";
RL Hum. Mutat. 7:187-192(1996).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS), CATALYTIC ACTIVITY, SUBUNIT,
RP MUTAGENESIS OF SER-63; ARG-65; THR-103; GLU-127; TYR-168; SER-197; LYS-220;
RP THR-227 AND THR-228, AND CHARACTERIZATION OF VARIANT CEP ALA-62.
RX PubMed=11689424; DOI=10.1093/emboj/20.21.5832;
RA Mathews M.A., Schubert H.L., Whitby F.G., Alexander K.J., Schadick K.,
RA Bergonia H.A., Phillips J.D., Hill C.P.;
RT "Crystal structure of human uroporphyrinogen III synthase.";
RL EMBO J. 20:5832-5839(2001).
RN [9]
RP VARIANTS CEP LEU-53 AND ARG-73.
RX PubMed=2331520;
RA Deybach J.-C., de Verneuil H., Boulechfar S., Grandchamp B., Nordmann Y.;
RT "Point mutations in the uroporphyrinogen III synthase gene in congenital
RT erythropoietic porphyria (Gunther's disease).";
RL Blood 75:1763-1765(1990).
RN [10]
RP VARIANTS CEP PHE-4; ARG-73 AND MET-228.
RX PubMed=1733834; DOI=10.1007/bf00197267;
RA Boulechfar S., da Silva V., Deybach J.-C., Nordmann Y., Grandchamp B.,
RA de Verneuil H.;
RT "Heterogeneity of mutations in the uroporphyrinogen III synthase gene in
RT congenital erythropoietic porphyria.";
RL Hum. Genet. 88:320-324(1992).
RN [11]
RP VARIANTS CEP ALA-62; VAL-66; ARG-73 AND MET-228.
RX PubMed=1737856; DOI=10.1172/jci115637;
RA Warner C.A., Yoo H.-W., Roberts A.G., Desnick R.J.;
RT "Congenital erythropoietic porphyria: identification and expression of
RT exonic mutations in the uroporphyrinogen III synthase gene.";
RL J. Clin. Invest. 89:693-700(1992).
RN [12]
RP VARIANTS CEP CYS-19; PHE-82; ALA-99; VAL-104 AND SER-225.
RX PubMed=7860775; DOI=10.1172/jci117742;
RA Xu W., Warner C.A., Desnick R.J.;
RT "Congenital erythropoietic porphyria: identification and expression of 10
RT mutations in the uroporphyrinogen III synthase gene.";
RL J. Clin. Invest. 95:905-912(1995).
RN [13]
RP VARIANT CEP PRO-212.
RX PubMed=8655129; DOI=10.1007/bf02281859;
RA Tanigawa K., Bensidhoum M., Takamura N., Namba H., Yamashita S.,
RA de Verneuil H., Ged C.;
RT "A novel point mutation in congenital erythropoietic porphyria in two
RT members of Japanese family.";
RL Hum. Genet. 97:557-560(1996).
RN [14]
RP VARIANT CEP PHE-3, AND CHARACTERIZATION OF VARIANT CEP PHE-3.
RX PubMed=9188670;
RX DOI=10.1002/(sici)1096-8628(19970613)70:3<299::aid-ajmg16>3.0.co;2-g;
RA Takamura N., Hombrados I., Tanigawa K., Namba H., Nagayama Y.,
RA de Verneuil H., Yamashita S.;
RT "Novel point mutation in the uroporphyrinogen III synthase gene causes
RT congenital erythropoietic porphyria of a Japanese family.";
RL Am. J. Med. Genet. 70:299-302(1997).
RN [15]
RP VARIANT CEP ARG-188.
RX PubMed=9834209;
RA Tezcan I., Xu W., Gurgey A., Tuncer M., Cetin M., Oener C., Yetgin S.,
RA Ersoy F., Aizencang G., Astrin K.H., Desnick R.J.;
RT "Congenital erythropoietic porphyria successfully treated by allogeneic
RT bone marrow transplantation.";
RL Blood 92:4053-4058(1998).
RN [16]
RP VARIANT CEP ARG-73.
RX PubMed=9803266; DOI=10.1046/j.1469-1809.1998.6230225.x;
RA Frank J., Wang X., Lam H.M., Aita V.M., Jugert F.K., Goerz G., Merk H.F.,
RA Poh-Fitzpatrick M.B., Christiano A.M.;
RT "C73R is a hotspot mutation in the uroporphyrinogen III synthase gene in
RT congenital erythropoietic porphyria.";
RL Ann. Hum. Genet. 62:225-230(1998).
RN [17]
RP VARIANT CEP THR-129, AND CHARACTERIZATION OF VARIANT CEP THR-129.
RX PubMed=11121156; DOI=10.1046/j.1523-1747.2000.0202a.x;
RA Rogounovitch T., Takamura N., Hombrados I., Morel C., Tanaka T.,
RA Kameyoshi Y., Shimizu-Yoshida Y., de Verneuil H., Yamashita S.;
RT "Congenital erythropoietic porphyria: a novel homozygous mutation in a
RT Japanese patient.";
RL J. Invest. Dermatol. 115:1156-1156(2000).
RN [18]
RP VARIANTS CEP THR-69; ARG-73; TRP-188; 210-GLU-LEU-211 DELINS
RP HIS-ILE-GLN-SER-GLN-ALA-GLN-SER-GLN-ALA-GLN-ASP-ASN; SER-219 AND MET-228,
RP AND CHARACTERIZATION OF VARIANTS CEP THR-69; TRP-188 AND SER-219.
RX PubMed=12060141; DOI=10.1046/j.1365-2141.2002.03558.x;
RA Shady A.A., Colby B.R., Cunha L.F., Astrin K.H., Bishop D.F., Desnick R.J.;
RT "Congenital erythropoietic porphyria: identification and expression of
RT eight novel mutations in the uroporphyrinogen III synthase gene.";
RL Br. J. Haematol. 117:980-987(2002).
RN [19]
RP VARIANT CEP PRO-47, AND CHARACTERIZATION OF VARIANT CEP PRO-47.
RX PubMed=15304101; DOI=10.1111/j.0022-202x.2004.23401.x;
RA Ged C., Megarbane H., Chouery E., Lalanne M., Megarbane A., de Verneuil H.;
RT "Congenital erythropoietic porphyria: report of a novel mutation with
RT absence of clinical manifestations in a homozygous mutant sibling.";
RL J. Invest. Dermatol. 123:589-591(2004).
RN [20]
RP VARIANT CEP GLN-248.
RX PubMed=21653323; DOI=10.1182/blood-2011-03-342873;
RA To-Figueras J., Ducamp S., Clayton J., Badenas C., Delaby C., Ged C.,
RA Lyoumi S., Gouya L., de Verneuil H., Beaumont C., Ferreira G.C.,
RA Deybach J.C., Herrero C., Puy H.;
RT "ALAS2 acts as a modifier gene in patients with congenital erythropoietic
RT porphyria.";
RL Blood 118:1443-1451(2011).
RN [21]
RP VARIANT CEP PRO-237.
RX PubMed=22350154; DOI=10.1007/s11033-012-1497-z;
RA Moghbeli M., Maleknejad M., Arabi A., Abbaszadegan M.R.;
RT "Mutational analysis of uroporphyrinogen III cosynthase gene in Iranian
RT families with congenital erythropoietic porphyria.";
RL Mol. Biol. Rep. 39:6731-6735(2012).
CC -!- FUNCTION: Catalyzes cyclization of the linear tetrapyrrole,
CC hydroxymethylbilane, to the macrocyclic uroporphyrinogen III, the
CC branch point for the various sub-pathways leading to the wide diversity
CC of porphyrins. Porphyrins act as cofactors for a multitude of enzymes
CC that perform a variety of processes within the cell such as methionine
CC synthesis (vitamin B12) or oxygen transport (heme).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hydroxymethylbilane = H2O + uroporphyrinogen III;
CC Xref=Rhea:RHEA:18965, ChEBI:CHEBI:15377, ChEBI:CHEBI:57308,
CC ChEBI:CHEBI:57845; EC=4.2.1.75;
CC Evidence={ECO:0000269|PubMed:11689424};
CC -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX
CC biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 3/4.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:11689424}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:11112350}.
CC -!- DISEASE: Congenital erythropoietic porphyria (CEP) [MIM:263700]:
CC Porphyrias are inherited defects in the biosynthesis of heme, resulting
CC in the accumulation and increased excretion of porphyrins or porphyrin
CC precursors. They are classified as erythropoietic or hepatic, depending
CC on whether the enzyme deficiency occurs in red blood cells or in the
CC liver. The manifestations of CEP are heterogeneous, ranging from
CC nonimmune hydrops fetalis due to severe hemolytic anemia in utero to
CC milder, later onset forms, which have only skin lesions due to
CC cutaneous photosensitivity in adult life. The deficiency in UROS
CC activity results in the non-enzymatic conversion of hydroxymethylbilane
CC (HMB) into the uroporphyrinogen-I isomer. {ECO:0000269|PubMed:11121156,
CC ECO:0000269|PubMed:11689424, ECO:0000269|PubMed:12060141,
CC ECO:0000269|PubMed:15304101, ECO:0000269|PubMed:1733834,
CC ECO:0000269|PubMed:1737856, ECO:0000269|PubMed:21653323,
CC ECO:0000269|PubMed:22350154, ECO:0000269|PubMed:2331520,
CC ECO:0000269|PubMed:7860775, ECO:0000269|PubMed:8655129,
CC ECO:0000269|PubMed:9188670, ECO:0000269|PubMed:9803266,
CC ECO:0000269|PubMed:9834209}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Note=Severe congenital erythropoietic porphyria is associated
CC with non-immune hydrops fetalis, a generalized edema of the fetus with
CC fluid accumulation in the body cavities due to non-immune causes. Non-
CC immune hydrops fetalis is not a diagnosis in itself but a symptom, a
CC feature of many genetic disorders, and the end-stage of a wide variety
CC of disorders.
CC -!- SIMILARITY: Belongs to the uroporphyrinogen-III synthase family.
CC {ECO:0000305}.
CC -!- CAUTION: Variant Ala-62 was originally reported to result in no
CC detectable enzyme activity (PubMed:1737856), as measured in recombinant
CC crude lysate extracts. Further experiments with the purified enzyme
CC have shown that this variant does not affect activity
CC (PubMed:11689424). {ECO:0000269|PubMed:11689424,
CC ECO:0000269|PubMed:1737856}.
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DR EMBL; J03824; AAA60273.1; -; mRNA.
DR EMBL; AF230665; AAG36795.1; -; mRNA.
DR EMBL; AH010036; AAG36794.1; -; Genomic_DNA.
DR EMBL; AK314896; BAG37410.1; -; mRNA.
DR EMBL; AL360176; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW49221.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49222.1; -; Genomic_DNA.
DR EMBL; BC002573; AAH02573.1; -; mRNA.
DR CCDS; CCDS7648.1; -.
DR PIR; A40483; A40483.
DR RefSeq; NP_000366.1; NM_000375.2.
DR PDB; 1JR2; X-ray; 1.84 A; A/B=1-265.
DR PDBsum; 1JR2; -.
DR AlphaFoldDB; P10746; -.
DR BMRB; P10746; -.
DR SMR; P10746; -.
DR BioGRID; 113236; 18.
DR IntAct; P10746; 7.
DR STRING; 9606.ENSP00000357787; -.
DR ChEMBL; CHEMBL4433; -.
DR iPTMnet; P10746; -.
DR PhosphoSitePlus; P10746; -.
DR BioMuta; UROS; -.
DR DMDM; 122849; -.
DR EPD; P10746; -.
DR jPOST; P10746; -.
DR MassIVE; P10746; -.
DR MaxQB; P10746; -.
DR PaxDb; P10746; -.
DR PeptideAtlas; P10746; -.
DR PRIDE; P10746; -.
DR ProteomicsDB; 52644; -.
DR Antibodypedia; 32416; 100 antibodies from 21 providers.
DR DNASU; 7390; -.
DR Ensembl; ENST00000368786.5; ENSP00000357775.1; ENSG00000188690.15.
DR Ensembl; ENST00000368797.10; ENSP00000357787.4; ENSG00000188690.15.
DR GeneID; 7390; -.
DR KEGG; hsa:7390; -.
DR MANE-Select; ENST00000368797.10; ENSP00000357787.4; NM_000375.3; NP_000366.1.
DR UCSC; uc001liw.5; human.
DR CTD; 7390; -.
DR DisGeNET; 7390; -.
DR GeneCards; UROS; -.
DR GeneReviews; UROS; -.
DR HGNC; HGNC:12592; UROS.
DR HPA; ENSG00000188690; Low tissue specificity.
DR MalaCards; UROS; -.
DR MIM; 263700; phenotype.
DR MIM; 606938; gene.
DR neXtProt; NX_P10746; -.
DR OpenTargets; ENSG00000188690; -.
DR Orphanet; 79277; Congenital erythropoietic porphyria.
DR PharmGKB; PA37222; -.
DR VEuPathDB; HostDB:ENSG00000188690; -.
DR eggNOG; KOG4132; Eukaryota.
DR GeneTree; ENSGT00390000009853; -.
DR HOGENOM; CLU_051874_1_1_1; -.
DR InParanoid; P10746; -.
DR OMA; VNCAQQY; -.
DR OrthoDB; 1557657at2759; -.
DR PhylomeDB; P10746; -.
DR TreeFam; TF324092; -.
DR BioCyc; MetaCyc:HS07569-MON; -.
DR BRENDA; 4.2.1.75; 2681.
DR PathwayCommons; P10746; -.
DR Reactome; R-HSA-189451; Heme biosynthesis.
DR SignaLink; P10746; -.
DR UniPathway; UPA00251; UER00320.
DR BioGRID-ORCS; 7390; 82 hits in 1078 CRISPR screens.
DR EvolutionaryTrace; P10746; -.
DR GenomeRNAi; 7390; -.
DR Pharos; P10746; Tbio.
DR PRO; PR:P10746; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P10746; protein.
DR Bgee; ENSG00000188690; Expressed in nucleus accumbens and 190 other tissues.
DR ExpressionAtlas; P10746; baseline and differential.
DR Genevisible; P10746; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005542; F:folic acid binding; IEA:Ensembl.
DR GO; GO:0004852; F:uroporphyrinogen-III synthase activity; IDA:UniProtKB.
DR GO; GO:0071418; P:cellular response to amine stimulus; IEA:Ensembl.
DR GO; GO:0071243; P:cellular response to arsenic-containing substance; IEA:Ensembl.
DR GO; GO:0006783; P:heme biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0046677; P:response to antibiotic; IEA:Ensembl.
DR GO; GO:0070541; P:response to platinum ion; IEA:Ensembl.
DR GO; GO:0006780; P:uroporphyrinogen III biosynthetic process; IDA:UniProtKB.
DR CDD; cd06578; HemD; 1.
DR Gene3D; 3.40.50.10090; -; 2.
DR InterPro; IPR036108; 4pyrrol_syn_uPrphyn_synt_sf.
DR InterPro; IPR003754; 4pyrrol_synth_uPrphyn_synth.
DR InterPro; IPR039793; UROS/Hem4.
DR PANTHER; PTHR12390; PTHR12390; 1.
DR Pfam; PF02602; HEM4; 1.
DR SUPFAM; SSF69618; SSF69618; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disease variant;
KW Heme biosynthesis; Lyase; Porphyrin biosynthesis; Reference proteome.
FT CHAIN 1..265
FT /note="Uroporphyrinogen-III synthase"
FT /id="PRO_0000135251"
FT VARIANT 3
FT /note="V -> F (in CEP; no residual activity;
FT dbSNP:rs773301339)"
FT /evidence="ECO:0000269|PubMed:9188670"
FT /id="VAR_021615"
FT VARIANT 4
FT /note="L -> F (in CEP; dbSNP:rs121908015)"
FT /evidence="ECO:0000269|PubMed:1733834"
FT /id="VAR_003674"
FT VARIANT 19
FT /note="Y -> C (in CEP)"
FT /evidence="ECO:0000269|PubMed:7860775"
FT /id="VAR_003675"
FT VARIANT 47
FT /note="S -> P (in CEP; severe cutaneous lesions; less than
FT 3% wild-type activity; dbSNP:rs397515527)"
FT /evidence="ECO:0000269|PubMed:15304101"
FT /id="VAR_021616"
FT VARIANT 53
FT /note="P -> L (in CEP; severe phenotype; no detectable
FT activity; dbSNP:rs121908013)"
FT /evidence="ECO:0000269|PubMed:2331520"
FT /id="VAR_003676"
FT VARIANT 62
FT /note="T -> A (in CEP; does not affect enzymatic activity;
FT dbSNP:rs28941775)"
FT /evidence="ECO:0000269|PubMed:11689424,
FT ECO:0000269|PubMed:1737856"
FT /id="VAR_003677"
FT VARIANT 66
FT /note="A -> V (in CEP; mild phenotype; residual activity;
FT dbSNP:rs28941774)"
FT /evidence="ECO:0000269|PubMed:1737856"
FT /id="VAR_003678"
FT VARIANT 69
FT /note="A -> T (in CEP; less than 2% wild-type activity)"
FT /evidence="ECO:0000269|PubMed:12060141"
FT /id="VAR_021617"
FT VARIANT 73
FT /note="C -> R (in CEP; frequent mutation in Western
FT countries; severe phenotype; no detectable activity;
FT dbSNP:rs121908012)"
FT /evidence="ECO:0000269|PubMed:12060141,
FT ECO:0000269|PubMed:1733834, ECO:0000269|PubMed:1737856,
FT ECO:0000269|PubMed:2331520, ECO:0000269|PubMed:9803266"
FT /id="VAR_003679"
FT VARIANT 82
FT /note="V -> F (in CEP; mild phenotype; high residual
FT activity; dbSNP:rs121908016)"
FT /evidence="ECO:0000269|PubMed:7860775"
FT /id="VAR_003680"
FT VARIANT 99
FT /note="V -> A (in CEP)"
FT /evidence="ECO:0000269|PubMed:7860775"
FT /id="VAR_003681"
FT VARIANT 104
FT /note="A -> V (in CEP; residual activity;
FT dbSNP:rs397515528)"
FT /evidence="ECO:0000269|PubMed:7860775"
FT /id="VAR_003682"
FT VARIANT 124
FT /note="K -> R (in dbSNP:rs17153561)"
FT /id="VAR_049345"
FT VARIANT 129
FT /note="I -> T (in CEP; no residual activity)"
FT /evidence="ECO:0000269|PubMed:11121156"
FT /id="VAR_021618"
FT VARIANT 171
FT /note="V -> G (in dbSNP:rs17173752)"
FT /id="VAR_049346"
FT VARIANT 188
FT /note="G -> R (in CEP; less than 5% wild-type activity;
FT dbSNP:rs121908017)"
FT /evidence="ECO:0000269|PubMed:9834209"
FT /id="VAR_013558"
FT VARIANT 188
FT /note="G -> W (in CEP; mild phenotype; less than 2% wild-
FT type activity; dbSNP:rs121908017)"
FT /evidence="ECO:0000269|PubMed:12060141"
FT /id="VAR_021619"
FT VARIANT 210..211
FT /note="EL -> HIQSQAQSQAQDN (in CEP)"
FT /evidence="ECO:0000269|PubMed:12060141"
FT /id="VAR_021620"
FT VARIANT 212
FT /note="S -> P (in CEP; no residual activity;
FT dbSNP:rs139388833)"
FT /evidence="ECO:0000269|PubMed:8655129"
FT /id="VAR_003683"
FT VARIANT 219
FT /note="I -> S (in CEP; moderately-severe phenotype; less
FT than 2% wild-type activity; dbSNP:rs767029901)"
FT /evidence="ECO:0000269|PubMed:12060141"
FT /id="VAR_021621"
FT VARIANT 225
FT /note="G -> S (in CEP; dbSNP:rs121908020)"
FT /evidence="ECO:0000269|PubMed:7860775"
FT /id="VAR_003684"
FT VARIANT 228
FT /note="T -> M (in CEP; no detectable activity;
FT dbSNP:rs121908014)"
FT /evidence="ECO:0000269|PubMed:12060141,
FT ECO:0000269|PubMed:1733834, ECO:0000269|PubMed:1737856"
FT /id="VAR_003685"
FT VARIANT 237
FT /note="L -> P (in CEP; dbSNP:rs777433697)"
FT /evidence="ECO:0000269|PubMed:22350154"
FT /id="VAR_067318"
FT VARIANT 248
FT /note="P -> Q (in CEP; dbSNP:rs121908021)"
FT /evidence="ECO:0000269|PubMed:21653323"
FT /id="VAR_066247"
FT MUTAGEN 63
FT /note="S->A: Does not affect enzymatic activity."
FT /evidence="ECO:0000269|PubMed:11689424"
FT MUTAGEN 65
FT /note="R->A: Slightly affects enzymatic activity."
FT /evidence="ECO:0000269|PubMed:11689424"
FT MUTAGEN 103
FT /note="T->A: Slightly affects enzymatic activity."
FT /evidence="ECO:0000269|PubMed:11689424"
FT MUTAGEN 127
FT /note="E->A: Does not affect enzymatic activity."
FT /evidence="ECO:0000269|PubMed:11689424"
FT MUTAGEN 168
FT /note="Y->F: Impairs enzymatic activity."
FT /evidence="ECO:0000269|PubMed:11689424"
FT MUTAGEN 197
FT /note="S->A: Does not affect enzymatic activity."
FT /evidence="ECO:0000269|PubMed:11689424"
FT MUTAGEN 220
FT /note="K->A: Does not affect enzymatic activity."
FT /evidence="ECO:0000269|PubMed:11689424"
FT MUTAGEN 227
FT /note="T->A: Does not affect enzymatic activity."
FT /evidence="ECO:0000269|PubMed:11689424"
FT MUTAGEN 228
FT /note="T->A: Impairs enzymatic activity."
FT /evidence="ECO:0000269|PubMed:11689424"
FT STRAND 2..9
FT /evidence="ECO:0007829|PDB:1JR2"
FT HELIX 18..24
FT /evidence="ECO:0007829|PDB:1JR2"
FT TURN 25..27
FT /evidence="ECO:0007829|PDB:1JR2"
FT STRAND 29..34
FT /evidence="ECO:0007829|PDB:1JR2"
FT STRAND 36..40
FT /evidence="ECO:0007829|PDB:1JR2"
FT HELIX 43..50
FT /evidence="ECO:0007829|PDB:1JR2"
FT HELIX 53..55
FT /evidence="ECO:0007829|PDB:1JR2"
FT STRAND 57..61
FT /evidence="ECO:0007829|PDB:1JR2"
FT HELIX 64..76
FT /evidence="ECO:0007829|PDB:1JR2"
FT HELIX 80..86
FT /evidence="ECO:0007829|PDB:1JR2"
FT HELIX 88..93
FT /evidence="ECO:0007829|PDB:1JR2"
FT STRAND 94..98
FT /evidence="ECO:0007829|PDB:1JR2"
FT HELIX 101..109
FT /evidence="ECO:0007829|PDB:1JR2"
FT HELIX 122..130
FT /evidence="ECO:0007829|PDB:1JR2"
FT STRAND 139..144
FT /evidence="ECO:0007829|PDB:1JR2"
FT HELIX 146..148
FT /evidence="ECO:0007829|PDB:1JR2"
FT HELIX 151..156
FT /evidence="ECO:0007829|PDB:1JR2"
FT TURN 157..159
FT /evidence="ECO:0007829|PDB:1JR2"
FT STRAND 162..166
FT /evidence="ECO:0007829|PDB:1JR2"
FT STRAND 168..172
FT /evidence="ECO:0007829|PDB:1JR2"
FT HELIX 176..187
FT /evidence="ECO:0007829|PDB:1JR2"
FT STRAND 191..197
FT /evidence="ECO:0007829|PDB:1JR2"
FT HELIX 198..212
FT /evidence="ECO:0007829|PDB:1JR2"
FT HELIX 213..218
FT /evidence="ECO:0007829|PDB:1JR2"
FT STRAND 219..225
FT /evidence="ECO:0007829|PDB:1JR2"
FT HELIX 226..234
FT /evidence="ECO:0007829|PDB:1JR2"
FT STRAND 240..242
FT /evidence="ECO:0007829|PDB:1JR2"
FT STRAND 244..247
FT /evidence="ECO:0007829|PDB:1JR2"
FT HELIX 248..258
FT /evidence="ECO:0007829|PDB:1JR2"
SQ SEQUENCE 265 AA; 28628 MW; CEF171401361F61E CRC64;
MKVLLLKDAK EDDCGQDPYI RELGLYGLEA TLIPVLSFEF LSLPSFSEKL SHPEDYGGLI
FTSPRAVEAA ELCLEQNNKT EVWERSLKEK WNAKSVYVVG NATASLVSKI GLDTEGETCG
NAEKLAEYIC SRESSALPLL FPCGNLKREI LPKALKDKGI AMESITVYQT VAHPGIQGNL
NSYYSQQGVP ASITFFSPSG LTYSLKHIQE LSGDNIDQIK FAAIGPTTAR ALAAQGLPVS
CTAESPTPQA LATGIRKALQ PHGCC
