ID   HEM4_YEAST              Reviewed;         275 AA.
AC   P06174; D6W2X7;
DT   01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 2.
DT   27-MAR-2024, entry version 169.
DE   RecName: Full=Uroporphyrinogen-III synthase {ECO:0000305};
DE            Short=UROIIIS;
DE            Short=UROS;
DE            EC=4.2.1.75 {ECO:0000305|PubMed:7597845};
DE   AltName: Full=Hydroxymethylbilane hydrolyase [cyclizing];
DE   AltName: Full=Uroporphyrinogen-III cosynthase;
GN   Name=HEM4 {ECO:0000303|PubMed:7597845}; Synonyms=ORF1;
GN   OrderedLocusNames=YOR278W; ORFNames=O5463;
OS   Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX   NCBI_TaxID=559292;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 28383 / FL100 / VTT C-80102;
RX   PubMed=2834088; DOI=10.1007/bf00420604;
RA   Langgut W., Entrup R., Schweizer E.;
RT   "Isolation of a nuclear yeast gene involved in the mitochondrial import of
RT   cytoplasmically synthesized precursor proteins.";
RL   Curr. Genet. 11:177-184(1986).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=8896271;
RX   DOI=10.1002/(sici)1097-0061(199609)12:10b%3c1059::aid-yea994%3e3.0.co;2-7;
RA   Cheret G., Bernardi A., Sor F.J.;
RT   "DNA sequence analysis of the VPH1-SNF2 region on chromosome XV of
RT   Saccharomyces cerevisiae.";
RL   Yeast 12:1059-1064(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169874;
RA   Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J.,
RA   Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A.,
RA   Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B.,
RA   Dang V.-D., de Haan M., Delius H., Durand P., Fairhead C., Feldmann H.,
RA   Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E.,
RA   Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U.,
RA   Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B.,
RA   Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A.,
RA   Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C.,
RA   Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G.,
RA   Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B.,
RA   Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B.,
RA   Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F.,
RA   Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E.,
RA   Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I.,
RA   Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H.,
RA   Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome XV.";
RL   Nature 387:98-102(1997).
RN   [4]
RP   GENOME REANNOTATION.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=24374639; DOI=10.1534/g3.113.008995;
RA   Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA   Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA   Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT   "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL   G3 (Bethesda) 4:389-398(2014).
RN   [5]
RP   FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX   PubMed=7597845; DOI=10.1002/yea.320110504;
RA   Amillet J.-M., Labbe-Bois R.;
RT   "Isolation of the gene HEM4 encoding uroporphyrinogen III synthase in
RT   Saccharomyces cerevisiae.";
RL   Yeast 11:419-424(1995).
RN   [6]
RP   LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX   PubMed=14562106; DOI=10.1038/nature02046;
RA   Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA   O'Shea E.K., Weissman J.S.;
RT   "Global analysis of protein expression in yeast.";
RL   Nature 425:737-741(2003).
CC   -!- FUNCTION: Catalyzes cyclization of the linear tetrapyrrole,
CC       hydroxymethylbilane, to the macrocyclic uroporphyrinogen III, the
CC       fourth step in the heme biosynthetic pathway.
CC       {ECO:0000305|PubMed:7597845}.
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:0000305|PubMed:7597845};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18966;
CC         Evidence={ECO:0000305|PubMed:7597845};
CC   -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX
CC       biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 3/4.
CC       {ECO:0000305|PubMed:7597845}.
CC   -!- MISCELLANEOUS: Present with 1360 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the uroporphyrinogen-III synthase family.
CC       {ECO:0000305}.
CC   -!- CAUTION: Was originally thought to be involved in mitochondrial import.
CC       {ECO:0000305|PubMed:2834088}.
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; X04694; CAA28399.1; -; Genomic_DNA.
DR   EMBL; X89633; CAA61783.1; -; Genomic_DNA.
DR   EMBL; Z75186; CAA99504.1; -; Genomic_DNA.
DR   EMBL; BK006948; DAA11043.1; -; Genomic_DNA.
DR   PIR; S67180; RGBY7K.
DR   RefSeq; NP_014921.1; NM_001183697.1.
DR   AlphaFoldDB; P06174; -.
DR   SMR; P06174; -.
DR   BioGRID; 34666; 113.
DR   IntAct; P06174; 2.
DR   STRING; 4932.YOR278W; -.
DR   MaxQB; P06174; -.
DR   PaxDb; 4932-YOR278W; -.
DR   PeptideAtlas; P06174; -.
DR   EnsemblFungi; YOR278W_mRNA; YOR278W; YOR278W.
DR   GeneID; 854452; -.
DR   KEGG; sce:YOR278W; -.
DR   AGR; SGD:S000005804; -.
DR   SGD; S000005804; HEM4.
DR   VEuPathDB; FungiDB:YOR278W; -.
DR   eggNOG; KOG4132; Eukaryota.
DR   GeneTree; ENSGT00390000009853; -.
DR   HOGENOM; CLU_051874_0_1_1; -.
DR   InParanoid; P06174; -.
DR   OMA; CDSMLRG; -.
DR   OrthoDB; 1472480at2759; -.
DR   BioCyc; YEAST:YOR278W-MONOMER; -.
DR   Reactome; R-SCE-189451; Heme biosynthesis.
DR   UniPathway; UPA00251; UER00320.
DR   BioGRID-ORCS; 854452; 0 hits in 10 CRISPR screens.
DR   PRO; PR:P06174; -.
DR   Proteomes; UP000002311; Chromosome XV.
DR   RNAct; P06174; Protein.
DR   GO; GO:0004852; F:uroporphyrinogen-III synthase activity; IMP:SGD.
DR   GO; GO:0006783; P:heme biosynthetic process; IMP:SGD.
DR   GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0006780; P:uroporphyrinogen III biosynthetic process; IBA:GO_Central.
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; UROPORPHYRINOGEN III SYNTHASE; 1.
DR   PANTHER; PTHR12390:SF0; UROPORPHYRINOGEN-III SYNTHASE; 1.
DR   Pfam; PF02602; HEM4; 1.
DR   SUPFAM; SSF69618; HemD-like; 1.
PE   1: Evidence at protein level;
KW   Heme biosynthesis; Lyase; Porphyrin biosynthesis; Reference proteome.
FT   CHAIN           1..275
FT                   /note="Uroporphyrinogen-III synthase"
FT                   /id="PRO_0000135254"
FT   CONFLICT        231..275
FT                   /note="HLRVASIGPTTKKYLDDNDVTSDVVSPKPDPKSLLDAIELYQRHK -> IYG
FT                   LRHRTYH (in Ref. 1; CAA28399)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   275 AA;  30912 MW;  CDC857C8CFB4E1A7 CRC64;
     MSSRKKVRVL LLKNKTVPID KYELECRSKA FEPIFVPLIK HTHVIQDFRN VLNTIPNYLN
     TINYIIITSQ RTVESLNEAI IPTLTSEQKA ALLSKTVYTV GPATANFIRR SGFINVKGGE
     DAGNGSILAD IIIDDLSTDI KACPPSELLF LVGEIRRDII PKKLHSKGIK VREVVTYKTE
     ELSDGFKRFI HAMKECDEDE VFSDWVVVFS PQGTKEITQY LGDSNRLPGS HLRVASIGPT
     TKKYLDDNDV TSDVVSPKPD PKSLLDAIEL YQRHK
//