ID   HEM2_YEAST              Reviewed;         342 AA.
AC   P05373; D6VU99;
DT   01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 2.
DT   27-MAR-2024, entry version 209.
DE   RecName: Full=Delta-aminolevulinic acid dehydratase;
DE            Short=ALADH;
DE            EC=4.2.1.24;
DE   AltName: Full=Porphobilinogen synthase;
GN   Name=HEM2; OrderedLocusNames=YGL040C;
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].
RX   PubMed=2445751; DOI=10.1016/s0021-9258(18)45458-0;
RA   Myers A.M., Crivellone M.D., Koerner T.J., Tzagoloff A.;
RT   "Characterization of the yeast HEM2 gene and transcriptional regulation of
RT   COX5 and COR1 by heme.";
RL   J. Biol. Chem. 262:16822-16829(1987).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169869;
RA   Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J.,
RA   Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M.,
RA   Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L.,
RA   Coblenz A., Coglievina M., Coissac E., Defoor E., Del Bino S., Delius H.,
RA   Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P.,
RA   Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M.,
RA   Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A.,
RA   Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K.,
RA   Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P.,
RA   Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E.,
RA   Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K.,
RA   Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A.,
RA   Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S.,
RA   Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M.,
RA   Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C.,
RA   Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M.,
RA   Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M.,
RA   Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y.,
RA   Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L.,
RA   Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D.,
RA   Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F.,
RA   Zaccaria P., Zimmermann M., Zollner A., Kleine K.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome VII.";
RL   Nature 387:81-84(1997).
RN   [3]
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   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=17322287; DOI=10.1101/gr.6037607;
RA   Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA   Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA   Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA   Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA   LaBaer J.;
RT   "Approaching a complete repository of sequence-verified protein-encoding
RT   clones for Saccharomyces cerevisiae.";
RL   Genome Res. 17:536-543(2007).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-41.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9234674;
RX   DOI=10.1002/(sici)1097-0061(199707)13:9<861::aid-yea125>3.0.co;2-9;
RA   Feuermann M., de Montigny J., Potier S., Souciet J.-L.;
RT   "The characterization of two new clusters of duplicated genes suggests a
RT   'Lego' organization of the yeast Saccharomyces cerevisiae chromosomes.";
RL   Yeast 13:861-869(1997).
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).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-254, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA   Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT   "A multidimensional chromatography technology for in-depth phosphoproteome
RT   analysis.";
RL   Mol. Cell. Proteomics 7:1389-1396(2008).
RN   [8]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA   Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA   Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA   Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT   "N-terminal acetylome analyses and functional insights of the N-terminal
RT   acetyltransferase NatB.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN   [9]
RP   X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH LEAD IONS, SUBUNIT,
RP   ACTIVITY REGULATION, AND ACTIVE SITE.
RX   PubMed=9406553; DOI=10.1038/nsb1297-1025;
RA   Erskine P.T., Senior N., Awan S., Lambert R., Lewis G., Tickle I.J.,
RA   Sarwar M., Spencer P., Thomas P., Warren M.J., Shoolingin-Jordan P.M.,
RA   Wood S.P., Cooper J.B.;
RT   "X-ray structure of 5-aminolaevulinate dehydratase, a hybrid aldolase.";
RL   Nat. Struct. Biol. 4:1025-1031(1997).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH LAEVULINIC ACID AND
RP   ZINC IONS, COFACTOR, AND ACTIVE SITE.
RX   PubMed=10386874; DOI=10.1110/ps.8.6.1250;
RA   Erskine P.T., Newbold R., Roper J., Coker A., Warren M.J.,
RA   Shoolingin-Jordan P.M., Wood S.P., Cooper J.B.;
RT   "The Schiff base complex of yeast 5-aminolaevulinic acid dehydratase with
RT   laevulinic acid.";
RL   Protein Sci. 8:1250-1256(1999).
RN   [11]
RP   X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH MERCURY IONS.
RX   PubMed=10739915; DOI=10.1107/s0907444900000597;
RA   Erskine P.T., Duke E.M., Tickle I.J., Senior N.M., Warren M.J.,
RA   Cooper J.B.;
RT   "MAD analyses of yeast 5-aminolaevulinate dehydratase: their use in
RT   structure determination and in defining the metal-binding sites.";
RL   Acta Crystallogr. D 56:421-430(2000).
RN   [12]
RP   X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEXES WITH ZINC IONS;
RP   4-OXOSEBACIC ACID AND 4,7-DIOXOSEBACIC ACID, AND ACTIVE SITE.
RX   PubMed=11513881; DOI=10.1016/s0014-5793(01)02721-1;
RA   Erskine P.T., Coates L., Newbold R., Brindley A.A., Stauffer F., Wood S.P.,
RA   Warren M.J., Cooper J.B., Shoolingin-Jordan P.M., Neier R.;
RT   "The X-ray structure of yeast 5-aminolaevulinic acid dehydratase complexed
RT   with two diacid inhibitors.";
RL   FEBS Lett. 503:196-200(2001).
RN   [13]
RP   X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEXES WITH ZINC IONS;
RP   5-AMINOLAEVULINIC ACID AND SUBSTRATE ANALOGS, ACTIVE SITE, AND SUBUNIT.
RX   PubMed=11545591; DOI=10.1006/jmbi.2001.4947;
RA   Erskine P.T., Newbold R., Brindley A.A., Wood S.P., Shoolingin-Jordan P.M.,
RA   Warren M.J., Cooper J.B.;
RT   "The X-ray structure of yeast 5-aminolaevulinic acid dehydratase complexed
RT   with substrate and three inhibitors.";
RL   J. Mol. Biol. 312:133-141(2001).
CC   -!- FUNCTION: Catalyzes an early step in the biosynthesis of tetrapyrroles.
CC       Binds two molecules of 5-aminolevulinate per subunit, each at a
CC       distinct site, and catalyzes their condensation to form
CC       porphobilinogen.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 5-aminolevulinate = H(+) + 2 H2O + porphobilinogen;
CC         Xref=Rhea:RHEA:24064, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:58126, ChEBI:CHEBI:356416; EC=4.2.1.24;
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000269|PubMed:10386874};
CC       Note=Binds 1 zinc ion per monomer. {ECO:0000269|PubMed:10386874};
CC   -!- ACTIVITY REGULATION: Inhibited by divalent lead ions.
CC       {ECO:0000269|PubMed:9406553}.
CC   -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX
CC       biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 1/4.
CC   -!- SUBUNIT: Homooctamer. {ECO:0000269|PubMed:10386874,
CC       ECO:0000269|PubMed:10739915, ECO:0000269|PubMed:11545591,
CC       ECO:0000269|PubMed:9406553}.
CC   -!- MISCELLANEOUS: Present with 11600 molecules/cell in log phase SD
CC       medium. {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the ALAD family. {ECO:0000305}.
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DR   EMBL; J03493; AAA34669.1; -; Genomic_DNA.
DR   EMBL; Z72562; CAA96742.1; -; Genomic_DNA.
DR   EMBL; AY692744; AAT92763.1; -; Genomic_DNA.
DR   EMBL; BK006941; DAA08060.1; -; Genomic_DNA.
DR   PIR; S64042; S64042.
DR   RefSeq; NP_011475.1; NM_001180905.1.
DR   PDB; 1AW5; X-ray; 2.30 A; A=1-340.
DR   PDB; 1EB3; X-ray; 1.75 A; A=1-340.
DR   PDB; 1GJP; X-ray; 1.80 A; A=1-340.
DR   PDB; 1H7N; X-ray; 1.60 A; A=1-342.
DR   PDB; 1H7O; X-ray; 1.75 A; A=1-341.
DR   PDB; 1H7P; X-ray; 1.64 A; A=1-342.
DR   PDB; 1H7R; X-ray; 2.00 A; A=1-342.
DR   PDB; 1OHL; X-ray; 1.60 A; A=1-342.
DR   PDB; 1QML; X-ray; 3.00 A; A=1-342.
DR   PDB; 1QNV; X-ray; 2.50 A; A=1-342.
DR   PDB; 1W31; X-ray; 1.90 A; A=1-342.
DR   PDB; 1YLV; X-ray; 2.15 A; A=1-342.
DR   PDBsum; 1AW5; -.
DR   PDBsum; 1EB3; -.
DR   PDBsum; 1GJP; -.
DR   PDBsum; 1H7N; -.
DR   PDBsum; 1H7O; -.
DR   PDBsum; 1H7P; -.
DR   PDBsum; 1H7R; -.
DR   PDBsum; 1OHL; -.
DR   PDBsum; 1QML; -.
DR   PDBsum; 1QNV; -.
DR   PDBsum; 1W31; -.
DR   PDBsum; 1YLV; -.
DR   AlphaFoldDB; P05373; -.
DR   SMR; P05373; -.
DR   BioGRID; 33206; 77.
DR   DIP; DIP-4311N; -.
DR   IntAct; P05373; 2.
DR   MINT; P05373; -.
DR   STRING; 4932.YGL040C; -.
DR   iPTMnet; P05373; -.
DR   MaxQB; P05373; -.
DR   PaxDb; 4932-YGL040C; -.
DR   PeptideAtlas; P05373; -.
DR   EnsemblFungi; YGL040C_mRNA; YGL040C; YGL040C.
DR   GeneID; 852842; -.
DR   KEGG; sce:YGL040C; -.
DR   AGR; SGD:S000003008; -.
DR   SGD; S000003008; HEM2.
DR   VEuPathDB; FungiDB:YGL040C; -.
DR   eggNOG; KOG2794; Eukaryota.
DR   GeneTree; ENSGT00390000006998; -.
DR   HOGENOM; CLU_035731_0_1_1; -.
DR   InParanoid; P05373; -.
DR   OMA; YQMDYAN; -.
DR   OrthoDB; 2782182at2759; -.
DR   BioCyc; YEAST:YGL040C-MONOMER; -.
DR   BRENDA; 4.2.1.24; 984.
DR   Reactome; R-SCE-189451; Heme biosynthesis.
DR   Reactome; R-SCE-6798695; Neutrophil degranulation.
DR   UniPathway; UPA00251; UER00318.
DR   BioGRID-ORCS; 852842; 0 hits in 10 CRISPR screens.
DR   EvolutionaryTrace; P05373; -.
DR   PRO; PR:P05373; -.
DR   Proteomes; UP000002311; Chromosome VII.
DR   RNAct; P05373; Protein.
DR   GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; HDA:SGD.
DR   GO; GO:0004655; F:porphobilinogen synthase activity; IDA:SGD.
DR   GO; GO:0008270; F:zinc ion binding; IDA:SGD.
DR   GO; GO:0006783; P:heme biosynthetic process; IMP:SGD.
DR   GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:UniProtKB-UniPathway.
DR   CDD; cd04824; eu_ALAD_PBGS_cysteine_rich; 1.
DR   Gene3D; 3.20.20.70; Aldolase class I; 1.
DR   InterPro; IPR001731; ALAD.
DR   InterPro; IPR030656; ALAD_AS.
DR   InterPro; IPR013785; Aldolase_TIM.
DR   PANTHER; PTHR11458; DELTA-AMINOLEVULINIC ACID DEHYDRATASE; 1.
DR   PANTHER; PTHR11458:SF0; DELTA-AMINOLEVULINIC ACID DEHYDRATASE; 1.
DR   Pfam; PF00490; ALAD; 1.
DR   PIRSF; PIRSF001415; Porphbilin_synth; 1.
DR   PRINTS; PR00144; DALDHYDRTASE.
DR   SMART; SM01004; ALAD; 1.
DR   SUPFAM; SSF51569; Aldolase; 1.
DR   PROSITE; PS00169; D_ALA_DEHYDRATASE; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Heme biosynthesis; Lyase; Metal-binding; Phosphoprotein;
KW   Porphyrin biosynthesis; Reference proteome; Zinc.
FT   CHAIN           1..342
FT                   /note="Delta-aminolevulinic acid dehydratase"
FT                   /id="PRO_0000140534"
FT   ACT_SITE        210
FT                   /note="Schiff-base intermediate with substrate"
FT   ACT_SITE        263
FT                   /note="Schiff-base intermediate with substrate"
FT   BINDING         133
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT   BINDING         135
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT   BINDING         143
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT   BINDING         220
FT                   /ligand="5-aminolevulinate"
FT                   /ligand_id="ChEBI:CHEBI:356416"
FT                   /ligand_label="1"
FT   BINDING         232
FT                   /ligand="5-aminolevulinate"
FT                   /ligand_id="ChEBI:CHEBI:356416"
FT                   /ligand_label="1"
FT   BINDING         290
FT                   /ligand="5-aminolevulinate"
FT                   /ligand_id="ChEBI:CHEBI:356416"
FT                   /ligand_label="2"
FT   BINDING         329
FT                   /ligand="5-aminolevulinate"
FT                   /ligand_id="ChEBI:CHEBI:356416"
FT                   /ligand_label="2"
FT   MOD_RES         254
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18407956"
FT   CONFLICT        291
FT                   /note="G -> D (in Ref. 1; AAA34669)"
FT                   /evidence="ECO:0000305"
FT   HELIX           14..16
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   HELIX           19..21
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   STRAND          22..24
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   HELIX           25..30
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   STRAND          32..34
FT                   /evidence="ECO:0007829|PDB:1EB3"
FT   HELIX           38..40
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   STRAND          41..50
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   STRAND          54..56
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   STRAND          58..60
FT                   /evidence="ECO:0007829|PDB:1W31"
FT   STRAND          64..66
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   HELIX           68..80
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   STRAND          85..91
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   HELIX           103..106
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   HELIX           111..122
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   STRAND          126..132
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   TURN            135..137
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   STRAND          138..140
FT                   /evidence="ECO:0007829|PDB:1OHL"
FT   STRAND          142..144
FT                   /evidence="ECO:0007829|PDB:1W31"
FT   STRAND          150..152
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   HELIX           154..171
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   STRAND          174..178
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   HELIX           185..195
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   TURN            199..201
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   STRAND          203..211
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   STRAND          213..215
FT                   /evidence="ECO:0007829|PDB:1H7P"
FT   HELIX           217..223
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   STRAND          228..230
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   TURN            233..235
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   HELIX           242..254
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   STRAND          258..265
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   HELIX           266..268
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   HELIX           269..278
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   TURN            279..281
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   STRAND          284..288
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   HELIX           290..301
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   HELIX           307..320
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   STRAND          324..328
FT                   /evidence="ECO:0007829|PDB:1H7N"
FT   HELIX           331..337
FT                   /evidence="ECO:0007829|PDB:1H7N"
SQ   SEQUENCE   342 AA;  37740 MW;  72F6EB11008BDF52 CRC64;
     MHTAEFLETE PTEISSVLAG GYNHPLLRQW QSERQLTKNM LIFPLFISDN PDDFTEIDSL
     PNINRIGVNR LKDYLKPLVA KGLRSVILFG VPLIPGTKDP VGTAADDPAG PVIQGIKFIR
     EYFPELYIIC DVCLCEYTSH GHCGVLYDDG TINRERSVSR LAAVAVNYAK AGAHCVAPSD
     MIDGRIRDIK RGLINANLAH KTFVLSYAAK FSGNLYGPFR DAACSAPSNG DRKCYQLPPA
     GRGLARRALE RDMSEGADGI IVKPSTFYLD IMRDASEICK DLPICAYHVS GEYAMLHAAA
     EKGVVDLKTI AFESHQGFLR AGARLIITYL APEFLDWLDE EN
//