HEM2_YEAST
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 03-AUG-2022, entry version 203.
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; 73.
DR DIP; DIP-4311N; -.
DR IntAct; P05373; 2.
DR MINT; P05373; -.
DR STRING; 4932.YGL040C; -.
DR iPTMnet; P05373; -.
DR MaxQB; P05373; -.
DR PaxDb; P05373; -.
DR PRIDE; P05373; -.
DR EnsemblFungi; YGL040C_mRNA; YGL040C; YGL040C.
DR GeneID; 852842; -.
DR KEGG; sce:YGL040C; -.
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 BioCyc; YEAST:YGL040C-MON; -.
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 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 Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR001731; ALAD.
DR InterPro; IPR030656; ALAD_AS.
DR InterPro; IPR013785; Aldolase_TIM.
DR PANTHER; PTHR11458; PTHR11458; 1.
DR Pfam; PF00490; ALAD; 1.
DR PIRSF; PIRSF001415; Porphbilin_synth; 1.
DR PRINTS; PR00144; DALDHYDRTASE.
DR SMART; SM01004; ALAD; 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
