ID HEM2_MACFA Reviewed; 330 AA. AC Q60HH9; DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot. DT 12-APR-2005, sequence version 2. DT 24-JAN-2024, entry version 71. DE RecName: Full=Delta-aminolevulinic acid dehydratase; DE Short=ALADH; DE EC=4.2.1.24; DE AltName: Full=Porphobilinogen synthase; GN Name=ALAD; ORFNames=QorA-10240; OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; OC Cercopithecidae; Cercopithecinae; Macaca. OX NCBI_TaxID=9541; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Occipital cortex; RA Kusuda J., Osada N., Tanuma R., Hirata M., Sugano S., Hashimoto K.; RT "Isolation and characterization of cDNA for macaque neurological disease RT genes."; RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases. 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 porphobilinogen CC (By similarity). {ECO:0000250}. 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; Evidence={ECO:0000250}; CC Note=Binds 8 zinc ions per octamer. Requires four zinc ions per octamer CC for full catalytic activity. Can bind up to 2 zinc ions per subunit. CC {ECO:0000250}; CC -!- ACTIVITY REGULATION: Can alternate between a fully active homooctamer CC and a low-activity homohexamer. A bound magnesium ion may promote the CC assembly of the fully active homooctamer. The magnesium-binding site is CC absent in the low-activity homohexamer. Inhibited by compounds that CC favor the hexameric state. Inhibited by divalent lead ions. The lead CC ions partially displace the zinc cofactor (By similarity). CC {ECO:0000250}. CC -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX CC biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 1/4. CC -!- SUBUNIT: Homooctamer; active form. Homohexamer; low activity form (By CC similarity). {ECO:0000250}. CC -!- SIMILARITY: Belongs to the ALAD family. {ECO:0000305}. 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; AB125148; BAD51936.1; ALT_SEQ; mRNA. DR AlphaFoldDB; Q60HH9; -. DR SMR; Q60HH9; -. DR STRING; 9541.ENSMFAP00000044557; -. DR eggNOG; KOG2794; Eukaryota. DR UniPathway; UPA00251; UER00318. DR Proteomes; UP000233100; Unplaced. DR GO; GO:0004655; F:porphobilinogen synthase activity; ISS:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB. DR GO; GO:0006783; P:heme biosynthetic process; ISS:UniProtKB. 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 2: Evidence at transcript level; KW Allosteric enzyme; Heme biosynthesis; Lyase; Metal-binding; Phosphoprotein; KW Porphyrin biosynthesis; Reference proteome; Zinc. FT CHAIN 1..330 FT /note="Delta-aminolevulinic acid dehydratase" FT /id="PRO_0000140527" FT ACT_SITE 199 FT /note="Schiff-base intermediate with substrate" FT /evidence="ECO:0000250" FT ACT_SITE 252 FT /note="Schiff-base intermediate with substrate" FT /evidence="ECO:0000250" FT BINDING 122 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT BINDING 124 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT BINDING 131 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 132 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT BINDING 209 FT /ligand="5-aminolevulinate" FT /ligand_id="ChEBI:CHEBI:356416" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 221 FT /ligand="5-aminolevulinate" FT /ligand_id="ChEBI:CHEBI:356416" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 223 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 279 FT /ligand="5-aminolevulinate" FT /ligand_id="ChEBI:CHEBI:356416" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 318 FT /ligand="5-aminolevulinate" FT /ligand_id="ChEBI:CHEBI:356416" FT /ligand_label="2" FT /evidence="ECO:0000250" FT MOD_RES 199 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:P10518" FT MOD_RES 215 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P10518" FT MOD_RES 252 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:P10518" SQ SEQUENCE 330 AA; 36246 MW; 70527006BE58BEAA CRC64; MQPQSVLHSG YFHPLLRAWQ TATTTLNASN LIYPIFVTDV PDDIQPIASL PGVARYGVNR LEEMLRPLVE EGLRCVLIFG IPSRVPKDER GSAADSEESP AIEAIHLLRK TFPNLLVACD ICLCPYTSHG HCGLLSENGA FRAEESRQRL AEVALAYAKA GCQVVAPSDM MDGRVEAIKE ALMAHGLGNR VSVMSYSAKF ASCFYGPFRD AAQSSPAFGD RRCYQLPPGA RGLALRAVDR DVREGADVLM VKPGMPYLDI VREVKDKHPD LPLAVYHVSG EFAMLWHGAQ AGAFDLKAAV LEAMTAFRRA GADIIITYYT PQLLQWLKKE //