HEM2_MACFA
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 03-AUG-2022, entry version 68.
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}.
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DR EMBL; AB125148; BAD51936.1; ALT_SEQ; mRNA.
DR AlphaFoldDB; Q60HH9; -.
DR SMR; Q60HH9; -.
DR STRING; 9541.XP_005581069.1; -.
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 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 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
