HEM2_BOVIN
ID HEM2_BOVIN Reviewed; 329 AA.
AC Q58DK5;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=Delta-aminolevulinic acid dehydratase;
DE Short=ALADH;
DE EC=4.2.1.24;
DE AltName: Full=Porphobilinogen synthase;
GN Name=ALAD;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
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; BT021592; AAX46439.1; -; mRNA.
DR RefSeq; NP_001014895.1; NM_001014895.1.
DR AlphaFoldDB; Q58DK5; -.
DR SMR; Q58DK5; -.
DR STRING; 9913.ENSBTAP00000000315; -.
DR PaxDb; Q58DK5; -.
DR PeptideAtlas; Q58DK5; -.
DR PRIDE; Q58DK5; -.
DR Ensembl; ENSBTAT00000000315; ENSBTAP00000000315; ENSBTAG00000000251.
DR GeneID; 510679; -.
DR KEGG; bta:510679; -.
DR CTD; 210; -.
DR VEuPathDB; HostDB:ENSBTAG00000000251; -.
DR VGNC; VGNC:25802; ALAD.
DR eggNOG; KOG2794; Eukaryota.
DR GeneTree; ENSGT00390000006998; -.
DR HOGENOM; CLU_035731_0_1_1; -.
DR InParanoid; Q58DK5; -.
DR OMA; YQMDYAN; -.
DR OrthoDB; 918089at2759; -.
DR TreeFam; TF300665; -.
DR Reactome; R-BTA-189451; Heme biosynthesis.
DR Reactome; R-BTA-6798695; Neutrophil degranulation.
DR UniPathway; UPA00251; UER00318.
DR Proteomes; UP000009136; Chromosome 8.
DR Bgee; ENSBTAG00000000251; Expressed in liver and 106 other tissues.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0004655; F:porphobilinogen synthase activity; IDA:CAFA.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0071353; P:cellular response to interleukin-4; IEA:Ensembl.
DR GO; GO:0006783; P:heme biosynthetic process; ISS:UniProtKB.
DR GO; GO:1901799; P:negative regulation of proteasomal protein catabolic process; IDA:CAFA.
DR GO; GO:0051260; P:protein homooligomerization; IEA:Ensembl.
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..329
FT /note="Delta-aminolevulinic acid dehydratase"
FT /id="PRO_0000328038"
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 329 AA; 36081 MW; 8BD0E141749B6465 CRC64;
MHPQSVLHSG YFHPLLRNWQ TAATSLSASN LIYPIFVTDV PDDKQPIASL PGVARYGVNR
LEEMLKPLVE EGLRCVLIFG VPSRVPKDER GSAADSEDSP AIEAIRLLRK NFPSLLVACD
VCLCPYTSHG HCGLLSENGS FQAEESRQRL AEVALAYAKA GCQVVAPSDM MDGRVEAIKE
ALMAHGFGNR VSVMSYSAKF ASCFYGPFRD AAQSSPAFGD RRCYQLPPGA RGLALRAVDR
DVREGADLLM VKPGTPYLDI VREVKNKHPE LPLAVYHVSG EFAMLWHGAQ AGAFDLKAAV
LEVMTAFRRA GADVIITYYT PQLLQWLKE
