UniProt functional annotation for P13716



	UniProt functional annotation for P13716

UniProt code: P13716.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Catalyzes an early step in the biosynthesis of tetrapyrroles. Binds two molecules of 5-aminolevulinate per subunit, each at a distinct site, and catalyzes their condensation to form porphobilinogen. {ECO:0000269|PubMed:11032836, ECO:0000269|PubMed:19812033}.

Catalytic activity: Reaction=2 5-aminolevulinate = H(+) + 2 H2O + porphobilinogen; Xref=Rhea:RHEA:24064, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58126, ChEBI:CHEBI:356416; EC=4.2.1.24; Evidence={ECO:0000269|PubMed:11032836, ECO:0000269|PubMed:12897770, ECO:0000269|PubMed:19812033};

Cofactor: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:11032836}; Note=Binds 8 zinc ions per octamer. Requires four zinc ions per octamer for full catalytic activity. Can bind up to 2 zinc ions per subunit. {ECO:0000269|PubMed:11032836};

Activity regulation: Can alternate between a fully active homooctamer and a low-activity homohexamer. A bound magnesium ion may promote the assembly of the fully active homooctamer. The magnesium-binding site is absent in the low-activity homohexamer. Inhibited by compounds that favor the hexameric state. Inhibited by divalent lead ions. The lead ions partially displace the zinc cofactor. {ECO:0000269|PubMed:11032836, ECO:0000269|PubMed:12897770, ECO:0000269|PubMed:19812033}.

Biophysicochemical properties: Kinetic parameters: KM=0.09 mM for 5-aminolevulinate at pH 7 {ECO:0000269|PubMed:11032836}; Vmax=43 umol/h/mg enzyme at pH 7 {ECO:0000269|PubMed:11032836}; pH dependence: Optimum pH is 6.8-7.3. {ECO:0000269|PubMed:11032836};

Pathway: Porphyrin-containing compound metabolism; protoporphyrin-IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 1/4.

Subunit: Homooctamer; active form. Homohexamer; low activity form. {ECO:0000269|PubMed:12897770, ECO:0000269|PubMed:19812033, ECO:0000269|Ref.16}.

Polymorphism: Genetic variation in ALAD influences susceptibility to lead poisoning in individuals exposed to high amount of environmental lead. There are two common alleles: allele ALAD*1 and allele ALAD*2 resulting in 3 isozymes: ALAD 1-1, ALAD 1-2, and ALAD 2-2. Individuals with ALAD 1-2 or ALAD 2-2 isozymes have levels of blood lead higher than those in individuals with ALAD 1-1 isozyme. The sequence shown corresponds to allele ALAD*1. {ECO:0000269|PubMed:1716854, ECO:0000269|PubMed:1769358, ECO:0000305|PubMed:17966070}.

Disease: Acute hepatic porphyria (AHEPP) [MIM:612740]: A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. AHP is characterized by attacks of gastrointestinal disturbances, abdominal colic, paralyses and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors. {ECO:0000269|PubMed:10706561, ECO:0000269|PubMed:1309003, ECO:0000269|PubMed:1569184, ECO:0000269|PubMed:17236137, ECO:0000269|PubMed:2063868}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the ALAD family. {ECO:0000305}.

Sequence caution: Sequence=AAH00977.3; Type=Erroneous initiation; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Catalyzes an early step in the biosynthesis of tetrapyrroles. Binds two molecules of 5-aminolevulinate per subunit, each at a distinct site, and catalyzes their condensation to form porphobilinogen. {ECO:0000269\|PubMed:11032836, ECO:0000269\|PubMed:19812033}.


Catalytic activity:		Reaction=2 5-aminolevulinate = H(+) + 2 H2O + porphobilinogen; Xref=Rhea:RHEA:24064, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58126, ChEBI:CHEBI:356416; EC=4.2.1.24; Evidence={ECO:0000269\|PubMed:11032836, ECO:0000269\|PubMed:12897770, ECO:0000269\|PubMed:19812033};
Cofactor:		Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269\|PubMed:11032836}; Note=Binds 8 zinc ions per octamer. Requires four zinc ions per octamer for full catalytic activity. Can bind up to 2 zinc ions per subunit. {ECO:0000269\|PubMed:11032836};
Activity regulation:		Can alternate between a fully active homooctamer and a low-activity homohexamer. A bound magnesium ion may promote the assembly of the fully active homooctamer. The magnesium-binding site is absent in the low-activity homohexamer. Inhibited by compounds that favor the hexameric state. Inhibited by divalent lead ions. The lead ions partially displace the zinc cofactor. {ECO:0000269\|PubMed:11032836, ECO:0000269\|PubMed:12897770, ECO:0000269\|PubMed:19812033}.
Biophysicochemical properties:		Kinetic parameters: KM=0.09 mM for 5-aminolevulinate at pH 7 {ECO:0000269\|PubMed:11032836}; Vmax=43 umol/h/mg enzyme at pH 7 {ECO:0000269\|PubMed:11032836}; pH dependence: Optimum pH is 6.8-7.3. {ECO:0000269\|PubMed:11032836};
Pathway:		Porphyrin-containing compound metabolism; protoporphyrin-IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 1/4.
Subunit:		Homooctamer; active form. Homohexamer; low activity form. {ECO:0000269\|PubMed:12897770, ECO:0000269\|PubMed:19812033, ECO:0000269\|Ref.16}.
Polymorphism:		Genetic variation in ALAD influences susceptibility to lead poisoning in individuals exposed to high amount of environmental lead. There are two common alleles: allele ALAD1 and allele ALAD2 resulting in 3 isozymes: ALAD 1-1, ALAD 1-2, and ALAD 2-2. Individuals with ALAD 1-2 or ALAD 2-2 isozymes have levels of blood lead higher than those in individuals with ALAD 1-1 isozyme. The sequence shown corresponds to allele ALAD*1. {ECO:0000269\|PubMed:1716854, ECO:0000269\|PubMed:1769358, ECO:0000305\|PubMed:17966070}.
Disease:		Acute hepatic porphyria (AHEPP) [MIM:612740]: A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. AHP is characterized by attacks of gastrointestinal disturbances, abdominal colic, paralyses and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors. {ECO:0000269\|PubMed:10706561, ECO:0000269\|PubMed:1309003, ECO:0000269\|PubMed:1569184, ECO:0000269\|PubMed:17236137, ECO:0000269\|PubMed:2063868}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the ALAD family. {ECO:0000305}.
Sequence caution:		Sequence=AAH00977.3; Type=Erroneous initiation; Evidence={ECO:0000305};