P06214 (HEM2_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Delta-aminolevulinic acid dehydratase
Short name=ALADH
EC=4.2.1.24

Alternative name(s):
Porphobilinogen synthase

Gene names

Name:

Alad

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	330 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 By similarity.
Catalytic activity	2 5-aminolevulinate = porphobilinogen + 2 H2O.
Cofactor	Binds 8 zinc ions per octamer. Only four zinc ions per octamer are required for full catalytic activity. Only four zinc ions per octamer are tightly bound. Can bind 2 zinc ions per subunit. The first zinc ion is important for catalysis By similarity.
Enzyme 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 By similarity.
Pathway	Porphyrin metabolism; protoporphyrin-IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 1/4.
Subunit structure	Homooctamer; active form. Homohexamer; low activity form By similarity.
Sequence similarities	Belongs to the ALADH family.

Ontologies

Keywords
Biological process	Heme biosynthesis Porphyrin biosynthesis
Ligand	Metal-binding Zinc
Molecular function	Lyase
Technical term	Allosteric enzyme Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to lead ion Inferred from expression pattern PubMed 16566714. Source: RGD heme biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB protoporphyrinogen IX biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway response to activity Inferred from expression pattern PubMed 12171438. Source: RGD response to aluminum ion Inferred from expression pattern PubMed 518129. Source: RGD response to amino acid stimulus Inferred from expression pattern PubMed 8295845. Source: RGD response to arsenic-containing substance Inferred from direct assay PubMed 17086449. Source: RGD response to cadmium ion Inferred from direct assay PubMed 7896311. Source: RGD response to cobalt ion Inferred from expression pattern PubMed 826600. Source: RGD response to drug Inferred from direct assay PubMed 8070841. Source: RGD response to ethanol Inferred from direct assay PubMed 2394940. Source: RGD response to fatty acid Inferred from expression pattern PubMed 20026167. Source: RGD response to glucocorticoid stimulus Inferred from expression pattern PubMed 12596873. Source: RGD response to herbicide Inferred from expression pattern PubMed 12180188. Source: RGD response to hypoxia Inferred from expression pattern PubMed 3697363. Source: RGD response to ionizing radiation Inferred from expression pattern PubMed 17916974. Source: RGD response to iron ion Inferred from expression pattern PubMed 14598909. Source: RGD response to lipopolysaccharide Inferred from expression pattern PubMed 19344711. Source: RGD response to mercury ion Inferred from expression pattern PubMed 17881112. Source: RGD response to methylmercury Inferred from expression pattern PubMed 19874286. Source: RGD response to oxidative stress Inferred from expression pattern PubMed 17916976. Source: RGD response to platinum ion Inferred from expression pattern PubMed 925603. Source: RGD response to selenium ion Inferred from expression pattern PubMed 15721883. Source: RGD response to vitamin B1 Inferred from expression pattern PubMed 20088549. Source: RGD response to vitamin E Inferred from expression pattern PubMed 17572058. Source: RGD response to zinc ion Inferred from direct assay PubMed 3987589. Source: RGD
Cellular_component	cytosol Inferred from direct assay PubMed 2394940. Source: RGD extracellular space Inferred from direct assay PubMed 19111884. Source: RGD
Molecular_function	lead ion binding Inferred from sequence or structural similarity. Source: UniProtKB porphobilinogen synthase activity Inferred from sequence or structural similarity. Source: UniProtKB zinc ion binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 330	330	Delta-aminolevulinic acid dehydratase		PRO_0000140530
Sites
	Active site	199	1	Schiff-base intermediate with substrate By similarity
	Active site	252	1	Schiff-base intermediate with substrate By similarity
	Metal binding	122	1	Zinc 1; catalytic By similarity
	Metal binding	124	1	Zinc 1; catalytic By similarity
	Metal binding	131	1	Zinc 2 By similarity
	Metal binding	132	1	Zinc 1; catalytic By similarity
	Metal binding	223	1	Zinc 2 By similarity
	Binding site	209	1	Substrate 1 By similarity
	Binding site	221	1	Substrate 1 By similarity
	Binding site	279	1	Substrate 2 By similarity
	Binding site	318	1	Substrate 2 By similarity

Sequences

	Sequence		Length	Mass (Da)
	P06214 [UniParc]. Last modified January 1, 1988. Version 1. Checksum: 617F6E85B647AB25	FASTA	330	36,032
	10 20 30 40 50 60 MHHQSVLHSG YFHPLLRAWQ TTPSTVSATN LIYPIFVTDV PDDVQPIASL PGVARYGVNQ 70 80 90 100 110 120 LEEMLRPLVE AGLRCVLIFG VPSRVPKDEQ GSAADSEDSP TIEAVRLLRK TFPTLLVACD 130 140 150 160 170 180 VCLCPYTSHG HCGLLSENGA FLAEESRQRL AEVALAYAKA GCQVVAPSDM MDGRVEAIKA 190 200 210 220 230 240 ALLKHGLGNR VSVMSYSAKF ASCFYGPFRD AAQSSPAFGD RRCYQLPPGA RGLALRAVAR 250 260 270 280 290 300 DIQEGADILM VKPGLPYLDM VQEVKDKHPE LPLAVYQVSG EFAMLWHGAK AGAFDLRTAV 310 320 330 LESMTAFRRA GADIIITYFA PQLLKWLKEE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of rat liver delta-aminolevulinic acid dehydratase cDNA." Bishop T.R., Frelin L.P., Boyer S.H. Nucleic Acids Res. 14:10115-10115(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Prostate.
[3]	"Isolation of a rat liver delta-aminolevulinate dehydrase (ALAD) cDNA clone: evidence for unequal ALAD gene dosage among inbred mouse strains." Bishop T.R., Cohen P.J., Boyer S.H., Noyes A.N., Frelin L.P. Proc. Natl. Acad. Sci. U.S.A. 83:5568-5572(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-45.
[4]	Lubec G., Afjehi-Sadat L. Submitted (NOV-2006) to UniProtKB Cited for: PROTEIN SEQUENCE OF 56-84 AND 200-209, MASS SPECTROMETRY. Strain: Sprague-Dawley. Tissue: Spinal cord.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X04959 mRNA. Translation: CAA28621.1. BC061806 mRNA. Translation: AAH61806.1.
IPI	IPI00201399.
PIR	A24724.
RefSeq	NP_037031.1. NM_012899.2.
UniGene	Rn.3941.
3D structure databases
ProteinModelPortal	P06214.
SMR	P06214. Positions 5-328.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000020625.
PTM databases
PhosphoSite	P06214.
Proteomic databases
PaxDb	P06214.
PRIDE	P06214.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000020625; ENSRNOP00000020625; ENSRNOG00000015206.
GeneID	25374.
KEGG	rno:25374.
UCSC	RGD:2083. rat.
Organism-specific databases
CTD	210.
RGD	2083. Alad.
Phylogenomic databases
eggNOG	COG0113.
GeneTree	ENSGT00390000006998.
HOGENOM	HOG000020323.
HOVERGEN	HBG001222.
InParanoid	P06214.
KO	K01698.
OMA	AVMEAMT.
OrthoDB	EOG4BRWM1.
Enzyme and pathway databases
UniPathway	UPA00251; UER00318.
Gene expression databases
Genevestigator	P06214.
GermOnline	ENSRNOG00000015206. Rattus norvegicus.
Family and domain databases
Gene3D	3.20.20.70. 1 hit.
InterPro	IPR013785. Aldolase_TIM. IPR001731. Porphobilinogen_synth. [Graphical view]
PANTHER	PTHR11458. PTHR11458. 1 hit.
Pfam	PF00490. ALAD. 1 hit. [Graphical view]
PIRSF	PIRSF001415. Porphbilin_synth. 1 hit.
PRINTS	PR00144. DALDHYDRTASE.
SMART	SM01004. ALAD. 1 hit. [Graphical view]
PROSITE	PS00169. D_ALA_DEHYDRATASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	606397.

Entry information

Entry name

HEM2_RAT

Accession

Primary (citable) accession number: P06214

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1988
Last sequence update:	January 1, 1988
Last modified:	April 3, 2013
This is version 107 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program