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Protein

Delta-aminolevulinic acid dehydratase

Gene

Alad

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

Catalytic activityi

2 5-aminolevulinate = porphobilinogen + 2 H2O.

Cofactori

Zn2+By similarityNote: 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.By similarity

Enzyme regulationi

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).By similarity

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi122 – 1221Zinc 1; catalyticBy similarity
Metal bindingi124 – 1241Zinc 1; catalyticBy similarity
Metal bindingi131 – 1311Zinc 2By similarity
Metal bindingi132 – 1321Zinc 1; catalyticBy similarity
Active sitei199 – 1991Schiff-base intermediate with substrateBy similarity
Binding sitei209 – 2091Substrate 1By similarity
Binding sitei221 – 2211Substrate 1By similarity
Metal bindingi223 – 2231Zinc 2By similarity
Active sitei252 – 2521Schiff-base intermediate with substrateBy similarity
Binding sitei279 – 2791Substrate 2By similarity
Binding sitei318 – 3181Substrate 2By similarity

GO - Molecular functioni

GO - Biological processi

  • cellular response to lead ion Source: RGD
  • heme biosynthetic process Source: UniProtKB
  • protoporphyrinogen IX biosynthetic process Source: UniProtKB-UniPathway
  • response to activity Source: RGD
  • response to aluminum ion Source: RGD
  • response to amino acid Source: RGD
  • response to arsenic-containing substance Source: RGD
  • response to cadmium ion Source: RGD
  • response to cobalt ion Source: RGD
  • response to drug Source: RGD
  • response to ethanol Source: RGD
  • response to fatty acid Source: RGD
  • response to glucocorticoid Source: RGD
  • response to herbicide Source: RGD
  • response to hormone Source: RGD
  • response to hypoxia Source: RGD
  • response to inorganic substance Source: RGD
  • response to ionizing radiation Source: RGD
  • response to iron ion Source: RGD
  • response to lead ion Source: RGD
  • response to lipopolysaccharide Source: RGD
  • response to mercury ion Source: RGD
  • response to metal ion Source: RGD
  • response to methylmercury Source: RGD
  • response to nutrient Source: RGD
  • response to nutrient levels Source: RGD
  • response to organic cyclic compound Source: RGD
  • response to organic substance Source: RGD
  • response to oxidative stress Source: RGD
  • response to platinum ion Source: RGD
  • response to selenium ion Source: RGD
  • response to toxic substance Source: RGD
  • response to vitamin Source: RGD
  • response to vitamin B1 Source: RGD
  • response to vitamin E Source: RGD
  • response to zinc ion Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Biological processi

Heme biosynthesis, Porphyrin biosynthesis

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_336296. Heme biosynthesis.
UniPathwayiUPA00251; UER00318.

Names & Taxonomyi

Protein namesi
Recommended name:
Delta-aminolevulinic acid dehydratase (EC:4.2.1.24)
Short name:
ALADH
Alternative name(s):
Porphobilinogen synthase
Gene namesi
Name:Alad
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 5

Organism-specific databases

RGDi2083. Alad.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: RGD
  • extracellular space Source: RGD
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 330330Delta-aminolevulinic acid dehydratasePRO_0000140530Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei199 – 1991N6-succinyllysineBy similarity
Modified residuei215 – 2151PhosphoserineBy similarity
Modified residuei252 – 2521N6-succinyllysineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP06214.
PRIDEiP06214.

PTM databases

PhosphoSiteiP06214.

Expressioni

Gene expression databases

GenevestigatoriP06214.

Interactioni

Subunit structurei

Homooctamer; active form. Homohexamer; low activity form (By similarity).By similarity

Protein-protein interaction databases

BioGridi247413. 1 interaction.
MINTiMINT-4567662.
STRINGi10116.ENSRNOP00000020625.

Structurei

3D structure databases

ProteinModelPortaliP06214.
SMRiP06214. Positions 5-328.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the ALAD family.Curated

Phylogenomic databases

eggNOGiCOG0113.
GeneTreeiENSGT00390000006998.
HOGENOMiHOG000020323.
HOVERGENiHBG001222.
InParanoidiP06214.
KOiK01698.
OMAiADCIITY.
OrthoDBiEOG751NFP.
PhylomeDBiP06214.
TreeFamiTF300665.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
InterProiIPR001731. ALAD.
IPR030656. ALAD_AS.
IPR013785. Aldolase_TIM.
[Graphical view]
PANTHERiPTHR11458. PTHR11458. 1 hit.
PfamiPF00490. ALAD. 1 hit.
[Graphical view]
PIRSFiPIRSF001415. Porphbilin_synth. 1 hit.
PRINTSiPR00144. DALDHYDRTASE.
SMARTiSM01004. ALAD. 1 hit.
[Graphical view]
PROSITEiPS00169. D_ALA_DEHYDRATASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P06214-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MHHQSVLHSG YFHPLLRAWQ TTPSTVSATN LIYPIFVTDV PDDVQPIASL
60 70 80 90 100
PGVARYGVNQ LEEMLRPLVE AGLRCVLIFG VPSRVPKDEQ GSAADSEDSP
110 120 130 140 150
TIEAVRLLRK TFPTLLVACD VCLCPYTSHG HCGLLSENGA FLAEESRQRL
160 170 180 190 200
AEVALAYAKA GCQVVAPSDM MDGRVEAIKA ALLKHGLGNR VSVMSYSAKF
210 220 230 240 250
ASCFYGPFRD AAQSSPAFGD RRCYQLPPGA RGLALRAVAR DIQEGADILM
260 270 280 290 300
VKPGLPYLDM VQEVKDKHPE LPLAVYQVSG EFAMLWHGAK AGAFDLRTAV
310 320 330
LESMTAFRRA GADIIITYFA PQLLKWLKEE
Length:330
Mass (Da):36,032
Last modified:January 1, 1988 - v1
Checksum:i617F6E85B647AB25
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X04959 mRNA. Translation: CAA28621.1.
BC061806 mRNA. Translation: AAH61806.1.
PIRiA24724.
RefSeqiNP_037031.1. NM_012899.2.
XP_006238296.1. XM_006238234.2.
XP_006238297.1. XM_006238235.1.
UniGeneiRn.3941.

Genome annotation databases

EnsembliENSRNOT00000020625; ENSRNOP00000020625; ENSRNOG00000015206.
ENSRNOT00000075916; ENSRNOP00000068140; ENSRNOG00000015206.
GeneIDi25374.
KEGGirno:25374.
UCSCiRGD:2083. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X04959 mRNA. Translation: CAA28621.1.
BC061806 mRNA. Translation: AAH61806.1.
PIRiA24724.
RefSeqiNP_037031.1. NM_012899.2.
XP_006238296.1. XM_006238234.2.
XP_006238297.1. XM_006238235.1.
UniGeneiRn.3941.

3D structure databases

ProteinModelPortaliP06214.
SMRiP06214. Positions 5-328.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247413. 1 interaction.
MINTiMINT-4567662.
STRINGi10116.ENSRNOP00000020625.

PTM databases

PhosphoSiteiP06214.

Proteomic databases

PaxDbiP06214.
PRIDEiP06214.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000020625; ENSRNOP00000020625; ENSRNOG00000015206.
ENSRNOT00000075916; ENSRNOP00000068140; ENSRNOG00000015206.
GeneIDi25374.
KEGGirno:25374.
UCSCiRGD:2083. rat.

Organism-specific databases

CTDi210.
RGDi2083. Alad.

Phylogenomic databases

eggNOGiCOG0113.
GeneTreeiENSGT00390000006998.
HOGENOMiHOG000020323.
HOVERGENiHBG001222.
InParanoidiP06214.
KOiK01698.
OMAiADCIITY.
OrthoDBiEOG751NFP.
PhylomeDBiP06214.
TreeFamiTF300665.

Enzyme and pathway databases

UniPathwayiUPA00251; UER00318.
ReactomeiREACT_336296. Heme biosynthesis.

Miscellaneous databases

NextBioi606397.
PROiP06214.

Gene expression databases

GenevestigatoriP06214.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
InterProiIPR001731. ALAD.
IPR030656. ALAD_AS.
IPR013785. Aldolase_TIM.
[Graphical view]
PANTHERiPTHR11458. PTHR11458. 1 hit.
PfamiPF00490. ALAD. 1 hit.
[Graphical view]
PIRSFiPIRSF001415. Porphbilin_synth. 1 hit.
PRINTSiPR00144. DALDHYDRTASE.
SMARTiSM01004. ALAD. 1 hit.
[Graphical view]
PROSITEiPS00169. D_ALA_DEHYDRATASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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, IDENTIFICATION BY MASS SPECTROMETRY.
    Strain: Sprague-Dawley.
    Tissue: Spinal cord.

Entry informationi

Entry nameiHEM2_RAT
AccessioniPrimary (citable) accession number: P06214
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 1, 1988
Last modified: April 29, 2015
This is version 123 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Allosteric enzyme, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.