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Protein

Delta-aminolevulinic acid dehydratase

Gene

Alad

Organism
Mus musculus (Mouse)
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: protoporphyrin-IX biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes coproporphyrinogen-III from 5-aminolevulinate.
Proteins known to be involved in the 4 steps of the subpathway in this organism are:
  1. Delta-aminolevulinic acid dehydratase (Alad)
  2. Porphobilinogen deaminase (Hmbs)
  3. Uroporphyrinogen-III synthase (Uros)
  4. Uroporphyrinogen decarboxylase (Urod)
This subpathway is part of the pathway protoporphyrin-IX biosynthesis, which is itself part of Porphyrin-containing compound metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes coproporphyrinogen-III from 5-aminolevulinate, the pathway protoporphyrin-IX biosynthesis and in Porphyrin-containing compound metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi122Zinc 1; catalyticBy similarity1
Metal bindingi124Zinc 1; catalyticBy similarity1
Metal bindingi131Zinc 2By similarity1
Metal bindingi132Zinc 1; catalyticBy similarity1
Active sitei199Schiff-base intermediate with substrateBy similarity1
Binding sitei209Substrate 1By similarity1
Binding sitei221Substrate 1By similarity1
Metal bindingi223Zinc 2By similarity1
Active sitei252Schiff-base intermediate with substrateBy similarity1
Binding sitei279Substrate 2By similarity1
Binding sitei318Substrate 2By similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Biological processi

Heme biosynthesis, Porphyrin biosynthesis

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-189451. Heme biosynthesis.
R-MMU-6798695. Neutrophil degranulation.
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
Synonyms:Lv
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:96853. Alad.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001405281 – 330Delta-aminolevulinic acid dehydrataseAdd BLAST330

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei199N6-succinyllysineCombined sources1
Modified residuei215PhosphoserineCombined sources1
Modified residuei252N6-succinyllysineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP10518.
MaxQBiP10518.
PaxDbiP10518.
PeptideAtlasiP10518.
PRIDEiP10518.

2D gel databases

REPRODUCTION-2DPAGEP10518.
SWISS-2DPAGEP10518.

PTM databases

iPTMnetiP10518.
PhosphoSitePlusiP10518.
SwissPalmiP10518.

Expressioni

Gene expression databases

BgeeiENSMUSG00000028393.
CleanExiMM_ALAD.
GenevisibleiP10518. MM.

Interactioni

Subunit structurei

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

GO - Molecular functioni

  • identical protein binding Source: MGI

Protein-protein interaction databases

BioGridi201229. 2 interactors.
IntActiP10518. 6 interactors.
MINTiMINT-1869777.
STRINGi10090.ENSMUSP00000030090.

Structurei

Secondary structure

1330
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi8 – 10Combined sources3
Helixi14 – 20Combined sources7
Helixi28 – 30Combined sources3
Beta strandi31 – 42Combined sources12
Beta strandi44 – 46Combined sources3
Beta strandi48 – 50Combined sources3
Beta strandi54 – 57Combined sources4
Helixi58 – 60Combined sources3
Helixi61 – 64Combined sources4
Helixi66 – 69Combined sources4
Turni70 – 72Combined sources3
Beta strandi75 – 81Combined sources7
Helixi100 – 111Combined sources12
Beta strandi113 – 119Combined sources7
Beta strandi133 – 135Combined sources3
Helixi144 – 160Combined sources17
Beta strandi163 – 165Combined sources3
Helixi174 – 183Combined sources10
Turni185 – 188Combined sources4
Beta strandi192 – 194Combined sources3
Helixi206 – 211Combined sources6
Helixi231 – 241Combined sources11
Helixi242 – 244Combined sources3
Beta strandi247 – 254Combined sources8
Helixi255 – 257Combined sources3
Helixi258 – 267Combined sources10
Beta strandi273 – 276Combined sources4
Helixi279 – 290Combined sources12
Helixi296 – 309Combined sources14
Beta strandi313 – 316Combined sources4
Helixi320 – 326Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2Z0IX-ray3.20A/B1-330[»]
2Z1BX-ray3.30A/B/C/D1-330[»]
ProteinModelPortaliP10518.
SMRiP10518.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP10518.

Family & Domainsi

Sequence similaritiesi

Belongs to the ALAD family.Curated

Phylogenomic databases

eggNOGiKOG2794. Eukaryota.
COG0113. LUCA.
GeneTreeiENSGT00390000006998.
HOGENOMiHOG000020323.
HOVERGENiHBG001222.
InParanoidiP10518.
KOiK01698.
OMAiMHHATLR.
OrthoDBiEOG091G0FMX.
PhylomeDBiP10518.
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.

P10518-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MHHQSVLHSG YFHPLLRSWQ TAASTVSASN LIYPIFVTDV PDDVQPIASL
60 70 80 90 100
PGVARYGVNQ LEEMLRPLVE AGLRCVLIFG VPSRVPKDEQ GSAADSEDSP
110 120 130 140 150
TIEAVRLLRK TFPSLLVACD VCLCPYTSHG HCGLLSENGA FLAEESRQRL
160 170 180 190 200
AEVALAYAKA GCQVVAPSDM MDGRVEAIKA ALLKHGLGNR VSVMSYSAKF
210 220 230 240 250
ASCFYGPFRD AAQSSPAFGD RRCYQLPPGA RGLALRAVAR DIQEGADMLM
260 270 280 290 300
VKPGLPYLDM VREVKDKHPE LPLAVYQVSG EFAMLWHGAQ AGAFDLRTAV
310 320 330
LETMTAFRRA GADIIITYFA PQLLKWLKEE
Length:330
Mass (Da):36,024
Last modified:July 1, 1989 - v1
Checksum:i84052DC911C153EB
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X13752 mRNA. Translation: CAA32015.1.
AK032908 mRNA. Translation: BAC28080.1.
AK167673 mRNA. Translation: BAE39722.1.
AK168119 mRNA. Translation: BAE40090.1.
AK168132 mRNA. Translation: BAE40101.1.
BC055930 mRNA. Translation: AAH55930.1.
CCDSiCCDS18243.1.
PIRiS03187.
RefSeqiNP_001263375.1. NM_001276446.1.
NP_032551.3. NM_008525.4.
XP_006537702.1. XM_006537639.2.
UniGeneiMm.6988.

Genome annotation databases

EnsembliENSMUST00000030090; ENSMUSP00000030090; ENSMUSG00000028393.
ENSMUST00000107444; ENSMUSP00000103068; ENSMUSG00000028393.
GeneIDi17025.
KEGGimmu:17025.
UCSCiuc008tez.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X13752 mRNA. Translation: CAA32015.1.
AK032908 mRNA. Translation: BAC28080.1.
AK167673 mRNA. Translation: BAE39722.1.
AK168119 mRNA. Translation: BAE40090.1.
AK168132 mRNA. Translation: BAE40101.1.
BC055930 mRNA. Translation: AAH55930.1.
CCDSiCCDS18243.1.
PIRiS03187.
RefSeqiNP_001263375.1. NM_001276446.1.
NP_032551.3. NM_008525.4.
XP_006537702.1. XM_006537639.2.
UniGeneiMm.6988.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2Z0IX-ray3.20A/B1-330[»]
2Z1BX-ray3.30A/B/C/D1-330[»]
ProteinModelPortaliP10518.
SMRiP10518.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201229. 2 interactors.
IntActiP10518. 6 interactors.
MINTiMINT-1869777.
STRINGi10090.ENSMUSP00000030090.

PTM databases

iPTMnetiP10518.
PhosphoSitePlusiP10518.
SwissPalmiP10518.

2D gel databases

REPRODUCTION-2DPAGEP10518.
SWISS-2DPAGEP10518.

Proteomic databases

EPDiP10518.
MaxQBiP10518.
PaxDbiP10518.
PeptideAtlasiP10518.
PRIDEiP10518.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000030090; ENSMUSP00000030090; ENSMUSG00000028393.
ENSMUST00000107444; ENSMUSP00000103068; ENSMUSG00000028393.
GeneIDi17025.
KEGGimmu:17025.
UCSCiuc008tez.2. mouse.

Organism-specific databases

CTDi210.
MGIiMGI:96853. Alad.

Phylogenomic databases

eggNOGiKOG2794. Eukaryota.
COG0113. LUCA.
GeneTreeiENSGT00390000006998.
HOGENOMiHOG000020323.
HOVERGENiHBG001222.
InParanoidiP10518.
KOiK01698.
OMAiMHHATLR.
OrthoDBiEOG091G0FMX.
PhylomeDBiP10518.
TreeFamiTF300665.

Enzyme and pathway databases

UniPathwayiUPA00251; UER00318.
ReactomeiR-MMU-189451. Heme biosynthesis.
R-MMU-6798695. Neutrophil degranulation.

Miscellaneous databases

EvolutionaryTraceiP10518.
PROiP10518.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000028393.
CleanExiMM_ALAD.
GenevisibleiP10518. MM.

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...

Entry informationi

Entry nameiHEM2_MOUSE
AccessioniPrimary (citable) accession number: P10518
Secondary accession number(s): Q3THV6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: November 30, 2016
This is version 149 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

3D-structure, Allosteric enzyme, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

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 one 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.