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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

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

  1. identical protein binding Source: MGI
  2. lead ion binding Source: UniProtKB
  3. porphobilinogen synthase activity Source: UniProtKB
  4. zinc ion binding Source: UniProtKB

GO - Biological processi

  1. cellular response to interleukin-4 Source: MGI
  2. heme biosynthetic process Source: UniProtKB
  3. protein homooligomerization Source: MGI
  4. protoporphyrinogen IX biosynthetic process Source: UniProtKB-UniPathway
Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Biological processi

Heme biosynthesis, Porphyrin biosynthesis

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_203298. 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
Synonyms:Lv
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 4

Organism-specific databases

MGIiMGI:96853. Alad.

Subcellular locationi

GO - Cellular componenti

  1. extracellular vesicular exosome Source: MGI
  2. nucleus Source: MGI
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 330330Delta-aminolevulinic acid dehydratasePRO_0000140528Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei199 – 1991N6-succinyllysine1 Publication
Modified residuei215 – 2151Phosphoserine1 Publication
Modified residuei252 – 2521N6-succinyllysine1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP10518.
PaxDbiP10518.
PRIDEiP10518.

2D gel databases

REPRODUCTION-2DPAGEP10518.
SWISS-2DPAGEP10518.

PTM databases

PhosphoSiteiP10518.

Expressioni

Gene expression databases

BgeeiP10518.
CleanExiMM_ALAD.
ExpressionAtlasiP10518. baseline and differential.
GenevestigatoriP10518.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi201229. 1 interaction.
IntActiP10518. 5 interactions.
MINTiMINT-1869777.

Structurei

Secondary structure

1
330
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi8 – 103Combined sources
Helixi14 – 207Combined sources
Helixi28 – 303Combined sources
Beta strandi31 – 4212Combined sources
Beta strandi44 – 463Combined sources
Beta strandi48 – 503Combined sources
Beta strandi54 – 574Combined sources
Helixi58 – 603Combined sources
Helixi61 – 644Combined sources
Helixi66 – 694Combined sources
Turni70 – 723Combined sources
Beta strandi75 – 817Combined sources
Helixi100 – 11112Combined sources
Beta strandi113 – 1197Combined sources
Helixi144 – 16017Combined sources
Beta strandi163 – 1653Combined sources
Helixi174 – 18310Combined sources
Turni185 – 1884Combined sources
Beta strandi192 – 1943Combined sources
Helixi206 – 2116Combined sources
Helixi231 – 24111Combined sources
Helixi242 – 2443Combined sources
Beta strandi247 – 2548Combined sources
Helixi255 – 2573Combined sources
Helixi258 – 26710Combined sources
Beta strandi273 – 2764Combined sources
Helixi279 – 29012Combined sources
Helixi296 – 30914Combined sources
Beta strandi313 – 3164Combined sources
Helixi320 – 3267Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2Z0IX-ray3.20A/B1-330[»]
2Z1BX-ray3.30A/B/C/D1-330[»]
ProteinModelPortaliP10518.
SMRiP10518. Positions 5-328.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP10518.

Family & Domainsi

Sequence similaritiesi

Belongs to the ALAD family.Curated

Phylogenomic databases

eggNOGiCOG0113.
GeneTreeiENSGT00390000006998.
HOGENOMiHOG000020323.
HOVERGENiHBG001222.
InParanoidiP10518.
KOiK01698.
OMAiADCIITY.
OrthoDBiEOG751NFP.
PhylomeDBiP10518.
TreeFamiTF300665.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
InterProiIPR013785. Aldolase_TIM.
IPR001731. Porphobilinogen_synth.
[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_006537639.1.
UniGeneiMm.6988.

Genome annotation databases

EnsembliENSMUST00000030090; ENSMUSP00000030090; ENSMUSG00000028393.
ENSMUST00000107444; ENSMUSP00000103068; ENSMUSG00000028393.
GeneIDi17025.
KEGGimmu:17025.
UCSCiuc008tez.1. 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_006537639.1.
UniGeneiMm.6988.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2Z0IX-ray3.20A/B1-330[»]
2Z1BX-ray3.30A/B/C/D1-330[»]
ProteinModelPortaliP10518.
SMRiP10518. Positions 5-328.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201229. 1 interaction.
IntActiP10518. 5 interactions.
MINTiMINT-1869777.

PTM databases

PhosphoSiteiP10518.

2D gel databases

REPRODUCTION-2DPAGEP10518.
SWISS-2DPAGEP10518.

Proteomic databases

MaxQBiP10518.
PaxDbiP10518.
PRIDEiP10518.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000030090; ENSMUSP00000030090; ENSMUSG00000028393.
ENSMUST00000107444; ENSMUSP00000103068; ENSMUSG00000028393.
GeneIDi17025.
KEGGimmu:17025.
UCSCiuc008tez.1. mouse.

Organism-specific databases

CTDi210.
MGIiMGI:96853. Alad.

Phylogenomic databases

eggNOGiCOG0113.
GeneTreeiENSGT00390000006998.
HOGENOMiHOG000020323.
HOVERGENiHBG001222.
InParanoidiP10518.
KOiK01698.
OMAiADCIITY.
OrthoDBiEOG751NFP.
PhylomeDBiP10518.
TreeFamiTF300665.

Enzyme and pathway databases

UniPathwayiUPA00251; UER00318.
ReactomeiREACT_203298. Heme biosynthesis.

Miscellaneous databases

EvolutionaryTraceiP10518.
NextBioi291138.
PROiP10518.
SOURCEiSearch...

Gene expression databases

BgeeiP10518.
CleanExiMM_ALAD.
ExpressionAtlasiP10518. baseline and differential.
GenevestigatoriP10518.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
InterProiIPR013785. Aldolase_TIM.
IPR001731. Porphobilinogen_synth.
[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. "Cloning and sequence of mouse erythroid delta-aminolevulinate dehydratase cDNA."
    Bishop T.R., Hodes Z.I., Frelin L.P., Boyer S.H.
    Nucleic Acids Res. 17:1775-1775(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: BALB/c.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: BALB/c, C57BL/6J and DBA/2.
    Tissue: Placenta.
  3. "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].
    Strain: FVB/N.
    Tissue: Colon.
  4. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-215, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  5. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
    Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
    Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-199 AND LYS-252, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  6. "Crystal structure of 5-aminolevulinic acid dehydratase (ALAD) from Mus musculus."
    RIKEN structural genomics initiative (RSGI)
    Submitted (FEB-2009) to the PDB data bank
    Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS).

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: February 4, 2015
This is version 132 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

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.