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P10518 (HEM2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Delta-aminolevulinic acid dehydratase

Short name=ALADH
EC=4.2.1.24
Alternative name(s):
Porphobilinogen synthase
Gene names
Name:Alad
Synonyms:Lv
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length330 AA.
Sequence statusComplete.
Protein existenceEvidence 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. Requires four zinc ions per octamer for full catalytic activity. Can bind up to 2 zinc ions per subunit 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-containing compound 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 330330Delta-aminolevulinic acid dehydratase
PRO_0000140528

Sites

Active site1991Schiff-base intermediate with substrate By similarity
Active site2521Schiff-base intermediate with substrate By similarity
Metal binding1221Zinc 1; catalytic By similarity
Metal binding1241Zinc 1; catalytic By similarity
Metal binding1311Zinc 2 By similarity
Metal binding1321Zinc 1; catalytic By similarity
Metal binding2231Zinc 2 By similarity
Binding site2091Substrate 1 By similarity
Binding site2211Substrate 1 By similarity
Binding site2791Substrate 2 By similarity
Binding site3181Substrate 2 By similarity

Amino acid modifications

Modified residue1991N6-succinyllysine Ref.5
Modified residue2151Phosphoserine Ref.4
Modified residue2521N6-succinyllysine Ref.5

Secondary structure

...................................................... 330
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P10518 [UniParc].

Last modified July 1, 1989. Version 1.
Checksum: 84052DC911C153EB

FASTA33036,024
        10         20         30         40         50         60 
MHHQSVLHSG YFHPLLRSWQ TAASTVSASN LIYPIFVTDV PDDVQPIASL PGVARYGVNQ 

        70         80         90        100        110        120 
LEEMLRPLVE AGLRCVLIFG VPSRVPKDEQ GSAADSEDSP TIEAVRLLRK TFPSLLVACD 

       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 
DIQEGADMLM VKPGLPYLDM VREVKDKHPE LPLAVYQVSG EFAMLWHGAQ AGAFDLRTAV 

       310        320        330 
LETMTAFRRA GADIIITYFA PQLLKWLKEE 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
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).
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRS03187.
RefSeqNP_001263375.1. NM_001276446.1.
NP_032551.3. NM_008525.4.
XP_006537702.1. XM_006537639.1.
UniGeneMm.6988.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2Z0IX-ray3.20A/B1-330[»]
2Z1BX-ray3.30A/B/C/D1-330[»]
ProteinModelPortalP10518.
SMRP10518. Positions 5-328.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP10518. 5 interactions.
MINTMINT-1869777.

PTM databases

PhosphoSiteP10518.

2D gel databases

REPRODUCTION-2DPAGEP10518.
SWISS-2DPAGEP10518.

Proteomic databases

PaxDbP10518.
PRIDEP10518.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000030090; ENSMUSP00000030090; ENSMUSG00000028393.
ENSMUST00000107444; ENSMUSP00000103068; ENSMUSG00000028393.
GeneID17025.
KEGGmmu:17025.
UCSCuc008tez.1. mouse.

Organism-specific databases

CTD210.
MGIMGI:96853. Alad.

Phylogenomic databases

eggNOGCOG0113.
GeneTreeENSGT00390000006998.
HOGENOMHOG000020323.
HOVERGENHBG001222.
InParanoidP10518.
KOK01698.
OMAIITYFTP.
OrthoDBEOG751NFP.
PhylomeDBP10518.
TreeFamTF300665.

Enzyme and pathway databases

UniPathwayUPA00251; UER00318.

Gene expression databases

ArrayExpressP10518.
BgeeP10518.
CleanExMM_ALAD.
GenevestigatorP10518.

Family and domain databases

Gene3D3.20.20.70. 1 hit.
InterProIPR013785. Aldolase_TIM.
IPR001731. Porphobilinogen_synth.
[Graphical view]
PANTHERPTHR11458. PTHR11458. 1 hit.
PfamPF00490. ALAD. 1 hit.
[Graphical view]
PIRSFPIRSF001415. Porphbilin_synth. 1 hit.
PRINTSPR00144. DALDHYDRTASE.
SMARTSM01004. ALAD. 1 hit.
[Graphical view]
PROSITEPS00169. D_ALA_DEHYDRATASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP10518.
NextBio291138.
PROP10518.
SOURCESearch...

Entry information

Entry nameHEM2_MOUSE
AccessionPrimary (citable) accession number: P10518
Secondary accession number(s): Q3THV6
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: April 16, 2014
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot