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Reviewed, UniProtKB/Swiss-Prot P13716 (HEM2_HUMAN)

Last modified November 3, 2009. Version 116. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length330 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Catalytic activity

2 5-aminolevulinate = porphobilinogen + 2 H2O.

Cofactor

Zinc.

Pathway

Porphyrin metabolism; protoporphyrin-IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 1/4.

Subunit structure

Homooctamer.

Polymorphism

There are two common alleles of ALAD. Individuals heterozygous or homozygous for ALAD*2 Asn-59 have significantly higher blood lead levels than do ALAD*1 Lys-59 homozygotes when exposed to environmental lead.

Involvement in disease

Defects in ALAD are the cause of acute hepatic porphyria (AHP) [MIM:125270]. AHP is a form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme. AHP is characterized by attacks of gastrointestinal disturbances, abdominal colic, paralysis, and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors. Ref.3 Ref.13 Ref.15

Sequence similarities

Belongs to the ALADH family.

Ontologies

Keywords
   Biological processHeme biosynthesis
Porphyrin biosynthesis
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   LigandMetal-binding
Zinc
   Molecular functionLyase
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Gene Ontology (GO)
   Biological processheme biosynthetic process

Traceable author statement. Source: ProtInc

   Cellular componentcytosol

Inferred from Experiment. Source: Reactome

   Molecular functionporphobilinogen synthase activity Ref.1

Traceable author statement. Source: ProtInc

zinc ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P13716-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P13716-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-38: MQPQSVLHSG...SNLIYPIFVT → MPPTSSTPSL...QSISHPRSCR

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 330330Delta-aminolevulinic acid dehydratase
PRO_0000140526

Sites

Active site2521 Ref.9
Metal binding1221Zinc; catalytic
Metal binding1241Zinc; catalytic
Metal binding1321Zinc; catalytic

Natural variations

Alternative sequence1 – 3838MQPQS…PIFVT → MPPTSSTPSLSRPGLGQAGK PDTGSHPPPTISTSIFLSCF PTIPLSRPRTTGPSHSYQSI SHPRSCR in isoform 2.
VSP_037866
Natural variant121F → L in an asymptomatic patient with ALAD deficiency; significant reduction of activity; also found in a hereditary coproporphyria patient carrying the R-279 mutation in CPOX. Ref.14 Ref.16
VAR_020973
Natural variant591K → N in allele ALAD*2; 10% of population. dbSNP rs1800435. Ref.5 Ref.12
VAR_003633
Natural variant1331G → R in AHP. Ref.13
VAR_003634
Natural variant1531V → M in AHP; reduction of activity. Ref.15
VAR_020974
Natural variant2401R → W in AHP. Ref.3
VAR_003635
Natural variant2741A → T in AHP. Ref.3
VAR_003636
Natural variant2751V → M in AHP. Ref.13
VAR_003637

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 1, 1990. Version 1.
Checksum: E005F3055F6D9403

FASTA33036,295
        10         20         30         40         50         60 
MQPQSVLHSG YFHPLLRAWQ TATTTLNASN LIYPIFVTDV PDDIQPITSL PGVARYGVKR 

        70         80         90        100        110        120 
LEEMLRPLVE EGLRCVLIFG VPSRVPKDER GSAADSEESP AIEAIHLLRK TFPNLLVACD 

       130        140        150        160        170        180 
VCLCPYTSHG HCGLLSENGA FRAEESRQRL AEVALAYAKA GCQVVAPSDM MDGRVEAIKE 

       190        200        210        220        230        240 
ALMAHGLGNR VSVMSYSAKF ASCFYGPFRD AAKSSPAFGD RRCYQLPPGA RGLALRAVDR 

       250        260        270        280        290        300 
DVREGADMLM VKPGMPYLDI VREVKDKHPD LPLAVYHVSG EFAMLWHGAQ AGAFDLKAAV 

       310        320        330 
LEAMTAFRRA GADIIITYYT PQLLQWLKEE 

« Hide

Isoform 2.

Checksum: 4AD5F3B2570ACD81
Show »

FASTA35939,034

References

« Hide 'large scale' references
[1]"Human delta-aminolevulinate dehydratase: nucleotide sequence of a full-length cDNA clone."
Wetmur J.G., Bishop D.F., Cantelmo C., Desnick R.J.
Proc. Natl. Acad. Sci. U.S.A. 83:7703-7707(1986) [PubMed: 3463993] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"RsaI polymorphism in the human delta-aminolevulinate dehydratase gene at 9q34."
Wetmur J.G.
Nucleic Acids Res. 19:4307-4307(1991) [PubMed: 1678509] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Liver.
[3]"Cloning and expression of the defective genes from a patient with delta-aminolevulinate dehydratase porphyria."
Ishida N., Fujita H., Fukuda Y., Noguchi T., Doss M., Kappas A., Sassa S.
J. Clin. Invest. 89:1431-1437(1992) [PubMed: 1569184] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS AHP TRP-240 AND THR-274.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Brain and Tongue.
[5]NIEHS SNPs program
Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ASN-59.
[6]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed: 15164053] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Placenta.
[8]"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides."
Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J.
Nat. Biotechnol. 21:566-569(2003) [PubMed: 12665801] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1-17.
Tissue: Platelet.
[9]"Identification of lysine at the active site of human 5-aminolaevulinate dehydratase."
Gibbs P.N.B., Jordan P.M.
Biochem. J. 236:447-451(1986) [PubMed: 3092810] [Abstract]
Cited for: ACTIVE SITE.
[10]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[11]Mills-Davies N.L., Thompson D., Cooper J.B., Shoolingin-Jordan P.M.
Submitted (OCT-1998) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.83 ANGSTROMS).
[12]"Molecular characterization of the human delta-aminolevulinate dehydratase 2 (ALAD2) allele: implications for molecular screening of individuals for genetic susceptibility to lead poisoning."
Wetmur J.G., Kaya A.H., Plewinska M., Desnick R.J.
Am. J. Hum. Genet. 49:757-763(1991) [PubMed: 1716854] [Abstract]
Cited for: VARIANT ASN-59.
[13]"Delta-aminolevulinate dehydratase deficient porphyria: identification of the molecular lesions in a severely affected homozygote."
Plewinska M., Thunell S., Holmberg L., Wetmur J.G., Desnick R.J.
Am. J. Hum. Genet. 49:167-174(1991) [PubMed: 2063868] [Abstract]
Cited for: VARIANTS AHP ARG-133 AND MET-275.
[14]"A novel mutation of delta-aminolaevulinate dehydratase in a healthy child with 12% erythrocyte enzyme activity."
Akagi R., Yasui Y., Harper P., Sassa S.
Br. J. Haematol. 106:931-937(1999) [PubMed: 10519994] [Abstract]
Cited for: VARIANT LEU-12, CHARACTERIZATION OF VARIANT LEU-12.
[15]"Novel molecular defects of the delta-aminolevulinate dehydratase gene in a patient with inherited acute hepatic porphyria."
Akagi R., Shimizu R., Furuyama K., Doss M.O., Sassa S.
Hepatology 31:704-708(2000) [PubMed: 10706561] [Abstract]
Cited for: VARIANT AHP MET-153, CHARACTERIZATION OF VARIANT AHP MET-153.
[16]"Dual gene defects involving delta-aminolaevulinate dehydratase and coproporphyrinogen oxidase in a porphyria patient."
Akagi R., Inoue R., Muranaka S., Tahara T., Taketani S., Anderson K.E., Phillips J.D., Sassa S.
Br. J. Haematol. 132:237-243(2006) [PubMed: 16398658] [Abstract]
Cited for: VARIANT LEU-12.
+Additional computationally mapped references.

Cross-references

Sequence databases

M13928 mRNA. Translation: AAA51687.1.
X64467 Genomic DNA. Translation: CAA45796.1.
S99468 mRNA. Translation: AAC60581.1.
S99471 mRNA. Translation: AAC60582.1.
AK290490 mRNA. Translation: BAF83179.1.
AK312552 mRNA. Translation: BAG35449.1.
AY319481 Genomic DNA. Translation: AAP72012.1.
AL137066 Genomic DNA. Translation: CAH70099.3.
BC000977 mRNA. Translation: AAH00977.3. Different initiation.
IPIIPI00442121.
IPI00937974.
PIRA26478.
RefSeqNP_000022.3.
UniGeneHs.1227

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1E51X-ray2.83A/B1-330[»]
1PV8X-ray2.20A/B1-330[»]
ModBaseSearch...

Protein-protein interaction databases

STRINGP13716.

PTM databases

PhosphoSiteP13716.

2-D gel databases

SWISS-2DPAGEP13716.
OGPP13716.
REPRODUCTION-2DPAGEP13716.

Proteomic databases

PRIDEP13716.

Genome annotation databases

EnsemblENST00000277315; ENSP00000277315; ENSG00000148218; Homo sapiens. [Genome view]
ENST00000374173; ENSP00000363288; ENSG00000148218; Homo sapiens. [Genome view]
ENST00000409155; ENSP00000386284; ENSG00000148218; Homo sapiens. [Genome view]
ENST00000445750; ENSP00000398438; ENSG00000148218; Homo sapiens. [Genome view]
ENST00000448137; ENSP00000392748; ENSG00000148218; Homo sapiens. [Genome view]
ENST00000452726; ENSP00000415737; ENSG00000148218; Homo sapiens. [Genome view]
GeneID210.
KEGGhsa:210.
NMPDRfig|9606.3.peg.31768.
UCSCuc004bhm.2. human.

Organism-specific databases

CTD210.
GeneCardsGC09M115188.
HGNCHGNC:395. ALAD.
HPAHPA021023.
HPA022124.
MIM125270. gene+phenotype.
Orphanet95157. Porphyria, acute hepatic.
PharmGKBPA24687.
GenAtlasSearch...

Phylogenomic databases

HOVERGENP13716.

Enzyme and pathway databases

BRENDA4.2.1.24. 247.
ReactomeREACT_9431. Metabolism of porphyrins.

Gene expression databases

ArrayExpressP13716.
BgeeP13716.
CleanExHS_ALAD.
GenevestigatorP13716.
GermOnlineENSG00000148218. Homo sapiens.

Family and domain databases

InterProIPR001731. 4pyrrol_synth_porphobiln_synth.
IPR013785. Aldolase_TIM.
[Graphical view]
Gene3DG3DSA:3.20.20.70. Aldolase_TIM. 1 hit.
PANTHERPTHR11458. AlaD_dehydratase. 1 hit.
PfamPF00490. ALAD. 1 hit.
[Graphical view]
PIRSFPIRSF001415. Porphbilin_synth. 1 hit.
PRINTSPR00144. DALDHYDRTASE.
ProDomPD002304. AlaD_dehydratase. 1 hit.
[Graphical view] [Entries sharing at least one domain]
PROSITEPS00169. D_ALA_DEHYDRATASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00855. Aminolevulinic acid.
NextBio840.
SOURCESearch...

Entry information

Entry nameHEM2_HUMAN
AccessionPrimary (citable) accession number: P13716
Secondary accession number(s): A8K375 expand/collapse secondary AC list , B2R6F2, Q16870, Q16871, Q9BVQ9
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 1, 1990
Last modified: November 3, 2009
This is version 116 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents