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P13716

- HEM2_HUMAN

UniProt

P13716 - HEM2_HUMAN

Protein

Delta-aminolevulinic acid dehydratase

Gene

ALAD

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 166 (01 Oct 2014)
      Sequence version 1 (01 Jan 1990)
      Previous versions | rss
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    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.2 Publications

    Catalytic activityi

    2 5-aminolevulinate = porphobilinogen + 2 H2O.3 Publications

    Cofactori

    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.1 Publication

    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.3 Publications

    Kineticsi

    1. KM=0.09 mM for 5-aminolevulinate at pH 71 Publication

    Vmax=43 µmol/h/mg enzyme at pH 71 Publication

    pH dependencei

    Optimum pH is 6.8-7.3.1 Publication

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi122 – 1221Zinc 1; catalytic
    Metal bindingi124 – 1241Zinc 1; catalytic
    Metal bindingi131 – 1311Zinc 2
    Metal bindingi132 – 1321Zinc 1; catalytic
    Active sitei199 – 1991Schiff-base intermediate with substrate1 Publication
    Binding sitei209 – 2091Substrate 1
    Binding sitei221 – 2211Substrate 1
    Metal bindingi223 – 2231Zinc 2
    Active sitei252 – 2521Schiff-base intermediate with substrate1 Publication
    Binding sitei279 – 2791Substrate 2
    Binding sitei318 – 3181Substrate 2

    GO - Molecular functioni

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

    GO - Biological processi

    1. cellular response to interleukin-4 Source: Ensembl
    2. heme biosynthetic process Source: UniProtKB
    3. porphyrin-containing compound metabolic process Source: Reactome
    4. protein homooligomerization Source: UniProtKB
    5. protoporphyrinogen IX biosynthetic process Source: UniProtKB-UniPathway
    6. small molecule metabolic process Source: Reactome

    Keywords - Molecular functioni

    Lyase

    Keywords - Biological processi

    Heme biosynthesis, Porphyrin biosynthesis

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    BioCyciMetaCyc:HS07501-MONOMER.
    ReactomeiREACT_9465. 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
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 9

    Organism-specific databases

    HGNCiHGNC:395. ALAD.

    Subcellular locationi

    GO - Cellular componenti

    1. cytosol Source: Reactome
    2. extracellular vesicular exosome Source: UniProt
    3. nucleus Source: UniProt

    Pathology & Biotechi

    Involvement in diseasei

    Acute hepatic porphyria (AHEPP) [MIM:612740]: A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. AHP is characterized by attacks of gastrointestinal disturbances, abdominal colic, paralyses and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors.4 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti133 – 1331G → R in AHEPP; mixture of about 50% hexamer and 50% octamer; about 10% residual activity. 1 Publication
    VAR_003634
    Natural varianti153 – 1531V → M in AHEPP; about 95% octamer; about 40% residual activity. 1 Publication
    VAR_020974
    Natural varianti240 – 2401R → W in AHEPP; mixture of about 80% hexamer and 20% octamer; about 4% residual activity. 2 Publications
    VAR_003635
    Natural varianti274 – 2741A → T in AHEPP; mixture of about 14% hexamer and 86% octamer; about 20% enzyme residual activity. 2 Publications
    VAR_003636
    Natural varianti275 – 2751V → M in AHEPP; mainly octamer; reduced activity. 1 Publication
    VAR_003637

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi122 – 1221C → A: Reduces enzyme activity about 1000000-fold; when associated with A-124 and A-132. 1 Publication
    Mutagenesisi124 – 1241C → A: Reduces enzyme activity about 1000000-fold; when associated with A-122 and A-132. 1 Publication
    Mutagenesisi131 – 1311H → A: No effect on catalytic activity; when associated with A-223. 1 Publication
    Mutagenesisi132 – 1321C → A: Reduces enzyme activity about 1000000-fold; when associated with A-122 and A-124. 1 Publication
    Mutagenesisi223 – 2231C → A: No effect on catalytic activity; when associated with A-131. 1 Publication

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi612740. phenotype.
    Orphaneti100924. Porphyria due to ALA dehydratase deficiency.
    PharmGKBiPA24687.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 330330Delta-aminolevulinic acid dehydratasePRO_0000140526Add
    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

    MaxQBiP13716.
    PaxDbiP13716.
    PRIDEiP13716.

    2D gel databases

    OGPiP13716.
    REPRODUCTION-2DPAGEP13716.
    SWISS-2DPAGEP13716.

    PTM databases

    PhosphoSiteiP13716.

    Expressioni

    Gene expression databases

    ArrayExpressiP13716.
    BgeeiP13716.
    CleanExiHS_ALAD.
    GenevestigatoriP13716.

    Organism-specific databases

    HPAiHPA021023.
    HPA022124.

    Interactioni

    Subunit structurei

    Homooctamer; active form. Homohexamer; low activity form.3 Publications

    Protein-protein interaction databases

    BioGridi106712. 18 interactions.
    STRINGi9606.ENSP00000386284.

    Structurei

    Secondary structure

    1
    330
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi8 – 103
    Helixi14 – 207
    Turni21 – 244
    Helixi28 – 303
    Beta strandi31 – 377
    Beta strandi44 – 463
    Beta strandi48 – 503
    Beta strandi54 – 563
    Helixi58 – 7114
    Beta strandi75 – 806
    Beta strandi83 – 853
    Beta strandi94 – 985
    Helixi100 – 11112
    Beta strandi115 – 1217
    Beta strandi123 – 1264
    Helixi141 – 16020
    Beta strandi163 – 1675
    Helixi174 – 18411
    Turni188 – 1903
    Beta strandi192 – 1943
    Beta strandi198 – 2003
    Helixi203 – 2053
    Helixi206 – 2105
    Helixi221 – 2233
    Helixi231 – 24313
    Beta strandi247 – 2537
    Helixi255 – 2573
    Helixi258 – 26710
    Beta strandi273 – 2775
    Helixi279 – 29012
    Helixi296 – 31015
    Beta strandi313 – 3175
    Helixi320 – 3267
    Turni327 – 3293

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1E51X-ray2.83A/B1-330[»]
    1PV8X-ray2.20A/B1-330[»]
    ProteinModelPortaliP13716.
    SMRiP13716. Positions 1-328.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP13716.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the ALADH family.Curated

    Phylogenomic databases

    eggNOGiCOG0113.
    HOGENOMiHOG000020323.
    HOVERGENiHBG001222.
    KOiK01698.
    OMAiDHPTACY.
    OrthoDBiEOG751NFP.
    PhylomeDBiP13716.
    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]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P13716-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MQPQSVLHSG YFHPLLRAWQ TATTTLNASN LIYPIFVTDV PDDIQPITSL    50
    PGVARYGVKR LEEMLRPLVE EGLRCVLIFG VPSRVPKDER GSAADSEESP 100
    AIEAIHLLRK TFPNLLVACD VCLCPYTSHG HCGLLSENGA FRAEESRQRL 150
    AEVALAYAKA GCQVVAPSDM MDGRVEAIKE ALMAHGLGNR VSVMSYSAKF 200
    ASCFYGPFRD AAKSSPAFGD RRCYQLPPGA RGLALRAVDR DVREGADMLM 250
    VKPGMPYLDI VREVKDKHPD LPLAVYHVSG EFAMLWHGAQ AGAFDLKAAV 300
    LEAMTAFRRA GADIIITYYT PQLLQWLKEE 330
    Length:330
    Mass (Da):36,295
    Last modified:January 1, 1990 - v1
    Checksum:iE005F3055F6D9403
    GO
    Isoform 2 (identifier: P13716-2) [UniParc]FASTAAdd to Basket

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

    Show »
    Length:359
    Mass (Da):39,034
    Checksum:i4AD5F3B2570ACD81
    GO

    Sequence cautioni

    The sequence AAH00977.3 differs from that shown. Reason: Erroneous initiation.

    Polymorphismi

    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.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti12 – 121F → L in an asymptomatic patient with ALAD deficiency; hexamer with almost no residual activity; also found in a hereditary coproporphyria patient carrying the R-279 mutation in CPOX. 2 Publications
    VAR_020973
    Natural varianti59 – 591K → N in allele ALAD*2; 10% of population; fully active octamer. 2 Publications
    Corresponds to variant rs1800435 [ dbSNP | Ensembl ].
    VAR_003633
    Natural varianti133 – 1331G → R in AHEPP; mixture of about 50% hexamer and 50% octamer; about 10% residual activity. 1 Publication
    VAR_003634
    Natural varianti153 – 1531V → M in AHEPP; about 95% octamer; about 40% residual activity. 1 Publication
    VAR_020974
    Natural varianti240 – 2401R → W in AHEPP; mixture of about 80% hexamer and 20% octamer; about 4% residual activity. 2 Publications
    VAR_003635
    Natural varianti274 – 2741A → T in AHEPP; mixture of about 14% hexamer and 86% octamer; about 20% enzyme residual activity. 2 Publications
    VAR_003636
    Natural varianti275 – 2751V → M in AHEPP; mainly octamer; reduced activity. 1 Publication
    VAR_003637

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 3838MQPQS…PIFVT → MPPTSSTPSLSRPGLGQAGK PDTGSHPPPTISTSIFLSCF PTIPLSRPRTTGPSHSYQSI SHPRSCR in isoform 2. 1 PublicationVSP_037866Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS6794.2. [P13716-1]
    PIRiA26478.
    RefSeqiNP_000022.3. NM_000031.5. [P13716-1]
    XP_005251856.1. XM_005251799.1. [P13716-2]
    UniGeneiHs.1227.

    Genome annotation databases

    EnsembliENST00000409155; ENSP00000386284; ENSG00000148218. [P13716-1]
    GeneIDi210.
    KEGGihsa:210.
    UCSCiuc004bhl.4. human. [P13716-2]
    uc011lxf.2. human. [P13716-1]

    Polymorphism databases

    DMDMi122833.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSi CCDS6794.2. [P13716-1 ]
    PIRi A26478.
    RefSeqi NP_000022.3. NM_000031.5. [P13716-1 ]
    XP_005251856.1. XM_005251799.1. [P13716-2 ]
    UniGenei Hs.1227.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1E51 X-ray 2.83 A/B 1-330 [» ]
    1PV8 X-ray 2.20 A/B 1-330 [» ]
    ProteinModelPortali P13716.
    SMRi P13716. Positions 1-328.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 106712. 18 interactions.
    STRINGi 9606.ENSP00000386284.

    Chemistry

    ChEMBLi CHEMBL3126.
    DrugBanki DB00855. Aminolevulinic acid.

    PTM databases

    PhosphoSitei P13716.

    Polymorphism databases

    DMDMi 122833.

    2D gel databases

    OGPi P13716.
    REPRODUCTION-2DPAGE P13716.
    SWISS-2DPAGE P13716.

    Proteomic databases

    MaxQBi P13716.
    PaxDbi P13716.
    PRIDEi P13716.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000409155 ; ENSP00000386284 ; ENSG00000148218 . [P13716-1 ]
    GeneIDi 210.
    KEGGi hsa:210.
    UCSCi uc004bhl.4. human. [P13716-2 ]
    uc011lxf.2. human. [P13716-1 ]

    Organism-specific databases

    CTDi 210.
    GeneCardsi GC09M116148.
    HGNCi HGNC:395. ALAD.
    HPAi HPA021023.
    HPA022124.
    MIMi 125270. gene.
    612740. phenotype.
    neXtProti NX_P13716.
    Orphaneti 100924. Porphyria due to ALA dehydratase deficiency.
    PharmGKBi PA24687.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0113.
    HOGENOMi HOG000020323.
    HOVERGENi HBG001222.
    KOi K01698.
    OMAi DHPTACY.
    OrthoDBi EOG751NFP.
    PhylomeDBi P13716.
    TreeFami TF300665.

    Enzyme and pathway databases

    UniPathwayi UPA00251 ; UER00318 .
    BioCyci MetaCyc:HS07501-MONOMER.
    Reactomei REACT_9465. Heme biosynthesis.

    Miscellaneous databases

    ChiTaRSi ALAD. human.
    EvolutionaryTracei P13716.
    GeneWikii ALAD.
    GenomeRNAii 210.
    NextBioi 840.
    PROi P13716.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P13716.
    Bgeei P13716.
    CleanExi HS_ALAD.
    Genevestigatori P13716.

    Family and domain databases

    Gene3Di 3.20.20.70. 1 hit.
    InterProi IPR013785. Aldolase_TIM.
    IPR001731. Porphobilinogen_synth.
    [Graphical view ]
    PANTHERi PTHR11458. PTHR11458. 1 hit.
    Pfami PF00490. ALAD. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF001415. Porphbilin_synth. 1 hit.
    PRINTSi PR00144. DALDHYDRTASE.
    SMARTi SM01004. ALAD. 1 hit.
    [Graphical view ]
    PROSITEi PS00169. D_ALA_DEHYDRATASE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS AHEPP 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.
      , 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] [Europe PMC] [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.
      , 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 1-17.
      Tissue: Platelet.
    9. "Identification of lysine at the active site of human 5-aminolevulinate dehydratase."
      Gibbs P.N.B., Jordan P.M.
      Biochem. J. 236:447-451(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACTIVE SITE.
    10. "The molecular mechanism of lead inhibition of human porphobilinogen synthase."
      Jaffe E.K., Martins J., Li J., Kervinen J., Dunbrack R.L. Jr.
      J. Biol. Chem. 276:1531-1537(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME REGULATION, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF CYS-122; CYS-124; HIS-131; CYS-132 AND CYS-223.
    11. Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, ENZYME REGULATION.
    12. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    13. "The crystal structure of human Ala-dehydratase."
      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) IN COMPLEX WITH PORPHOBILINOGEN AND ZINC IONS.
    14. "Control of tetrapyrrole biosynthesis by alternate quaternary forms of porphobilinogen synthase."
      Breinig S., Kervinen J., Stith L., Wasson A.S., Fairman R., Wlodawer A., Zdanov A., Jaffe E.K.
      Nat. Struct. Biol. 10:757-763(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF MUTANT LEU-12 IN COMPLEX WITH SUBSTRATE ANALOG, SUBUNIT, IDENTIFICATION BY MASS SPECTROMETRY, CATALYTIC ACTIVITY, ENZYME REGULATION.
    15. "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] [Europe PMC] [Abstract]
      Cited for: VARIANT ASN-59.
    16. "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] [Europe PMC] [Abstract]
      Cited for: VARIANTS AHEPP ARG-133 AND MET-275.
    17. "Cloning and expression of the defective genes in delta-aminolevulinate dehydratase porphyria: compound heterozygosity in this hereditary liver disease."
      Sassa S., Ishida N., Fujita H., Fukuda Y., Noguchi T., Doss M., Kappas A.
      Trans. Assoc. Am. Physicians 105:250-259(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS AHEPP TRP-240 AND THR-274, CHARACTERIZATION OF VARIANTS AHEPP TRP-240 AND THR-274.
    18. "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] [Europe PMC] [Abstract]
      Cited for: VARIANT LEU-12, CHARACTERIZATION OF VARIANT LEU-12.
    19. "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] [Europe PMC] [Abstract]
      Cited for: VARIANT AHEPP MET-153, CHARACTERIZATION OF VARIANT AHEPP MET-153.
    20. "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] [Europe PMC] [Abstract]
      Cited for: VARIANT LEU-12.
    21. "ALAD porphyria is a conformational disease."
      Jaffe E.K., Stith L.
      Am. J. Hum. Genet. 80:329-337(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION OF VARIANTS AHEPP ARG-133; MET-153; TRP-240; THR-274 AND MET-275, CHARACTERIZATION OF VARIANTS LEU-12 AND ASN-59.

    Entry informationi

    Entry nameiHEM2_HUMAN
    AccessioniPrimary (citable) accession number: P13716
    Secondary accession number(s): A8K375
    , B2R6F2, Q16870, Q16871, Q9BVQ9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 1, 1990
    Last sequence update: January 1, 1990
    Last modified: October 1, 2014
    This is version 166 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Allosteric enzyme, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 9
      Human chromosome 9: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3