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P22557

- HEM0_HUMAN

UniProt

P22557 - HEM0_HUMAN

Protein

5-aminolevulinate synthase, erythroid-specific, mitochondrial

Gene

ALAS2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 161 (01 Oct 2014)
      Sequence version 2 (23 Jan 2002)
      Previous versions | rss
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    Functioni

    Catalytic activityi

    Succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2.1 Publication

    Cofactori

    Pyridoxal phosphate.

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei163 – 1631SubstrateBy similarity
    Binding sitei280 – 2801SubstrateBy similarity
    Binding sitei299 – 2991SubstrateBy similarity
    Binding sitei332 – 3321Pyridoxal phosphateBy similarity
    Binding sitei360 – 3601Pyridoxal phosphateBy similarity
    Binding sitei388 – 3881Pyridoxal phosphateBy similarity
    Active sitei391 – 3911By similarity
    Binding sitei420 – 4201Pyridoxal phosphateBy similarity
    Binding sitei421 – 4211Pyridoxal phosphateBy similarity
    Binding sitei508 – 5081SubstrateBy similarity

    GO - Molecular functioni

    1. 5-aminolevulinate synthase activity Source: UniProtKB
    2. coenzyme binding Source: UniProtKB
    3. glycine binding Source: UniProtKB
    4. protein binding Source: UniProtKB
    5. pyridoxal phosphate binding Source: InterPro

    GO - Biological processi

    1. cellular iron ion homeostasis Source: UniProtKB
    2. erythrocyte differentiation Source: UniProtKB
    3. heme biosynthetic process Source: UniProtKB
    4. hemoglobin biosynthetic process Source: UniProtKB
    5. oxygen homeostasis Source: UniProtKB
    6. porphyrin-containing compound metabolic process Source: Reactome
    7. protoporphyrinogen IX biosynthetic process Source: UniProtKB-UniPathway
    8. response to hypoxia Source: UniProtKB
    9. small molecule metabolic process Source: Reactome

    Keywords - Molecular functioni

    Acyltransferase, Transferase

    Keywords - Biological processi

    Heme biosynthesis

    Keywords - Ligandi

    Pyridoxal phosphate

    Enzyme and pathway databases

    BioCyciMetaCyc:HS08311-MONOMER.
    ReactomeiREACT_9465. Heme biosynthesis.
    UniPathwayiUPA00251; UER00375.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    5-aminolevulinate synthase, erythroid-specific, mitochondrial (EC:2.3.1.37)
    Short name:
    ALAS-E
    Alternative name(s):
    5-aminolevulinic acid synthase 2
    Delta-ALA synthase 2
    Delta-aminolevulinate synthase 2
    Gene namesi
    Name:ALAS2
    Synonyms:ALASE, ASB
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome X

    Organism-specific databases

    HGNCiHGNC:397. ALAS2.

    Subcellular locationi

    Mitochondrion matrix 1 Publication

    GO - Cellular componenti

    1. mitochondrial inner membrane Source: UniProtKB
    2. mitochondrial matrix Source: Reactome
    3. mitochondrion Source: UniProtKB

    Keywords - Cellular componenti

    Mitochondrion

    Pathology & Biotechi

    Involvement in diseasei

    Anemia, sideroblastic, X-linked (XLSA) [MIM:300751]: A form of sideroblastic anemia that shows a variable hematologic response to pharmacologic doses of pyridoxine. Sideroblastic anemia is characterized by anemia of varying severity, hypochromic peripheral erythrocytes, systemic iron overload secondary to chronic ineffective erythropoiesis, and the presence of bone marrow ringed sideroblasts. Sideroblasts are characterized by iron-loaded mitochondria clustered around the nucleus.9 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti156 – 1561K → E in XLSA; significantly reduced activity. 1 Publication
    VAR_066232
    Natural varianti159 – 1591D → Y in XLSA. 1 Publication
    VAR_018604
    Natural varianti170 – 1701R → H in XLSA; significantly increased thermosensitivity. 1 Publication
    VAR_066233
    Natural varianti199 – 1991Y → H in XLSA. 1 Publication
    VAR_012334
    Natural varianti204 – 2041R → Q in XLSA; 15% to 35% activity of wild-type. 1 Publication
    VAR_012335
    Natural varianti218 – 2181R → H in XLSA; significantly increased thermosensitivity. 1 Publication
    Corresponds to variant rs185504937 [ dbSNP | Ensembl ].
    VAR_066234
    Natural varianti242 – 2421E → K in XLSA; significantly reduced activity. 1 Publication
    VAR_066235
    Natural varianti263 – 2631D → N in XLSA; significantly reduced activity. 1 Publication
    VAR_066236
    Natural varianti339 – 3391P → L in XLSA; significantly reduced activity. 1 Publication
    VAR_066237
    Natural varianti375 – 3751R → C in XLSA; significantly reduced activity. 1 Publication
    VAR_066238
    Natural varianti388 – 3881T → S in XLSA. 1 Publication
    VAR_000562
    Natural varianti411 – 4111R → C in XLSA; 12% to 25% activity of wild-type. 2 Publications
    VAR_000563
    Natural varianti411 – 4111R → H in XLSA; significantly reduced activity. 1 Publication
    VAR_066239
    Natural varianti448 – 4481R → Q in XLSA. 1 Publication
    VAR_012336
    Natural varianti452 – 4521R → C in XLSA. 2 Publications
    VAR_012337
    Natural varianti452 – 4521R → G in XLSA; does not affect activity. 1 Publication
    VAR_066240
    Natural varianti452 – 4521R → H in XLSA. 1 Publication
    VAR_066241
    Natural varianti476 – 4761I → N in XLSA. 1 Publication
    VAR_000564
    Natural varianti560 – 5601R → H in XLSA. 1 Publication
    VAR_018605
    Natural varianti572 – 5721R → H in XLSA; does not affect activity. 1 Publication
    VAR_066243
    Erythropoietic protoporphyria, X-linked dominant (XLDPT) [MIM:300752]: 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. XLDPT is characterized biochemically by a high proportion of zinc-protoporphyrin in erythrocytes, in which a mismatch between protoporphyrin production and the heme requirement of differentiating erythroid cells leads to overproduction of protoporphyrin in amounts sufficient to cause photosensitivity and liver disease.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry. Gain of function mutations in ALS2 are responsible for XLDPT, but they can also be a possible aggravating factor in congenital erythropoietic porphyria and other erythropoietic disorders caused by mutations in other genes (PubMed:21309041).1 Publication

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi300751. phenotype.
    300752. phenotype.
    Orphaneti79278. Erythropoietic protoporphyria.
    75563. X-linked sideroblastic anemia.
    PharmGKBiPA24689.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 4949Mitochondrion1 PublicationAdd
    BLAST
    Chaini50 – 5875385-aminolevulinate synthase, erythroid-specific, mitochondrialPRO_0000001223Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei391 – 3911N6-(pyridoxal phosphate)lysineCurated

    Proteomic databases

    MaxQBiP22557.
    PaxDbiP22557.
    PRIDEiP22557.

    PTM databases

    PhosphoSiteiP22557.

    Expressioni

    Tissue specificityi

    Erythroid specific.

    Gene expression databases

    ArrayExpressiP22557.
    BgeeiP22557.
    CleanExiHS_ALAS2.
    GenevestigatoriP22557.

    Organism-specific databases

    HPAiHPA001638.

    Interactioni

    Subunit structurei

    Homodimer. Interacts with SUCLA2.1 Publication

    Protein-protein interaction databases

    BioGridi106714. 2 interactions.
    IntActiP22557. 1 interaction.
    STRINGi9606.ENSP00000332369.

    Structurei

    3D structure databases

    ProteinModelPortaliP22557.
    SMRiP22557. Positions 1-49, 151-540.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiCOG0156.
    HOGENOMiHOG000221020.
    HOVERGENiHBG005954.
    InParanoidiP22557.
    KOiK00643.
    OMAiHYLQSIN.
    PhylomeDBiP22557.
    TreeFamiTF300724.

    Family and domain databases

    Gene3Di3.40.640.10. 1 hit.
    3.90.1150.10. 1 hit.
    InterProiIPR010961. 4pyrrol_synth_NH2levulA_synth.
    IPR015118. 5aminolev_synth_preseq.
    IPR001917. Aminotrans_II_pyridoxalP_BS.
    IPR004839. Aminotransferase_I/II.
    IPR015424. PyrdxlP-dep_Trfase.
    IPR015421. PyrdxlP-dep_Trfase_major_sub1.
    IPR015422. PyrdxlP-dep_Trfase_major_sub2.
    [Graphical view]
    PfamiPF00155. Aminotran_1_2. 1 hit.
    PF09029. Preseq_ALAS. 1 hit.
    [Graphical view]
    SUPFAMiSSF53383. SSF53383. 1 hit.
    TIGRFAMsiTIGR01821. 5aminolev_synth. 1 hit.
    PROSITEiPS00599. AA_TRANSFER_CLASS_2. 1 hit.
    [Graphical view]

    Sequences (4)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 4 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P22557-1) [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

    MVTAAMLLQC CPVLARGPTS LLGKVVKTHQ FLFGIGRCPI LATQGPNCSQ    50
    IHLKATKAGG DSPSWAKGHC PFMLSELQDG KSKIVQKAAP EVQEDVKAFK 100
    TDLPSSLVSV SLRKPFSGPQ EQEQISGKVT HLIQNNMPGN YVFSYDQFFR 150
    DKIMEKKQDH TYRVFKTVNR WADAYPFAQH FSEASVASKD VSVWCSNDYL 200
    GMSRHPQVLQ ATQETLQRHG AGAGGTRNIS GTSKFHVELE QELAELHQKD 250
    SALLFSSCFV ANDSTLFTLA KILPGCEIYS DAGNHASMIQ GIRNSGAAKF 300
    VFRHNDPDHL KKLLEKSNPK IPKIVAFETV HSMDGAICPL EELCDVSHQY 350
    GALTFVDEVH AVGLYGSRGA GIGERDGIMH KIDIISGTLG KAFGCVGGYI 400
    ASTRDLVDMV RSYAAGFIFT TSLPPMVLSG ALESVRLLKG EEGQALRRAH 450
    QRNVKHMRQL LMDRGLPVIP CPSHIIPIRV GNAALNSKLC DLLLSKHGIY 500
    VQAINYPTVP RGEELLRLAP SPHHSPQMME DFVEKLLLAW TAVGLPLQDV 550
    SVAACNFCRR PVHFELMSEW ERSYFGNMGP QYVTTYA 587
    Length:587
    Mass (Da):64,633
    Last modified:January 23, 2002 - v2
    Checksum:iFD821BE245C440B5
    GO
    Isoform 2 (identifier: P22557-2) [UniParc]FASTAAdd to Basket

    Also known as: Delta4

    The sequence of this isoform differs from the canonical sequence as follows:
         102-138: Missing.

    Note: Constitutes 35-45% of erythrocytes ALAS2 mRNAs. Catalytic activity is 70% of isoform 1 activity.

    Show »
    Length:550
    Mass (Da):60,589
    Checksum:iBB28A593D343264F
    GO
    Isoform 3 (identifier: P22557-3) [UniParc]FASTAAdd to Basket

    Also known as: F143M

    The sequence of this isoform differs from the canonical sequence as follows:
         1-142: Missing.
         143-143: F → M

    Note: Catalytic activity is 80% of isoform 1 activity.

    Show »
    Length:445
    Mass (Da):49,395
    Checksum:i3304747E4DE0CC2E
    GO
    Isoform 4 (identifier: P22557-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-1: M → MRGGEVALGWNKKKRLFCEDFRFKM
         102-138: Missing.

    Show »
    Length:574
    Mass (Da):63,487
    Checksum:i7F5E13D5F36738CD
    GO

    Sequence cautioni

    The sequence CAA39795.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti182 – 1821S → F in CAA39795. (PubMed:2263504)Curated
    Sequence conflicti221 – 2211A → V in AAH30230. (PubMed:15489334)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti156 – 1561K → E in XLSA; significantly reduced activity. 1 Publication
    VAR_066232
    Natural varianti159 – 1591D → Y in XLSA. 1 Publication
    VAR_018604
    Natural varianti170 – 1701R → H in XLSA; significantly increased thermosensitivity. 1 Publication
    VAR_066233
    Natural varianti199 – 1991Y → H in XLSA. 1 Publication
    VAR_012334
    Natural varianti204 – 2041R → Q in XLSA; 15% to 35% activity of wild-type. 1 Publication
    VAR_012335
    Natural varianti218 – 2181R → H in XLSA; significantly increased thermosensitivity. 1 Publication
    Corresponds to variant rs185504937 [ dbSNP | Ensembl ].
    VAR_066234
    Natural varianti242 – 2421E → K in XLSA; significantly reduced activity. 1 Publication
    VAR_066235
    Natural varianti263 – 2631D → N in XLSA; significantly reduced activity. 1 Publication
    VAR_066236
    Natural varianti339 – 3391P → L in XLSA; significantly reduced activity. 1 Publication
    VAR_066237
    Natural varianti375 – 3751R → C in XLSA; significantly reduced activity. 1 Publication
    VAR_066238
    Natural varianti388 – 3881T → S in XLSA. 1 Publication
    VAR_000562
    Natural varianti411 – 4111R → C in XLSA; 12% to 25% activity of wild-type. 2 Publications
    VAR_000563
    Natural varianti411 – 4111R → H in XLSA; significantly reduced activity. 1 Publication
    VAR_066239
    Natural varianti448 – 4481R → Q in XLSA. 1 Publication
    VAR_012336
    Natural varianti452 – 4521R → C in XLSA. 2 Publications
    VAR_012337
    Natural varianti452 – 4521R → G in XLSA; does not affect activity. 1 Publication
    VAR_066240
    Natural varianti452 – 4521R → H in XLSA. 1 Publication
    VAR_066241
    Natural varianti476 – 4761I → N in XLSA. 1 Publication
    VAR_000564
    Natural varianti520 – 5201P → L.1 Publication
    Corresponds to variant rs201062903 [ dbSNP | Ensembl ].
    VAR_066242
    Natural varianti560 – 5601R → H in XLSA. 1 Publication
    VAR_018605
    Natural varianti572 – 5721R → H in XLSA; does not affect activity. 1 Publication
    VAR_066243
    Natural varianti586 – 5861Y → F Rare variant found in a congenital erythropoietic porphyria patient that also carries UROS mutations R-73R and Q-248; increased enzyme activity. 1 Publication
    Corresponds to variant rs139596860 [ dbSNP | Ensembl ].
    VAR_066244

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 142142Missing in isoform 3. CuratedVSP_042851Add
    BLAST
    Alternative sequencei1 – 11M → MRGGEVALGWNKKKRLFCED FRFKM in isoform 4. 1 PublicationVSP_047330
    Alternative sequencei102 – 13837Missing in isoform 2 and isoform 4. 2 PublicationsVSP_042852Add
    BLAST
    Alternative sequencei143 – 1431F → M in isoform 3. CuratedVSP_042853

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X56352 mRNA. Translation: CAA39795.1. Different initiation.
    X60364 mRNA. Translation: CAA42916.1.
    AF068624 Genomic DNA. Translation: AAC39838.1.
    AK290565 mRNA. Translation: BAF83254.1.
    AK291589 mRNA. Translation: BAF84278.1.
    AK313118 mRNA. Translation: BAG35939.1.
    Z83821 Genomic DNA. No translation available.
    AL020991 Genomic DNA. Translation: CAA15886.1.
    AL020991 Genomic DNA. Translation: CAX15017.1.
    CH471154 Genomic DNA. Translation: EAW93211.1.
    CH471154 Genomic DNA. Translation: EAW93213.1.
    BC030230 mRNA. Translation: AAH30230.2.
    CCDSiCCDS14366.1. [P22557-1]
    CCDS35303.1. [P22557-2]
    CCDS43960.1. [P22557-4]
    PIRiS16347. SYHUAE.
    RefSeqiNP_000023.2. NM_000032.4. [P22557-1]
    NP_001033056.1. NM_001037967.3. [P22557-2]
    NP_001033057.1. NM_001037968.3. [P22557-4]
    UniGeneiHs.522666.
    Hs.555936.

    Genome annotation databases

    EnsembliENST00000330807; ENSP00000332369; ENSG00000158578. [P22557-1]
    ENST00000335854; ENSP00000337131; ENSG00000158578. [P22557-2]
    ENST00000396198; ENSP00000379501; ENSG00000158578. [P22557-4]
    GeneIDi212.
    KEGGihsa:212.
    UCSCiuc004dua.4. human. [P22557-1]
    uc004dub.4. human.
    uc004dud.4. human. [P22557-2]

    Polymorphism databases

    DMDMi20141346.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X56352 mRNA. Translation: CAA39795.1 . Different initiation.
    X60364 mRNA. Translation: CAA42916.1 .
    AF068624 Genomic DNA. Translation: AAC39838.1 .
    AK290565 mRNA. Translation: BAF83254.1 .
    AK291589 mRNA. Translation: BAF84278.1 .
    AK313118 mRNA. Translation: BAG35939.1 .
    Z83821 Genomic DNA. No translation available.
    AL020991 Genomic DNA. Translation: CAA15886.1 .
    AL020991 Genomic DNA. Translation: CAX15017.1 .
    CH471154 Genomic DNA. Translation: EAW93211.1 .
    CH471154 Genomic DNA. Translation: EAW93213.1 .
    BC030230 mRNA. Translation: AAH30230.2 .
    CCDSi CCDS14366.1. [P22557-1 ]
    CCDS35303.1. [P22557-2 ]
    CCDS43960.1. [P22557-4 ]
    PIRi S16347. SYHUAE.
    RefSeqi NP_000023.2. NM_000032.4. [P22557-1 ]
    NP_001033056.1. NM_001037967.3. [P22557-2 ]
    NP_001033057.1. NM_001037968.3. [P22557-4 ]
    UniGenei Hs.522666.
    Hs.555936.

    3D structure databases

    ProteinModelPortali P22557.
    SMRi P22557. Positions 1-49, 151-540.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 106714. 2 interactions.
    IntActi P22557. 1 interaction.
    STRINGi 9606.ENSP00000332369.

    Chemistry

    DrugBanki DB00145. Glycine.

    PTM databases

    PhosphoSitei P22557.

    Polymorphism databases

    DMDMi 20141346.

    Proteomic databases

    MaxQBi P22557.
    PaxDbi P22557.
    PRIDEi P22557.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000330807 ; ENSP00000332369 ; ENSG00000158578 . [P22557-1 ]
    ENST00000335854 ; ENSP00000337131 ; ENSG00000158578 . [P22557-2 ]
    ENST00000396198 ; ENSP00000379501 ; ENSG00000158578 . [P22557-4 ]
    GeneIDi 212.
    KEGGi hsa:212.
    UCSCi uc004dua.4. human. [P22557-1 ]
    uc004dub.4. human.
    uc004dud.4. human. [P22557-2 ]

    Organism-specific databases

    CTDi 212.
    GeneCardsi GC0XM055053.
    GeneReviewsi ALAS2.
    HGNCi HGNC:397. ALAS2.
    HPAi HPA001638.
    MIMi 300751. phenotype.
    300752. phenotype.
    301300. gene.
    neXtProti NX_P22557.
    Orphaneti 79278. Erythropoietic protoporphyria.
    75563. X-linked sideroblastic anemia.
    PharmGKBi PA24689.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0156.
    HOGENOMi HOG000221020.
    HOVERGENi HBG005954.
    InParanoidi P22557.
    KOi K00643.
    OMAi HYLQSIN.
    PhylomeDBi P22557.
    TreeFami TF300724.

    Enzyme and pathway databases

    UniPathwayi UPA00251 ; UER00375 .
    BioCyci MetaCyc:HS08311-MONOMER.
    Reactomei REACT_9465. Heme biosynthesis.

    Miscellaneous databases

    ChiTaRSi ALAS2. human.
    GeneWikii ALAS2.
    GenomeRNAii 212.
    NextBioi 852.
    PROi P22557.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P22557.
    Bgeei P22557.
    CleanExi HS_ALAS2.
    Genevestigatori P22557.

    Family and domain databases

    Gene3Di 3.40.640.10. 1 hit.
    3.90.1150.10. 1 hit.
    InterProi IPR010961. 4pyrrol_synth_NH2levulA_synth.
    IPR015118. 5aminolev_synth_preseq.
    IPR001917. Aminotrans_II_pyridoxalP_BS.
    IPR004839. Aminotransferase_I/II.
    IPR015424. PyrdxlP-dep_Trfase.
    IPR015421. PyrdxlP-dep_Trfase_major_sub1.
    IPR015422. PyrdxlP-dep_Trfase_major_sub2.
    [Graphical view ]
    Pfami PF00155. Aminotran_1_2. 1 hit.
    PF09029. Preseq_ALAS. 1 hit.
    [Graphical view ]
    SUPFAMi SSF53383. SSF53383. 1 hit.
    TIGRFAMsi TIGR01821. 5aminolev_synth. 1 hit.
    PROSITEi PS00599. AA_TRANSFER_CLASS_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Two different genes encode delta-aminolevulinate synthase in humans: nucleotide sequences of cDNAs for the housekeeping and erythroid genes."
      Bishop D.F.
      Nucleic Acids Res. 18:7187-7188(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Liver.
    2. "Human erythroid 5-aminolevulinate synthase: promoter analysis and identification of an iron-responsive element in the mRNA."
      Cox T.C., Bawden M.J., Martin A., May B.K.
      EMBO J. 10:1891-1902(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Liver.
    3. "Identification and characterization of a conserved erythroid-specific enhancer located in intron 8 of the human 5-aminolevulinate synthase 2 gene."
      Surinya K.H., Cox T.C., May B.K.
      J. Biol. Chem. 273:16798-16809(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    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: Lung, Placenta and Umbilical cord blood.
    5. "The DNA sequence of the human X chromosome."
      Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.
      , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
      Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. 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 4).
      Tissue: Pancreas.
    8. "The major splice variant of human 5-aminolevulinate synthase-2 contributes significantly to erythroid heme biosynthesis."
      Cox T.C., Sadlon T.J., Schwarz Q.P., Matthews C.S., Wise P.D., Cox L.L., Bottomley S.S., May B.K.
      Int. J. Biochem. Cell Biol. 36:281-295(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: ALTERNATIVE SPLICING, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, TRANSIT PEPTIDE CLEAVAGE SITE, INTERACTION WITH SUCLA2.
    9. "X-linked pyridoxine-responsive sideroblastic anemia due to a Thr388-to-Ser substitution in erythroid 5-aminolevulinate synthase."
      Cox T.C., Bottomley S.S., Wiley J.S., Bawden M.J., Matthews C.S., May B.K.
      N. Engl. J. Med. 330:675-679(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT XLSA SER-388.
    10. "Enzymatic defect in 'X-linked' sideroblastic anemia: molecular evidence for erythroid delta-aminolevulinate synthase deficiency."
      Cotter P.D., Baumann M., Bishop D.F.
      Proc. Natl. Acad. Sci. U.S.A. 89:4028-4032(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT XLSA ASN-476.
    11. "R411C mutation of the ALAS2 gene encodes a pyridoxine-responsive enzyme with low activity."
      Furuyama K., Uno R., Urabe A., Hayashi N., Fujita H., Kondo M., Sassa S., Yamamoto M.
      Br. J. Haematol. 103:839-841(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT XLSA CYS-411.
    12. "A novel mutation of the erythroid-specific gamma-aminolevulinate synthase gene in a patient with non-inherited pyridoxine-responsive sideroblastic anemia."
      Harigae H., Furuyama K., Kudo K., Hayashi N., Yamamoto M., Sassa S., Sasaki T.
      Am. J. Hematol. 62:112-114(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT XLSA GLN-204.
    13. "Four new mutations in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causing X-linked sideroblastic anemia: increased pyridoxine responsiveness after removal of iron overload by phlebotomy and coinheritance of hereditary hemochromatosis."
      Cotter P.D., May A., Li L., Al-Sabah A.I., Fitzsimons E.J., Cazzola M., Bishop D.F.
      Blood 93:1757-1769(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS XLSA HIS-199; CYS-411; GLN-448 AND CYS-452.
    14. "Absent phenotypic expression of X-linked sideroblastic anemia in one of 2 brothers with a novel ALAS2 mutation."
      Cazzola M., May A., Bergamaschi G., Cerani P., Ferrillo S., Bishop D.F.
      Blood 100:4236-4238(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT XLSA HIS-560.
    15. "A novel mutation in exon 5 of the ALAS2 gene results in X-linked sideroblastic anemia."
      Hurford M.T., Marshall-Taylor C., Vicki S.L., Zhou J.Z., Silverman L.M., Rezuke W.N., Altman A., Tsongalis G.J.
      Clin. Chim. Acta 321:49-53(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT XLSA TYR-159.
    16. "C-terminal deletions in the ALAS2 gene lead to gain of function and cause X-linked dominant protoporphyria without anemia or iron overload."
      Whatley S.D., Ducamp S., Gouya L., Grandchamp B., Beaumont C., Badminton M.N., Elder G.H., Holme S.A., Anstey A.V., Parker M., Corrigall A.V., Meissner P.N., Hift R.J., Marsden J.T., Ma Y., Mieli-Vergani G., Deybach J.C., Puy H.
      Am. J. Hum. Genet. 83:408-414(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN XLDPT.
    17. "New mutation in erythroid-specific delta-aminolevulinate synthase as the cause of X-linked sideroblastic anemia responsive to pyridoxine."
      Kucerova J., Horvathova M., Mojzikova R., Belohlavkova P., Cermak J., Divoky V.
      Acta Haematol. 125:193-197(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS XLSA GLU-156; CYS-452 AND HIS-452, CHARACTERIZATION OF VARIANT XLSA GLU-156.
    18. Cited for: VARIANT PHE-586, CHARACTERIZATION OF VARIANT PHE-586, POSSIBLE ROLE AS MODIFIER GENE IN ERYTHROPOIETIC DISORDERS.
    19. "Sideroblastic anemia: molecular analysis of the ALAS2 gene in a series of 29 probands and functional studies of 10 missense mutations."
      Ducamp S., Kannengiesser C., Touati M., Garcon L., Guerci-Bresler A., Guichard J.F., Vermylen C., Dochir J., Poirel H.A., Fouyssac F., Mansuy L., Leroux G., Tertian G., Girot R., Heimpel H., Matthes T., Talbi N., Deybach J.C.
      , Beaumont C., Puy H., Grandchamp B.
      Hum. Mutat. 32:590-597(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS XLSA HIS-170; HIS-218; LYS-242; ASN-263; LEU-339; CYS-375; HIS-411; GLY-452 AND HIS-572, VARIANT LEU-520, CHARACTERIZATION OF VARIANTS XLSA HIS-170; HIS-218; LYS-242; ASN-263; LEU-339; CYS-375; HIS-411; GLY-452 AND HIS-572.

    Entry informationi

    Entry nameiHEM0_HUMAN
    AccessioniPrimary (citable) accession number: P22557
    Secondary accession number(s): A8K3F0
    , A8K6C4, Q13735, Q5JZF5, Q8N6H3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1991
    Last sequence update: January 23, 2002
    Last modified: October 1, 2014
    This is version 161 of the entry and version 2 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

    Miscellaneous

    There are two delta-ALA synthases in vertebrates: an erythroid- specific form and one (housekeeping) which is expressed in all tissues.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome X
      Human chromosome X: 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3