ID   HEM0_DANRE              Reviewed;         583 AA.
AC   Q9YHT4; Q6NXC5;
DT   23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   03-AUG-2022, entry version 140.
DE   RecName: Full=5-aminolevulinate synthase, erythroid-specific, mitochondrial;
DE            Short=ALAS-E;
DE            EC=2.3.1.37 {ECO:0000250|UniProtKB:P22557};
DE   AltName: Full=5-aminolevulinic acid synthase 2;
DE   AltName: Full=Delta-ALA synthase 2;
DE   AltName: Full=Delta-aminolevulinate synthase 2;
DE   Flags: Precursor;
GN   Name=alas2; Synonyms=alas-e;
OS   Danio rerio (Zebrafish) (Brachydanio rerio).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Danionidae; Danioninae; Danio.
OX   NCBI_TaxID=7955;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Kidney;
RX   PubMed=9806542; DOI=10.1038/3049;
RA   Brownlie A., Donovan A., Pratt S.J., Paw B.H., Oates A.C., Brugnara C.,
RA   Witkowska H.E., Sassa S., Zon L.I.;
RT   "Positional cloning of the zebrafish sauternes gene: a model for congenital
RT   sideroblastic anaemia.";
RL   Nat. Genet. 20:244-250(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
RG   NIH - Zebrafish Gene Collection (ZGC) project;
RL   Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Catalyzes the pyridoxal 5'-phosphate (PLP)-dependent
CC       condensation of succinyl-CoA and glycine to form aminolevulinic acid
CC       (ALA), with CoA and CO2 as by-products (By similarity). Contributes
CC       significantly to heme formation during erythropoiesis (By similarity).
CC       {ECO:0000250|UniProtKB:P22557}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=glycine + H(+) + succinyl-CoA = 5-aminolevulinate + CO2 + CoA;
CC         Xref=Rhea:RHEA:12921, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC         ChEBI:CHEBI:57287, ChEBI:CHEBI:57292, ChEBI:CHEBI:57305,
CC         ChEBI:CHEBI:356416; EC=2.3.1.37;
CC         Evidence={ECO:0000250|UniProtKB:P22557};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12922;
CC         Evidence={ECO:0000250|UniProtKB:P22557};
CC   -!- COFACTOR:
CC       Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC         Evidence={ECO:0000250|UniProtKB:P22557};
CC   -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX
CC       biosynthesis; 5-aminolevulinate from glycine: step 1/1.
CC       {ECO:0000250|UniProtKB:P22557}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P22557}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC       {ECO:0000250|UniProtKB:P22557}; Peripheral membrane protein
CC       {ECO:0000250|UniProtKB:P22557}. Note=Localizes to the matrix side of
CC       the mitochondrion inner membrane. {ECO:0000250|UniProtKB:P22557}.
CC   -!- DOMAIN: C-terminus is a mobile self-inhibitory loop which interferes
CC       directly with active site. {ECO:0000250|UniProtKB:P22557}.
CC   -!- SIMILARITY: Belongs to the class-II pyridoxal-phosphate-dependent
CC       aminotransferase family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH67149.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AF095747; AAC72835.1; -; mRNA.
DR   EMBL; BC056338; AAH56338.1; -; mRNA.
DR   EMBL; BC067149; AAH67149.1; ALT_INIT; mRNA.
DR   RefSeq; NP_571757.1; NM_131682.2.
DR   AlphaFoldDB; Q9YHT4; -.
DR   SMR; Q9YHT4; -.
DR   STRING; 7955.ENSDARP00000056419; -.
DR   PaxDb; Q9YHT4; -.
DR   Ensembl; ENSDART00000056420; ENSDARP00000056419; ENSDARG00000038643.
DR   GeneID; 64607; -.
DR   KEGG; dre:64607; -.
DR   CTD; 212; -.
DR   ZFIN; ZDB-GENE-001229-1; alas2.
DR   eggNOG; KOG1360; Eukaryota.
DR   GeneTree; ENSGT00940000159912; -.
DR   HOGENOM; CLU_015846_6_1_1; -.
DR   InParanoid; Q9YHT4; -.
DR   OMA; NHASMIV; -.
DR   OrthoDB; 930001at2759; -.
DR   PhylomeDB; Q9YHT4; -.
DR   TreeFam; TF300724; -.
DR   Reactome; R-DRE-189451; Heme biosynthesis.
DR   UniPathway; UPA00251; UER00375.
DR   PRO; PR:Q9YHT4; -.
DR   Proteomes; UP000000437; Genome assembly.
DR   Proteomes; UP000814640; Chromosome 8.
DR   Bgee; ENSDARG00000038643; Expressed in spleen and 19 other tissues.
DR   GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR   GO; GO:0005759; C:mitochondrial matrix; IEA:InterPro.
DR   GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR   GO; GO:0003870; F:5-aminolevulinate synthase activity; ISS:UniProtKB.
DR   GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR   GO; GO:0035162; P:embryonic hemopoiesis; IMP:ZFIN.
DR   GO; GO:0048821; P:erythrocyte development; IMP:ZFIN.
DR   GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB.
DR   GO; GO:0006783; P:heme biosynthetic process; IMP:ZFIN.
DR   GO; GO:0042541; P:hemoglobin biosynthetic process; IMP:ZFIN.
DR   GO; GO:0020027; P:hemoglobin metabolic process; IMP:ZFIN.
DR   GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0001666; P:response to hypoxia; ISS:UniProtKB.
DR   Gene3D; 3.40.640.10; -; 1.
DR   Gene3D; 3.90.1150.10; -; 1.
DR   InterPro; IPR010961; 4pyrrol_synth_NH2levulA_synth.
DR   InterPro; IPR015118; 5aminolev_synth_preseq.
DR   InterPro; IPR001917; Aminotrans_II_pyridoxalP_BS.
DR   InterPro; IPR004839; Aminotransferase_I/II.
DR   InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR   InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR   InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR   Pfam; PF00155; Aminotran_1_2; 1.
DR   Pfam; PF09029; Preseq_ALAS; 1.
DR   SUPFAM; SSF53383; SSF53383; 1.
DR   TIGRFAMs; TIGR01821; 5aminolev_synth; 1.
DR   PROSITE; PS00599; AA_TRANSFER_CLASS_2; 1.
PE   2: Evidence at transcript level;
KW   Acyltransferase; Heme biosynthesis; Membrane; Mitochondrion;
KW   Mitochondrion inner membrane; Pyridoxal phosphate; Reference proteome;
KW   Transferase; Transit peptide.
FT   TRANSIT         1..?
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           ?..583
FT                   /note="5-aminolevulinate synthase, erythroid-specific,
FT                   mitochondrial"
FT                   /id="PRO_0000001227"
FT   ACT_SITE        386
FT                   /evidence="ECO:0000250|UniProtKB:P18079"
FT   BINDING         158
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P18079"
FT   BINDING         253
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000250|UniProtKB:P22557"
FT   BINDING         254
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000250|UniProtKB:P22557"
FT   BINDING         275
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P18079"
FT   BINDING         327
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000250|UniProtKB:P18079"
FT   BINDING         355
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000250|UniProtKB:P22557"
FT   BINDING         383
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000250|UniProtKB:P22557"
FT   BINDING         415
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /evidence="ECO:0000250|UniProtKB:P22557"
FT   BINDING         416
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /evidence="ECO:0000250|UniProtKB:P22557"
FT   BINDING         503
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P18079"
FT   MOD_RES         386
FT                   /note="N6-(pyridoxal phosphate)lysine"
FT                   /evidence="ECO:0000250|UniProtKB:P08680"
SQ   SEQUENCE   583 AA;  63909 MW;  9C542B4C75299ABD CRC64;
     MSAFLHHCPF LKSSPGPSAR KVATYLNLAD RCPIIVRQIS AKAAQSSEQN GLLPHKEPKR
     QLATTATQVA VSMSQSCPFV SSKIGLVKAS PQVQEDVQPN LENQDTSGLI SSLFSGLQSH
     QSTGPTHLLQ DNFNRPTFSY DEFFTQKIVE KKKDHTYRIF KTVNRFAEVF PFAEDYSIAG
     RLGSQVSVWC SNDYLGMSRH PRVVKAIGDA LKKHGAGAGG TRNISGTSNY HVALENELAR
     LHQKDGALVF SSCFVANDST LFTLAKMLPG CEIYSDMGNH ASMIQGIRNS GAKRFIFRHN
     DASHLEELLS RSDPLTPKIV AFETVHSMDG AICPLEELCD VAHKYGALTF VDEVHAVGLY
     GAHGAGVGER DNVMHKIDIV SGTLGKAFGC VGGYIASTAA LVDTVRSFAA GFIFTTSLPP
     MVLAGALESV RVLKSDEGQA LRRAHQRNVK HMRQLLLDAG LPVVNCPSHI IPIRVGNAAK
     NSEVCDILLE KHNIYVQAIN YPTVPRGEEL LRLAPSPFHN PIMMNYFAEK LLDVWQEVGL
     PLNGPAQASC TFCDRPLHFD LMSEWEKSYF GNMEPRYITV AAQ