ID   HEM1_EMENI              Reviewed;         648 AA.
AC   P38092; C8VN31; Q5BAZ6;
DT   01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT   26-MAY-2009, sequence version 2.
DT   27-MAR-2024, entry version 139.
DE   RecName: Full=5-aminolevulinate synthase, mitochondrial;
DE            EC=2.3.1.37;
DE   AltName: Full=5-aminolevulinic acid synthase;
DE   AltName: Full=Delta-ALA synthase;
DE   AltName: Full=Delta-aminolevulinate synthase;
DE   Flags: Precursor;
GN   Name=hemA; ORFNames=AN2284;
OS   Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 /
OS   M139) (Aspergillus nidulans).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Nidulantes.
OX   NCBI_TaxID=227321;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=R153;
RX   PubMed=8319309; DOI=10.1007/bf00312642;
RA   Bradshaw R.E., Dixon S.W.C., Raitt D.C., Pillar T.M.;
RT   "Isolation and nucleotide sequence of the 5-aminolevulinate synthase gene
RT   from Aspergillus nidulans.";
RL   Curr. Genet. 23:501-507(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX   PubMed=16372000; DOI=10.1038/nature04341;
RA   Galagan J.E., Calvo S.E., Cuomo C., Ma L.-J., Wortman J.R., Batzoglou S.,
RA   Lee S.-I., Bastuerkmen M., Spevak C.C., Clutterbuck J., Kapitonov V.,
RA   Jurka J., Scazzocchio C., Farman M.L., Butler J., Purcell S., Harris S.,
RA   Braus G.H., Draht O., Busch S., D'Enfert C., Bouchier C., Goldman G.H.,
RA   Bell-Pedersen D., Griffiths-Jones S., Doonan J.H., Yu J., Vienken K.,
RA   Pain A., Freitag M., Selker E.U., Archer D.B., Penalva M.A., Oakley B.R.,
RA   Momany M., Tanaka T., Kumagai T., Asai K., Machida M., Nierman W.C.,
RA   Denning D.W., Caddick M.X., Hynes M., Paoletti M., Fischer R., Miller B.L.,
RA   Dyer P.S., Sachs M.S., Osmani S.A., Birren B.W.;
RT   "Sequencing of Aspergillus nidulans and comparative analysis with A.
RT   fumigatus and A. oryzae.";
RL   Nature 438:1105-1115(2005).
RN   [3]
RP   GENOME REANNOTATION.
RC   STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX   PubMed=19146970; DOI=10.1016/j.fgb.2008.12.003;
RA   Wortman J.R., Gilsenan J.M., Joardar V., Deegan J., Clutterbuck J.,
RA   Andersen M.R., Archer D., Bencina M., Braus G., Coutinho P., von Dohren H.,
RA   Doonan J., Driessen A.J., Durek P., Espeso E., Fekete E., Flipphi M.,
RA   Estrada C.G., Geysens S., Goldman G., de Groot P.W., Hansen K.,
RA   Harris S.D., Heinekamp T., Helmstaedt K., Henrissat B., Hofmann G.,
RA   Homan T., Horio T., Horiuchi H., James S., Jones M., Karaffa L.,
RA   Karanyi Z., Kato M., Keller N., Kelly D.E., Kiel J.A., Kim J.M.,
RA   van der Klei I.J., Klis F.M., Kovalchuk A., Krasevec N., Kubicek C.P.,
RA   Liu B., Maccabe A., Meyer V., Mirabito P., Miskei M., Mos M., Mullins J.,
RA   Nelson D.R., Nielsen J., Oakley B.R., Osmani S.A., Pakula T., Paszewski A.,
RA   Paulsen I., Pilsyk S., Pocsi I., Punt P.J., Ram A.F., Ren Q., Robellet X.,
RA   Robson G., Seiboth B., van Solingen P., Specht T., Sun J.,
RA   Taheri-Talesh N., Takeshita N., Ussery D., vanKuyk P.A., Visser H.,
RA   van de Vondervoort P.J., de Vries R.P., Walton J., Xiang X., Xiong Y.,
RA   Zeng A.P., Brandt B.W., Cornell M.J., van den Hondel C.A., Visser J.,
RA   Oliver S.G., Turner G.;
RT   "The 2008 update of the Aspergillus nidulans genome annotation: a community
RT   effort.";
RL   Fungal Genet. Biol. 46:S2-13(2009).
CC   -!- FUNCTION: Catalyzes the synthesis of 5-aminolevulinate (ALA) from
CC       succinyl-CoA and glycine, the first and rate-limiting step in heme
CC       biosynthesis. {ECO:0000250|UniProtKB:P09950}.
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:P09950};
CC   -!- COFACTOR:
CC       Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC         Evidence={ECO:0000250|UniProtKB:P09950};
CC   -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX
CC       biosynthesis; 5-aminolevulinate from glycine: step 1/1.
CC       {ECO:0000250|UniProtKB:P09950}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P09950}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC       {ECO:0000250|UniProtKB:P09950}.
CC   -!- SIMILARITY: Belongs to the class-II pyridoxal-phosphate-dependent
CC       aminotransferase family. {ECO:0000305}.
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DR   EMBL; X64170; CAA45508.1; -; Genomic_DNA.
DR   EMBL; AACD01000038; EAA64395.1; -; Genomic_DNA.
DR   EMBL; BN001307; CBF86531.1; -; Genomic_DNA.
DR   PIR; S31846; S31846.
DR   RefSeq; XP_659888.1; XM_654796.1.
DR   AlphaFoldDB; P38092; -.
DR   SMR; P38092; -.
DR   STRING; 227321.P38092; -.
DR   EnsemblFungi; CBF86531; CBF86531; ANIA_02284.
DR   GeneID; 2874789; -.
DR   KEGG; ani:AN2284.2; -.
DR   VEuPathDB; FungiDB:AN2284; -.
DR   eggNOG; KOG1360; Eukaryota.
DR   HOGENOM; CLU_015846_6_0_1; -.
DR   InParanoid; P38092; -.
DR   OMA; ARRCPIM; -.
DR   OrthoDB; 9643at2759; -.
DR   UniPathway; UPA00251; UER00375.
DR   Proteomes; UP000000560; Chromosome VII.
DR   GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR   GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR   GO; GO:0003870; F:5-aminolevulinate synthase activity; IBA:GO_Central.
DR   GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR   GO; GO:0006783; P:heme biosynthetic process; IBA:GO_Central.
DR   GO; GO:1902117; P:positive regulation of organelle assembly; IEA:EnsemblFungi.
DR   GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:UniProtKB-UniPathway.
DR   CDD; cd06454; KBL_like; 1.
DR   Gene3D; 3.90.1150.10; Aspartate Aminotransferase, domain 1; 1.
DR   Gene3D; 3.40.640.10; Type I PLP-dependent aspartate aminotransferase-like (Major domain); 1.
DR   InterPro; IPR010961; 4pyrrol_synth_NH2levulA_synth.
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   NCBIfam; TIGR01821; 5aminolev_synth; 1.
DR   PANTHER; PTHR13693:SF105; 5-AMINOLEVULINATE SYNTHASE; 1.
DR   PANTHER; PTHR13693; CLASS II AMINOTRANSFERASE/8-AMINO-7-OXONONANOATE SYNTHASE; 1.
DR   Pfam; PF00155; Aminotran_1_2; 1.
DR   SUPFAM; SSF53383; PLP-dependent transferases; 1.
DR   PROSITE; PS00599; AA_TRANSFER_CLASS_2; 1.
PE   3: Inferred from homology;
KW   Acyltransferase; Heme biosynthesis; Mitochondrion; Pyridoxal phosphate;
KW   Reference proteome; Transferase; Transit peptide.
FT   TRANSIT         1..26
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           27..648
FT                   /note="5-aminolevulinate synthase, mitochondrial"
FT                   /id="PRO_0000001240"
FT   REGION          69..109
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        412
FT                   /evidence="ECO:0000250|UniProtKB:P18079"
FT   BINDING         170
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P18079"
FT   BINDING         283
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P18079"
FT   BINDING         302
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P18079"
FT   BINDING         335
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         363
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         409
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         441
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /evidence="ECO:0000250|UniProtKB:P18079"
FT   BINDING         442
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /evidence="ECO:0000250|UniProtKB:P18079"
FT   BINDING         527
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P18079"
FT   MOD_RES         412
FT                   /note="N6-(pyridoxal phosphate)lysine"
FT                   /evidence="ECO:0000250|UniProtKB:P18079"
FT   CONFLICT        300
FT                   /note="A -> R (in Ref. 1; CAA45508)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   648 AA;  68960 MW;  1D450D773925F13F CRC64;
     MEALLQQSRA MCPFLKRSSP NTLRSLATAT RPSTSPGGGT MTNLQRIARR CPVMSKALAV
     QSARMTGTKR FTSSAAGVPG AGAGTPKPTR GSPGKRALHS TGGNGANMST EFHKGAQQIH
     PGLSNATRSH VGASATVSGP TPRAPVAAPF DYDAFYNAEL QKKHQDKSYR YFNNINRLAQ
     EFPRAHTASK DEKVTVWCSN DYLGMGRNPE VLATMHKTLD TYGAGAGGTR NISGHNQHAV
     SLENTLAKLH GKEAALVFSS CFVANDATLA TLGSKMPDCV ILSDSLNHAS MIQGIRHSGA
     KKMVFKHNDL VDLETKLASL PLHVPKIIAF ESVYSMCGSI APIEAICDLA DKYGAITFLD
     EVHAVGMYGP HGAGVAEHLD YEIYASQDTA NPLSTKGTVM DRINIITGTL GKAYGCVGGY
     IAGSAALVDT IRSLAPGFIF TTSLPPATMA GADTAIRYQA RHQQDRILQQ LHTRAVKQSF
     KDLDIPVIPN PSHIVPLLVG DAELAKQASD KLLEEHGIYV QAINYPTVPR GEERLRITPT
     PGHTQELRDH LVEAVNTVWN DLGIKRASDW KAMGGFVGVG VEAAELENQP IWTDAQLNMR
     PDETLEAAVE REFQAAVPGM KAGGAKAKPV GSIAANPIGA SIPVAAAA
//