ID   HEM1_SCHPO              Reviewed;         558 AA.
AC   O14092;
DT   27-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   27-MAR-2024, entry version 140.
DE   RecName: Full=5-aminolevulinate synthase, mitochondrial {ECO:0000305|PubMed:25733668};
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=hem1 {ECO:0000303|PubMed:25733668}; ORFNames=SPAC2F3.09;
OS   Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC   Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC   Schizosaccharomyces.
OX   NCBI_TaxID=284812;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=972 / ATCC 24843;
RX   PubMed=11859360; DOI=10.1038/nature724;
RA   Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA   Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA   Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA   Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA   Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA   Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA   Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA   Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA   O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA   Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA   Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA   Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA   Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA   Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA   Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA   Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA   Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA   Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA   Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA   Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA   del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA   Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA   Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA   Nurse P.;
RT   "The genome sequence of Schizosaccharomyces pombe.";
RL   Nature 415:871-880(2002).
RN   [2]
RP   SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX   PubMed=16823372; DOI=10.1038/nbt1222;
RA   Matsuyama A., Arai R., Yashiroda Y., Shirai A., Kamata A., Sekido S.,
RA   Kobayashi Y., Hashimoto A., Hamamoto M., Hiraoka Y., Horinouchi S.,
RA   Yoshida M.;
RT   "ORFeome cloning and global analysis of protein localization in the fission
RT   yeast Schizosaccharomyces pombe.";
RL   Nat. Biotechnol. 24:841-847(2006).
RN   [3]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=25733668; DOI=10.1074/jbc.m115.642058;
RA   Mourer T., Jacques J.F., Brault A., Bisaillon M., Labbe S.;
RT   "Shu1 is a cell-surface protein involved in iron acquisition from heme in
RT   Schizosaccharomyces pombe.";
RL   J. Biol. Chem. 290:10176-10190(2015).
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:0000269|PubMed:16823372}.
CC   -!- DISRUPTION PHENOTYPE: Lethal, unless exogenous ALA is provided,
CC       allowing heme biosynthesis from step 2 to proceed. An additional way to
CC       maintain cells alive is to add exogenous hemin (heme chloride), thereby
CC       fostering cells to use their heme uptake system.
CC       {ECO:0000269|PubMed:25733668}.
CC   -!- SIMILARITY: Belongs to the class-II pyridoxal-phosphate-dependent
CC       aminotransferase family. {ECO:0000305}.
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DR   EMBL; CU329670; CAB16265.1; -; Genomic_DNA.
DR   PIR; T38542; T38542.
DR   RefSeq; NP_594388.1; NM_001019809.2.
DR   AlphaFoldDB; O14092; -.
DR   SMR; O14092; -.
DR   BioGRID; 278510; 5.
DR   STRING; 284812.O14092; -.
DR   iPTMnet; O14092; -.
DR   MaxQB; O14092; -.
DR   PaxDb; 4896-SPAC2F3-09-1; -.
DR   EnsemblFungi; SPAC2F3.09.1; SPAC2F3.09.1:pep; SPAC2F3.09.
DR   GeneID; 2542028; -.
DR   KEGG; spo:SPAC2F3.09; -.
DR   PomBase; SPAC2F3.09; hem1.
DR   VEuPathDB; FungiDB:SPAC2F3.09; -.
DR   eggNOG; KOG1360; Eukaryota.
DR   HOGENOM; CLU_015846_6_0_1; -.
DR   InParanoid; O14092; -.
DR   OMA; CDIMMNR; -.
DR   PhylomeDB; O14092; -.
DR   Reactome; R-SPO-189451; Heme biosynthesis.
DR   UniPathway; UPA00251; UER00375.
DR   PRO; PR:O14092; -.
DR   Proteomes; UP000002485; Chromosome I.
DR   GO; GO:0005759; C:mitochondrial matrix; ISS:PomBase.
DR   GO; GO:0005739; C:mitochondrion; HDA:PomBase.
DR   GO; GO:0003870; F:5-aminolevulinate synthase activity; IMP:PomBase.
DR   GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR   GO; GO:0008483; F:transaminase activity; ISM:PomBase.
DR   GO; GO:0006783; P:heme biosynthetic process; IMP:PomBase.
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..25
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           26..558
FT                   /note="5-aminolevulinate synthase, mitochondrial"
FT                   /id="PRO_0000001243"
FT   REGION          103..124
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        377
FT                   /evidence="ECO:0000250|UniProtKB:P18079"
FT   BINDING         152
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P18079"
FT   BINDING         265
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P18079"
FT   BINDING         284
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P18079"
FT   BINDING         317
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         345
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         374
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         406
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         407
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         492
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P18079"
FT   MOD_RES         377
FT                   /note="N6-(pyridoxal phosphate)lysine"
FT                   /evidence="ECO:0000250|UniProtKB:P18079"
SQ   SEQUENCE   558 AA;  60960 MW;  C599FE2B91F3BD3D CRC64;
     MERVVKLAAK HCPFVSKADP SALRRMAGAG LIRAGARCPV VRHALPVAAA TGADVSRGFK
     SDSKQMAMEP SLDEIHLKAG VVNTGSRTCR HADAVKAAAE AATTTPVTKK HQMPKHYASD
     LNGVGPATTP RFDYDTFYRE ELDKKHRDKS YRYFNNINRL AKEYPLAHLA DPNTRVEVWC
     SNDYLNMGGH KKIREAMHQC IETYGGGAGG TRNIAGHNQH AVRLEKSLAD LHQKPAALVF
     GSCYVANDAT LSTLGRKLPN CIFLSDEMNH ASMINGIRNS RCEKIIFKHN DLVDLEAKLA
     SLPLNRPKII AFESVYSMSG NVAPISEICD LAKKYGAITF LDEVHAVGMY GPRGAGVAEE
     TPGLLSRVDI ITGTLAKSYG CVGGYIAASS TLVDMIRSLA PGFIFTTSLP PHVMVGALTA
     VEHLKVSNVE REQQRSAVRR VKQSLSEIGI PVLSNDTHIV PAMVGDAHLA KLASDSLLHD
     HNIYVQSINF PTVSVGTERL RITPTPAHNT EHYVQSLTNA MNDVWSKFNI NRIDGWEKRG
     IDVGRLCKFP VLPFTTTH
//