HEM1_SCHPO
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 03-AUG-2022, entry version 134.
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; 4.
DR STRING; 4896.SPAC2F3.09.1; -.
DR iPTMnet; O14092; -.
DR MaxQB; O14092; -.
DR PaxDb; O14092; -.
DR PRIDE; O14092; -.
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 Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 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 Pfam; PF00155; Aminotran_1_2; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
DR TIGRFAMs; TIGR01821; 5aminolev_synth; 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
