HEM1_YEAST
ID HEM1_YEAST Reviewed; 548 AA.
AC P09950; D6VSL3; E9P946;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=5-aminolevulinate synthase, mitochondrial {ECO:0000303|PubMed:6381051};
DE EC=2.3.1.37 {ECO:0000269|PubMed:6381051};
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:3516694}; Synonyms=CYD1;
GN OrderedLocusNames=YDR232W {ECO:0000312|SGD:S000002640}; ORFNames=YD9934.16;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3516694; DOI=10.1111/j.1432-1033.1986.tb09610.x;
RA Urban-Grimal D., Volland C., Garnier T., Dehoux P., Labbe-Bois R.;
RT "The nucleotide sequence of the HEM1 gene and evidence for a precursor form
RT of the mitochondrial 5-aminolevulinate synthase in Saccharomyces
RT cerevisiae.";
RL Eur. J. Biochem. 156:511-519(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169867;
RA Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G.,
RA Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C.,
RA Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F.,
RA Delaveau T., del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M.,
RA Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T.,
RA Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C.,
RA Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S.,
RA Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L.,
RA Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H.,
RA Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M.,
RA Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M.,
RA Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A.,
RA Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G.,
RA Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E.,
RA Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S.,
RA Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D.,
RA Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V.,
RA Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E.,
RA Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M.,
RA Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D.,
RA Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A.,
RA Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R.,
RA Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T.,
RA Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L.,
RA Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E.,
RA Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L.,
RA Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M.,
RA Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K.,
RA Mewes H.-W., Zollner A., Zaccaria P.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV.";
RL Nature 387:75-78(1997).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-75, AND SUBCELLULAR LOCATION.
RX PubMed=3023841; DOI=10.1128/mcb.6.2.355-364.1986;
RA Keng T., Alani E., Guarente L.;
RT "The nine amino-terminal residues of delta-aminolevulinate synthase direct
RT beta-galactosidase into the mitochondrial matrix.";
RL Mol. Cell. Biol. 6:355-364(1986).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-2.
RX PubMed=3321068; DOI=10.1073/pnas.84.24.9113;
RA Keng T., Guarente L.;
RT "Constitutive expression of the yeast HEM1 gene is actually a composite of
RT activation and repression.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:9113-9117(1987).
RN [7]
RP FUNCTION, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, CATALYTIC
RP ACTIVITY, ACTIVITY REGULATION, AND SUBCELLULAR LOCATION.
RX PubMed=6381051; DOI=10.1111/j.1432-1033.1984.tb08321.x;
RA Volland C., Felix F.;
RT "Isolation and properties of 5-aminolevulinate synthase from the yeast
RT Saccharomyces cerevisiae.";
RL Eur. J. Biochem. 142:551-557(1984).
RN [8]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [9]
RP DISRUPTION PHENOTYPE, MUTAGENESIS OF GLY-275, AND INTERACTION WITH MCX1.
RX PubMed=25957689; DOI=10.1016/j.cell.2015.04.017;
RA Kardon J.R., Yien Y.Y., Huston N.C., Branco D.S., Hildick-Smith G.J.,
RA Rhee K.Y., Paw B.H., Baker T.A.;
RT "Mitochondrial ClpX activates a key enzyme for heme biosynthesis and
RT erythropoiesis.";
RL Cell 161:858-867(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:0000269|PubMed:6381051}.
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:0000269|PubMed:6381051};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000269|PubMed:6381051};
CC -!- ACTIVITY REGULATION: Ihnhibited by hemin. {ECO:0000269|PubMed:6381051}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3 mM for glycine {ECO:0000269|PubMed:6381051};
CC KM=2 uM for succinyl-CoA {ECO:0000269|PubMed:6381051};
CC pH dependence:
CC Optimum pH is 7.4. {ECO:0000269|PubMed:6381051};
CC -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX
CC biosynthesis; 5-aminolevulinate from glycine: step 1/1.
CC {ECO:0000305|PubMed:6381051}.
CC -!- SUBUNIT: Homodimer (PubMed:6381051). Interacts with MCX1
CC (PubMed:25957689). {ECO:0000269|PubMed:25957689,
CC ECO:0000269|PubMed:6381051}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000269|PubMed:3023841,
CC ECO:0000269|PubMed:6381051}.
CC -!- DISRUPTION PHENOTYPE: In combination with a disruption of MCX1,
CC abrogates mitochondrial respiration. {ECO:0000269|PubMed:25957689}.
CC -!- MISCELLANEOUS: Present with 22600 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the class-II pyridoxal-phosphate-dependent
CC aminotransferase family. {ECO:0000305}.
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DR EMBL; M26329; AAA34668.1; -; Genomic_DNA.
DR EMBL; Z48612; CAA88511.1; -; Genomic_DNA.
DR EMBL; AY723780; AAU09697.1; -; Genomic_DNA.
DR EMBL; J03556; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BK006938; DAA12073.1; -; Genomic_DNA.
DR PIR; A24870; SYBYAL.
DR RefSeq; NP_010518.1; NM_001180540.1.
DR PDB; 5TXR; X-ray; 1.90 A; A/B=58-548.
DR PDB; 5TXT; X-ray; 2.70 A; A/B/C/D/E/F=58-548.
DR PDBsum; 5TXR; -.
DR PDBsum; 5TXT; -.
DR AlphaFoldDB; P09950; -.
DR SMR; P09950; -.
DR BioGRID; 32283; 192.
DR IntAct; P09950; 5.
DR STRING; 4932.YDR232W; -.
DR MaxQB; P09950; -.
DR PaxDb; P09950; -.
DR PRIDE; P09950; -.
DR EnsemblFungi; YDR232W_mRNA; YDR232W; YDR232W.
DR GeneID; 851818; -.
DR KEGG; sce:YDR232W; -.
DR SGD; S000002640; HEM1.
DR VEuPathDB; FungiDB:YDR232W; -.
DR eggNOG; KOG1360; Eukaryota.
DR GeneTree; ENSGT00940000170004; -.
DR HOGENOM; CLU_015846_6_0_1; -.
DR InParanoid; P09950; -.
DR OMA; NHASMIV; -.
DR BioCyc; YEAST:YDR232W-MON; -.
DR BRENDA; 2.3.1.37; 984.
DR Reactome; R-SCE-189451; Heme biosynthesis.
DR UniPathway; UPA00251; UER00375.
DR PRO; PR:P09950; -.
DR Proteomes; UP000002311; Chromosome IV.
DR RNAct; P09950; protein.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:SGD.
DR GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR GO; GO:0003870; F:5-aminolevulinate synthase activity; IDA:SGD.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0006783; P:heme biosynthetic process; IMP:SGD.
DR GO; GO:1902117; P:positive regulation of organelle assembly; IMP:SGD.
DR GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:UniProtKB-UniPathway.
DR DisProt; DP02768; -.
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 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Heme biosynthesis; Mitochondrion;
KW Pyridoxal phosphate; Reference proteome; Transferase; Transit peptide.
FT TRANSIT 1..22
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 23..548
FT /note="5-aminolevulinate synthase, mitochondrial"
FT /id="PRO_0000001245"
FT ACT_SITE 337
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 91
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 204
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 223
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 256
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 284
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 334
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 366
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 367
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 452
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT MOD_RES 337
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT MUTAGEN 275
FT /note="G->R: Lethal in combination with a MCX1 disruption."
FT /evidence="ECO:0000269|PubMed:25957689"
FT CONFLICT 181
FT /note="S -> P (in Ref. 4; AAU09697)"
FT /evidence="ECO:0000305"
FT HELIX 73..86
FT /evidence="ECO:0007829|PDB:5TXR"
FT STRAND 100..102
FT /evidence="ECO:0007829|PDB:5TXT"
FT STRAND 105..107
FT /evidence="ECO:0007829|PDB:5TXR"
FT STRAND 114..117
FT /evidence="ECO:0007829|PDB:5TXR"
FT HELIX 126..128
FT /evidence="ECO:0007829|PDB:5TXR"
FT HELIX 130..143
FT /evidence="ECO:0007829|PDB:5TXR"
FT TURN 151..153
FT /evidence="ECO:0007829|PDB:5TXR"
FT HELIX 158..171
FT /evidence="ECO:0007829|PDB:5TXR"
FT STRAND 174..180
FT /evidence="ECO:0007829|PDB:5TXR"
FT HELIX 182..196
FT /evidence="ECO:0007829|PDB:5TXR"
FT STRAND 201..205
FT /evidence="ECO:0007829|PDB:5TXR"
FT HELIX 210..219
FT /evidence="ECO:0007829|PDB:5TXR"
FT STRAND 221..226
FT /evidence="ECO:0007829|PDB:5TXR"
FT HELIX 231..239
FT /evidence="ECO:0007829|PDB:5TXR"
FT STRAND 247..255
FT /evidence="ECO:0007829|PDB:5TXR"
FT TURN 256..259
FT /evidence="ECO:0007829|PDB:5TXR"
FT HELIX 264..274
FT /evidence="ECO:0007829|PDB:5TXR"
FT STRAND 276..281
FT /evidence="ECO:0007829|PDB:5TXR"
FT TURN 283..288
FT /evidence="ECO:0007829|PDB:5TXR"
FT HELIX 296..300
FT /evidence="ECO:0007829|PDB:5TXR"
FT HELIX 302..308
FT /evidence="ECO:0007829|PDB:5TXR"
FT HELIX 324..327
FT /evidence="ECO:0007829|PDB:5TXR"
FT STRAND 329..337
FT /evidence="ECO:0007829|PDB:5TXR"
FT STRAND 344..348
FT /evidence="ECO:0007829|PDB:5TXR"
FT HELIX 350..359
FT /evidence="ECO:0007829|PDB:5TXR"
FT HELIX 361..364
FT /evidence="ECO:0007829|PDB:5TXR"
FT HELIX 371..385
FT /evidence="ECO:0007829|PDB:5TXR"
FT HELIX 389..408
FT /evidence="ECO:0007829|PDB:5TXR"
FT STRAND 416..418
FT /evidence="ECO:0007829|PDB:5TXR"
FT STRAND 420..423
FT /evidence="ECO:0007829|PDB:5TXR"
FT HELIX 427..441
FT /evidence="ECO:0007829|PDB:5TXR"
FT TURN 450..452
FT /evidence="ECO:0007829|PDB:5TXR"
FT STRAND 459..462
FT /evidence="ECO:0007829|PDB:5TXR"
FT HELIX 470..487
FT /evidence="ECO:0007829|PDB:5TXR"
FT HELIX 492..497
FT /evidence="ECO:0007829|PDB:5TXR"
FT HELIX 518..521
FT /evidence="ECO:0007829|PDB:5TXR"
FT HELIX 525..527
FT /evidence="ECO:0007829|PDB:5TXR"
FT HELIX 530..532
FT /evidence="ECO:0007829|PDB:5TXR"
FT HELIX 541..543
FT /evidence="ECO:0007829|PDB:5TXR"
SQ SEQUENCE 548 AA; 59362 MW; FAAEDBAFCEDBE429 CRC64;
MQRSIFARFG NSSAAVSTLN RLSTTAAPHA KNGYATATGA GAAAATATAS STHAAAAAAA
AANHSTQESG FDYEGLIDSE LQKKRLDKSY RYFNNINRLA KEFPLAHRQR EADKVTVWCS
NDYLALSKHP EVLDAMHKTI DKYGCGAGGT RNIAGHNIPT LNLEAELATL HKKEGALVFS
SCYVANDAVL SLLGQKMKDL VIFSDELNHA SMIVGIKHAN VKKHIFKHND LNELEQLLQS
YPKSVPKLIA FESVYSMAGS VADIEKICDL ADKYGALTFL DEVHAVGLYG PHGAGVAEHC
DFESHRASGI ATPKTNDKGG AKTVMDRVDM ITGTLGKSFG SVGGYVAASR KLIDWFRSFA
PGFIFTTTLP PSVMAGATAA IRYQRCHIDL RTSQQKHTMY VKKAFHELGI PVIPNPSHIV
PVLIGNADLA KQASDILINK HQIYVQAINF PTVARGTERL RITPTPGHTN DLSDILINAV
DDVFNELQLP RVRDWESQGG LLGVGESGFV EESNLWTSSQ LSLTNDDLNP NVRDPIVKQL
EVSSGIKQ
