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Protein

5-aminolevulinate synthase, mitochondrial

Gene

HEM1

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the synthesis of 5-aminolevulinate (ALA) from succinyl-CoA and glycine, the first and rate-limiting step in heme biosynthesis.1 Publication

Catalytic activityi

Succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2.1 Publication

Cofactori

pyridoxal 5'-phosphate1 Publication

Enzyme regulationi

Ihnhibited by hemin.1 Publication

Kineticsi

  1. KM=3 mM for glycine1 Publication
  2. KM=2 µM for succinyl-CoA1 Publication

    pH dependencei

    Optimum pH is 7.4.1 Publication

    Pathwayi: protoporphyrin-IX biosynthesis

    This protein is involved in step 1 of the subpathway that synthesizes 5-aminolevulinate from glycine.1 Publication
    Proteins known to be involved in this subpathway in this organism are:
    1. 5-aminolevulinate synthase, mitochondrial (HEM1)
    This subpathway is part of the pathway protoporphyrin-IX biosynthesis, which is itself part of Porphyrin-containing compound metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes 5-aminolevulinate from glycine, the pathway protoporphyrin-IX biosynthesis and in Porphyrin-containing compound metabolism.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei91 – 911SubstrateBy similarity
    Binding sitei204 – 2041SubstrateBy similarity
    Binding sitei223 – 2231SubstrateBy similarity
    Binding sitei256 – 2561Pyridoxal phosphateBy similarity
    Binding sitei284 – 2841Pyridoxal phosphateBy similarity
    Binding sitei334 – 3341Pyridoxal phosphateBy similarity
    Active sitei337 – 3371By similarity
    Binding sitei366 – 3661Pyridoxal phosphate; shared with dimeric partnerBy similarity
    Binding sitei367 – 3671Pyridoxal phosphate; shared with dimeric partnerBy similarity
    Binding sitei452 – 4521SubstrateBy similarity

    GO - Molecular functioni

    • 5-aminolevulinate synthase activity Source: SGD
    • pyridoxal phosphate binding Source: InterPro

    GO - Biological processi

    • heme biosynthetic process Source: SGD
    • protoporphyrinogen IX biosynthetic process Source: UniProtKB-UniPathway
    Complete GO annotation...

    Keywords - Molecular functioni

    Acyltransferase, Transferase

    Keywords - Biological processi

    Heme biosynthesis

    Keywords - Ligandi

    Pyridoxal phosphate

    Enzyme and pathway databases

    BioCyciYEAST:YDR232W-MONOMER.
    ReactomeiR-SCE-189451. Heme biosynthesis.
    UniPathwayiUPA00251; UER00375.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    5-aminolevulinate synthase, mitochondrial1 Publication (EC:2.3.1.371 Publication)
    Alternative name(s):
    5-aminolevulinic acid synthase
    Delta-ALA synthase
    Delta-aminolevulinate synthase
    Gene namesi
    Name:HEM11 Publication
    Synonyms:CYD1
    Ordered Locus Names:YDR232WImported
    ORF Names:YD9934.16
    OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
    Taxonomic identifieri559292 [NCBI]
    Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
    ProteomesiUP000002311 Componenti: Chromosome IV

    Organism-specific databases

    EuPathDBiFungiDB:YDR232W.
    SGDiS000002640. HEM1.

    Subcellular locationi

    • Mitochondrion matrix 2 Publications

    GO - Cellular componenti

    • mitochondrial matrix Source: SGD
    Complete GO annotation...

    Keywords - Cellular componenti

    Mitochondrion

    Pathology & Biotechi

    Disruption phenotypei

    In combination with a disruption of MCX1, abrogates mitochondrial respiration.1 Publication

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi275 – 2751G → R: Lethal in combination with a MCX1 disruption. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 2222MitochondrionSequence analysisAdd
    BLAST
    Chaini23 – 5485265-aminolevulinate synthase, mitochondrialPRO_0000001245Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei337 – 3371N6-(pyridoxal phosphate)lysineBy similarity

    Proteomic databases

    MaxQBiP09950.
    PeptideAtlasiP09950.

    Interactioni

    Subunit structurei

    Homodimer (PubMed:6381051). Interacts with MCX1 (PubMed:25957689).2 Publications

    Protein-protein interaction databases

    BioGridi32283. 38 interactions.
    IntActiP09950. 5 interactions.
    MINTiMINT-4481528.

    Structurei

    3D structure databases

    ProteinModelPortaliP09950.
    SMRiP09950. Positions 72-481.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi26 – 6237Ala-richPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    GeneTreeiENSGT00530000063111.
    HOGENOMiHOG000221020.
    InParanoidiP09950.
    KOiK00643.
    OMAiKLAQYPK.
    OrthoDBiEOG7HHX1P.

    Family and domain databases

    Gene3Di3.40.640.10. 1 hit.
    3.90.1150.10. 1 hit.
    InterProiIPR010961. 4pyrrol_synth_NH2levulA_synth.
    IPR001917. Aminotrans_II_pyridoxalP_BS.
    IPR004839. Aminotransferase_I/II.
    IPR015424. PyrdxlP-dep_Trfase.
    IPR015421. PyrdxlP-dep_Trfase_major_sub1.
    IPR015422. PyrdxlP-dep_Trfase_major_sub2.
    [Graphical view]
    PfamiPF00155. Aminotran_1_2. 1 hit.
    [Graphical view]
    SUPFAMiSSF53383. SSF53383. 1 hit.
    TIGRFAMsiTIGR01821. 5aminolev_synth. 1 hit.
    PROSITEiPS00599. AA_TRANSFER_CLASS_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P09950-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MQRSIFARFG NSSAAVSTLN RLSTTAAPHA KNGYATATGA GAAAATATAS
    60 70 80 90 100
    STHAAAAAAA AANHSTQESG FDYEGLIDSE LQKKRLDKSY RYFNNINRLA
    110 120 130 140 150
    KEFPLAHRQR EADKVTVWCS NDYLALSKHP EVLDAMHKTI DKYGCGAGGT
    160 170 180 190 200
    RNIAGHNIPT LNLEAELATL HKKEGALVFS SCYVANDAVL SLLGQKMKDL
    210 220 230 240 250
    VIFSDELNHA SMIVGIKHAN VKKHIFKHND LNELEQLLQS YPKSVPKLIA
    260 270 280 290 300
    FESVYSMAGS VADIEKICDL ADKYGALTFL DEVHAVGLYG PHGAGVAEHC
    310 320 330 340 350
    DFESHRASGI ATPKTNDKGG AKTVMDRVDM ITGTLGKSFG SVGGYVAASR
    360 370 380 390 400
    KLIDWFRSFA PGFIFTTTLP PSVMAGATAA IRYQRCHIDL RTSQQKHTMY
    410 420 430 440 450
    VKKAFHELGI PVIPNPSHIV PVLIGNADLA KQASDILINK HQIYVQAINF
    460 470 480 490 500
    PTVARGTERL RITPTPGHTN DLSDILINAV DDVFNELQLP RVRDWESQGG
    510 520 530 540
    LLGVGESGFV EESNLWTSSQ LSLTNDDLNP NVRDPIVKQL EVSSGIKQ
    Length:548
    Mass (Da):59,362
    Last modified:July 1, 1989 - v1
    Checksum:iFAAEDBAFCEDBE429
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti181 – 1811S → P in AAU09697 (PubMed:17322287).Curated

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M26329 Genomic DNA. Translation: AAA34668.1.
    Z48612 Genomic DNA. Translation: CAA88511.1.
    AY723780 Genomic DNA. Translation: AAU09697.1.
    J03556 Genomic DNA. No translation available.
    BK006938 Genomic DNA. Translation: DAA12073.1.
    PIRiA24870. SYBYAL.
    RefSeqiNP_010518.1. NM_001180540.1.

    Genome annotation databases

    EnsemblFungiiYDR232W; YDR232W; YDR232W.
    GeneIDi851818.
    KEGGisce:YDR232W.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M26329 Genomic DNA. Translation: AAA34668.1.
    Z48612 Genomic DNA. Translation: CAA88511.1.
    AY723780 Genomic DNA. Translation: AAU09697.1.
    J03556 Genomic DNA. No translation available.
    BK006938 Genomic DNA. Translation: DAA12073.1.
    PIRiA24870. SYBYAL.
    RefSeqiNP_010518.1. NM_001180540.1.

    3D structure databases

    ProteinModelPortaliP09950.
    SMRiP09950. Positions 72-481.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi32283. 38 interactions.
    IntActiP09950. 5 interactions.
    MINTiMINT-4481528.

    Proteomic databases

    MaxQBiP09950.
    PeptideAtlasiP09950.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblFungiiYDR232W; YDR232W; YDR232W.
    GeneIDi851818.
    KEGGisce:YDR232W.

    Organism-specific databases

    EuPathDBiFungiDB:YDR232W.
    SGDiS000002640. HEM1.

    Phylogenomic databases

    GeneTreeiENSGT00530000063111.
    HOGENOMiHOG000221020.
    InParanoidiP09950.
    KOiK00643.
    OMAiKLAQYPK.
    OrthoDBiEOG7HHX1P.

    Enzyme and pathway databases

    UniPathwayiUPA00251; UER00375.
    BioCyciYEAST:YDR232W-MONOMER.
    ReactomeiR-SCE-189451. Heme biosynthesis.

    Miscellaneous databases

    NextBioi969683.
    PROiP09950.

    Family and domain databases

    Gene3Di3.40.640.10. 1 hit.
    3.90.1150.10. 1 hit.
    InterProiIPR010961. 4pyrrol_synth_NH2levulA_synth.
    IPR001917. Aminotrans_II_pyridoxalP_BS.
    IPR004839. Aminotransferase_I/II.
    IPR015424. PyrdxlP-dep_Trfase.
    IPR015421. PyrdxlP-dep_Trfase_major_sub1.
    IPR015422. PyrdxlP-dep_Trfase_major_sub2.
    [Graphical view]
    PfamiPF00155. Aminotran_1_2. 1 hit.
    [Graphical view]
    SUPFAMiSSF53383. SSF53383. 1 hit.
    TIGRFAMsiTIGR01821. 5aminolev_synth. 1 hit.
    PROSITEiPS00599. AA_TRANSFER_CLASS_2. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "The nucleotide sequence of the HEM1 gene and evidence for a precursor form of the mitochondrial 5-aminolevulinate synthase in Saccharomyces cerevisiae."
      Urban-Grimal D., Volland C., Garnier T., Dehoux P., Labbe-Bois R.
      Eur. J. Biochem. 156:511-519(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV."
      Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G., Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C., Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F., Delaveau T.
      , del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M., Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T., Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C., Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S., Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L., Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H., Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M., Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M., Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A., Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G., Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E., Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S., Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D., Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V., Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E., Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M., Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D., Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X., Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A., Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R., Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T., Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L., Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E., Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L., Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M., Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K., Mewes H.-W., Zollner A., Zaccaria P.
      Nature 387:75-78(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: ATCC 204508 / S288c.
    3. Cited for: GENOME REANNOTATION.
      Strain: ATCC 204508 / S288c.
    4. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: ATCC 204508 / S288c.
    5. "The nine amino-terminal residues of delta-aminolevulinate synthase direct beta-galactosidase into the mitochondrial matrix."
      Keng T., Alani E., Guarente L.
      Mol. Cell. Biol. 6:355-364(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-75, SUBCELLULAR LOCATION.
    6. "Constitutive expression of the yeast HEM1 gene is actually a composite of activation and repression."
      Keng T., Guarente L.
      Proc. Natl. Acad. Sci. U.S.A. 84:9113-9117(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-2.
    7. "Isolation and properties of 5-aminolevulinate synthase from the yeast Saccharomyces cerevisiae."
      Volland C., Felix F.
      Eur. J. Biochem. 142:551-557(1984) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, CATALYTIC ACTIVITY, ENZYME REGULATION, SUBCELLULAR LOCATION.
    8. Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
    9. "Mitochondrial ClpX activates a key enzyme for heme biosynthesis and erythropoiesis."
      Kardon J.R., Yien Y.Y., Huston N.C., Branco D.S., Hildick-Smith G.J., Rhee K.Y., Paw B.H., Baker T.A.
      Cell 161:858-867(2015) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, MUTAGENESIS OF GLY-275, INTERACTION WITH MCX1.

    Entry informationi

    Entry nameiHEM1_YEAST
    AccessioniPrimary (citable) accession number: P09950
    Secondary accession number(s): D6VSL3, E9P946
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 1, 1989
    Last sequence update: July 1, 1989
    Last modified: December 9, 2015
    This is version 147 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programFungal Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Present with 22600 molecules/cell in log phase SD medium.1 Publication

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. SIMILARITY comments
      Index of protein domains and families
    3. Yeast
      Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
    4. Yeast chromosome IV
      Yeast (Saccharomyces cerevisiae) chromosome IV: entries and gene names

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.