HEM1_CHICK
ID HEM1_CHICK Reviewed; 635 AA.
AC P07997;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 2.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=5-aminolevulinate synthase, non-specific, mitochondrial;
DE Short=ALAS-H;
DE EC=2.3.1.37 {ECO:0000250|UniProtKB:P13196};
DE AltName: Full=5-aminolevulinic acid synthase 1;
DE AltName: Full=Delta-ALA synthase 1;
DE AltName: Full=Delta-aminolevulinate synthase 1;
DE Flags: Precursor;
GN Name=ALAS1; Synonyms=ALASN;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF N-TERMINUS, AND PARTIAL
RP PROTEIN SEQUENCE.
RC TISSUE=Liver;
RX PubMed=3839458; DOI=10.1111/j.1432-1033.1985.tb09047.x;
RA Borthwick I.A., Srivastava G., Day A.R., Pirola B.A., Snoswell M.A.,
RA May B.K., Elliott W.H.;
RT "Complete nucleotide sequence of hepatic 5-aminolaevulinate synthase
RT precursor.";
RL Eur. J. Biochem. 150:481-484(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Liver;
RX PubMed=3005973; DOI=10.1093/nar/14.3.1379;
RA Maguire D.J., Day A.R., Borthwick I.A., Srivastava G., Wigley P.L.,
RA May B.K., Elliott W.H.;
RT "Nucleotide sequence of the chicken 5-aminolevulinate synthase gene.";
RL Nucleic Acids Res. 14:1379-1391(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=2915978; DOI=10.1073/pnas.86.3.792;
RA Riddle R.D., Yamamoto M., Engel J.D.;
RT "Expression of delta-aminolevulinate synthase in avian cells: separate
RT genes encode erythroid-specific and nonspecific isozymes.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:792-796(1989).
CC -!- FUNCTION: Catalyzes the pyridoxal 5'-phosphate (PLP)-dependent
CC condensation of succinyl-CoA and glycine to form aminolevulinic acid
CC (ALA), with CoA and CO2 as by-products. {ECO:0000250|UniProtKB:P13196}.
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:P13196};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12922;
CC Evidence={ECO:0000250|UniProtKB:P13196};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000250|UniProtKB:P13196};
CC -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX
CC biosynthesis; 5-aminolevulinate from glycine: step 1/1.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P22557}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:P22557}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P22557}. Note=Localizes to the matrix side of
CC the mitochondrion inner membrane. {ECO:0000250|UniProtKB:P22557}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:2915978}.
CC -!- SIMILARITY: Belongs to the class-II pyridoxal-phosphate-dependent
CC aminotransferase family. {ECO:0000305}.
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DR EMBL; X02827; CAA26595.1; -; mRNA.
DR EMBL; X03517; CAA27223.1; -; Genomic_DNA.
DR EMBL; X03627; CAA27223.1; JOINED; Genomic_DNA.
DR PIR; A23538; SYCHAL.
DR RefSeq; NP_001018012.1; NM_001018012.1.
DR AlphaFoldDB; P07997; -.
DR SMR; P07997; -.
DR STRING; 9031.ENSGALP00000035503; -.
DR GeneID; 552895; -.
DR KEGG; gga:552895; -.
DR CTD; 211; -.
DR VEuPathDB; HostDB:geneid_552895; -.
DR eggNOG; KOG1360; Eukaryota.
DR InParanoid; P07997; -.
DR OrthoDB; 930001at2759; -.
DR PhylomeDB; P07997; -.
DR Reactome; R-GGA-421984; Heme synthesis.
DR UniPathway; UPA00251; UER00375.
DR PRO; PR:P07997; -.
DR Proteomes; UP000000539; Unplaced.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0003870; F:5-aminolevulinate synthase activity; ISS:UniProtKB.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0048821; P:erythrocyte development; IBA:GO_Central.
DR GO; GO:0006783; P:heme biosynthetic process; IBA:GO_Central.
DR GO; GO:0042541; P:hemoglobin biosynthetic process; IBA:GO_Central.
DR GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:1903412; P:response to bile acid; ISS:UniProtKB.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR InterPro; IPR010961; 4pyrrol_synth_NH2levulA_synth.
DR InterPro; IPR015118; 5aminolev_synth_preseq.
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 Pfam; PF09029; Preseq_ALAS; 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 Acyltransferase; Direct protein sequencing; Heme biosynthesis;
KW Hydroxylation; Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Pyridoxal phosphate; Reference proteome; Transferase; Transit peptide.
FT TRANSIT 1..56
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:3839458"
FT CHAIN 57..635
FT /note="5-aminolevulinate synthase, non-specific,
FT mitochondrial"
FT /id="PRO_0000001233"
FT REGION 44..94
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 440
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 212
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 329
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 348
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 381
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 437
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 469
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 470
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 557
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT MOD_RES 440
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT CONFLICT 53
FT /note="S -> A (in Ref. 1; CAA26595 and 3; no nucleotide
FT entry)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 635 AA; 69948 MW; EEE708B85C1539BA CRC64;
MEAVVRRCPF LARVSQAFLQ KAGPSLLFYA QHCPKMMEAA PPAAARGLAT SASRGQQVEE
TPAAQPEAKK AKEVAQQNTD GSQPPAGHPP AAAVQSSATK CPFLAAQMNH KSSNVFCKAS
LELQEDVKEM QVDRKGKEFA KIPTNSVVRN TEAEGEEQSG LLKKFKDIML KQRPESVSHL
LQDNLPKSVS TFQYDQFFEK KIDEKKKDHT YRVFKTVNRK AQIFPMADDY SDSLITKKEV
SVWCSNDYLG MSRHPRVCGA VMDTLKQHGA GAGGTRNISG TSKFHVDLEK ELADLHGKDA
ALLFSSCFVA NDSTLFTLAK MLPGCEIYSD SGNHASMIQG IRNSRVPKHI FRHNDVNHLR
ELLKKSDPST PKIVAFETVH SMDGAVCPLE ELCDVAHEHG AITFVDEVHA VGLYGARGGG
IGDRDGVMHK MDIISGTLGK AFACVGGYIS STSALIDTVR SYAAGFIFTT SLPPMLLAGA
LESVRTLKSA EGQVLRRQHQ RNVKLMRQML MDAGLPVVHC PSHIIPIRVA DAAKNTEICD
KLMSQHSIYV QAINYPTVPR GEELLRIAPT PHHTPQMMSY FLEKLLATWK DVGLELKPHS
SAECNFCRRP LHFEVMSERE RSYFSGMSKL LSVSA
