HEM1_DELLE
ID HEM1_DELLE Reviewed; 640 AA.
AC Q9XS79;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 99.
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=ALS1;
OS Delphinapterus leucas (Beluga whale).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Whippomorpha; Cetacea; Odontoceti;
OC Monodontidae; Delphinapterus.
OX NCBI_TaxID=9749;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=10425720; DOI=10.1016/s0305-0491(99)00052-8;
RA Kreiling J.A., Duncan R., Faggart M.A., Cornell N.W.;
RT "Comparison of the beluga whale (Delphinapterus leucas) expressed genes for
RT 5-aminolevulinate synthase with those in other vertebrates.";
RL Comp. Biochem. Physiol. 123B:163-174(1999).
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 -!- SIMILARITY: Belongs to the class-II pyridoxal-phosphate-dependent
CC aminotransferase family. {ECO:0000305}.
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DR EMBL; AF073337; AAD20806.1; -; mRNA.
DR AlphaFoldDB; Q9XS79; -.
DR SMR; Q9XS79; -.
DR STRING; 9749.Q9XS79; -.
DR PRIDE; Q9XS79; -.
DR UniPathway; UPA00251; UER00375.
DR Proteomes; UP000248483; Unplaced.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:InterPro.
DR GO; GO:0003870; F:5-aminolevulinate synthase activity; ISS:UniProtKB.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
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 2: Evidence at transcript level;
KW Acyltransferase; Heme biosynthesis; Hydroxylation; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Pyridoxal phosphate; Reference proteome;
KW Transferase; Transit peptide.
FT TRANSIT 1..56
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:P07997"
FT CHAIN 57..640
FT /note="5-aminolevulinate synthase, non-specific,
FT mitochondrial"
FT /id="PRO_0000001229"
FT REGION 60..102
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 76..102
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 445
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 217
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 334
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 353
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 386
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 414
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 442
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 474
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 475
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 562
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT MOD_RES 445
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:P18079"
SQ SEQUENCE 640 AA; 70620 MW; 357BC41CE8EDBA91 CRC64;
METVVRRCPF LSRVPQAFLQ KAGKSLLFYA QNCPKMMEVG AKPAPRALSA SAVLCQQVKE
TPPANEKDKT AKAKVQQAPD GSQQTPDGTQ LPSGHPSLAA SQGTASKCPF LAAQMSQGGS
SVFCKASLEL QEDVQEMHAV REEVAQTSVN PSVISVKTDG GELSGLLKNF QDIMRKQRPE
GVSHLLQDNL PKSVSTFQYD HFFEKKIDEK KNDHTYRVFK TVNRRAQFFP MADDYSDSLV
TKKQVSVWCS NDYLGMSCHP RVCGAVMDTL KQHGTGAGGT RNISGTSKFH VDLEQELADL
HGKDAALLFS SCFVANDSTL FTLAKMMPGC EIYSDSGNHA SMIQGIWNSR VPKYIYRHND
VDHLRELLQR SDPAVPKIVA FETVHSMDGA VCPLEELCDV AHEFGAITFV DEVHAVGLYG
AQGGGIGDRD GVMPKMDIIS GTLGKAFGCV GGYIASTSSL IDTIRSYAAG FIFTTSLPPM
LLAGALESVR ILKSTEGRVL RRQHQRNVKL MRQMLMDASL PVVHCPSHII PVRVADAAKN
TEVCNELMSR HNIYVQAINY PTVRRGEELL RIAPTPHHTP QMMNYFVENL LATWKRVGLE
LKPHSSAECN FCRRPLHFEV MSEREKSYFF GMSKLVSAQD
