HEM0_DELLE
ID HEM0_DELLE Reviewed; 582 AA.
AC Q9XT75;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=5-aminolevulinate synthase, erythroid-specific, mitochondrial;
DE Short=ALAS-E;
DE EC=2.3.1.37 {ECO:0000250|UniProtKB:P22557};
DE AltName: Full=5-aminolevulinic acid synthase 2;
DE AltName: Full=Delta-ALA synthase 2;
DE AltName: Full=Delta-aminolevulinate synthase 2;
DE Flags: Precursor;
GN Name=ALAS2; Synonyms=ALS2;
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].
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 (By similarity). Contributes
CC significantly to heme formation during erythropoiesis (By similarity).
CC {ECO:0000250|UniProtKB:P22557}.
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:P22557};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12922;
CC Evidence={ECO:0000250|UniProtKB:P22557};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000250|UniProtKB:P22557};
CC -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX
CC biosynthesis; 5-aminolevulinate from glycine: step 1/1.
CC {ECO:0000250|UniProtKB:P22557}.
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 -!- DOMAIN: C-terminus is a mobile self-inhibitory loop which interferes
CC directly with active site. {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; AF086786; AAD41464.1; -; mRNA.
DR AlphaFoldDB; Q9XT75; -.
DR SMR; Q9XT75; -.
DR STRING; 9749.Q9XT75; -.
DR Ensembl; ENSDLET00000013305; ENSDLEP00000012060; ENSDLEG00000008810.
DR UniPathway; UPA00251; UER00375.
DR Proteomes; UP000248483; Unplaced.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:InterPro.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0003870; F:5-aminolevulinate synthase activity; ISS:UniProtKB.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0006783; P:heme biosynthetic process; ISS:UniProtKB.
DR GO; GO:0042541; P:hemoglobin biosynthetic process; ISS:UniProtKB.
DR GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0001666; P:response to hypoxia; 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; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Pyridoxal phosphate; Reference proteome;
KW Transferase; Transit peptide.
FT TRANSIT 1..?44
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?45..582
FT /note="5-aminolevulinate synthase, erythroid-specific,
FT mitochondrial"
FT /id="PRO_0000001222"
FT ACT_SITE 386
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 158
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 253
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:P22557"
FT BINDING 254
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:P22557"
FT BINDING 275
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 294
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 327
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 355
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:P22557"
FT BINDING 383
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:P22557"
FT BINDING 415
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:P22557"
FT BINDING 416
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:P22557"
FT BINDING 503
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT MOD_RES 386
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:P22557"
SQ SEQUENCE 582 AA; 64555 MW; 7C15EBF6C154C34D CRC64;
MLLQRCPVLI RSPTAILGKM IKTHQFLIGI GRCPILATQG TTCSQIHLKA TKAGGDSPSW
AKSHCPFMLL ELQDGKSKIV QKAAPEVQED VKTFKTDLPI SLASTSLRKP FFSPQEPEKN
SEKVTHLIQN NMAGNHVFGY DQFFRNKIME KKQDHTYRVF KTVNRWADAY PFAEHFFEAS
VASKDVSVWC SNDYLGMSRH PRVLQATQET LQRHGAGAGG TRNISGTSRF HVELEQELAE
LHQKDSALLF SSCFVANDST LFTLAKILPG CEIYSDAGNH ASMIQGIRNS GAAKFVFRHN
DPDHLKKLLK KSNPETPKIV AFETVHSMDG AICPLEELCD VAHQYGALTF VDEVHAVGLY
GSRGAGIGER DGIMHKIDII SGTLGKAFGC VGGYIASTRD LVDMVRSYAA GFIFTTSLPP
MVLSGALESV RLLKGEEGQA LRRAHQRNVK HMRQLLMDRG LPVIPCPSHI IPIRVGDAAL
NSRICDLLLS KHGIYVQAIN YPTVPRGEEL LRLAPSPHHS PQMMEDFVEK LLAAWTEVGL
PLQDVSIAAC NFCRRPVHFE LMSEWERSYF GNMGPQYVTT YA
