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 13-SEP-2023, entry version 105. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF086786; AAD41464.1; -; mRNA. DR AlphaFoldDB; Q9XT75; -. DR SMR; Q9XT75; -. DR STRING; 9749.Q9XT75; -. DR Ensembl; ENSDLET00000013305; ENSDLEP00000012060; ENSDLEG00000008810. DR InParanoid; Q9XT75; -. 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 CDD; cd06454; KBL_like; 1. DR Gene3D; 4.10.92.10; Aminolevulinic Acid Synthase 2; 1. DR Gene3D; 3.90.1150.10; Aspartate Aminotransferase, domain 1; 1. DR Gene3D; 3.40.640.10; Type I PLP-dependent aspartate aminotransferase-like (Major domain); 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 NCBIfam; TIGR01821; 5aminolev_synth; 1. DR PANTHER; PTHR13693:SF58; 5-AMINOLEVULINATE SYNTHASE, ERYTHROID-SPECIFIC, MITOCHONDRIAL; 1. DR PANTHER; PTHR13693; CLASS II AMINOTRANSFERASE/8-AMINO-7-OXONONANOATE SYNTHASE; 1. DR Pfam; PF00155; Aminotran_1_2; 1. DR Pfam; PF09029; Preseq_ALAS; 1. DR SUPFAM; SSF53383; PLP-dependent transferases; 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 //