ID HEM0_BOVIN Reviewed; 587 AA. AC Q3ZC31; DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot. DT 27-SEP-2005, sequence version 1. DT 24-JAN-2024, entry version 116. 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; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Hereford; TISSUE=Fetal liver; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases. 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. Interacts with SUCLA2. CC {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; BC102938; AAI02939.1; -; mRNA. DR RefSeq; NP_001030275.1; NM_001035103.2. DR AlphaFoldDB; Q3ZC31; -. DR SMR; Q3ZC31; -. DR STRING; 9913.ENSBTAP00000067103; -. DR PaxDb; 9913-ENSBTAP00000017538; -. DR Ensembl; ENSBTAT00000017538.4; ENSBTAP00000017538.3; ENSBTAG00000013178.4. DR GeneID; 511791; -. DR KEGG; bta:511791; -. DR CTD; 212; -. DR VEuPathDB; HostDB:ENSBTAG00000013178; -. DR VGNC; VGNC:25804; ALAS2. DR eggNOG; KOG1360; Eukaryota. DR GeneTree; ENSGT00940000159912; -. DR HOGENOM; CLU_015846_6_1_1; -. DR InParanoid; Q3ZC31; -. DR OrthoDB; 9643at2759; -. DR TreeFam; TF300724; -. DR Reactome; R-BTA-189451; Heme biosynthesis. DR UniPathway; UPA00251; UER00375. DR Proteomes; UP000009136; Chromosome X. DR Bgee; ENSBTAG00000013178; Expressed in adrenal gland and 33 other cell types or tissues. DR ExpressionAtlas; Q3ZC31; differential. 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; 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: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..49 FT /note="Mitochondrion" FT /evidence="ECO:0000250|UniProtKB:P22557" FT CHAIN 50..587 FT /note="5-aminolevulinate synthase, erythroid-specific, FT mitochondrial" FT /id="PRO_0000280705" FT ACT_SITE 391 FT /evidence="ECO:0000250|UniProtKB:P18079" FT BINDING 163 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P18079" FT BINDING 258 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 259 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 280 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P18079" FT BINDING 299 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P18079" FT BINDING 332 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 360 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 388 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 420 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 421 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 508 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P18079" FT MOD_RES 391 FT /note="N6-(pyridoxal phosphate)lysine" FT /evidence="ECO:0000250|UniProtKB:P22557" SQ SEQUENCE 587 AA; 65137 MW; 8D0D94383137F5DC CRC64; MVTAAMLLQR CPVLIRSPTG LLGKMIKTHQ FLFGIGRCPI LATQGPSFSQ IHLKATKAGG DSPSWAKSHC PFMLLELQDG KSKIVQKAAP EVQEDVKTFK TDLPTSLAST SLKKTFSSPQ EPEKNSEKVT HLIQNNMAGD HVFGYDQFFR DKIMEKKQDH TYRVFKTVNR WADAYPFAEH FFEASVASKD VSVWCSNDYL GMSRHPRVLQ ATQEILQRHG AGAGGTRNIS GTSKFHVELE QELAELHQKD SALLFSSCFV ANDSTLFTLA KILPGCEIYS DAGNHASMIQ GIRNSGAAKF VFRHNDPDHL KKLLKKSNPE TPKIVAFETV HSMDGAICPL EELCDVAHQY GALTFVDEVH AVGLYGSRGA GIGERDGIMH KIDIISGTLG KAFGCVGGYI ASTRDLVDMV RSYAAGFIFT TSLPPMVLSG ALESVRLLKG EEGQALRRAH QRNVKHMRQL LMDRGLPVIP CPSHIIPIRV GDAMLNTRIC DLLLSKYGIY VQAINYPTVP RGEELLRLAP SPHHSPQMME DFVEKLLEAW TEVGLPLQDI SIAACNFCRR PVHFELMSEW ERSYFGNMGP QYVTTYA //