ID HEM0_RAT Reviewed; 587 AA. AC Q63147; Q63895; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 24-JAN-2024, entry version 135. DE RecName: Full=5-aminolevulinate synthase, erythroid-specific, mitochondrial; DE Short=ALAS-E {ECO:0000303|PubMed:8407861}; DE EC=2.3.1.37 {ECO:0000269|PubMed:8407861}; 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=Alase; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, TISSUE RP SPECIFICITY, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=8407861; DOI=10.1093/oxfordjournals.jbchem.a124123; RA Munakata H., Yamagami T., Nagai T., Yamamoto M., Hayashi N.; RT "Purification and structure of rat erythroid-specific delta-aminolevulinate RT synthase."; RL J. Biochem. 114:103-111(1993). RN [2] RP SEQUENCE REVISION. RA Furuyama K.; RL Submitted (JUN-1996) to the EMBL/GenBank/DDBJ databases. RN [3] RP SUBCELLULAR LOCATION. RX PubMed=2369125; DOI=10.1016/0003-9861(90)90338-y; RA Rohde M., Srivastava G., Rylatt D.B., Bundesen P., Zamattia J., Crane D.I., RA May B.K.; RT "Immunocytochemical studies on the localization of 5-aminolevulinate RT synthase in rat liver."; RL Arch. Biochem. Biophys. 280:331-335(1990). 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 (PubMed:8407861). Contributes CC significantly to heme formation during erythropoiesis (By similarity). CC {ECO:0000250|UniProtKB:P22557, ECO:0000269|PubMed:8407861}. 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:0000269|PubMed:8407861}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12922; CC Evidence={ECO:0000305|PubMed:8407861}; CC -!- COFACTOR: CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326; CC Evidence={ECO:0000250|UniProtKB:P22557}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=6.5 mM for glycine {ECO:0000269|PubMed:8407861}; CC KM=2 uM for succinyl-CoA {ECO:0000269|PubMed:8407861}; CC -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX CC biosynthesis; 5-aminolevulinate from glycine: step 1/1. CC {ECO:0000305|PubMed:8407861}. CC -!- SUBUNIT: Homodimer. Interacts with SUCLA2. CC {ECO:0000250|UniProtKB:P22557}. CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:2369125}; Peripheral membrane protein CC {ECO:0000305}. Note=Localizes to the matrix side of the mitochondrion CC inner membrane. {ECO:0000269|PubMed:2369125}. CC -!- TISSUE SPECIFICITY: Erythroid-specific. {ECO:0000305|PubMed:8407861}. 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; D86297; BAA13063.1; -; mRNA. DR PIR; JX0278; JX0278. DR RefSeq; NP_037329.1; NM_013197.1. DR AlphaFoldDB; Q63147; -. DR SMR; Q63147; -. DR STRING; 10116.ENSRNOP00000000180; -. DR PhosphoSitePlus; Q63147; -. DR PaxDb; 10116-ENSRNOP00000000180; -. DR DNASU; 25748; -. DR GeneID; 25748; -. DR KEGG; rno:25748; -. DR AGR; RGD:2084; -. DR CTD; 212; -. DR RGD; 2084; Alas2. DR eggNOG; KOG1360; Eukaryota. DR InParanoid; Q63147; -. DR OrthoDB; 9643at2759; -. DR PhylomeDB; Q63147; -. DR Reactome; R-RNO-189451; Heme biosynthesis. DR UniPathway; UPA00251; UER00375. DR PRO; PR:Q63147; -. DR Proteomes; UP000002494; 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; IDA:UniProtKB. DR GO; GO:0120225; F:coenzyme A binding; IDA:RGD. DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro. DR GO; GO:0048821; P:erythrocyte development; IBA:GO_Central. 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:0006879; P:intracellular iron ion homeostasis; ISO:RGD. DR GO; GO:0007595; P:lactation; IEP:RGD. DR GO; GO:0097421; P:liver regeneration; IEP:RGD. DR GO; GO:0060135; P:maternal process involved in female pregnancy; IEP:RGD. DR GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:UniProtKB-UniPathway. DR GO; GO:1901423; P:response to benzene; IEP:RGD. DR GO; GO:0032025; P:response to cobalt ion; IEP:RGD. DR GO; GO:0070542; P:response to fatty acid; IEP:RGD. DR GO; GO:0001666; P:response to hypoxia; IEP:RGD. DR GO; GO:0010288; P:response to lead ion; IEP:RGD. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD. 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 1: Evidence at protein level; KW Acyltransferase; Direct protein sequencing; Heme biosynthesis; Membrane; KW Mitochondrion; Mitochondrion inner membrane; Pyridoxal phosphate; KW Reference proteome; 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_0000001225" 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:P08680" SQ SEQUENCE 587 AA; 64842 MW; A6287CA9543DECAF CRC64; MVAAAMLLRS CPVLSKGPTG LLGKVAKTYQ FLFGIGRCPI LATQGPTCSQ IHLKATKAGA DSPSWTKSHC PFMLSELQDR KSKIVQRAAP EVQEDVKTFK TDLLSFMEST TRSQSVPRFQ DPEQTGGAPP LLIQNNMTGS QAFGYDQFFR DKIMEKKQDH TYRVFKTVNR WANAYPFAQH FSEASMDSKD VSVWCSNDYL GISRHPRVLQ AIEETLKNHG AGAGGTRNIS GTSKFHVELE QELAELHHKD SALLFSSCFV ANDSTLFTLA KLLPGCEIYS DAGNHASMIQ GIRNSGAVKF VFRHNDPGHL KKLLEKSDPK TPKIVAFETV HSMDGAICPL EELCDVAHQY GALTFVDEVH AVGLYGTRGA GIGERDGIMH KLDIISGTLG KAFGCVGGYI ASTRDLVDMV RSYAAGFIFT TSLPPMVLSG ALESVRLLKG EEGQALRRAH QRNVKHMRQL LMDRGFPVIP CPSHIIPIRV GNAALNSKIC DLLLAKHSIY VQAINYPTVP RGEELLRLAP SPHHSPQMME NFVEKLLLAW TEVGLPLQDV SVAACNFCRR PVHFELMSEW ERSYFGNMGP QYVTTYA //