ID HEM1_PONAB Reviewed; 640 AA. AC Q5R9R9; DT 14-OCT-2008, integrated into UniProtKB/Swiss-Prot. DT 21-DEC-2004, sequence version 1. DT 27-MAR-2024, entry version 86. 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; OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Pongo. OX NCBI_TaxID=9601; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Kidney; RG The German cDNA consortium; RL Submitted (NOV-2004) 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. {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 (By similarity). Interacts (hydroxylated form) with CC VHL (By similarity). {ECO:0000250|UniProtKB:P13196, 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 -!- PTM: In normoxia, is hydroxylated at Pro-576, promoting interaction CC with VHL, initiating ubiquitination and subsequent degradation via the CC proteasome. {ECO:0000250|UniProtKB:P13196}. CC -!- PTM: Ubiquitinated; in normoxia following hydroxylation and interaction CC with VHL, leading to its subsequent degradation via the proteasome. CC {ECO:0000250|UniProtKB:P13196}. 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; CR859313; CAH91491.1; -; mRNA. DR RefSeq; NP_001125877.1; NM_001132405.1. DR AlphaFoldDB; Q5R9R9; -. DR SMR; Q5R9R9; -. DR STRING; 9601.ENSPPYP00000015461; -. DR GeneID; 100172808; -. DR KEGG; pon:100172808; -. DR CTD; 211; -. DR eggNOG; KOG1360; Eukaryota. DR InParanoid; Q5R9R9; -. DR OrthoDB; 9643at2759; -. DR UniPathway; UPA00251; UER00375. DR Proteomes; UP000001595; 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 CDD; cd06454; KBL_like; 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:SF50; 5-AMINOLEVULINATE SYNTHASE, NON-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; Hydroxylation; Membrane; Mitochondrion; KW Mitochondrion inner membrane; Pyridoxal phosphate; Reference proteome; KW Transferase; Transit peptide; Ubl conjugation. 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_0000352677" FT REGION 60..103 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 143..163 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 75..103 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" FT MOD_RES 576 FT /note="Hydroxyproline" FT /evidence="ECO:0000250|UniProtKB:P13196" SQ SEQUENCE 640 AA; 70514 MW; D0F107895D03F7DA CRC64; METVVRSCPF LSRVPQAFLQ KAGKSLLFYA QNCPKMMEVG AKPAPRALST AAVHYQQIKE TPPASEKDKT AKAKVQQTPD GSQQSPDGTQ LPSGHPLPAT SQGTASKCPF LAAQMNQRGS SVFCKASLEL QEDVQEMNAV RKEVAETSGG PSVVSVKTDG GDPSGLLKNF QDIMQKQRPE RVSHLLQDDL PKSVSTFQYD RFFEKKIDEK KNDHTYRVFK TVNRRAHIFP MADDYSDSLI TKKQVSVWCS NDYLGMSRHP RVCGAVMDTL KQHGAGAGGT RNISGTSKFH VDLERELADL HGKDAALLFS SCFVANDSTL FTLAKMMPGC EIYSDSGNHA SMIQGIRNSR VPKYIFRHND VSHLRELLQR SDPSVPKIVA FETVHSMDGA VCPLEELCDV AHEFGAITFV DEVHAVGLYG ARGGGIGDRD GVMPKMDIIS GTLGKAFGCV GGYIASTSSL IDTVRSYAAG FIFTTSLPPM LLAGALESVR ILKSAEGRVL RRQHQRNVKL MRQMLMDAGL PVVHCPSHII PVRVADAAKN TEVCDELMSR HNIYVQAINY PTVPRGEELL RIAPTPHHTP QMMNYFLENL LVTWKQVGLE LEPHSSAECN FCRRPLHFEV MSEREKSYFS GLSKLVSAQA //