HEM1_PONAB
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 03-AUG-2022, entry version 82.
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}.
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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; 930001at2759; -.
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 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; 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
