HEM1_BOVIN
ID HEM1_BOVIN Reviewed; 647 AA.
AC A6QLI6;
DT 14-OCT-2008, integrated into UniProtKB/Swiss-Prot.
DT 21-AUG-2007, sequence version 1.
DT 03-AUG-2022, 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 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=Brain cortex;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUN-2007) 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-583, 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; BC147978; AAI47979.1; -; mRNA.
DR RefSeq; NP_001094624.1; NM_001101154.1.
DR AlphaFoldDB; A6QLI6; -.
DR SMR; A6QLI6; -.
DR STRING; 9913.ENSBTAP00000005380; -.
DR PaxDb; A6QLI6; -.
DR PRIDE; A6QLI6; -.
DR GeneID; 534286; -.
DR KEGG; bta:534286; -.
DR CTD; 211; -.
DR eggNOG; KOG1360; Eukaryota.
DR HOGENOM; CLU_015846_6_1_1; -.
DR InParanoid; A6QLI6; -.
DR OrthoDB; 930001at2759; -.
DR TreeFam; TF300724; -.
DR UniPathway; UPA00251; UER00375.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
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: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..647
FT /note="5-aminolevulinate synthase, non-specific,
FT mitochondrial"
FT /id="PRO_0000352676"
FT REGION 61..112
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 77..112
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 452
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 224
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 341
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 360
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 393
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 421
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 449
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 481
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 482
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 569
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT MOD_RES 452
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT MOD_RES 583
FT /note="Hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:P13196"
SQ SEQUENCE 647 AA; 71062 MW; DF0A4622352C9401 CRC64;
METVVRRCPF LSRVPQAFLQ KAGKSLLFYA QNCPKMMEIG AKPAPRALST SAVLCQQVTE
TPPANEKDKA AKAEVQQAPD GSQQAPDGSQ QTADGTQLPS GHPSLASSQG TGSKCPFLAA
EMSQGGSSVF RKASLALQED VQEMHAVREE VAQTSVNPSV INVKTEGGEL NGLLKNFQDI
MRKQRPERVS HLLQDNLPKS VCTFQYDRFF EKKIDEKKND HSYRVFKTVN RKAQCFPMAD
DYSDSLISKK QVSVWCSNDY LGMSRHPRVC GAVIDTLKQH GTGAGGTRNI SGTSKFHVDL
EQELADLHGK DAALLFSSCF VANDSTLFTL AKMMPGCEIY SDAGNHASMI QGIRNSGVPK
YIFRHNDVSH LRELLQRSDP AVPKIVAFET VHSMDGAVCP LEELCDVAHE FGAITFVDEV
HAVGLYGLQG GGIGDRDGVM PKMDIISGTL GKAIGCVGGY IASTSSLIDT VRSYAAGFIF
TTSLPPMLLA GALESVRILR STEGRTLRRQ HQRNVKLMRQ MLMDAGLPVV HCPSHIIPVR
VADAAKNTEV CDELMTRHNI YVQAINYPTV PRGEELLRIA PTPHHTPQMM SYFVDNLLAT
WKRVGLELKP HSSAECNFCR RPLHFEMMSE REKSYFSGMS KLVSAQA
