ID HEM1_MOUSE Reviewed; 642 AA.
AC Q8VC19; Q64453;
DT 27-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2004, sequence version 2.
DT 27-MAR-2024, entry version 159.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 188-642.
RC STRAIN=DBA/2J; TISSUE=Liver;
RA Young E.G., Dierks P.M.;
RL Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, and Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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-578, 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; BC022110; AAH22110.1; -; mRNA.
DR EMBL; M63245; AAA91867.1; -; mRNA.
DR CCDS; CCDS40756.2; -.
DR RefSeq; NP_001278764.1; NM_001291835.1.
DR RefSeq; NP_065584.2; NM_020559.2.
DR AlphaFoldDB; Q8VC19; -.
DR SMR; Q8VC19; -.
DR BioGRID; 198058; 2.
DR STRING; 10090.ENSMUSP00000117014; -.
DR iPTMnet; Q8VC19; -.
DR PhosphoSitePlus; Q8VC19; -.
DR SwissPalm; Q8VC19; -.
DR MaxQB; Q8VC19; -.
DR PaxDb; 10090-ENSMUSP00000108143; -.
DR ProteomicsDB; 269693; -.
DR Pumba; Q8VC19; -.
DR Antibodypedia; 4303; 372 antibodies from 34 providers.
DR DNASU; 11655; -.
DR Ensembl; ENSMUST00000112524.9; ENSMUSP00000108143.3; ENSMUSG00000032786.17.
DR Ensembl; ENSMUST00000141118.9; ENSMUSP00000117014.2; ENSMUSG00000032786.17.
DR GeneID; 11655; -.
DR KEGG; mmu:11655; -.
DR UCSC; uc009rjj.2; mouse.
DR AGR; MGI:87989; -.
DR CTD; 211; -.
DR MGI; MGI:87989; Alas1.
DR VEuPathDB; HostDB:ENSMUSG00000032786; -.
DR eggNOG; KOG1360; Eukaryota.
DR GeneTree; ENSGT00940000156030; -.
DR HOGENOM; CLU_015846_6_1_1; -.
DR InParanoid; Q8VC19; -.
DR OMA; RAYFSGM; -.
DR OrthoDB; 9643at2759; -.
DR PhylomeDB; Q8VC19; -.
DR TreeFam; TF300724; -.
DR Reactome; R-MMU-189451; Heme biosynthesis.
DR UniPathway; UPA00251; UER00375.
DR BioGRID-ORCS; 11655; 6 hits in 81 CRISPR screens.
DR ChiTaRS; Alas1; mouse.
DR PRO; PR:Q8VC19; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q8VC19; Protein.
DR Bgee; ENSMUSG00000032786; Expressed in adrenal gland and 274 other cell types or tissues.
DR ExpressionAtlas; Q8VC19; baseline and differential.
DR Genevisible; Q8VC19; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0003870; F:5-aminolevulinate synthase activity; IMP:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0048821; P:erythrocyte development; IBA:GO_Central.
DR GO; GO:0006784; P:heme A biosynthetic process; IMP:MGI.
DR GO; GO:0006785; P:heme B biosynthetic process; IMP:MGI.
DR GO; GO:0006783; P:heme biosynthetic process; IBA:GO_Central.
DR GO; GO:0048034; P:heme O biosynthetic process; IMP:MGI.
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 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 1: Evidence at protein 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..642
FT /note="5-aminolevulinate synthase, non-specific,
FT mitochondrial"
FT /id="PRO_0000001231"
FT REGION 50..109
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 144..163
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 76..109
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 447
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 219
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 336
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 355
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
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:P18079"
FT BINDING 416
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 444
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 476
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 477
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 564
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT MOD_RES 447
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT MOD_RES 578
FT /note="Hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:P13196"
FT CONFLICT 192
FT /note="L -> S (in Ref. 2; AAA91867)"
FT /evidence="ECO:0000305"
FT CONFLICT 391
FT /note="Missing (in Ref. 1; AAH22110)"
FT /evidence="ECO:0000305"
FT CONFLICT 463
FT /note="I -> T (in Ref. 2; AAA91867)"
FT /evidence="ECO:0000305"
FT CONFLICT 501
FT /note="A -> P (in Ref. 2; AAA91867)"
FT /evidence="ECO:0000305"
FT CONFLICT 602
FT /note="E -> V (in Ref. 2; AAA91867)"
FT /evidence="ECO:0000305"
FT CONFLICT 625
FT /note="E -> V (in Ref. 2; AAA91867)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 642 AA; 71018 MW; 34E0CBEB8599CFE5 CRC64;
METVVRRCPF LSRVPQAFLQ KAGKSLLFYA QNCPKMMEVG AKPAPRTLST SAVHCQQVKE
TPPANEKEKT AKAAVQQAPD ESQMAQTPDG TQLPSGHPSP ATSQGSGSKC PFLAAQLSQT
GSSVFRKASL ELQEDVQEMH AVRKEAAQSP VPPSLVNVKT DGEDPSRLLK NFQDIMRKQR
PERVSHLLQD NLPKSVSTFQ YDHFFEKKID EKKNDHTYRV FKTVNRRAQI FPMADDYTDS
LITKKQVSVW CSNDYLGMSR HPRVCGAVME TVKQHGAGAG GTRNISGTSK FHVELEQALA
DLHGKDAALL FSSCFVANDS TLFTLAKMMP GCEIYSDSGN HASMIQGIRN SRVPKYIFRH
NDVNHLRELL QRSDPSVPKI VAFETVHSMD GAVCPLEELC DVAHEFGAIT FVDEVHAVGL
YGARGGGIGD RDGVMPKMDI ISGTLGKAFG CVGGYIASTS LLIDTVRSYA AGFIFTTSLP
PMLLAGALES VRILKSSEGR ALRRQHQRNV KLLRQMLMDA GLPVIHCPSH IIPVRVADAA
KNTEICDELM TRHNIYVQAI NYPTVPRGEE LLRIAPTPHH TPQMMNFFVE KLLVTWKRVG
LELKPHSSAE CNFCRRPLHF EVMSEREKAY FSGMSKMVSA QA
//
