HEM1_RAT
ID HEM1_RAT Reviewed; 642 AA.
AC P13195; Q6P782;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2004, sequence version 2.
DT 03-AUG-2022, entry version 137.
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 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], TISSUE SPECIFICITY, AND INDUCTION.
RC TISSUE=Liver;
RX PubMed=3356687; DOI=10.1016/s0021-9258(18)60700-8;
RA Srivastava G., Borthwick I.A., Maguire D.J., Elferink C.J., Bawden M.J.,
RA Mercer J.F.B., May B.K.;
RT "Regulation of 5-aminolevulinate synthase mRNA in different rat tissues.";
RL J. Biol. Chem. 263:5202-5209(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION.
RC TISSUE=Liver;
RX PubMed=3182776; DOI=10.1016/s0021-9258(18)37544-6;
RA Yamamoto M., Kure S., Engel J.D., Hiraga K.;
RT "Structure, turnover, and heme-mediated suppression of the level of mRNA
RT encoding rat liver delta-aminolevulinate synthase.";
RL J. Biol. Chem. 263:15973-15979(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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).
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 -!- TISSUE SPECIFICITY: Expressed in the liver, kidney, brain and testis.
CC {ECO:0000269|PubMed:3356687}.
CC -!- INDUCTION: Down-regulated by hemin in the liver and by 6-amino-
CC levulinate (or its methyl ester) in the liver, kidney, heart, testis
CC and brain. {ECO:0000269|PubMed:3182776, ECO:0000269|PubMed:3356687}.
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; J03190; AAA40790.1; -; mRNA.
DR EMBL; J04044; AAA40724.1; -; mRNA.
DR EMBL; BC061793; AAH61793.1; -; mRNA.
DR PIR; A28191; SYRTAL.
DR RefSeq; NP_077810.2; NM_024484.2.
DR AlphaFoldDB; P13195; -.
DR SMR; P13195; -.
DR STRING; 10116.ENSRNOP00000065087; -.
DR PaxDb; P13195; -.
DR GeneID; 65155; -.
DR KEGG; rno:65155; -.
DR CTD; 211; -.
DR RGD; 68392; Alas1.
DR eggNOG; KOG1360; Eukaryota.
DR InParanoid; P13195; -.
DR OrthoDB; 930001at2759; -.
DR PhylomeDB; P13195; -.
DR Reactome; R-RNO-189451; Heme biosynthesis.
DR UniPathway; UPA00251; UER00375.
DR PRO; PR:P13195; -.
DR Proteomes; UP000002494; 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; IDA:RGD.
DR GO; GO:0003870; F:5-aminolevulinate synthase activity; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEP:RGD.
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 GO; GO:0051591; P:response to cAMP; IEP:RGD.
DR GO; GO:0032025; P:response to cobalt ion; IEP:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0034698; P:response to gonadotropin; IEP:RGD.
DR GO; GO:0009635; P:response to herbicide; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0010045; P:response to nickel cation; IEP:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR GO; GO:0070541; P:response to platinum ion; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
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..642
FT /note="5-aminolevulinate synthase, non-specific,
FT mitochondrial"
FT /id="PRO_0000001232"
FT REGION 51..109
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 118..136
FT /note="SQTGSSVFRKASLELQEDV -> ARRAAASSARPVWSFRRTW (in Ref.
FT 1; AAA40790)"
FT /evidence="ECO:0000305"
FT CONFLICT 144
FT /note="K -> T (in Ref. 1; AAA40790)"
FT /evidence="ECO:0000305"
FT CONFLICT 195
FT /note="S -> V (in Ref. 1; AAA40790)"
FT /evidence="ECO:0000305"
FT CONFLICT 244..245
FT /note="KK -> NN (in Ref. 1; AAA40790)"
FT /evidence="ECO:0000305"
FT CONFLICT 251
FT /note="C -> S (in Ref. 1; AAA40790)"
FT /evidence="ECO:0000305"
FT CONFLICT 377
FT /note="V -> L (in Ref. 2; AAA40724)"
FT /evidence="ECO:0000305"
FT CONFLICT 587
FT /note="F -> Y (in Ref. 1; AAA40790)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 642 AA; 71021 MW; B28FC05D5F834886 CRC64;
METVVRRCPF LSRVPQAFLQ KAGKSLLFYA QNCPKMMEVG AKPAPRTVST SAAQCQQVKE
TPPANEKEKT AKAAVQQAPD ESQMAQTPDG TQLPPGHPSP STSQSSGSKC PFLAAQLSQT
GSSVFRKASL ELQEDVQEMH AVRKEVAQSP VLPSLVNAKR DGEGPSPLLK NFQDIMRKQR
PERVSHLLQD NLPKSVSTFQ YDHFFEKKID EKKNDHTYRV FKTVNRRAQI FPMADDYTDS
LITKKQVSVW CSNDYLGMSR HPRVCGAVIE TVKQHGAGAG GTRNISGTSK FHVELEQELA
DLHGKDAALL FSSCFVANDS TLFTLAKMMP GCEIYSDSGN HASMIQGIRN SRVPKYIFRH
NDVNHLRELL QRSDPSVPKI VAFETVHSMD GAVCPLEELC DVAHEFGAIT FVDEVHAVGL
YGASGGGIGD RDGVMPKMDI ISGTLGKAFG CVGGYIASTS LLIDTVRSYA AGFIFTTSLP
PMLLAGALES VRILKSNEGR ALRRQHQRNV KLMRQMLMDA GLPVIHCPSH IIPVRVADAA
KNTEICDELM TRHNIYVQAI NYPTVPRGEE LLRIAPTPHH TPQMMNFFLE KLLLTWKRVG
LELKPHSSAE CNFCRRPLHF EVMSEREKAY FSGMSKMVSA QA
