HEM0_RAT
ID HEM0_RAT Reviewed; 587 AA.
AC Q63147; Q63895;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=5-aminolevulinate synthase, erythroid-specific, mitochondrial;
DE Short=ALAS-E {ECO:0000303|PubMed:8407861};
DE EC=2.3.1.37 {ECO:0000269|PubMed:8407861};
DE AltName: Full=5-aminolevulinic acid synthase 2;
DE AltName: Full=Delta-ALA synthase 2;
DE AltName: Full=Delta-aminolevulinate synthase 2;
DE Flags: Precursor;
GN Name=Alas2; Synonyms=Alase;
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], PARTIAL PROTEIN SEQUENCE, FUNCTION, TISSUE
RP SPECIFICITY, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=8407861; DOI=10.1093/oxfordjournals.jbchem.a124123;
RA Munakata H., Yamagami T., Nagai T., Yamamoto M., Hayashi N.;
RT "Purification and structure of rat erythroid-specific delta-aminolevulinate
RT synthase.";
RL J. Biochem. 114:103-111(1993).
RN [2]
RP SEQUENCE REVISION.
RA Furuyama K.;
RL Submitted (JUN-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=2369125; DOI=10.1016/0003-9861(90)90338-y;
RA Rohde M., Srivastava G., Rylatt D.B., Bundesen P., Zamattia J., Crane D.I.,
RA May B.K.;
RT "Immunocytochemical studies on the localization of 5-aminolevulinate
RT synthase in rat liver.";
RL Arch. Biochem. Biophys. 280:331-335(1990).
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 (PubMed:8407861). Contributes
CC significantly to heme formation during erythropoiesis (By similarity).
CC {ECO:0000250|UniProtKB:P22557, ECO:0000269|PubMed:8407861}.
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:0000269|PubMed:8407861};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12922;
CC Evidence={ECO:0000305|PubMed:8407861};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000250|UniProtKB:P22557};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.5 mM for glycine {ECO:0000269|PubMed:8407861};
CC KM=2 uM for succinyl-CoA {ECO:0000269|PubMed:8407861};
CC -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX
CC biosynthesis; 5-aminolevulinate from glycine: step 1/1.
CC {ECO:0000305|PubMed:8407861}.
CC -!- SUBUNIT: Homodimer. Interacts with SUCLA2.
CC {ECO:0000250|UniProtKB:P22557}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:2369125}; Peripheral membrane protein
CC {ECO:0000305}. Note=Localizes to the matrix side of the mitochondrion
CC inner membrane. {ECO:0000269|PubMed:2369125}.
CC -!- TISSUE SPECIFICITY: Erythroid-specific. {ECO:0000305|PubMed:8407861}.
CC -!- DOMAIN: C-terminus is a mobile self-inhibitory loop which interferes
CC directly with active site. {ECO:0000250|UniProtKB:P22557}.
CC -!- SIMILARITY: Belongs to the class-II pyridoxal-phosphate-dependent
CC aminotransferase family. {ECO:0000305}.
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DR EMBL; D86297; BAA13063.1; -; mRNA.
DR PIR; JX0278; JX0278.
DR RefSeq; NP_037329.1; NM_013197.1.
DR AlphaFoldDB; Q63147; -.
DR SMR; Q63147; -.
DR STRING; 10116.ENSRNOP00000000180; -.
DR DNASU; 25748; -.
DR GeneID; 25748; -.
DR KEGG; rno:25748; -.
DR CTD; 212; -.
DR RGD; 2084; Alas2.
DR eggNOG; KOG1360; Eukaryota.
DR InParanoid; Q63147; -.
DR OrthoDB; 930001at2759; -.
DR PhylomeDB; Q63147; -.
DR Reactome; R-RNO-189451; Heme biosynthesis.
DR UniPathway; UPA00251; UER00375.
DR PRO; PR:Q63147; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
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:UniProtKB.
DR GO; GO:0120225; F:coenzyme A binding; IDA:RGD.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0006879; P:cellular iron ion homeostasis; ISO:RGD.
DR GO; GO:0048821; P:erythrocyte development; IBA:GO_Central.
DR GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0006783; P:heme biosynthetic process; ISS:UniProtKB.
DR GO; GO:0042541; P:hemoglobin biosynthetic process; ISS:UniProtKB.
DR GO; GO:0007595; P:lactation; IEP:RGD.
DR GO; GO:0097421; P:liver regeneration; IEP:RGD.
DR GO; GO:0060135; P:maternal process involved in female pregnancy; IEP:RGD.
DR GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:1901423; P:response to benzene; IEP:RGD.
DR GO; GO:0032025; P:response to cobalt ion; IEP:RGD.
DR GO; GO:0070542; P:response to fatty acid; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0010288; P:response to lead 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 1: Evidence at protein level;
KW Acyltransferase; Direct protein sequencing; Heme biosynthesis; Membrane;
KW Mitochondrion; Mitochondrion inner membrane; Pyridoxal phosphate;
KW Reference proteome; Transferase; Transit peptide.
FT TRANSIT 1..49
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:P22557"
FT CHAIN 50..587
FT /note="5-aminolevulinate synthase, erythroid-specific,
FT mitochondrial"
FT /id="PRO_0000001225"
FT ACT_SITE 391
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 163
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 258
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:P22557"
FT BINDING 259
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:P22557"
FT BINDING 280
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 299
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 332
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 360
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:P22557"
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:P22557"
FT BINDING 420
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:P22557"
FT BINDING 421
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:P22557"
FT BINDING 508
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT MOD_RES 391
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:P08680"
SQ SEQUENCE 587 AA; 64842 MW; A6287CA9543DECAF CRC64;
MVAAAMLLRS CPVLSKGPTG LLGKVAKTYQ FLFGIGRCPI LATQGPTCSQ IHLKATKAGA
DSPSWTKSHC PFMLSELQDR KSKIVQRAAP EVQEDVKTFK TDLLSFMEST TRSQSVPRFQ
DPEQTGGAPP LLIQNNMTGS QAFGYDQFFR DKIMEKKQDH TYRVFKTVNR WANAYPFAQH
FSEASMDSKD VSVWCSNDYL GISRHPRVLQ AIEETLKNHG AGAGGTRNIS GTSKFHVELE
QELAELHHKD SALLFSSCFV ANDSTLFTLA KLLPGCEIYS DAGNHASMIQ GIRNSGAVKF
VFRHNDPGHL KKLLEKSDPK TPKIVAFETV HSMDGAICPL EELCDVAHQY GALTFVDEVH
AVGLYGTRGA GIGERDGIMH KLDIISGTLG KAFGCVGGYI ASTRDLVDMV RSYAAGFIFT
TSLPPMVLSG ALESVRLLKG EEGQALRRAH QRNVKHMRQL LMDRGFPVIP CPSHIIPIRV
GNAALNSKIC DLLLAKHSIY VQAINYPTVP RGEELLRLAP SPHHSPQMME NFVEKLLLAW
TEVGLPLQDV SVAACNFCRR PVHFELMSEW ERSYFGNMGP QYVTTYA
