HEM0_CHICK
ID HEM0_CHICK Reviewed; 513 AA.
AC P18080;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 2.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=5-aminolevulinate synthase, erythroid-specific, mitochondrial;
DE Short=ALAS-E;
DE EC=2.3.1.37 {ECO:0000250|UniProtKB:P22557};
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 Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Erythroid cell;
RX PubMed=2915978; DOI=10.1073/pnas.86.3.792;
RA Riddle R.D., Yamamoto M., Engel J.D.;
RT "Expression of delta-aminolevulinate synthase in avian cells: separate
RT genes encode erythroid-specific and nonspecific isozymes.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:792-796(1989).
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 (By similarity). Contributes
CC significantly to heme formation during erythropoiesis (By similarity).
CC {ECO:0000250|UniProtKB:P22557}.
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:P22557};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12922;
CC Evidence={ECO:0000250|UniProtKB:P22557};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000250|UniProtKB:P22557};
CC -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX
CC biosynthesis; 5-aminolevulinate from glycine: step 1/1.
CC {ECO:0000250|UniProtKB:P22557}.
CC -!- SUBUNIT: Homodimer. {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: Erythroid-specific. {ECO:0000269|PubMed:2915978}.
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; M24367; AAA20400.1; -; mRNA.
DR PIR; A31452; SYCHLE.
DR AlphaFoldDB; P18080; -.
DR SMR; P18080; -.
DR VEuPathDB; HostDB:geneid_552895; -.
DR InParanoid; P18080; -.
DR PhylomeDB; P18080; -.
DR Reactome; R-GGA-421984; Heme synthesis.
DR UniPathway; UPA00251; UER00375.
DR Proteomes; UP000000539; Unplaced.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
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 Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR InterPro; IPR010961; 4pyrrol_synth_NH2levulA_synth.
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 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; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Pyridoxal phosphate; Reference proteome;
KW Transferase; Transit peptide.
FT TRANSIT 1..18
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 19..513
FT /note="5-aminolevulinate synthase, erythroid-specific,
FT mitochondrial"
FT /id="PRO_0000001226"
FT ACT_SITE 323
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 98
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 190
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 191
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 212
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 231
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 264
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 292
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 320
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 352
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 353
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 437
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT MOD_RES 323
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:P08680"
SQ SEQUENCE 513 AA; 54778 MW; C319A4DE5294CF74 CRC64;
MAAFLRCPLL ARHPPLARAF ATGARCPFMG FAHRAAPELQ EDVERPQIPA VEVLEELLRD
GGAALNRTVR DCMDEDAFPY EEQFQAQLGA LRRTHTYRVV TAVGRRADAP PLGTRGTAPH
TSVELWCSSD YLGLSRHPAV LRAARAALDA HGLGAGGTRN IGGTSPLHGA LERALALLHR
QPRAALFSSC FAANDTALDT LARILPGCQV YSDAGNHASM IQGIRRRGVP KFIFRHNDPH
HLEQLLGRSP PGVPKIVAFE SLHSMDGSIA PLEELCDVAH AYGALTFVDE VHAVGLYGAR
GAGIAERDGV QHKVDVVSGT LGKALGAVGG YIAGSEALVD AVRSLGPGFI FTTALPPQRG
GGALAALQVV GSAEGAALRR AHQRHAKHLR VLLRDRGLPA LPSHIVPVRW DAEANTRLSR
ALLEEHGLYV QAINHPTVPR GQELLLRIAP TPHHSPPMLE NLADKLSECW GAVGLPREDP
PGPSCSSCHR PLHLSLLSPL ERDQFGVRGA AAG
