ID   HEM0_MOUSE              Reviewed;         587 AA.
AC   P08680; Q64452; Q9DCN0;
DT   01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2002, sequence version 3.
DT   24-JAN-2024, entry version 196.
DE   RecName: Full=5-aminolevulinate synthase, erythroid-specific, mitochondrial;
DE            Short=ALAS-E;
DE            EC=2.3.1.37 {ECO:0000269|PubMed:3557128, ECO:0000269|PubMed:8268805};
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;
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 [MRNA], FUNCTION, CATALYTIC ACTIVITY, TISSUE
RP   SPECIFICITY, AND SUBCELLULAR LOCATION.
RC   TISSUE=Liver;
RX   PubMed=3557128; DOI=10.1016/0378-1119(86)90351-3;
RA   Schoenhaut D.S., Curtis P.J.;
RT   "Nucleotide sequence of mouse 5-aminolevulinic acid synthase cDNA and
RT   expression of its gene in hepatic and erythroid tissues.";
RL   Gene 48:55-63(1986).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=DBA/2J; TISSUE=Erythroleukemia;
RA   Young E.G., Dierks P.M.;
RT   "Two genes encode Ala synthase in DBA/2 mouse: housekeeping and erythroid-
RT   specific.";
RL   Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Kidney;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [4]
RP   FUNCTION, CATALYTIC ACTIVITY, PYRIDOXAL PHOSPHATE AT LYS-391, AND
RP   MUTAGENESIS OF LYS-391.
RX   PubMed=8268805; DOI=10.1002/pro.5560021117;
RA   Ferreira G.C., Neame P.J., Dailey H.A.;
RT   "Heme biosynthesis in mammalian systems: evidence of a Schiff base linkage
RT   between the pyridoxal 5'-phosphate cofactor and a lysine residue in 5-
RT   aminolevulinate synthase.";
RL   Protein Sci. 2:1959-1965(1993).
RN   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Spleen;
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).
RN   [6]
RP   STRUCTURE BY NMR OF 1-49, AND TRANSIT PEPTIDE CLEAVAGE SITE.
RX   PubMed=11566198; DOI=10.1016/s0014-5793(01)02818-6;
RA   Goodfellow B.J., Dias J.S., Ferreira G.C., Henklein P., Wray V.,
RA   Macedo A.L.;
RT   "The solution structure and heme binding of the presequence of murine 5-
RT   aminolevulinate synthase.";
RL   FEBS Lett. 505:325-331(2001).
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:3557128,
CC       PubMed:8268805). Contributes significantly to heme formation during
CC       erythropoiesis (By similarity). {ECO:0000250|UniProtKB:P22557,
CC       ECO:0000269|PubMed:3557128, ECO:0000269|PubMed:8268805}.
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:3557128, ECO:0000269|PubMed:8268805};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12922;
CC         Evidence={ECO:0000305|PubMed:3557128};
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. Interacts with SUCLA2.
CC       {ECO:0000250|UniProtKB:P22557}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC       {ECO:0000250|UniProtKB:P22557}; Peripheral membrane protein
CC       {ECO:0000250|UniProtKB:P22557}. Mitochondrion
CC       {ECO:0000269|PubMed:3557128}. Note=Localizes to the matrix side of the
CC       mitochondrion inner membrane. {ECO:0000250|UniProtKB:P22557}.
CC   -!- TISSUE SPECIFICITY: Predomnantly expressed in erythroid cells.
CC       {ECO:0000269|PubMed:3557128}.
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}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA37207.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; M15268; AAA37207.1; ALT_INIT; mRNA.
DR   EMBL; M63244; AAA91866.1; -; mRNA.
DR   EMBL; AK002642; BAB22254.1; -; mRNA.
DR   EMBL; AK077610; BAC36898.1; -; mRNA.
DR   CCDS; CCDS41173.1; -.
DR   PIR; A29040; SYMSAL.
DR   RefSeq; NP_001095916.1; NM_001102446.1.
DR   RefSeq; NP_033783.1; NM_009653.3.
DR   PDB; 1H7D; NMR; -; A=1-49.
DR   PDB; 1H7J; NMR; -; A=1-26.
DR   PDBsum; 1H7D; -.
DR   PDBsum; 1H7J; -.
DR   AlphaFoldDB; P08680; -.
DR   SMR; P08680; -.
DR   BioGRID; 198059; 3.
DR   IntAct; P08680; 4.
DR   STRING; 10090.ENSMUSP00000066040; -.
DR   iPTMnet; P08680; -.
DR   PhosphoSitePlus; P08680; -.
DR   MaxQB; P08680; -.
DR   PaxDb; 10090-ENSMUSP00000066040; -.
DR   ProteomicsDB; 269586; -.
DR   Antibodypedia; 457; 357 antibodies from 31 providers.
DR   DNASU; 11656; -.
DR   Ensembl; ENSMUST00000066337.13; ENSMUSP00000066040.7; ENSMUSG00000025270.14.
DR   GeneID; 11656; -.
DR   KEGG; mmu:11656; -.
DR   UCSC; uc009uoj.1; mouse.
DR   AGR; MGI:87990; -.
DR   CTD; 212; -.
DR   MGI; MGI:87990; Alas2.
DR   VEuPathDB; HostDB:ENSMUSG00000025270; -.
DR   eggNOG; KOG1360; Eukaryota.
DR   GeneTree; ENSGT00940000159912; -.
DR   InParanoid; P08680; -.
DR   OMA; ARRCPIM; -.
DR   OrthoDB; 9643at2759; -.
DR   PhylomeDB; P08680; -.
DR   TreeFam; TF300724; -.
DR   BRENDA; 2.3.1.37; 3474.
DR   Reactome; R-MMU-189451; Heme biosynthesis.
DR   UniPathway; UPA00251; UER00375.
DR   BioGRID-ORCS; 11656; 2 hits in 77 CRISPR screens.
DR   EvolutionaryTrace; P08680; -.
DR   PRO; PR:P08680; -.
DR   Proteomes; UP000000589; Chromosome X.
DR   RNAct; P08680; Protein.
DR   Bgee; ENSMUSG00000025270; Expressed in blood and 172 other cell types or tissues.
DR   ExpressionAtlas; P08680; baseline and differential.
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:UniProtKB.
DR   GO; GO:0003870; F:5-aminolevulinate synthase activity; IDA:UniProtKB.
DR   GO; GO:0120225; F:coenzyme A 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:0030218; P:erythrocyte differentiation; IMP:UniProtKB.
DR   GO; GO:0006783; P:heme biosynthetic process; IMP:UniProtKB.
DR   GO; GO:0042541; P:hemoglobin biosynthetic process; IMP:UniProtKB.
DR   GO; GO:0006879; P:intracellular iron ion homeostasis; IMP:MGI.
DR   GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0001666; P:response to hypoxia; ISS:UniProtKB.
DR   CDD; cd06454; KBL_like; 1.
DR   Gene3D; 4.10.92.10; Aminolevulinic Acid Synthase 2; 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:SF58; 5-AMINOLEVULINATE SYNTHASE, ERYTHROID-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.
DR   Genevisible; P08680; MM.
PE   1: Evidence at protein level;
KW   3D-structure; Acyltransferase; Heme biosynthesis; Membrane; Mitochondrion;
KW   Mitochondrion inner membrane; Pyridoxal phosphate; Reference proteome;
KW   Transferase; Transit peptide.
FT   TRANSIT         1..49
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000269|PubMed:11566198"
FT   CHAIN           50..587
FT                   /note="5-aminolevulinate synthase, erythroid-specific,
FT                   mitochondrial"
FT                   /id="PRO_0000001224"
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:0000269|PubMed:8268805"
FT   MUTAGEN         391
FT                   /note="K->A,H: Abolishes enzyme activity."
FT                   /evidence="ECO:0000269|PubMed:8268805"
FT   CONFLICT        61..75
FT                   /note="Missing (in Ref. 1; AAA37207)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        66
FT                   /note="A -> R (in Ref. 3; BAB22254)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        171
FT                   /note="W -> R (in Ref. 2; AAA91866)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        338
FT                   /note="C -> V (in Ref. 2; AAA91866)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        368..372
FT                   /note="RGAGI -> GVQVS (in Ref. 2; AAA91866)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        427
FT                   /note="V -> M (in Ref. 1; AAA37207)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        479
FT                   /note="R -> W (in Ref. 2; AAA91866)"
FT                   /evidence="ECO:0000305"
FT   TURN            5..8
FT                   /evidence="ECO:0007829|PDB:1H7J"
FT   STRAND          14..16
FT                   /evidence="ECO:0007829|PDB:1H7J"
FT   TURN            23..27
FT                   /evidence="ECO:0007829|PDB:1H7D"
FT   HELIX           28..32
FT                   /evidence="ECO:0007829|PDB:1H7D"
SQ   SEQUENCE   587 AA;  64753 MW;  A878D79FAD5B9856 CRC64;
     MVAAAMLLRS CPVLSQGPTG LLGKVAKTYQ FLFSIGRCPI LATQGPTCSQ IHLKATKAGG
     DSPSWAKSHC PFMLSELQDR KSKIVQRAAP EVQEDVKTFK TDLLSTMDST TRSHSFPSFQ
     EPEQTEGAVP HLIQNNMTGS QAFGYDQFFR DKIMEKKQDH TYRVFKTVNR WANAYPFAQH
     FSEASMASKD VSVWCSNDYL GISRHPRVLQ AIEETLKNHG AGAGGTRNIS GTSKFHVELE
     QELAELHQKD SALLFSSCFV ANDSTLFTLA KLLPGCEIYS DAGNHASMIQ GIRNSGAAKF
     VFRHNDPGHL KKLLEKSDPK TPKIVAFETV HSMDGAICPL EELCDVAHQY GALTFVDEVH
     AVGLYGARGA GIGERDGIMH KLDIISGTLG KAFGCVGGYI ASTRDLVDMV RSYAAGFIFT
     TSLPPMVLSG ALESVRLLKG EEGQALRRAH QRNVKHMRQL LMDRGFPVIP CPSHIIPIRV
     GNAALNSKIC DLLLSKHSIY VQAINYPTVP RGEELLRLAP SPHHSPQMME NFVEKLLLAW
     TEVGLPLQDV SVAACNFCHR PVHFELMSEW ERSYFGNMGP QYVTTYA
//