HEM0_MOUSE
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 03-AUG-2022, entry version 188.
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; P08680; -.
DR PRIDE; P08680; -.
DR ProteomicsDB; 269586; -.
DR Antibodypedia; 457; 311 antibodies from 31 providers.
DR DNASU; 11656; -.
DR Ensembl; ENSMUST00000066337; ENSMUSP00000066040; ENSMUSG00000025270.
DR GeneID; 11656; -.
DR KEGG; mmu:11656; -.
DR UCSC; uc009uoj.1; mouse.
DR CTD; 212; -.
DR MGI; MGI:87990; Alas2.
DR VEuPathDB; HostDB:ENSMUSG00000025270; -.
DR eggNOG; KOG1360; Eukaryota.
DR GeneTree; ENSGT00940000159912; -.
DR InParanoid; P08680; -.
DR OMA; NHASMIV; -.
DR OrthoDB; 930001at2759; -.
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 72 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 169 other tissues.
DR ExpressionAtlas; P08680; baseline and differential.
DR Genevisible; P08680; MM.
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:0006879; P:cellular iron ion homeostasis; IMP:MGI.
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:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0001666; P:response to hypoxia; ISS:UniProtKB.
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 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
