HEM2_MOUSE
ID HEM2_MOUSE Reviewed; 330 AA.
AC P10518; Q3THV6;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Delta-aminolevulinic acid dehydratase;
DE Short=ALADH;
DE EC=4.2.1.24;
DE AltName: Full=Porphobilinogen synthase;
GN Name=Alad; Synonyms=Lv;
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].
RC STRAIN=BALB/cJ;
RX PubMed=2922298; DOI=10.1093/nar/17.4.1775;
RA Bishop T.R., Hodes Z.I., Frelin L.P., Boyer S.H.;
RT "Cloning and sequence of mouse erythroid delta-aminolevulinate dehydratase
RT cDNA.";
RL Nucleic Acids Res. 17:1775-1775(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=BALB/cJ, C57BL/6J, and DBA/2J; TISSUE=Placenta;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon;
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).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-215, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-215, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
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 SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-199 AND LYS-252, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS).
RG RIKEN structural genomics initiative (RSGI);
RT "Crystal structure of 5-aminolevulinic acid dehydratase (ALAD) from Mus
RT musculus.";
RL Submitted (FEB-2009) to the PDB data bank.
CC -!- FUNCTION: Catalyzes an early step in the biosynthesis of tetrapyrroles.
CC Binds two molecules of 5-aminolevulinate per subunit, each at a
CC distinct site, and catalyzes their condensation to form porphobilinogen
CC (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 5-aminolevulinate = H(+) + 2 H2O + porphobilinogen;
CC Xref=Rhea:RHEA:24064, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:58126, ChEBI:CHEBI:356416; EC=4.2.1.24;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 8 zinc ions per octamer. Requires four zinc ions per octamer
CC for full catalytic activity. Can bind up to 2 zinc ions per subunit.
CC {ECO:0000250};
CC -!- ACTIVITY REGULATION: Can alternate between a fully active homooctamer
CC and a low-activity homohexamer. A bound magnesium ion may promote the
CC assembly of the fully active homooctamer. The magnesium-binding site is
CC absent in the low-activity homohexamer. Inhibited by compounds that
CC favor the hexameric state. Inhibited by divalent lead ions. The lead
CC ions partially displace the zinc cofactor (By similarity).
CC {ECO:0000250}.
CC -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX
CC biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 1/4.
CC -!- SUBUNIT: Homooctamer; active form. Homohexamer; low activity form (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the ALAD family. {ECO:0000305}.
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DR EMBL; X13752; CAA32015.1; -; mRNA.
DR EMBL; AK032908; BAC28080.1; -; mRNA.
DR EMBL; AK167673; BAE39722.1; -; mRNA.
DR EMBL; AK168119; BAE40090.1; -; mRNA.
DR EMBL; AK168132; BAE40101.1; -; mRNA.
DR EMBL; BC055930; AAH55930.1; -; mRNA.
DR CCDS; CCDS18243.1; -.
DR PIR; S03187; S03187.
DR RefSeq; NP_001263375.1; NM_001276446.1.
DR RefSeq; NP_032551.3; NM_008525.4.
DR RefSeq; XP_006537702.1; XM_006537639.2.
DR PDB; 2Z0I; X-ray; 3.20 A; A/B=1-330.
DR PDB; 2Z1B; X-ray; 3.30 A; A/B/C/D=1-330.
DR PDBsum; 2Z0I; -.
DR PDBsum; 2Z1B; -.
DR AlphaFoldDB; P10518; -.
DR SMR; P10518; -.
DR BioGRID; 201229; 15.
DR IntAct; P10518; 2.
DR STRING; 10090.ENSMUSP00000030090; -.
DR iPTMnet; P10518; -.
DR PhosphoSitePlus; P10518; -.
DR SwissPalm; P10518; -.
DR REPRODUCTION-2DPAGE; P10518; -.
DR SWISS-2DPAGE; P10518; -.
DR EPD; P10518; -.
DR jPOST; P10518; -.
DR MaxQB; P10518; -.
DR PaxDb; P10518; -.
DR PeptideAtlas; P10518; -.
DR PRIDE; P10518; -.
DR ProteomicsDB; 269694; -.
DR Antibodypedia; 15306; 236 antibodies from 26 providers.
DR DNASU; 17025; -.
DR Ensembl; ENSMUST00000030090; ENSMUSP00000030090; ENSMUSG00000028393.
DR Ensembl; ENSMUST00000107444; ENSMUSP00000103068; ENSMUSG00000028393.
DR GeneID; 17025; -.
DR KEGG; mmu:17025; -.
DR UCSC; uc008tez.2; mouse.
DR CTD; 210; -.
DR MGI; MGI:96853; Alad.
DR VEuPathDB; HostDB:ENSMUSG00000028393; -.
DR eggNOG; KOG2794; Eukaryota.
DR GeneTree; ENSGT00390000006998; -.
DR HOGENOM; CLU_035731_0_1_1; -.
DR InParanoid; P10518; -.
DR OMA; YQMDYAN; -.
DR OrthoDB; 918089at2759; -.
DR PhylomeDB; P10518; -.
DR TreeFam; TF300665; -.
DR Reactome; R-MMU-189451; Heme biosynthesis.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR UniPathway; UPA00251; UER00318.
DR BioGRID-ORCS; 17025; 4 hits in 75 CRISPR screens.
DR ChiTaRS; Alad; mouse.
DR EvolutionaryTrace; P10518; -.
DR PRO; PR:P10518; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; P10518; protein.
DR Bgee; ENSMUSG00000028393; Expressed in fetal liver hematopoietic progenitor cell and 252 other tissues.
DR Genevisible; P10518; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0004655; F:porphobilinogen synthase activity; IDA:MGI.
DR GO; GO:1904854; F:proteasome core complex binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0071353; P:cellular response to interleukin-4; IDA:MGI.
DR GO; GO:0071284; P:cellular response to lead ion; IEA:Ensembl.
DR GO; GO:0006783; P:heme biosynthetic process; IDA:MGI.
DR GO; GO:1901799; P:negative regulation of proteasomal protein catabolic process; ISO:MGI.
DR GO; GO:0051260; P:protein homooligomerization; ISO:MGI.
DR GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0014823; P:response to activity; IEA:Ensembl.
DR GO; GO:0010044; P:response to aluminum ion; IEA:Ensembl.
DR GO; GO:0043200; P:response to amino acid; IEA:Ensembl.
DR GO; GO:0046685; P:response to arsenic-containing substance; ISO:MGI.
DR GO; GO:0046686; P:response to cadmium ion; ISO:MGI.
DR GO; GO:0032025; P:response to cobalt ion; IEA:Ensembl.
DR GO; GO:0045471; P:response to ethanol; ISO:MGI.
DR GO; GO:0070542; P:response to fatty acid; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR GO; GO:0009635; P:response to herbicide; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0010212; P:response to ionizing radiation; IEA:Ensembl.
DR GO; GO:0010039; P:response to iron ion; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0046689; P:response to mercury ion; IEA:Ensembl.
DR GO; GO:0010038; P:response to metal ion; ISO:MGI.
DR GO; GO:0051597; P:response to methylmercury; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; ISO:MGI.
DR GO; GO:0010033; P:response to organic substance; ISO:MGI.
DR GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl.
DR GO; GO:0070541; P:response to platinum ion; IEA:Ensembl.
DR GO; GO:0010269; P:response to selenium ion; IEA:Ensembl.
DR GO; GO:0010266; P:response to vitamin B1; IEA:Ensembl.
DR GO; GO:0033197; P:response to vitamin E; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:MGI.
DR GO; GO:0010043; P:response to zinc ion; ISO:MGI.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR001731; ALAD.
DR InterPro; IPR030656; ALAD_AS.
DR InterPro; IPR013785; Aldolase_TIM.
DR PANTHER; PTHR11458; PTHR11458; 1.
DR Pfam; PF00490; ALAD; 1.
DR PIRSF; PIRSF001415; Porphbilin_synth; 1.
DR PRINTS; PR00144; DALDHYDRTASE.
DR SMART; SM01004; ALAD; 1.
DR PROSITE; PS00169; D_ALA_DEHYDRATASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Allosteric enzyme; Heme biosynthesis; Lyase; Metal-binding;
KW Phosphoprotein; Porphyrin biosynthesis; Reference proteome; Zinc.
FT CHAIN 1..330
FT /note="Delta-aminolevulinic acid dehydratase"
FT /id="PRO_0000140528"
FT ACT_SITE 199
FT /note="Schiff-base intermediate with substrate"
FT /evidence="ECO:0000250"
FT ACT_SITE 252
FT /note="Schiff-base intermediate with substrate"
FT /evidence="ECO:0000250"
FT BINDING 122
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 124
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 131
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 132
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 209
FT /ligand="5-aminolevulinate"
FT /ligand_id="ChEBI:CHEBI:356416"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 221
FT /ligand="5-aminolevulinate"
FT /ligand_id="ChEBI:CHEBI:356416"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 223
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 279
FT /ligand="5-aminolevulinate"
FT /ligand_id="ChEBI:CHEBI:356416"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 318
FT /ligand="5-aminolevulinate"
FT /ligand_id="ChEBI:CHEBI:356416"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT MOD_RES 199
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 215
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 252
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT HELIX 8..10
FT /evidence="ECO:0007829|PDB:2Z0I"
FT HELIX 14..20
FT /evidence="ECO:0007829|PDB:2Z0I"
FT HELIX 28..30
FT /evidence="ECO:0007829|PDB:2Z0I"
FT STRAND 31..42
FT /evidence="ECO:0007829|PDB:2Z0I"
FT STRAND 44..46
FT /evidence="ECO:0007829|PDB:2Z0I"
FT STRAND 48..50
FT /evidence="ECO:0007829|PDB:2Z1B"
FT STRAND 54..57
FT /evidence="ECO:0007829|PDB:2Z0I"
FT HELIX 58..60
FT /evidence="ECO:0007829|PDB:2Z0I"
FT HELIX 61..64
FT /evidence="ECO:0007829|PDB:2Z0I"
FT HELIX 66..69
FT /evidence="ECO:0007829|PDB:2Z0I"
FT TURN 70..72
FT /evidence="ECO:0007829|PDB:2Z0I"
FT STRAND 75..81
FT /evidence="ECO:0007829|PDB:2Z0I"
FT HELIX 100..111
FT /evidence="ECO:0007829|PDB:2Z0I"
FT STRAND 113..119
FT /evidence="ECO:0007829|PDB:2Z0I"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:2Z1B"
FT HELIX 144..160
FT /evidence="ECO:0007829|PDB:2Z0I"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:2Z0I"
FT HELIX 174..183
FT /evidence="ECO:0007829|PDB:2Z0I"
FT TURN 185..188
FT /evidence="ECO:0007829|PDB:2Z1B"
FT STRAND 192..194
FT /evidence="ECO:0007829|PDB:2Z0I"
FT HELIX 206..211
FT /evidence="ECO:0007829|PDB:2Z0I"
FT HELIX 231..241
FT /evidence="ECO:0007829|PDB:2Z0I"
FT HELIX 242..244
FT /evidence="ECO:0007829|PDB:2Z0I"
FT STRAND 247..254
FT /evidence="ECO:0007829|PDB:2Z0I"
FT HELIX 255..257
FT /evidence="ECO:0007829|PDB:2Z0I"
FT HELIX 258..267
FT /evidence="ECO:0007829|PDB:2Z0I"
FT STRAND 273..276
FT /evidence="ECO:0007829|PDB:2Z0I"
FT HELIX 279..290
FT /evidence="ECO:0007829|PDB:2Z0I"
FT HELIX 296..309
FT /evidence="ECO:0007829|PDB:2Z0I"
FT STRAND 313..316
FT /evidence="ECO:0007829|PDB:2Z0I"
FT HELIX 320..326
FT /evidence="ECO:0007829|PDB:2Z0I"
SQ SEQUENCE 330 AA; 36024 MW; 84052DC911C153EB CRC64;
MHHQSVLHSG YFHPLLRSWQ TAASTVSASN LIYPIFVTDV PDDVQPIASL PGVARYGVNQ
LEEMLRPLVE AGLRCVLIFG VPSRVPKDEQ GSAADSEDSP TIEAVRLLRK TFPSLLVACD
VCLCPYTSHG HCGLLSENGA FLAEESRQRL AEVALAYAKA GCQVVAPSDM MDGRVEAIKA
ALLKHGLGNR VSVMSYSAKF ASCFYGPFRD AAQSSPAFGD RRCYQLPPGA RGLALRAVAR
DIQEGADMLM VKPGLPYLDM VREVKDKHPE LPLAVYQVSG EFAMLWHGAQ AGAFDLRTAV
LETMTAFRRA GADIIITYFA PQLLKWLKEE
