HEM3_RAT
ID HEM3_RAT Reviewed; 361 AA.
AC P19356; O08568;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Porphobilinogen deaminase {ECO:0000305|PubMed:9344466};
DE Short=PBG-D;
DE EC=2.5.1.61 {ECO:0000269|PubMed:9344466};
DE AltName: Full=Hydroxymethylbilane synthase;
DE Short=HMBS;
DE AltName: Full=Pre-uroporphyrinogen synthase;
GN Name=Hmbs;
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] (ISOFORM 2).
RX PubMed=3368319; DOI=10.1093/nar/16.7.3102;
RA Stubnicer A.C., Picat C., Grandchamp B.;
RT "Rat porphobilinogen deaminase cDNA: nucleotide sequence of the
RT erythropoietic form.";
RL Nucleic Acids Res. 16:3102-3102(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, AND SUBUNIT.
RC STRAIN=CHBB THOM;
RX PubMed=9344466; DOI=10.1006/abbi.1997.0310;
RA Cardalda C.A., Juknat A.A., Princ F.G., Batlle A.;
RT "Rat harderian gland porphobilinogen deaminase: characterization studies
RT and regulatory action of protoporphyrin IX.";
RL Arch. Biochem. Biophys. 347:69-77(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9712715; DOI=10.1006/bbrc.1998.9021;
RA Cardalda C.A., Batlle A., Juknat A.A.;
RT "Sequence and structure of the rat housekeeping PBG-D isoform.";
RL Biochem. Biophys. Res. Commun. 249:438-443(1998).
CC -!- FUNCTION: As part of the heme biosynthetic pathway, catalyzes the
CC sequential polymerization of four molecules of porphobilinogen to form
CC hydroxymethylbilane, also known as preuroporphyrinogen. Catalysis
CC begins with the assembly of the dipyrromethane cofactor by the
CC apoenzyme from two molecules of porphobilinogen or from
CC preuroporphyrinogen. The covalently linked cofactor acts as a primer,
CC around which the tetrapyrrole product is assembled. In the last step of
CC catalysis, the product, preuroporphyrinogen, is released, leaving the
CC cofactor bound to the holodeaminase intact.
CC {ECO:0000305|PubMed:9344466}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + 4 porphobilinogen = hydroxymethylbilane + 4 NH4(+);
CC Xref=Rhea:RHEA:13185, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:57845, ChEBI:CHEBI:58126; EC=2.5.1.61;
CC Evidence={ECO:0000269|PubMed:9344466};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13186;
CC Evidence={ECO:0000305|PubMed:9344466};
CC -!- COFACTOR:
CC Name=dipyrromethane; Xref=ChEBI:CHEBI:60342;
CC Evidence={ECO:0000250|UniProtKB:P08397};
CC Note=Binds 1 dipyrromethane group covalently.
CC {ECO:0000250|UniProtKB:P08397};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.1 uM for porphobilinogen (at pH 8.0 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:9344466};
CC Vmax=170 pmol/min/mg enzyme (at pH 8.0 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:9344466};
CC pH dependence:
CC Optimum pH is 8.0-8.2. {ECO:0000269|PubMed:9344466};
CC -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX
CC biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 2/4.
CC {ECO:0000305|PubMed:9344466}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:9344466}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Non-erythropoietic;
CC IsoId=P19356-1; Sequence=Displayed;
CC Name=2; Synonyms=Erythrocyte;
CC IsoId=P19356-2; Sequence=VSP_002069;
CC -!- SIMILARITY: Belongs to the HMBS family. {ECO:0000305}.
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DR EMBL; X06827; CAA29984.1; -; mRNA.
DR EMBL; Y12006; CAA72734.1; -; mRNA.
DR PIR; JE0285; IBRTE.
DR AlphaFoldDB; P19356; -.
DR SMR; P19356; -.
DR STRING; 10116.ENSRNOP00000014128; -.
DR iPTMnet; P19356; -.
DR PhosphoSitePlus; P19356; -.
DR SwissPalm; P19356; -.
DR jPOST; P19356; -.
DR PaxDb; P19356; -.
DR PRIDE; P19356; -.
DR UCSC; RGD:2801; rat. [P19356-1]
DR RGD; 2801; Hmbs.
DR eggNOG; KOG2892; Eukaryota.
DR InParanoid; P19356; -.
DR PhylomeDB; P19356; -.
DR BRENDA; 2.5.1.61; 5301.
DR Reactome; R-RNO-189451; Heme biosynthesis.
DR SABIO-RK; P19356; -.
DR UniPathway; UPA00251; UER00319.
DR PRO; PR:P19356; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0043176; F:amine binding; IPI:RGD.
DR GO; GO:0031406; F:carboxylic acid binding; IPI:RGD.
DR GO; GO:0004418; F:hydroxymethylbilane synthase activity; IDA:RGD.
DR GO; GO:0004852; F:uroporphyrinogen-III synthase activity; IDA:RGD.
DR GO; GO:0031100; P:animal organ regeneration; IEP:RGD.
DR GO; GO:0048708; P:astrocyte differentiation; IEP:RGD.
DR GO; GO:0071418; P:cellular response to amine stimulus; IEP:RGD.
DR GO; GO:0071236; P:cellular response to antibiotic; IEP:RGD.
DR GO; GO:0071243; P:cellular response to arsenic-containing substance; IEP:RGD.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; IEP:RGD.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEP:RGD.
DR GO; GO:0071284; P:cellular response to lead ion; IEP:RGD.
DR GO; GO:0006783; P:heme biosynthetic process; ISO:RGD.
DR GO; GO:0001889; P:liver development; IDA:RGD.
DR GO; GO:0018160; P:peptidyl-pyrromethane cofactor linkage; IEA:InterPro.
DR GO; GO:0006779; P:porphyrin-containing compound biosynthetic process; IDA:RGD.
DR GO; GO:0006778; P:porphyrin-containing compound metabolic process; IDA:RGD.
DR GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0043200; P:response to amino acid; IEP:RGD.
DR GO; GO:0009743; P:response to carbohydrate; IEP:RGD.
DR GO; GO:0032025; P:response to cobalt ion; IEP:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0009725; P:response to hormone; 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:0010038; P:response to metal ion; IEP:RGD.
DR GO; GO:0051597; P:response to methylmercury; IEP:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0033273; P:response to vitamin; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IDA:RGD.
DR GO; GO:0010043; P:response to zinc ion; IEP:RGD.
DR GO; GO:0033014; P:tetrapyrrole biosynthetic process; IDA:RGD.
DR Gene3D; 3.30.160.40; -; 1.
DR HAMAP; MF_00260; Porphobil_deam; 1.
DR InterPro; IPR000860; HemC.
DR InterPro; IPR022419; Porphobilin_deaminase_cofac_BS.
DR InterPro; IPR022417; Porphobilin_deaminase_N.
DR InterPro; IPR022418; Porphobilinogen_deaminase_C.
DR InterPro; IPR036803; Porphobilinogen_deaminase_C_sf.
DR PANTHER; PTHR11557; PTHR11557; 1.
DR Pfam; PF01379; Porphobil_deam; 1.
DR Pfam; PF03900; Porphobil_deamC; 1.
DR PIRSF; PIRSF001438; 4pyrrol_synth_OHMeBilane_synth; 1.
DR PRINTS; PR00151; PORPHBDMNASE.
DR SUPFAM; SSF54782; SSF54782; 1.
DR TIGRFAMs; TIGR00212; hemC; 1.
DR PROSITE; PS00533; PORPHOBILINOGEN_DEAM; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Heme biosynthesis; Phosphoprotein;
KW Porphyrin biosynthesis; Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P08397"
FT CHAIN 2..361
FT /note="Porphobilinogen deaminase"
FT /id="PRO_0000143036"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:P08397"
FT MOD_RES 69
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P08397"
FT MOD_RES 74
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P22907"
FT MOD_RES 147
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P08397"
FT MOD_RES 261
FT /note="S-(dipyrrolylmethanemethyl)cysteine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..17
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:3368319"
FT /id="VSP_002069"
FT CONFLICT 126..127
FT /note="HP -> EG (in Ref. 1; CAA29984)"
FT /evidence="ECO:0000305"
FT CONFLICT 252
FT /note="A -> D (in Ref. 1; CAA29984)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 361 AA; 39361 MW; CE00570010E4121E CRC64;
MSGNGGAATT AEENGSMMRV IRVGTRKSQL ARIQTDTVVA MLKTLYPGIQ FEIIAMSTTG
DKILDTALSK IGEKSLFTKE LENALEKNEV DLVVHSLKDV PTILPPGFTI GAICKRENPC
DAVVFHPKFI GKTLETLPEK SAVGTSSLRR VAQLQRKFPH LEFKSIRGNL NTRLRKLDEQ
LEFSAIILAV AGLQRMGWQN RVGQILHPEE CMYAVGQGAL AVEVRAKDQD ILDLVGVLHD
PETLLRCIAE RAFLRHLEGG CSVPVAVHTV MKDGQLYLTG GVWSLDGSDS MQETMQATIQ
VPVQQEDGPE DDPQLVGITA RNIPRGAQLA AENLGISLAS LLLNKGAKNI LDVARQLNDV
R
