HEM3_MOUSE
ID HEM3_MOUSE Reviewed; 361 AA.
AC P22907; Q3TIV0;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Porphobilinogen deaminase {ECO:0000305};
DE Short=PBG-D;
DE EC=2.5.1.61 {ECO:0000250|UniProtKB:P08397};
DE AltName: Full=Hydroxymethylbilane synthase;
DE Short=HMBS;
DE AltName: Full=Pre-uroporphyrinogen synthase;
GN Name=Hmbs; Synonyms=Uros1;
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 [GENOMIC DNA] (ISOFORMS 1 AND 2).
RX PubMed=2768242; DOI=10.1016/s0021-9258(18)63775-5;
RA Beaumont C., Porcher C., Picat C., Nordmann Y., Grandchamp B.;
RT "The mouse porphobilinogen deaminase gene. Structural organization,
RT sequence, and transcriptional analysis.";
RL J. Biol. Chem. 264:14829-14834(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Amnion;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen,
RC 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 [4]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-74, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
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).
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:0000250|UniProtKB:P08397}.
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:0000250|UniProtKB:P08397};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13186;
CC Evidence={ECO:0000250|UniProtKB:P08397};
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 -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX
CC biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 2/4.
CC {ECO:0000250|UniProtKB:P08397}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P08397}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Non-erythropoietic;
CC IsoId=P22907-1; Sequence=Displayed;
CC Name=2; Synonyms=Erythrocyte;
CC IsoId=P22907-2; Sequence=VSP_002068;
CC -!- SIMILARITY: Belongs to the HMBS family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA39890.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; M28666; AAA39890.1; ALT_SEQ; Genomic_DNA.
DR EMBL; M28663; AAA39890.1; JOINED; Genomic_DNA.
DR EMBL; M28664; AAA39890.1; JOINED; Genomic_DNA.
DR EMBL; M28665; AAA39890.1; JOINED; Genomic_DNA.
DR EMBL; M28666; AAA39891.1; -; Genomic_DNA.
DR EMBL; M28663; AAA39891.1; JOINED; Genomic_DNA.
DR EMBL; M28664; AAA39891.1; JOINED; Genomic_DNA.
DR EMBL; M28665; AAA39891.1; JOINED; Genomic_DNA.
DR EMBL; AK166734; BAE38979.1; -; mRNA.
DR EMBL; AK167702; BAE39746.1; -; mRNA.
DR CCDS; CCDS23106.1; -. [P22907-1]
DR CCDS; CCDS52779.1; -. [P22907-2]
DR PIR; A36513; IBMSN.
DR RefSeq; NP_038579.2; NM_013551.2. [P22907-1]
DR AlphaFoldDB; P22907; -.
DR SMR; P22907; -.
DR BioGRID; 200321; 3.
DR IntAct; P22907; 2.
DR STRING; 10090.ENSMUSP00000076575; -.
DR iPTMnet; P22907; -.
DR PhosphoSitePlus; P22907; -.
DR EPD; P22907; -.
DR jPOST; P22907; -.
DR MaxQB; P22907; -.
DR PaxDb; P22907; -.
DR PeptideAtlas; P22907; -.
DR PRIDE; P22907; -.
DR ProteomicsDB; 269587; -. [P22907-1]
DR ProteomicsDB; 269588; -. [P22907-2]
DR Antibodypedia; 54687; 418 antibodies from 35 providers.
DR DNASU; 15288; -.
DR Ensembl; ENSMUST00000077353; ENSMUSP00000076575; ENSMUSG00000032126. [P22907-1]
DR Ensembl; ENSMUST00000097558; ENSMUSP00000095166; ENSMUSG00000032126. [P22907-2]
DR GeneID; 15288; -.
DR KEGG; mmu:15288; -.
DR UCSC; uc009pcz.2; mouse. [P22907-1]
DR CTD; 3145; -.
DR MGI; MGI:96112; Hmbs.
DR VEuPathDB; HostDB:ENSMUSG00000032126; -.
DR eggNOG; KOG2892; Eukaryota.
DR GeneTree; ENSGT00390000009083; -.
DR HOGENOM; CLU_019704_0_1_1; -.
DR InParanoid; P22907; -.
DR OMA; LWQANHI; -.
DR PhylomeDB; P22907; -.
DR TreeFam; TF105389; -.
DR BRENDA; 2.5.1.61; 3474.
DR Reactome; R-MMU-189451; Heme biosynthesis.
DR UniPathway; UPA00251; UER00319.
DR BioGRID-ORCS; 15288; 9 hits in 76 CRISPR screens.
DR ChiTaRS; Hmbs; mouse.
DR PRO; PR:P22907; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; P22907; protein.
DR Bgee; ENSMUSG00000032126; Expressed in fetal liver hematopoietic progenitor cell and 245 other tissues.
DR ExpressionAtlas; P22907; baseline and differential.
DR Genevisible; P22907; MM.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0000793; C:condensed chromosome; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0043176; F:amine binding; ISO:MGI.
DR GO; GO:0031406; F:carboxylic acid binding; ISO:MGI.
DR GO; GO:0004418; F:hydroxymethylbilane synthase activity; ISO:MGI.
DR GO; GO:0004852; F:uroporphyrinogen-III synthase activity; ISO:MGI.
DR GO; GO:0006783; P:heme biosynthetic process; ISO:MGI.
DR GO; GO:0001889; P:liver development; ISO:MGI.
DR GO; GO:0018160; P:peptidyl-pyrromethane cofactor linkage; IEA:InterPro.
DR GO; GO:0006779; P:porphyrin-containing compound biosynthetic process; ISO:MGI.
DR GO; GO:0006778; P:porphyrin-containing compound metabolic process; ISO:MGI.
DR GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:MGI.
DR GO; GO:0033014; P:tetrapyrrole biosynthetic process; ISO:MGI.
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_0000143035"
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:0007744|PubMed:23806337"
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:0000305"
FT /id="VSP_002068"
FT CONFLICT 36
FT /note="D -> E (in Ref. 1; AAA39890/AAA39891)"
FT /evidence="ECO:0000305"
FT CONFLICT 64
FT /note="L -> V (in Ref. 1; AAA39890/AAA39891)"
FT /evidence="ECO:0000305"
FT CONFLICT 117
FT /note="E -> Q (in Ref. 1; AAA39890/AAA39891)"
FT /evidence="ECO:0000305"
FT CONFLICT 160
FT /note="H -> N (in Ref. 1; AAA39890/AAA39891)"
FT /evidence="ECO:0000305"
FT CONFLICT 271
FT /note="M -> I (in Ref. 1; AAA39890/AAA39891)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 361 AA; 39344 MW; F184C439F4F7B55D CRC64;
MSGNGGAATT AEENGSKMRV IRVGTRKSQL ARIQTDTVVA MLKALYPGIQ FEIIAMSTTG
DKILDTALSK IGEKSLFTKE LENALEKNEV DLVVHSLKDV PTILPPGFTI GAICKRENPC
DAVVFHPKFI GKTLETLPEK SAVGTSSLRR VAQLQRKFPH LEFKSIRGNL NTRLRKLDEL
QEFSAIVLAV AGLQRMGWQN RVGQILHPEE CMYAVGQGAL AVEVRAKDQD ILDLVSVLHD
PETLLRCIAE RAFLRHLEGG CSVPVAVHTV MKDGQLYLTG GVWSLDGSDS MQETMQATIQ
VPVQQEDGPE DDPQLVGITA RNIPRGAQLA AENLGISLAS LLLNKGAKNI LDVARQLNDV
R
