ID   HEM3_ARATH              Reviewed;         382 AA.
AC   Q43316; Q8LBT0;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 1.
DT   24-JAN-2024, entry version 173.
DE   RecName: Full=Porphobilinogen deaminase, chloroplastic;
DE            Short=PBG;
DE            EC=2.5.1.61 {ECO:0000305|PubMed:8192681};
DE   AltName: Full=Hydroxymethylbilane synthase;
DE            Short=HMBS;
DE   AltName: Full=Pre-uroporphyrinogen synthase;
DE   AltName: Full=Protein RUGOSA1;
DE   Flags: Precursor;
GN   Name=HEMC; Synonyms=RUG1; OrderedLocusNames=At5g08280;
GN   ORFNames=F8L15_10;
OS   Arabidopsis thaliana (Mouse-ear cress).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC   rosids; malvids; Brassicales; Brassicaceae; Camelineae; Arabidopsis.
OX   NCBI_TaxID=3702;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=cv. Landsberg erecta;
RX   PubMed=8000000; DOI=10.1007/bf00028854;
RA   Lim S.H., Witty M., Wallace-Cook A.D.M., Ilag L.I., Smith A.G.;
RT   "Porphobilinogen deaminase is encoded by a single gene in Arabidopsis
RT   thaliana and is targeted to the chloroplasts.";
RL   Plant Mol. Biol. 26:863-872(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=cv. Columbia;
RX   PubMed=11130714; DOI=10.1038/35048507;
RA   Tabata S., Kaneko T., Nakamura Y., Kotani H., Kato T., Asamizu E.,
RA   Miyajima N., Sasamoto S., Kimura T., Hosouchi T., Kawashima K., Kohara M.,
RA   Matsumoto M., Matsuno A., Muraki A., Nakayama S., Nakazaki N., Naruo K.,
RA   Okumura S., Shinpo S., Takeuchi C., Wada T., Watanabe A., Yamada M.,
RA   Yasuda M., Sato S., de la Bastide M., Huang E., Spiegel L., Gnoj L.,
RA   O'Shaughnessy A., Preston R., Habermann K., Murray J., Johnson D.,
RA   Rohlfing T., Nelson J., Stoneking T., Pepin K., Spieth J., Sekhon M.,
RA   Armstrong J., Becker M., Belter E., Cordum H., Cordes M., Courtney L.,
RA   Courtney W., Dante M., Du H., Edwards J., Fryman J., Haakensen B.,
RA   Lamar E., Latreille P., Leonard S., Meyer R., Mulvaney E., Ozersky P.,
RA   Riley A., Strowmatt C., Wagner-McPherson C., Wollam A., Yoakum M., Bell M.,
RA   Dedhia N., Parnell L., Shah R., Rodriguez M., Hoon See L., Vil D.,
RA   Baker J., Kirchoff K., Toth K., King L., Bahret A., Miller B., Marra M.A.,
RA   Martienssen R., McCombie W.R., Wilson R.K., Murphy G., Bancroft I.,
RA   Volckaert G., Wambutt R., Duesterhoeft A., Stiekema W., Pohl T.,
RA   Entian K.-D., Terryn N., Hartley N., Bent E., Johnson S., Langham S.-A.,
RA   McCullagh B., Robben J., Grymonprez B., Zimmermann W., Ramsperger U.,
RA   Wedler H., Balke K., Wedler E., Peters S., van Staveren M., Dirkse W.,
RA   Mooijman P., Klein Lankhorst R., Weitzenegger T., Bothe G., Rose M.,
RA   Hauf J., Berneiser S., Hempel S., Feldpausch M., Lamberth S.,
RA   Villarroel R., Gielen J., Ardiles W., Bents O., Lemcke K., Kolesov G.,
RA   Mayer K.F.X., Rudd S., Schoof H., Schueller C., Zaccaria P., Mewes H.-W.,
RA   Bevan M., Fransz P.F.;
RT   "Sequence and analysis of chromosome 5 of the plant Arabidopsis thaliana.";
RL   Nature 408:823-826(2000).
RN   [3]
RP   GENOME REANNOTATION.
RC   STRAIN=cv. Columbia;
RX   PubMed=27862469; DOI=10.1111/tpj.13415;
RA   Cheng C.Y., Krishnakumar V., Chan A.P., Thibaud-Nissen F., Schobel S.,
RA   Town C.D.;
RT   "Araport11: a complete reannotation of the Arabidopsis thaliana reference
RT   genome.";
RL   Plant J. 89:789-804(2017).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=cv. Columbia;
RX   PubMed=14593172; DOI=10.1126/science.1088305;
RA   Yamada K., Lim J., Dale J.M., Chen H., Shinn P., Palm C.J., Southwick A.M.,
RA   Wu H.C., Kim C.J., Nguyen M., Pham P.K., Cheuk R.F., Karlin-Newmann G.,
RA   Liu S.X., Lam B., Sakano H., Wu T., Yu G., Miranda M., Quach H.L.,
RA   Tripp M., Chang C.H., Lee J.M., Toriumi M.J., Chan M.M., Tang C.C.,
RA   Onodera C.S., Deng J.M., Akiyama K., Ansari Y., Arakawa T., Banh J.,
RA   Banno F., Bowser L., Brooks S.Y., Carninci P., Chao Q., Choy N., Enju A.,
RA   Goldsmith A.D., Gurjal M., Hansen N.F., Hayashizaki Y., Johnson-Hopson C.,
RA   Hsuan V.W., Iida K., Karnes M., Khan S., Koesema E., Ishida J., Jiang P.X.,
RA   Jones T., Kawai J., Kamiya A., Meyers C., Nakajima M., Narusaka M.,
RA   Seki M., Sakurai T., Satou M., Tamse R., Vaysberg M., Wallender E.K.,
RA   Wong C., Yamamura Y., Yuan S., Shinozaki K., Davis R.W., Theologis A.,
RA   Ecker J.R.;
RT   "Empirical analysis of transcriptional activity in the Arabidopsis
RT   genome.";
RL   Science 302:842-846(2003).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Brover V.V., Troukhan M.E., Alexandrov N.A., Lu Y.-P., Flavell R.B.,
RA   Feldmann K.A.;
RT   "Full-length cDNA from Arabidopsis thaliana.";
RL   Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   PROTEIN SEQUENCE OF 63-74, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP   PROPERTIES, SUBUNIT, COFACTOR, AND ACTIVITY REGULATION.
RC   STRAIN=cv. Columbia;
RX   PubMed=8192681; DOI=10.1042/bj2990895;
RA   Jones R.M., Jordan P.M.;
RT   "Purification and properties of porphobilinogen deaminase from Arabidopsis
RT   thaliana.";
RL   Biochem. J. 299:895-902(1994).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-123, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19376835; DOI=10.1104/pp.109.138677;
RA   Reiland S., Messerli G., Baerenfaller K., Gerrits B., Endler A.,
RA   Grossmann J., Gruissem W., Baginsky S.;
RT   "Large-scale Arabidopsis phosphoproteome profiling reveals novel
RT   chloroplast kinase substrates and phosphorylation networks.";
RL   Plant Physiol. 150:889-903(2009).
RN   [8]
RP   FUNCTION, AND MUTAGENESIS OF ALA-246.
RC   STRAIN=cv. Landsberg erecta;
RX   PubMed=23308205; DOI=10.1371/journal.pone.0053378;
RA   Quesada V., Sarmiento-Manus R., Gonzalez-Bayon R., Hricova A., Ponce M.R.,
RA   Micol J.L.;
RT   "PORPHOBILINOGEN DEAMINASE deficiency alters vegetative and reproductive
RT   development and causes lesions in Arabidopsis.";
RL   PLoS ONE 8:E53378-E53378(2013).
RN   [9]
RP   X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 63-382 IN COMPLEX WITH
RP   DIPYRROMETHENONE, ACTIVE SITE, AND PROSTHETIC GROUP AT CYS-316.
RX   PubMed=23519422; DOI=10.1107/s0907444912052134;
RA   Roberts A., Gill R., Hussey R.J., Mikolajek H., Erskine P.T., Cooper J.B.,
RA   Wood S.P., Chrystal E.J., Shoolingin-Jordan P.M.;
RT   "Insights into the mechanism of pyrrole polymerization catalysed by
RT   porphobilinogen deaminase: high-resolution X-ray studies of the Arabidopsis
RT   thaliana enzyme.";
RL   Acta Crystallogr. D 69:471-485(2013).
CC   -!- FUNCTION: Tetrapolymerization of the monopyrrole PBG into the
CC       hydroxymethylbilane pre-uroporphyrinogen in several discrete steps.
CC       {ECO:0000269|PubMed:23308205, ECO:0000269|PubMed:8192681}.
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:0000305|PubMed:8192681};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13186;
CC         Evidence={ECO:0000305|PubMed:8192681};
CC   -!- COFACTOR:
CC       Name=dipyrromethane; Xref=ChEBI:CHEBI:60342;
CC         Evidence={ECO:0000269|PubMed:8192681};
CC       Note=Binds 1 dipyrromethane group covalently.
CC       {ECO:0000269|PubMed:8192681};
CC   -!- ACTIVITY REGULATION: Inhibited by NH(3), heavy-metal ions,
CC       hydroxylamine and 2-bromoporphobilinogen. Not inhibited by N-
CC       ethylmaleimide. {ECO:0000269|PubMed:8192681}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=17 uM for porphobilinogen {ECO:0000269|PubMed:8192681};
CC       pH dependence:
CC         Optimum pH is 7.7-8.5.;
CC       Temperature dependence:
CC         Heat stable and fully active up to 70 degrees Celsius.;
CC   -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX
CC       biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 2/4.
CC   -!- PATHWAY: Porphyrin-containing compound metabolism; chlorophyll
CC       biosynthesis.
CC   -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:23519422,
CC       ECO:0000269|PubMed:8192681}.
CC   -!- SUBCELLULAR LOCATION: Plastid, chloroplast.
CC   -!- MISCELLANEOUS: The porphobilinogen subunits are added sequentially to
CC       the dipyrromethane cofactor that is covalently attached to the enzyme.
CC       The last step of the reaction involves the hydrolysis of the bound
CC       polypyrrole chain and the release of hydroxymethylbilane.
CC   -!- SIMILARITY: Belongs to the HMBS family. {ECO:0000305}.
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DR   EMBL; X73839; CAA52061.1; -; Genomic_DNA.
DR   EMBL; X73535; CAA51941.1; -; Genomic_DNA.
DR   EMBL; AL392174; CAC08328.1; -; Genomic_DNA.
DR   EMBL; CP002688; AED91277.1; -; Genomic_DNA.
DR   EMBL; AF419614; AAL31946.1; -; mRNA.
DR   EMBL; AY070431; AAL49926.1; -; mRNA.
DR   EMBL; AY123037; AAM67570.1; -; mRNA.
DR   EMBL; AY087012; AAM64573.1; -; mRNA.
DR   PIR; S50762; S50762.
DR   RefSeq; NP_196445.1; NM_120911.4.
DR   PDB; 4HTG; X-ray; 1.45 A; A=63-382.
DR   PDBsum; 4HTG; -.
DR   AlphaFoldDB; Q43316; -.
DR   SMR; Q43316; -.
DR   BioGRID; 16002; 4.
DR   IntAct; Q43316; 1.
DR   STRING; 3702.Q43316; -.
DR   iPTMnet; Q43316; -.
DR   MetOSite; Q43316; -.
DR   PaxDb; 3702-AT5G08280-1; -.
DR   ProteomicsDB; 232214; -.
DR   EnsemblPlants; AT5G08280.1; AT5G08280.1; AT5G08280.
DR   GeneID; 830724; -.
DR   Gramene; AT5G08280.1; AT5G08280.1; AT5G08280.
DR   KEGG; ath:AT5G08280; -.
DR   Araport; AT5G08280; -.
DR   TAIR; AT5G08280; HEMC.
DR   eggNOG; KOG2892; Eukaryota.
DR   HOGENOM; CLU_019704_1_2_1; -.
DR   InParanoid; Q43316; -.
DR   OMA; NAHEWAG; -.
DR   OrthoDB; 788at2759; -.
DR   PhylomeDB; Q43316; -.
DR   BioCyc; ARA:AT5G08280-MONOMER; -.
DR   BioCyc; MetaCyc:AT5G08280-MONOMER; -.
DR   BRENDA; 2.5.1.61; 399.
DR   UniPathway; UPA00251; UER00319.
DR   UniPathway; UPA00668; -.
DR   PRO; PR:Q43316; -.
DR   Proteomes; UP000006548; Chromosome 5.
DR   ExpressionAtlas; Q43316; baseline and differential.
DR   GO; GO:0048046; C:apoplast; HDA:TAIR.
DR   GO; GO:0009507; C:chloroplast; HDA:TAIR.
DR   GO; GO:0009941; C:chloroplast envelope; HDA:TAIR.
DR   GO; GO:0009570; C:chloroplast stroma; HDA:TAIR.
DR   GO; GO:0005886; C:plasma membrane; HDA:TAIR.
DR   GO; GO:0004418; F:hydroxymethylbilane synthase activity; IDA:TAIR.
DR   GO; GO:0015995; P:chlorophyll biosynthetic process; TAS:TAIR.
DR   GO; GO:1900865; P:chloroplast RNA modification; IMP:TAIR.
DR   GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:UniProtKB-UniPathway.
DR   CDD; cd13648; PBP2_PBGD_1; 1.
DR   Gene3D; 3.40.190.10; Periplasmic binding protein-like II; 2.
DR   Gene3D; 3.30.160.40; Porphobilinogen deaminase, C-terminal domain; 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   NCBIfam; TIGR00212; hemC; 1.
DR   PANTHER; PTHR11557; PORPHOBILINOGEN DEAMINASE; 1.
DR   PANTHER; PTHR11557:SF0; PORPHOBILINOGEN DEAMINASE; 1.
DR   Pfam; PF01379; Porphobil_deam; 1.
DR   Pfam; PF03900; Porphobil_deamC; 1.
DR   PRINTS; PR00151; PORPHBDMNASE.
DR   SUPFAM; SSF53850; Periplasmic binding protein-like II; 1.
DR   SUPFAM; SSF54782; Porphobilinogen deaminase (hydroxymethylbilane synthase), C-terminal domain; 1.
DR   PROSITE; PS00533; PORPHOBILINOGEN_DEAM; 1.
DR   Genevisible; Q43316; AT.
PE   1: Evidence at protein level;
KW   3D-structure; Chlorophyll biosynthesis; Chloroplast;
KW   Direct protein sequencing; Phosphoprotein; Plastid; Porphyrin biosynthesis;
KW   Reference proteome; Transferase; Transit peptide.
FT   TRANSIT         1..62
FT                   /note="Chloroplast"
FT                   /evidence="ECO:0000269|PubMed:8192681"
FT   CHAIN           63..382
FT                   /note="Porphobilinogen deaminase, chloroplastic"
FT                   /id="PRO_0000013322"
FT   ACT_SITE        157
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000269|PubMed:23519422"
FT   BINDING         80
FT                   /ligand="dipyrromethane"
FT                   /ligand_id="ChEBI:CHEBI:60342"
FT                   /evidence="ECO:0000305|PubMed:23519422,
FT                   ECO:0007744|PDB:4HTG"
FT   BINDING         82
FT                   /ligand="dipyrromethane"
FT                   /ligand_id="ChEBI:CHEBI:60342"
FT                   /evidence="ECO:0000305|PubMed:23519422,
FT                   ECO:0007744|PDB:4HTG"
FT   BINDING         156..157
FT                   /ligand="dipyrromethane"
FT                   /ligand_id="ChEBI:CHEBI:60342"
FT                   /evidence="ECO:0000305|PubMed:23519422,
FT                   ECO:0007744|PDB:4HTG"
FT   BINDING         200..206
FT                   /ligand="dipyrromethane"
FT                   /ligand_id="ChEBI:CHEBI:60342"
FT                   /evidence="ECO:0000305|PubMed:23519422,
FT                   ECO:0007744|PDB:4HTG"
FT   BINDING         223..229
FT                   /ligand="dipyrromethane"
FT                   /ligand_id="ChEBI:CHEBI:60342"
FT                   /evidence="ECO:0000305|PubMed:23519422,
FT                   ECO:0007744|PDB:4HTG"
FT   MOD_RES         123
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19376835"
FT   MOD_RES         316
FT                   /note="S-(dipyrrolylmethanemethyl)cysteine"
FT                   /evidence="ECO:0000305|PubMed:23519422,
FT                   ECO:0007744|PDB:4HTG"
FT   MUTAGEN         246
FT                   /note="A->V: In rug1; reduced growth and necrotic leaf
FT                   lesions."
FT                   /evidence="ECO:0000269|PubMed:23308205"
FT   CONFLICT        157
FT                   /note="D -> Y (in Ref. 5; AAM64573)"
FT                   /evidence="ECO:0000305"
FT   STRAND          74..79
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   HELIX           83..99
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   HELIX           101..103
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   STRAND          108..113
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   HELIX           117..119
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   HELIX           126..128
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   TURN            134..136
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   HELIX           137..144
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   STRAND          149..154
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   HELIX           155..157
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   STRAND          166..171
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   STRAND          179..185
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   HELIX           189..191
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   STRAND          197..199
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   HELIX           203..212
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   STRAND          216..219
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   HELIX           226..234
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   STRAND          237..244
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   HELIX           245..251
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   HELIX           254..256
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   STRAND          258..260
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   TURN            263..265
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   TURN            270..273
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   STRAND          275..280
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   HELIX           284..291
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   HELIX           296..311
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   STRAND          318..326
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   STRAND          330..339
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   STRAND          346..355
FT                   /evidence="ECO:0007829|PDB:4HTG"
FT   HELIX           357..372
FT                   /evidence="ECO:0007829|PDB:4HTG"
SQ   SEQUENCE   382 AA;  41043 MW;  3DB771BD4E6C9D37 CRC64;
     MDIASSSLSQ AHKVVLTRQP SSRVNTCSLG SVSAIGFSLP QISSPALGKC RRKQSSSGFV
     KACVAVEQKT RTAIIRIGTR GSPLALAQAY ETREKLKKKH PELVEDGAIH IEIIKTTGDK
     ILSQPLADIG GKGLFTKEID EALINGHIDI AVHSMKDVPT YLPEKTILPC NLPREDVRDA
     FICLTAATLA ELPAGSVVGT ASLRRKSQIL HKYPALHVEE NFRGNVQTRL SKLQGGKVQA
     TLLALAGLKR LSMTENVASI LSLDEMLPAV AQGAIGIACR TDDDKMATYL ASLNHEETRL
     AISCERAFLE TLDGSCRTPI AGYASKDEEG NCIFRGLVAS PDGTKVLETS RKGPYVYEDM
     VKMGKDAGQE LLSRAGPGFF GN
//