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Protein

Siroheme synthase

Gene

cysG

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Multifunctional enzyme that catalyzes the SAM-dependent methylations of uroporphyrinogen III at position C-2 and C-7 to form precorrin-2 via precorrin-1. Then it catalyzes the NAD-dependent ring dehydrogenation of precorrin-2 to yield sirohydrochlorin. Finally, it catalyzes the ferrochelation of sirohydrochlorin to yield siroheme.5 PublicationsUniRule annotation

Catalytic activityi

S-adenosyl-L-methionine + uroporphyrinogen III = S-adenosyl-L-homocysteine + precorrin-1.UniRule annotation
S-adenosyl-L-methionine + precorrin-1 = S-adenosyl-L-homocysteine + precorrin-2.UniRule annotation
Precorrin-2 + NAD+ = sirohydrochlorin + NADH.UniRule annotation
Siroheme + 2 H+ = sirohydrochlorin + Fe2+.UniRule annotation

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei225 – 2251S-adenosyl-L-methionine; via carbonyl oxygenUniRule annotation
Active sitei248 – 2481Proton acceptorUniRule annotation
Active sitei270 – 2701Proton donorUniRule annotation
Binding sitei306 – 3061S-adenosyl-L-methionine; via carbonyl oxygenUniRule annotation
Binding sitei382 – 3821S-adenosyl-L-methionine; via amide nitrogenUniRule annotation
Binding sitei411 – 4111S-adenosyl-L-methionine; via amide nitrogen and carbonyl oxygenUniRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi22 – 232NADUniRule annotation
Nucleotide bindingi43 – 442NADUniRule annotation

GO - Molecular functioni

  1. NAD binding Source: InterPro
  2. precorrin-2 dehydrogenase activity Source: EcoCyc
  3. sirohydrochlorin ferrochelatase activity Source: EcoCyc
  4. uroporphyrin-III C-methyltransferase activity Source: EcoCyc

GO - Biological processi

  1. cobalamin biosynthetic process Source: UniProtKB-HAMAP
  2. response to osmotic stress Source: EcoCyc
  3. siroheme biosynthetic process Source: EcoCyc
Complete GO annotation...

Keywords - Molecular functioni

Lyase, Methyltransferase, Oxidoreductase, Transferase

Keywords - Biological processi

Cobalamin biosynthesis, Porphyrin biosynthesis

Keywords - Ligandi

NAD, S-adenosyl-L-methionine

Enzyme and pathway databases

BioCyciEcoCyc:SIROHEMESYN-MONOMER.
ECOL316407:JW3331-MONOMER.
MetaCyc:SIROHEMESYN-MONOMER.
UniPathwayiUPA00148; UER00211.
UPA00148; UER00222.
UPA00262; UER00211.
UPA00262; UER00222.
UPA00262; UER00376.

Names & Taxonomyi

Protein namesi
Recommended name:
Siroheme synthaseUniRule annotation
Including the following 3 domains:
Uroporphyrinogen-III C-methyltransferaseUniRule annotation (EC:2.1.1.107UniRule annotation)
Short name:
Urogen III methylaseUniRule annotation
Alternative name(s):
SUMTUniRule annotation
Uroporphyrinogen III methylaseUniRule annotation
Short name:
UROMUniRule annotation
Precorrin-2 dehydrogenaseUniRule annotation (EC:1.3.1.76UniRule annotation)
Sirohydrochlorin ferrochelataseUniRule annotation (EC:4.99.1.4UniRule annotation)
Gene namesi
Name:cysGUniRule annotation
Ordered Locus Names:b3368, JW3331
OrganismiEscherichia coli (strain K12)
Taxonomic identifieri83333 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
ProteomesiUP000000318: Chromosome, UP000000625: Chromosome

Organism-specific databases

EcoGeneiEG10188. cysG.

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi21 – 211G → D: It has methyltransferase and ferrochelatase activities but a greatly reduced dehydrogenase activity. It is able to bind AdoMet. 1 Publication
Mutagenesisi224 – 2241G → A: It abolishes methyltransferase activity, but has dehydrogenase and ferrochelatase activities. It is unable to bind AdoMet. 1 Publication
Mutagenesisi227 – 2271D → A: It has all activities of CysG. 1 Publication
Mutagenesisi248 – 2481D → A: It abolishes methyltransferase activity, but has dehydrogenase and ferrochelatase activities. It is able to bind AdoMet.
Mutagenesisi270 – 2701K → I: It has all activities of CysG. It is able to bind AdoMet. 1 Publication
Mutagenesisi298 – 2981R → L: It abolishes methyltransferase activity, but has dehydrogenase and ferrochelatase activities. It is unable to bind AdoMet. 1 Publication
Mutagenesisi303 – 3031D → A: It has all activities of CysG. It is able to bind AdoMet. 1 Publication
Mutagenesisi309 – 3091R → L: It abolishes methyltransferase activity, but has dehydrogenase and ferrochelatase activities. It is able to bind AdoMet. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 457457Siroheme synthasePRO_0000150378Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei128 – 1281PhosphoserineUniRule annotation

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP0AEA8.
PRIDEiP0AEA8.

Expressioni

Gene expression databases

GenevestigatoriP0AEA8.

Interactioni

Subunit structurei

Monomer.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
nadEP188431EBI-1132623,EBI-548960

Protein-protein interaction databases

IntActiP0AEA8. 1 interaction.
STRINGi511145.b3368.

Structurei

3D structure databases

ProteinModelPortaliP0AEA8.
SMRiP0AEA8. Positions 1-457.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni4 – 204201Precorrin-2 dehydrogenase / sirohydrochlorin ferrochelataseBy similarityAdd
BLAST
Regioni216 – 448233Uroporphyrinogen-III C-methyltransferaseUniRule annotationAdd
BLAST
Regioni301 – 3033S-adenosyl-L-methionine bindingUniRule annotation
Regioni331 – 3322S-adenosyl-L-methionine bindingUniRule annotation

Sequence similaritiesi

In the N-terminal section; belongs to the precorrin-2 dehydrogenase / sirohydrochlorin ferrochelatase family.UniRule annotation
In the C-terminal section; belongs to the precorrin methyltransferase family.UniRule annotation

Phylogenomic databases

eggNOGiCOG0007.
HOGENOMiHOG000290518.
InParanoidiP0AEA8.
KOiK02302.
OMAiQASFIMP.
OrthoDBiEOG6DRPFR.
PhylomeDBiP0AEA8.

Family and domain databases

Gene3Di1.10.8.210. 1 hit.
3.30.950.10. 1 hit.
3.40.1010.10. 1 hit.
3.40.50.720. 1 hit.
HAMAPiMF_01646. Siroheme_synth.
InterProiIPR000878. 4pyrrol_Mease.
IPR014777. 4pyrrole_Mease_sub1.
IPR014776. 4pyrrole_Mease_sub2.
IPR006366. CobA/CysG_C.
IPR016040. NAD(P)-bd_dom.
IPR012409. Sirohaem_synth.
IPR019478. Sirohaem_synthase_dimer_dom.
IPR006367. Sirohaem_synthase_N.
IPR003043. Uropor_MeTrfase_CS.
[Graphical view]
PfamiPF10414. CysG_dimeriser. 1 hit.
PF13241. NAD_binding_7. 1 hit.
PF00590. TP_methylase. 1 hit.
[Graphical view]
PIRSFiPIRSF036426. Sirohaem_synth. 1 hit.
SUPFAMiSSF53790. SSF53790. 1 hit.
TIGRFAMsiTIGR01469. cobA_cysG_Cterm. 1 hit.
TIGR01470. cysG_Nterm. 1 hit.
PROSITEiPS00839. SUMT_1. 1 hit.
PS00840. SUMT_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P0AEA8-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MDHLPIFCQL RDRDCLIVGG GDVAERKARL LLDAGARLTV NALAFIPQFT
60 70 80 90 100
AWADAGMLTL VEGPFDESLL DTCWLAIAAT DDDALNQRVS EAAEARRIFC
110 120 130 140 150
NVVDAPKAAS FIMPSIIDRS PLMVAVSSGG TSPVLARLLR EKLESLLPLH
160 170 180 190 200
LGQVAKYAGQ LRGRVKQQFA TMGERRRFWE KLFVNDRLAQ SLANNDQKAI
210 220 230 240 250
TETTEQLINE PLDHRGEVVL VGAGPGDAGL LTLKGLQQIQ QADVVVYDRL
260 270 280 290 300
VSDDIMNLVR RDADRVFVGK RAGYHCVPQE EINQILLREA QKGKRVVRLK
310 320 330 340 350
GGDPFIFGRG GEELETLCNA GIPFSVVPGI TAASGCSAYS GIPLTHRDYA
360 370 380 390 400
QSVRLITGHL KTGGELDWEN LAAEKQTLVF YMGLNQAATI QQKLIEHGMP
410 420 430 440 450
GEMPVAIVEN GTAVTQRVID GTLTQLGELA QQMNSPSLII IGRVVGLRDK

LNWFSNH
Length:457
Mass (Da):49,951
Last modified:December 6, 2005 - v1
Checksum:iDDDE0DC90C5CF2F4
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti26 – 261R → P in CAA32419. (PubMed:2543955)Curated
Sequence conflicti26 – 261R → P in AAA58165. (PubMed:2200672)Curated
Sequence conflicti90 – 912SE → RQ in CAA32419. (PubMed:2543955)Curated
Sequence conflicti90 – 912SE → RQ in AAA58165. (PubMed:2200672)Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X14202 Genomic DNA. Translation: CAA32419.1.
U18997 Genomic DNA. Translation: AAA58165.1.
U00096 Genomic DNA. Translation: AAC76393.1.
AP009048 Genomic DNA. Translation: BAE77922.1.
PIRiC65131.
RefSeqiNP_417827.1. NC_000913.3.
YP_492063.1. NC_007779.1.

Genome annotation databases

EnsemblBacteriaiAAC76393; AAC76393; b3368.
BAE77922; BAE77922; BAE77922.
GeneIDi12933484.
947880.
KEGGiecj:Y75_p3807.
eco:b3368.
PATRICi32122170. VBIEscCol129921_3462.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X14202 Genomic DNA. Translation: CAA32419.1.
U18997 Genomic DNA. Translation: AAA58165.1.
U00096 Genomic DNA. Translation: AAC76393.1.
AP009048 Genomic DNA. Translation: BAE77922.1.
PIRiC65131.
RefSeqiNP_417827.1. NC_000913.3.
YP_492063.1. NC_007779.1.

3D structure databases

ProteinModelPortaliP0AEA8.
SMRiP0AEA8. Positions 1-457.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP0AEA8. 1 interaction.
STRINGi511145.b3368.

Proteomic databases

PaxDbiP0AEA8.
PRIDEiP0AEA8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAC76393; AAC76393; b3368.
BAE77922; BAE77922; BAE77922.
GeneIDi12933484.
947880.
KEGGiecj:Y75_p3807.
eco:b3368.
PATRICi32122170. VBIEscCol129921_3462.

Organism-specific databases

EchoBASEiEB0185.
EcoGeneiEG10188. cysG.

Phylogenomic databases

eggNOGiCOG0007.
HOGENOMiHOG000290518.
InParanoidiP0AEA8.
KOiK02302.
OMAiQASFIMP.
OrthoDBiEOG6DRPFR.
PhylomeDBiP0AEA8.

Enzyme and pathway databases

UniPathwayiUPA00148; UER00211.
UPA00148; UER00222.
UPA00262; UER00211.
UPA00262; UER00222.
UPA00262; UER00376.
BioCyciEcoCyc:SIROHEMESYN-MONOMER.
ECOL316407:JW3331-MONOMER.
MetaCyc:SIROHEMESYN-MONOMER.

Miscellaneous databases

PROiP0AEA8.

Gene expression databases

GenevestigatoriP0AEA8.

Family and domain databases

Gene3Di1.10.8.210. 1 hit.
3.30.950.10. 1 hit.
3.40.1010.10. 1 hit.
3.40.50.720. 1 hit.
HAMAPiMF_01646. Siroheme_synth.
InterProiIPR000878. 4pyrrol_Mease.
IPR014777. 4pyrrole_Mease_sub1.
IPR014776. 4pyrrole_Mease_sub2.
IPR006366. CobA/CysG_C.
IPR016040. NAD(P)-bd_dom.
IPR012409. Sirohaem_synth.
IPR019478. Sirohaem_synthase_dimer_dom.
IPR006367. Sirohaem_synthase_N.
IPR003043. Uropor_MeTrfase_CS.
[Graphical view]
PfamiPF10414. CysG_dimeriser. 1 hit.
PF13241. NAD_binding_7. 1 hit.
PF00590. TP_methylase. 1 hit.
[Graphical view]
PIRSFiPIRSF036426. Sirohaem_synth. 1 hit.
SUPFAMiSSF53790. SSF53790. 1 hit.
TIGRFAMsiTIGR01469. cobA_cysG_Cterm. 1 hit.
TIGR01470. cysG_Nterm. 1 hit.
PROSITEiPS00839. SUMT_1. 1 hit.
PS00840. SUMT_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning of binding sequences for the Escherichia coli transcription activators, FNR and CRP: location of bases involved in discrimination between FNR and CRP."
    Bell A.I., Gaston K.L., Cole J.A., Busby S.J.W.
    Nucleic Acids Res. 17:3865-3874(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: K12.
  2. "Nucleotide sequence, organisation and structural analysis of the products of genes in the nirB-cysG region of the Escherichia coli K-12 chromosome."
    Peakman T., Crouzet J., Mayaux J.F., Busby S.J.W., Mohan S., Harborne N., Wootton J., Nicolson R., Cole J.A.
    Eur. J. Biochem. 191:315-323(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: K12.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12 / MG1655 / ATCC 47076.
  4. "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110."
    Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.
    Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
  5. "Enzymatic synthesis of dihydrosirohydrochlorin (precorrin-2) and of a novel pyrrocorphin by uroporphyrinogen III methylase."
    Warren M.J., Stolowich N.J., Santander P.J., Roessner C.A., Sowa B.A., Scott A.I.
    FEBS Lett. 261:76-80(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 1-18, FUNCTION, CATALYTIC ACTIVITY.
  6. "The Escherichia coli cysG gene encodes S-adenosylmethionine-dependent uroporphyrinogen III methylase."
    Warren M.J., Roessner C.A., Santander P.J., Scott A.I.
    Biochem. J. 265:725-729(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS A METHYLTRANSFERASE, CATALYTIC ACTIVITY, SUBUNIT.
  7. "The Escherichia coli cysG gene encodes the multifunctional protein, siroheme synthase."
    Spencer J.B., Stolowich N.J., Roessner C.A., Scott A.I.
    FEBS Lett. 335:57-60(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AND CATALYTIC ACTIVITY.
  8. "Evidence for a covalent intermediate in the S-adenosyl-L-methionine-dependent transmethylation reaction catalysed by sirohaem synthase."
    Woodcock S.C., Warren M.J.
    Biochem. J. 313:415-421(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "Effect of mutations in the transmethylase and dehydrogenase/chelatase domains of sirohaem synthase (CysG) on sirohaem and cobalamin biosynthesis."
    Woodcock S.C., Raux E., Levillayer F., Thermes C., Rambach A., Warren M.J.
    Biochem. J. 330:121-129(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF GLY-21; GLY-224; ASP-227; LYS-270; ARG-298; ASP-303 AND ARG-309.

Entry informationi

Entry nameiCYSG_ECOLI
AccessioniPrimary (citable) accession number: P0AEA8
Secondary accession number(s): P11098, P76685, Q2M734
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: December 6, 2005
Last modified: January 7, 2015
This is version 87 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Multifunctional enzyme, Reference proteome

Documents

  1. Escherichia coli
    Escherichia coli (strain K12): entries and cross-references to EcoGene
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.