Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P0AEA8 (CYSG_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 84. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Siroheme synthase

Including the following 3 domains:

  1. Uroporphyrinogen-III C-methyltransferase
    Short name=Urogen III methylase
    EC=2.1.1.107
    Alternative name(s):
    SUMT
    Uroporphyrinogen III methylase
    Short name=UROM
  2. Precorrin-2 dehydrogenase
    EC=1.3.1.76
  3. Sirohydrochlorin ferrochelatase
    EC=4.99.1.4
Gene names
Name:cysG
Ordered Locus Names:b3368, JW3331
OrganismEscherichia coli (strain K12) [Reference proteome] [HAMAP]
Taxonomic identifier83333 [NCBI]
Taxonomic lineageBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia

Protein attributes

Sequence length457 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9

Catalytic activity

S-adenosyl-L-methionine + uroporphyrinogen III = S-adenosyl-L-homocysteine + precorrin-1. Ref.5 Ref.6 Ref.7 Ref.9

S-adenosyl-L-methionine + precorrin-1 = S-adenosyl-L-homocysteine + precorrin-2. Ref.5 Ref.6 Ref.7 Ref.9

Precorrin-2 + NAD+ = sirohydrochlorin + NADH. Ref.5 Ref.6 Ref.7 Ref.9

Siroheme + 2 H+ = sirohydrochlorin + Fe2+. Ref.5 Ref.6 Ref.7 Ref.9

Pathway

Cofactor biosynthesis; adenosylcobalamin biosynthesis; precorrin-2 from uroporphyrinogen III: step 1/1. HAMAP-Rule MF_01646

Cofactor biosynthesis; adenosylcobalamin biosynthesis; sirohydrochlorin from precorrin-2: step 1/1.

Porphyrin-containing compound metabolism; siroheme biosynthesis; precorrin-2 from uroporphyrinogen III: step 1/1. HAMAP-Rule MF_01646

Porphyrin-containing compound metabolism; siroheme biosynthesis; siroheme from sirohydrochlorin: step 1/1.

Porphyrin-containing compound metabolism; siroheme biosynthesis; sirohydrochlorin from precorrin-2: step 1/1.

Subunit structure

Monomer. Ref.6

Sequence similarities

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

In the C-terminal section; belongs to the precorrin methyltransferase family.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

nadEP188431EBI-1132623,EBI-548960

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 457457Siroheme synthase HAMAP-Rule MF_01646
PRO_0000150378

Regions

Nucleotide binding22 – 232NAD By similarity
Nucleotide binding43 – 442NAD By similarity
Region4 – 204201Precorrin-2 dehydrogenase / sirohydrochlorin ferrochelatase By similarity
Region216 – 448233Uroporphyrinogen-III C-methyltransferase By similarity
Region301 – 3033S-adenosyl-L-methionine binding By similarity
Region331 – 3322S-adenosyl-L-methionine binding By similarity

Sites

Active site2481Proton acceptor Potential
Active site2701Proton donor Potential
Binding site2251S-adenosyl-L-methionine; via carbonyl oxygen By similarity
Binding site3061S-adenosyl-L-methionine; via carbonyl oxygen By similarity
Binding site3821S-adenosyl-L-methionine; via amide nitrogen By similarity
Binding site4111S-adenosyl-L-methionine; via amide nitrogen and carbonyl oxygen By similarity

Amino acid modifications

Modified residue1281Phosphoserine By similarity

Experimental info

Mutagenesis211G → D: It has methyltransferase and ferrochelatase activities but a greatly reduced dehydrogenase activity. It is able to bind AdoMet. Ref.9
Mutagenesis2241G → A: It abolishes methyltransferase activity, but has dehydrogenase and ferrochelatase activities. It is unable to bind AdoMet. Ref.9
Mutagenesis2271D → A: It has all activities of CysG. Ref.9
Mutagenesis2481D → A: It abolishes methyltransferase activity, but has dehydrogenase and ferrochelatase activities. It is able to bind AdoMet.
Mutagenesis2701K → I: It has all activities of CysG. It is able to bind AdoMet. Ref.9
Mutagenesis2981R → L: It abolishes methyltransferase activity, but has dehydrogenase and ferrochelatase activities. It is unable to bind AdoMet. Ref.9
Mutagenesis3031D → A: It has all activities of CysG. It is able to bind AdoMet. Ref.9
Mutagenesis3091R → L: It abolishes methyltransferase activity, but has dehydrogenase and ferrochelatase activities. It is able to bind AdoMet. Ref.9
Sequence conflict261R → P in CAA32419. Ref.1
Sequence conflict261R → P in AAA58165. Ref.2
Sequence conflict90 – 912SE → RQ in CAA32419. Ref.1
Sequence conflict90 – 912SE → RQ in AAA58165. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P0AEA8 [UniParc].

Last modified December 6, 2005. Version 1.
Checksum: DDDE0DC90C5CF2F4

FASTA45749,951
        10         20         30         40         50         60 
MDHLPIFCQL RDRDCLIVGG GDVAERKARL LLDAGARLTV NALAFIPQFT AWADAGMLTL 

        70         80         90        100        110        120 
VEGPFDESLL DTCWLAIAAT DDDALNQRVS EAAEARRIFC NVVDAPKAAS FIMPSIIDRS 

       130        140        150        160        170        180 
PLMVAVSSGG TSPVLARLLR EKLESLLPLH LGQVAKYAGQ LRGRVKQQFA TMGERRRFWE 

       190        200        210        220        230        240 
KLFVNDRLAQ SLANNDQKAI TETTEQLINE PLDHRGEVVL VGAGPGDAGL LTLKGLQQIQ 

       250        260        270        280        290        300 
QADVVVYDRL VSDDIMNLVR RDADRVFVGK RAGYHCVPQE EINQILLREA QKGKRVVRLK 

       310        320        330        340        350        360 
GGDPFIFGRG GEELETLCNA GIPFSVVPGI TAASGCSAYS GIPLTHRDYA QSVRLITGHL 

       370        380        390        400        410        420 
KTGGELDWEN LAAEKQTLVF YMGLNQAATI QQKLIEHGMP GEMPVAIVEN GTAVTQRVID 

       430        440        450 
GTLTQLGELA QQMNSPSLII IGRVVGLRDK LNWFSNH 

« Hide

References

« Hide 'large scale' references
[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]"The complete genome sequence of Escherichia coli K-12."
Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., Shao Y.
Science 277:1453-1462(1997) [PubMed] [Europe PMC] [Abstract]
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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X14202 Genomic DNA. Translation: CAA32419.1.
U18997 Genomic DNA. Translation: AAA58165.1.
U00096 Genomic DNA. Translation: AAC76393.1.
AP009048 Genomic DNA. Translation: BAE77922.1.
PIRC65131.
RefSeqNP_417827.1. NC_000913.3.
YP_492063.1. NC_007779.1.

3D structure databases

ProteinModelPortalP0AEA8.
SMRP0AEA8. Positions 1-457.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP0AEA8. 1 interaction.
STRING511145.b3368.

Proteomic databases

PaxDbP0AEA8.
PRIDEP0AEA8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaAAC76393; AAC76393; b3368.
BAE77922; BAE77922; BAE77922.
GeneID12933484.
947880.
KEGGecj:Y75_p3807.
eco:b3368.
PATRIC32122170. VBIEscCol129921_3462.

Organism-specific databases

EchoBASEEB0185.
EcoGeneEG10188. cysG.

Phylogenomic databases

eggNOGCOG0007.
HOGENOMHOG000290518.
KOK02302.
OMAQASFIMP.
OrthoDBEOG6DRPFR.
PhylomeDBP0AEA8.

Enzyme and pathway databases

BioCycEcoCyc:SIROHEMESYN-MONOMER.
ECOL316407:JW3331-MONOMER.
MetaCyc:SIROHEMESYN-MONOMER.
UniPathwayUPA00148; UER00211.
UPA00148; UER00222.
UPA00262; UER00211.
UPA00262; UER00222.
UPA00262; UER00376.

Gene expression databases

GenevestigatorP0AEA8.

Family and domain databases

Gene3D1.10.8.210. 1 hit.
3.30.950.10. 1 hit.
3.40.1010.10. 1 hit.
3.40.50.720. 1 hit.
HAMAPMF_01646. Siroheme_synth.
InterProIPR000878. 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]
PfamPF10414. CysG_dimeriser. 1 hit.
PF13241. NAD_binding_7. 1 hit.
PF00590. TP_methylase. 1 hit.
[Graphical view]
PIRSFPIRSF036426. Sirohaem_synth. 1 hit.
SUPFAMSSF53790. SSF53790. 1 hit.
TIGRFAMsTIGR01469. cobA_cysG_Cterm. 1 hit.
TIGR01470. cysG_Nterm. 1 hit.
PROSITEPS00839. SUMT_1. 1 hit.
PS00840. SUMT_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

PROP0AEA8.

Entry information

Entry nameCYSG_ECOLI
AccessionPrimary (citable) accession number: P0AEA8
Secondary accession number(s): P11098, P76685, Q2M734
Entry history
Integrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: December 6, 2005
Last modified: June 11, 2014
This is version 84 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

Escherichia coli

Escherichia coli (strain K12): entries and cross-references to EcoGene