P74838 (FKBM_STRTA) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
31-O-demethyl-FK506 methyltransferase FkbM
EC=2.1.1.-

Alternative name(s):
FKMT

Gene names

Name:

fkbM

Organism

Streptomyces tacrolimicus

Taxonomic identifier

330919 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Actinobacteria › Actinobacteria › Actinobacteridae › Actinomycetales › Streptomycineae › Streptomycetaceae › Streptomyces

Protein attributes

Sequence length	260 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in the biosynthesis of FK506, which is a macrolide antibiotic with immunosuppressant activity. Catalyzes the transfer of a methyl group from S-adenosyl-L-methionine to the 31-O-position of 31-O-demethyl-FK506. Also catalyzes the methylation of 31-O-demethylimmunomycin, the C31 transmethylation reaction of 13,31-O-bis-demethyl-, 15,31-O-bisdemethyl-, 13,15,31-O-trisdemethyl- and 31-O-19,22-cyclic-hemiketalimmunomycins, which are all structural analogs of FK506. Ref.2
Cofactor	Magnesium. Ref.2
Enzyme regulation	Inhibited by S-adenosylhomocysteine and sinefungin. Ref.2
Subunit structure	Monomer. Ref.2
Subcellular location	Cytoplasm Ref.2.
Sequence similarities	Belongs to the FkbM methyltransferase family.
Biophysicochemical properties	Kinetic parameters: KM=23 µM for 31-O-demethyl-FK506 (at pH 7.4 and 34 degrees Celsius) Ref.2 KM=28 µM for S-adenosyl-L-methionine (at pH 7.4 and 34 degrees Celsius) Vmax=2.33 nmol/min/mg enzyme toward 31-O-demethyl-FK506 (at pH 7.4 and 34 degrees Celsius) Vmax=2.01 nmol/min/mg enzyme toward S-adenosyl-L-methionine (at pH 7.4 and 34 degrees Celsius) pH dependence: Optimum pH is 8.5. Temperature dependence: Optimum temperature is 34 degrees Celsius.

Ontologies

Keywords
Cellular component	Cytoplasm
Ligand	Magnesium
Molecular function	Methyltransferase Transferase
Technical term	Direct protein sequencing
Gene Ontology (GO)
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	methyltransferase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.2
	Chain	2 – 260	259	31-O-demethyl-FK506 methyltransferase FkbM		PRO_0000415368

Sequences

	Sequence		Length	Mass (Da)
	P74838 [UniParc]. Last modified February 1, 1997. Version 1. Checksum: F7F129736351B36C	FASTA	260	28,213
	10 20 30 40 50 60 MSDVVETLRL PNGATVAHVN AGEAQFLYRE IFTDRCYLRH GVELRPGDVV FDVGANIGMF 70 80 90 100 110 120 MLFAHLEHPG VTVHAFEPAP VPFAALRANA VRHRVAGRVD QCAVSDEAGV RRMTFYPDAT 130 140 150 160 170 180 LMSGFHPDAA ARKELLRTLG LNGGYTAEDV DMMLAQLPDT GEEIETSVVR LSDVIAERGI 190 200 210 220 230 240 AAIGLLKIDV EKSERRVLAG VEDADWPRIR QVVAEVHDVD GALGEVVALL RGHGFTVVAE 250 260 QDPLFAGTEI HQVAARRTAG

References

[1]

"Characterization of methyltransferase and hydroxylase genes involved in the biosynthesis of the immunosuppressants FK506 and FK520." Motamedi H., Shafiee A., Cai S.J., Streicher S.L., Arison B.H., Miller R.R. J. Bacteriol. 178:5243-5248(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 55098 / MA 6858.

[2]

"Enzymology of FK-506 biosynthesis. Purification and characterization of 31-O-desmethylFK-506 O:methyltransferase from Streptomyces sp. MA6858." Shafiee A., Motamedi H., Chen T. Eur. J. Biochem. 225:755-764(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-40, FUNCTION, COFACTOR, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION. Strain: ATCC 55098 / MA 6858.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U65940 Genomic DNA. Translation: AAC44360.1.
3D structure databases
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Enzyme and pathway databases
BioCyc	MetaCyc:MONOMER-13930.
Family and domain databases
InterPro	IPR006342. FkbM_mtfrase. [Graphical view]
Pfam	PF05050. Methyltransf_21. 1 hit. [Graphical view]
TIGRFAMs	TIGR01444. fkbM_fam. 1 hit.
ProtoNet	Search...

Entry information

Entry name

FKBM_STRTA

Accession

Primary (citable) accession number: P74838

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 25, 2012
Last sequence update:	February 1, 1997
Last modified:	April 3, 2013
This is version 41 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program