GTFA_STRPN
ID GTFA_STRPN Reviewed; 503 AA.
AC A0A0H2URG7;
DT 08-MAY-2019, integrated into UniProtKB/Swiss-Prot.
DT 16-SEP-2015, sequence version 1.
DT 03-AUG-2022, entry version 33.
DE RecName: Full=UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase GtfA subunit {ECO:0000255|HAMAP-Rule:MF_01472, ECO:0000305};
DE EC=2.4.1.- {ECO:0000255|HAMAP-Rule:MF_01472, ECO:0000269|PubMed:24936067};
DE AltName: Full=Glycosyltransferase GtfA {ECO:0000255|HAMAP-Rule:MF_01472, ECO:0000303|PubMed:24936067};
DE AltName: Full=O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase {ECO:0000303|PubMed:24936067};
GN Name=gtfA {ECO:0000255|HAMAP-Rule:MF_01472, ECO:0000303|PubMed:24936067};
GN OrderedLocusNames=SP_1758;
OS Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4).
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Streptococcaceae;
OC Streptococcus.
OX NCBI_TaxID=170187;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-334 / TIGR4;
RX PubMed=11463916; DOI=10.1126/science.1061217;
RA Tettelin H., Nelson K.E., Paulsen I.T., Eisen J.A., Read T.D.,
RA Peterson S.N., Heidelberg J.F., DeBoy R.T., Haft D.H., Dodson R.J.,
RA Durkin A.S., Gwinn M.L., Kolonay J.F., Nelson W.C., Peterson J.D.,
RA Umayam L.A., White O., Salzberg S.L., Lewis M.R., Radune D.,
RA Holtzapple E.K., Khouri H.M., Wolf A.M., Utterback T.R., Hansen C.L.,
RA McDonald L.A., Feldblyum T.V., Angiuoli S.V., Dickinson T., Hickey E.K.,
RA Holt I.E., Loftus B.J., Yang F., Smith H.O., Venter J.C., Dougherty B.A.,
RA Morrison D.A., Hollingshead S.K., Fraser C.M.;
RT "Complete genome sequence of a virulent isolate of Streptococcus
RT pneumoniae.";
RL Science 293:498-506(2001).
RN [2]
RP DISCUSSION OF SEQUENCE.
RC STRAIN=ATCC BAA-334 / TIGR4;
RX PubMed=16861665; DOI=10.1128/iai.00316-06;
RA Obert C., Sublett J., Kaushal D., Hinojosa E., Barton T., Tuomanen E.I.,
RA Orihuela C.J.;
RT "Identification of a candidate Streptococcus pneumoniae core genome and
RT regions of diversity correlated with invasive pneumococcal disease.";
RL Infect. Immun. 74:4766-4777(2006).
RN [3]
RP FUNCTION, AND PATHWAY.
RC STRAIN=ATCC BAA-334 / TIGR4;
RX PubMed=28246170; DOI=10.1074/jbc.m116.770446;
RA Jiang Y.L., Jin H., Yang H.B., Zhao R.L., Wang S., Chen Y., Zhou C.Z.;
RT "Defining the enzymatic pathway for polymorphic O-glycosylation of the
RT pneumococcal serine-rich repeat protein PsrP.";
RL J. Biol. Chem. 292:6213-6224(2017).
RN [4] {ECO:0007744|PDB:4PQG}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH
RP N-ACETYL-D-GLUCOSAMINE AND UDP, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, DOMAIN, AND MUTAGENESIS OF ASN-98;
RP ARG-103; TYR-116; GLU-244; ARG-328; GLU-332; LYS-333 AND SER-403.
RC STRAIN=ATCC BAA-334 / TIGR4;
RX PubMed=24936067; DOI=10.1074/jbc.m114.581934;
RA Shi W.W., Jiang Y.L., Zhu F., Yang Y.H., Shao Q.Y., Yang H.B., Ren Y.M.,
RA Wu H., Chen Y., Zhou C.Z.;
RT "Structure of a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc)
RT transferase, GtfA, reveals insights into the glycosylation of pneumococcal
RT serine-rich repeat adhesins.";
RL J. Biol. Chem. 289:20898-20907(2014).
CC -!- FUNCTION: Required for the polymorphic O-glycosylation of serine-rich
CC repeat protein PsrP. Catalyzes the first step in glycosylation by
CC transferring N-acetylglucosamine from UDP-GlcNAc to serine residues in
CC PsrP (PubMed:24936067, PubMed:28246170). Part of the accessory
CC SecA2/SecY2 system specifically required to export serine-rich repeat
CC cell wall proteins encoded upstream in the same operon (Probable). The
CC GtfA-GtfB complex adds GlcNAc from UDP-GlcNAc to PsrP (experimentally
CC characterized with truncated PsrP-SSR1 constructs); this subunit alone
CC has weak N-acetylglucosaminyl transferase activity that is 10-fold
CC stimulated by GtfB. The complex requires at least a 25 residue-long
CC peptide for activity; the in vitro assay has only been seen to
CC glycosylate Ser residues (PubMed:24936067). The alpha linkage was shown
CC in L.reuteri. {ECO:0000250|UniProtKB:A0A0S4NM89,
CC ECO:0000269|PubMed:24936067, ECO:0000269|PubMed:28246170,
CC ECO:0000305|PubMed:16861665}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-seryl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = 3-O-[N-
CC acetyl-alpha-D-glucosaminyl]-L-seryl-[protein] + H(+) + UDP;
CC Xref=Rhea:RHEA:59872, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:15471,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:57705,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:143279;
CC Evidence={ECO:0000250|UniProtKB:A0A0S4NM89, ECO:0000255|HAMAP-
CC Rule:MF_01472, ECO:0000305|PubMed:24936067};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Note=kcat for hydrolysis of UDP-N-acetyl-alpha-D-glucosamine with
CC transfer of GlcNAc to PsrP-SSR1 and generation of UDP is 76.0 min(-1)
CC for GtfA-GtfB and 7.35 min(-1) for GtfA alone.
CC {ECO:0000269|PubMed:24936067};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000255|HAMAP-Rule:MF_01472, ECO:0000269|PubMed:24936067,
CC ECO:0000269|PubMed:28246170}.
CC -!- SUBUNIT: Monomer (PubMed:24936067). Interacts with stabilizing protein
CC GtfB, probably as a heterotetramer with 2 subunits each of GtfA and
CC GtfB, part of the accessory SecA2/SecY2 protein translocation apparatus
CC (PubMed:24936067). {ECO:0000269|PubMed:24936067}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_01472}. Cell
CC membrane {ECO:0000250|UniProtKB:A1C3L9, ECO:0000255|HAMAP-
CC Rule:MF_01472}; Peripheral membrane protein {ECO:0000255|HAMAP-
CC Rule:MF_01472}. Note=Cell membrane association requires GtfB.
CC {ECO:0000250|UniProtKB:A1C3L9, ECO:0000255|HAMAP-Rule:MF_01472}.
CC -!- DOMAIN: Has 2 Rossmann-like domains, called R-fold-1 and R-fold-2. R-
CC fold-1 is interrupted by an extended beta-sheet domain that loops out
CC of the structure and is required for recognizing both PsrP substrate
CC and coactivator GtfB. UDP and N-acetyl-D-glucosamine bind between the
CC Rossmann-like folds. {ECO:0000269|PubMed:24936067}.
CC -!- MISCELLANEOUS: Encoded in RD10, a pathogenicity island with an atypical
CC GC content that is associated with invasive pneumococcal disease.
CC Pathogenicity islands account for greater than half the genomic
CC diversity observed between isolates (PubMed:11463916, PubMed:16861665).
CC The main function of this island seems to be correct synthesis and
CC export of pneumococcal serine-rich repeat protein PsrP (Probable).
CC {ECO:0000303|PubMed:11463916, ECO:0000303|PubMed:16861665,
CC ECO:0000305}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase group 1 family.
CC Glycosyltransferase 4 subfamily. {ECO:0000255|HAMAP-Rule:MF_01472}.
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DR EMBL; AE005672; AAK75833.1; -; Genomic_DNA.
DR RefSeq; WP_000158460.1; NZ_AKVY01000001.1.
DR PDB; 4PQG; X-ray; 2.00 A; A/B=1-503.
DR PDBsum; 4PQG; -.
DR AlphaFoldDB; A0A0H2URG7; -.
DR SMR; A0A0H2URG7; -.
DR STRING; 170187.SP_1758; -.
DR EnsemblBacteria; AAK75833; AAK75833; SP_1758.
DR GeneID; 66806831; -.
DR KEGG; spn:SP_1758; -.
DR eggNOG; COG0438; Bacteria.
DR OMA; HIDWLVA; -.
DR PhylomeDB; A0A0H2URG7; -.
DR BioCyc; SPNE170187:G1FZB-1783-MON; -.
DR BRENDA; 2.4.1.255; 9553.
DR UniPathway; UPA00378; -.
DR Proteomes; UP000000585; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0017122; C:protein N-acetylglucosaminyltransferase complex; IDA:UniProtKB.
DR GO; GO:0016757; F:glycosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0018242; P:protein O-linked glycosylation via serine; IDA:UniProtKB.
DR HAMAP; MF_01472; GtfA; 1.
DR InterPro; IPR001296; Glyco_trans_1.
DR InterPro; IPR014267; GtfA.
DR Pfam; PF00534; Glycos_transf_1; 1.
DR TIGRFAMs; TIGR02918; TIGR02918; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cytoplasm; Glycosyltransferase; Membrane;
KW Nucleotide-binding; Transferase.
FT CHAIN 1..503
FT /note="UDP-N-acetylglucosamine--peptide N-
FT acetylglucosaminyltransferase GtfA subunit"
FT /id="PRO_0000447202"
FT REGION 1..78
FT /note="N-terminus R-fold-1"
FT /evidence="ECO:0000269|PubMed:24936067"
FT REGION 79..195
FT /note="Extended beta-sheet domain"
FT /evidence="ECO:0000269|PubMed:24936067"
FT REGION 196..306
FT /note="C-terminus R-fold-1"
FT /evidence="ECO:0000269|PubMed:24936067"
FT REGION 307..503
FT /note="R-fold-2"
FT /evidence="ECO:0000269|PubMed:24936067"
FT BINDING 16..19
FT /ligand="UDP"
FT /ligand_id="ChEBI:CHEBI:58223"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01472,
FT ECO:0000269|PubMed:24936067, ECO:0007744|PDB:4PQG"
FT BINDING 242
FT /ligand="N-acetyl-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:506227"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01472,
FT ECO:0000269|PubMed:24936067, ECO:0007744|PDB:4PQG"
FT BINDING 328
FT /ligand="UDP"
FT /ligand_id="ChEBI:CHEBI:58223"
FT /evidence="ECO:0000269|PubMed:24936067,
FT ECO:0007744|PDB:4PQG"
FT BINDING 332
FT /ligand="N-acetyl-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:506227"
FT /evidence="ECO:0007744|PDB:4PQG"
FT BINDING 333
FT /ligand="UDP"
FT /ligand_id="ChEBI:CHEBI:58223"
FT /evidence="ECO:0000269|PubMed:24936067,
FT ECO:0007744|PDB:4PQG"
FT BINDING 358
FT /ligand="UDP"
FT /ligand_id="ChEBI:CHEBI:58223"
FT /evidence="ECO:0000269|PubMed:24936067,
FT ECO:0007744|PDB:4PQG"
FT BINDING 384..385
FT /ligand="UDP"
FT /ligand_id="ChEBI:CHEBI:58223"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01472,
FT ECO:0000269|PubMed:24936067, ECO:0007744|PDB:4PQG"
FT BINDING 404..407
FT /ligand="N-acetyl-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:506227"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01472,
FT ECO:0000269|PubMed:24936067, ECO:0007744|PDB:4PQG"
FT BINDING 408..412
FT /ligand="UDP"
FT /ligand_id="ChEBI:CHEBI:58223"
FT /evidence="ECO:0000269|PubMed:24936067,
FT ECO:0007744|PDB:4PQG"
FT MUTAGEN 98
FT /note="N->A: Decreased N-acetylglucosaminyl transferase
FT activity, decreased binding of PsrP."
FT /evidence="ECO:0000269|PubMed:24936067"
FT MUTAGEN 103
FT /note="R->A: Decreased N-acetylglucosaminyl transferase
FT activity, decreased binding of PsrP."
FT /evidence="ECO:0000269|PubMed:24936067"
FT MUTAGEN 116
FT /note="Y->A: Decreased N-acetylglucosaminyl transferase
FT activity, decreased binding of PsrP."
FT /evidence="ECO:0000269|PubMed:24936067"
FT MUTAGEN 244
FT /note="E->A: Loss of N-acetylglucosaminyl transferase
FT activity."
FT /evidence="ECO:0000269|PubMed:24936067"
FT MUTAGEN 328
FT /note="R->A: Loss of N-acetylglucosaminyl transferase
FT activity."
FT /evidence="ECO:0000269|PubMed:24936067"
FT MUTAGEN 332
FT /note="E->A: Loss of N-acetylglucosaminyl transferase
FT activity, nearly wild-type binding of PsrP."
FT /evidence="ECO:0000269|PubMed:24936067"
FT MUTAGEN 333
FT /note="K->A: Loss of N-acetylglucosaminyl transferase
FT activity."
FT /evidence="ECO:0000269|PubMed:24936067"
FT MUTAGEN 403
FT /note="S->A: Significant loss of N-acetylglucosaminyl
FT transferase activity."
FT /evidence="ECO:0000269|PubMed:24936067"
FT STRAND 2..8
FT /evidence="ECO:0007829|PDB:4PQG"
FT HELIX 16..30
FT /evidence="ECO:0007829|PDB:4PQG"
FT STRAND 34..39
FT /evidence="ECO:0007829|PDB:4PQG"
FT HELIX 48..55
FT /evidence="ECO:0007829|PDB:4PQG"
FT HELIX 59..61
FT /evidence="ECO:0007829|PDB:4PQG"
FT STRAND 62..64
FT /evidence="ECO:0007829|PDB:4PQG"
FT HELIX 65..68
FT /evidence="ECO:0007829|PDB:4PQG"
FT HELIX 81..85
FT /evidence="ECO:0007829|PDB:4PQG"
FT STRAND 92..98
FT /evidence="ECO:0007829|PDB:4PQG"
FT STRAND 101..108
FT /evidence="ECO:0007829|PDB:4PQG"
FT STRAND 111..119
FT /evidence="ECO:0007829|PDB:4PQG"
FT STRAND 124..132
FT /evidence="ECO:0007829|PDB:4PQG"
FT STRAND 135..155
FT /evidence="ECO:0007829|PDB:4PQG"
FT STRAND 158..167
FT /evidence="ECO:0007829|PDB:4PQG"
FT STRAND 173..180
FT /evidence="ECO:0007829|PDB:4PQG"
FT STRAND 183..188
FT /evidence="ECO:0007829|PDB:4PQG"
FT STRAND 193..196
FT /evidence="ECO:0007829|PDB:4PQG"
FT HELIX 197..207
FT /evidence="ECO:0007829|PDB:4PQG"
FT STRAND 215..219
FT /evidence="ECO:0007829|PDB:4PQG"
FT TURN 222..224
FT /evidence="ECO:0007829|PDB:4PQG"
FT HELIX 225..232
FT /evidence="ECO:0007829|PDB:4PQG"
FT STRAND 235..240
FT /evidence="ECO:0007829|PDB:4PQG"
FT TURN 248..250
FT /evidence="ECO:0007829|PDB:4PQG"
FT TURN 260..262
FT /evidence="ECO:0007829|PDB:4PQG"
FT HELIX 263..267
FT /evidence="ECO:0007829|PDB:4PQG"
FT HELIX 269..271
FT /evidence="ECO:0007829|PDB:4PQG"
FT STRAND 273..279
FT /evidence="ECO:0007829|PDB:4PQG"
FT HELIX 280..293
FT /evidence="ECO:0007829|PDB:4PQG"
FT STRAND 300..302
FT /evidence="ECO:0007829|PDB:4PQG"
FT STRAND 308..310
FT /evidence="ECO:0007829|PDB:4PQG"
FT STRAND 322..327
FT /evidence="ECO:0007829|PDB:4PQG"
FT HELIX 331..333
FT /evidence="ECO:0007829|PDB:4PQG"
FT HELIX 335..345
FT /evidence="ECO:0007829|PDB:4PQG"
FT TURN 346..348
FT /evidence="ECO:0007829|PDB:4PQG"
FT STRAND 353..357
FT /evidence="ECO:0007829|PDB:4PQG"
FT HELIX 363..372
FT /evidence="ECO:0007829|PDB:4PQG"
FT TURN 376..378
FT /evidence="ECO:0007829|PDB:4PQG"
FT STRAND 379..384
FT /evidence="ECO:0007829|PDB:4PQG"
FT TURN 388..390
FT /evidence="ECO:0007829|PDB:4PQG"
FT HELIX 391..393
FT /evidence="ECO:0007829|PDB:4PQG"
FT STRAND 394..398
FT /evidence="ECO:0007829|PDB:4PQG"
FT STRAND 404..406
FT /evidence="ECO:0007829|PDB:4PQG"
FT HELIX 408..415
FT /evidence="ECO:0007829|PDB:4PQG"
FT STRAND 420..424
FT /evidence="ECO:0007829|PDB:4PQG"
FT HELIX 428..432
FT /evidence="ECO:0007829|PDB:4PQG"
FT TURN 435..437
FT /evidence="ECO:0007829|PDB:4PQG"
FT STRAND 438..442
FT /evidence="ECO:0007829|PDB:4PQG"
FT HELIX 450..466
FT /evidence="ECO:0007829|PDB:4PQG"
FT HELIX 470..481
FT /evidence="ECO:0007829|PDB:4PQG"
FT HELIX 482..484
FT /evidence="ECO:0007829|PDB:4PQG"
FT HELIX 486..500
FT /evidence="ECO:0007829|PDB:4PQG"
SQ SEQUENCE 503 AA; 57782 MW; 128E7F4F393B7084 CRC64;
MTIYNINLGI GWASSGVEYA QAYRAGVFRK LNLSSKFIFT DMILADNIQH LTANIGFDDN
QVIWLYNHFT DIKIAPTSVT VDDVLAYFGG EESHREKNGK VLRVFFFDQD KFVTCYLVDE
NKDLVQHAEY VFKGNLIRKD YFSYTRYCSE YFAPKDNVAV LYQRTFYNED GTPVYDILMN
QGKEEVYHFK DKIFYGKQAF VRAFMKSLNL NKSDLVILDR ETGIGQVVFE EAQTAHLAVV
VHAEHYSENA TNEDYILWNN YYDYQFTNAD KVDFFIVSTD RQNEVLQEQF AKYTQHQPKI
VTIPVGSIDS LTDSSQGRKP FSLITASRLA KEKHIDWLVK AVIEAHKELP ELTFDIYGSG
GEDSLLREII ANHQAEDYIQ LKGHAELSQI YSQYEVYLTA STSEGFGLTL MEAIGSGLPL
IGFDVPYGNQ TFIEDGQNGY LIPSSSDHVE DQIKQAYAAK ICQLYQENRL EAMRAYSYQI
AEGFLTKEIL EKWKKTVEEV LHD
