OFUT2_TOXGG
ID OFUT2_TOXGG Reviewed; 858 AA.
AC S7WCF5;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 16-OCT-2013, sequence version 1.
DT 03-AUG-2022, entry version 20.
DE RecName: Full=GDP-fucose protein O-fucosyltransferase 2 {ECO:0000305};
DE EC=2.4.1.221 {ECO:0000305|PubMed:30514763, ECO:0000305|PubMed:30538131};
DE AltName: Full=Protein O-fucosyltransferase 2 {ECO:0000303|PubMed:30514763};
GN Name=POFUT2 {ECO:0000303|PubMed:30514763};
GN ORFNames=TGGT1_273550 {ECO:0000312|EMBL:EPR64539.1};
OS Toxoplasma gondii (strain ATCC 50853 / GT1).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Conoidasida; Coccidia;
OC Eucoccidiorida; Eimeriorina; Sarcocystidae; Toxoplasma.
OX NCBI_TaxID=507601 {ECO:0000312|Proteomes:UP000005641};
RN [1] {ECO:0000312|Proteomes:UP000005641}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 50853 / GT1 {ECO:0000312|Proteomes:UP000005641};
RA Sibley D., Venepally P., Karamycheva S., Hadjithomas M., Khan A., Brunk B.,
RA Roos D., Caler E., Lorenzi H.;
RL Submitted (MAY-2013) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND DISRUPTION PHENOTYPE.
RX PubMed=30514763; DOI=10.1074/jbc.ra118.005357;
RA Khurana S., Coffey M.J., John A., Uboldi A.D., Huynh M.H., Stewart R.J.,
RA Carruthers V.B., Tonkin C.J., Goddard-Borger E.D., Scott N.E.;
RT "Protein O-fucosyltransferase 2-mediated O-glycosylation of the adhesin
RT MIC2 is dispensable for Toxoplasma gondii tachyzoite infection.";
RL J. Biol. Chem. 294:1541-1553(2019).
RN [3] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, DEVELOPMENTAL
RP STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=30538131; DOI=10.1074/jbc.ra118.005179;
RA Bandini G., Leon D.R., Hoppe C.M., Zhang Y., Agop-Nersesian C.,
RA Shears M.J., Mahal L.K., Routier F.H., Costello C.E., Samuelson J.;
RT "O-Fucosylation of thrombospondin-like repeats is required for processing
RT of microneme protein 2 and for efficient host cell invasion by Toxoplasma
RT gondii tachyzoites.";
RL J. Biol. Chem. 294:1967-1983(2019).
CC -!- FUNCTION: Catalyzes the reaction that attaches fucose through an O-
CC glycosidic linkage to a conserved serine or threonine residue in the
CC consensus sequence C1-X-X-S/T-C2 of thrombospondin type I repeats
CC (TSRs) where C1 and C2 are the first and second cysteines of the
CC repeat, respectively (PubMed:30514763, PubMed:30538131). O-fucosylates
CC microneme protein MIC2 and may play a role in its stabilization
CC (PubMed:30514763, PubMed:30538131). Probably by regulating protein O-
CC fucosylation, may play a role in tachyzoite adhesion to and/or invasion
CC of host cells; however, POFUT2 involvement in adhesion/invasion is
CC controversial (PubMed:30514763, PubMed:30538131).
CC {ECO:0000269|PubMed:30514763, ECO:0000269|PubMed:30538131}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GDP-beta-L-fucose + L-seryl-[protein] = 3-O-(alpha-L-fucosyl)-
CC L-seryl-[protein] + GDP + H(+); Xref=Rhea:RHEA:63644, Rhea:RHEA-
CC COMP:9863, Rhea:RHEA-COMP:17914, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29999, ChEBI:CHEBI:57273, ChEBI:CHEBI:58189,
CC ChEBI:CHEBI:189632; EC=2.4.1.221;
CC Evidence={ECO:0000305|PubMed:30514763, ECO:0000305|PubMed:30538131};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63645;
CC Evidence={ECO:0000305|PubMed:30514763, ECO:0000305|PubMed:30538131};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GDP-beta-L-fucose + L-threonyl-[protein] = 3-O-(alpha-L-
CC fucosyl)-L-threonyl-[protein] + GDP + H(+); Xref=Rhea:RHEA:70491,
CC Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:17915, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30013, ChEBI:CHEBI:57273, ChEBI:CHEBI:58189,
CC ChEBI:CHEBI:189631; EC=2.4.1.221;
CC Evidence={ECO:0000305|PubMed:30514763, ECO:0000305|PubMed:30538131};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70492;
CC Evidence={ECO:0000305|PubMed:30514763, ECO:0000305|PubMed:30538131};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000269|PubMed:30514763, ECO:0000269|PubMed:30538131}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:30538131}; Single-pass type II membrane protein
CC {ECO:0000305}.
CC -!- DEVELOPMENTAL STAGE: Expressed in tachyzoites (at protein level).
CC {ECO:0000269|PubMed:30538131}.
CC -!- DISRUPTION PHENOTYPE: Loss of MIC2 O-fucosylation (PubMed:30514763,
CC PubMed:30538131). Nuclear O-fucosylation is normal (PubMed:30538131).
CC MIC2 protein levels are decreased by 50 percent. Abnormal MIC2
CC accumulation in the early/mid-secretory pathway (PubMed:30538131). The
CC number of plaques caused by tachyzoite infection of human foreskin
CC fibroblasts (HFF) is reduced by 40 percent (PubMed:30538131). The
CC number of tachyzoites that are attached to or invaded the host HFFs is
CC reduced. Egress from the HFFs is also partially impaired
CC (PubMed:30538131). However, another study shows that loss of POFUT2
CC only leads to a small decrease in MIC2 protein levels and has no effect
CC on MIC2 trafficking and interaction with M2AP (PubMed:30514763). Also,
CC the number of plaques caused by tachyzoite infection of HFFs is reduced
CC by only 20 percent and tachyzoite adhesion to and invasion of HFFs are
CC normal (PubMed:30514763). {ECO:0000269|PubMed:30514763,
CC ECO:0000269|PubMed:30538131}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 68 family.
CC {ECO:0000305}.
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DR EMBL; AAQM03000021; EPR64539.1; -; Genomic_DNA.
DR EnsemblProtists; EPR64539; EPR64539; TGGT1_273550.
DR VEuPathDB; ToxoDB:TGGT1_273550; -.
DR BRENDA; 2.4.1.221; 6411.
DR UniPathway; UPA00378; -.
DR Proteomes; UP000005641; Unassembled WGS sequence.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0046922; F:peptide-O-fucosyltransferase activity; IMP:UniProtKB.
DR GO; GO:0006004; P:fucose metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0036066; P:protein O-linked fucosylation; IMP:UniProtKB.
DR InterPro; IPR019378; GDP-Fuc_O-FucTrfase.
DR InterPro; IPR045130; OFUT2-like.
DR PANTHER; PTHR13398; PTHR13398; 2.
DR Pfam; PF10250; O-FucT; 1.
PE 1: Evidence at protein level;
KW Carbohydrate metabolism; Endoplasmic reticulum; Fucose metabolism;
KW Glycosyltransferase; Membrane; Signal-anchor; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..858
FT /note="GDP-fucose protein O-fucosyltransferase 2"
FT /id="PRO_0000455544"
FT TOPO_DOM 1..150
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 151..171
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 172..858
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT REGION 448..510
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 819..858
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 460..510
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 832..848
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 238
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2G5"
FT BINDING 237..241
FT /ligand="GDP-beta-L-fucose"
FT /ligand_id="ChEBI:CHEBI:57273"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2G5"
FT BINDING 646..648
FT /ligand="GDP-beta-L-fucose"
FT /ligand_id="ChEBI:CHEBI:57273"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2G5"
FT BINDING 787..788
FT /ligand="GDP-beta-L-fucose"
FT /ligand_id="ChEBI:CHEBI:57273"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2G5"
FT SITE 795
FT /note="Essential for catalytic activity"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2G5"
SQ SEQUENCE 858 AA; 95964 MW; B87490ACFEBAAF25 CRC64;
MHCQLGGQAR ALIFLMFESC RNSWHVSPWS SVPFLPSPCL FFSFSALPFL HPLSQLIACR
GSSATWLFPV SSGTLVLRYA LAASPPRGTM RPSTNPRTAE EGRPWLIHAT QTGPQTASVL
SLFPAVNAGF FSACRQHRGG RPPCLLNHRR LLLGLVSVLT VFLSCLPFTN ATVSPAALQD
VCYAFGNISR KLSSFLVPSR VTCPRGATPL SGVEAQDSLE HPEIPDFRFL VYDVKNGEGF
HLQKEVIYRV ALVISLLNAR SAQQGRMTDV HTAEKAREDR GHPQASHMLC ASSSFSHACS
ARSTFPFFPM WVLVLPPWCR LAHWHFSEET ITAMAENSWL KHVRWGTFFD FQDLGERLPV
MEYEDFLTYQ LMRPDPWGER RQRKEKQTTP VELDVVLSVR FSSTPSSRSL PFCACLSSRA
SEIADEQAQR DDVCCNVNDL PGCPQIHAAL TPQERQRAPA QRGGDPREEI DEQTGEFNEG
HNPSGDGERE KRKPGRRSDT SRSRKEIQEE AKVSDTWSGV SLWLAGFCET VRALEMWCAS
LYIADAPRIA DLLWRSVAER PPGAIQTVWL KFGENLLVPW PDVLLDAHLL DMLHVHPKLR
QIGDLFINKF LSNRDKTETG KGERASTEGG TEGDENLAKH GYIAAHLRRT DFLYLKRSVP
LQRAAAYLVS RMKEHGVFKA FICTDGSEDE KRELRDAVRR VGDAASSSPY TVVFFDLPTV
RRLMIKTLEA SSHVSDDGSF HDLKAVETPG YSGPNHISLL LHPGITALIE VWIAARAAYF
IGTKDSRFSQ AIRWERHLMG HPLDSSLEVF CVDSSPDQTG GQAQGKCFAT KSHDPPEGRS
RSELRRKYWP SLDPSSTL
