PMT4_CANAL
ID PMT4_CANAL Reviewed; 755 AA.
AC Q59X23; A0A1D8PHJ9;
DT 29-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2017, sequence version 2.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=Dolichyl-phosphate-mannose--protein mannosyltransferase 4 {ECO:0000305};
DE Short=Protein mannosyltransferase 4;
DE EC=2.4.1.109 {ECO:0000250|UniProtKB:P33775, ECO:0000303|PubMed:15659169};
GN Name=PMT4 {ECO:0000303|PubMed:15659169};
GN OrderedLocusNames=CAALFM_C206100WA; ORFNames=CaO19.11590, CaO19.4109;
OS Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX NCBI_TaxID=237561;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=15123810; DOI=10.1073/pnas.0401648101;
RA Jones T., Federspiel N.A., Chibana H., Dungan J., Kalman S., Magee B.B.,
RA Newport G., Thorstenson Y.R., Agabian N., Magee P.T., Davis R.W.,
RA Scherer S.;
RT "The diploid genome sequence of Candida albicans.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:7329-7334(2004).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=17419877; DOI=10.1186/gb-2007-8-4-r52;
RA van het Hoog M., Rast T.J., Martchenko M., Grindle S., Dignard D.,
RA Hogues H., Cuomo C., Berriman M., Scherer S., Magee B.B., Whiteway M.,
RA Chibana H., Nantel A., Magee P.T.;
RT "Assembly of the Candida albicans genome into sixteen supercontigs aligned
RT on the eight chromosomes.";
RL Genome Biol. 8:RESEARCH52.1-RESEARCH52.12(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=24025428; DOI=10.1186/gb-2013-14-9-r97;
RA Muzzey D., Schwartz K., Weissman J.S., Sherlock G.;
RT "Assembly of a phased diploid Candida albicans genome facilitates allele-
RT specific measurements and provides a simple model for repeat and indel
RT structure.";
RL Genome Biol. 14:RESEARCH97.1-RESEARCH97.14(2013).
RN [4]
RP FUNCTION.
RX PubMed=15470244; DOI=10.1128/ec.3.5.1164-1168.2004;
RA Weber Y., Prill S.K., Ernst J.F.;
RT "Pmt-mediated O mannosylation stabilizes an essential component of the
RT secretory apparatus, Sec20p, in Candida albicans.";
RL Eukaryot. Cell 3:1164-1168(2004).
RN [5]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=16040968; DOI=10.1128/iai.73.8.4571-4580.2005;
RA Rouabhia M., Schaller M., Corbucci C., Vecchiarelli A., Prill S.K.,
RA Giasson L., Ernst J.F.;
RT "Virulence of the fungal pathogen Candida albicans requires the five
RT isoforms of protein mannosyltransferases.";
RL Infect. Immun. 73:4571-4580(2005).
RN [6]
RP IDENTIFICATION, DISRUPTION PHENOTYPE, INDUCTION, AND FUNCTION.
RX PubMed=15659169; DOI=10.1111/j.1365-2958.2004.04401.x;
RA Prill S.K., Klinkert B., Timpel C., Gale C.A., Schroppel K., Ernst J.F.;
RT "PMT family of Candida albicans: five protein mannosyltransferase isoforms
RT affect growth, morphogenesis and antifungal resistance.";
RL Mol. Microbiol. 55:546-560(2005).
RN [7]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=17005840; DOI=10.1128/aac.00606-06;
RA Peltroche-Llacsahuanga H., Goyard S., d'Enfert C., Prill S.K., Ernst J.F.;
RT "Protein O-mannosyltransferase isoforms regulate biofilm formation in
RT Candida albicans.";
RL Antimicrob. Agents Chemother. 50:3488-3491(2006).
RN [8]
RP INDUCTION.
RX PubMed=21375589; DOI=10.1111/j.1365-2958.2011.07604.x;
RA Cantero P.D., Ernst J.F.;
RT "Damage to the glycoshield activates PMT-directed O-mannosylation via the
RT Msb2-Cek1 pathway in Candida albicans.";
RL Mol. Microbiol. 80:715-725(2011).
RN [9]
RP INDUCTION.
RX PubMed=23563485; DOI=10.1128/ec.00071-13;
RA Srikantha T., Daniels K.J., Pujol C., Kim E., Soll D.R.;
RT "Identification of genes upregulated by the transcription factor Bcr1 that
RT are involved in impermeability, impenetrability, and drug resistance of
RT Candida albicans a/alpha biofilms.";
RL Eukaryot. Cell 12:875-888(2013).
CC -!- FUNCTION: Protein mannosyltransferase (PMT) involved in hyphal growth
CC and drug sensitivity. Transfers mannose from Dol-P-mannose to Ser or
CC Thr residues on proteins. PMT1, PMT2 and PMT4 account for most of the
CC protein-O-glycosylation activity, while PMT5 and PMT6 may specifically
CC modulate a much narrower spectrum of target proteins. Accounts for the
CC O-glycosylation of AXL2, responsible for bud site selection, as well as
CC of the SEC20 t-SNARE component. O-glycosylation of SEC20 is essential
CC for its stability. Required for biofilm formation.
CC {ECO:0000269|PubMed:15470244, ECO:0000269|PubMed:15659169,
CC ECO:0000269|PubMed:16040968, ECO:0000269|PubMed:17005840}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a dolichyl beta-D-mannosyl phosphate + L-seryl-[protein] = 3-
CC O-(alpha-D-mannosyl)-L-seryl-[protein] + a dolichyl phosphate + H(+);
CC Xref=Rhea:RHEA:17377, Rhea:RHEA-COMP:9517, Rhea:RHEA-COMP:9527,
CC Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:13546, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29999, ChEBI:CHEBI:57683, ChEBI:CHEBI:58211,
CC ChEBI:CHEBI:137321; EC=2.4.1.109;
CC Evidence={ECO:0000250|UniProtKB:P33775, ECO:0000303|PubMed:15659169};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a dolichyl beta-D-mannosyl phosphate + L-threonyl-[protein] =
CC 3-O-(alpha-D-mannosyl)-L-threonyl-[protein] + a dolichyl phosphate +
CC H(+); Xref=Rhea:RHEA:53396, Rhea:RHEA-COMP:9517, Rhea:RHEA-COMP:9527,
CC Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:13547, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30013, ChEBI:CHEBI:57683, ChEBI:CHEBI:58211,
CC ChEBI:CHEBI:137323; EC=2.4.1.109;
CC Evidence={ECO:0000250|UniProtKB:P33775, ECO:0000303|PubMed:15659169};
CC -!- PATHWAY: Protein modification; protein glycosylation. {ECO:0000305}.
CC -!- SUBUNIT: Forms a functional homodimer. {ECO:0000250|UniProtKB:P46971}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P46971}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- INDUCTION: Transcribed in the yeast form, but expression is increased
CC two to threefold during hyphal induction. Also up-regulated more than
CC twofold when PMT1 expression is impaired. MSB2 functions not only to
CC secure basal levels of the PMT4 transcripts but is needed also for up-
CC regulation of both transcripts upon PMT1 inhibition. Repressed by BCR1.
CC {ECO:0000269|PubMed:15659169, ECO:0000269|PubMed:21375589,
CC ECO:0000269|PubMed:23563485}.
CC -!- DISRUPTION PHENOTYPE: Impairs biofilm formation and shows reduced
CC virulence in a mouse model of hematogenously disseminated candidiasis
CC (HDC) and using reconstituted human epithelium (RHE).
CC {ECO:0000269|PubMed:16040968, ECO:0000269|PubMed:17005840}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 39 family.
CC {ECO:0000305}.
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DR EMBL; CP017624; AOW27618.1; -; Genomic_DNA.
DR RefSeq; XP_714280.2; XM_709187.2.
DR AlphaFoldDB; Q59X23; -.
DR SMR; Q59X23; -.
DR STRING; 237561.Q59X23; -.
DR PRIDE; Q59X23; -.
DR GeneID; 3644096; -.
DR KEGG; cal:CAALFM_C206100WA; -.
DR CGD; CAL0000192933; PMT4.
DR VEuPathDB; FungiDB:C2_06100W_A; -.
DR eggNOG; KOG3359; Eukaryota.
DR HOGENOM; CLU_008438_0_0_1; -.
DR InParanoid; Q59X23; -.
DR OMA; FWTQNDT; -.
DR OrthoDB; 203029at2759; -.
DR BRENDA; 2.4.1.109; 1096.
DR UniPathway; UPA00378; -.
DR PHI-base; PHI:399; -.
DR PRO; PR:Q59X23; -.
DR Proteomes; UP000000559; Chromosome 2.
DR GO; GO:0097586; C:dolichyl-phosphate-mannose-protein mannosyltransferase Pmt4p homodimer complex; IEA:EnsemblFungi.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:CGD.
DR GO; GO:0004169; F:dolichyl-phosphate-mannose-protein mannosyltransferase activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IEA:EnsemblFungi.
DR GO; GO:0000030; F:mannosyltransferase activity; IMP:CGD.
DR GO; GO:0000032; P:cell wall mannoprotein biosynthetic process; IEA:EnsemblFungi.
DR GO; GO:0036244; P:cellular response to neutral pH; IMP:CGD.
DR GO; GO:0030447; P:filamentous growth; IMP:CGD.
DR GO; GO:0044182; P:filamentous growth of a population of unicellular organisms; IMP:CGD.
DR GO; GO:0036178; P:filamentous growth of a population of unicellular organisms in response to neutral pH; IMP:CGD.
DR GO; GO:0031505; P:fungal-type cell wall organization; IMP:CGD.
DR GO; GO:0045861; P:negative regulation of proteolysis; IMP:CGD.
DR GO; GO:0035269; P:protein O-linked mannosylation; IMP:CGD.
DR GO; GO:1900101; P:regulation of endoplasmic reticulum unfolded protein response; IEA:EnsemblFungi.
DR GO; GO:0044011; P:single-species biofilm formation on inanimate substrate; IMP:CGD.
DR InterPro; IPR027005; GlyclTrfase_39-like.
DR InterPro; IPR003342; Glyco_trans_39/83.
DR InterPro; IPR036300; MIR_dom_sf.
DR InterPro; IPR016093; MIR_motif.
DR InterPro; IPR032421; PMT_4TMC.
DR PANTHER; PTHR10050; PTHR10050; 1.
DR Pfam; PF02815; MIR; 1.
DR Pfam; PF02366; PMT; 1.
DR Pfam; PF16192; PMT_4TMC; 1.
DR SMART; SM00472; MIR; 3.
DR SUPFAM; SSF82109; SSF82109; 1.
DR PROSITE; PS50919; MIR; 3.
PE 2: Evidence at transcript level;
KW Endoplasmic reticulum; Glycoprotein; Glycosyltransferase; Membrane;
KW Reference proteome; Repeat; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..755
FT /note="Dolichyl-phosphate-mannose--protein
FT mannosyltransferase 4"
FT /id="PRO_0000430578"
FT TRANSMEM 92..112
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 147..167
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 185..205
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TRANSMEM 212..232
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 237..257
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 278..298
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TRANSMEM 595..615
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TRANSMEM 640..660
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TRANSMEM 670..690
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TRANSMEM 706..726
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT DOMAIN 325..389
FT /note="MIR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 396..454
FT /note="MIR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 466..523
FT /note="MIR 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..20
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 11
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 445
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 691
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 755 AA; 86658 MW; FDB0CB1189179D3D CRC64;
MSQTLKKRGG NSSGRKSPTT SNIEFDDKKT EFDLNAIVPP KEPEYKYLAA LTLVTLLAIY
TRFTKLGTPN KVVFDEVHFG KFASYYLERT YFFDLHPPFA KLLIAFVGWL IGYDGKFKFE
AIGDSYIENN VPYIAYRSLS AIQGAAIVPI MFLTMKTLGF SVAACLFSSI IVCFDNAQVT
DSRLILLDAT LILSVALTIF SYSKFSTFRK QSFSSKWWTW LLATGVSLSC VISTKYVGVF
TYLTIGIAVI HELWILLDYR KGLTLQEFAK HFFARLWALI IVPFCIYLYW FYLHFAILTR
SGPGDAFMSS EFQETLLESP LAAHSKPVQY FDQITIKHKD TGAFLHSHQH EYPLRYEDGR
ISSNGQQVTC VVQENAANDP NNQWEIVPTS EGANKGTKVY TNDIVRFRHV GTGGYLLTHD
VASPLKPTNE EFTVVYDDVA QQRYNETLFR LRLHVPGSNP KKEKNKKEIK TLATDLRILH
VDTVVAMWTH NDELLPEWAF NQQEVSGNKK IPDKDNIWNF DLITNLQSTD PRNQYVPKKV
KTLPFLRKWW ELQMLMFHHN NQLSSEHPFA TQPGEWPLAL SGVSFYNDNT EKKQIFFIGN
IIGFWLEVCF LSIYIGILLA DQITRRRNVH VLSDRARSRL YNTLGFLFVG WAAHYLPFFL
MNRQKFLHHY LPAHLVAALF SGGLVEFICS NNSARPNGKP VGVNKYKIIA VVAACSTAII
WFFFYFRPLT YGDVYLTPEE VKARQWLDIK LHYGK
