MCD4_YEAST
ID MCD4_YEAST Reviewed; 919 AA.
AC P36051; D6VX34;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=GPI ethanolamine phosphate transferase 1;
DE EC=2.-.-.-;
DE AltName: Full=Morphogenesis checkpoint-dependent protein 4;
DE AltName: Full=Supersecretion of u-PA protein 21;
GN Name=MCD4; Synonyms=FSR2, SSU21, ZRG16; OrderedLocusNames=YKL165C;
GN ORFNames=YKL619;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8091859; DOI=10.1002/yea.320100005;
RA Vandenbol M., Bolle P.-A., Dion C., Portetelle D., Hilger F.;
RT "DNA sequencing of a 36.2 kb fragment located between the FAS1 and LAP loci
RT of chromosome XI of Saccharomyces cerevisiae.";
RL Yeast 10:S35-S40(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8196765; DOI=10.1038/369371a0;
RA Dujon B., Alexandraki D., Andre B., Ansorge W., Baladron V.,
RA Ballesta J.P.G., Banrevi A., Bolle P.-A., Bolotin-Fukuhara M., Bossier P.,
RA Bou G., Boyer J., Buitrago M.J., Cheret G., Colleaux L.,
RA Daignan-Fornier B., del Rey F., Dion C., Domdey H., Duesterhoeft A.,
RA Duesterhus S., Entian K.-D., Erfle H., Esteban P.F., Feldmann H.,
RA Fernandes L., Fobo G.M., Fritz C., Fukuhara H., Gabel C., Gaillon L.,
RA Garcia-Cantalejo J.M., Garcia-Ramirez J.J., Gent M.E., Ghazvini M.,
RA Goffeau A., Gonzalez A., Grothues D., Guerreiro P., Hegemann J.H.,
RA Hewitt N., Hilger F., Hollenberg C.P., Horaitis O., Indge K.J.,
RA Jacquier A., James C.M., Jauniaux J.-C., Jimenez A., Keuchel H.,
RA Kirchrath L., Kleine K., Koetter P., Legrain P., Liebl S., Louis E.J.,
RA Maia e Silva A., Marck C., Monnier A.-L., Moestl D., Mueller S.,
RA Obermaier B., Oliver S.G., Pallier C., Pascolo S., Pfeiffer F.,
RA Philippsen P., Planta R.J., Pohl F.M., Pohl T.M., Poehlmann R.,
RA Portetelle D., Purnelle B., Puzos V., Ramezani Rad M., Rasmussen S.W.,
RA Remacha M.A., Revuelta J.L., Richard G.-F., Rieger M.,
RA Rodrigues-Pousada C., Rose M., Rupp T., Santos M.A., Schwager C.,
RA Sensen C., Skala J., Soares H., Sor F., Stegemann J., Tettelin H.,
RA Thierry A., Tzermia M., Urrestarazu L.A., van Dyck L.,
RA van Vliet-Reedijk J.C., Valens M., Vandenbol M., Vilela C., Vissers S.,
RA von Wettstein D., Voss H., Wiemann S., Xu G., Zimmermann J., Haasemann M.,
RA Becker I., Mewes H.-W.;
RT "Complete DNA sequence of yeast chromosome XI.";
RL Nature 369:371-378(1994).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, GLYCOSYLATION, AND MUTAGENESIS OF GLY-227
RP AND 916-LYS-LYS-917.
RX PubMed=10069808; DOI=10.1091/mbc.10.3.627;
RA Gaynor E.C., Mondesert G., Grimme S.J., Reed S.I., Orlean P., Emr S.D.;
RT "MCD4 encodes a conserved endoplasmic reticulum membrane protein essential
RT for glycosylphosphatidylinositol anchor synthesis in yeast.";
RL Mol. Biol. Cell 10:627-648(1999).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10514566;
RX DOI=10.1002/(sici)1097-0061(199910)15:14<1485::aid-yea477>3.0.co;2-4;
RA Packeiser A.N., Urakov V.N., Polyakova Y.A., Shimanova N.I.,
RA Shcherbukhin V.D., Smirnov V.N., Ter-Avanesyan M.D.;
RT "A novel vacuolar protein encoded by SSU21 / MCD4 is involved in cell wall
RT integrity in yeast.";
RL Yeast 15:1485-1501(1999).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF PRO-302.
RX PubMed=11470244; DOI=10.1016/s1388-1981(01)00129-9;
RA Storey M.K., Wu W.-I., Voelker D.R.;
RT "A genetic screen for ethanolamine auxotrophs in Saccharomyces cerevisiae
RT identifies a novel mutation in Mcd4p, a protein implicated in
RT glycosylphosphatidylinositol anchor synthesis.";
RL Biochim. Biophys. Acta 1532:234-247(2001).
RN [7]
RP FUNCTION.
RX PubMed=12023081; DOI=10.1111/j.1574-6968.2002.tb11163.x;
RA Kalebina T.S., Laurinavichiute D.K., Packeiser A.N., Morenkov O.S.,
RA Ter-Avanesyan M.D., Kulaev I.S.;
RT "Correct GPI-anchor synthesis is required for the incorporation of
RT endoglucanase/glucanosyltransferase Bgl2p into the Saccharomyces cerevisiae
RT cell wall.";
RL FEMS Microbiol. Lett. 210:81-85(2002).
RN [8]
RP FUNCTION.
RX PubMed=12807869; DOI=10.1074/jbc.m305785200;
RA Zhong X., Malhotra R., Guidotti G.;
RT "ATP uptake in the Golgi and extracellular release require Mcd4 protein and
RT the vacuolar H+-ATPase.";
RL J. Biol. Chem. 278:33436-33444(2003).
RN [9]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [10]
RP FUNCTION.
RX PubMed=16233801; DOI=10.1263/jbb.99.354;
RA Maneesri J., Azuma M., Sakai Y., Igarashi K., Matsumoto T., Fukuda H.,
RA Kondo A., Ooshima H.;
RT "Deletion of MCD 4 involved in glycosylphosphatidylinositol (GPI) anchor
RT synthesis leads to an increase in beta-1,6-glucan level and a decrease in
RT GPI-anchored protein and mannan levels in the cell wall of Saccharomyces
RT cerevisiae.";
RL J. Biosci. Bioeng. 99:354-360(2005).
RN [11]
RP FUNCTION.
RX PubMed=16704983; DOI=10.1074/jbc.m601425200;
RA Zhu Y., Vionnet C., Conzelmann A.;
RT "Ethanolaminephosphate side chain added to glycosylphosphatidylinositol
RT (GPI) anchor by mcd4p is required for ceramide remodeling and forward
RT transport of GPI proteins from endoplasmic reticulum to Golgi.";
RL J. Biol. Chem. 281:19830-19839(2006).
CC -!- FUNCTION: Ethanolamine phosphate transferase involved in
CC glycosylphosphatidylinositol-anchor biosynthesis. Transfers
CC ethanolamine phosphate to the first alpha-1,4-linked mannose of the
CC glycosylphosphatidylinositol precursor of GPI-anchor. Ethanolamine
CC phosphate on the alpha-1,4-linked mannose is essential for further
CC mannosylation by GPI10 and is necessary for an efficient recognition of
CC GPI lipids and GPI proteins by the GPI transamidase, for the efficient
CC transport of GPI anchored proteins from endoplasmic reticulum to Golgi
CC and for the physiological incorporation of ceramides into GPI anchors
CC by lipid remodeling. Also involved in non-mitochondrial ATP movements
CC across membrane and participates in Golgi and endoplasmic reticulum
CC function, Also required for the incorporation of BGL2 into the cell
CC wall. {ECO:0000269|PubMed:10069808, ECO:0000269|PubMed:10514566,
CC ECO:0000269|PubMed:11470244, ECO:0000269|PubMed:12023081,
CC ECO:0000269|PubMed:12807869, ECO:0000269|PubMed:16233801,
CC ECO:0000269|PubMed:16704983}.
CC -!- PATHWAY: Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor
CC biosynthesis.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass
CC membrane protein. Golgi apparatus membrane; Multi-pass membrane
CC protein. Vacuole membrane; Multi-pass membrane protein.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:10069808}.
CC -!- MISCELLANEOUS: Target of the inhibitor of GPI biosynthesis
CC YW3548/BE49385A.
CC -!- SIMILARITY: Belongs to the PIGG/PIGN/PIGO family. PIGN subfamily.
CC {ECO:0000305}.
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DR EMBL; Z26877; CAA81489.1; -; Genomic_DNA.
DR EMBL; Z28165; CAA82007.1; -; Genomic_DNA.
DR EMBL; BK006944; DAA09000.1; -; Genomic_DNA.
DR PIR; S37786; S37786.
DR RefSeq; NP_012756.1; NM_001179731.1.
DR AlphaFoldDB; P36051; -.
DR SMR; P36051; -.
DR BioGRID; 33972; 32.
DR DIP; DIP-8272N; -.
DR IntAct; P36051; 1.
DR MINT; P36051; -.
DR STRING; 4932.YKL165C; -.
DR TCDB; 9.A.6.1.1; the atp exporter (atp-e) family.
DR iPTMnet; P36051; -.
DR MaxQB; P36051; -.
DR PaxDb; P36051; -.
DR PRIDE; P36051; -.
DR EnsemblFungi; YKL165C_mRNA; YKL165C; YKL165C.
DR GeneID; 853690; -.
DR KEGG; sce:YKL165C; -.
DR SGD; S000001648; MCD4.
DR VEuPathDB; FungiDB:YKL165C; -.
DR eggNOG; KOG2124; Eukaryota.
DR GeneTree; ENSGT00390000017600; -.
DR HOGENOM; CLU_007676_0_0_1; -.
DR InParanoid; P36051; -.
DR OMA; TISHFCI; -.
DR BioCyc; YEAST:G3O-31933-MON; -.
DR BRENDA; 2.7.7.B25; 984.
DR Reactome; R-SCE-162710; Synthesis of glycosylphosphatidylinositol (GPI).
DR UniPathway; UPA00196; -.
DR PRO; PR:P36051; -.
DR Proteomes; UP000002311; Chromosome XI.
DR RNAct; P36051; protein.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:SGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0009277; C:fungal-type cell wall; IDA:SGD.
DR GO; GO:0000324; C:fungal-type vacuole; IDA:SGD.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005774; C:vacuolar membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0051377; F:mannose-ethanolamine phosphotransferase activity; IMP:SGD.
DR GO; GO:0008484; F:sulfuric ester hydrolase activity; IEA:InterPro.
DR GO; GO:0015867; P:ATP transport; IDA:SGD.
DR GO; GO:0071555; P:cell wall organization; IEA:UniProtKB-KW.
DR GO; GO:0006506; P:GPI anchor biosynthetic process; IDA:SGD.
DR CDD; cd16020; GPI_EPT_1; 1.
DR Gene3D; 3.40.720.10; -; 1.
DR InterPro; IPR017850; Alkaline_phosphatase_core_sf.
DR InterPro; IPR007070; GPI_EtnP_transferase_1.
DR InterPro; IPR017852; GPI_EtnP_transferase_1_C.
DR InterPro; IPR037671; PIGN_N.
DR InterPro; IPR000917; Sulfatase_N.
DR PANTHER; PTHR12250; PTHR12250; 1.
DR Pfam; PF04987; PigN; 1.
DR Pfam; PF00884; Sulfatase; 1.
DR SUPFAM; SSF53649; SSF53649; 1.
PE 1: Evidence at protein level;
KW Cell wall biogenesis/degradation; Endoplasmic reticulum; Glycoprotein;
KW Golgi apparatus; GPI-anchor biosynthesis; Membrane; Reference proteome;
KW Transferase; Transmembrane; Transmembrane helix; Vacuole.
FT CHAIN 1..919
FT /note="GPI ethanolamine phosphate transferase 1"
FT /id="PRO_0000211412"
FT TOPO_DOM 1..9
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 10..30
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 31..457
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 458..478
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 479..488
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 489..509
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 510..512
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 513..533
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 534..553
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 554..574
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 575..576
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 577..597
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 598
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 599..619
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 620..626
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 627..647
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 648..655
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 656..676
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 677..687
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 688..708
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 709..720
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 721..741
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 742..776
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 777..797
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 798..807
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 808..828
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 829..848
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 849..869
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 870..885
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 886..906
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 907..919
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT CARBOHYD 90
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 138
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 198
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 202
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 286
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 312
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 227
FT /note="G->E: In mcd4-174; defective in endoplasmic
FT reticulum-to-Golgi transport of GPI-anchored proteins."
FT /evidence="ECO:0000269|PubMed:10069808"
FT MUTAGEN 302
FT /note="P->L: Induces auxotrophy for ethanolamine."
FT /evidence="ECO:0000269|PubMed:11470244"
FT MUTAGEN 916..917
FT /note="KK->SS: No effect on subcellular location."
FT /evidence="ECO:0000269|PubMed:10069808"
SQ SEQUENCE 919 AA; 105693 MW; B8F1D0BF80792C6A CRC64;
MWNKTRTTLL AVGVLFHLFY LWSIFDIYFI SPLVHGMSPY QSTPTPPAKR LFLIVGDGLR
ADTTFDKVTH PVSGKTEFLA PFIRSLVMNN ATYGISHTRM PTESRPGHVA MIAGFYEDVS
AVTKGWKSNP VNFDSFFNQS THTYSFGSPD ILPMFKDGAS DPNKVDTWMY DHTFEDFTQS
SIELDAFVFR HLDQLFHNST LNSTLDYEIR QDGNVFFLHL LGCDTAGHSY RPYSAEYYDN
VKYIDDQIPI LIDKVNKFFA DDKTAFIFTA DHGMSAFGSH GDGHPNNTRT PLVAWGAGLN
KPVHNPFPVS DNYTENWELS SIKRNDVKQA DIASLMSYLI GVNYPKNSVG ELPIAYIDGK
ESDKLAALYN NARSILEQYL VKQDEVIDSQ FFYKEYFKFV EKSHSHYLEE IETLIQRISE
GENYLEQEAI TLTEELMQIT LEGLHYLTTY NWRFIRTIVT FGFVGWIFFS FIIFLKSFIL
ENVIDDQKAS PLSHAVFGSI GILLNWILFY QHSPFNFYMY LLFPLYFWSY IFTNRSVLRS
GIKEFFKGTS PWKRVLITIS IISVYEGIVY GFFHRWTFTL ITNILAFYPF ICGVRELSVN
ILWIITSVLL STFTLFDAVK IEDLNQIHLA GLLIILSAFY ALYKIHSRIN SYTRAIFAIQ
ISLVAAMLAV THRSVISLQL RQGLPRESQV AGWIIFFVSL FVMPILHYRK PNNDYKVRLL
IIYLTFAPSF IILTISFESL FYFLFTSYMV QWIEIENKIK EMKTQKDENW LQVLRVSVIG
FFLLQVAFFG TGNVASISSF SLESVCRLLP IFDPFLMGAL LMLKLIIPYG LLSTCLGILN
LKLNFKDYTI SSLIISMSDI LSLNFFYLLR TEGSWLDIGI TISNYCLAIL SSLFMLILEV
LGHVLLKNVI IQDKTKKTQ
