PIGA_HUMAN
ID PIGA_HUMAN Reviewed; 484 AA.
AC P37287; B4E0V2; Q16025; Q16250;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1994, sequence version 1.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Phosphatidylinositol N-acetylglucosaminyltransferase subunit A {ECO:0000305};
DE EC=2.4.1.198 {ECO:0000305|PubMed:16162815};
DE AltName: Full=GlcNAc-PI synthesis protein;
DE AltName: Full=Phosphatidylinositol-glycan biosynthesis class A protein;
DE Short=PIG-A;
GN Name=PIGA {ECO:0000312|HGNC:HGNC:8957};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=7680492; DOI=10.1126/science.7680492;
RA Miyata T., Takeda J., Iida Y., Yamada N., Inoue N., Takahashi M., Maeda K.,
RA Kitani T., Kinoshita T.;
RT "The cloning of PIG-A, a component in the early step of GPI-anchor
RT biosynthesis.";
RL Science 259:1318-1320(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=8081362; DOI=10.1093/hmg/3.5.751;
RA Bessler M., Hillmen P., Longo L., Luzzatto L., Mason P.J.;
RT "Genomic organization of the X-linked gene (PIG-A) that is mutated in
RT paroxysmal nocturnal haemoglobinuria and of a related autosomal pseudogene
RT mapped to 12q21.";
RL Hum. Mol. Genet. 3:751-757(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=8193350;
RA Iida Y., Takeda J., Miyata T., Inoue N., Nishimura J., Kitani T., Maeda K.,
RA Kinoshita T.;
RT "Characterization of genomic PIG-A gene: a gene for
RT glycosylphosphatidylinositol-anchor biosynthesis and paroxysmal nocturnal
RT hemoglobinuria.";
RL Blood 83:3126-3131(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=8081230;
RA Yu J., Nagarajan S., Ueda E., Knez J.J., Petersen R.B., Medof M.E.;
RT "Characterization of alternatively spliced PIG-A transcripts in normal and
RT paroxysmal nocturnal hemoglobinuria cells.";
RL Braz. J. Med. Biol. Res. 27:195-201(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 301-420, AND INVOLVEMENT IN PNH1.
RX PubMed=8500164; DOI=10.1016/0092-8674(93)90250-t;
RA Takeda J., Miyata T., Kawagoe K., Iida Y., Endo Y., Fujita T.,
RA Takahashi M., Kitani T., Kinoshita T.;
RT "Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A
RT gene in paroxysmal nocturnal hemoglobinuria.";
RL Cell 73:703-711(1993).
RN [9]
RP COMPONENT OF GPI-GNT COMPLEX, AND INTERACTION WITH PIGQ.
RX PubMed=9463366; DOI=10.1093/emboj/17.4.877;
RA Watanabe R., Inoue N., Westfall B., Taron C.H., Orlean P., Takeda J.,
RA Kinoshita T.;
RT "The first step of glycosylphosphatidylinositol biosynthesis is mediated by
RT a complex of PIG-A, PIG-H, PIG-C and GPI1.";
RL EMBO J. 17:877-885(1998).
RN [10]
RP INTERACTION WITH PIGC; PIGH; PIGP; PIGQ; PIGY AND DPM2, COMPONENT OF
RP GPI-GNT COMPLEX, CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=16162815; DOI=10.1091/mbc.e05-08-0743;
RA Murakami Y., Siripanyaphinyo U., Hong Y., Tashima Y., Maeda Y.,
RA Kinoshita T.;
RT "The initial enzyme for glycosylphosphatidylinositol biosynthesis requires
RT PIG-Y, a seventh component.";
RL Mol. Biol. Cell 16:5236-5246(2005).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [12]
RP INVOLVEMENT IN MCAHS2.
RX PubMed=22305531; DOI=10.1016/j.ajhg.2011.11.031;
RA Johnston J.J., Gropman A.L., Sapp J.C., Teer J.K., Martin J.M., Liu C.F.,
RA Yuan X., Ye Z., Cheng L., Brodsky R.A., Biesecker L.G.;
RT "The phenotype of a germline mutation in PIGA: the gene somatically mutated
RT in paroxysmal nocturnal hemoglobinuria.";
RL Am. J. Hum. Genet. 90:295-300(2012).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21 AND SER-24, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [14]
RP VARIANT PNH1 PHE-155.
RX PubMed=8306954; DOI=10.1002/j.1460-2075.1994.tb06240.x;
RA Bessler M., Mason P.J., Hilmen P., Miyata T., Yamada N., Takeda J.,
RA Luzzato L., Kinoshita T.;
RT "Paroxysmal nocturnal haemoglobinuria (PNH) is caused by somatic mutations
RT in the PIG-A gene.";
RL EMBO J. 13:110-117(1994).
RN [15]
RP VARIANT PNH1 ASP-297.
RX PubMed=8167330;
RA Ware R.E., Rosse W.F., Howard T.A.;
RT "Mutations within the Piga gene in patients with paroxysmal nocturnal
RT hemoglobinuria.";
RL Blood 83:2418-2422(1994).
RN [16]
RP VARIANTS PNH1 TRP-19; HIS-40; ALA-48; ASP-48; ARG-128 AND ARG-239.
RX PubMed=10087994; DOI=10.1006/bcmd.1998.0203;
RA Nafa K., Bessler M., Castro-Malaspina H., Jhanwar S., Luzzatto L.;
RT "The spectrum of somatic mutations in the PIG-A gene in paroxysmal
RT nocturnal hemoglobinuria includes large deletions and small duplications.";
RL Blood Cells Mol. Dis. 24:370-384(1998).
RN [17]
RP VARIANT PNH1 VAL-48.
RX PubMed=12037021; DOI=10.1136/jcp.55.6.410;
RA Yoon J.H., Cho H.I., Park S.S., Chang Y.H., Kim B.K.;
RT "Mutation analysis of the PIG-A gene in Korean patients with paroxysmal
RT nocturnal haemoglobinuria.";
RL J. Clin. Pathol. 55:410-413(2002).
RN [18]
RP VARIANT MCAHS2 LEU-344 DEL.
RX PubMed=24259288; DOI=10.1002/ajmg.a.36189;
RA Swoboda K.J., Margraf R.L., Carey J.C., Zhou H., Newcomb T.M., Coonrod E.,
RA Durtschi J., Mallempati K., Kumanovics A., Katz B.E., Voelkerding K.V.,
RA Opitz J.M.;
RT "A novel germline PIGA mutation in Ferro-Cerebro-Cutaneous syndrome: a
RT neurodegenerative X-linked epileptic encephalopathy with systemic iron-
RT overload.";
RL Am. J. Med. Genet. A 164A:17-28(2014).
RN [19]
RP VARIANT MCAHS2 LEU-93.
RX PubMed=24259184; DOI=10.1002/ajmg.a.36184;
RA van der Crabben S.N., Harakalova M., Brilstra E.H., van Berkestijn F.M.,
RA Hofstede F.C., van Vught A.J., Cuppen E., Kloosterman W.,
RA Ploos van Amstel H.K., van Haaften G., van Haelst M.M.;
RT "Expanding the spectrum of phenotypes associated with germline PIGA
RT mutations: a child with developmental delay, accelerated linear growth,
RT facial dysmorphisms, elevated alkaline phosphatase, and progressive CNS
RT abnormalities.";
RL Am. J. Med. Genet. A 164A:29-35(2014).
RN [20]
RP VARIANTS MCAHS2 LEU-77; TRP-119 AND PHE-206.
RX PubMed=24706016; DOI=10.1212/wnl.0000000000000389;
RA Kato M., Saitsu H., Murakami Y., Kikuchi K., Watanabe S., Iai M., Miya K.,
RA Matsuura R., Takayama R., Ohba C., Nakashima M., Tsurusaki Y., Miyake N.,
RA Hamano S., Osaka H., Hayasaka K., Kinoshita T., Matsumoto N.;
RT "PIGA mutations cause early-onset epileptic encephalopathies and
RT distinctive features.";
RL Neurology 82:1587-1596(2014).
RN [21]
RP VARIANT MCAHS2 SER-355.
RX PubMed=26993267; DOI=10.1136/jmedgenet-2015-103263;
RA Trump N., McTague A., Brittain H., Papandreou A., Meyer E., Ngoh A.,
RA Palmer R., Morrogh D., Boustred C., Hurst J.A., Jenkins L., Kurian M.A.,
RA Scott R.H.;
RT "Improving diagnosis and broadening the phenotypes in early-onset seizure
RT and severe developmental delay disorders through gene panel analysis.";
RL J. Med. Genet. 53:310-317(2016).
RN [22]
RP VARIANT VAL-135.
RX PubMed=27864847; DOI=10.1002/humu.23149;
RG Clinical Study Group;
RA Parrini E., Marini C., Mei D., Galuppi A., Cellini E., Pucatti D.,
RA Chiti L., Rutigliano D., Bianchini C., Virdo S., De Vita D., Bigoni S.,
RA Barba C., Mari F., Montomoli M., Pisano T., Rosati A., Guerrini R.;
RT "Diagnostic targeted resequencing in 349 patients with drug-resistant
RT pediatric epilepsies identifies causative mutations in 30 different
RT genes.";
RL Hum. Mutat. 38:216-225(2017).
CC -!- FUNCTION: Catalytic subunit of the glycosylphosphatidylinositol-N-
CC acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the
CC transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to
CC phosphatidylinositol and participates in the first step of GPI
CC biosynthesis. {ECO:0000305|PubMed:16162815}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + UDP-N-
CC acetyl-alpha-D-glucosamine = a 6-(N-acetyl-alpha-D-glucosaminyl)-1-
CC phosphatidyl-1D-myo-inositol + H(+) + UDP; Xref=Rhea:RHEA:14789,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57265, ChEBI:CHEBI:57705,
CC ChEBI:CHEBI:57880, ChEBI:CHEBI:58223; EC=2.4.1.198;
CC Evidence={ECO:0000305|PubMed:16162815};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14790;
CC Evidence={ECO:0000305|PubMed:16162815};
CC -!- PATHWAY: Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor
CC biosynthesis. {ECO:0000269|PubMed:16162815}.
CC -!- SUBUNIT: Component of the glycosylphosphatidylinositol-N-
CC acetylglucosaminyltransferase (GPI-GnT) complex composed at least by
CC PIGA, PIGC, PIGH, PIGP, PIGQ, PIGY and DPM2 (PubMed:16162815,
CC PubMed:9463366). Interacts with PIGC, PIGH, PIGP, PIGQ and DPM2
CC (PubMed:16162815). Interacts directly with PIGY; this interaction
CC regulates glycosylphosphatidylinositol-N-acetylglucosaminyltransferase
CC activity (PubMed:16162815). Interacts with PIGQ (PubMed:9463366).
CC {ECO:0000269|PubMed:16162815, ECO:0000269|PubMed:9463366}.
CC -!- INTERACTION:
CC P37287; O94777: DPM2; NbExp=4; IntAct=EBI-26643054, EBI-9097061;
CC P37287; Q14442: PIGH; NbExp=5; IntAct=EBI-26643054, EBI-2803676;
CC P37287; P57054: PIGP; NbExp=5; IntAct=EBI-26643054, EBI-17630288;
CC P37287; Q9BRB3: PIGQ; NbExp=5; IntAct=EBI-26643054, EBI-2339260;
CC P37287; Q3MUY2: PIGY; NbExp=6; IntAct=EBI-26643054, EBI-3920125;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass
CC membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P37287-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P37287-2; Sequence=VSP_001802;
CC Name=3;
CC IsoId=P37287-3; Sequence=VSP_043366, VSP_043367;
CC -!- DISEASE: Paroxysmal nocturnal hemoglobinuria 1 (PNH1) [MIM:300818]: A
CC disorder characterized by hemolytic anemia with hemoglobinuria,
CC thromboses in large vessels, and a deficiency in hematopoiesis. Red
CC blood cell breakdown with release of hemoglobin into the urine is
CC manifested most prominently by dark-colored urine in the morning.
CC {ECO:0000269|PubMed:10087994, ECO:0000269|PubMed:12037021,
CC ECO:0000269|PubMed:8167330, ECO:0000269|PubMed:8306954,
CC ECO:0000269|PubMed:8500164}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry.
CC -!- DISEASE: Multiple congenital anomalies-hypotonia-seizures syndrome 2
CC (MCAHS2) [MIM:300868]: An X-linked recessive developmental disorder
CC characterized by dysmorphic features, neonatal hypotonia, myoclonic
CC seizures, and variable congenital anomalies involving the central
CC nervous, cardiac, and urinary systems. Most affected individuals die in
CC infancy. {ECO:0000269|PubMed:22305531, ECO:0000269|PubMed:24259184,
CC ECO:0000269|PubMed:24259288, ECO:0000269|PubMed:24706016,
CC ECO:0000269|PubMed:26993267}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the glycosyltransferase group 1 family.
CC Glycosyltransferase 4 subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - GTase;
CC Note=Phosphatidylinositol N-acetylglucosaminyltransferase subunit A;
CC URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_555";
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DR EMBL; D11466; BAA02019.1; -; mRNA.
DR EMBL; X77725; CAB57276.1; ALT_SEQ; Genomic_DNA.
DR EMBL; X77726; CAB57276.1; JOINED; Genomic_DNA.
DR EMBL; X77727; CAB57276.1; JOINED; Genomic_DNA.
DR EMBL; X77728; CAB57276.1; JOINED; Genomic_DNA.
DR EMBL; D28791; BAA05966.1; -; Genomic_DNA.
DR EMBL; S74936; AAD14160.1; -; mRNA.
DR EMBL; AK303538; BAG64564.1; -; mRNA.
DR EMBL; AC095351; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC038236; AAH38236.1; -; mRNA.
DR EMBL; S61523; AAD13929.1; -; mRNA.
DR CCDS; CCDS14165.1; -. [P37287-1]
DR CCDS; CCDS48086.2; -. [P37287-3]
DR PIR; A46217; A46217.
DR RefSeq; NP_002632.1; NM_002641.3. [P37287-1]
DR RefSeq; NP_065206.3; NM_020473.3. [P37287-3]
DR RefSeq; XP_016885070.1; XM_017029581.1.
DR AlphaFoldDB; P37287; -.
DR SMR; P37287; -.
DR BioGRID; 111295; 46.
DR ComplexPortal; CPX-6502; Glycosylphosphatidylinositol-N-acetylglucosaminyltransferase complex.
DR CORUM; P37287; -.
DR IntAct; P37287; 27.
DR STRING; 9606.ENSP00000369820; -.
DR CAZy; GT4; Glycosyltransferase Family 4.
DR GlyGen; P37287; 1 site.
DR iPTMnet; P37287; -.
DR PhosphoSitePlus; P37287; -.
DR BioMuta; PIGA; -.
DR DMDM; 585696; -.
DR EPD; P37287; -.
DR jPOST; P37287; -.
DR MassIVE; P37287; -.
DR MaxQB; P37287; -.
DR PaxDb; P37287; -.
DR PeptideAtlas; P37287; -.
DR PRIDE; P37287; -.
DR ProteomicsDB; 55273; -. [P37287-1]
DR ProteomicsDB; 55274; -. [P37287-2]
DR ProteomicsDB; 55275; -. [P37287-3]
DR Antibodypedia; 23929; 214 antibodies from 29 providers.
DR DNASU; 5277; -.
DR Ensembl; ENST00000333590.6; ENSP00000369820.3; ENSG00000165195.16. [P37287-1]
DR Ensembl; ENST00000482148.6; ENSP00000489528.1; ENSG00000165195.16. [P37287-2]
DR Ensembl; ENST00000542278.6; ENSP00000442653.2; ENSG00000165195.16. [P37287-1]
DR Ensembl; ENST00000634582.1; ENSP00000489540.1; ENSG00000165195.16. [P37287-3]
DR GeneID; 5277; -.
DR KEGG; hsa:5277; -.
DR MANE-Select; ENST00000333590.6; ENSP00000369820.3; NM_002641.4; NP_002632.1.
DR UCSC; uc004cwr.4; human. [P37287-1]
DR CTD; 5277; -.
DR DisGeNET; 5277; -.
DR GeneCards; PIGA; -.
DR HGNC; HGNC:8957; PIGA.
DR HPA; ENSG00000165195; Low tissue specificity.
DR MalaCards; PIGA; -.
DR MIM; 300818; phenotype.
DR MIM; 300868; phenotype.
DR MIM; 311770; gene.
DR neXtProt; NX_P37287; -.
DR OpenTargets; ENSG00000165195; -.
DR Orphanet; 397922; Ferro-cerebro-cutaneous syndrome.
DR Orphanet; 3451; Infantile spasms syndrome.
DR Orphanet; 293181; Malignant migrating focal seizures of infancy.
DR Orphanet; 300496; Multiple congenital anomalies-hypotonia-seizures syndrome type 2.
DR Orphanet; 447; Paroxysmal nocturnal hemoglobinuria.
DR PharmGKB; PA33288; -.
DR VEuPathDB; HostDB:ENSG00000165195; -.
DR eggNOG; KOG1111; Eukaryota.
DR GeneTree; ENSGT00390000014405; -.
DR HOGENOM; CLU_009583_19_3_1; -.
DR InParanoid; P37287; -.
DR OMA; FFCPNAG; -.
DR PhylomeDB; P37287; -.
DR TreeFam; TF105675; -.
DR PathwayCommons; P37287; -.
DR Reactome; R-HSA-162710; Synthesis of glycosylphosphatidylinositol (GPI).
DR SignaLink; P37287; -.
DR UniPathway; UPA00196; -.
DR BioGRID-ORCS; 5277; 18 hits in 705 CRISPR screens.
DR GeneWiki; PIGA; -.
DR GenomeRNAi; 5277; -.
DR Pharos; P37287; Tbio.
DR PRO; PR:P37287; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; P37287; protein.
DR Bgee; ENSG00000165195; Expressed in secondary oocyte and 177 other tissues.
DR ExpressionAtlas; P37287; baseline and differential.
DR Genevisible; P37287; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:HGNC-UCL.
DR GO; GO:0000506; C:glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex; IDA:HGNC-UCL.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0017176; F:phosphatidylinositol N-acetylglucosaminyltransferase activity; IBA:GO_Central.
DR GO; GO:0008194; F:UDP-glycosyltransferase activity; TAS:Reactome.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl.
DR GO; GO:0006506; P:GPI anchor biosynthetic process; IBA:GO_Central.
DR GO; GO:0016254; P:preassembly of GPI anchor in ER membrane; TAS:Reactome.
DR CDD; cd03796; GT4_PIG-A-like; 1.
DR InterPro; IPR001296; Glyco_trans_1.
DR InterPro; IPR039507; PIG-A/GPI3.
DR InterPro; IPR013234; PIGA_GPI_anchor_biosynthesis.
DR Pfam; PF00534; Glycos_transf_1; 1.
DR Pfam; PF08288; PIGA; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Endoplasmic reticulum; Epilepsy;
KW Glycoprotein; Glycosyltransferase; GPI-anchor biosynthesis;
KW Lipid metabolism; Membrane; Phosphoprotein; Reference proteome;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..484
FT /note="Phosphatidylinositol N-acetylglucosaminyltransferase
FT subunit A"
FT /id="PRO_0000080326"
FT TOPO_DOM 1..421
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 422..442
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 443..484
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CARBOHYD 467
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT VAR_SEQ 1..4
FT /note="MACR -> MELT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043366"
FT VAR_SEQ 5..238
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043367"
FT VAR_SEQ 115..283
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8081230"
FT /id="VSP_001802"
FT VARIANT 19
FT /note="R -> W (in PNH1; dbSNP:rs34422225)"
FT /evidence="ECO:0000269|PubMed:10087994"
FT /id="VAR_015442"
FT VARIANT 40
FT /note="D -> H (in PNH1)"
FT /evidence="ECO:0000269|PubMed:10087994"
FT /id="VAR_015436"
FT VARIANT 48
FT /note="G -> A (in PNH1)"
FT /evidence="ECO:0000269|PubMed:10087994"
FT /id="VAR_015437"
FT VARIANT 48
FT /note="G -> D (in PNH1)"
FT /evidence="ECO:0000269|PubMed:10087994"
FT /id="VAR_015438"
FT VARIANT 48
FT /note="G -> V (in PNH1)"
FT /evidence="ECO:0000269|PubMed:12037021"
FT /id="VAR_015439"
FT VARIANT 77
FT /note="R -> L (in MCAHS2; dbSNP:rs587777398)"
FT /evidence="ECO:0000269|PubMed:24706016"
FT /id="VAR_071069"
FT VARIANT 93
FT /note="P -> L (in MCAHS2; dbSNP:rs587777400)"
FT /evidence="ECO:0000269|PubMed:24259184"
FT /id="VAR_071070"
FT VARIANT 119
FT /note="R -> W (in MCAHS2; dbSNP:rs587777396)"
FT /evidence="ECO:0000269|PubMed:24706016"
FT /id="VAR_071071"
FT VARIANT 128
FT /note="H -> R (in PNH1)"
FT /evidence="ECO:0000269|PubMed:10087994"
FT /id="VAR_015440"
FT VARIANT 135
FT /note="A -> V (probable disease-associated variant found in
FT a patient with infantile onset epileptic encephalopathy
FT with dyskinesia and microcephaly)"
FT /evidence="ECO:0000269|PubMed:27864847"
FT /id="VAR_078230"
FT VARIANT 155
FT /note="S -> F (in PNH1)"
FT /evidence="ECO:0000269|PubMed:8306954"
FT /id="VAR_005531"
FT VARIANT 206
FT /note="I -> F (in MCAHS2; dbSNP:rs201119959)"
FT /evidence="ECO:0000269|PubMed:24706016"
FT /id="VAR_071072"
FT VARIANT 239
FT /note="G -> R (in PNH1)"
FT /evidence="ECO:0000269|PubMed:10087994"
FT /id="VAR_015441"
FT VARIANT 297
FT /note="N -> D (in PNH1)"
FT /evidence="ECO:0000269|PubMed:8167330"
FT /id="VAR_005532"
FT VARIANT 344
FT /note="Missing (in MCAHS2)"
FT /evidence="ECO:0000269|PubMed:24259288"
FT /id="VAR_071073"
FT VARIANT 355
FT /note="L -> S (in MCAHS2; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:26993267"
FT /id="VAR_078721"
SQ SEQUENCE 484 AA; 54127 MW; 34DCD074A3920852 CRC64;
MACRGGAGNG HRASATLSRV SPGSLYTCRT RTHNICMVSD FFYPNMGGVE SHIYQLSQCL
IERGHKVIIV THAYGNRKGI RYLTSGLKVY YLPLKVMYNQ STATTLFHSL PLLRYIFVRE
RVTIIHSHSS FSAMAHDALF HAKTMGLQTV FTDHSLFGFA DVSSVLTNKL LTVSLCDTNH
IICVSYTSKE NTVLRAALNP EIVSVIPNAV DPTDFTPDPF RRHDSITIVV VSRLVYRKGI
DLLSGIIPEL CQKYPDLNFI IGGEGPKRII LEEVRERYQL HDRVRLLGAL EHKDVRNVLV
QGHIFLNTSL TEAFCMAIVE AASCGLQVVS TRVGGIPEVL PENLIILCEP SVKSLCEGLE
KAIFQLKSGT LPAPENIHNI VKTFYTWRNV AERTEKVYDR VSVEAVLPMD KRLDRLISHC
GPVTGYIFAL LAVFNFLFLI FLRWMTPDSI IDVAIDATGP RGAWTNNYSH SKRGGENNEI
SETR
