PIGC_HUMAN
ID PIGC_HUMAN Reviewed; 297 AA.
AC Q92535; O14491;
DT 11-JUL-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Phosphatidylinositol N-acetylglucosaminyltransferase subunit C {ECO:0000305};
DE AltName: Full=Phosphatidylinositol-glycan biosynthesis class C protein;
DE Short=PIG-C;
GN Name=PIGC {ECO:0000312|HGNC:HGNC:8960}; Synonyms=GPI2;
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], FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=8806613; DOI=10.1006/bbrc.1996.1332;
RA Inoue N., Watanabe R., Takeda J., Kinoshita T.;
RT "PIG-C, one of the three human genes involved in the first step of
RT glycosylphosphatidylinositol biosynthesis is a homologue of Saccharomyces
RT cerevisiae GPI2.";
RL Biochem. Biophys. Res. Commun. 226:193-199(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-266.
RC TISSUE=Fibroblast;
RX PubMed=9325057; DOI=10.1006/geno.1997.4893;
RA Hong Y., Ohishi K., Inoue N., Endo Y., Fujita T., Takeda J., Kinoshita T.;
RT "Structures and chromosomal localizations of the
RT glycosylphosphatidylinositol synthesis gene PIGC and its pseudogene
RT PIGCP1.";
RL Genomics 44:347-349(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [7]
RP COMPONENT OF GPI-GNT COMPLEX, AND INTERACTION WITH PIGQ AND PIGA:PIGH
RP HETERODIMER.
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 [8]
RP COMPONENT OF GPI-GNT COMPLEX, 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 [9]
RP FUNCTION, INVOLVEMENT IN GPIBD16, VARIANTS GPIBD16 21-ARG--SER-297 DEL;
RP TRP-189 AND PRO-212, AND CHARACTERIZATION OF VARIANTS GPIBD16
RP 21-ARG--SER-297 DEL; TRP-189 AND PRO-212.
RX PubMed=27694521; DOI=10.1136/jmedgenet-2016-104202;
RA Edvardson S., Murakami Y., Nguyen T.T., Shahrour M., St-Denis A., Shaag A.,
RA Damseh N., Le Deist F., Bryceson Y., Abu-Libdeh B., Campeau P.M.,
RA Kinoshita T., Elpeleg O.;
RT "Mutations in the phosphatidylinositol glycan C (PIGC) gene are associated
RT with epilepsy and intellectual disability.";
RL J. Med. Genet. 54:196-201(2017).
CC -!- FUNCTION: Part 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:0000269|PubMed:16162815,
CC ECO:0000269|PubMed:27694521, ECO:0000269|PubMed:8806613}.
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 PIGQ (PubMed:9463366). Interacts with
CC the heterodimer PIGA:PIGH (PubMed:9463366).
CC {ECO:0000269|PubMed:16162815, ECO:0000269|PubMed:9463366}.
CC -!- INTERACTION:
CC Q92535; O94777: DPM2; NbExp=2; IntAct=EBI-721918, EBI-9097061;
CC Q92535; Q9BRB3: PIGQ; NbExp=4; IntAct=EBI-721918, EBI-2339260;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:8806613}; Multi-pass membrane protein
CC {ECO:0000305}.
CC -!- DISEASE: Glycosylphosphatidylinositol biosynthesis defect 16 (GPIBD16)
CC [MIM:617816]: An autosomal recessive disorder characterized by delayed
CC psychomotor development, intellectual disability, and seizures.
CC {ECO:0000269|PubMed:27694521}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the PIGC family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - GTase;
CC Note=Phosphatidylinositol N-acetylglucosaminyltransferase subunit C8;
CC URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_556";
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DR EMBL; D85418; BAA12812.1; -; mRNA.
DR EMBL; AB000360; BAA22866.1; -; Genomic_DNA.
DR EMBL; BT006734; AAP35380.1; -; mRNA.
DR EMBL; CR450292; CAG29288.1; -; mRNA.
DR EMBL; Z97195; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC006539; AAH06539.1; -; mRNA.
DR CCDS; CCDS1302.1; -.
DR PIR; JC4969; JC4969.
DR RefSeq; NP_002633.1; NM_002642.3.
DR RefSeq; NP_714969.1; NM_153747.1.
DR AlphaFoldDB; Q92535; -.
DR BioGRID; 111297; 11.
DR ComplexPortal; CPX-6502; Glycosylphosphatidylinositol-N-acetylglucosaminyltransferase complex.
DR CORUM; Q92535; -.
DR IntAct; Q92535; 6.
DR MINT; Q92535; -.
DR STRING; 9606.ENSP00000356702; -.
DR iPTMnet; Q92535; -.
DR PhosphoSitePlus; Q92535; -.
DR BioMuta; PIGC; -.
DR DMDM; 14916629; -.
DR MassIVE; Q92535; -.
DR MaxQB; Q92535; -.
DR PaxDb; Q92535; -.
DR PeptideAtlas; Q92535; -.
DR PRIDE; Q92535; -.
DR ProteomicsDB; 75293; -.
DR Antibodypedia; 34384; 88 antibodies from 24 providers.
DR DNASU; 5279; -.
DR Ensembl; ENST00000344529.5; ENSP00000356701.3; ENSG00000135845.10.
DR Ensembl; ENST00000367728.1; ENSP00000356702.1; ENSG00000135845.10.
DR GeneID; 5279; -.
DR KEGG; hsa:5279; -.
DR MANE-Select; ENST00000344529.5; ENSP00000356701.3; NM_153747.2; NP_714969.1.
DR UCSC; uc001gio.4; human.
DR CTD; 5279; -.
DR DisGeNET; 5279; -.
DR GeneCards; PIGC; -.
DR HGNC; HGNC:8960; PIGC.
DR HPA; ENSG00000135845; Low tissue specificity.
DR MalaCards; PIGC; -.
DR MIM; 601730; gene.
DR MIM; 617816; phenotype.
DR neXtProt; NX_Q92535; -.
DR OpenTargets; ENSG00000135845; -.
DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability.
DR PharmGKB; PA33291; -.
DR VEuPathDB; HostDB:ENSG00000135845; -.
DR eggNOG; KOG3059; Eukaryota.
DR GeneTree; ENSGT00390000005496; -.
DR HOGENOM; CLU_024002_0_0_1; -.
DR InParanoid; Q92535; -.
DR OMA; HAFVMVT; -.
DR OrthoDB; 1241278at2759; -.
DR PhylomeDB; Q92535; -.
DR TreeFam; TF314325; -.
DR PathwayCommons; Q92535; -.
DR Reactome; R-HSA-162710; Synthesis of glycosylphosphatidylinositol (GPI).
DR SignaLink; Q92535; -.
DR UniPathway; UPA00196; -.
DR BioGRID-ORCS; 5279; 86 hits in 1067 CRISPR screens.
DR GeneWiki; PIGC; -.
DR GenomeRNAi; 5279; -.
DR Pharos; Q92535; Tbio.
DR PRO; PR:Q92535; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q92535; protein.
DR Bgee; ENSG00000135845; Expressed in calcaneal tendon and 207 other tissues.
DR Genevisible; Q92535; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:ComplexPortal.
DR GO; GO:0000506; C:glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0003824; F:catalytic activity; TAS:ProtInc.
DR GO; GO:0006506; P:GPI anchor biosynthetic process; IDA:UniProtKB.
DR InterPro; IPR009450; Plno_GlcNAc_GPI2.
DR PANTHER; PTHR12982; PTHR12982; 1.
DR Pfam; PF06432; GPI2; 1.
DR PIRSF; PIRSF016104; GPI2; 1.
PE 1: Evidence at protein level;
KW Disease variant; Endoplasmic reticulum; GPI-anchor biosynthesis;
KW Intellectual disability; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..297
FT /note="Phosphatidylinositol N-acetylglucosaminyltransferase
FT subunit C"
FT /id="PRO_0000058431"
FT TRANSMEM 51..71
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 80..100
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 117..137
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 153..173
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 174..194
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 196..216
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 227..244
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 250..270
FT /note="Helical"
FT /evidence="ECO:0000255"
FT VARIANT 21..297
FT /note="Missing (in GPIBD16; decreased function in GPI-
FT anchor biosynthesis as indicated by reduced surface
FT expression of various GPI-anchored proteins)"
FT /evidence="ECO:0000269|PubMed:27694521"
FT /id="VAR_080520"
FT VARIANT 189
FT /note="L -> W (in GPIBD16; decreased function in GPI-anchor
FT biosynthesis as indicated by reduced surface expression of
FT various GPI-anchored proteins; dbSNP:rs1553259614)"
FT /evidence="ECO:0000269|PubMed:27694521"
FT /id="VAR_080521"
FT VARIANT 212
FT /note="L -> P (in GPIBD16; decreased function in GPI-anchor
FT biosynthesis as indicated by reduced surface expression of
FT various GPI-anchored proteins; dbSNP:rs1553259602)"
FT /evidence="ECO:0000269|PubMed:27694521"
FT /id="VAR_080522"
FT VARIANT 266
FT /note="P -> S (in dbSNP:rs1063412)"
FT /evidence="ECO:0000269|PubMed:9325057"
FT /id="VAR_011360"
SQ SEQUENCE 297 AA; 33583 MW; BD9584C5D5203A4B CRC64;
MYAQPVTNTK EVKWQKVLYE RQPFPDNYVD RRFLEELRKN IHARKYQYWA VVFESSVVIQ
QLCSVCVFVV IWWYMDEGLL APHWLLGTGL ASSLIGYVLF DLIDGGEGRK KSGQTRWADL
KSALVFITFT YGFSPVLKTL TESVSTDTIY AMSVFMLLGH LIFFDYGANA AIVSSTLSLN
MAIFASVCLA SRLPRSLHAF IMVTFAIQIF ALWPMLQKKL KACTPRSYVG VTLLFAFSAV
GGLLSISAVG AVLFALLLMS ISCLCPFYLI RLQLFKENIH GPWDEAEIKE DLSRFLS
