PIGS_HUMAN
ID PIGS_HUMAN Reviewed; 555 AA.
AC Q96S52; Q6UVX6;
DT 11-JUL-2002, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=GPI transamidase component PIG-S;
DE AltName: Full=Phosphatidylinositol-glycan biosynthesis class S protein;
GN Name=PIGS; ORFNames=UNQ1873/PRO4316;
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), PROTEIN SEQUENCE OF 2-21, FUNCTION,
RP SUBUNIT, SUBCELLULAR LOCATION, AND MEMBRANE TOPOLOGY.
RX PubMed=11483512; DOI=10.1093/emboj/20.15.4088;
RA Ohishi K., Inoue N., Kinoshita T.;
RT "PIG-S and PIG-T, essential for GPI anchor attachment to proteins, form a
RT complex with GAA1 and GPI8.";
RL EMBO J. 20:4088-4098(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [6]
RP INVOLVEMENT IN GPIBD18, VARIANTS GPIBD18 PRO-34; 36-TRP--ASP-555 DEL;
RP GLY-308 AND 439-THR--LYS-451 DELINS ARG-LEU-LEU, PATHWAY, AND FUNCTION.
RX PubMed=30269814; DOI=10.1016/j.ajhg.2018.08.014;
RA Nguyen T.T.M., Murakami Y., Wigby K.M., Baratang N.V., Rousseau J.,
RA St-Denis A., Rosenfeld J.A., Laniewski S.C., Jones J., Iglesias A.D.,
RA Jones M.C., Masser-Frye D., Scheuerle A.E., Perry D.L., Taft R.J.,
RA Le Deist F., Thompson M., Kinoshita T., Campeau P.M.;
RT "Mutations in PIGS, encoding a GPI transamidase, cause a neurological
RT syndrome ranging from fetal akinesia to epileptic encephalopathy.";
RL Am. J. Hum. Genet. 103:602-611(2018).
RN [7]
RP VARIANT [LARGE SCALE ANALYSIS] ILE-159.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Component of the GPI transamidase complex. Essential for
CC transfer of GPI to proteins, particularly for formation of carbonyl
CC intermediates. {ECO:0000269|PubMed:11483512,
CC ECO:0000269|PubMed:30269814}.
CC -!- PATHWAY: Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor
CC biosynthesis. {ECO:0000269|PubMed:30269814}.
CC -!- SUBUNIT: Forms a complex with PIGK/GPI8, PIGT, PIGU and GAA1.
CC {ECO:0000269|PubMed:11483512}.
CC -!- INTERACTION:
CC Q96S52; Q6A162: KRT40; NbExp=3; IntAct=EBI-2908273, EBI-10171697;
CC Q96S52; Q8IUG1: KRTAP1-3; NbExp=3; IntAct=EBI-2908273, EBI-11749135;
CC Q96S52; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-2908273, EBI-10171774;
CC Q96S52; P60411: KRTAP10-9; NbExp=3; IntAct=EBI-2908273, EBI-10172052;
CC Q96S52; Q3LHN2: KRTAP19-2; NbExp=3; IntAct=EBI-2908273, EBI-12196745;
CC Q96S52; Q9BYR9: KRTAP2-4; NbExp=3; IntAct=EBI-2908273, EBI-14065470;
CC Q96S52; Q9BYQ4: KRTAP9-2; NbExp=3; IntAct=EBI-2908273, EBI-1044640;
CC Q96S52; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-2908273, EBI-945833;
CC Q96S52; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-2908273, EBI-22310682;
CC Q96S52; Q969N2: PIGT; NbExp=11; IntAct=EBI-2908273, EBI-726383;
CC Q96S52; Q15654: TRIP6; NbExp=3; IntAct=EBI-2908273, EBI-742327;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:11483512}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:11483512}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96S52-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96S52-2; Sequence=VSP_013158;
CC -!- DISEASE: Glycosylphosphatidylinositol biosynthesis defect 18 (GPIBD18)
CC [MIM:618143]: An autosomal recessive disorder with onset in utero or
CC early infancy and characterized by severe global developmental delay,
CC seizures, hypotonia, weakness, ataxia, and dysmorphic facial features.
CC {ECO:0000269|PubMed:30269814}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the PIGS family. {ECO:0000305}.
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DR EMBL; AB057723; BAB60853.1; -; mRNA.
DR EMBL; AY359112; AAQ89470.1; -; mRNA.
DR EMBL; BC069228; AAH69228.1; -; mRNA.
DR CCDS; CCDS11235.1; -. [Q96S52-1]
DR RefSeq; NP_149975.1; NM_033198.3. [Q96S52-1]
DR PDB; 7W72; EM; 3.10 A; S=7-539.
DR PDBsum; 7W72; -.
DR AlphaFoldDB; Q96S52; -.
DR SMR; Q96S52; -.
DR BioGRID; 125082; 165.
DR ComplexPortal; CPX-6503; GPI-anchor transamidase complex.
DR CORUM; Q96S52; -.
DR IntAct; Q96S52; 45.
DR MINT; Q96S52; -.
DR STRING; 9606.ENSP00000309430; -.
DR GlyConnect; 1285; 1 N-Linked glycan (1 site).
DR GlyGen; Q96S52; 3 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; Q96S52; -.
DR PhosphoSitePlus; Q96S52; -.
DR BioMuta; PIGS; -.
DR DMDM; 21759353; -.
DR EPD; Q96S52; -.
DR jPOST; Q96S52; -.
DR MassIVE; Q96S52; -.
DR MaxQB; Q96S52; -.
DR PaxDb; Q96S52; -.
DR PeptideAtlas; Q96S52; -.
DR PRIDE; Q96S52; -.
DR ProteomicsDB; 78065; -. [Q96S52-1]
DR ProteomicsDB; 78066; -. [Q96S52-2]
DR Antibodypedia; 2984; 118 antibodies from 24 providers.
DR DNASU; 94005; -.
DR Ensembl; ENST00000308360.8; ENSP00000309430.7; ENSG00000087111.21. [Q96S52-1]
DR Ensembl; ENST00000395346.6; ENSP00000378755.2; ENSG00000087111.21. [Q96S52-2]
DR GeneID; 94005; -.
DR KEGG; hsa:94005; -.
DR MANE-Select; ENST00000308360.8; ENSP00000309430.7; NM_033198.4; NP_149975.1.
DR UCSC; uc002hbn.3; human. [Q96S52-1]
DR CTD; 94005; -.
DR DisGeNET; 94005; -.
DR GeneCards; PIGS; -.
DR HGNC; HGNC:14937; PIGS.
DR HPA; ENSG00000087111; Low tissue specificity.
DR MalaCards; PIGS; -.
DR MIM; 610271; gene.
DR MIM; 618143; phenotype.
DR neXtProt; NX_Q96S52; -.
DR OpenTargets; ENSG00000087111; -.
DR PharmGKB; PA33301; -.
DR VEuPathDB; HostDB:ENSG00000087111; -.
DR eggNOG; KOG2459; Eukaryota.
DR GeneTree; ENSGT00390000017203; -.
DR HOGENOM; CLU_010026_3_0_1; -.
DR InParanoid; Q96S52; -.
DR OMA; AEHKYAV; -.
DR PhylomeDB; Q96S52; -.
DR TreeFam; TF105857; -.
DR PathwayCommons; Q96S52; -.
DR Reactome; R-HSA-162791; Attachment of GPI anchor to uPAR.
DR SignaLink; Q96S52; -.
DR SIGNOR; Q96S52; -.
DR UniPathway; UPA00196; -.
DR BioGRID-ORCS; 94005; 89 hits in 1088 CRISPR screens.
DR ChiTaRS; PIGS; human.
DR GeneWiki; PIGS_(gene); -.
DR GenomeRNAi; 94005; -.
DR Pharos; Q96S52; Tdark.
DR PRO; PR:Q96S52; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q96S52; protein.
DR Bgee; ENSG00000087111; Expressed in stromal cell of endometrium and 99 other tissues.
DR ExpressionAtlas; Q96S52; baseline and differential.
DR Genevisible; Q96S52; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0042765; C:GPI-anchor transamidase complex; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0016255; P:attachment of GPI anchor to protein; IBA:GO_Central.
DR InterPro; IPR019540; PtdIno-glycan_biosynth_class_S.
DR PANTHER; PTHR21072; PTHR21072; 1.
DR Pfam; PF10510; PIG-S; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Direct protein sequencing;
KW Disease variant; Endoplasmic reticulum; Epilepsy; Glycoprotein;
KW GPI-anchor biosynthesis; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:11483512"
FT CHAIN 2..555
FT /note="GPI transamidase component PIG-S"
FT /id="PRO_0000218604"
FT TOPO_DOM 2..18
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 19..39
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 40..520
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 521..541
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 542..555
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 267
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 370
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..11
FT /note="MAAAGAAATHL -> MPS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_013158"
FT VARIANT 34
FT /note="L -> P (in GPIBD18; partial loss of function; when
FT tested in PIGS-knockout cells, mediates partial restoration
FT of GPI-anchored protein expression at the cell surface;
FT dbSNP:rs1567618413)"
FT /evidence="ECO:0000269|PubMed:30269814"
FT /id="VAR_081579"
FT VARIANT 36..555
FT /note="Missing (in GPIBD18; almost complete loss of
FT function; when tested in PIGS-knockout cells, mediates only
FT very partial restoration of GPI-anchored protein expression
FT at the cell surface; strong decrease in protein level,
FT possibly due to nonsense-mediated mRNA decay)"
FT /evidence="ECO:0000269|PubMed:30269814"
FT /id="VAR_081580"
FT VARIANT 159
FT /note="M -> I (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036510"
FT VARIANT 253
FT /note="R -> H (in dbSNP:rs34669811)"
FT /id="VAR_053582"
FT VARIANT 308
FT /note="E -> G (in GPIBD18; dbSNP:rs1426262136)"
FT /evidence="ECO:0000269|PubMed:30269814"
FT /id="VAR_081581"
FT VARIANT 439..451
FT /note="TTTLTSLAQLLGK -> RLL (in GPIBD18; unknown
FT pathological significance)"
FT /evidence="ECO:0000269|PubMed:30269814"
FT /id="VAR_081582"
SQ SEQUENCE 555 AA; 61656 MW; A20B323C5475EF4F CRC64;
MAAAGAAATH LEVARGKRAA LFFAAVAIVL GLPLWWKTTE TYRASLPYSQ ISGLNALQLR
LMVPVTVVFT RESVPLDDQE KLPFTVVHER EIPLKYKMKI KCRFQKAYRR ALDHEEEALS
SGSVQEAEAM LDEPQEQAEG SLTVYVISEH SSLLPQDMMS YIGPKRTAVV RGIMHREAFN
IIGRRIVQVA QAMSLTEDVL AAALADHLPE DKWSAEKRRP LKSSLGYEIT FSLLNPDPKS
HDVYWDIEGA VRRYVQPFLN ALGAAGNFSV DSQILYYAML GVNPRFDSAS SSYYLDMHSL
PHVINPVESR LGSSAASLYP VLNFLLYVPE LAHSPLYIQD KDGAPVATNA FHSPRWGGIM
VYNVDSKTYN ASVLPVRVEV DMVRVMEVFL AQLRLLFGIA QPQLPPKCLL SGPTSEGLMT
WELDRLLWAR SVENLATATT TLTSLAQLLG KISNIVIKDD VASEVYKAVA AVQKSAEELA
SGHLASAFVA SQEAVTSSEL AFFDPSLLHL LYFPDDQKFA IYIPLFLPMA VPILLSLVKI
FLETRKSWRK PEKTD
