PIGU_HUMAN
ID PIGU_HUMAN Reviewed; 435 AA.
AC Q9H490; Q7Z489; Q8N2F2;
DT 25-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Phosphatidylinositol glycan anchor biosynthesis class U protein;
DE AltName: Full=Cell division cycle protein 91-like 1;
DE Short=Protein CDC91-like 1;
DE AltName: Full=GPI transamidase component PIG-U;
GN Name=PIGU; Synonyms=CDC91L1; ORFNames=PSEC0205, UNQ3055/PRO9875;
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 2-8, FUNCTION,
RP AND SUBUNIT.
RC TISSUE=Embryo;
RX PubMed=12802054; DOI=10.1091/mbc.e02-12-0794;
RA Hong Y., Ohishi K., Kang J.Y., Tanaka S., Inoue N., Nishimura J., Maeda Y.,
RA Kinoshita T.;
RT "Human PIG-U and yeast Cdc91p are the fifth subunit of GPI transamidase
RT that attaches GPI-anchors to proteins.";
RL Mol. Biol. Cell 14:1780-1789(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Guo Z., Wu G., Sidransky D., Trink B.;
RT "PIG-U is a novel oncogene in human bladder cancer.";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Lin L., Yu R., Ke R., Li H., Zhou G., Shen C., Zheng G., Zhong G., Li M.,
RA Xiao W., Yang S.;
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Embryo;
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
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 VARIANTS NEDBSS LYS-70 AND LYS-383, AND INVOLVEMENT IN NEDBSS.
RX PubMed=31353022; DOI=10.1016/j.ajhg.2019.06.009;
RA Knaus A., Kortuem F., Kleefstra T., Stray-Pedersen A., Dukic D.,
RA Murakami Y., Gerstner T., van Bokhoven H., Iqbal Z., Horn D., Kinoshita T.,
RA Hempel M., Krawitz P.M.;
RT "Mutations in PIGU impair the function of the GPI transamidase complex,
RT causing severe intellectual disability, epilepsy, and brain anomalies.";
RL Am. J. Hum. Genet. 105:395-402(2019).
CC -!- FUNCTION: Component of the GPI transamidase complex. May be involved in
CC the recognition of either the GPI attachment signal or the lipid
CC portion of GPI. {ECO:0000269|PubMed:12802054}.
CC -!- PATHWAY: Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor
CC biosynthesis.
CC -!- SUBUNIT: Forms a complex with PIGK/GPI8, PIGS, PIGT and GPAA1/GAA1.
CC {ECO:0000269|PubMed:12802054}.
CC -!- INTERACTION:
CC Q9H490; Q8N6L0: KASH5; NbExp=3; IntAct=EBI-11290294, EBI-749265;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H490-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H490-2; Sequence=VSP_009543;
CC -!- DISEASE: Neurodevelopmental disorder with brain anomalies, seizures,
CC and scoliosis (NEDBSS) [MIM:618590]: An autosomal recessive disorder
CC characterized by global developmental delay, severe-to-profound
CC intellectual disability, muscular hypotonia, seizures, brain anomalies,
CC including thin corpus callosum and cerebellar atrophy, scoliosis, and
CC mild facial dysmorphism. {ECO:0000269|PubMed:31353022}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the PIGU family. {ECO:0000305}.
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DR EMBL; AB086842; BAC53626.1; -; mRNA.
DR EMBL; AY422169; AAR23798.1; -; mRNA.
DR EMBL; AY339061; AAQ18022.1; -; mRNA.
DR EMBL; AY358816; AAQ89175.1; -; mRNA.
DR EMBL; AK075507; BAC11660.1; -; mRNA.
DR EMBL; AL118520; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC030512; AAH30512.1; -; mRNA.
DR CCDS; CCDS13239.1; -. [Q9H490-1]
DR RefSeq; NP_536724.1; NM_080476.4. [Q9H490-1]
DR PDB; 7W72; EM; 3.10 A; U=1-420.
DR PDBsum; 7W72; -.
DR AlphaFoldDB; Q9H490; -.
DR SMR; Q9H490; -.
DR BioGRID; 126171; 129.
DR ComplexPortal; CPX-6503; GPI-anchor transamidase complex.
DR CORUM; Q9H490; -.
DR IntAct; Q9H490; 23.
DR MINT; Q9H490; -.
DR STRING; 9606.ENSP00000217446; -.
DR iPTMnet; Q9H490; -.
DR MetOSite; Q9H490; -.
DR PhosphoSitePlus; Q9H490; -.
DR SwissPalm; Q9H490; -.
DR BioMuta; PIGU; -.
DR DMDM; 29336947; -.
DR EPD; Q9H490; -.
DR jPOST; Q9H490; -.
DR MassIVE; Q9H490; -.
DR MaxQB; Q9H490; -.
DR PaxDb; Q9H490; -.
DR PeptideAtlas; Q9H490; -.
DR PRIDE; Q9H490; -.
DR ProteomicsDB; 80796; -. [Q9H490-1]
DR ProteomicsDB; 80797; -. [Q9H490-2]
DR Antibodypedia; 60375; 32 antibodies from 11 providers.
DR DNASU; 128869; -.
DR Ensembl; ENST00000217446.8; ENSP00000217446.3; ENSG00000101464.11. [Q9H490-1]
DR Ensembl; ENST00000374820.6; ENSP00000363953.2; ENSG00000101464.11. [Q9H490-2]
DR GeneID; 128869; -.
DR KEGG; hsa:128869; -.
DR MANE-Select; ENST00000217446.8; ENSP00000217446.3; NM_080476.5; NP_536724.1.
DR UCSC; uc002xas.4; human. [Q9H490-1]
DR CTD; 128869; -.
DR DisGeNET; 128869; -.
DR GeneCards; PIGU; -.
DR HGNC; HGNC:15791; PIGU.
DR HPA; ENSG00000101464; Low tissue specificity.
DR MalaCards; PIGU; -.
DR MIM; 608528; gene.
DR MIM; 618590; phenotype.
DR neXtProt; NX_Q9H490; -.
DR OpenTargets; ENSG00000101464; -.
DR PharmGKB; PA162399506; -.
DR VEuPathDB; HostDB:ENSG00000101464; -.
DR eggNOG; KOG2552; Eukaryota.
DR GeneTree; ENSGT00390000014941; -.
DR HOGENOM; CLU_030193_2_0_1; -.
DR InParanoid; Q9H490; -.
DR OMA; ALWHLWI; -.
DR OrthoDB; 1339553at2759; -.
DR PhylomeDB; Q9H490; -.
DR TreeFam; TF101063; -.
DR PathwayCommons; Q9H490; -.
DR Reactome; R-HSA-162791; Attachment of GPI anchor to uPAR.
DR SignaLink; Q9H490; -.
DR UniPathway; UPA00196; -.
DR BioGRID-ORCS; 128869; 23 hits in 1021 CRISPR screens.
DR ChiTaRS; PIGU; human.
DR GeneWiki; PIGU; -.
DR GenomeRNAi; 128869; -.
DR Pharos; Q9H490; Tbio.
DR PRO; PR:Q9H490; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9H490; protein.
DR Bgee; ENSG00000101464; Expressed in mucosa of transverse colon and 166 other tissues.
DR ExpressionAtlas; Q9H490; baseline and differential.
DR Genevisible; Q9H490; 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:0005886; C:plasma membrane; IDA:HGNC-UCL.
DR GO; GO:0016255; P:attachment of GPI anchor to protein; IMP:UniProtKB.
DR GO; GO:0006506; P:GPI anchor biosynthetic process; IDA:HGNC-UCL.
DR GO; GO:0034394; P:protein localization to cell surface; IBA:GO_Central.
DR GO; GO:0046425; P:regulation of receptor signaling pathway via JAK-STAT; IDA:HGNC-UCL.
DR InterPro; IPR009600; PIG-U.
DR PANTHER; PTHR13121; PTHR13121; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Direct protein sequencing;
KW Disease variant; Endoplasmic reticulum; Epilepsy; GPI-anchor biosynthesis;
KW Intellectual disability; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:12802054"
FT CHAIN 2..435
FT /note="Phosphatidylinositol glycan anchor biosynthesis
FT class U protein"
FT /id="PRO_0000121394"
FT TRANSMEM 66..86
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 166..186
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 188..208
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 237..257
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 259..279
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 286..306
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 313..333
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 355..375
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 386..406
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 269..289
FT /note="May be involved in recognition of long-chain fatty
FT acids in GPI"
FT VAR_SEQ 66..85
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_009543"
FT VARIANT 70
FT /note="I -> K (in NEDBSS; dbSNP:rs1600656141)"
FT /evidence="ECO:0000269|PubMed:31353022"
FT /id="VAR_083263"
FT VARIANT 383
FT /note="N -> K (in NEDBSS; dbSNP:rs756912205)"
FT /evidence="ECO:0000269|PubMed:31353022"
FT /id="VAR_083264"
FT CONFLICT 407
FT /note="Y -> N (in Ref. 5; BAC11660)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 435 AA; 50052 MW; 65FDD796AB533027 CRC64;
MAAPLVLVLV VAVTVRAALF RSSLAEFISE RVEVVSPLSS WKRVVEGLSL LDLGVSPYSG
AVFHETPLII YLFHFLIDYA ELVFMITDAL TAIALYFAIQ DFNKVVFKKQ KLLLELDQYA
PDVAELIRTP MEMRYIPLKV ALFYLLNPYT ILSCVAKSTC AINNTLIAFF ILTTIKGSAF
LSAIFLALAT YQSLYPLTLF VPGLLYLLQR QYIPVKMKSK AFWIFSWEYA MMYVGSLVVI
ICLSFFLLSS WDFIPAVYGF ILSVPDLTPN IGLFWYFFAE MFEHFSLFFV CVFQINVFFY
TIPLAIKLKE HPIFFMFIQI AVIAIFKSYP TVGDVALYMA FFPVWNHLYR FLRNIFVLTC
IIIVCSLLFP VLWHLWIYAG SANSNFFYAI TLTFNVGQIL LISDYFYAFL RREYYLTHGL
YLTAKDGTEA MLVLK
