PIGV_HUMAN
ID PIGV_HUMAN Reviewed; 493 AA.
AC Q9NUD9; D3DPL2; Q5JYG7; Q5JYG8; Q5JYG9; Q9NX26;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=GPI mannosyltransferase 2;
DE EC=2.4.1.-;
DE AltName: Full=GPI mannosyltransferase II;
DE Short=GPI-MT-II;
DE AltName: Full=Phosphatidylinositol-glycan biosynthesis class V protein;
DE Short=PIG-V;
GN Name=PIGV;
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 [LARGE SCALE MRNA].
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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [5]
RP DESCRIPTION OF HYPERPHOSPHATASIA WITH MENTAL RETARDATION SYNDROME.
RX PubMed=5465362; DOI=10.1016/s0022-3476(70)80047-6;
RA Mabry C.C., Bautista A., Kirk R.F., Dubilier L.D., Braunstein H.,
RA Koepke J.A.;
RT "Familial hyperphosphatase with mental retardation, seizures, and
RT neurologic deficits.";
RL J. Pediatr. 77:74-85(1970).
RN [6]
RP FUNCTION.
RX PubMed=15720390; DOI=10.1111/j.1742-4658.2005.04551.x;
RA Fabre A.-L., Orlean P., Taron C.H.;
RT "Saccharomyces cerevisiae Ybr004c and its human homologue are required for
RT addition of the second mannose during glycosylphosphatidylinositol
RT precursor assembly.";
RL FEBS J. 272:1160-1168(2005).
RN [7]
RP FUNCTION, PATHWAY, SUBCELLULAR LOCATION, TOPOLOGY, LACK OF GLYCOSYLATION,
RP AND MUTAGENESIS OF TRP-66; ASP-67; 293-PRO-PRO-294; GLN-308 AND TRP-312.
RX PubMed=15623507; DOI=10.1074/jbc.m413867200;
RA Kang J.Y., Hong Y., Ashida H., Shishioh N., Murakami Y., Morita Y.S.,
RA Maeda Y., Kinoshita T.;
RT "PIG-V involved in transferring the second mannose in
RT glycosylphosphatidylinositol.";
RL J. Biol. Chem. 280:9489-9497(2005).
RN [8]
RP VARIANTS HPMRS1 LYS-256; VAL-341; GLU-341 AND PRO-385, AND INVOLVEMENT IN
RP HPMRS1.
RX PubMed=20802478; DOI=10.1038/ng.653;
RA Krawitz P.M., Schweiger M.R., Rodelsperger C., Marcelis C., Kolsch U.,
RA Meisel C., Stephani F., Kinoshita T., Murakami Y., Bauer S., Isau M.,
RA Fischer A., Dahl A., Kerick M., Hecht J., Kohler S., Jager M.,
RA Grunhagen J., de Condor B.J., Doelken S., Brunner H.G., Meinecke P.,
RA Passarge E., Thompson M.D., Cole D.E., Horn D., Roscioli T., Mundlos S.,
RA Robinson P.N.;
RT "Identity-by-descent filtering of exome sequence data identifies PIGV
RT mutations in hyperphosphatasia mental retardation syndrome.";
RL Nat. Genet. 42:827-829(2010).
CC -!- FUNCTION: Alpha-1,6-mannosyltransferase involved in
CC glycosylphosphatidylinositol-anchor biosynthesis. Transfers the second
CC mannose to the glycosylphosphatidylinositol during GPI precursor
CC assembly. {ECO:0000269|PubMed:15623507, ECO:0000269|PubMed:15720390}.
CC -!- PATHWAY: Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor
CC biosynthesis. {ECO:0000269|PubMed:15623507}.
CC -!- INTERACTION:
CC Q9NUD9; P45973: CBX5; NbExp=3; IntAct=EBI-25836582, EBI-78219;
CC Q9NUD9; P50454: SERPINH1; NbExp=3; IntAct=EBI-25836582, EBI-350723;
CC Q9NUD9; P37173: TGFBR2; NbExp=3; IntAct=EBI-25836582, EBI-296151;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:15623507}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:15623507}.
CC -!- PTM: Not N-glycosylated. {ECO:0000269|PubMed:15623507}.
CC -!- DISEASE: Hyperphosphatasia with intellectual disability syndrome 1
CC (HPMRS1) [MIM:239300]: A severe syndrome characterized by elevated
CC serum alkaline phosphatase, severe intellectual disability, seizures,
CC hypotonia, facial dysmorphism, and hypoplastic terminal phalanges.
CC {ECO:0000269|PubMed:20802478}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the PIGV family. {ECO:0000305}.
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DR EMBL; AK000484; BAA91196.1; -; mRNA.
DR EMBL; AL034380; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX07790.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07791.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07792.1; -; Genomic_DNA.
DR EMBL; BC013568; AAH13568.1; -; mRNA.
DR CCDS; CCDS287.1; -.
DR RefSeq; NP_001189483.1; NM_001202554.1.
DR RefSeq; NP_060307.2; NM_017837.3.
DR AlphaFoldDB; Q9NUD9; -.
DR BioGRID; 120782; 1.
DR IntAct; Q9NUD9; 3.
DR STRING; 9606.ENSP00000363260; -.
DR CAZy; GT76; Glycosyltransferase Family 76.
DR iPTMnet; Q9NUD9; -.
DR PhosphoSitePlus; Q9NUD9; -.
DR BioMuta; PIGV; -.
DR DMDM; 74752975; -.
DR MassIVE; Q9NUD9; -.
DR MaxQB; Q9NUD9; -.
DR PaxDb; Q9NUD9; -.
DR PeptideAtlas; Q9NUD9; -.
DR PRIDE; Q9NUD9; -.
DR ProteomicsDB; 82666; -.
DR Antibodypedia; 30687; 106 antibodies from 17 providers.
DR DNASU; 55650; -.
DR Ensembl; ENST00000078527.9; ENSP00000078527.4; ENSG00000060642.12.
DR Ensembl; ENST00000374145.6; ENSP00000363260.1; ENSG00000060642.12.
DR Ensembl; ENST00000455364.2; ENSP00000406080.2; ENSG00000060642.12.
DR Ensembl; ENST00000674202.1; ENSP00000501479.1; ENSG00000060642.12.
DR Ensembl; ENST00000674222.1; ENSP00000501335.1; ENSG00000060642.12.
DR Ensembl; ENST00000674273.1; ENSP00000501527.1; ENSG00000060642.12.
DR Ensembl; ENST00000688522.1; ENSP00000508665.1; ENSG00000060642.12.
DR Ensembl; ENST00000691135.1; ENSP00000510357.1; ENSG00000060642.12.
DR GeneID; 55650; -.
DR KEGG; hsa:55650; -.
DR MANE-Select; ENST00000674202.1; ENSP00000501479.1; NM_017837.4; NP_060307.2.
DR UCSC; uc001bmz.4; human.
DR CTD; 55650; -.
DR DisGeNET; 55650; -.
DR GeneCards; PIGV; -.
DR HGNC; HGNC:26031; PIGV.
DR HPA; ENSG00000060642; Low tissue specificity.
DR MalaCards; PIGV; -.
DR MIM; 239300; phenotype.
DR MIM; 610274; gene.
DR neXtProt; NX_Q9NUD9; -.
DR OpenTargets; ENSG00000060642; -.
DR Orphanet; 247262; Hyperphosphatasia-intellectual disability syndrome.
DR PharmGKB; PA134952230; -.
DR VEuPathDB; HostDB:ENSG00000060642; -.
DR eggNOG; KOG2647; Eukaryota.
DR GeneTree; ENSGT00390000013174; -.
DR HOGENOM; CLU_029048_3_2_1; -.
DR InParanoid; Q9NUD9; -.
DR OMA; EYFLHIA; -.
DR OrthoDB; 960696at2759; -.
DR PhylomeDB; Q9NUD9; -.
DR TreeFam; TF314515; -.
DR PathwayCommons; Q9NUD9; -.
DR Reactome; R-HSA-162710; Synthesis of glycosylphosphatidylinositol (GPI).
DR SignaLink; Q9NUD9; -.
DR UniPathway; UPA00196; -.
DR BioGRID-ORCS; 55650; 36 hits in 1079 CRISPR screens.
DR ChiTaRS; PIGV; human.
DR GeneWiki; PIGV; -.
DR GenomeRNAi; 55650; -.
DR Pharos; Q9NUD9; Tbio.
DR PRO; PR:Q9NUD9; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9NUD9; protein.
DR Bgee; ENSG00000060642; Expressed in sperm and 196 other tissues.
DR ExpressionAtlas; Q9NUD9; baseline and differential.
DR Genevisible; Q9NUD9; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0031501; C:mannosyltransferase complex; IBA:GO_Central.
DR GO; GO:0000009; F:alpha-1,6-mannosyltransferase activity; IEA:InterPro.
DR GO; GO:0004376; F:glycolipid mannosyltransferase activity; TAS:Reactome.
DR GO; GO:0000030; F:mannosyltransferase activity; IMP:UniProtKB.
DR GO; GO:0006506; P:GPI anchor biosynthetic process; IMP:UniProtKB.
DR GO; GO:0016254; P:preassembly of GPI anchor in ER membrane; TAS:Reactome.
DR InterPro; IPR007315; PIG-V/Gpi18.
DR PANTHER; PTHR12468; PTHR12468; 1.
DR Pfam; PF04188; Mannosyl_trans2; 1.
PE 1: Evidence at protein level;
KW Disease variant; Endoplasmic reticulum; Glycosyltransferase;
KW GPI-anchor biosynthesis; Intellectual disability; Membrane;
KW Reference proteome; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..493
FT /note="GPI mannosyltransferase 2"
FT /id="PRO_0000246234"
FT TOPO_DOM 1..13
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 14..34
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 35..77
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 78..98
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 99..113
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 114..134
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 135..136
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 137..157
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 158..161
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 162..182
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 183..192
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 193..213
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 214..234
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 235..255
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 256..327
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 328..348
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 349..378
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 379..399
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 400..469
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 470..490
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 491..493
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT VARIANT 256
FT /note="Q -> K (in HPMRS1; dbSNP:rs267606952)"
FT /evidence="ECO:0000269|PubMed:20802478"
FT /id="VAR_064190"
FT VARIANT 341
FT /note="A -> E (in HPMRS1; dbSNP:rs139073416)"
FT /evidence="ECO:0000269|PubMed:20802478"
FT /id="VAR_064191"
FT VARIANT 341
FT /note="A -> V (in HPMRS1; dbSNP:rs139073416)"
FT /evidence="ECO:0000269|PubMed:20802478"
FT /id="VAR_064192"
FT VARIANT 385
FT /note="H -> P (in HPMRS1; dbSNP:rs267606951)"
FT /evidence="ECO:0000269|PubMed:20802478"
FT /id="VAR_064193"
FT MUTAGEN 66
FT /note="W->L: Loss of function."
FT /evidence="ECO:0000269|PubMed:15623507"
FT MUTAGEN 67
FT /note="D->A: Loss of function."
FT /evidence="ECO:0000269|PubMed:15623507"
FT MUTAGEN 293..294
FT /note="PP->TA: N-glycosylated due to the creation of an
FT acceptor site for N-glycosylation."
FT /evidence="ECO:0000269|PubMed:15623507"
FT MUTAGEN 308
FT /note="Q->A: Induces a reduces enzyme activity."
FT /evidence="ECO:0000269|PubMed:15623507"
FT MUTAGEN 312
FT /note="W->L: Loss of function."
FT /evidence="ECO:0000269|PubMed:15623507"
FT CONFLICT 33
FT /note="I -> T (in Ref. 1; BAA91196)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 493 AA; 55713 MW; 087AE31E51BDD519 CRC64;
MWPQDPSRKE VLRFAVSCRI LTLMLQALFN AIIPDHHAEA FSPPRLAPSG FVDQLVEGLL
GGLSHWDAEH FLFIAEHGYL YEHNFAFFPG FPLALLVGTE LLRPLRGLLS LRSCLLISVA
SLNFLFFMLA AVALHDLGCL VLHCPHQSFY AALLFCLSPA NVFLAAGYSE ALFALLTFSA
MGQLERGRVW TSVLLFAFAT GVRSNGLVSV GFLMHSQCQG FFSSLTMLNP LRQLFKLMAS
LFLSVFTLGL PFALFQYYAY TQFCLPGSAR PIPEPLVQLA VDKGYRIAEG NEPPWCFWDV
PLIYSYIQDV YWNVGFLKYY ELKQVPNFLL AAPVAILVAW ATWTYVTTHP WLCLTLGLQR
SKNNKTLEKP DLGFLSPQVF VYVVHAAVLL LFGGLCMHVQ VLTRFLGSST PIMYWFPAHL
LQDQEPLLRS LKTVPWKPLA EDSPPGQKVP RNPIMGLLYH WKTCSPVTRY ILGYFLTYWL
LGLLLHCNFL PWT
