PIGM_HUMAN
ID PIGM_HUMAN Reviewed; 423 AA.
AC Q9H3S5;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=GPI mannosyltransferase 1;
DE EC=2.4.1.-;
DE AltName: Full=GPI mannosyltransferase I;
DE Short=GPI-MT-I;
DE AltName: Full=Phosphatidylinositol-glycan biosynthesis class M protein;
DE Short=PIG-M;
GN Name=PIGM;
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, SUBCELLULAR LOCATION, TOPOLOGY, AND
RP MUTAGENESIS OF ASP-49 AND ASP-51.
RX PubMed=11226175; DOI=10.1093/emboj/20.1.250;
RA Maeda Y., Watanabe R., Harris C.L., Hong Y., Ohishi K., Kinoshita K.,
RA Kinoshita T.;
RT "PIG-M transfers the first mannose to glycosylphosphatidylinositol on the
RT lumenal side of the ER.";
RL EMBO J. 20:250-261(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary gland;
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Eye;
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 INVOLVEMENT IN GPIBD1.
RX PubMed=16767100; DOI=10.1038/nm1410;
RA Almeida A.M., Murakami Y., Layton D.M., Hillmen P., Sellick G.S., Maeda Y.,
RA Richards S., Patterson S., Kotsianidis I., Mollica L., Crawford D.H.,
RA Baker A., Ferguson M., Roberts I., Houlston R., Kinoshita T.,
RA Karadimitris A.;
RT "Hypomorphic promoter mutation in PIGM causes inherited
RT glycosylphosphatidylinositol deficiency.";
RL Nat. Med. 12:846-851(2006).
RN [6]
RP INVOLVEMENT IN GPIBD1.
RX PubMed=31445883; DOI=10.1016/j.ymgme.2019.08.003;
RA Pode-Shakked B., Heimer G., Vilboux T., Marek-Yagel D., Ben-Zeev B.,
RA Davids M., Ferreira C.R., Philosoph A.M., Veber A., Pode-Shakked N.,
RA Kenet G., Soudack M., Hoffmann C., Vernitsky H., Safaniev M., Lodzki M.,
RA Lahad A., Shouval D.S., Levinkopf D., Weiss B., Barg A.A., Daka A.,
RA Amariglio N., Malicdan M.C.V., Gahl W.A., Anikster Y.;
RT "Cerebral and portal vein thrombosis, macrocephaly and atypical absence
RT seizures in Glycosylphosphatidyl inositol deficiency due to a PIGM promoter
RT mutation.";
RL Mol. Genet. Metab. 128:151-161(2019).
CC -!- FUNCTION: Mannosyltransferase involved in glycosylphosphatidylinositol-
CC anchor biosynthesis. Transfers the first alpha-1,4-mannose to GlcN-
CC acyl-PI during GPI precursor assembly. {ECO:0000269|PubMed:11226175}.
CC -!- PATHWAY: Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor
CC biosynthesis.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:11226175}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:11226175}.
CC -!- DISEASE: Glycosylphosphatidylinositol biosynthesis defect 1 (GPIBD1)
CC [MIM:610293]: An autosomal recessive disorder characterized by portal
CC vein thrombosis and portal hypertension, absence seizures,
CC macrocephaly, splenomegaly, cytopenias and early-onset cerebral
CC infarctions. {ECO:0000269|PubMed:16767100,
CC ECO:0000269|PubMed:31445883}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the PIGM family. {ECO:0000305}.
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DR EMBL; AB028127; BAB18567.1; -; mRNA.
DR EMBL; AK074655; BAC11116.1; -; mRNA.
DR EMBL; AL513302; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001803; AAH01803.1; -; mRNA.
DR EMBL; BC019865; AAH19865.1; -; mRNA.
DR CCDS; CCDS1192.1; -.
DR RefSeq; NP_660150.1; NM_145167.2.
DR AlphaFoldDB; Q9H3S5; -.
DR SMR; Q9H3S5; -.
DR BioGRID; 125010; 41.
DR IntAct; Q9H3S5; 11.
DR MINT; Q9H3S5; -.
DR STRING; 9606.ENSP00000357069; -.
DR CAZy; GT50; Glycosyltransferase Family 50.
DR iPTMnet; Q9H3S5; -.
DR PhosphoSitePlus; Q9H3S5; -.
DR BioMuta; PIGM; -.
DR DMDM; 74752622; -.
DR EPD; Q9H3S5; -.
DR jPOST; Q9H3S5; -.
DR MassIVE; Q9H3S5; -.
DR MaxQB; Q9H3S5; -.
DR PaxDb; Q9H3S5; -.
DR PeptideAtlas; Q9H3S5; -.
DR PRIDE; Q9H3S5; -.
DR ProteomicsDB; 80749; -.
DR Antibodypedia; 34265; 77 antibodies from 17 providers.
DR DNASU; 93183; -.
DR Ensembl; ENST00000368090.5; ENSP00000357069.2; ENSG00000143315.8.
DR GeneID; 93183; -.
DR KEGG; hsa:93183; -.
DR MANE-Select; ENST00000368090.5; ENSP00000357069.2; NM_145167.3; NP_660150.1.
DR UCSC; uc001fuv.2; human.
DR CTD; 93183; -.
DR DisGeNET; 93183; -.
DR GeneCards; PIGM; -.
DR HGNC; HGNC:18858; PIGM.
DR HPA; ENSG00000143315; Low tissue specificity.
DR MalaCards; PIGM; -.
DR MIM; 610273; gene.
DR MIM; 610293; phenotype.
DR neXtProt; NX_Q9H3S5; -.
DR OpenTargets; ENSG00000143315; -.
DR Orphanet; 83639; Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency.
DR PharmGKB; PA38718; -.
DR VEuPathDB; HostDB:ENSG00000143315; -.
DR eggNOG; KOG3893; Eukaryota.
DR GeneTree; ENSGT00390000017728; -.
DR HOGENOM; CLU_024220_3_1_1; -.
DR InParanoid; Q9H3S5; -.
DR OMA; VTSQYFI; -.
DR OrthoDB; 1003258at2759; -.
DR PhylomeDB; Q9H3S5; -.
DR TreeFam; TF314752; -.
DR PathwayCommons; Q9H3S5; -.
DR Reactome; R-HSA-162710; Synthesis of glycosylphosphatidylinositol (GPI).
DR SignaLink; Q9H3S5; -.
DR UniPathway; UPA00196; -.
DR BioGRID-ORCS; 93183; 35 hits in 1080 CRISPR screens.
DR ChiTaRS; PIGM; human.
DR GenomeRNAi; 93183; -.
DR Pharos; Q9H3S5; Tbio.
DR PRO; PR:Q9H3S5; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9H3S5; protein.
DR Bgee; ENSG00000143315; Expressed in ileal mucosa and 187 other tissues.
DR Genevisible; Q9H3S5; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:1990529; C:glycosylphosphatidylinositol-mannosyltransferase I complex; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0051751; F:alpha-1,4-mannosyltransferase activity; IEA:InterPro.
DR GO; GO:0004376; F:glycolipid mannosyltransferase activity; IEA:InterPro.
DR GO; GO:0000030; F:mannosyltransferase activity; IBA:GO_Central.
DR GO; GO:0006506; P:GPI anchor biosynthetic process; IBA:GO_Central.
DR InterPro; IPR007704; PIG-M.
DR PANTHER; PTHR12886; PTHR12886; 1.
DR Pfam; PF05007; Mannosyl_trans; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Glycosyltransferase; GPI-anchor biosynthesis;
KW Membrane; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..423
FT /note="GPI mannosyltransferase 1"
FT /id="PRO_0000246213"
FT TOPO_DOM 1..17
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 18..38
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 39..79
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 80..100
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 101..138
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 139..161
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 162..169
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 170..190
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 191..225
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 226..246
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 247..287
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 288..308
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 309..314
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 315..337
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 338
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 339..350
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 351..357
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 358..378
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 379..384
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 385..405
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 406..423
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT VARIANT 365
FT /note="F -> L (in dbSNP:rs12409352)"
FT /id="VAR_027026"
FT MUTAGEN 49
FT /note="D->A: Almost abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:11226175"
FT MUTAGEN 51
FT /note="D->A: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:11226175"
SQ SEQUENCE 423 AA; 49460 MW; E17DCD8252E28EF0 CRC64;
MGSTKHWGEW LLNLKVAPAG VFGVAFLARV ALVFYGVFQD RTLHVRYTDI DYQVFTDAAR
FVTEGRSPYL RATYRYTPLL GWLLTPNIYL SELFGKFLFI SCDLLTAFLL YRLLLLKGLG
RRQACGYCVF WLLNPLPMAV SSRGNADSIV ASLVLMVLYL IKKRLVACAA VFYGFAVHMK
IYPVTYILPI TLHLLPDRDN DKSLRQFRYT FQACLYELLK RLCNRAVLLF VAVAGLTFFA
LSFGFYYEYG WEFLEHTYFY HLTRRDIRHN FSPYFYMLYL TAESKWSFSL GIAAFLPQLI
LLSAVSFAYY RDLVFCCFLH TSIFVTFNKV CTSQYFLWYL CLLPLVMPLV RMPWKRAVVL
LMLWFIGQAM WLAPAYVLEF QGKNTFLFIW LAGLFFLLIN CSILIQIISH YKEEPLTERI
KYD
