PIGB_HUMAN
ID PIGB_HUMAN Reviewed; 554 AA.
AC Q92521; Q53FF9; Q8WVN7;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=GPI mannosyltransferase 3 {ECO:0000305};
DE EC=2.4.1.-;
DE AltName: Full=GPI mannosyltransferase III;
DE Short=GPI-MT-III;
DE AltName: Full=Phosphatidylinositol-glycan biosynthesis class B protein;
DE Short=PIG-B;
GN Name=PIGB {ECO:0000312|HGNC:HGNC:8959};
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=8861954; DOI=10.1002/j.1460-2075.1996.tb00800.x;
RA Takahashi M., Inoue N., Ohishi K., Maeda Y., Nakamura N., Endo Y.,
RA Fujita T., Takeda J., Kinoshita T.;
RT "PIG-B, a membrane protein of the endoplasmic reticulum with a large
RT lumenal domain, is involved in transferring the third mannose of the GPI
RT anchor.";
RL EMBO J. 15:4254-4261(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS LEU-68; LEU-299 AND
RP SER-484.
RC TISSUE=Testis;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-299.
RC TISSUE=Prostate;
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.
RX PubMed=7907094; DOI=10.1016/s0021-9258(17)37405-7;
RA Mohney R.P., Knez J.J., Ravi L., Sevlever D., Rosenberry T.L., Hirose S.,
RA Medof M.E.;
RT "Glycoinositol phospholipid anchor-defective K562 mutants with biochemical
RT lesions distinct from those in Thy-1- murine lymphoma mutants.";
RL J. Biol. Chem. 269:6536-6542(1994).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [6]
RP VARIANTS DEE80 GLN-71; PRO-90; 131-LEU--PHE-554 DEL; HIS-155; HIS-232;
RP ARG-CYS-GLN-TRP-282 INS; LEU-286; PRO-388; ARG-407 AND MET-537, AND
RP CHARACTERIZATION OF VARIANTS DEE80 GLN-71; HIS-232; ARG-CYS-GLN-TRP-282
RP INS; LEU-286; PRO-388 AND ARG-407.
RX PubMed=31256876; DOI=10.1016/j.ajhg.2019.05.019;
RA Murakami Y., Nguyen T.T.M., Baratang N., Raju P.K., Knaus A., Ellard S.,
RA Jones G., Lace B., Rousseau J., Ajeawung N.F., Kamei A., Minase G.,
RA Akasaka M., Araya N., Koshimizu E., van den Ende J., Erger F.,
RA Altmueller J., Krumina Z., Strautmanis J., Inashkina I., Stavusis J.,
RA El-Gharbawy A., Sebastian J., Puri R.D., Kulshrestha S., Verma I.C.,
RA Maier E.M., Haack T.B., Israni A., Baptista J., Gunning A., Rosenfeld J.A.,
RA Liu P., Joosten M., Rocha M.E., Hashem M.O., Aldhalaan H.M., Alkuraya F.S.,
RA Miyatake S., Matsumoto N., Krawitz P.M., Rossignol E., Kinoshita T.,
RA Campeau P.M.;
RT "Mutations in PIGB Cause an Inherited GPI Biosynthesis Defect with an
RT Axonal Neuropathy and Metabolic Abnormality in Severe Cases.";
RL Am. J. Hum. Genet. 105:384-394(2019).
CC -!- FUNCTION: Mannosyltransferase involved in glycosylphosphatidylinositol-
CC anchor biosynthesis. Transfers the third alpha-1,2-mannose to Man2-
CC GlcN-acyl-PI during GPI precursor assembly.
CC {ECO:0000269|PubMed:8861954}.
CC -!- PATHWAY: Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor
CC biosynthesis.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:8861954}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:8861954}.
CC -!- DISEASE: Developmental and epileptic encephalopathy 80 (DEE80)
CC [MIM:618580]: A form of epileptic encephalopathy, a heterogeneous group
CC of severe early-onset epilepsies characterized by refractory seizures,
CC neurodevelopmental impairment, and poor prognosis. Development is
CC normal prior to seizure onset, after which cognitive and motor delays
CC become apparent. DEE80 is an autosomal recessive form characterized by
CC onset of refractory seizures in the first year of life, severe global
CC developmental delay and/or intellectual disability. Additional variable
CC features include polyneuropathy, hearing loss, visual impairment,
CC dysmorphic or coarse facial features, and distal skeletal
CC abnormalities. {ECO:0000269|PubMed:31256876}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 22 family. PIGB
CC subfamily. {ECO:0000305}.
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DR EMBL; D42138; BAA07709.1; -; mRNA.
DR EMBL; AK223330; BAD97050.1; -; mRNA.
DR EMBL; BC017711; AAH17711.1; -; mRNA.
DR CCDS; CCDS61641.1; -.
DR PIR; S71751; S71751.
DR RefSeq; NP_004846.4; NM_004855.4.
DR AlphaFoldDB; Q92521; -.
DR BioGRID; 114870; 21.
DR IntAct; Q92521; 7.
DR STRING; 9606.ENSP00000164305; -.
DR CAZy; GT22; Glycosyltransferase Family 22.
DR GlyGen; Q92521; 2 sites.
DR iPTMnet; Q92521; -.
DR PhosphoSitePlus; Q92521; -.
DR BioMuta; PIGB; -.
DR DMDM; 74716597; -.
DR EPD; Q92521; -.
DR jPOST; Q92521; -.
DR MassIVE; Q92521; -.
DR MaxQB; Q92521; -.
DR PaxDb; Q92521; -.
DR PeptideAtlas; Q92521; -.
DR PRIDE; Q92521; -.
DR ProteomicsDB; 75280; -.
DR Antibodypedia; 25067; 95 antibodies from 20 providers.
DR DNASU; 9488; -.
DR Ensembl; ENST00000164305.10; ENSP00000164305.5; ENSG00000069943.10.
DR GeneID; 9488; -.
DR KEGG; hsa:9488; -.
DR MANE-Select; ENST00000164305.10; ENSP00000164305.5; NM_004855.5; NP_004846.4.
DR UCSC; uc002act.4; human.
DR CTD; 9488; -.
DR DisGeNET; 9488; -.
DR GeneCards; PIGB; -.
DR HGNC; HGNC:8959; PIGB.
DR HPA; ENSG00000069943; Low tissue specificity.
DR MalaCards; PIGB; -.
DR MIM; 604122; gene.
DR MIM; 618580; phenotype.
DR neXtProt; NX_Q92521; -.
DR OpenTargets; ENSG00000069943; -.
DR PharmGKB; PA33290; -.
DR VEuPathDB; HostDB:ENSG00000069943; -.
DR eggNOG; KOG1771; Eukaryota.
DR GeneTree; ENSGT00950000183090; -.
DR HOGENOM; CLU_012353_2_0_1; -.
DR InParanoid; Q92521; -.
DR OrthoDB; 901894at2759; -.
DR PhylomeDB; Q92521; -.
DR TreeFam; TF313518; -.
DR PathwayCommons; Q92521; -.
DR Reactome; R-HSA-162710; Synthesis of glycosylphosphatidylinositol (GPI).
DR SignaLink; Q92521; -.
DR UniPathway; UPA00196; -.
DR BioGRID-ORCS; 9488; 61 hits in 1057 CRISPR screens.
DR ChiTaRS; PIGB; human.
DR GeneWiki; PIGB; -.
DR GenomeRNAi; 9488; -.
DR Pharos; Q92521; Tbio.
DR PRO; PR:Q92521; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q92521; protein.
DR Bgee; ENSG00000069943; Expressed in granulocyte and 170 other tissues.
DR ExpressionAtlas; Q92521; baseline and differential.
DR Genevisible; Q92521; 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:0000026; F:alpha-1,2-mannosyltransferase activity; IBA:GO_Central.
DR GO; GO:0004376; F:glycolipid mannosyltransferase activity; TAS:Reactome.
DR GO; GO:0000030; F:mannosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0006506; P:GPI anchor biosynthetic process; IDA:UniProtKB.
DR GO; GO:0097502; P:mannosylation; IDA:UniProtKB.
DR GO; GO:0016254; P:preassembly of GPI anchor in ER membrane; TAS:Reactome.
DR InterPro; IPR005599; GPI_mannosylTrfase.
DR InterPro; IPR039521; PIG-B/GPI10.
DR PANTHER; PTHR22760; PTHR22760; 1.
DR PANTHER; PTHR22760:SF4; PTHR22760:SF4; 1.
DR Pfam; PF03901; Glyco_transf_22; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Epilepsy; Glycoprotein; Glycosyltransferase;
KW GPI-anchor biosynthesis; Membrane; Reference proteome; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..554
FT /note="GPI mannosyltransferase 3"
FT /id="PRO_0000246251"
FT TRANSMEM 63..83
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 136..156
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 192..212
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 224..244
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 255..275
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 315..335
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 340..360
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 362..382
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 387..407
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 26
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 427
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 68
FT /note="I -> L (in dbSNP:rs17851556)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_027027"
FT VARIANT 71
FT /note="R -> Q (in DEE80; strongly decreased protein levels;
FT slightly decreased cell surface presence of GPI-anchored
FT proteins; dbSNP:rs369838467)"
FT /evidence="ECO:0000269|PubMed:31256876"
FT /id="VAR_083070"
FT VARIANT 90
FT /note="S -> P (in DEE80)"
FT /evidence="ECO:0000269|PubMed:31256876"
FT /id="VAR_083071"
FT VARIANT 131..554
FT /note="Missing (in DEE80; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:31256876"
FT /id="VAR_083072"
FT VARIANT 155
FT /note="D -> H (in DEE80; unknown pathological significance;
FT dbSNP:rs372158001)"
FT /evidence="ECO:0000269|PubMed:31256876"
FT /id="VAR_083073"
FT VARIANT 162
FT /note="M -> T (in dbSNP:rs2290344)"
FT /id="VAR_027028"
FT VARIANT 232
FT /note="R -> H (in DEE80; no effect on protein levels;
FT decreased cell surface presence of GPI-anchored proteins;
FT dbSNP:rs758196959)"
FT /evidence="ECO:0000269|PubMed:31256876"
FT /id="VAR_083074"
FT VARIANT 282
FT /note="Q -> QRCQ (in DEE80; strongly decreased protein
FT levels; decreased cell surface presence of GPI-anchored
FT proteins)"
FT /evidence="ECO:0000269|PubMed:31256876"
FT /id="VAR_083075"
FT VARIANT 286
FT /note="V -> L (in DEE80; decreased protein levels;
FT decreased cell surface presence of GPI-anchored proteins;
FT dbSNP:rs1595791368)"
FT /evidence="ECO:0000269|PubMed:31256876"
FT /id="VAR_083076"
FT VARIANT 299
FT /note="W -> L (in dbSNP:rs678892)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.2"
FT /id="VAR_027029"
FT VARIANT 388
FT /note="A -> P (in DEE80; decreased protein levels;
FT decreased cell surface presence of GPI-anchored proteins;
FT dbSNP:rs1595805026)"
FT /evidence="ECO:0000269|PubMed:31256876"
FT /id="VAR_083077"
FT VARIANT 407
FT /note="H -> R (in DEE80; decreased protein levels; slightly
FT decreased cell surface presence of GPI-anchored proteins;
FT dbSNP:rs1566960044)"
FT /evidence="ECO:0000269|PubMed:31256876"
FT /id="VAR_083078"
FT VARIANT 484
FT /note="L -> S (in dbSNP:rs17851554)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_027030"
FT VARIANT 502
FT /note="S -> G (in dbSNP:rs652397)"
FT /id="VAR_049224"
FT VARIANT 537
FT /note="I -> M (in DEE80; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:31256876"
FT /id="VAR_083079"
FT VARIANT 551
FT /note="K -> T (in dbSNP:rs2444042)"
FT /id="VAR_027031"
FT CONFLICT 198
FT /note="T -> I (in Ref. 2; BAD97050)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 554 AA; 65056 MW; B2AF87D13ADF90B3 CRC64;
MRRPLSKCGM EPGGGDASLT LHGLQNRSHG KIKLRKRKST LYFNTQEKSA RRRGDLLGEN
IYLLLFTIAL RILNCFLVQT SFVPDEYWQS LEVSHHMVFN YGYLTWEWTE RLRSYTYPLI
FASIYKILHL LGKDSVQLLI WIPRLAQALL SAVADVRLYS LMKQLENQEV ARWVFFCQLC
SWFTWYCCTR TLTNTMETVL TIIALFYYPL EGSKSMNSVK YSSLVALAFI IRPTAVILWT
PLLFRHFCQE PRKLDLILHH FLPVGFVTLS LSLMIDRIFF GQWTLVQFNF LKFNVLQNWG
TFYGSHPWHW YFSQGFPVIL GTHLPFFIHG CYLAPKRYRI LLVTVLWTLL VYSMLSHKEF
RFIYPVLPFC MVFCGYSLTH LKTWKKPALS FLFLSNLFLA LYTGLVHQRG TLDVMSHIQK
VCYNNPNKSS ASIFIMMPCH STPYYSHVHC PLPMRFLQCP PDLTGKSHYL DEADVFYLNP
LNWLHREFHD DASLPTHLIT FSILEEEISA FLISSNYKRT AVFFHTHLPE GRIGSHIYVY
ERKLKGKFNM KMKF
