GLT18_HUMAN
ID GLT18_HUMAN Reviewed; 607 AA.
AC Q6P9A2; O95903; Q8NDY9;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Polypeptide N-acetylgalactosaminyltransferase 18;
DE EC=2.4.1.41 {ECO:0000305|PubMed:22186971};
DE AltName: Full=Polypeptide GalNAc transferase 18;
DE Short=GalNAc-T18;
DE AltName: Full=Polypeptide GalNAc transferase-like protein 4;
DE Short=GalNAc-T-like protein 4;
DE Short=pp-GaNTase-like protein 4;
DE AltName: Full=Polypeptide N-acetylgalactosaminyltransferase-like protein 4;
DE AltName: Full=Protein-UDP acetylgalactosaminyltransferase-like protein 4;
DE AltName: Full=UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase-like protein 4;
GN Name=GALNT18; Synonyms=GALNTL4;
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] (ISOFORM 2).
RC TISSUE=Brain;
RA Mei G., Yu W., Gibbs R.A.;
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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 [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=22186971; DOI=10.1093/glycob/cwr183;
RA Raman J., Guan Y., Perrine C.L., Gerken T.A., Tabak L.A.;
RT "UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-
RT acetylgalactosaminyltransferases: completion of the family tree.";
RL Glycobiology 22:768-777(2012).
CC -!- FUNCTION: Catalyzes the initial reaction in O-linked oligosaccharide
CC biosynthesis, the transfer of an N-acetyl-D-galactosamine (GalNAc)
CC residue from UDP-GalNAc to a serine or threonine residue on the protein
CC receptor. {ECO:0000269|PubMed:22186971}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-seryl-[protein] + UDP-N-acetyl-alpha-D-galactosamine = 3-O-
CC [N-acetyl-alpha-D-galactosaminyl]-L-seryl-[protein] + H(+) + UDP;
CC Xref=Rhea:RHEA:23956, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:12788,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:53604,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:67138; EC=2.4.1.41;
CC Evidence={ECO:0000305|PubMed:22186971};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23957;
CC Evidence={ECO:0000305|PubMed:22186971};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-threonyl-[protein] + UDP-N-acetyl-alpha-D-galactosamine = 3-
CC O-[N-acetyl-alpha-D-galactosaminyl]-L-threonyl-[protein] + H(+) +
CC UDP; Xref=Rhea:RHEA:52424, Rhea:RHEA-COMP:11060, Rhea:RHEA-
CC COMP:11689, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:67138, ChEBI:CHEBI:87075; EC=2.4.1.41;
CC Evidence={ECO:0000305|PubMed:22186971};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52425;
CC Evidence={ECO:0000305|PubMed:22186971};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000305|PubMed:22186971}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000250}; Single-
CC pass type II membrane protein {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6P9A2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6P9A2-2; Sequence=VSP_011234, VSP_011235;
CC -!- DOMAIN: There are two conserved domains in the glycosyltransferase
CC region: the N-terminal domain (domain A, also called GT1 motif), which
CC is probably involved in manganese coordination and substrate binding
CC and the C-terminal domain (domain B, also called Gal/GalNAc-T motif),
CC which is probably involved in catalytic reaction and UDP-Gal binding.
CC {ECO:0000250}.
CC -!- DOMAIN: The ricin B-type lectin domain binds to GalNAc and contributes
CC to the glycopeptide specificity. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 2 family. GalNAc-T
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD20062.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF131852; AAD20062.1; ALT_INIT; mRNA.
DR EMBL; BC060864; AAH60864.1; -; mRNA.
DR EMBL; BC037341; AAH37341.3; -; mRNA.
DR CCDS; CCDS7807.1; -. [Q6P9A2-1]
DR RefSeq; NP_940918.2; NM_198516.2. [Q6P9A2-1]
DR AlphaFoldDB; Q6P9A2; -.
DR SMR; Q6P9A2; -.
DR BioGRID; 131894; 86.
DR IntAct; Q6P9A2; 13.
DR STRING; 9606.ENSP00000227756; -.
DR CAZy; CBM13; Carbohydrate-Binding Module Family 13.
DR CAZy; GT27; Glycosyltransferase Family 27.
DR GlyGen; Q6P9A2; 4 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q6P9A2; -.
DR PhosphoSitePlus; Q6P9A2; -.
DR BioMuta; GALNT18; -.
DR DMDM; 116242498; -.
DR EPD; Q6P9A2; -.
DR jPOST; Q6P9A2; -.
DR MassIVE; Q6P9A2; -.
DR PaxDb; Q6P9A2; -.
DR PeptideAtlas; Q6P9A2; -.
DR PRIDE; Q6P9A2; -.
DR ProteomicsDB; 67031; -. [Q6P9A2-1]
DR ProteomicsDB; 67032; -. [Q6P9A2-2]
DR Antibodypedia; 2327; 50 antibodies from 18 providers.
DR DNASU; 374378; -.
DR Ensembl; ENST00000227756.5; ENSP00000227756.4; ENSG00000110328.6. [Q6P9A2-1]
DR GeneID; 374378; -.
DR KEGG; hsa:374378; -.
DR MANE-Select; ENST00000227756.5; ENSP00000227756.4; NM_198516.3; NP_940918.2.
DR UCSC; uc001mjo.3; human. [Q6P9A2-1]
DR CTD; 374378; -.
DR DisGeNET; 374378; -.
DR GeneCards; GALNT18; -.
DR HGNC; HGNC:30488; GALNT18.
DR HPA; ENSG00000110328; Low tissue specificity.
DR MIM; 615136; gene.
DR neXtProt; NX_Q6P9A2; -.
DR OpenTargets; ENSG00000110328; -.
DR PharmGKB; PA134950929; -.
DR VEuPathDB; HostDB:ENSG00000110328; -.
DR eggNOG; KOG3736; Eukaryota.
DR GeneTree; ENSGT00940000155456; -.
DR HOGENOM; CLU_013477_4_0_1; -.
DR InParanoid; Q6P9A2; -.
DR OMA; NQHIHET; -.
DR PhylomeDB; Q6P9A2; -.
DR TreeFam; TF313267; -.
DR BRENDA; 2.4.1.41; 2681.
DR PathwayCommons; Q6P9A2; -.
DR Reactome; R-HSA-913709; O-linked glycosylation of mucins.
DR SignaLink; Q6P9A2; -.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 374378; 11 hits in 1069 CRISPR screens.
DR ChiTaRS; GALNT18; human.
DR GenomeRNAi; 374378; -.
DR Pharos; Q6P9A2; Tbio.
DR PRO; PR:Q6P9A2; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q6P9A2; protein.
DR Bgee; ENSG00000110328; Expressed in right lung and 149 other tissues.
DR ExpressionAtlas; Q6P9A2; baseline and differential.
DR Genevisible; Q6P9A2; HS.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004653; F:polypeptide N-acetylgalactosaminyltransferase activity; IDA:UniProtKB.
DR GO; GO:0006493; P:protein O-linked glycosylation; IDA:UniProtKB.
DR CDD; cd02510; pp-GalNAc-T; 1.
DR CDD; cd00161; RICIN; 1.
DR Gene3D; 3.90.550.10; -; 1.
DR InterPro; IPR045885; GalNAc-T.
DR InterPro; IPR001173; Glyco_trans_2-like.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR InterPro; IPR035992; Ricin_B-like_lectins.
DR InterPro; IPR000772; Ricin_B_lectin.
DR Pfam; PF00535; Glycos_transf_2; 1.
DR Pfam; PF00652; Ricin_B_lectin; 1.
DR SMART; SM00458; RICIN; 1.
DR SUPFAM; SSF50370; SSF50370; 1.
DR SUPFAM; SSF53448; SSF53448; 1.
DR PROSITE; PS50231; RICIN_B_LECTIN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disulfide bond; Glycoprotein; Glycosyltransferase;
KW Golgi apparatus; Lectin; Manganese; Membrane; Metal-binding;
KW Reference proteome; Signal-anchor; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..607
FT /note="Polypeptide N-acetylgalactosaminyltransferase 18"
FT /id="PRO_0000059141"
FT TOPO_DOM 1..12
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 13..35
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 36..607
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT DOMAIN 469..599
FT /note="Ricin B-type lectin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00174"
FT REGION 153..267
FT /note="Catalytic subdomain A"
FT REGION 324..385
FT /note="Catalytic subdomain B"
FT BINDING 194
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q10471"
FT BINDING 251
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:Q10471"
FT BINDING 253
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:Q10471"
FT BINDING 382
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:Q10471"
FT BINDING 385
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q10471"
FT BINDING 390
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q10471"
FT CARBOHYD 146
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 195
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 320
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 144..377
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00174"
FT DISULFID 368..447
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00174"
FT DISULFID 482..498
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00174"
FT DISULFID 530..543
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00174"
FT DISULFID 571..591
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00174"
FT VAR_SEQ 79..91
FT /note="EAPAKPEEAEAEP -> GYRRNFSLLNVSN (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_011234"
FT VAR_SEQ 92..607
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_011235"
FT CONFLICT 133
FT /note="D -> G (in Ref. 2; AAH60864)"
FT /evidence="ECO:0000305"
FT CONFLICT 541
FT /note="I -> T (in Ref. 2; AAH60864)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 607 AA; 69561 MW; 8FFA7BCB5016FF0C CRC64;
MVCTRKTKTL VSTCVILSGM TNIICLLYVG WVTNYIASVY VRGQEPAPDK KLEEDKGDTL
KIIERLDHLE NVIKQHIQEA PAKPEEAEAE PFTDSSLFAH WGQELSPEGR RVALKQFQYY
GYNAYLSDRL PLDRPLPDLR PSGCRNLSFP DSLPEVSIVF IFVNEALSVL LRSIHSAMER
TPPHLLKEII LVDDNSSNEE LKEKLTEYVD KVNSQKPGFI KVVRHSKQEG LIRSRVSGWR
AATAPVVALF DAHVEFNVGW AEPVLTRIKE NRKRIISPSF DNIKYDNFEI EEYPLAAQGF
DWELWCRYLN PPKAWWKLEN STAPIRSPAL IGCFIVDRQY FQEIGLLDEG MEVYGGENVE
LGIRVWQCGG SVEVLPCSRI AHIERAHKPY TEDLTAHVRR NALRVAEVWM DEFKSHVYMA
WNIPQEDSGI DIGDITARKA LRKQLQCKTF RWYLVSVYPE MRMYSDIIAY GVLQNSLKTD
LCLDQGPDTE NVPIMYICHG MTPQNVYYTS SQQIHVGILS PTVDDDDNRC LVDVNSRPRL
IECSYAKAKR MKLHWQFSQG GPIQNRKSKR CLELQENSDL EFGFQLVLQK CSGQHWSITN
VLRSLAS
