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   24-JAN-2024, entry version 162.
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   GlyCosmos; Q6P9A2; 4 sites, 1 glycan.
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; 9606-ENSP00000227756; -.
DR   PeptideAtlas; Q6P9A2; -.
DR   ProteomicsDB; 67031; -. [Q6P9A2-1]
DR   ProteomicsDB; 67032; -. [Q6P9A2-2]
DR   Antibodypedia; 2327; 64 antibodies from 19 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   AGR; HGNC:30488; -.
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; WHRGNKS; -.
DR   OrthoDB; 202750at2759; -.
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 1147 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 150 other cell types or tissues.
DR   ExpressionAtlas; Q6P9A2; baseline and differential.
DR   GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR   GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
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; 2.80.10.50; -; 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   PANTHER; PTHR11675; N-ACETYLGALACTOSAMINYLTRANSFERASE; 1.
DR   PANTHER; PTHR11675:SF37; POLYPEPTIDE N-ACETYLGALACTOSAMINYLTRANSFERASE 18; 1.
DR   Pfam; PF00535; Glycos_transf_2; 1.
DR   Pfam; PF00652; Ricin_B_lectin; 1.
DR   SMART; SM00458; RICIN; 1.
DR   SUPFAM; SSF53448; Nucleotide-diphospho-sugar transferases; 1.
DR   SUPFAM; SSF50370; Ricin B-like lectins; 1.
DR   PROSITE; PS50231; RICIN_B_LECTIN; 1.
DR   Genevisible; Q6P9A2; HS.
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
//