GALT4_DROME
ID GALT4_DROME Reviewed; 644 AA.
AC Q8IA42; Q8IQ11;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 16-MAR-2016, sequence version 3.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=N-acetylgalactosaminyltransferase 4;
DE EC=2.4.1.41 {ECO:0000269|PubMed:12829714};
DE AltName: Full=Protein-UDP acetylgalactosaminyltransferase 4;
DE AltName: Full=UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 4;
DE Short=pp-GaNTase 4;
GN Name=Pgant4 {ECO:0000312|FlyBase:FBgn0051956};
GN ORFNames=CG31956 {ECO:0000312|FlyBase:FBgn0051956};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=Canton-S; TISSUE=Embryo;
RX PubMed=12829714; DOI=10.1074/jbc.m303836200;
RA Ten Hagen K.G., Tran D.T., Gerken T.A., Stein D.S., Zhang Z.;
RT "Functional characterization and expression analysis of members of the UDP-
RT GalNAc:polypeptide N-acetylgalactosaminyltransferase family from Drosophila
RT melanogaster.";
RL J. Biol. Chem. 278:35039-35048(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11925450; DOI=10.1074/jbc.m202684200;
RA Schwientek T., Bennett E.P., Flores C., Thacker J., Hollmann M., Reis C.A.,
RA Behrens J., Mandel U., Keck B., Schaefer M.A., Haselmann K., Zubarev R.,
RA Roepstorff P., Burchell J.M., Taylor-Papadimitriou J., Hollingsworth M.A.,
RA Clausen H.;
RT "Functional conservation of subfamilies of putative UDP-N-
RT acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferases in
RT Drosophila, Caenorhabditis elegans, and mammals. One subfamily composed of
RT l(2)35Aa is essential in Drosophila.";
RL J. Biol. Chem. 277:22623-22638(2002).
RN [5]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=16251381; DOI=10.1093/glycob/cwj051;
RA Tian E., Ten Hagen K.G.;
RT "Expression of the UDP-GalNAc: polypeptide N-
RT acetylgalactosaminyltransferase family is spatially and temporally
RT regulated during Drosophila development.";
RL Glycobiology 16:83-95(2006).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=22157008; DOI=10.1074/jbc.m111.306159;
RA Tran D.T., Zhang L., Zhang Y., Tian E., Earl L.A., Ten Hagen K.G.;
RT "Multiple members of the UDP-GalNAc: polypeptide N-
RT acetylgalactosaminyltransferase family are essential for viability in
RT Drosophila.";
RL J. Biol. Chem. 287:5243-5252(2012).
CC -!- FUNCTION: Glycopeptide transferase involved in O-linked oligosaccharide
CC biosynthesis, which catalyzes the transfer of an N-acetyl-D-
CC galactosamine residue to an already glycosylated peptide. In contrast
CC to other proteins of the family, it does not act as a peptide
CC transferase that transfers GalNAc onto serine or threonine residue on
CC the protein receptor, but instead requires the prior addition of a
CC GalNAc on a peptide before adding additional GalNAc moieties. Some
CC peptide transferase activity is however not excluded, considering that
CC its appropriate peptide substrate may remain unidentified. Prefers the
CC diglycosylated Muc5AC-3/13 as substrate. {ECO:0000269|PubMed:12829714}.
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:0000269|PubMed:12829714};
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:0000269|PubMed:12829714};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000305|PubMed:12829714}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000250}; Single-
CC pass type II membrane protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in developing oocytes and egg chambers.
CC During embryonic stages 9-11, expressed in the primordium of the
CC foregut, midgut and hindgut. During embryonic stages 12-13, shows
CC specific expression in the proventriculus that continues until the end
CC of embryogenesis. In third instar larvae, ubiquitously expressed in
CC wing, eye-antennal, leg and haltere imaginal disks.
CC {ECO:0000269|PubMed:12829714, ECO:0000269|PubMed:16251381}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC Expressed during embryonic, larval, pupal and adult stages. Weakly
CC expressed during early embryonic stages but displays a dramatic
CC increase at 12-24 hours of embryonic development. Continues to be in
CC adult but displays much lower levels in the female adult as compared
CC with the male. {ECO:0000269|PubMed:12829714,
CC ECO:0000269|PubMed:16251381}.
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|UniProtKB:O08912}.
CC -!- DOMAIN: The ricin B-type lectin domain binds to GalNAc and contributes
CC to the glycopeptide specificity. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown in the whole body or the
CC digestive system and reproductive tract is lethal (PubMed:22157008).
CC RNAi-mediated knockdowin in hemocytes, epiderm, endoderm, mesoderm,
CC respiratory system or nervous system causes no defect
CC (PubMed:22157008). {ECO:0000269|PubMed:22157008}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 2 family. GalNAc-T
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAQ56701.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY268065; AAQ56701.1; ALT_INIT; mRNA.
DR EMBL; AE014134; AAN10370.2; -; Genomic_DNA.
DR EMBL; AF324752; AAN75751.1; -; mRNA.
DR RefSeq; NP_001137779.1; NM_001144307.2.
DR RefSeq; NP_722910.2; NM_164539.2.
DR AlphaFoldDB; Q8IA42; -.
DR SMR; Q8IA42; -.
DR BioGRID; 76436; 2.
DR IntAct; Q8IA42; 1.
DR STRING; 7227.FBpp0305447; -.
DR CAZy; CBM13; Carbohydrate-Binding Module Family 13.
DR CAZy; GT27; Glycosyltransferase Family 27.
DR GlyGen; Q8IA42; 5 sites.
DR PaxDb; Q8IA42; -.
DR DNASU; 261610; -.
DR EnsemblMetazoa; FBtr0114524; FBpp0113016; FBgn0051956.
DR EnsemblMetazoa; FBtr0333248; FBpp0305447; FBgn0051956.
DR GeneID; 261610; -.
DR KEGG; dme:Dmel_CG31956; -.
DR CTD; 261610; -.
DR FlyBase; FBgn0051956; Pgant4.
DR VEuPathDB; VectorBase:FBgn0051956; -.
DR eggNOG; KOG3736; Eukaryota.
DR GeneTree; ENSGT00940000166027; -.
DR HOGENOM; CLU_013477_0_1_1; -.
DR InParanoid; Q8IA42; -.
DR OMA; FGFVNHT; -.
DR OrthoDB; 276134at2759; -.
DR BRENDA; 2.4.1.41; 1994.
DR Reactome; R-DME-913709; O-linked glycosylation of mucins.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 261610; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 261610; -.
DR PRO; PR:Q8IA42; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0051956; Expressed in thoracico-abdominal ganglion (Drosophila) and 20 other tissues.
DR ExpressionAtlas; Q8IA42; baseline and differential.
DR Genevisible; Q8IA42; DM.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005795; C:Golgi stack; NAS:UniProtKB.
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:0009312; P:oligosaccharide biosynthetic process; IDA:UniProtKB.
DR GO; GO:0051047; P:positive regulation of secretion; IMP:FlyBase.
DR GO; GO:0006493; P:protein O-linked glycosylation; IMP:FlyBase.
DR GO; GO:0033363; P:secretory granule organization; IMP:FlyBase.
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 Disulfide bond; Glycoprotein; Glycosyltransferase; Golgi apparatus; Lectin;
KW Manganese; Membrane; Metal-binding; Reference proteome; Signal-anchor;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..644
FT /note="N-acetylgalactosaminyltransferase 4"
FT /id="PRO_0000059158"
FT TOPO_DOM 1..13
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 14..34
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 35..644
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT DOMAIN 496..629
FT /note="Ricin B-type lectin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00174"
FT REGION 177..288
FT /note="Catalytic subdomain A"
FT /evidence="ECO:0000250|UniProtKB:O08912"
FT REGION 345..407
FT /note="Catalytic subdomain B"
FT /evidence="ECO:0000250|UniProtKB:O08912"
FT BINDING 218
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q10471"
FT BINDING 249
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q10471"
FT BINDING 272
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:Q10471"
FT BINDING 273
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q10471"
FT BINDING 274
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:Q10471"
FT BINDING 376
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q10471"
FT BINDING 404
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:Q10471"
FT BINDING 407
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q10471"
FT CARBOHYD 157
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 179
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 529
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 565
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 632
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 509..526
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00174"
FT DISULFID 556..573
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00174"
FT DISULFID 600..617
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00174"
SQ SEQUENCE 644 AA; 74040 MW; 884B9D91B4978F46 CRC64;
MAIKKRYVKR LLRKVVLLLV VIVTVSLVTT LVVERRMKNA AELTEQLDPN GDPITPVFRA
ANIHPTRKAP RPPFQDRNSV VDIPRSDKLQ GFRLPEPKGE RKDWHDYAAM EADRKRSGFG
EHGVAVKIEN PDEKQLEKEH YEMNGFNGLI SDRISVNRSV PDLRLEACKT RKYLAKLPNI
SVIFIFFNEH FNTLLRSIYS VINRTPPELL KQIVLVDDGS EWDVLKQPLD DYVQQHFPHL
VTIVRNPERQ GLIGARIAGA KVAVGQVMVF FDSHIEVNYN WLPPLIEPIA INPKISTCPM
VDTISHEDFS YFSGNKDGAR GGFDWKMLYK QLPVLPEDAL DKSMPYRSPV MMGGLFAINT
DFFWDLGGYD DQLDIWGGEQ YELSFKIWMC GGMLLDVPCS RVAHIFRGPM KPRGNPRGHN
FVAKNHKRVA EVWMDEYKQY VYKRDPKTYD NLDAGDLTRQ RGVRERLKCK SFHWFMTEVA
PDFLVKFPPV EPPSYAAGII QNVANPVYCL DNMGKSTEEA VGMFSCADNR THPQPNQFWE
LSIFRDLRMK GFDSVCLDVH EGPPNATVWM WSCHSQGGNQ FWYYDRQTQR LVHGENNKRC
LEGFVENGIA KVVANSCENG NDRQRWEFGF VNHTMLDTFY DGLK
