GALT2_MOUSE
ID GALT2_MOUSE Reviewed; 570 AA.
AC Q6PB93; Q7TSI5; Q8BL27; Q922K5; Q99ME1;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Polypeptide N-acetylgalactosaminyltransferase 2;
DE EC=2.4.1.41;
DE AltName: Full=Polypeptide GalNAc transferase 2;
DE Short=GalNAc-T2;
DE Short=pp-GaNTase 2;
DE AltName: Full=Protein-UDP acetylgalactosaminyltransferase 2;
DE AltName: Full=UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 2;
DE Contains:
DE RecName: Full=Polypeptide N-acetylgalactosaminyltransferase 2 soluble form;
GN Name=Galnt2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Colon adenocarcinoma;
RA Miyahara N., Kanoh A., Irimura T.;
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Adipose tissue;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and Czech II; TISSUE=Brain, and Mammary tumor;
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 TISSUE SPECIFICITY.
RX PubMed=12651884; DOI=10.1093/glycob/cwg062;
RA Young W.W. Jr., Holcomb D.R., Ten Hagen K.G., Tabak L.A.;
RT "Expression of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase
RT isoforms in murine tissues determined by real-time PCR: a new view of a
RT large family.";
RL Glycobiology 13:549-557(2003).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, and
RC Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=27508872; DOI=10.1016/j.cmet.2016.07.012;
RG Myocardial Infarction Exome Sequencing Study;
RA Khetarpal S.A., Schjoldager K.T., Christoffersen C., Raghavan A.,
RA Edmondson A.C., Reutter H.M., Ahmed B., Ouazzani R., Peloso G.M.,
RA Vitali C., Zhao W., Somasundara A.V., Millar J.S., Park Y., Fernando G.,
RA Livanov V., Choi S., Noe E., Patel P., Ho S.P., Kirchgessner T.G.,
RA Wandall H.H., Hansen L., Bennett E.P., Vakhrushev S.Y., Saleheen D.,
RA Kathiresan S., Brown C.D., Abou Jamra R., LeGuern E., Clausen H.,
RA Rader D.J.;
RT "Loss of function of GALNT2 lowers high-density lipoproteins in humans,
RT nonhuman primates, and rodents.";
RL Cell Metab. 24:234-245(2016).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=32293671; DOI=10.1093/brain/awaa063;
RA Zilmer M., Edmondson A.C., Khetarpal S.A., Alesi V., Zaki M.S., Rostasy K.,
RA Madsen C.G., Lepri F.R., Sinibaldi L., Cusmai R., Novelli A., Issa M.Y.,
RA Fenger C.D., Abou Jamra R., Reutter H., Briuglia S., Agolini E., Hansen L.,
RA Petaejae-Repo U.E., Hintze J., Raymond K.M., Liedtke K., Stanley V.,
RA Musaev D., Gleeson J.G., Vitali C., O'Brien W.T., Gardella E., Rubboli G.,
RA Rader D.J., Schjoldager K.T., Moeller R.S.;
RT "Novel congenital disorder of O-linked glycosylation caused by GALNT2 loss
RT of function.";
RL Brain 143:1114-1126(2020).
CC -!- FUNCTION: Catalyzes the initial reaction in O-linked oligosaccharide
CC biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a
CC serine or threonine residue on the protein receptor. Has a broad
CC spectrum of substrates for peptides such as EA2, Muc5AC, Muc1a, Muc1b.
CC Probably involved in O-linked glycosylation of the immunoglobulin A1
CC (IgA1) hinge region (By similarity). Involved in O-linked glycosylation
CC of APOC-III, ANGPTL3 and PLTP. It participates in the regulation of
CC HDL-C metabolism (PubMed:27508872). {ECO:0000250,
CC ECO:0000269|PubMed:27508872}.
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 -!- 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 -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack membrane; Single-
CC pass type II membrane protein. Secreted. Note=Resides preferentially in
CC the trans and medial parts of the Golgi stack. A secreted form also
CC exists.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6PB93-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6PB93-2; Sequence=VSP_011201;
CC -!- TISSUE SPECIFICITY: Widely expressed at high level.
CC {ECO:0000269|PubMed:12651884}.
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 -!- DISRUPTION PHENOTYPE: GALNT2 knockout results in significant embryonic
CC lethality. Surviving mice show decreased body weight, abnormal
CC craniofacial features, and neuro-behavioral abnormalities, including
CC deficits in coordination and impaired responses to acoustic stimuli
CC (PubMed:32293671). Knockout mice have reduced HDL-C levels compared to
CC wild-type littermate (PubMed:27508872). {ECO:0000269|PubMed:27508872,
CC ECO:0000269|PubMed:32293671}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 2 family. GalNAc-T
CC subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - GTase;
CC Note=Polypeptide N-acetylgalactosaminyltransferase 2;
CC URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_mou_511";
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DR EMBL; AF348968; AAK37548.1; -; mRNA.
DR EMBL; AK046567; BAC32790.1; -; mRNA.
DR EMBL; BC007172; AAH07172.1; -; mRNA.
DR EMBL; BC053063; AAH53063.1; -; mRNA.
DR EMBL; BC059818; AAH59818.1; -; mRNA.
DR CCDS; CCDS22769.1; -. [Q6PB93-1]
DR RefSeq; NP_644678.2; NM_139272.2. [Q6PB93-1]
DR AlphaFoldDB; Q6PB93; -.
DR SMR; Q6PB93; -.
DR BioGRID; 223865; 3.
DR STRING; 10090.ENSMUSP00000034458; -.
DR CAZy; CBM13; Carbohydrate-Binding Module Family 13.
DR CAZy; GT27; Glycosyltransferase Family 27.
DR GlyGen; Q6PB93; 1 site.
DR PhosphoSitePlus; Q6PB93; -.
DR SwissPalm; Q6PB93; -.
DR EPD; Q6PB93; -.
DR MaxQB; Q6PB93; -.
DR PaxDb; Q6PB93; -.
DR PeptideAtlas; Q6PB93; -.
DR PRIDE; Q6PB93; -.
DR ProteomicsDB; 267419; -. [Q6PB93-1]
DR ProteomicsDB; 267420; -. [Q6PB93-2]
DR DNASU; 108148; -.
DR Ensembl; ENSMUST00000034458; ENSMUSP00000034458; ENSMUSG00000089704. [Q6PB93-1]
DR GeneID; 108148; -.
DR KEGG; mmu:108148; -.
DR UCSC; uc009nwz.2; mouse. [Q6PB93-1]
DR CTD; 2590; -.
DR MGI; MGI:894694; Galnt2.
DR VEuPathDB; HostDB:ENSMUSG00000089704; -.
DR VEuPathDB; HostDB:ENSMUSG00000092329; -.
DR eggNOG; KOG3738; Eukaryota.
DR GeneTree; ENSGT00940000156958; -.
DR HOGENOM; CLU_013477_0_2_1; -.
DR InParanoid; Q6PB93; -.
DR OMA; LVFRWEF; -.
DR OrthoDB; 606683at2759; -.
DR PhylomeDB; Q6PB93; -.
DR TreeFam; TF313267; -.
DR Reactome; R-MMU-6811436; COPI-independent Golgi-to-ER retrograde traffic.
DR Reactome; R-MMU-913709; O-linked glycosylation of mucins.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 108148; 2 hits in 70 CRISPR screens.
DR ChiTaRS; Galnt2; mouse.
DR PRO; PR:Q6PB93; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q6PB93; protein.
DR Bgee; ENSMUSG00000089704; Expressed in embryonic brain and 73 other tissues.
DR Genevisible; Q6PB93; MM.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005796; C:Golgi lumen; TAS:MGI.
DR GO; GO:0005795; C:Golgi stack; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW.
DR GO; GO:0030145; F:manganese ion binding; ISS:UniProtKB.
DR GO; GO:0004653; F:polypeptide N-acetylgalactosaminyltransferase activity; ISS:UniProtKB.
DR GO; GO:0016266; P:O-glycan processing; ISO:MGI.
DR GO; GO:0051604; P:protein maturation; ISO:MGI.
DR GO; GO:0006493; P:protein O-linked glycosylation; ISS:UniProtKB.
DR GO; GO:0018242; P:protein O-linked glycosylation via serine; ISO:MGI.
DR GO; GO:0018243; P:protein O-linked glycosylation via threonine; ISO:MGI.
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 Phosphoprotein; Reference proteome; Secreted; Signal-anchor; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..570
FT /note="Polypeptide N-acetylgalactosaminyltransferase 2"
FT /id="PRO_0000223392"
FT CHAIN 51..570
FT /note="Polypeptide N-acetylgalactosaminyltransferase 2
FT soluble form"
FT /id="PRO_0000012267"
FT TOPO_DOM 1..6
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 7..24
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 25..570
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT DOMAIN 442..565
FT /note="Ricin B-type lectin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00174"
FT REGION 134..239
FT /note="Catalytic subdomain A"
FT REGION 299..361
FT /note="Catalytic subdomain B"
FT BINDING 142
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 175
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 200
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 223
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250"
FT BINDING 224
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 225
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250"
FT BINDING 330
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 358
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250"
FT BINDING 361
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 364
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 366
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 535
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q10471"
FT CARBOHYD 515
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 125..353
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00174"
FT DISULFID 344..422
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00174"
FT DISULFID 455..472
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00174"
FT DISULFID 495..512
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00174"
FT DISULFID 538..554
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00174"
FT VAR_SEQ 1..41
FT /note="MRRRSRMLLCFALLWVLGIAYYMYSGGGSALAAGGGGAGRK -> MALHNPQ
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_011201"
FT CONFLICT 2
FT /note="R -> L (in Ref. 1; AAK37548)"
FT /evidence="ECO:0000305"
FT CONFLICT 226
FT /note="C -> Y (in Ref. 2; BAC32790)"
FT /evidence="ECO:0000305"
FT CONFLICT 516..518
FT /note="DSR -> NSK (in Ref. 1; AAK37548)"
FT /evidence="ECO:0000305"
FT CONFLICT 564
FT /note="F -> V (in Ref. 1; AAK37548)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 570 AA; 64514 MW; 90D5DC02C85A8EEA CRC64;
MRRRSRMLLC FALLWVLGIA YYMYSGGGSA LAAGGGGAGR KGDWNDIDSI KKKDLHHSRG
DEKAQGVETL PPGKVRWPDF NQEAYVGGTM VRSGQDPYAR NKFNQVESDK LHMDRGIPDT
RHDQCQRKQW RVDLPATSVV ITFHNEARSA LLRTVVSVLK RSPPHLIKEI ILVDDYSNDP
EDGALLGKIE KVRVLRNDRR EGLMRSRVRG ADAAQAKVLT FLDSHCECNE RWLEPLLERV
AEDRTRVVSP IIDVINMDNF QYVGASADLK GGFDWNLVFK WDYMTPEQRR SRQGNPVAPI
KTPMIAGGLF VMDKLYFEEL GKYDMMMDVW GGENLEISFR VWQCGGSLEI IPCSRVGHVF
RKQHPYTFPG GSGTVFARNT RRAAEVWMDE YKHFYYAAVP SARNVPYGNI QSRLELRKKL
GCKPFKWYLD NVYPELRVPD HQDIAFGALQ QGTNCLDTLG HFADGVVGIY ECHNAGGNQE
WALTKEKSVK HMDLCLTVVD RSPGSLIRLQ GCRENDSRQK WEQIEGNSKL RHVGSNLCLD
SRTAKSGGLS VEVCGPALSQ QWKFSLNLQQ
