SIA4A_MOUSE
ID SIA4A_MOUSE Reviewed; 337 AA.
AC P54751; Q11202;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,3-sialyltransferase 1;
DE Short=Alpha 2,3-ST 1;
DE Short=Beta-galactoside alpha-2,3-sialyltransferase 1;
DE EC=2.4.99.4 {ECO:0000269|PubMed:10755614, ECO:0000269|PubMed:8144500, ECO:0000269|PubMed:8375377};
DE AltName: Full=Gal-NAc6S;
DE AltName: Full=Gal-beta-1,3-GalNAc-alpha-2,3-sialyltransferase;
DE AltName: Full=Monosialoganglioside sialyltransferase;
DE EC=2.4.99.2 {ECO:0000305|PubMed:8144500, ECO:0000305|PubMed:8375377};
DE AltName: Full=ST3Gal I;
DE Short=ST3GalI;
DE AltName: Full=ST3GalA.1;
DE AltName: Full=ST3O;
DE AltName: Full=Sialyltransferase 4A;
DE Short=SIAT4-A;
GN Name=St3gal1; Synonyms=Siat4, Siat4a;
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], FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE
RP SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=8375377; DOI=10.1111/j.1432-1033.1993.tb18155.x;
RA Lee Y.-C., Kurosawa N., Hamamoto T., Nakaoka T., Tsuji S.;
RT "Molecular cloning and expression of Gal beta 1,3GalNAc alpha 2,3-
RT sialyltransferase from mouse brain.";
RL Eur. J. Biochem. 216:377-385(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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, AND CATALYTIC ACTIVITY.
RX PubMed=8144500; DOI=10.1016/s0021-9258(17)36985-5;
RA Lee Y.-C., Kojima N., Wada E., Kurosawa N., Nakaoka T., Hamamoto T.,
RA Tsuji S.;
RT "Cloning and expression of cDNA for a new type of Gal beta 1,3GalNAc alpha
RT 2,3-sialyltransferase.";
RL J. Biol. Chem. 269:10028-10033(1994).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RC TISSUE=Brain;
RX PubMed=9184827; DOI=10.1093/glycob/7.4.469;
RA Kono M., Ohyama Y., Lee Y.-C., Hamamoto T., Kojima N., Tsuji S.;
RT "Mouse beta-galactoside alpha2,3-sialyltransferases: comparison of in vitro
RT substrate specificities and tissue specific expression.";
RL Glycobiology 7:469-479(1997).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=10755614; DOI=10.1016/s1074-7613(00)80180-6;
RA Priatel J.J., Chui D., Hiraoka N., Simmons C.J., Richardson K.B.,
RA Page D.M., Fukuda M., Varki N.M., Marth J.D.;
RT "The ST3Gal-I sialyltransferase controls CD8+ T lymphocyte homeostasis by
RT modulating O-glycan biosynthesis.";
RL Immunity 12:273-283(2000).
CC -!- FUNCTION: A beta-galactoside alpha2-3 sialyltransferase involved in
CC terminal sialylation of glycoproteins and glycolipids (PubMed:8375377,
CC PubMed:9184827). Catalyzes the transfer of sialic acid (N-acetyl-
CC neuraminic acid; Neu5Ac) from the nucleotide sugar donor CMP-Neu5Ac
CC onto acceptor Galbeta-(1->3)-GalNAc-terminated glycoconjugates through
CC an alpha2-3 linkage (PubMed:8144500, PubMed:8375377, PubMed:9184827,
CC PubMed:10755614). Adds sialic acid to the core 1 O-glycan, Galbeta-
CC (1->3)-GalNAc-O-Ser/Thr, which is a major structure of mucin-type O-
CC glycans. As part of a homeostatic mechanism that regulates CD8-positive
CC T cell numbers, sialylates core 1 O-glycans of T cell glycoproteins,
CC SPN/CD43 and PTPRC/CD45. Prevents premature apoptosis of thymic CD8-
CC positive T cells prior to peripheral emigration, whereas in the
CC secondary lymphoid organs controls the survival of CD8-positive memory
CC T cells generated following a successful immune response
CC (PubMed:10755614). Transfers sialic acid to asialofetuin, presumably
CC onto Galbeta-(1->3)-GalNAc-O-Ser (PubMed:8375377). Sialylates GM1a, GA1
CC and GD1b gangliosides to form GD1a, GM1b and GT1b, respectively
CC (PubMed:8144500, PubMed:8375377, PubMed:9184827).
CC {ECO:0000269|PubMed:10755614, ECO:0000269|PubMed:8144500,
CC ECO:0000269|PubMed:8375377, ECO:0000269|PubMed:9184827}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-D-galactosyl-(1->3)-N-acetyl-alpha-D-galactosaminyl
CC derivative + CMP-N-acetyl-beta-neuraminate = an N-acetyl-alpha-
CC neuraminyl-(2->3)-beta-D-galactosyl-(1->3)-N-acetyl-alpha-D-
CC galactosaminyl derivative + CMP + H(+); Xref=Rhea:RHEA:21616,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57812, ChEBI:CHEBI:60377,
CC ChEBI:CHEBI:133470, ChEBI:CHEBI:139596; EC=2.4.99.4;
CC Evidence={ECO:0000269|PubMed:10755614, ECO:0000269|PubMed:8144500,
CC ECO:0000269|PubMed:8375377};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21617;
CC Evidence={ECO:0000305|PubMed:10755614, ECO:0000305|PubMed:8144500,
CC ECO:0000305|PubMed:8375377};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=CMP-N-acetyl-beta-neuraminate + ganglioside GM1 (d18:1(4E)) =
CC CMP + ganglioside GD1a (d18:1(4E)) + H(+); Xref=Rhea:RHEA:18021,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57812, ChEBI:CHEBI:60377,
CC ChEBI:CHEBI:77709, ChEBI:CHEBI:78445; EC=2.4.99.2;
CC Evidence={ECO:0000305|PubMed:8144500, ECO:0000305|PubMed:8375377};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18022;
CC Evidence={ECO:0000305|PubMed:8144500, ECO:0000305|PubMed:8375377};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=CMP-N-acetyl-beta-neuraminate + ganglioside GM1
CC (d18:1(4E)/18:0) = CMP + ganglioside GD1a (18:1(4E)/18:0) + H(+);
CC Xref=Rhea:RHEA:48248, ChEBI:CHEBI:15378, ChEBI:CHEBI:57812,
CC ChEBI:CHEBI:60377, ChEBI:CHEBI:73110, ChEBI:CHEBI:90153;
CC Evidence={ECO:0000269|PubMed:8144500, ECO:0000269|PubMed:8375377};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48249;
CC Evidence={ECO:0000305|PubMed:8144500, ECO:0000305|PubMed:8375377};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=CMP-N-acetyl-beta-neuraminate + ganglioside GA1 = CMP +
CC ganglioside GM1b + H(+); Xref=Rhea:RHEA:48244, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57812, ChEBI:CHEBI:60377, ChEBI:CHEBI:88069,
CC ChEBI:CHEBI:90151; Evidence={ECO:0000269|PubMed:8144500,
CC ECO:0000269|PubMed:8375377, ECO:0000269|PubMed:9184827};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48245;
CC Evidence={ECO:0000305|PubMed:8144500};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=CMP-N-acetyl-beta-neuraminate + ganglioside GA1 (d18:1(4E)) =
CC CMP + ganglioside GM1b (d18:1(4E)) + H(+); Xref=Rhea:RHEA:47560,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:27938, ChEBI:CHEBI:57812,
CC ChEBI:CHEBI:60377, ChEBI:CHEBI:78568;
CC Evidence={ECO:0000250|UniProtKB:Q02745};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47561;
CC Evidence={ECO:0000250|UniProtKB:Q02745};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=CMP-N-acetyl-beta-neuraminate + ganglioside GD1b = CMP +
CC ganglioside GT1b + H(+); Xref=Rhea:RHEA:48240, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57812, ChEBI:CHEBI:60377, ChEBI:CHEBI:82939,
CC ChEBI:CHEBI:82940; Evidence={ECO:0000269|PubMed:8144500,
CC ECO:0000269|PubMed:8375377};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48241;
CC Evidence={ECO:0000305|PubMed:8144500};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.2 mM for Gal-beta-1,3-GlcNAc {ECO:0000269|PubMed:9184827};
CC KM=51 uM for Gal-beta-1,3-GalNAc {ECO:0000269|PubMed:9184827};
CC KM=0.11 mM for Gal-beta-1,3-GalNAc {ECO:0000269|PubMed:8375377};
CC KM=0.03 mM for CMP-N-acetyl-beta-neuraminate
CC {ECO:0000269|PubMed:8375377};
CC KM=1.5 mM for ganglioside GM1 {ECO:0000269|PubMed:8375377};
CC KM=0.37 mM for ganglioside GA1 {ECO:0000269|PubMed:8375377};
CC Note=Vmax is 4 fold higher with Gal-beta-1,3-GalNAc than with Gal-
CC beta-1,3-GlcNAc as substrate. {ECO:0000269|PubMed:9184827};
CC pH dependence:
CC Optimum pH is 6.4. {ECO:0000269|PubMed:8375377};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000305|PubMed:10755614}.
CC -!- PATHWAY: Glycolipid biosynthesis. {ECO:0000305|PubMed:8375377}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack membrane
CC {ECO:0000250|UniProtKB:Q11201}; Single-pass type II membrane protein
CC {ECO:0000255}. Golgi apparatus, trans-Golgi network membrane
CC {ECO:0000250|UniProtKB:Q11201}; Single-pass type II membrane protein
CC {ECO:0000255}. Secreted. Note=Membrane-bound form in medial and trans
CC cisternae of Golgi (By similarity). Secreted into the body fluid.
CC {ECO:0000250|UniProtKB:Q11201}.
CC -!- TISSUE SPECIFICITY: Highly expressed in submaxillary gland and to a
CC much lesser extent in liver, lung, kidney, heart and brain.
CC {ECO:0000269|PubMed:8375377}.
CC -!- PTM: The soluble form derives from the membrane form by proteolytic
CC processing.
CC -!- DISRUPTION PHENOTYPE: Knockout mice are deficient in CD8-positive T
CC cells due to increased apoptosis. This is associated with a reduction
CC of naive to memory T cells ratio in blood and peripheral lymphoid
CC organs. {ECO:0000269|PubMed:10755614}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 29 family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - GTase; Note=ST3Gal I;
CC URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_mou_642";
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DR EMBL; X73523; CAA51919.1; -; mRNA.
DR EMBL; BC084730; AAH84730.1; -; mRNA.
DR CCDS; CCDS27511.1; -.
DR PIR; S36824; S36824.
DR RefSeq; NP_033203.1; NM_009177.4.
DR RefSeq; XP_006520727.1; XM_006520664.3.
DR RefSeq; XP_006520728.1; XM_006520665.3.
DR RefSeq; XP_011243831.1; XM_011245529.2.
DR AlphaFoldDB; P54751; -.
DR SMR; P54751; -.
DR STRING; 10090.ENSMUSP00000090307; -.
DR SwissLipids; SLP:000001413; -.
DR CAZy; GT29; Glycosyltransferase Family 29.
DR GlyGen; P54751; 3 sites.
DR iPTMnet; P54751; -.
DR PhosphoSitePlus; P54751; -.
DR EPD; P54751; -.
DR PaxDb; P54751; -.
DR PeptideAtlas; P54751; -.
DR PRIDE; P54751; -.
DR ProteomicsDB; 257231; -.
DR Antibodypedia; 27484; 74 antibodies from 17 providers.
DR DNASU; 20442; -.
DR Ensembl; ENSMUST00000092640; ENSMUSP00000090307; ENSMUSG00000013846.
DR Ensembl; ENSMUST00000229028; ENSMUSP00000154853; ENSMUSG00000013846.
DR Ensembl; ENSMUST00000229213; ENSMUSP00000155359; ENSMUSG00000013846.
DR GeneID; 20442; -.
DR KEGG; mmu:20442; -.
DR UCSC; uc007wba.1; mouse.
DR CTD; 6482; -.
DR MGI; MGI:98304; St3gal1.
DR VEuPathDB; HostDB:ENSMUSG00000013846; -.
DR eggNOG; KOG2692; Eukaryota.
DR GeneTree; ENSGT00940000154725; -.
DR HOGENOM; CLU_032020_2_1_1; -.
DR InParanoid; P54751; -.
DR OMA; LLNYTHQ; -.
DR OrthoDB; 891104at2759; -.
DR PhylomeDB; P54751; -.
DR TreeFam; TF354325; -.
DR BRENDA; 2.4.99.2; 3474.
DR Reactome; R-MMU-2022854; Keratan sulfate biosynthesis.
DR Reactome; R-MMU-4085001; Sialic acid metabolism.
DR Reactome; R-MMU-977068; Termination of O-glycan biosynthesis.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 20442; 3 hits in 74 CRISPR screens.
DR ChiTaRS; St3gal1; mouse.
DR PRO; PR:P54751; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; P54751; protein.
DR Bgee; ENSMUSG00000013846; Expressed in cortical plate and 184 other tissues.
DR ExpressionAtlas; P54751; baseline and differential.
DR Genevisible; P54751; MM.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:1990675; C:Golgi medial cisterna membrane; ISS:UniProtKB.
DR GO; GO:1990676; C:Golgi trans cisterna membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0032588; C:trans-Golgi network membrane; ISS:UniProtKB.
DR GO; GO:0003836; F:beta-galactoside (CMP) alpha-2,3-sialyltransferase activity; IDA:UniProtKB.
DR GO; GO:0047288; F:monosialoganglioside sialyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0010706; P:ganglioside biosynthetic process via lactosylceramide; IDA:UniProtKB.
DR GO; GO:0002319; P:memory B cell differentiation; IMP:UniProtKB.
DR GO; GO:0006054; P:N-acetylneuraminate metabolic process; ISS:UniProtKB.
DR GO; GO:1905403; P:negative regulation of activated CD8-positive, alpha-beta T cell apoptotic process; IMP:UniProtKB.
DR GO; GO:0006486; P:protein glycosylation; IDA:MGI.
DR GO; GO:0006487; P:protein N-linked glycosylation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
DR GO; GO:1990743; P:protein sialylation; IDA:UniProtKB.
DR GO; GO:0097503; P:sialylation; ISS:UniProtKB.
DR Gene3D; 3.90.1480.20; -; 1.
DR InterPro; IPR001675; Glyco_trans_29.
DR InterPro; IPR038578; GT29-like_sf.
DR InterPro; IPR012163; Sialyl_trans.
DR Pfam; PF00777; Glyco_transf_29; 1.
DR PIRSF; PIRSF005557; Sialyl_trans; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Glycoprotein; Glycosyltransferase; Golgi apparatus;
KW Lipid metabolism; Membrane; Reference proteome; Secreted; Signal-anchor;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..337
FT /note="CMP-N-acetylneuraminate-beta-galactosamide-alpha-
FT 2,3-sialyltransferase 1"
FT /id="PRO_0000149254"
FT TOPO_DOM 1..4
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 5..25
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 26..337
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT BINDING 102
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q02745"
FT BINDING 144
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q02745"
FT BINDING 167
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q02745"
FT BINDING 227
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q02745"
FT BINDING 263
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q02745"
FT BINDING 267
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q02745"
FT BINDING 287
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q02745"
FT BINDING 296
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q02745"
FT BINDING 313
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q02745"
FT CARBOHYD 76
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 109
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 56..61
FT /evidence="ECO:0000250|UniProtKB:Q02745"
FT DISULFID 58..136
FT /evidence="ECO:0000250|UniProtKB:Q02745"
FT DISULFID 139..278
FT /evidence="ECO:0000250|UniProtKB:Q02745"
SQ SEQUENCE 337 AA; 39073 MW; CB54929D1EC047D1 CRC64;
MRRKTLKYLT FFLLFIFLTS FVLNYSNTGV PSAWFPKQML LELSENFRRF IKSQPCTCRH
CISQDKVSYW FDQRFNKTMQ PLLTVHNALM EEDTYRWWLR LQRERKPNNL SDTVKELFRL
VPGNVDPMLN KRLVGCRRCA VVGNSGNLKD SSYGPEIDSH DFVLRMNKAP TVGFEADVGS
RTTHHLVYPE SFRELGENVN MVLVPFKTTD LQWVISATTT GTITHTYVPV PPKIKVKQEK
ILIYHPAFIK YVFDNWLQGH GRYPSTGILS IIFSIHICDE VDLYGFGADS KGNWHHYWEN
NPSAGAFRKT GVHDGDFEYN ITTTLAAINK IRIFKGR
