SIA4C_MOUSE
ID SIA4C_MOUSE Reviewed; 333 AA.
AC Q91Y74; P97354; Q61325;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,3-sialyltransferase 4;
DE Short=Alpha 2,3-ST 4;
DE Short=Beta-galactoside alpha-2,3-sialyltransferase 4;
DE EC=2.4.99.2 {ECO:0000250|UniProtKB:Q11206};
DE EC=2.4.99.4 {ECO:0000250|UniProtKB:Q11206};
DE AltName: Full=Alpha 2,3-sialyltransferase IV;
DE AltName: Full=Gal-beta-1,3-GalNAc-alpha-2,3-sialyltransferase;
DE AltName: Full=Gal-beta-1,4-GlcNAc-alpha-2,3-sialyltransferase;
DE AltName: Full=N-acetyllactosaminide alpha-2,3-sialyltransferase;
DE EC=2.4.99.6 {ECO:0000250|UniProtKB:Q11206};
DE AltName: Full=ST3Gal IV;
DE Short=ST3GalIV;
DE AltName: Full=Sialyltransferase 4C;
DE Short=SIAT4-C;
GN Name=St3gal4; Synonyms=Siat4c;
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, TISSUE SPECIFICITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RC TISSUE=Liver;
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=ddY; TISSUE=Brain;
RX PubMed=11389169; DOI=10.1046/j.1471-4159.2001.00319.x;
RA Okaba A., Tawara Y., Masa T., Oka T., Machida A., Tanaka T., Matsuhashi H.,
RA Shiosaka S., Kato K.;
RT "Differential expression of mRNAs for sialyltransferase isoenzymes induced
RT in the hippocampus of mouse following kindled seizures.";
RL J. Neurochem. 77:1185-1197(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC 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 [4]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=12097641; DOI=10.1073/pnas.142005099;
RA Ellies L.G., Ditto D., Levy G.G., Wahrenbrock M., Ginsburg D., Varki A.,
RA Le D.T., Marth J.D.;
RT "Sialyltransferase ST3Gal-IV operates as a dominant modifier of hemostasis
RT by concealing asialoglycoprotein receptor ligands.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:10042-10047(2002).
RN [5]
RP FUNCTION.
RX PubMed=18519646; DOI=10.1084/jem.20070846;
RA Frommhold D., Ludwig A., Bixel M.G., Zarbock A., Babushkina I.,
RA Weissinger M., Cauwenberghs S., Ellies L.G., Marth J.D.,
RA Beck-Sickinger A.G., Sixt M., Lange-Sperandio B., Zernecke A., Brandt E.,
RA Weber C., Vestweber D., Ley K., Sperandio M.;
RT "Sialyltransferase ST3Gal-IV controls CXCR2-mediated firm leukocyte arrest
RT during inflammation.";
RL J. Exp. Med. 205:1435-1446(2008).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver, and Testis;
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 [7]
RP FUNCTION.
RX PubMed=25498912; DOI=10.1182/blood-2014-07-588590;
RA Mondal N., Buffone A. Jr., Stolfa G., Antonopoulos A., Lau J.T.,
RA Haslam S.M., Dell A., Neelamegham S.;
RT "ST3Gal-4 is the primary sialyltransferase regulating the synthesis of E-,
RT P-, and L-selectin ligands on human myeloid leukocytes.";
RL Blood 125:687-696(2015).
CC -!- FUNCTION: A beta-galactoside alpha2-3 sialyltransferase involved in
CC terminal sialylation of glycoproteins and glycolipids (PubMed:12097641)
CC (By similarity). 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- and Galbeta-(1->4)-GlcNAc-
CC terminated glycoconjugates through an alpha2-3 linkage (PubMed:9184827)
CC (By similarity). Plays a major role in hemostasis. Responsible for
CC sialylation of plasma VWF/von Willebrand factor, preventing its
CC recognition by asialoglycoprotein receptors (ASGPR) and subsequent
CC clearance. Regulates ASGPR-mediated clearance of platelets
CC (PubMed:12097641). Participates in the biosynthesis of the sialyl Lewis
CC X epitopes, both on O- and N-glycans, which are recognized by SELE/E-
CC selectin, SELP/P-selectin and SELL/L-selectin. Essential for selectin-
CC mediated rolling and adhesion of leukocytes during extravasation
CC (PubMed:25498912). Contributes to adhesion and transendothelial
CC migration of neutrophils likely through terminal sialylation of CXCR2
CC (PubMed:18519646). In glycosphingolipid biosynthesis, sialylates GM1
CC and GA1 gangliosides to form GD1a and GM1b, respectively (By
CC similarity). Metabolizes brain c-series ganglioside GT1c forming GQ1c
CC (By similarity). Synthesizes ganglioside LM1 (IV3Neu5Ac-nLc4Cer), a
CC major structural component of peripheral nerve myelin (By similarity).
CC {ECO:0000250|UniProtKB:P61131, ECO:0000250|UniProtKB:Q11206,
CC ECO:0000269|PubMed:12097641, ECO:0000269|PubMed:18519646,
CC ECO:0000269|PubMed:25498912, ECO:0000269|PubMed:9184827}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-D-galactosyl-(1->3)-N-acetyl-beta-D-galactosaminyl
CC derivative + CMP-N-acetyl-beta-neuraminate = an N-acetyl-alpha-
CC neuraminyl-(2->3)-beta-D-galactosyl-(1->3)-N-acetyl-beta-D-
CC galactosaminyl derivative + CMP + H(+); Xref=Rhea:RHEA:52380,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57812, ChEBI:CHEBI:60377,
CC ChEBI:CHEBI:136588, ChEBI:CHEBI:136589; EC=2.4.99.2;
CC Evidence={ECO:0000250|UniProtKB:Q11206};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52381;
CC Evidence={ECO:0000250|UniProtKB:Q11206};
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:0000250|UniProtKB:Q11206};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21617;
CC Evidence={ECO:0000250|UniProtKB:Q11206};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl
CC derivative + CMP-N-acetyl-beta-neuraminate = an N-acetyl-alpha-
CC neuraminyl-(2->3)-beta-D-galactosyl-(1->4)-N-acetyl-beta-D-
CC glucosaminyl derivative + CMP + H(+); Xref=Rhea:RHEA:52316,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57812, ChEBI:CHEBI:60377,
CC ChEBI:CHEBI:133507, ChEBI:CHEBI:136545; EC=2.4.99.6;
CC Evidence={ECO:0000250|UniProtKB:Q11206};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52317;
CC Evidence={ECO:0000250|UniProtKB:Q11206};
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:0000250|UniProtKB:Q11206};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18022;
CC Evidence={ECO:0000250|UniProtKB:Q11206};
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:Q11206};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47561;
CC Evidence={ECO:0000250|UniProtKB:Q11206};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=CMP-N-acetyl-beta-neuraminate + ganglioside GT1c (d18:1(4E)) =
CC CMP + ganglioside GQ1c (d18:1(4E)) + H(+); Xref=Rhea:RHEA:47588,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57812, ChEBI:CHEBI:60377,
CC ChEBI:CHEBI:87789, ChEBI:CHEBI:87791;
CC Evidence={ECO:0000250|UniProtKB:P61131};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47589;
CC Evidence={ECO:0000250|UniProtKB:P61131};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a neolactoside nLc4Cer + CMP-N-acetyl-beta-neuraminate = a
CC neolactoside IV(3)-alpha-NeuAc-nLc4Cer + CMP + H(+);
CC Xref=Rhea:RHEA:65432, ChEBI:CHEBI:15378, ChEBI:CHEBI:57812,
CC ChEBI:CHEBI:60377, ChEBI:CHEBI:90376, ChEBI:CHEBI:90390;
CC Evidence={ECO:0000250|UniProtKB:Q11206};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65433;
CC Evidence={ECO:0000250|UniProtKB:Q11206};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a neolactoside nLc4Cer(d18:1(4E)) + CMP-N-acetyl-beta-
CC neuraminate = a neolactoside IV(3)-alpha-NeuAc-nLc4Cer(d18:1(4E)) +
CC CMP + H(+); Xref=Rhea:RHEA:18913, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17006, ChEBI:CHEBI:57812, ChEBI:CHEBI:58665,
CC ChEBI:CHEBI:60377; EC=2.4.99.6;
CC Evidence={ECO:0000250|UniProtKB:Q11206};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18914;
CC Evidence={ECO:0000250|UniProtKB:Q11206};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.75 mM for Gal-beta-1,3-GlcNAc {ECO:0000269|PubMed:9184827};
CC KM=0.22 mM for Gal-beta-1,4-GlcNAc {ECO:0000269|PubMed:9184827};
CC KM=3.0 mM for Gal-beta-1,3-GalNAc {ECO:0000269|PubMed:9184827};
CC Note=Relative Vmax is 2:5:1 for Gal-beta-1,3-GlcNAc, Gal-beta-1,4-
CC GlcNAc and Gal-beta-1,3-GalNAc as substrate, respectively.
CC {ECO:0000269|PubMed:9184827};
CC pH dependence:
CC Optimum pH is 6.4. {ECO:0000269|PubMed:9184827};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack membrane
CC {ECO:0000250}; Single-pass type II membrane protein {ECO:0000250}.
CC Note=Membrane-bound form in trans cisternae of Golgi. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Broadly expressed among tissues with highest levels
CC in the small intestine and colon. {ECO:0000269|PubMed:12097641,
CC ECO:0000269|PubMed:9184827}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice suffer from bleeding disorders and
CC thrombocytopenia due to deficient ASGPR-mediated clearance of plasma
CC VWF/von Willebrand factor. {ECO:0000269|PubMed:12097641}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 29 family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - GTase; Note=ST3Gal
CC IV;
CC URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_mou_645";
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DR EMBL; X95809; CAA65076.1; -; mRNA.
DR EMBL; AB061305; BAB47508.1; -; mRNA.
DR EMBL; BC050773; AAH50773.1; -; mRNA.
DR CCDS; CCDS22956.1; -.
DR RefSeq; NP_033204.2; NM_009178.4.
DR RefSeq; XP_011240735.1; XM_011242433.1.
DR AlphaFoldDB; Q91Y74; -.
DR SMR; Q91Y74; -.
DR BioGRID; 203237; 1.
DR STRING; 10090.ENSMUSP00000034537; -.
DR CAZy; GT29; Glycosyltransferase Family 29.
DR GlyGen; Q91Y74; 4 sites.
DR iPTMnet; Q91Y74; -.
DR PhosphoSitePlus; Q91Y74; -.
DR EPD; Q91Y74; -.
DR MaxQB; Q91Y74; -.
DR PaxDb; Q91Y74; -.
DR PRIDE; Q91Y74; -.
DR ProteomicsDB; 257233; -.
DR Antibodypedia; 33000; 167 antibodies from 25 providers.
DR DNASU; 20443; -.
DR Ensembl; ENSMUST00000034537; ENSMUSP00000034537; ENSMUSG00000032038.
DR GeneID; 20443; -.
DR KEGG; mmu:20443; -.
DR UCSC; uc009osm.1; mouse.
DR CTD; 6484; -.
DR MGI; MGI:1316743; St3gal4.
DR VEuPathDB; HostDB:ENSMUSG00000032038; -.
DR eggNOG; KOG2692; Eukaryota.
DR GeneTree; ENSGT00940000158893; -.
DR HOGENOM; CLU_032020_1_0_1; -.
DR InParanoid; Q91Y74; -.
DR OMA; KSPPLCM; -.
DR OrthoDB; 891104at2759; -.
DR PhylomeDB; Q91Y74; -.
DR TreeFam; TF354325; -.
DR BRENDA; 2.4.99.2; 3474.
DR BRENDA; 2.4.99.6; 3474.
DR Reactome; R-MMU-2022854; Keratan sulfate biosynthesis.
DR Reactome; R-MMU-4085001; Sialic acid metabolism.
DR Reactome; R-MMU-9037629; Lewis blood group biosynthesis.
DR Reactome; R-MMU-975577; N-Glycan antennae elongation.
DR Reactome; R-MMU-977068; Termination of O-glycan biosynthesis.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 20443; 3 hits in 76 CRISPR screens.
DR ChiTaRS; St3gal4; mouse.
DR PRO; PR:Q91Y74; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q91Y74; protein.
DR Bgee; ENSMUSG00000032038; Expressed in ileal epithelium and 215 other tissues.
DR ExpressionAtlas; Q91Y74; baseline and differential.
DR Genevisible; Q91Y74; MM.
DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0003836; F:beta-galactoside (CMP) alpha-2,3-sialyltransferase activity; IDA:MGI.
DR GO; GO:0047288; F:monosialoganglioside sialyltransferase activity; ISO:MGI.
DR GO; GO:0008118; F:N-acetyllactosaminide alpha-2,3-sialyltransferase activity; IMP:UniProtKB.
DR GO; GO:0004513; F:neolactotetraosylceramide alpha-2,3-sialyltransferase activity; ISS:UniProtKB.
DR GO; GO:0008373; F:sialyltransferase activity; IBA:GO_Central.
DR GO; GO:0050890; P:cognition; ISO:MGI.
DR GO; GO:0009247; P:glycolipid biosynthetic process; ISO:MGI.
DR GO; GO:0009101; P:glycoprotein biosynthetic process; ISO:MGI.
DR GO; GO:0030259; P:lipid glycosylation; ISO:MGI.
DR GO; GO:0009312; P:oligosaccharide biosynthetic process; ISO:MGI.
DR GO; GO:0030194; P:positive regulation of blood coagulation; IMP:UniProtKB.
DR GO; GO:1903238; P:positive regulation of leukocyte tethering or rolling; IMP:UniProtKB.
DR GO; GO:0006486; P:protein glycosylation; IDA:MGI.
DR GO; GO:1990743; P:protein sialylation; ISO:MGI.
DR GO; GO:0097503; P:sialylation; ISO:MGI.
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; Signal-anchor; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..333
FT /note="CMP-N-acetylneuraminate-beta-galactosamide-alpha-
FT 2,3-sialyltransferase 4"
FT /id="PRO_0000149263"
FT TOPO_DOM 1..8
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 9..26
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 27..333
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT CARBOHYD 61
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 131
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 310
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 329
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 120..273
FT /evidence="ECO:0000250"
FT CONFLICT 131
FT /note="N -> T (in Ref. 1; CAA65076)"
FT /evidence="ECO:0000305"
FT CONFLICT 262
FT /note="G -> V (in Ref. 1; CAA65076)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 333 AA; 38058 MW; 4EAB2F09502B54F4 CRC64;
MTSKSHWKLL ALALVLVVVM VWYSISREDR YIEFFYFPIS EKKEPCFQGE AERQASKIFG
NRSREQPIFL QLKDYFWVKT PSTYELPFGT KGSEDLLLRV LAITSYSIPE SIKSLECRRC
VVVGNGHRLR NSSLGGVINK YDVVIRLNNA PVAGYEGDVG SKTTIRLFYP ESAHFDPKIE
NNPDTLLVLV AFKAMDFHWI ETILSDKKRV RKGFWKQPPL IWDVNPKQVR ILNPFFMEIA
ADKLLSLPIQ QPRKIKQKPT TGLLAITLAL HLCDLVHIAG FGYPDASNKK QTIHYYEQIT
LKSMAGSGHN VSQEAIAIKR MLEMGAVKNL TYF
