MGT5A_RAT
ID MGT5A_RAT Reviewed; 740 AA.
AC Q08834;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A;
DE EC=2.4.1.155 {ECO:0000269|PubMed:7615638, ECO:0000269|PubMed:8340368};
DE AltName: Full=Alpha-mannoside beta-1,6-N-acetylglucosaminyltransferase;
DE AltName: Full=GlcNAc-T V {ECO:0000303|PubMed:7615638, ECO:0000303|PubMed:8340368};
DE Short=GNT-V;
DE AltName: Full=Mannoside acetylglucosaminyltransferase 5;
DE AltName: Full=N-acetylglucosaminyl-transferase V {ECO:0000303|PubMed:8340368};
DE Contains:
DE RecName: Full=Secreted alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A {ECO:0000305};
DE AltName: Full=Secreted beta-1,6-N-acetylglucosaminyltransferase V {ECO:0000305};
DE Short=Secreted GNT-V {ECO:0000305};
DE Flags: Precursor;
GN Name=Mgat5;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 375-386; 546-557 AND
RP 592-607, FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=8340368; DOI=10.1016/s0021-9258(18)82268-2;
RA Shoreibah M., Perng G.-S., Adler B., Weinstein J., Basu R., Cupples R.,
RA Wen D., Browne J.K., Buckhaults P., Fregien N., Pierce M.;
RT "Isolation, characterization, and expression of a cDNA encoding N-
RT acetylglucosaminyltransferase V.";
RL J. Biol. Chem. 268:15381-15385(1993).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=7615638; DOI=10.1083/jcb.130.2.383;
RA Demetriou M., Nabi I.R., Coppolino M., Dedhar S., Dennis J.W.;
RT "Reduced contact-inhibition and substratum adhesion in epithelial cells
RT expressing GlcNAc-transferase V.";
RL J. Cell Biol. 130:383-392(1995).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
CC -!- FUNCTION: Catalyzes the addition of N-acetylglucosamine (GlcNAc) in
CC beta 1-6 linkage to the alpha-linked mannose of biantennary N-linked
CC oligosaccharides (PubMed:8340368, PubMed:7615638). Catalyzes an
CC important step in the biosynthesis of branched, complex-type N-glycans,
CC such as those found on EGFR, TGFR (TGF-beta receptor) and CDH2 (By
CC similarity). Via its role in the biosynthesis of complex N-glycans,
CC plays an important role in the activation of cellular signaling
CC pathways, reorganization of the actin cytoskeleton, cell-cell adhesion
CC and cell migration (PubMed:7615638). MGAT5-dependent EGFR N-
CC glycosylation enhances the interaction between EGFR and LGALS3 and
CC thereby prevents rapid EGFR endocytosis and prolongs EGFR signaling.
CC Required for efficient interaction between TGFB1 and its receptor.
CC Enhances activation of intracellular signaling pathways by several
CC types of growth factors, including FGF2, PDGF, IGF, TGFB1 and EGF.
CC MGAT5-dependent CDH2 N-glycosylation inhibits CDH2-mediated homotypic
CC cell-cell adhesion and contributes to the regulation of downstream
CC signaling pathways. Promotes cell migration. Contributes to the
CC regulation of the inflammatory response. MGAT5-dependent TCR N-
CC glycosylation enhances the interaction between TCR and LGALS3, limits
CC agonist-induced TCR clustering, and thereby dampens TCR-mediated
CC responses to antigens. Required for normal leukocyte evasation and
CC accumulation at sites of inflammation (By similarity). Inhibits
CC attachment of monocytes to the vascular endothelium and subsequent
CC monocyte diapedesis (By similarity). {ECO:0000250|UniProtKB:Q09328,
CC ECO:0000250|UniProtKB:Q8R4G6, ECO:0000269|PubMed:7615638,
CC ECO:0000269|PubMed:8340368}.
CC -!- FUNCTION: [Secreted alpha-1,6-mannosylglycoprotein 6-beta-N-
CC acetylglucosaminyltransferase A]: Promotes proliferation of umbilical
CC vein endothelial cells and angiogenesis, at least in part by promoting
CC the release of the growth factor FGF2 from the extracellular matrix.
CC {ECO:0000250|UniProtKB:Q09328}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(4)-{beta-D-GlcNAc-(1->2)-[beta-D-GlcNAc-(1->4)]-alpha-D-Man-
CC (1->3)-[beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-
CC beta-D-GlcNAcl-(1->4)-beta-D-GlcNAc}-L-asparaginyl-[protein] + UDP-N-
CC acetyl-alpha-D-glucosamine = H(+) + N(4)-{beta-D-GlcNAc-(1->2)-[beta-
CC D-GlcNAc-(1->4)]-alpha-D-Man-(1->3)-[beta-D-GlcNAc-(1->2)-[beta-D-
CC GlcNAc-(1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAcl-
CC (1->4)-beta-D-GlcNAc}-L-asparaginyl-[protein] + UDP;
CC Xref=Rhea:RHEA:16921, Rhea:RHEA-COMP:14374, Rhea:RHEA-COMP:14377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57705, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:139507, ChEBI:CHEBI:139510; EC=2.4.1.155;
CC Evidence={ECO:0000269|PubMed:7615638, ECO:0000269|PubMed:8340368};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000269|PubMed:7615638, ECO:0000269|PubMed:8340368}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:P97259}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q09328}.
CC -!- SUBCELLULAR LOCATION: [Secreted alpha-1,6-mannosylglycoprotein 6-beta-
CC N-acetylglucosaminyltransferase A]: Secreted
CC {ECO:0000250|UniProtKB:Q09328}.
CC -!- TISSUE SPECIFICITY: Detected in kidney (at protein level). Detected in
CC kidney. {ECO:0000269|PubMed:8340368}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q09328}.
CC -!- PTM: A secreted form is released from the membrane after cleavage by
CC gamma-secretase. {ECO:0000250|UniProtKB:Q09328}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 18 family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; L14284; AAA41665.1; -; mRNA.
DR PIR; A47134; A47134.
DR RefSeq; NP_075583.1; NM_023095.1.
DR RefSeq; XP_008767721.2; XM_008769499.2.
DR RefSeq; XP_017454423.1; XM_017598934.1.
DR AlphaFoldDB; Q08834; -.
DR SMR; Q08834; -.
DR STRING; 10116.ENSRNOP00000004995; -.
DR ChEMBL; CHEMBL1795132; -.
DR CAZy; GT18; Glycosyltransferase Family 18.
DR GlyGen; Q08834; 6 sites.
DR iPTMnet; Q08834; -.
DR PhosphoSitePlus; Q08834; -.
DR PaxDb; Q08834; -.
DR PRIDE; Q08834; -.
DR Ensembl; ENSRNOT00000004995; ENSRNOP00000004995; ENSRNOG00000003614.
DR GeneID; 65271; -.
DR KEGG; rno:65271; -.
DR UCSC; RGD:620100; rat.
DR CTD; 4249; -.
DR RGD; 620100; Mgat5.
DR eggNOG; ENOG502QTNG; Eukaryota.
DR GeneTree; ENSGT00940000153470; -.
DR HOGENOM; CLU_016749_1_0_1; -.
DR InParanoid; Q08834; -.
DR OMA; DGRRKHC; -.
DR OrthoDB; 179031at2759; -.
DR PhylomeDB; Q08834; -.
DR TreeFam; TF313714; -.
DR BRENDA; 2.4.1.155; 5301.
DR Reactome; R-RNO-975577; N-Glycan antennae elongation.
DR UniPathway; UPA00378; -.
DR PRO; PR:Q08834; -.
DR Proteomes; UP000002494; Chromosome 13.
DR Bgee; ENSRNOG00000003614; Expressed in frontal cortex and 18 other tissues.
DR ExpressionAtlas; Q08834; baseline and differential.
DR Genevisible; Q08834; RN.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD.
DR GO; GO:0000139; C:Golgi membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0008375; F:acetylglucosaminyltransferase activity; ISO:RGD.
DR GO; GO:0030144; F:alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase activity; ISS:UniProtKB.
DR GO; GO:0016757; F:glycosyltransferase activity; ISO:RGD.
DR GO; GO:0030145; F:manganese ion binding; ISS:UniProtKB.
DR GO; GO:0004864; F:protein phosphatase inhibitor activity; ISO:RGD.
DR GO; GO:1903614; P:negative regulation of protein tyrosine phosphatase activity; ISO:RGD.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD.
DR GO; GO:1904894; P:positive regulation of receptor signaling pathway via STAT; ISO:RGD.
DR GO; GO:0006487; P:protein N-linked glycosylation; ISO:RGD.
DR GO; GO:0018279; P:protein N-linked glycosylation via asparagine; ISS:UniProtKB.
DR InterPro; IPR027833; DUF4525.
DR InterPro; IPR026116; GlyclTrfase_18.
DR Pfam; PF15027; DUF4525; 1.
DR Pfam; PF15024; Glyco_transf_18; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Glycosyltransferase; Golgi apparatus; Membrane; Reference proteome;
KW Secreted; Signal-anchor; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..740
FT /note="Alpha-1,6-mannosylglycoprotein 6-beta-N-
FT acetylglucosaminyltransferase A"
FT /id="PRO_0000080524"
FT CHAIN 31..740
FT /note="Secreted alpha-1,6-mannosylglycoprotein 6-beta-N-
FT acetylglucosaminyltransferase A"
FT /evidence="ECO:0000250|UniProtKB:Q09328"
FT /id="PRO_0000445694"
FT TOPO_DOM 1..13
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 14..30
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 31..740
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 212..740
FT /note="Sufficient for catalytic activity"
FT /evidence="ECO:0000250|UniProtKB:Q09328"
FT BINDING 377..378
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q09328"
FT BINDING 525
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000250|UniProtKB:Q09328"
FT BINDING 553
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q09328"
FT CARBOHYD 109
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 114
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 117
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 333
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 432
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 446
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 144..182
FT /evidence="ECO:0000250|UniProtKB:Q09328"
FT DISULFID 155..195
FT /evidence="ECO:0000250|UniProtKB:Q09328"
FT DISULFID 171..337
FT /evidence="ECO:0000250|UniProtKB:Q09328"
FT DISULFID 371..625
FT /evidence="ECO:0000250|UniProtKB:Q09328"
FT DISULFID 648..723
FT /evidence="ECO:0000250|UniProtKB:Q09328"
FT DISULFID 652..725
FT /evidence="ECO:0000250|UniProtKB:Q09328"
FT DISULFID 659..712
FT /evidence="ECO:0000250|UniProtKB:Q09328"
FT DISULFID 680..701
FT /evidence="ECO:0000250|UniProtKB:Q09328"
FT DISULFID 736..739
FT /evidence="ECO:0000250|UniProtKB:Q09328"
SQ SEQUENCE 740 AA; 84562 MW; C0BD7F820FEA959C CRC64;
MAFFSPWKLS SQKLGFFLVT FGFIWGMMLL HFTIQQRTQP ESSSMLREQI LDLSKRYIKA
LAEENRNVVD GPYAGVMTAY DLKKTLAVLL DNILQRIGKL ESKVDNLVNG TGANSTNSTT
AVPSLVSLEK INVADIINGV QEKCVLPPMD GYPHCEGKIK WMKDMWRSDP CYADYGVDGT
SCSFFIYLSE VENWCPRLPW RAKNPYEEAD HNSLAEIRTD FNILYGMMKK HEEFRWMRLR
IRRMADAWIQ AIKSLAEKQN LEKRKRKKIL VHLGLLTKES GFKIAETAFS GGPLGELVQW
SDLITSLYLL GHDIRISASL AELKEIMKKV VGNRSGCPTV GDRIVELIYI DIVGLAQFKK
TLGPSWVHYQ CMLRVLDSFG TEPEFNHASY AQSKGHKTPW GKWNLNPQQF YTMFPHTPDN
SFLGFVVEQH LNSSDIHHIN EIKRQNQSLV YGKVDSFWKN KKIYLDIIHT YMEVHATVYG
SSTKNIPSYV KNHGILSGRD LQFLLRETKL FVGLGFPYEG PAPLEAIANG CAFLNPKFNP
PKSSKNTDFF IGKPTLRELT SQHPYAEVFI GRPHVWTVDL NNREEVEDAV KAILNQKIEP
YMPYEFTCEG MLQRINAFIE KQDFCHGQVM WPPLSALQVK LAEPGQSCKQ VCQESQLICE
PSFFQHLNKE KDLLKYKVIC QSSELYKDIL VPSFYPKSKH CVFQGDLLLF SCAGAHPTHQ
RICPCRDFIK GQVALCKDCL
