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 //