MGT5A_CRIGR
ID MGT5A_CRIGR Reviewed; 740 AA.
AC P97259; P70100; P70101;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A;
DE EC=2.4.1.155 {ECO:0000269|PubMed:8910328};
DE AltName: Full=Alpha-mannoside beta-1,6-N-acetylglucosaminyltransferase;
DE AltName: Full=GlcNAc-T V;
DE Short=GNT-V;
DE AltName: Full=Mannoside acetylglucosaminyltransferase 5;
DE AltName: Full=N-acetylglucosaminyl-transferase V;
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 Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LEC4 AND LEC4A, FUNCTION, CATALYTIC
RP ACTIVITY, PATHWAY, AND SUBCELLULAR LOCATION.
RX PubMed=8910328; DOI=10.1074/jbc.271.44.27462;
RA Weinstein J., Sundaram S., Wang X., Delgado D., Basu R., Stanley P.;
RT "A point mutation causes mistargeting of Golgi GlcNAc-TV in the Lec4A
RT Chinese hamster ovary glycosylation mutant.";
RL J. Biol. Chem. 271:27462-27469(1996).
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:8910328). Catalyzes an important step in the
CC biosynthesis of branched, complex-type N-glycans, such as those found
CC on EGFR, TGFR (TGF-beta receptor) and CDH2. Via its role in the
CC biosynthesis of complex N-glycans, plays an important role in the
CC activation of cellular signaling pathways, reorganization of the actin
CC cytoskeleton, cell-cell adhesion and cell migration. MGAT5-dependent
CC EGFR N-glycosylation enhances the interaction between EGFR and LGALS3
CC and thereby prevents rapid EGFR endocytosis and prolongs EGFR
CC signaling. Required for efficient interaction between TGFB1 and its
CC receptor. Enhances activation of intracellular signaling pathways by
CC several types of growth factors, including FGF2, PDGF, IGF, TGFB1 and
CC EGF. MGAT5-dependent CDH2 N-glycosylation inhibits CDH2-mediated
CC homotypic cell-cell adhesion and contributes to the regulation of
CC downstream signaling pathways. Promotes cell migration. Contributes to
CC the 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:8910328}.
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:8910328};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000269|PubMed:8910328}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:8910328}; 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 -!- 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}.
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DR EMBL; U62587; AAC52925.1; -; mRNA.
DR EMBL; U62588; AAC52926.1; -; mRNA.
DR RefSeq; XP_007613026.1; XM_007614836.2.
DR RefSeq; XP_016822211.1; XM_016966722.1.
DR RefSeq; XP_016822214.1; XM_016966725.1.
DR RefSeq; XP_016822216.1; XM_016966727.1.
DR AlphaFoldDB; P97259; -.
DR SMR; P97259; -.
DR STRING; 10029.XP_007622398.1; -.
DR CAZy; GT18; Glycosyltransferase Family 18.
DR PRIDE; P97259; -.
DR Ensembl; ENSCGRT00001027389; ENSCGRP00001023144; ENSCGRG00001021442.
DR GeneID; 100760162; -.
DR KEGG; cge:100760162; -.
DR CTD; 4249; -.
DR eggNOG; ENOG502QTNG; Eukaryota.
DR GeneTree; ENSGT00940000153470; -.
DR OMA; DGRRKHC; -.
DR OrthoDB; 179031at2759; -.
DR BRENDA; 2.4.1.155; 1309.
DR UniPathway; UPA00378; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0030144; F:alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase activity; IDA:UniProtKB.
DR GO; GO:0030145; F:manganese ion binding; ISS:UniProtKB.
DR GO; GO:0004864; F:protein phosphatase inhibitor activity; IEA:Ensembl.
DR GO; GO:1903614; P:negative regulation of protein tyrosine phosphatase activity; IEA:Ensembl.
DR GO; GO:0030335; P:positive regulation of cell migration; IEA:Ensembl.
DR GO; GO:1904894; P:positive regulation of receptor signaling pathway via STAT; IEA:Ensembl.
DR GO; GO:0018279; P:protein N-linked glycosylation via asparagine; IDA: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 Disulfide bond; Glycoprotein; Glycosyltransferase; Golgi apparatus;
KW Membrane; Secreted; Signal-anchor; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..740
FT /note="Alpha-1,6-mannosylglycoprotein 6-beta-N-
FT acetylglucosaminyltransferase A"
FT /id="PRO_0000080521"
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_0000445691"
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"
FT VARIANT 135..155
FT /note="DIINGVQEKCVLPPMDGYPHC -> VQHPNSIGWCCPHLEWVFPVS (in
FT LEC4; loss of activity)"
FT VARIANT 156..740
FT /note="Missing (in LEC4)"
FT VARIANT 188
FT /note="L -> R (in LEC4A; loss of activity)"
SQ SEQUENCE 740 AA; 84561 MW; DFAFCFBA7C172AE2 CRC64;
MAFFTPWKLS SQKLGFFLVT FGFIWGMMLL HFTIQQRTQP ESSSMLREQI LDLSKRYIKA
LAEENRNVVD GPYAGVMTAY DLKKTLAVLL DNILQRIGKL ESKVDNLVNG TGANSTNSTT
AVPSLVSLEK ISVADIINGV QEKCVLPPMD GYPHCEGKIK WMKDMWRSDP CYADYGVDGT
SCSFFIYLSE VENWCPRLPW RAKNPYEEAD HNSLAEIRTD FNILYSMMKK 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 CAFLNPKFSP
PKSSKNTDFF IGKPTLRELT SQHPYAEVFI GRPHVWTVDL NNREEVEDAV KAILNQKIEP
YMPYEFTCEG MLQRINAFIE KQDFCHGQVM WPPLSALQVK LAEPGQSCKQ VCQENQLICE
PSFFQHLNKE KDLLKYRVTC QSSELYKDIL VPSFYPKSKH CVLQGDLLLF SCAGAHPTHQ
RICPCRDFIK GQVALCKDCL
