OGT1_RABIT
ID OGT1_RABIT Reviewed; 1046 AA.
AC P81436; G1TCQ9;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 22-FEB-2012, sequence version 2.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase 110 kDa subunit;
DE EC=2.4.1.255 {ECO:0000269|PubMed:2137449};
DE AltName: Full=O-GlcNAc transferase subunit p110;
DE AltName: Full=O-linked N-acetylglucosamine transferase 110 kDa subunit;
DE Short=OGT;
GN Name=OGT;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Thorbecke;
RG The Genome Sequencing Platform;
RA Di Palma F., Heiman D., Young S., Gnerre S., Johnson J., Lander E.S.,
RA Lindblad-Toh K.;
RT "Genome Sequence of Oryctolagus cuniculus (European rabbit).";
RL Submitted (AUG-2009) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PROTEIN SEQUENCE OF 217-239 AND 958-971.
RC TISSUE=Blood;
RX PubMed=9083068; DOI=10.1074/jbc.272.14.9316;
RA Lubas W.A., Frank D.W., Krause M., Hanover J.A.;
RT "O-linked GlcNAc transferase is a conserved nucleocytoplasmic protein
RT containing tetratricopeptide repeats.";
RL J. Biol. Chem. 272:9316-9324(1997).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND PATHWAY.
RC TISSUE=Reticulocyte;
RX PubMed=2137449; DOI=10.1016/s0021-9258(19)39838-2;
RA Haltiwanger R.S., Holt G.D., Hart G.W.;
RT "Enzymatic addition of O-GlcNAc to nuclear and cytoplasmic proteins.
RT Identification of a uridine diphospho-N-acetylglucosamine:peptide beta-N-
RT acetylglucosaminyltransferase.";
RL J. Biol. Chem. 265:2563-2568(1990).
CC -!- FUNCTION: Catalyzes the transfer of a single N-acetylglucosamine from
CC UDP-GlcNAc to a serine or threonine residue (PubMed:2137449). Acts on
CC cytoplasmic and nuclear proteins resulting in their modification with a
CC beta-linked N-acetylglucosamine (O-GlcNAc). Glycosylates a large and
CC diverse number of proteins including histone H2B, AKT1, ATG4B, EZH2,
CC PFKL, KMT2E/MLL5, MAPT/TAU and HCFC1. Can regulate their cellular
CC processes via cross-talk between glycosylation and phosphorylation or
CC by affecting proteolytic processing. Probably by glycosylating
CC KMT2E/MLL5, stabilizes KMT2E/MLL5 by preventing its ubiquitination (By
CC similarity). Involved in insulin resistance in muscle and adipocyte
CC cells via glycosylating insulin signaling components and inhibiting the
CC 'Thr-308' phosphorylation of AKT1, enhancing IRS1 phosphorylation and
CC attenuating insulin signaling (By similarity). Involved in glycolysis
CC regulation by mediating glycosylation of 6-phosphofructokinase PFKL,
CC inhibiting its activity. Component of a THAP1/THAP3-HCFC1-OGT complex
CC that is required for the regulation of the transcriptional activity of
CC RRM1. Plays a key role in chromatin structure by mediating O-
CC GlcNAcylation of 'Ser-112' of histone H2B: recruited to CpG-rich
CC transcription start sites of active genes via its interaction with TET
CC proteins (TET1, TET2 or TET3). As part of the NSL complex indirectly
CC involved in acetylation of nucleosomal histone H4 on several lysine
CC residues. O-GlcNAcylation of 'Ser-75' of EZH2 increases its stability,
CC and facilitating the formation of H3K27me3 by the PRC2/EED-EZH2
CC complex. Regulates circadian oscillation of the clock genes and glucose
CC homeostasis in the liver. Stabilizes clock proteins ARNTL/BMAL1 and
CC CLOCK through O-glycosylation, which prevents their ubiquitination and
CC subsequent degradation. Promotes the CLOCK-ARNTL/BMAL1-mediated
CC transcription of genes in the negative loop of the circadian clock such
CC as PER1/2 and CRY1/2. O-glycosylates HCFC1 and regulates its
CC proteolytic processing and transcriptional activity (By similarity).
CC Regulates mitochondrial motility in neurons by mediating glycosylation
CC of TRAK1 (By similarity). Glycosylates HOXA1 (By similarity). O-
CC glycosylates FNIP1 (By similarity). Promotes autophagy by mediating O-
CC glycosylation of ATG4B (By similarity). {ECO:0000250|UniProtKB:O15294,
CC ECO:0000250|UniProtKB:P56558, ECO:0000250|UniProtKB:Q8CGY8,
CC ECO:0000269|PubMed:2137449}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-seryl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = 3-O-(N-
CC acetyl-beta-D-glucosaminyl)-L-seryl-[protein] + H(+) + UDP;
CC Xref=Rhea:RHEA:48904, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:12251,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:57705,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:90838; EC=2.4.1.255;
CC Evidence={ECO:0000305|PubMed:2137449};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-threonyl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = 3-O-
CC (N-acetyl-beta-D-glucosaminyl)-L-threonyl-[protein] + H(+) + UDP;
CC Xref=Rhea:RHEA:48908, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:12252,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:57705,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:90840; EC=2.4.1.255;
CC Evidence={ECO:0000305|PubMed:2137449};
CC -!- ACTIVITY REGULATION: Inhibited by UDP. {ECO:0000269|PubMed:2137449}.
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000269|PubMed:2137449}.
CC -!- SUBUNIT: Homotrimer, oligomerizes via TPR repeats 6 and 7.
CC Trimerization is not necessary for activity in vitro, however it
CC increases affinity for UDP-GlcNAc (By similarity). Component of a
CC THAP1/THAP3-HCFC1-OGT complex. Component of the NSL complex at least
CC composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT,
CC WDR5 and HCFC1. Interacts directly with HCFC1; the interaction O-
CC glycosylates HCFC1, regulates its proteolytic processing and
CC transcriptional activity and, in turn, stabilizes OGT in the nucleus.
CC Interacts (via TPRs 1-6) with SIN3A; the interaction mediates
CC transcriptional repression in parallel with histone deacetylase.
CC Interacts (via TPR 5-6) with TET1, TET2 and TET3 (By similarity).
CC Interacts (via TPR repeats 6 and 7) with ATXN10 (By similarity).
CC Interacts with histone H2B (By similarity). Interacts with ARNTL/BMAL1.
CC Found in a complex composed of at least SINHCAF, SIN3A, HDAC1, SAP30,
CC RBBP4, OGT and TET1. Interacts with SINHCAF (By similarity). Component
CC of a complex composed of KMT2E/MLL5, OGT and USP7; the complex
CC stabilizes KMT2E/MLL5, preventing KMT2E/MLL5 ubiquitination and
CC proteosomal-mediated degradation. Interacts (via TRP repeats) with
CC KMT2E/MLL5 (via N-terminus). Interacts with USP7. Interacts with TRAK1;
CC this interaction is not required for glycosylation of TRAK1 by this
CC protein. Found in a complex with KIF5B, RHOT1, RHOT2 and TRAK1 (By
CC similarity). Interacts (via TPR repeats domain) with HOXA1; the
CC interaction takes place mainly in the nucleus (By similarity).
CC Interacts with NSD2 (By similarity). {ECO:0000250|UniProtKB:O15294,
CC ECO:0000250|UniProtKB:P56558, ECO:0000250|UniProtKB:Q8CGY8}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O15294}. Nucleus
CC {ECO:0000250|UniProtKB:O15294}. Cell membrane
CC {ECO:0000250|UniProtKB:O15294}. Mitochondrion membrane
CC {ECO:0000250|UniProtKB:P56558}. Cell projection
CC {ECO:0000250|UniProtKB:P56558}. Note=Mostly in the nucleus. Retained in
CC the nucleus via interaction with HCFC1. After insulin induction,
CC translocated from the nucleus to the cell membrane via
CC phosphatidylinositide binding. Colocalizes with AKT1 at the plasma
CC membrane (By similarity). TRAK1 recruits this protein to mitochondria.
CC In the absence of TRAK1, localizes in cytosol and nucleus (By
CC similarity). {ECO:0000250|UniProtKB:O15294,
CC ECO:0000250|UniProtKB:P56558}.
CC -!- DOMAIN: The TPR repeat domain is required for substrate binding and
CC oligomerization. {ECO:0000250|UniProtKB:O15294}.
CC -!- PTM: Ubiquitinated, leading to its proteasomal degradation.
CC {ECO:0000250}.
CC -!- PTM: Phosphorylation on Ser-3 or Ser-4 by GSK3-beta positively
CC regulates its activity. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 41 family. O-GlcNAc
CC transferase subfamily. {ECO:0000305}.
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DR RefSeq; XP_002720149.1; XM_002720103.3.
DR AlphaFoldDB; P81436; -.
DR SMR; P81436; -.
DR STRING; 9986.ENSOCUP00000014582; -.
DR Ensembl; ENSOCUT00000016973; ENSOCUP00000014582; ENSOCUG00000016965.
DR GeneID; 100354727; -.
DR KEGG; ocu:100354727; -.
DR CTD; 8473; -.
DR eggNOG; KOG1124; Eukaryota.
DR eggNOG; KOG4626; Eukaryota.
DR GeneTree; ENSGT00940000155085; -.
DR HOGENOM; CLU_001721_1_0_1; -.
DR InParanoid; P81436; -.
DR OMA; HAYSEKL; -.
DR OrthoDB; 142546at2759; -.
DR TreeFam; TF105785; -.
DR UniPathway; UPA00378; -.
DR Proteomes; UP000001811; Chromosome X.
DR Bgee; ENSOCUG00000016965; Expressed in upper lobe of left lung and 14 other tissues.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-SubCell.
DR GO; GO:0000123; C:histone acetyltransferase complex; ISS:UniProtKB.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0017122; C:protein N-acetylglucosaminyltransferase complex; IDA:UniProtKB.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; ISS:UniProtKB.
DR GO; GO:0016262; F:protein N-acetylglucosaminyltransferase activity; ISS:UniProtKB.
DR GO; GO:0097363; F:protein O-GlcNAc transferase activity; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; ISS:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0080182; P:histone H3-K4 trimethylation; ISS:UniProtKB.
DR GO; GO:0043984; P:histone H4-K16 acetylation; ISS:UniProtKB.
DR GO; GO:0043981; P:histone H4-K5 acetylation; ISS:UniProtKB.
DR GO; GO:0043982; P:histone H4-K8 acetylation; ISS:UniProtKB.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; ISS:UniProtKB.
DR GO; GO:0061087; P:positive regulation of histone H3-K27 methylation; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0006493; P:protein O-linked glycosylation; ISS:UniProtKB.
DR GO; GO:0016485; P:protein processing; ISS:UniProtKB.
DR GO; GO:0006111; P:regulation of gluconeogenesis; ISS:UniProtKB.
DR GO; GO:0006110; P:regulation of glycolytic process; ISS:UniProtKB.
DR Gene3D; 1.25.40.10; -; 2.
DR InterPro; IPR037919; OGT.
DR InterPro; IPR029489; OGT/SEC/SPY_C.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR001440; TPR_1.
DR InterPro; IPR019734; TPR_repeat.
DR PANTHER; PTHR44366; PTHR44366; 1.
DR Pfam; PF13844; Glyco_transf_41; 1.
DR Pfam; PF00515; TPR_1; 2.
DR Pfam; PF13181; TPR_8; 2.
DR SMART; SM00028; TPR; 12.
DR SUPFAM; SSF48452; SSF48452; 2.
DR PROSITE; PS50005; TPR; 12.
DR PROSITE; PS50293; TPR_REGION; 1.
PE 1: Evidence at protein level;
KW Acetylation; Biological rhythms; Cell membrane; Cell projection;
KW Chromatin regulator; Cytoplasm; Direct protein sequencing; Glycoprotein;
KW Glycosyltransferase; Lipid-binding; Membrane; Mitochondrion; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; TPR repeat; Transferase;
KW Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O15294"
FT CHAIN 2..1046
FT /note="UDP-N-acetylglucosamine--peptide N-
FT acetylglucosaminyltransferase 110 kDa subunit"
FT /id="PRO_0000191773"
FT REPEAT 21..54
FT /note="TPR 1"
FT REPEAT 89..122
FT /note="TPR 2"
FT REPEAT 123..156
FT /note="TPR 3"
FT REPEAT 157..190
FT /note="TPR 4"
FT REPEAT 191..224
FT /note="TPR 5"
FT REPEAT 225..258
FT /note="TPR 6"
FT REPEAT 259..292
FT /note="TPR 7"
FT REPEAT 293..326
FT /note="TPR 8"
FT REPEAT 327..360
FT /note="TPR 9"
FT REPEAT 361..394
FT /note="TPR 10"
FT REPEAT 395..428
FT /note="TPR 11"
FT REPEAT 429..462
FT /note="TPR 12"
FT REPEAT 463..473
FT /note="TPR 13; truncated"
FT REGION 991..1010
FT /note="Required for phosphatidylinositol 3,4,5-triphosphate
FT binding"
FT /evidence="ECO:0000250"
FT MOTIF 487..503
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT ACT_SITE 508
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:O15294"
FT BINDING 849
FT /ligand="UDP"
FT /ligand_id="ChEBI:CHEBI:58223"
FT /evidence="ECO:0000250|UniProtKB:O15294"
FT BINDING 852
FT /ligand="UDP"
FT /ligand_id="ChEBI:CHEBI:58223"
FT /evidence="ECO:0000250|UniProtKB:O15294"
FT BINDING 906..908
FT /ligand="UDP"
FT /ligand_id="ChEBI:CHEBI:58223"
FT /evidence="ECO:0000250|UniProtKB:O15294"
FT BINDING 911..914
FT /ligand="UDP"
FT /ligand_id="ChEBI:CHEBI:58223"
FT /evidence="ECO:0000250|UniProtKB:O15294"
FT BINDING 930..932
FT /ligand="UDP"
FT /ligand_id="ChEBI:CHEBI:58223"
FT /evidence="ECO:0000250|UniProtKB:O15294"
FT BINDING 935
FT /ligand="UDP"
FT /ligand_id="ChEBI:CHEBI:58223"
FT /evidence="ECO:0000250|UniProtKB:O15294"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:O15294"
FT MOD_RES 3
FT /note="Phosphoserine; by GSK3-beta; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8CGY8"
FT MOD_RES 4
FT /note="Phosphoserine; by GSK3-beta; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8CGY8"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15294"
FT MOD_RES 989
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P56558"
FT CARBOHYD 3
FT /note="O-linked (GlcNAc) serine; alternate"
FT /evidence="ECO:0000250"
FT CARBOHYD 4
FT /note="O-linked (GlcNAc) serine; alternate"
FT /evidence="ECO:0000250"
SQ SEQUENCE 1046 AA; 116939 MW; 6A31D68BDDF1380E CRC64;
MASSVGNVAD STEPTKRMLS FQGLAELAHR EYQAGDFEAA ERHCMQLWRQ EPDNTGVLLL
LSSIHFQCRR LDRSAHFSTL AIKQNPLLAE AYSNLGNVYK ERGQLQEAIE HYRHALRLKP
DFIDGYINLA AALVAAGDME GAVQAYVSAL QYNPDLYCVR SDLGNLLKAL GRLEEAKACY
LKAIETQPNF AVAWSNLGCV FNAQGEIWLA IHHFEKAVTL DPNFLDAYIN LGNVLKEARI
FDRAVAAYLR ALSLSPNHAV VHGNLACVYY EQGLIDLAID TYRRAIELQP HFPDAYCNLA
NALKEKGSVA EAEDCYNTAL RLCPTHADSL NNLANIKREQ GNIEEAVRLY RKALEVFPEF
AAAHSNLASV LQQQGKLQEA LMHYKEAIRI SPTFADAYSN MGNTLKEMQD VQGALQCYTR
AIQINPAFAD AHSNLASIHK DSGNIPEAIA SYRTALKLKP DFPDAYCNLA HCLQIVCDWT
DYDERMKKLV SIVADQLEKN RLPSVHPHHS MLYPLSHGFR KAIAERHGNL CLDKINVLHK
PPYEHPKDLK LSDGRLRVGY VSSDFGNHPT SHLMQSIPGM HNPDKFEVFC YALSPDDGTN
FRVKVMAEAN HFIDLSQIPC NGKAADRIHQ DGIHILVNMN GYTKGARNEL FALRPAPIQA
MWLGYPGTSG ALFMDYIITD QETSPAEVAE QYSEKLAYMP HTFFIGDHAN MFPHLKKKAV
IDFKSNGHIY DNRIVLNGID LKAFLDSLPD VKIVKMKCPD GGDNADSSNT ALNMPVIPMN
TIAEAVIEMI NRGQIQITIN GFSISNGLAT TQINNKAATG EEVPRTIIVT TRSQYGLPED
AIVYCNFNQL YKIDPSTLQM WANILKRVPN SVLWLLRFPA VGEPNIQQYA QNMGLPQNRI
IFSPVAPKEE HVRRGQLADV CLDTPLCNGH TTGMDVLWAG TPMVTMPGET LASRVAASQL
TCLGCLELIA KNRQEYEDIA VKLGTDLEYL KKIRGKVWKQ RISSPLFNTK QYTMELERLY
LQMWEHYAAG NKPDHMIKPV EVTESA
