Bifunctional protein NCOAT - Rattus norvegicus (Rat)

Preferred order of sections

Names and origin

Protein names

Recommended name:
Bifunctional protein NCOAT

Alternative name(s):
Meningioma-expressed antigen 5
Nuclear cytoplasmic O-GlcNAcase and acetyltransferase

Including the following 2 domains:

Beta-hexosaminidase
EC=3.2.1.52
Alternative name(s):
Beta-N-acetylhexosaminidase
Hexosaminidase C
N-acetyl-beta-D-glucosaminidase
N-acetyl-beta-glucosaminidase
O-GlcNAcase
Histone acetyltransferase
Short name=HAT
EC=2.3.1.48

Gene names

Name:	Mgea5
Synonyms:	Hexc, Mea5

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	916 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Possesses hyaluronidase activity By similarity. Cleaves GlcNAc but not GalNAc from glycopeptides. Can use p-nitrophenyl-beta-GlcNAc as substrate but not p-nitrophenyl-beta-GalNAc or p-nitrophenyl-alpha-GlcNAc. Acetylates 'Lys-8' of histone H4 and 'Lys-14' of histone H3. Ref.2 Ref.3
Catalytic activity	Hydrolysis of terminal non-reducing N-acetyl-D-hexosamine residues in N-acetyl-beta-D-hexosaminides. Acetyl-CoA + [histone] = CoA + acetyl-[histone].
Enzyme regulation	Inhibited by Cu²⁺, Hg²⁺, Cd²⁺ and Zn²⁺ at 1 mM. Not inhibited by Co²⁺, Mg²⁺, Ca²⁺, Mn²⁺, Fe³⁺ and EDTA. Also inhibited by sodium chloride at 1M and 2-amino-2-hydroxymethyl-1,3-propanediol (trishydroxymethylaminomethane) at 75mM. Ref.3
Subunit structure	Monomer. Binds both acetylated and unacetylated histone H4 tail but acetylation on 'Lys-8' of histone H4 abolishes binding By similarity. According to Ref.3 it is a heterodimer of an alpha and beta chain. Ref.3
Subcellular location	Nucleus. Cytoplasm Ref.3.
Tissue specificity	Ubiquitous. Expressed at highest levels in the brain and spleen. Ref.3
Post-translational modification	Proteolytically cleaved by caspase-3 By similarity.
Biophysicochemical properties	Kinetic parameters: K_M=2.55 mM for pNP-O-GLcNAc Ref.3 pH dependence: Optimum pH is 6.4. Activity decreases sharply at pH below 5.0. Temperature dependence: Optimum temperature is 37 degrees Celsius. Less active at room temperature and shows very little activity at 4 degrees Celsius. Loses activity at 57 degrees Celsius within 5 minutes.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Molecular function	Acyltransferase Glycosidase Hydrolase Transferase
PTM	Disulfide bond Phosphoprotein
Technical term	Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	N-acetylglucosamine metabolic process Inferred from mutant phenotype PubMed 19139380. Source: RGD aging Inferred from expression pattern PubMed 18185980. Source: RGD dATP metabolic process Inferred from mutant phenotype PubMed 17573462. Source: RGD necrotic cell death Inferred from mutant phenotype PubMed 16899550. Source: RGD negative regulation of cardiac muscle adaptation Inferred from mutant phenotype PubMed 17573462. Source: RGD negative regulation of protein glycosylation Inferred from mutant phenotype PubMed 16332679. Source: RGD positive regulation of DNA metabolic process Inferred from mutant phenotype PubMed 19139380. Source: RGD positive regulation of calcium ion transport into cytosol Inferred from mutant phenotype PubMed 16107505. Source: RGD positive regulation of cell killing Inferred from mutant phenotype PubMed 19139380. Source: RGD positive regulation of glucose import Inferred from mutant phenotype PubMed 16000877. Source: RGD positive regulation of growth hormone secretion Inferred from mutant phenotype PubMed 12242036. Source: RGD positive regulation of insulin secretion Inferred from mutant phenotype PubMed 17095531. Source: RGD positive regulation of mitochondrial depolarization Inferred from mutant phenotype PubMed 19139380. Source: RGD positive regulation of protein complex disassembly Inferred from mutant phenotype PubMed 17573462. Source: RGD positive regulation of proteolysis Inferred from mutant phenotype PubMed 17573462. Source: RGD protein targeting to membrane Inferred from mutant phenotype PubMed 16000877. Source: RGD response to steroid hormone stimulus Inferred from expression pattern PubMed 19139380. Source: RGD
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	beta-N-acetylhexosaminidase activity Inferred from electronic annotation. Source: EC histone acetyltransferase activity Inferred from mutant phenotype Ref.2. Source: RGD
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8VIJ5-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8VIJ5-2) The sequence of this isoform differs from the canonical sequence as follows: 250-398: Missing.
Note: Lack hexosaminidase activity.

Isoform 3 (identifier: Q8VIJ5-3) The sequence of this isoform differs from the canonical sequence as follows: 250-345: Missing.
Note: Lack hexosaminidase activity.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 916

916

Bifunctional protein NCOAT

PRO_0000252120

Regions

Region

583 – 916

334

Histone acetyltransferase activity

Region

695 – 814

120

Required for histone H4 binding By similarity

Sites

Active site

175

1

Nucleophile; for O-GlcNAcase activity By similarity

Active site

177

1

Proton donor; for O-GlcNAcase activity By similarity

Amino acid modifications

Modified residue

364

1

Phosphoserine By similarity

Disulfide bond

777 ↔ 793

By similarity

Natural variations

Alternative sequence

250 – 398

149

Missing in isoform 2.

VSP_020873

Alternative sequence

250 – 345

96

Missing in isoform 3.

VSP_020874

Experimental info

Mutagenesis

853

1

D → N: Loss of histone acetyltransferase activity. Ref.2

Mutagenesis

884

1

D → N: Loss of histone acetyltransferase activity. Ref.2

Mutagenesis

891

1

Y → F: Loss of histone acetyltransferase activity. Ref.2

Sequences

Sequence		Length	Mass (Da)
Isoform 1 [UniParc]. Last modified March 1, 2002. Version 1. Checksum: 4BA1746F0AF2E380 Show »	FASTA	916	102,918
10 20 30 40 50 60 MVQKESQAAL EERESERNAN PASVSGASLE PSAAPAPGED NPSGAGAAAG TGAAGGARRF 70 80 90 100 110 120 LCGVVEGFYG RPWVMEQRKE LFRRLQKWEL NTYLYAPKDD YKHRMFWREM YSVEEAEQLM 130 140 150 160 170 180 TLISAAREYE IEFIYAISPG LDITFSNPKE VSTLKRKLDQ VSQFGCRSFA LLFDDIDHNM 190 200 210 220 230 240 CAADKEVFSS FAHAQVSITN EIYQYLGEPE TFLFCPTEYC GTFCYPSVSQ SPYLRTVGEK 250 260 270 280 290 300 LLPGIEVLWT GPKVVSKEIP VESIEEVSKI IKRAPVIWDN IHANDYDQKR LFLGPYKGRS 310 320 330 340 350 360 TELIPRLKGV LTNPNCEFEA NYVAIHTLAT WYKSNMNGVR KDVVMTDSED STVSIQIKLE 370 380 390 400 410 420 NEGSDEDIET DVLYSPQMAL KLALTEWLQE FGVPHQYSSR QVAHSGAKTS VVDGTPLVAA 430 440 450 460 470 480 PSLNATTVVT TVYQEPIMSQ GAALSGEPSA LTKEEEKKQP DEEPMDMVVE KQEESEHKSD 490 500 510 520 530 540 NQILTEIVEA KMAEELKPMD TDKESIAESK SPEMSMQEDC INDIAPMQTD EQANKEQFVP 550 560 570 580 590 600 GPNEKPLYAA EPVTLEDLQL LADLFYLPYE HGPKGAQMLR EFQWLRANSS VVSVNCKGKD 610 620 630 640 650 660 SEKIEEWRSR AAKFEEMCAL VMGMFTRLSN CANRTILYDM YSYVWDIKSI MSMVKSFVQW 670 680 690 700 710 720 LGCRSHSSAQ FLIGDQEPWA FRGGLAGEFQ RLLPIDGAND LFFQPPPLTP TSKVYTIRPY 730 740 750 760 770 780 FPKDEASVYK ICREMYDDGV GLPFQSQPDL IGDKLVGGLL SLSLDYCFVL EDEDGICGYA 790 800 810 820 830 840 LGTVDVTPFI KKCKISWIPF MQEKYTKPNG DKELSEAEKI MLSFHEEQEV LPETFLANFP 850 860 870 880 890 900 SLIKMDIHKK VTDPSVAKSM MACLLSSLKA NGSRGAFCEV RPDDKRILEF YSKLGCFEIA 910 KMEGFPKDVV ILGRSL « Hide
Isoform 2 [UniParc]. Checksum: 7DD1EF0F9D55E766 Show »	FASTA	767	86,010
10 20 30 40 50 60 MVQKESQAAL EERESERNAN PASVSGASLE PSAAPAPGED NPSGAGAAAG TGAAGGARRF 70 80 90 100 110 120 LCGVVEGFYG RPWVMEQRKE LFRRLQKWEL NTYLYAPKDD YKHRMFWREM YSVEEAEQLM 130 140 150 160 170 180 TLISAAREYE IEFIYAISPG LDITFSNPKE VSTLKRKLDQ VSQFGCRSFA LLFDDIDHNM 190 200 210 220 230 240 CAADKEVFSS FAHAQVSITN EIYQYLGEPE TFLFCPTEYC GTFCYPSVSQ SPYLRTVGEK 250 260 270 280 290 300 LLPGIEVLWS RQVAHSGAKT SVVDGTPLVA APSLNATTVV TTVYQEPIMS QGAALSGEPS 310 320 330 340 350 360 ALTKEEEKKQ PDEEPMDMVV EKQEESEHKS DNQILTEIVE AKMAEELKPM DTDKESIAES 370 380 390 400 410 420 KSPEMSMQED CINDIAPMQT DEQANKEQFV PGPNEKPLYA AEPVTLEDLQ LLADLFYLPY 430 440 450 460 470 480 EHGPKGAQML REFQWLRANS SVVSVNCKGK DSEKIEEWRS RAAKFEEMCA LVMGMFTRLS 490 500 510 520 530 540 NCANRTILYD MYSYVWDIKS IMSMVKSFVQ WLGCRSHSSA QFLIGDQEPW AFRGGLAGEF 550 560 570 580 590 600 QRLLPIDGAN DLFFQPPPLT PTSKVYTIRP YFPKDEASVY KICREMYDDG VGLPFQSQPD 610 620 630 640 650 660 LIGDKLVGGL LSLSLDYCFV LEDEDGICGY ALGTVDVTPF IKKCKISWIP FMQEKYTKPN 670 680 690 700 710 720 GDKELSEAEK IMLSFHEEQE VLPETFLANF PSLIKMDIHK KVTDPSVAKS MMACLLSSLK 730 740 750 760 ANGSRGAFCE VRPDDKRILE FYSKLGCFEI AKMEGFPKDV VILGRSL « Hide
Isoform 3 [UniParc]. Checksum: 0A62BBF2AF31A0FD Show »	FASTA	820	91,993
10 20 30 40 50 60 MVQKESQAAL EERESERNAN PASVSGASLE PSAAPAPGED NPSGAGAAAG TGAAGGARRF 70 80 90 100 110 120 LCGVVEGFYG RPWVMEQRKE LFRRLQKWEL NTYLYAPKDD YKHRMFWREM YSVEEAEQLM 130 140 150 160 170 180 TLISAAREYE IEFIYAISPG LDITFSNPKE VSTLKRKLDQ VSQFGCRSFA LLFDDIDHNM 190 200 210 220 230 240 CAADKEVFSS FAHAQVSITN EIYQYLGEPE TFLFCPTEYC GTFCYPSVSQ SPYLRTVGEK 250 260 270 280 290 300 LLPGIEVLWT DSEDSTVSIQ IKLENEGSDE DIETDVLYSP QMALKLALTE WLQEFGVPHQ 310 320 330 340 350 360 YSSRQVAHSG AKTSVVDGTP LVAAPSLNAT TVVTTVYQEP IMSQGAALSG EPSALTKEEE 370 380 390 400 410 420 KKQPDEEPMD MVVEKQEESE HKSDNQILTE IVEAKMAEEL KPMDTDKESI AESKSPEMSM 430 440 450 460 470 480 QEDCINDIAP MQTDEQANKE QFVPGPNEKP LYAAEPVTLE DLQLLADLFY LPYEHGPKGA 490 500 510 520 530 540 QMLREFQWLR ANSSVVSVNC KGKDSEKIEE WRSRAAKFEE MCALVMGMFT RLSNCANRTI 550 560 570 580 590 600 LYDMYSYVWD IKSIMSMVKS FVQWLGCRSH SSAQFLIGDQ EPWAFRGGLA GEFQRLLPID 610 620 630 640 650 660 GANDLFFQPP PLTPTSKVYT IRPYFPKDEA SVYKICREMY DDGVGLPFQS QPDLIGDKLV 670 680 690 700 710 720 GGLLSLSLDY CFVLEDEDGI CGYALGTVDV TPFIKKCKIS WIPFMQEKYT KPNGDKELSE 730 740 750 760 770 780 AEKIMLSFHE EQEVLPETFL ANFPSLIKMD IHKKVTDPSV AKSMMACLLS SLKANGSRGA 790 800 810 820 FCEVRPDDKR ILEFYSKLGC FEIAKMEGFP KDVVILGRSL « Hide

References

[1]	"The O-GlcNAcase gene is a candidate for diabetes susceptibility in GK rats." Liu K., Paterson A.J., Van Tine B.A., Konrad R.J., Parlow A.F., Jimi S., Chin E. Jr., Kudlow J.E. Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Strain: Fischer 344.
[2]	"Characterization of the histone acetyltransferase (HAT) domain of a bifunctional protein with activable O-GlcNAcase and HAT activities." Toleman C., Paterson A.J., Whisenhunt T.R., Kudlow J.E. J. Biol. Chem. 279:53665-53673(2004) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION OF ISOFORMS 2 AND 3, FUNCTION, MUTAGENESIS OF ASP-853; ASP-884 AND TYR-891. Strain: GK and Sprague-Dawley.
[3]	"Purification and characterization of an O-GlcNAc selective N-acetyl-beta-D-glucosaminidase from rat spleen cytosol." Dong D.-L., Hart G.W. J. Biol. Chem. 269:19321-19330(1994) [PubMed] [Europe PMC] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, ENZYME REGULATION, TISSUE SPECIFICITY. Tissue: Spleen.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY039679 mRNA. Translation: AAK72103.1.
IPI	IPI00208152. IPI00778199. IPI00786819.
RefSeq	NP_571979.1. NM_131904.1.
UniGene	Rn.162539.
3D structure databases
ProteinModelPortal	Q8VIJ5.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000024198.
Protein family/group databases
CAZy	GH84. Glycoside Hydrolase Family 84.
PTM databases
PhosphoSite	Q8VIJ5.
Proteomic databases
PaxDb	Q8VIJ5.
PRIDE	Q8VIJ5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000065172; ENSRNOP00000059568; ENSRNOG00000017822.
GeneID	154968.
KEGG	rno:154968.
UCSC	RGD:621077. rat.
Organism-specific databases
CTD	10724.
RGD	621077. Mgea5.
Phylogenomic databases
eggNOG	COG0454.
GeneTree	ENSGT00390000007726.
HOGENOM	HOG000044964.
HOVERGEN	HBG053044.
InParanoid	Q8VIJ5.
KO	K15719.
OMA	AHSGAKT.
OrthoDB	EOG469QT2.
Gene expression databases
ArrayExpress	Q8VIJ5.
Genevestigator	Q8VIJ5.
GermOnline	ENSRNOG00000017822. Rattus norvegicus.
Family and domain databases
Gene3D	3.40.630.30. 2 hits.
InterPro	IPR016181. Acyl_CoA_acyltransferase. IPR011496. Beta-N-acetylglucosaminidase. IPR017853. Glycoside_hydrolase_SF. [Graphical view]
Pfam	PF07555. NAGidase. 1 hit. [Graphical view]
SUPFAM	SSF55729. Acyl_CoA_acyltransferase. 1 hit. SSF51445. Glyco_hydro_cat. 1 hit.
ProtoNet	Search...
Other
NextBio	620868.

Entry information

Entry name

NCOAT_RAT

Accession

Primary (citable) accession number: Q8VIJ5

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 3, 2006
Last sequence update:	March 1, 2002
Last modified:	April 3, 2013
This is version 68 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Preferred order of sections

Names and origin

Including the following 2 domains:

Protein attributes

General annotation (Comments)

Ontologies

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Protein family/group databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information