GNA1_HUMAN
ID GNA1_HUMAN Reviewed; 184 AA.
AC Q96EK6;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Glucosamine 6-phosphate N-acetyltransferase;
DE EC=2.3.1.4 {ECO:0000269|PubMed:18601654, ECO:0000269|PubMed:18675810};
DE AltName: Full=Phosphoglucosamine acetylase;
DE AltName: Full=Phosphoglucosamine transacetylase;
GN Name=GNPNAT1; Synonyms=GNA1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH THE SUBSTRATE
RP GLUCOSAMINE-6-PHOSPHATE, CATALYTIC ACTIVITY, MUTAGENESIS OF GLU-156, AND
RP SUBUNIT.
RX PubMed=18675810; DOI=10.1016/j.febslet.2008.07.040;
RA Wang J., Liu X., Liang Y.-H., Li L.-F., Su X.-D.;
RT "Acceptor substrate binding revealed by crystal structure of human
RT glucosamine-6-phosphate N-acetyltransferase 1.";
RL FEBS Lett. 582:2973-2978(2008).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH THE ACETYL-COA ANALOG
RP COENZYME A AND THE SUBSTRATE N-ACETYLGLUCOSAMINE-6-PHOSPHATE, CATALYTIC
RP ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=18601654; DOI=10.1042/bj20081000;
RA Hurtado-Guerrero R., Raimi O.G., Min J., Zeng H., Vallius L., Shepherd S.,
RA Ibrahim A.F.M., Wu H., Plotnikov A.N., van Aalten D.M.F.;
RT "Structural and kinetic differences between human and Aspergillus fumigatus
RT D-glucosamine-6-phosphate N-acetyltransferase.";
RL Biochem. J. 415:217-223(2008).
RN [7]
RP INVOLVEMENT IN RHZDAN, AND VARIANT RHZDAN LYS-76.
RX PubMed=32591345; DOI=10.1136/jmedgenet-2020-106929;
RA Ain N.U., Baroncelli M., Costantini A., Ishaq T., Taylan F., Nilsson O.,
RA Maekitie O., Naz S.;
RT "Novel form of rhizomelic skeletal dysplasia associated with a homozygous
RT variant in GNPNAT1.";
RL J. Med. Genet. 58:351-356(2021).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + D-glucosamine 6-phosphate = CoA + H(+) + N-
CC acetyl-D-glucosamine 6-phosphate; Xref=Rhea:RHEA:10292,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:57513, ChEBI:CHEBI:58725; EC=2.3.1.4;
CC Evidence={ECO:0000269|PubMed:18601654, ECO:0000269|PubMed:18675810};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=26 uM for acetyl-coenzyme A {ECO:0000269|PubMed:18601654};
CC KM=97 uM for glucosamine-6-phosphate {ECO:0000269|PubMed:18601654};
CC -!- PATHWAY: Nucleotide-sugar biosynthesis; UDP-N-acetyl-alpha-D-
CC glucosamine biosynthesis; N-acetyl-alpha-D-glucosamine 1-phosphate from
CC alpha-D-glucosamine 6-phosphate (route I): step 1/2.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:18601654,
CC ECO:0000269|PubMed:18675810}.
CC -!- INTERACTION:
CC Q96EK6; Q96EK6: GNPNAT1; NbExp=2; IntAct=EBI-3913338, EBI-3913338;
CC Q96EK6; P28062-2: PSMB8; NbExp=3; IntAct=EBI-3913338, EBI-372312;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane; Peripheral membrane
CC protein. Endosome membrane {ECO:0000250}; Peripheral membrane protein
CC {ECO:0000250}.
CC -!- DISEASE: Rhizomelic dysplasia, Ain-Naz type (RHZDAN) [MIM:619598]: An
CC autosomal recessive skeletal dysplasia characterized by short stature,
CC marked rhizomelic shortening of the limbs, platyspondyly, hip
CC dysplasia, and large hands and feet relative to height.
CC {ECO:0000269|PubMed:32591345}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the acetyltransferase family. GNA1 subfamily.
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; AK090577; BAC03482.1; -; mRNA.
DR EMBL; BC012179; AAH12179.1; -; mRNA.
DR CCDS; CCDS9712.1; -.
DR RefSeq; NP_932332.1; NM_198066.3.
DR RefSeq; XP_005268069.1; XM_005268012.2.
DR RefSeq; XP_006720301.1; XM_006720238.3.
DR PDB; 2HUZ; X-ray; 2.67 A; A/B=1-184.
DR PDB; 2O28; X-ray; 1.80 A; A/B=1-184.
DR PDB; 3CXP; X-ray; 2.01 A; A=1-184.
DR PDB; 3CXQ; X-ray; 2.30 A; A=1-184.
DR PDB; 3CXS; X-ray; 2.70 A; A=1-184.
DR PDBsum; 2HUZ; -.
DR PDBsum; 2O28; -.
DR PDBsum; 3CXP; -.
DR PDBsum; 3CXQ; -.
DR PDBsum; 3CXS; -.
DR AlphaFoldDB; Q96EK6; -.
DR SMR; Q96EK6; -.
DR BioGRID; 122317; 27.
DR IntAct; Q96EK6; 10.
DR MINT; Q96EK6; -.
DR STRING; 9606.ENSP00000216410; -.
DR GlyGen; Q96EK6; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96EK6; -.
DR MetOSite; Q96EK6; -.
DR PhosphoSitePlus; Q96EK6; -.
DR BioMuta; GNPNAT1; -.
DR DMDM; 47116568; -.
DR EPD; Q96EK6; -.
DR jPOST; Q96EK6; -.
DR MassIVE; Q96EK6; -.
DR MaxQB; Q96EK6; -.
DR PaxDb; Q96EK6; -.
DR PeptideAtlas; Q96EK6; -.
DR PRIDE; Q96EK6; -.
DR ProteomicsDB; 76418; -.
DR Antibodypedia; 10869; 117 antibodies from 22 providers.
DR DNASU; 64841; -.
DR Ensembl; ENST00000216410.8; ENSP00000216410.3; ENSG00000100522.10.
DR Ensembl; ENST00000650397.1; ENSP00000496934.1; ENSG00000100522.10.
DR GeneID; 64841; -.
DR KEGG; hsa:64841; -.
DR MANE-Select; ENST00000216410.8; ENSP00000216410.3; NM_198066.4; NP_932332.1.
DR UCSC; uc001xab.4; human.
DR CTD; 64841; -.
DR DisGeNET; 64841; -.
DR GeneCards; GNPNAT1; -.
DR HGNC; HGNC:19980; GNPNAT1.
DR HPA; ENSG00000100522; Tissue enhanced (liver).
DR MIM; 616510; gene.
DR MIM; 619598; phenotype.
DR neXtProt; NX_Q96EK6; -.
DR OpenTargets; ENSG00000100522; -.
DR PharmGKB; PA134901326; -.
DR VEuPathDB; HostDB:ENSG00000100522; -.
DR eggNOG; KOG3396; Eukaryota.
DR GeneTree; ENSGT00390000008666; -.
DR InParanoid; Q96EK6; -.
DR OMA; NQRYDWI; -.
DR OrthoDB; 1479446at2759; -.
DR PhylomeDB; Q96EK6; -.
DR TreeFam; TF313790; -.
DR BRENDA; 2.3.1.4; 2681.
DR PathwayCommons; Q96EK6; -.
DR Reactome; R-HSA-446210; Synthesis of UDP-N-acetyl-glucosamine.
DR SABIO-RK; Q96EK6; -.
DR SignaLink; Q96EK6; -.
DR UniPathway; UPA00113; UER00529.
DR BioGRID-ORCS; 64841; 110 hits in 1077 CRISPR screens.
DR ChiTaRS; GNPNAT1; human.
DR EvolutionaryTrace; Q96EK6; -.
DR GenomeRNAi; 64841; -.
DR Pharos; Q96EK6; Tbio.
DR PRO; PR:Q96EK6; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q96EK6; protein.
DR Bgee; ENSG00000100522; Expressed in ileal mucosa and 178 other tissues.
DR ExpressionAtlas; Q96EK6; baseline and differential.
DR Genevisible; Q96EK6; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IBA:GO_Central.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004343; F:glucosamine 6-phosphate N-acetyltransferase activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0048029; F:monosaccharide binding; IBA:GO_Central.
DR GO; GO:0008080; F:N-acetyltransferase activity; IBA:GO_Central.
DR GO; GO:0006048; P:UDP-N-acetylglucosamine biosynthetic process; IBA:GO_Central.
DR InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR InterPro; IPR000182; GNAT_dom.
DR InterPro; IPR039143; GNPNAT1.
DR PANTHER; PTHR13355; PTHR13355; 1.
DR Pfam; PF00583; Acetyltransf_1; 1.
DR SUPFAM; SSF55729; SSF55729; 1.
DR PROSITE; PS51186; GNAT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Disease variant; Dwarfism; Endosome;
KW Golgi apparatus; Membrane; Reference proteome; Transferase.
FT CHAIN 1..184
FT /note="Glucosamine 6-phosphate N-acetyltransferase"
FT /id="PRO_0000074553"
FT DOMAIN 39..184
FT /note="N-acetyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00532"
FT BINDING 61
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:18675810,
FT ECO:0000305|PubMed:18601654, ECO:0007744|PDB:3CXQ"
FT BINDING 108..111
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:18675810,
FT ECO:0000305|PubMed:18601654, ECO:0007744|PDB:3CXQ"
FT BINDING 120..122
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:18675810,
FT ECO:0000305|PubMed:18601654, ECO:0007744|PDB:3CXQ"
FT BINDING 130..135
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000305|PubMed:18601654,
FT ECO:0007744|PDB:2O28"
FT BINDING 151..152
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:18675810,
FT ECO:0000305|PubMed:18601654, ECO:0007744|PDB:3CXQ"
FT BINDING 165..167
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000305|PubMed:18601654,
FT ECO:0007744|PDB:2O28"
FT BINDING 175
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:18675810,
FT ECO:0000305|PubMed:18601654, ECO:0007744|PDB:3CXQ"
FT BINDING 181
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:18675810,
FT ECO:0000305|PubMed:18601654, ECO:0007744|PDB:3CXQ"
FT VARIANT 76
FT /note="E -> K (in RHZDAN)"
FT /evidence="ECO:0000269|PubMed:32591345"
FT /id="VAR_086302"
FT MUTAGEN 156
FT /note="E->A: Reduces affinity for glucosamine-6-phosphate
FT 6-fold."
FT /evidence="ECO:0000269|PubMed:18675810"
FT MUTAGEN 156
FT /note="E->D: Slightly reduced catalytic activity."
FT /evidence="ECO:0000269|PubMed:18675810"
FT STRAND 7..9
FT /evidence="ECO:0007829|PDB:2O28"
FT HELIX 12..16
FT /evidence="ECO:0007829|PDB:2O28"
FT HELIX 19..21
FT /evidence="ECO:0007829|PDB:2O28"
FT STRAND 32..34
FT /evidence="ECO:0007829|PDB:3CXQ"
FT STRAND 39..43
FT /evidence="ECO:0007829|PDB:2O28"
FT HELIX 46..50
FT /evidence="ECO:0007829|PDB:2O28"
FT HELIX 53..57
FT /evidence="ECO:0007829|PDB:2O28"
FT TURN 58..60
FT /evidence="ECO:0007829|PDB:2O28"
FT HELIX 68..81
FT /evidence="ECO:0007829|PDB:2O28"
FT STRAND 84..91
FT /evidence="ECO:0007829|PDB:2O28"
FT TURN 92..95
FT /evidence="ECO:0007829|PDB:2O28"
FT STRAND 96..107
FT /evidence="ECO:0007829|PDB:2O28"
FT HELIX 110..113
FT /evidence="ECO:0007829|PDB:2O28"
FT STRAND 115..124
FT /evidence="ECO:0007829|PDB:2O28"
FT HELIX 126..128
FT /evidence="ECO:0007829|PDB:2O28"
FT HELIX 133..147
FT /evidence="ECO:0007829|PDB:2O28"
FT STRAND 150..157
FT /evidence="ECO:0007829|PDB:2O28"
FT HELIX 159..161
FT /evidence="ECO:0007829|PDB:2O28"
FT HELIX 162..166
FT /evidence="ECO:0007829|PDB:2O28"
FT TURN 167..169
FT /evidence="ECO:0007829|PDB:2O28"
FT STRAND 174..182
FT /evidence="ECO:0007829|PDB:2O28"
SQ SEQUENCE 184 AA; 20749 MW; E9F31803CF633BBF CRC64;
MKPDETPMFD PSLLKEVDWS QNTATFSPAI SPTHPGEGLV LRPLCTADLN RGFFKVLGQL
TETGVVSPEQ FMKSFEHMKK SGDYYVTVVE DVTLGQIVAT ATLIIEHKFI HSCAKRGRVE
DVVVSDECRG KQLGKLLLST LTLLSKKLNC YKITLECLPQ NVGFYKKFGY TVSEENYMCR
RFLK
