ASNS_HUMAN
ID ASNS_HUMAN Reviewed; 561 AA.
AC P08243; A4D1I8; B4DXZ1; B7ZAA9; D6W5R3; E9PCI3; E9PCX6; P08184; Q15666;
AC Q549T9; Q96HD0;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 229.
DE RecName: Full=Asparagine synthetase [glutamine-hydrolyzing];
DE EC=6.3.5.4;
DE AltName: Full=Cell cycle control protein TS11;
DE AltName: Full=Glutamine-dependent asparagine synthetase;
GN Name=ASNS; Synonyms=TS11;
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 [MRNA] (ISOFORM 1).
RX PubMed=2886907; DOI=10.1128/mcb.7.7.2435-2443.1987;
RA Andrulis I.L., Chen J., Ray P.N.;
RT "Isolation of human cDNAs for asparagine synthetase and expression in
RT Jensen rat sarcoma cells.";
RL Mol. Cell. Biol. 7:2435-2443(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2565875; DOI=10.1016/0888-7543(89)90329-7;
RA Zhang Y.P., Lambert M.A., Cairney A.E., Wills D., Ray P.N., Andrulis I.L.;
RT "Molecular structure of the human asparagine synthetase gene.";
RL Genomics 4:259-265(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), AND VARIANT
RP GLU-210.
RC TISSUE=Testis;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLU-210.
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLU-210.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLU-210.
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLU-210.
RC TISSUE=Muscle;
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 [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 23-561 (ISOFORM 1).
RX PubMed=3470743; DOI=10.1073/pnas.84.6.1565;
RA Greco A., Ittmann M., Basilico C.;
RT "Molecular cloning of a gene that is necessary for G1 progression in
RT mammalian cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:1565-1569(1987).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-83.
RX PubMed=2569668; DOI=10.1128/mcb.9.6.2350-2359.1989;
RA Greco A., Gong S.S., Ittmann M., Basilico C.;
RT "Organization and expression of the cell cycle gene, ts11, that encodes
RT asparagine synthetase.";
RL Mol. Cell. Biol. 9:2350-2359(1989).
RN [11]
RP ACTIVE SITE.
RX PubMed=2564390; DOI=10.1016/s0021-9258(18)83573-6;
RA van Heeke G., Schuster S.M.;
RT "Expression of human asparagine synthetase in Escherichia coli.";
RL J. Biol. Chem. 264:5503-5509(1989).
RN [12]
RP MUTAGENESIS OF CYS-2, CATALYTIC ACTIVITY, AND ACTIVE SITE.
RX PubMed=2573597; DOI=10.1016/s0021-9258(19)47138-x;
RA van Heeke G., Schuster S.M.;
RT "The N-terminal cysteine of human asparagine synthetase is essential for
RT glutamine-dependent activity.";
RL J. Biol. Chem. 264:19475-19477(1989).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-385, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [15]
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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-545 AND SER-557, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [17]
RP VARIANTS ASNSD GLU-6; VAL-362 AND CYS-550, AND CHARACTERIZATION OF VARIANTS
RP ASNSD GLU-6; VAL-362 AND CYS-550.
RX PubMed=24139043; DOI=10.1016/j.neuron.2013.08.013;
RA Ruzzo E.K., Capo-Chichi J.M., Ben-Zeev B., Chitayat D., Mao H.,
RA Pappas A.L., Hitomi Y., Lu Y.F., Yao X., Hamdan F.F., Pelak K.,
RA Reznik-Wolf H., Bar-Joseph I., Oz-Levi D., Lev D., Lerman-Sagie T.,
RA Leshinsky-Silver E., Anikster Y., Ben-Asher E., Olender T., Colleaux L.,
RA Decarie J.C., Blaser S., Banwell B., Joshi R.B., He X.P., Patry L.,
RA Silver R.J., Dobrzeniecka S., Islam M.S., Hasnat A., Samuels M.E.,
RA Aryal D.K., Rodriguiz R.M., Jiang Y.H., Wetsel W.C., McNamara J.O.,
RA Rouleau G.A., Silver D.L., Lancet D., Pras E., Mitchell G.A., Michaud J.L.,
RA Goldstein D.B.;
RT "Deficiency of asparagine synthetase causes congenital microcephaly and a
RT progressive form of encephalopathy.";
RL Neuron 80:429-441(2013).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + L-aspartate + L-glutamine = AMP + diphosphate +
CC H(+) + L-asparagine + L-glutamate; Xref=Rhea:RHEA:12228,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29985,
CC ChEBI:CHEBI:29991, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:58048, ChEBI:CHEBI:58359, ChEBI:CHEBI:456215; EC=6.3.5.4;
CC Evidence={ECO:0000269|PubMed:2573597};
CC -!- PATHWAY: Amino-acid biosynthesis; L-asparagine biosynthesis; L-
CC asparagine from L-aspartate (L-Gln route): step 1/1.
CC -!- INTERACTION:
CC P08243; Q86WT6: TRIM69; NbExp=4; IntAct=EBI-722989, EBI-749955;
CC P08243; Q86WT6-2: TRIM69; NbExp=3; IntAct=EBI-722989, EBI-11525489;
CC P08243; A2RRH5: WDR27; NbExp=3; IntAct=EBI-722989, EBI-9476803;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P08243-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P08243-2; Sequence=VSP_045818;
CC Name=3;
CC IsoId=P08243-3; Sequence=VSP_045817;
CC -!- DISEASE: Asparagine synthetase deficiency (ASNSD) [MIM:615574]: An
CC inborn error of asparagine biosynthesis that results in a severe
CC neurologic disorder characterized by microcephaly, severely delayed
CC psychomotor development, progressive encephalopathy, cortical atrophy,
CC and seizure or hyperekplexic activity. {ECO:0000269|PubMed:24139043}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/ASNSID44323ch7q21.html";
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DR EMBL; M27396; AAA51789.1; -; mRNA.
DR EMBL; L35946; AAA52756.1; -; Genomic_DNA.
DR EMBL; L35936; AAA52756.1; JOINED; Genomic_DNA.
DR EMBL; L35937; AAA52756.1; JOINED; Genomic_DNA.
DR EMBL; L35938; AAA52756.1; JOINED; Genomic_DNA.
DR EMBL; L35939; AAA52756.1; JOINED; Genomic_DNA.
DR EMBL; L35940; AAA52756.1; JOINED; Genomic_DNA.
DR EMBL; L35941; AAA52756.1; JOINED; Genomic_DNA.
DR EMBL; L35942; AAA52756.1; JOINED; Genomic_DNA.
DR EMBL; L35943; AAA52756.1; JOINED; Genomic_DNA.
DR EMBL; L35944; AAA52756.1; JOINED; Genomic_DNA.
DR EMBL; L35945; AAA52756.1; JOINED; Genomic_DNA.
DR EMBL; BT007113; AAP35777.1; -; mRNA.
DR EMBL; AK302189; BAG63553.1; -; mRNA.
DR EMBL; AK316224; BAH14595.1; -; mRNA.
DR EMBL; AC005326; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC079781; AAQ96856.1; -; Genomic_DNA.
DR EMBL; CH236949; EAL24115.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76730.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76723.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76731.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76732.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76733.1; -; Genomic_DNA.
DR EMBL; BC008723; AAH08723.1; -; mRNA.
DR EMBL; BC014621; AAH14621.1; -; mRNA.
DR EMBL; M15798; AAA36781.1; -; mRNA.
DR EMBL; M27054; AAA63266.1; -; Genomic_DNA.
DR CCDS; CCDS55131.1; -. [P08243-3]
DR CCDS; CCDS55132.1; -. [P08243-2]
DR CCDS; CCDS5652.1; -. [P08243-1]
DR PIR; A27062; AJHUN1.
DR RefSeq; NP_001171546.1; NM_001178075.1. [P08243-2]
DR RefSeq; NP_001171547.1; NM_001178076.1. [P08243-3]
DR RefSeq; NP_001171548.1; NM_001178077.1. [P08243-3]
DR RefSeq; NP_001664.3; NM_001673.4. [P08243-1]
DR RefSeq; NP_597680.2; NM_133436.3. [P08243-1]
DR RefSeq; NP_899199.2; NM_183356.3. [P08243-1]
DR PDB; 6GQ3; X-ray; 1.85 A; A/B=1-561.
DR PDBsum; 6GQ3; -.
DR AlphaFoldDB; P08243; -.
DR SMR; P08243; -.
DR BioGRID; 106932; 145.
DR IntAct; P08243; 26.
DR MINT; P08243; -.
DR STRING; 9606.ENSP00000175506; -.
DR BindingDB; P08243; -.
DR ChEMBL; CHEMBL3120; -.
DR DrugBank; DB00174; Asparagine.
DR DrugBank; DB00128; Aspartic acid.
DR DrugBank; DB00171; ATP.
DR DrugBank; DB00142; Glutamic acid.
DR DrugBank; DB00130; L-Glutamine.
DR DrugCentral; P08243; -.
DR MEROPS; C44.974; -.
DR GlyGen; P08243; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P08243; -.
DR MetOSite; P08243; -.
DR PhosphoSitePlus; P08243; -.
DR SwissPalm; P08243; -.
DR BioMuta; ASNS; -.
DR DMDM; 13432102; -.
DR EPD; P08243; -.
DR jPOST; P08243; -.
DR MassIVE; P08243; -.
DR MaxQB; P08243; -.
DR PaxDb; P08243; -.
DR PeptideAtlas; P08243; -.
DR PRIDE; P08243; -.
DR ProteomicsDB; 19452; -.
DR ProteomicsDB; 19538; -.
DR ProteomicsDB; 52098; -. [P08243-1]
DR Antibodypedia; 30203; 398 antibodies from 35 providers.
DR DNASU; 440; -.
DR Ensembl; ENST00000175506.8; ENSP00000175506.4; ENSG00000070669.17. [P08243-1]
DR Ensembl; ENST00000394308.8; ENSP00000377845.3; ENSG00000070669.17. [P08243-1]
DR Ensembl; ENST00000394309.7; ENSP00000377846.3; ENSG00000070669.17. [P08243-1]
DR Ensembl; ENST00000422745.5; ENSP00000414901.1; ENSG00000070669.17. [P08243-2]
DR Ensembl; ENST00000437628.5; ENSP00000414379.1; ENSG00000070669.17. [P08243-3]
DR Ensembl; ENST00000444334.5; ENSP00000406994.1; ENSG00000070669.17. [P08243-2]
DR Ensembl; ENST00000455086.5; ENSP00000408472.1; ENSG00000070669.17. [P08243-3]
DR GeneID; 440; -.
DR KEGG; hsa:440; -.
DR MANE-Select; ENST00000394308.8; ENSP00000377845.3; NM_001673.5; NP_001664.3.
DR UCSC; uc003uot.5; human. [P08243-1]
DR CTD; 440; -.
DR DisGeNET; 440; -.
DR GeneCards; ASNS; -.
DR GeneReviews; ASNS; -.
DR HGNC; HGNC:753; ASNS.
DR HPA; ENSG00000070669; Tissue enhanced (pancreas).
DR MalaCards; ASNS; -.
DR MIM; 108370; gene.
DR MIM; 615574; phenotype.
DR neXtProt; NX_P08243; -.
DR OpenTargets; ENSG00000070669; -.
DR Orphanet; 391376; Congenital microcephaly-severe encephalopathy-progressive cerebral atrophy syndrome.
DR PharmGKB; PA25052; -.
DR VEuPathDB; HostDB:ENSG00000070669; -.
DR eggNOG; KOG0571; Eukaryota.
DR GeneTree; ENSGT00390000001994; -.
DR HOGENOM; CLU_014658_2_1_1; -.
DR InParanoid; P08243; -.
DR OMA; DIHTWMR; -.
DR OrthoDB; 782607at2759; -.
DR PhylomeDB; P08243; -.
DR TreeFam; TF300603; -.
DR BRENDA; 6.3.5.4; 2681.
DR PathwayCommons; P08243; -.
DR Reactome; R-HSA-380994; ATF4 activates genes in response to endoplasmic reticulum stress.
DR Reactome; R-HSA-8963693; Aspartate and asparagine metabolism.
DR Reactome; R-HSA-9633012; Response of EIF2AK4 (GCN2) to amino acid deficiency.
DR Reactome; R-HSA-9648895; Response of EIF2AK1 (HRI) to heme deficiency.
DR SignaLink; P08243; -.
DR SIGNOR; P08243; -.
DR UniPathway; UPA00134; UER00195.
DR BioGRID-ORCS; 440; 93 hits in 1072 CRISPR screens.
DR ChiTaRS; ASNS; human.
DR GenomeRNAi; 440; -.
DR Pharos; P08243; Tchem.
DR PRO; PR:P08243; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P08243; protein.
DR Bgee; ENSG00000070669; Expressed in cerebellar hemisphere and 95 other tissues.
DR ExpressionAtlas; P08243; baseline and differential.
DR Genevisible; P08243; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0004066; F:asparagine synthase (glutamine-hydrolyzing) activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0006529; P:asparagine biosynthetic process; IDA:MGI.
DR GO; GO:0042149; P:cellular response to glucose starvation; IDA:UniProtKB.
DR GO; GO:0006541; P:glutamine metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0070981; P:L-asparagine biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; IDA:UniProtKB.
DR CDD; cd01991; Asn_Synthase_B_C; 1.
DR CDD; cd00712; AsnB; 1.
DR Gene3D; 3.40.50.620; -; 1.
DR Gene3D; 3.60.20.10; -; 1.
DR InterPro; IPR006426; Asn_synth_AEB.
DR InterPro; IPR001962; Asn_synthase.
DR InterPro; IPR033738; AsnB_N.
DR InterPro; IPR017932; GATase_2_dom.
DR InterPro; IPR029055; Ntn_hydrolases_N.
DR InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR Pfam; PF00733; Asn_synthase; 1.
DR Pfam; PF13537; GATase_7; 1.
DR PIRSF; PIRSF001589; Asn_synthetase_glu-h; 1.
DR SUPFAM; SSF56235; SSF56235; 1.
DR TIGRFAMs; TIGR01536; asn_synth_AEB; 1.
DR PROSITE; PS51278; GATASE_TYPE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Amino-acid biosynthesis;
KW Asparagine biosynthesis; ATP-binding; Disease variant;
KW Glutamine amidotransferase; Intellectual disability; Ligase;
KW Nucleotide-binding; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250"
FT CHAIN 2..561
FT /note="Asparagine synthetase [glutamine-hydrolyzing]"
FT /id="PRO_0000056910"
FT DOMAIN 2..191
FT /note="Glutamine amidotransferase type-2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00609"
FT DOMAIN 213..536
FT /note="Asparagine synthetase"
FT ACT_SITE 2
FT /note="For GATase activity"
FT /evidence="ECO:0000269|PubMed:2564390,
FT ECO:0000269|PubMed:2573597"
FT BINDING 49..53
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000250"
FT BINDING 75..77
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000250"
FT BINDING 97
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000250"
FT BINDING 256
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 288
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 363..364
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT SITE 365
FT /note="Important for beta-aspartyl-AMP intermediate
FT formation"
FT /evidence="ECO:0000250"
FT MOD_RES 385
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 545
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 557
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..83
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045817"
FT VAR_SEQ 1..21
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045818"
FT VARIANT 6
FT /note="A -> E (in ASNSD; dramatic reduction in protein
FT abundance; dbSNP:rs398122975)"
FT /evidence="ECO:0000269|PubMed:24139043"
FT /id="VAR_070896"
FT VARIANT 210
FT /note="V -> E (in dbSNP:rs1049674)"
FT /evidence="ECO:0000269|PubMed:12690205,
FT ECO:0000269|PubMed:12853948, ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.6"
FT /id="VAR_023443"
FT VARIANT 362
FT /note="F -> V (in ASNSD; dramatic reduction in protein
FT abundance; dbSNP:rs398122973)"
FT /evidence="ECO:0000269|PubMed:24139043"
FT /id="VAR_070897"
FT VARIANT 550
FT /note="R -> C (in ASNSD; increases level of protein
FT abundance; dbSNP:rs398122974)"
FT /evidence="ECO:0000269|PubMed:24139043"
FT /id="VAR_070898"
FT MUTAGEN 2
FT /note="C->A: Loss of the glutamine-dependent asparagine
FT synthetase activity, while the ammonia-dependent activity
FT remained unaffected."
FT /evidence="ECO:0000269|PubMed:2573597"
FT CONFLICT 333..343
FT /note="TYDITTVRASV -> LMTLQQFVLRI (in Ref. 9; AAA36781)"
FT /evidence="ECO:0000305"
FT CONFLICT 353..360
FT /note="RKNTDSVV -> GRTQIAWL (in Ref. 9; AAA36781)"
FT /evidence="ECO:0000305"
FT CONFLICT 426
FT /note="S -> F (in Ref. 1 and 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 462
FT /note="I -> V (in Ref. 4; BAG63553)"
FT /evidence="ECO:0000305"
FT STRAND 3..9
FT /evidence="ECO:0007829|PDB:6GQ3"
FT HELIX 15..18
FT /evidence="ECO:0007829|PDB:6GQ3"
FT HELIX 20..27
FT /evidence="ECO:0007829|PDB:6GQ3"
FT STRAND 30..37
FT /evidence="ECO:0007829|PDB:6GQ3"
FT STRAND 40..49
FT /evidence="ECO:0007829|PDB:6GQ3"
FT TURN 55..57
FT /evidence="ECO:0007829|PDB:6GQ3"
FT STRAND 60..62
FT /evidence="ECO:0007829|PDB:6GQ3"
FT STRAND 70..78
FT /evidence="ECO:0007829|PDB:6GQ3"
FT HELIX 81..88
FT /evidence="ECO:0007829|PDB:6GQ3"
FT HELIX 99..114
FT /evidence="ECO:0007829|PDB:6GQ3"
FT STRAND 119..127
FT /evidence="ECO:0007829|PDB:6GQ3"
FT TURN 128..131
FT /evidence="ECO:0007829|PDB:6GQ3"
FT STRAND 132..137
FT /evidence="ECO:0007829|PDB:6GQ3"
FT STRAND 146..149
FT /evidence="ECO:0007829|PDB:6GQ3"
FT STRAND 155..160
FT /evidence="ECO:0007829|PDB:6GQ3"
FT HELIX 161..163
FT /evidence="ECO:0007829|PDB:6GQ3"
FT TURN 164..166
FT /evidence="ECO:0007829|PDB:6GQ3"
FT STRAND 177..179
FT /evidence="ECO:0007829|PDB:6GQ3"
FT STRAND 184..190
FT /evidence="ECO:0007829|PDB:6GQ3"
FT STRAND 196..203
FT /evidence="ECO:0007829|PDB:6GQ3"
FT HELIX 228..245
FT /evidence="ECO:0007829|PDB:6GQ3"
FT STRAND 250..256
FT /evidence="ECO:0007829|PDB:6GQ3"
FT HELIX 261..276
FT /evidence="ECO:0007829|PDB:6GQ3"
FT STRAND 284..292
FT /evidence="ECO:0007829|PDB:6GQ3"
FT HELIX 294..306
FT /evidence="ECO:0007829|PDB:6GQ3"
FT STRAND 309..314
FT /evidence="ECO:0007829|PDB:6GQ3"
FT HELIX 317..331
FT /evidence="ECO:0007829|PDB:6GQ3"
FT HELIX 336..355
FT /evidence="ECO:0007829|PDB:6GQ3"
FT STRAND 358..362
FT /evidence="ECO:0007829|PDB:6GQ3"
FT HELIX 367..371
FT /evidence="ECO:0007829|PDB:6GQ3"
FT HELIX 375..379
FT /evidence="ECO:0007829|PDB:6GQ3"
FT HELIX 383..396
FT /evidence="ECO:0007829|PDB:6GQ3"
FT TURN 397..400
FT /evidence="ECO:0007829|PDB:6GQ3"
FT HELIX 401..410
FT /evidence="ECO:0007829|PDB:6GQ3"
FT TURN 411..413
FT /evidence="ECO:0007829|PDB:6GQ3"
FT STRAND 415..417
FT /evidence="ECO:0007829|PDB:6GQ3"
FT HELIX 419..421
FT /evidence="ECO:0007829|PDB:6GQ3"
FT HELIX 423..430
FT /evidence="ECO:0007829|PDB:6GQ3"
FT HELIX 434..437
FT /evidence="ECO:0007829|PDB:6GQ3"
FT STRAND 440..443
FT /evidence="ECO:0007829|PDB:6GQ3"
FT HELIX 446..451
FT /evidence="ECO:0007829|PDB:6GQ3"
FT TURN 452..456
FT /evidence="ECO:0007829|PDB:6GQ3"
FT HELIX 460..463
FT /evidence="ECO:0007829|PDB:6GQ3"
FT HELIX 481..492
FT /evidence="ECO:0007829|PDB:6GQ3"
FT HELIX 495..499
FT /evidence="ECO:0007829|PDB:6GQ3"
FT HELIX 501..504
FT /evidence="ECO:0007829|PDB:6GQ3"
FT HELIX 513..525
FT /evidence="ECO:0007829|PDB:6GQ3"
FT HELIX 530..532
FT /evidence="ECO:0007829|PDB:6GQ3"
SQ SEQUENCE 561 AA; 64370 MW; 3E9B75E21D799FBE CRC64;
MCGIWALFGS DDCLSVQCLS AMKIAHRGPD AFRFENVNGY TNCCFGFHRL AVVDPLFGMQ
PIRVKKYPYL WLCYNGEIYN HKKMQQHFEF EYQTKVDGEI ILHLYDKGGI EQTICMLDGV
FAFVLLDTAN KKVFLGRDTY GVRPLFKAMT EDGFLAVCSE AKGLVTLKHS ATPFLKVEPF
LPGHYEVLDL KPNGKVASVE MVKYHHCRDV PLHALYDNVE KLFPGFEIET VKNNLRILFN
NAVKKRLMTD RRIGCLLSGG LDSSLVAATL LKQLKEAQVQ YPLQTFAIGM EDSPDLLAAR
KVADHIGSEH YEVLFNSEEG IQALDEVIFS LETYDITTVR ASVGMYLISK YIRKNTDSVV
IFSGEGSDEL TQGYIYFHKA PSPEKAEEES ERLLRELYLF DVLRADRTTA AHGLELRVPF
LDHRFSSYYL SLPPEMRIPK NGIEKHLLRE TFEDSNLIPK EILWRPKEAF SDGITSVKNS
WFKILQEYVE HQVDDAMMAN AAQKFPFNTP KTKEGYYYRQ VFERHYPGRA DWLSHYWMPK
WINATDPSAR TLTHYKSAVK A
