ASNS_MOUSE
ID ASNS_MOUSE Reviewed; 561 AA.
AC Q61024; Q3TJA1; Q8BPC8;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Asparagine synthetase [glutamine-hydrolyzing];
DE EC=6.3.5.4;
DE AltName: Full=Glutamine-dependent asparagine synthetase;
GN Name=Asns;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Liver;
RA Goodwin L., Sellati L., Millan C., Guzowski D., Leeds N., Broome J.,
RA Pergolizzi R.;
RL Submitted (OCT-1995) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Placenta;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP DISRUPTION PHENOTYPE.
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 -!- PATHWAY: Amino-acid biosynthesis; L-asparagine biosynthesis; L-
CC asparagine from L-aspartate (L-Gln route): step 1/1.
CC -!- DISRUPTION PHENOTYPE: Mice carrying a gene trap insertion in the gene
CC express 20% of the normal level of mRNA. The hypomorphic mutant
CC displays a number of defects that mirror ASNSD syndrome, although the
CC phenotype is milder. Mice have structural brain abnormalities,
CC including reduced cortical thickness and enlarged ventricles. Mutant
CC mice also show deficits in learning and memory. Mutant mice do not show
CC abnormal motor activity or seizure activity.
CC {ECO:0000269|PubMed:24139043}.
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DR EMBL; U38940; AAA85125.1; -; mRNA.
DR EMBL; AK076207; BAC36254.1; -; mRNA.
DR EMBL; AK167524; BAE39594.1; -; mRNA.
DR EMBL; BC005552; AAH05552.1; -; mRNA.
DR CCDS; CCDS19907.1; -.
DR RefSeq; NP_036185.1; NM_012055.3.
DR RefSeq; XP_006505155.1; XM_006505092.3.
DR RefSeq; XP_006505156.1; XM_006505093.3.
DR AlphaFoldDB; Q61024; -.
DR SMR; Q61024; -.
DR BioGRID; 205108; 21.
DR IntAct; Q61024; 2.
DR STRING; 10090.ENSMUSP00000031766; -.
DR ChEMBL; CHEMBL3243906; -.
DR MEROPS; C44.974; -.
DR iPTMnet; Q61024; -.
DR PhosphoSitePlus; Q61024; -.
DR SwissPalm; Q61024; -.
DR EPD; Q61024; -.
DR jPOST; Q61024; -.
DR MaxQB; Q61024; -.
DR PaxDb; Q61024; -.
DR PeptideAtlas; Q61024; -.
DR PRIDE; Q61024; -.
DR ProteomicsDB; 281921; -.
DR Antibodypedia; 30203; 398 antibodies from 35 providers.
DR DNASU; 27053; -.
DR Ensembl; ENSMUST00000031766; ENSMUSP00000031766; ENSMUSG00000029752.
DR Ensembl; ENSMUST00000115542; ENSMUSP00000111204; ENSMUSG00000029752.
DR GeneID; 27053; -.
DR KEGG; mmu:27053; -.
DR UCSC; uc009axf.1; mouse.
DR CTD; 440; -.
DR MGI; MGI:1350929; Asns.
DR VEuPathDB; HostDB:ENSMUSG00000029752; -.
DR eggNOG; KOG0571; Eukaryota.
DR GeneTree; ENSGT00390000001994; -.
DR HOGENOM; CLU_014658_2_1_1; -.
DR InParanoid; Q61024; -.
DR OMA; DIHTWMR; -.
DR OrthoDB; 782607at2759; -.
DR PhylomeDB; Q61024; -.
DR TreeFam; TF300603; -.
DR Reactome; R-MMU-8963693; Aspartate and asparagine metabolism.
DR UniPathway; UPA00134; UER00195.
DR BioGRID-ORCS; 27053; 2 hits in 74 CRISPR screens.
DR PRO; PR:Q61024; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q61024; protein.
DR Bgee; ENSMUSG00000029752; Expressed in parotid gland and 276 other tissues.
DR ExpressionAtlas; Q61024; baseline and differential.
DR Genevisible; Q61024; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0004066; F:asparagine synthase (glutamine-hydrolyzing) activity; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0006529; P:asparagine biosynthetic process; ISO:MGI.
DR GO; GO:0042149; P:cellular response to glucose starvation; ISO:MGI.
DR GO; GO:0032870; P:cellular response to hormone stimulus; IEA:Ensembl.
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:0001889; P:liver development; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; ISO:MGI.
DR GO; GO:0043200; P:response to amino acid; IEA:Ensembl.
DR GO; GO:0032354; P:response to follicle-stimulating hormone; IEA:Ensembl.
DR GO; GO:0009416; P:response to light stimulus; IEA:Ensembl.
DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl.
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 Acetylation; Amino-acid biosynthesis; Asparagine biosynthesis; ATP-binding;
KW Glutamine amidotransferase; Ligase; Nucleotide-binding; Phosphoprotein;
KW 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_0000056912"
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:0000250"
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:0000250|UniProtKB:P08243"
FT MOD_RES 545
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P08243"
FT MOD_RES 557
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P08243"
FT CONFLICT 5
FT /note="W -> G (in Ref. 2; BAC36254)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 561 AA; 64283 MW; 1981956B69E1F9F1 CRC64;
MCGIWALFGS DDCLSVQCLS AMKIAHRGPD AFRFENVNGY TNCCFGFHRL AVVDPLFGMQ
PIRVRKYPYL WLCYNGEIYN HKALQQRFEF EYQTNVDGEI ILHLYDKGGI EKTICMLDGV
FAFILLDTAN KKVFLGRDTY GVRPLFKAMT EDGFLAVCSE AKGLVSLKHS TTPFLKVEPF
LPGHYEVLDL KPNGKVASVE MVKYHHCTDE PLHAIYDSVE KLFPGFDLET VKNNLRILFD
NAIKKRLMTD RRIGCLLSGG LDSSLVAASL LKQLKEAQVQ YPLQTFAIGM EDSPDLLAAR
KVANYIGSEH HEVLFNSEEG IQALDEVIFS LETYDITTVR ASVGMYLISK YIRKNTDSVV
IFSGEGSDEL TQGYIYFHKA PSPEKAEEES ERLLKELYLF DVLRADRTTA AHGLELRVPF
LDHRFSSYYL SLPPDMRIPK NGIEKHLLRE TFEDCNLLPK EILWRPKEAF SDGITSVKNS
WFKILQDYVE HQVDDEMMSA ASQKFPFNTP KTKEGYFYRQ IFERHYPGRA DWLTHYWMPK
WINATDPSAR TLTHYKSAAK A
