NEUA_MOUSE
ID NEUA_MOUSE Reviewed; 432 AA.
AC Q99KK2; O88719; Q8C330; Q8K2G7;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 2.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=N-acylneuraminate cytidylyltransferase;
DE EC=2.7.7.43;
DE AltName: Full=CMP-N-acetylneuraminic acid synthase;
DE Short=CMP-NeuNAc synthase;
GN Name=Cmas;
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] (ISOFORM 1), FUNCTION, ENZYME ACTIVITY,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9689047; DOI=10.1073/pnas.95.16.9140;
RA Muenster A.-K., Eckhardt M., Potvin B., Muehlenhoff M., Stanley P.,
RA Gerardy-Schahn R.;
RT "Mammalian cytidine 5-prime-monophosphate N-acetylneuraminic acid
RT synthetase: a nuclear protein with evolutionarily conserved structural
RT motifs.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:9140-9145(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Lung;
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] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Colon, and Mammary tumor;
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 SUBCELLULAR LOCATION, ENZYME ACTIVITY, AND MUTAGENESIS OF LYS-198; ARG-199;
RP PRO-200; ARG-201; ARG-202; GLN-203 AND ASP-204.
RX PubMed=11893746; DOI=10.1074/jbc.m201093200;
RA Muenster A.-K., Weinhold B., Gotza B., Muehlenhoff M., Frosch M.,
RA Gerardy-Schahn R.;
RT "Nuclear localization signal of murine CMP-Neu5Ac synthetase includes
RT residues required for both nuclear targeting and enzymatic activity.";
RL J. Biol. Chem. 277:19688-19696(2002).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Liver, and Pancreas;
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 [6]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-35 AND ARG-50, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 40-268 IN COMPLEX WITH CMP-NEUNAC,
RP AND SUBUNIT.
RX PubMed=14636592; DOI=10.1016/j.jmb.2003.09.080;
RA Krapp S., Muenster-Kuehnel A.-K., Kaiser J.T., Huber R., Tiralongo J.,
RA Gerardy-Schahn R., Jacob U.;
RT "The crystal structure of murine CMP-5-N-acetylneuraminic acid
RT synthetase.";
RL J. Mol. Biol. 334:625-637(2003).
CC -!- FUNCTION: Catalyzes the activation of N-acetylneuraminic acid (NeuNAc)
CC to cytidine 5'-monophosphate N-acetylneuraminic acid (CMP-NeuNAc), a
CC substrate required for the addition of sialic acid. Has some activity
CC toward NeuNAc, N-glycolylneuraminic acid (Neu5Gc) or 2-keto-3-deoxy-D-
CC glycero-D-galacto-nononic acid (KDN). {ECO:0000269|PubMed:9689047}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-acylneuraminate + CTP = a CMP-N-acyl-beta-neuraminate +
CC diphosphate; Xref=Rhea:RHEA:11344, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:37563, ChEBI:CHEBI:60073, ChEBI:CHEBI:68671; EC=2.7.7.43;
CC Evidence={ECO:0000269|PubMed:11893746, ECO:0000269|PubMed:9689047};
CC -!- PATHWAY: Amino-sugar metabolism; N-acetylneuraminate metabolism.
CC -!- SUBUNIT: Homotetramer; the active enzyme is formed by a dimer of
CC dimers. {ECO:0000269|PubMed:14636592}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11893746,
CC ECO:0000269|PubMed:9689047}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q99KK2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99KK2-2; Sequence=VSP_012765;
CC -!- TISSUE SPECIFICITY: Highly expressed in brain and heart, and at
CC intermediate level muscle and liver. {ECO:0000269|PubMed:9689047}.
CC -!- DOMAIN: The BC2 (basic cluster 2) motif is necessary and sufficient for
CC the nuclear localization and contains the catalytic active site. The
CC localization in the nucleus is however not required for the enzyme
CC activity.
CC -!- MISCELLANEOUS: [Isoform 2]: Inactive. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the CMP-NeuNAc synthase family. {ECO:0000305}.
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DR EMBL; AJ006215; CAA06915.1; -; mRNA.
DR EMBL; AK087150; BAC39813.1; -; mRNA.
DR EMBL; BC004606; AAH04606.1; -; mRNA.
DR EMBL; BC031500; AAH31500.1; -; mRNA.
DR EMBL; BC063776; AAH63776.1; -; mRNA.
DR CCDS; CCDS20687.1; -. [Q99KK2-1]
DR RefSeq; NP_034038.2; NM_009908.2.
DR PDB; 1QWJ; X-ray; 2.80 A; A/B/C/D=40-268.
DR PDB; 3EWI; X-ray; 1.90 A; A/B=267-432.
DR PDBsum; 1QWJ; -.
DR PDBsum; 3EWI; -.
DR AlphaFoldDB; Q99KK2; -.
DR SMR; Q99KK2; -.
DR BioGRID; 198764; 2.
DR STRING; 10090.ENSMUSP00000032419; -.
DR ChEMBL; CHEMBL4523436; -.
DR iPTMnet; Q99KK2; -.
DR PhosphoSitePlus; Q99KK2; -.
DR SwissPalm; Q99KK2; -.
DR EPD; Q99KK2; -.
DR MaxQB; Q99KK2; -.
DR PaxDb; Q99KK2; -.
DR PeptideAtlas; Q99KK2; -.
DR PRIDE; Q99KK2; -.
DR ProteomicsDB; 252823; -. [Q99KK2-1]
DR ProteomicsDB; 252824; -. [Q99KK2-2]
DR DNASU; 12764; -.
DR GeneID; 12764; -.
DR KEGG; mmu:12764; -.
DR UCSC; uc009eps.2; mouse. [Q99KK2-1]
DR CTD; 55907; -.
DR MGI; MGI:1337124; Cmas.
DR eggNOG; ENOG502QQH3; Eukaryota.
DR InParanoid; Q99KK2; -.
DR OrthoDB; 781897at2759; -.
DR PhylomeDB; Q99KK2; -.
DR TreeFam; TF324840; -.
DR BioCyc; MetaCyc:MON-14521; -.
DR BRENDA; 2.7.7.43; 3474.
DR BRENDA; 2.7.7.92; 3474.
DR Reactome; R-MMU-4085001; Sialic acid metabolism.
DR SABIO-RK; Q99KK2; -.
DR UniPathway; UPA00628; -.
DR BioGRID-ORCS; 12764; 23 hits in 75 CRISPR screens.
DR ChiTaRS; Cmas; mouse.
DR EvolutionaryTrace; Q99KK2; -.
DR PRO; PR:Q99KK2; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q99KK2; protein.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0008781; F:N-acylneuraminate cytidylyltransferase activity; ISO:MGI.
DR GO; GO:0006055; P:CMP-N-acetylneuraminate biosynthetic process; ISO:MGI.
DR GO; GO:0006054; P:N-acetylneuraminate metabolic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.40.50.1000; -; 1.
DR Gene3D; 3.90.550.10; -; 1.
DR InterPro; IPR003329; Cytidylyl_trans.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR023214; HAD_sf.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR Pfam; PF02348; CTP_transf_3; 1.
DR SUPFAM; SSF53448; SSF53448; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Methylation;
KW Nucleotidyltransferase; Nucleus; Reference proteome; Transferase.
FT CHAIN 1..432
FT /note="N-acylneuraminate cytidylyltransferase"
FT /id="PRO_0000213200"
FT REGION 1..38
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 15..31
FT /note="BC1 motif"
FT MOTIF 198..204
FT /note="BC2 motif"
FT MOTIF 267..274
FT /note="BC3 motif"
FT ACT_SITE 199
FT BINDING 50
FT /ligand="substrate"
FT BINDING 60
FT /ligand="substrate"
FT BINDING 109
FT /ligand="substrate"
FT BINDING 118
FT /ligand="substrate"
FT BINDING 120
FT /ligand="substrate"
FT BINDING 141
FT /ligand="substrate"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q8NFW8"
FT MOD_RES 35
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 50
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT VAR_SEQ 1..232
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_012765"
FT MUTAGEN 196
FT /note="P->A: Does not affect the nuclear localization."
FT MUTAGEN 198
FT /note="K->A: Abolishes the nuclear localization but does
FT not affect the enzyme activity; when associated with A-
FT 201."
FT /evidence="ECO:0000269|PubMed:11893746"
FT MUTAGEN 199
FT /note="R->A: Abolishes both the nuclear localization and
FT the enzyme activity."
FT /evidence="ECO:0000269|PubMed:11893746"
FT MUTAGEN 200
FT /note="P->A: Does not affect neither the nuclear
FT localization nor the enzyme activity."
FT /evidence="ECO:0000269|PubMed:11893746"
FT MUTAGEN 201
FT /note="R->A: Abolishes the nuclear localization but does
FT not affect the enzyme activity; when associated with A-
FT 198."
FT /evidence="ECO:0000269|PubMed:11893746"
FT MUTAGEN 202
FT /note="R->A: Does not strongly affect the nuclear
FT localization but strongly affects the enzyme activity."
FT /evidence="ECO:0000269|PubMed:11893746"
FT MUTAGEN 203
FT /note="Q->A: Does not affect the nuclear localization but
FT affects the enzyme activity."
FT /evidence="ECO:0000269|PubMed:11893746"
FT MUTAGEN 204
FT /note="D->A: Does not affect the nuclear localization."
FT /evidence="ECO:0000269|PubMed:11893746"
FT CONFLICT 9
FT /note="V -> A (in Ref. 3; AAH31500/AAH63776)"
FT /evidence="ECO:0000305"
FT STRAND 43..48
FT /evidence="ECO:0007829|PDB:1QWJ"
FT STRAND 54..57
FT /evidence="ECO:0007829|PDB:1QWJ"
FT TURN 59..61
FT /evidence="ECO:0007829|PDB:1QWJ"
FT STRAND 62..64
FT /evidence="ECO:0007829|PDB:1QWJ"
FT HELIX 69..80
FT /evidence="ECO:0007829|PDB:1QWJ"
FT STRAND 84..91
FT /evidence="ECO:0007829|PDB:1QWJ"
FT HELIX 93..101
FT /evidence="ECO:0007829|PDB:1QWJ"
FT STRAND 105..108
FT /evidence="ECO:0007829|PDB:1QWJ"
FT HELIX 111..113
FT /evidence="ECO:0007829|PDB:1QWJ"
FT HELIX 120..128
FT /evidence="ECO:0007829|PDB:1QWJ"
FT STRAND 135..140
FT /evidence="ECO:0007829|PDB:1QWJ"
FT HELIX 149..160
FT /evidence="ECO:0007829|PDB:1QWJ"
FT STRAND 165..173
FT /evidence="ECO:0007829|PDB:1QWJ"
FT STRAND 191..195
FT /evidence="ECO:0007829|PDB:1QWJ"
FT TURN 202..204
FT /evidence="ECO:0007829|PDB:1QWJ"
FT STRAND 208..219
FT /evidence="ECO:0007829|PDB:1QWJ"
FT HELIX 220..224
FT /evidence="ECO:0007829|PDB:1QWJ"
FT STRAND 231..237
FT /evidence="ECO:0007829|PDB:1QWJ"
FT HELIX 240..242
FT /evidence="ECO:0007829|PDB:1QWJ"
FT HELIX 246..249
FT /evidence="ECO:0007829|PDB:1QWJ"
FT HELIX 252..262
FT /evidence="ECO:0007829|PDB:1QWJ"
FT STRAND 275..279
FT /evidence="ECO:0007829|PDB:3EWI"
FT HELIX 280..284
FT /evidence="ECO:0007829|PDB:3EWI"
FT STRAND 298..302
FT /evidence="ECO:0007829|PDB:3EWI"
FT HELIX 303..314
FT /evidence="ECO:0007829|PDB:3EWI"
FT STRAND 318..322
FT /evidence="ECO:0007829|PDB:3EWI"
FT HELIX 329..333
FT /evidence="ECO:0007829|PDB:3EWI"
FT HELIX 348..358
FT /evidence="ECO:0007829|PDB:3EWI"
FT HELIX 363..365
FT /evidence="ECO:0007829|PDB:3EWI"
FT STRAND 366..369
FT /evidence="ECO:0007829|PDB:3EWI"
FT HELIX 373..375
FT /evidence="ECO:0007829|PDB:3EWI"
FT HELIX 376..381
FT /evidence="ECO:0007829|PDB:3EWI"
FT STRAND 382..387
FT /evidence="ECO:0007829|PDB:3EWI"
FT HELIX 393..396
FT /evidence="ECO:0007829|PDB:3EWI"
FT STRAND 400..402
FT /evidence="ECO:0007829|PDB:3EWI"
FT TURN 407..410
FT /evidence="ECO:0007829|PDB:3EWI"
FT HELIX 411..426
FT /evidence="ECO:0007829|PDB:3EWI"
SQ SEQUENCE 432 AA; 48058 MW; BF7295535E7F6CE5 CRC64;
MDALEKGAVT SGPAPRGRPS RGRPPKLQRS RGAGRGLEKP PHLAALVLAR GGSKGIPLKN
IKRLAGVPLI GWVLRAALDA GVFQSVWVST DHDEIENVAK QFGAQVHRRS SETSKDSSTS
LDAIVEFLNY HNEVDIVGNI QATSPCLHPT DLQKVAEMIR EEGYDSVFSV VRRHQFRWSE
IQKGVREVTE PLNLNPAKRP RRQDWDGELY ENGSFYFAKR HLIEMGYLQG GKMAYYEMRA
EHSVDIDVDI DWPIAEQRVL RFGYFGKEKL KEIKLLVCNI DGCLTNGHIY VSGDQKEIIS
YDVKDAIGIS LLKKSGIEVR LISERACSKQ TLSALKLDCK TEVSVSDKLA TVDEWRKEMG
LCWKEVAYLG NEVSDEECLK RVGLSAVPAD ACSGAQKAVG YICKCSGGRG AIREFAEHIF
LLIEKVNNSC QK
