NEUA_HUMAN
ID NEUA_HUMAN Reviewed; 434 AA.
AC Q8NFW8; Q96AX5; Q9NQZ0;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 2.
DT 03-AUG-2022, entry version 159.
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 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), SUBCELLULAR LOCATION, ENZYME
RP ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=11602804; DOI=10.1023/a:1012452705349;
RA Lawrence S.M., Huddleston K.A., Tomiya N., Nguyen N., Lee Y.C., Vann W.F.,
RA Coleman T.A., Betenbaugh M.J.;
RT "Cloning and expression of human sialic acid pathway genes to generate CMP-
RT sialic acids in insect cells.";
RL Glycoconj. J. 18:205-213(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Bouquin T., Mundy J.;
RT "Human mRNA for CMP-N-acetylneuraminic acid synthase.";
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Stomach;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta;
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 [6]
RP PROTEIN SEQUENCE OF 1-16; 38-52; 189-200; 307-316 AND 384-399, ACETYLATION
RP AT MET-1, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Mammary carcinoma;
RA Bienvenut W.V., Lourenco F., Olson M.F.;
RL Submitted (AUG-2009) to UniProtKB.
RN [7]
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 [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [9]
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).
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).
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:11602804};
CC -!- PATHWAY: Amino-sugar metabolism; N-acetylneuraminate metabolism.
CC -!- SUBUNIT: Homotetramer; the active enzyme is formed by a dimer of
CC dimers.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11602804}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8NFW8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NFW8-2; Sequence=VSP_012764;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Expressed in pancreas,
CC kidney, liver, skeletal muscle, lung, placenta, brain, heart, colon,
CC PBL, small intestine, ovary, testis, prostate, thymus and spleen.
CC {ECO:0000269|PubMed:11602804}.
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 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the CMP-NeuNAc synthase family. {ECO:0000305}.
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DR EMBL; AF397212; AAM90580.1; -; mRNA.
DR EMBL; AF271388; AAF76203.1; -; mRNA.
DR EMBL; AK022927; BAB14311.1; -; mRNA.
DR EMBL; AL832975; CAH56346.1; -; mRNA.
DR EMBL; BC016609; AAH16609.1; -; mRNA.
DR CCDS; CCDS8696.1; -. [Q8NFW8-1]
DR RefSeq; NP_061156.1; NM_018686.5. [Q8NFW8-1]
DR AlphaFoldDB; Q8NFW8; -.
DR SMR; Q8NFW8; -.
DR BioGRID; 120993; 117.
DR IntAct; Q8NFW8; 28.
DR MINT; Q8NFW8; -.
DR STRING; 9606.ENSP00000229329; -.
DR DrugBank; DB02485; Cytidine-5'-Monophosphate-5-N-Acetylneuraminic Acid.
DR iPTMnet; Q8NFW8; -.
DR PhosphoSitePlus; Q8NFW8; -.
DR SwissPalm; Q8NFW8; -.
DR BioMuta; CMAS; -.
DR DMDM; 68059539; -.
DR EPD; Q8NFW8; -.
DR jPOST; Q8NFW8; -.
DR MassIVE; Q8NFW8; -.
DR MaxQB; Q8NFW8; -.
DR PaxDb; Q8NFW8; -.
DR PeptideAtlas; Q8NFW8; -.
DR PRIDE; Q8NFW8; -.
DR ProteomicsDB; 73375; -. [Q8NFW8-1]
DR ProteomicsDB; 73376; -. [Q8NFW8-2]
DR Antibodypedia; 24116; 108 antibodies from 25 providers.
DR DNASU; 55907; -.
DR Ensembl; ENST00000229329.7; ENSP00000229329.2; ENSG00000111726.13. [Q8NFW8-1]
DR Ensembl; ENST00000534981.5; ENSP00000446239.1; ENSG00000111726.13. [Q8NFW8-2]
DR GeneID; 55907; -.
DR KEGG; hsa:55907; -.
DR MANE-Select; ENST00000229329.7; ENSP00000229329.2; NM_018686.6; NP_061156.1.
DR UCSC; uc001rfm.5; human. [Q8NFW8-1]
DR CTD; 55907; -.
DR DisGeNET; 55907; -.
DR GeneCards; CMAS; -.
DR HGNC; HGNC:18290; CMAS.
DR HPA; ENSG00000111726; Low tissue specificity.
DR MIM; 603316; gene.
DR neXtProt; NX_Q8NFW8; -.
DR OpenTargets; ENSG00000111726; -.
DR PharmGKB; PA38519; -.
DR VEuPathDB; HostDB:ENSG00000111726; -.
DR eggNOG; ENOG502QQH3; Eukaryota.
DR GeneTree; ENSGT00390000004237; -.
DR HOGENOM; CLU_042930_0_1_1; -.
DR InParanoid; Q8NFW8; -.
DR OMA; FHGFVWR; -.
DR OrthoDB; 781897at2759; -.
DR PhylomeDB; Q8NFW8; -.
DR TreeFam; TF324840; -.
DR BRENDA; 2.7.7.43; 2681.
DR PathwayCommons; Q8NFW8; -.
DR Reactome; R-HSA-4085001; Sialic acid metabolism.
DR SignaLink; Q8NFW8; -.
DR UniPathway; UPA00628; -.
DR BioGRID-ORCS; 55907; 38 hits in 1092 CRISPR screens.
DR ChiTaRS; CMAS; human.
DR GeneWiki; CMAS_(gene); -.
DR GenomeRNAi; 55907; -.
DR Pharos; Q8NFW8; Tbio.
DR PRO; PR:Q8NFW8; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q8NFW8; protein.
DR Bgee; ENSG00000111726; Expressed in adrenal tissue and 193 other tissues.
DR ExpressionAtlas; Q8NFW8; baseline and differential.
DR Genevisible; Q8NFW8; HS.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0008781; F:N-acylneuraminate cytidylyltransferase activity; IBA:GO_Central.
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 Acetylation; Alternative splicing; Direct protein sequencing; Methylation;
KW Nucleotidyltransferase; Nucleus; Reference proteome; Transferase.
FT CHAIN 1..434
FT /note="N-acylneuraminate cytidylyltransferase"
FT /id="PRO_0000213199"
FT REGION 1..42
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 15..31
FT /note="BC1 motif"
FT MOTIF 200..206
FT /note="BC2 motif"
FT MOTIF 269..276
FT /note="BC3 motif"
FT COMPBIAS 1..17
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 201
FT /evidence="ECO:0000250"
FT BINDING 52
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 62
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 111
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 120
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 122
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 143
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PubMed:22814378"
FT MOD_RES 37
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q99KK2"
FT MOD_RES 52
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q99KK2"
FT VAR_SEQ 264..434
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_012764"
FT CONFLICT 396
FT /note="T -> Y (in Ref. 1; AAM90580)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 434 AA; 48379 MW; B303B6647EF81A3A CRC64;
MDSVEKGAAT SVSNPRGRPS RGRPPKLQRN SRGGQGRGVE KPPHLAALIL ARGGSKGIPL
KNIKHLAGVP LIGWVLRAAL DSGAFQSVWV STDHDEIENV AKQFGAQVHR RSSEVSKDSS
TSLDAIIEFL NYHNEVDIVG NIQATSPCLH PTDLQKVAEM IREEGYDSVF SVVRRHQFRW
SEIQKGVREV TEPLNLNPAK RPRRQDWDGE LYENGSFYFA KRHLIEMGYL QGGKMAYYEM
RAEHSVDIDV DIDWPIAEQR VLRYGYFGKE KLKEIKLLVC NIDGCLTNGH IYVSGDQKEI
ISYDVKDAIG ISLLKKSGIE VRLISERACS KQTLSSLKLD CKMEVSVSDK LAVVDEWRKE
MGLCWKEVAY LGNEVSDEEC LKRVGLSGAP ADACSTAQKA VGYICKCNGG RGAIREFAEH
ICLLMEKVNN SCQK
