NPL_MOUSE
ID NPL_MOUSE Reviewed; 320 AA.
AC Q9DCJ9;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=N-acetylneuraminate lyase {ECO:0000305};
DE Short=NALase;
DE EC=4.1.3.3 {ECO:0000269|PubMed:22692205};
DE AltName: Full=N-acetylneuraminate pyruvate-lyase;
DE AltName: Full=N-acetylneuraminic acid aldolase;
DE AltName: Full=Sialate lyase;
DE AltName: Full=Sialate-pyruvate lyase;
DE AltName: Full=Sialic acid aldolase;
DE AltName: Full=Sialic acid lyase;
GN Name=Npl {ECO:0000312|MGI:MGI:1921341};
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Kidney, and Thymus;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-308, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC 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 [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=22692205; DOI=10.1074/jbc.m112.363549;
RA Bergfeld A.K., Pearce O.M., Diaz S.L., Pham T., Varki A.;
RT "Metabolism of vertebrate amino sugars with N-glycolyl groups: elucidating
RT the intracellular fate of the non-human sialic acid N-glycolylneuraminic
RT acid.";
RL J. Biol. Chem. 287:28865-28881(2012).
CC -!- FUNCTION: Catalyzes the cleavage of N-acetylneuraminic acid (sialic
CC acid) to form pyruvate and N-acetylmannosamine via a Schiff base
CC intermediate. It prevents sialic acids from being recycled and
CC returning to the cell surface. Involved in the N-glycolylneuraminic
CC acid (Neu5Gc) degradation pathway. {ECO:0000269|PubMed:22692205}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=aceneuramate = N-acetyl-D-mannosamine + pyruvate;
CC Xref=Rhea:RHEA:23296, ChEBI:CHEBI:15361, ChEBI:CHEBI:17122,
CC ChEBI:CHEBI:173083; EC=4.1.3.3;
CC Evidence={ECO:0000269|PubMed:22692205};
CC -!- PATHWAY: Amino-sugar metabolism; N-acetylneuraminate degradation.
CC {ECO:0000269|PubMed:22692205}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:Q9BXD5}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the DapA family. NanA subfamily. {ECO:0000305}.
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DR EMBL; AK002734; BAB22314.1; -; mRNA.
DR EMBL; AK088859; BAC40618.1; -; mRNA.
DR EMBL; BC022734; AAH22734.1; -; mRNA.
DR CCDS; CCDS15374.1; -.
DR RefSeq; NP_083025.1; NM_028749.1.
DR AlphaFoldDB; Q9DCJ9; -.
DR SMR; Q9DCJ9; -.
DR BioGRID; 216484; 2.
DR STRING; 10090.ENSMUSP00000037454; -.
DR iPTMnet; Q9DCJ9; -.
DR PhosphoSitePlus; Q9DCJ9; -.
DR EPD; Q9DCJ9; -.
DR jPOST; Q9DCJ9; -.
DR MaxQB; Q9DCJ9; -.
DR PaxDb; Q9DCJ9; -.
DR PeptideAtlas; Q9DCJ9; -.
DR PRIDE; Q9DCJ9; -.
DR ProteomicsDB; 295513; -.
DR Antibodypedia; 34441; 131 antibodies from 20 providers.
DR DNASU; 74091; -.
DR Ensembl; ENSMUST00000041874; ENSMUSP00000037454; ENSMUSG00000042684.
DR GeneID; 74091; -.
DR KEGG; mmu:74091; -.
DR UCSC; uc007dac.1; mouse.
DR CTD; 80896; -.
DR MGI; MGI:1921341; Npl.
DR VEuPathDB; HostDB:ENSMUSG00000042684; -.
DR eggNOG; ENOG502QQA3; Eukaryota.
DR GeneTree; ENSGT00530000063604; -.
DR HOGENOM; CLU_049343_6_1_1; -.
DR InParanoid; Q9DCJ9; -.
DR OMA; LPPMRYK; -.
DR OrthoDB; 1238597at2759; -.
DR PhylomeDB; Q9DCJ9; -.
DR TreeFam; TF353639; -.
DR Reactome; R-MMU-4085001; Sialic acid metabolism.
DR UniPathway; UPA00629; -.
DR BioGRID-ORCS; 74091; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Npl; mouse.
DR PRO; PR:Q9DCJ9; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q9DCJ9; protein.
DR Bgee; ENSMUSG00000042684; Expressed in stroma of bone marrow and 225 other tissues.
DR Genevisible; Q9DCJ9; MM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0008747; F:N-acetylneuraminate lyase activity; IDA:UniProtKB.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0019262; P:N-acetylneuraminate catabolic process; ISS:UniProtKB.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR002220; DapA-like.
DR PANTHER; PTHR12128; PTHR12128; 1.
DR Pfam; PF00701; DHDPS; 1.
DR PIRSF; PIRSF001365; DHDPS; 1.
DR PRINTS; PR00146; DHPICSNTHASE.
DR SMART; SM01130; DHDPS; 1.
PE 1: Evidence at protein level;
KW Carbohydrate metabolism; Cytoplasm; Lyase; Phosphoprotein;
KW Reference proteome; Schiff base.
FT CHAIN 1..320
FT /note="N-acetylneuraminate lyase"
FT /id="PRO_0000273353"
FT ACT_SITE 173
FT /note="Schiff-base intermediate with substrate"
FT /evidence="ECO:0000250"
FT BINDING 51..52
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT SITE 143
FT /note="Involved in proton transfer during cleavage"
FT /evidence="ECO:0000250"
FT MOD_RES 308
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 320 AA; 35130 MW; 9426AD7CC8438468 CRC64;
MAFPKKKLRG LVAATITPMT ENGEINFPVI GQYVDYLVKE QGVKNIFVNG TTGEGLSLSV
SERRQVAEEW VNQGRNKLDQ VVIHVGALNV KESQELAQHA AEIGADGIAV IAPFFFKSQN
KDALISFLRE VAAAAPTLPF YYYHMPSMTG VKIRAEELLD GIQDKIPTFQ GLKFTDTDLL
DFGQCVDQNH QRQFALLFGV DEQLLSALVM GATGAVGSTY NYLGKKTNQM LEAFEQKDLA
SALSYQFRIQ RFINYVIKLG FGVSQTKAIM TLVSGIPMGP PRLPLQKATQ EFTAKAEAKL
KSLDFLSSPS VKEGKPLASA
