Description: Homo sapiens N-acetylneuraminate pyruvate lyase (dihydrodipicolinate synthase) (NPL), transcript variant 1, mRNA. RefSeq Summary (NM_030769): This gene encodes a member of the N-acetylneuraminate lyase sub-family of (beta/alpha)(8)-barrel enzymes. N-acetylneuraminate lyases regulate cellular concentrations of N-acetyl-neuraminic acid (sialic acid) by mediating the reversible conversion of sialic acid into N-acetylmannosamine and pyruvate. A pseudogene of this gene is located on the short arm of chromosome 2. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]. Transcript (Including UTRs) Position: hg19 chr1:182,758,584-182,799,519 Size: 40,936 Total Exon Count: 13 Strand: + Coding Region Position: hg19 chr1:182,763,507-182,798,043 Size: 34,537 Coding Exon Count: 11
ID:NPL_HUMAN DESCRIPTION: RecName: Full=N-acetylneuraminate lyase; Short=NALase; EC=4.1.3.3; AltName: Full=N-acetylneuraminate pyruvate-lyase; AltName: Full=N-acetylneuraminic acid aldolase; AltName: Full=Sialate lyase; AltName: Full=Sialate-pyruvate lyase; AltName: Full=Sialic acid aldolase; AltName: Full=Sialic acid lyase; FUNCTION: Catalyzes the cleavage of N-acetylneuraminic acid (sialic acid) to form pyruvate and N-acetylmannosamine via a Schiff base intermediate. It prevents sialic acids from being recycled and returning to the cell surface. Involved in the N- glycolylneuraminic acid (Neu5Gc) degradation pathway. Although human is not able to catalyze formation of Neu5Gc due to the inactive CMAHP enzyme, Neu5Gc is present in food and must be degraded (By similarity). CATALYTIC ACTIVITY: N-acetylneuraminate = N-acetyl-D-mannosamine + pyruvate. PATHWAY: Amino-sugar metabolism; N-acetylneuraminate degradation. SUBUNIT: Homotetramer (By similarity). SUBCELLULAR LOCATION: Cytoplasm (By similarity). TISSUE SPECIFICITY: Isoform 2 is expressed in placenta, liver, kidney, pancreas, spleen, thymus, ovary, small intestine and peripheral blood leukocyte. SIMILARITY: Belongs to the DHDPS family. NanA subfamily. SEQUENCE CAUTION: Sequence=BC042003; Type=Frameshift; Positions=213;
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Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): NPL CDC HuGE Published Literature: NPL Positive Disease Associations: Cholesterol, HDL Related Studies:
Cholesterol, HDL Sekar Kathiresan et al. BMC medical genetics 2007, A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study., BMC medical genetics.
[PubMed 17903299]
Using a 100K genome-wide scan, we have generated a set of putative associations for common sequence variants and lipid phenotypes. Validation of selected hypotheses in additional samples did not identify any new loci underlying variability in blood lipids. Lack of replication may be due to inadequate statistical power to detect modest quantitative trait locus effects (i.e., <1% of trait variance explained) or reduced genomic coverage of the 100K array. GWAS in FHS using a denser genome-wide genotyping platform and a better-powered replication strategy may identify novel loci underlying blood lipids.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9BXD5
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
BC042003 - Homo sapiens N-acetylneuraminate pyruvate lyase (dihydrodipicolinate synthase), mRNA (cDNA clone IMAGE:5311213), containing frame-shift errors. BC034966 - Homo sapiens N-acetylneuraminate pyruvate lyase (dihydrodipicolinate synthase), mRNA (cDNA clone IMAGE:4825500). AK313225 - Homo sapiens cDNA, FLJ93727, highly similar to Homo sapiens N-acetylneuraminate pyruvate lyase (dihydrodipicolinate synthase) (NPL), mRNA. BC058003 - Homo sapiens N-acetylneuraminate pyruvate lyase (dihydrodipicolinate synthase), mRNA (cDNA clone MGC:61869 IMAGE:4607228), complete cds. AK297017 - Homo sapiens cDNA FLJ51988 complete cds, highly similar to Homo sapiens N-acetylneuraminate pyruvate lyase (dihydrodipicolinate synthase) (NPL), mRNA. AK301068 - Homo sapiens cDNA FLJ53104 complete cds, moderately similar to Homo sapiens N-acetylneuraminate pyruvate lyase (dihydrodipicolinate synthase) (NPL), mRNA. AY336748 - Homo sapiens N-acetylneuraminate pyruvate lyase-like protein mRNA, complete cds. AF338436 - Homo sapiens C1orf13 mRNA, complete cds. BC034429 - Homo sapiens, Similar to chromosome 1 open reading frame 13, clone IMAGE:4778103, mRNA. BC125051 - Homo sapiens N-acetylneuraminate pyruvate lyase (dihydrodipicolinate synthase), mRNA (cDNA clone MGC:149582 IMAGE:40116439), complete cds. KJ906337 - Synthetic construct Homo sapiens clone ccsbBroadEn_16007 NPL gene, encodes complete protein. KJ899661 - Synthetic construct Homo sapiens clone ccsbBroadEn_09055 NPL gene, encodes complete protein. CU691282 - Synthetic construct Homo sapiens gateway clone IMAGE:100022158 5' read NPL mRNA. KJ903319 - Synthetic construct Homo sapiens clone ccsbBroadEn_12713 NPL gene, encodes complete protein. AK310364 - Homo sapiens cDNA, FLJ17406. JD515473 - Sequence 496497 from Patent EP1572962. JD263744 - Sequence 244768 from Patent EP1572962. JD241615 - Sequence 222639 from Patent EP1572962. JD504347 - Sequence 485371 from Patent EP1572962. JD148616 - Sequence 129640 from Patent EP1572962.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa00520 - Amino sugar and nucleotide sugar metabolism
BioCyc Knowledge Library GLCMANNANAUT-PWY - superpathway of N-acetylglucosamine, N-acetylmannosamine and N-acetylneuraminate degradation PWY0-1324 - N-acetylneuraminate and N-acetylmannosamine degradation
Reactome (by CSHL, EBI, and GO)
Protein Q9BXD5 (Reactome details) participates in the following event(s):
R-HSA-4085217 NPL cleaves Neu5Ac,Neu5Gc to ManNAc,ManNGc and pyruvate R-HSA-4085001 Sialic acid metabolism R-HSA-446219 Synthesis of substrates in N-glycan biosythesis R-HSA-446193 Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein R-HSA-446203 Asparagine N-linked glycosylation R-HSA-597592 Post-translational protein modification R-HSA-392499 Metabolism of proteins