Disease relevance of NAP1L4

• Mutation analysis of H19 and NAP1L4 (hNAP2) candidate genes and IGF2 DMR2 in Beckwith-Wiedemann syndrome [1].
• Functional analysis of recombinant NAP-2 protein purified from Escherichia coli demonstrates that this protein can interact with both core and linker histones [2].
• Deposition of CTAP-III in tissues, such as synovium, spleen, and kidney, is associated with partial processing to NAP-2-like isoforms and the potential to induce neutrophil and fibroblast activation in patients with rheumatic or end-stage renal disease [3].
• Several chemokines that are produced in the ground state, including MCP-1, NAP 2 and RANTES, are upregulated significantly by KSHV infection [4].
• We carried out studies to determine whether the neutrophil-activation peptide-2 (NAP-2) plays a role in the recruitment and/or degranulation of neutrophils into the lungs of patients with the adult respiratory distress syndrome (ARDS) or congestive heart failure (CHF) [5].

High impact information on NAP1L4

• One of the truncated products of LDGF, NAP-2, is a potent neutrophil chemoattractant [6].
• Sequence analysis of the LDGF peptide revealed that it is a precursor of other known peptides including platelet basic protein (PBP), connective tissue activating peptide III (CTAP-III), and neutrophil activating peptide 2 (NAP-2) [6].
• Platelet-derived CTAP-III and a cleavage isoform with the electrophoretic mobility of CTAP-III-des 1-15/neutrophil-activating peptide-2 (NAP-2) and PGE2 were found in biologically active extracts of synovial samples from patients with RA and OA [7].
• Here, we demonstrate that casein kinase 2 (CKII) from HeLa cell nuclear extracts interacts with immobilized NAP-II, and phosphorylates both NAP-2 and nucleosome assembly protein 1 (NAP-1) in vitro [8].
• NAP-2: histone chaperone function and phosphorylation state through the cell cycle [8].

Biological context of NAP1L4

• Phosphorylated NAP-2 remains in the cytoplasm in a complex with histones during the G0/G1 transition, whereas its dephosphorylation triggers its transport into the nucleus, at the G1/S-boundary, with the histone cargo, suggesting that binding to histones does not depend on phosphorylation status [8].
• Finally, indirect immunofluorescence shows that NAP-2 is present during metaphase of HeLa and COS cells, and its localization is distinct from metaphase chromosomes [8].
• The deduced amino acid sequence of NAP-2 indicates that it encodes a protein with a potential nuclear localization motif and two clusters of highly acidic residues [2].
• Deletion mutagenesis of NAP-2 demonstrates that both NH3- and COOH-terminal domains are required for histone transfer activity [2].
• During early inflammation, the chemoattractants neutrophil-activating peptide-2 (NAP-2), platelet-activating factor (PAF), and complement component C5a are rapidly generated within the vasculature and potently induce effector functions in neutrophils, such as chemotaxis and degranulation [9].

Anatomical context of NAP1L4

• NAP-2 (0.1-1.5 microns) caused the release of human granulocyte elastase from cytochalasin B-treated neutrophils in a dose-dependent manner [10].
• RESULTS: Crude (24.2 micrograms/mL-2.42 mg/mL), void (5.4 micrograms/mL-0.54 mg/mL), peak 2 (3.5 micrograms/mL-0.35 mg/mL), and NAP-2 (1-20 micrograms/mL) failed to release histamine from lung mast cells [11].
• Radial nerve was first stimulated with a single shock and then with double shocks at intervals of 2, 3, 4, 5, 6, 7, and 8 ms; NAP amplitudes and NAP1/NAP2 ratios were calculated in normals and diabetics [12].
• Chemotactically active NAP-2 was also demonstrated in PEFs but not in plasmas from patients with CHF and ARDS [5].

Associations of NAP1L4 with chemical compounds

• Second, a negatively charged resin (heparin) was used, which retained small amounts of NAP-2 (a very acidic polypeptide) and topoisomerase I. This fraction, although able to supercoil relaxed DNA, did so to a lesser extent than the Q-Sepharose fraction [13].
• Here, using HeLa cell nuclear extracts, we found NAP-2 migrates in a blue-native polyacrylamide gel with an apparent molecular weight of 300 kDa [13].
• HeLa cell NAP-2, labeled in vivo with radioactive orthophosphate, co-precipitated with at least two phosphoproteins, with an apparent mass of 100 and 175 kDa, respectively, as determined by SDS-PAGE [13].

Other interactions of NAP1L4

• Two of these genes, NAP1L4 and KCNA9, had been previously reported [14].
• We previously reported that a complex of nuclear proteins from HeLa cells, among them histone H1 and casein kinase 2 co-eluted from immobilized nucleosome assembly protein 2 (NAP-2)-Sepharose [13].

Analytical, diagnostic and therapeutic context of NAP1L4

• NAP-2, the shortest form of CXCL7 detected in the coculture media, was confirmed to decrease the size and number of CFU-Meg colonies [15].
• Sensitive immunological identification of NAP-2 based on nonequilibrium isoelectric focusing and immunoblotting is described [10].
• Neutrophil-activating peptide 2 (NAP-2), corresponding to platelet basic protein fragment 25-94, was prepared by chymotryptic digestion of its precursors, low affinity platelet factor 4 or beta-thromboglobulin, followed by purification by high performance liquid chromatography [10].

References