Gene Summary

Gene:NACA; nascent polypeptide associated complex subunit alpha
Aliases: HSD48, NACA1, skNAC, NAC-alpha
Summary:This gene encodes a protein that associates with basic transcription factor 3 (BTF3) to form the nascent polypeptide-associated complex (NAC). This complex binds to nascent proteins that lack a signal peptide motif as they emerge from the ribosome, blocking interaction with the signal recognition particle (SRP) and preventing mistranslocation to the endoplasmic reticulum. This protein is an IgE autoantigen in atopic dermatitis patients. Alternative splicing results in multiple transcript variants, but the full length nature of some of these variants, including those encoding very large proteins, has not been determined. There are multiple pseudogenes of this gene on different chromosomes. [provided by RefSeq, Feb 2016]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:nascent polypeptide-associated complex subunit alpha
Source:NCBIAccessed: 31 August, 2019


What does this gene/protein do?
Show (9)

Cancer Overview

Research Indicators

Publications Per Year (1994-2019)
Graph generated 31 August 2019 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • KMT2A protein, human
  • Leukemia, Myelomonocytic, Acute
  • Up-Regulation
  • Acute Myeloid Leukaemia
  • Single Nucleotide Polymorphism
  • Sequence Analysis, RNA
  • Whole Exome Sequencing
  • Chromosome 12
  • Leukemic Gene Expression Regulation
  • Gene Expression Profiling
  • Western Blotting
  • Renal Cell Carcinoma
  • Northern Blotting
  • Gene Deletion
  • Down-Regulation
  • Homozygote
  • Interleukin-18
  • Histone-Lysine N-Methyltransferase
  • FISH
  • Molecular Chaperones
  • Southern Blotting
  • Messenger RNA
  • Annexin A2
  • SLC7A11 protein, human
  • KMT2A
  • Trans-Activators
  • Gene Expression
  • NF-kappa B
  • Cancer RNA
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction
  • Age of Onset
  • Kidney Cancer
  • nascent-polypeptide-associated complex
  • Amino Acid Transport System y+
  • Gene Expression Regulation
  • Kidney
Tag cloud generated 31 August, 2019 using data from PubMed, MeSH and CancerIndex

Specific Cancers (2)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: NACA (cancer-related)

Bhunia S, Radha V, Chaudhuri A
CDC20siRNA and paclitaxel co-loaded nanometric liposomes of a nipecotic acid-derived cationic amphiphile inhibit xenografted neuroblastoma.
Nanoscale. 2017; 9(3):1201-1212 [PubMed] Related Publications
Despite significant recent progress in the area of translational genomics of neuroblastoma, the overall survival rates for children with high-risk NB continue to be not more than 5 years due to tumor relapse and/or drug-resistant tumors. Herein we report on the development of a neuroblastoma targeting nanometric (130-150 nm) circulation stable liposomal system prepared from a novel nipecotic acid-derived cationic amphiphile (NACA). The size ranges of liposomes (130-150 nm) were confirmed by both dynamic light scattering and transmission electron microscopy. The findings in the gel electrophoresis assay revealed that siRNAs encapsulated within the liposomes of NACA (with 90% entrapment efficiency) are protected from attack by RNase. Cellular uptake experiments using FAM-siRNA loaded liposomes of NACA showed the liposomal entry in human neuroblastoma cells (IMR-32) to be mediated via the GABA

Wang J, Papanicolau-Sengos A, Chintala S, et al.
Collecting duct carcinoma of the kidney is associated with CDKN2A deletion and SLC family gene up-regulation.
Oncotarget. 2016; 7(21):29901-15 [PubMed] Free Access to Full Article Related Publications
The genetic landscape and molecular features of collecting duct carcinoma (CDC) of the kidney remain largely unknown. Herein, we performed whole exome sequencing (WES) and transcriptome sequencing (RNASeq) on 7 CDC samples (CDC1 -7). Among the 7 samples, 4 samples with matched non-tumor tissue were used for copy number analysis by SNP array data. No recurrent somatic SNVs were observed except for MLL, which was found to be mutated (p.V297I and p.F407C) in 2 samples. We identified somatic SNVs in 14 other cancer census genes including: ATM, CREBBP, PRDM1, CBFB, FBXW7, IKZF1, KDR, KRAS, NACA, NF2, NUP98, SS18, TP53, and ZNF521. SNP array data identified a CDKN2A homozygous deletion in 3 samples and SNV analysis showed a non-sense mutation of the CDKN2A gene with unknown somatic status. To estimate the recurrent rate of CDKN2A abnormalities, we performed FISH screening of additional samples and confirmed the frequent loss (62.5%) of CDKN2A expression. Since cisplatin based therapy is the common treatment option for CDC, we investigated the expression of solute carrier (SLC) family transporters and found 45% alteration. In addition, SLC7A11 (cystine transporter, xCT), a cisplatin resistance associated gene, was found to be overexpressed in 4 out of 5 (80%) cases of CDC tumors tested, as compared to matched non-tumor tissue. In summary, our study provides a comprehensive genomic analysis of CDC and identifies potential pathways suitable for targeted therapies.

Berkholz J, Kuzyniak W, Hoepfner M, Munz B
Overexpression of the skNAC gene in human rhabdomyosarcoma cells enhances their differentiation potential and inhibits tumor cell growth and spreading.
Clin Exp Metastasis. 2014; 31(8):869-79 [PubMed] Related Publications
Skeletal and heart muscle-specific variant of the alpha subunit of nascent polypeptide complex (skNAC) is exclusively present in striated muscle cells. During skeletal muscle cell differentiation, skNAC expression is strongly induced, suggesting that the protein might be a regulator of the differentiation process. Rhabdomyosarcoma is a tumor of skeletal muscle origin. Since there is a strong inverse correlation between rhabdomyosarcoma cell differentiation status and metastatic potential, we analyzed skNAC expression patterns in a set of rhabdomyosarcoma cell lines: Whereas RD/12 and RD/18 cells showed a marked induction of skNAC gene expression upon the induction of differentiation-similarly as the one seen in nontransformed myoblasts-skNAC was not induced in CCA or Rh30 cells. Overexpressing skNAC in CCA and Rh30 cells led to a reduction in cell cycle progression and cell proliferation accompanied by an upregulation of specific myogenic differentiation markers, such as Myogenin or Myosin Heavy Chain. Furthermore, in contrast to vector-transfected controls, a high percentage of the cells formed long, Myosin Heavy Chain-positive, multinucleate myotubes. Consistently, soft agar assays revealed a drop in the metastatic potential of skNAC-overexpressing cells. Taken together, these data indicate that reconstitution of skNAC expression can enhance the differentiation potential of rhabdomyosarcoma cells and reduces their metastatic potential, a finding which might have important therapeutic implications.

Sertel S, Eichhorn T, Sieber S, et al.
Factors determining sensitivity or resistance of tumor cell lines towards artesunate.
Chem Biol Interact. 2010; 185(1):42-52 [PubMed] Related Publications
Clinical oncology is still challenged by the development of drug resistance of tumors that result in poor prognosis for patients. There is an urgent necessity to understand the molecular mechanisms of resistance and to develop novel therapy strategies. Artesunate (ART) is an anti-malarial drug, which also exerts profound cytotoxic activity towards cancer cells. We first applied a gene-hunting approach using cluster and COMPARE analyses of microarray-based transcriptome-wide mRNA expression profiles. Among the genes identified by this approach were genes from diverse functional groups such as structural constituents of ribosomes (RPL6, RPL7, RPS12, RPS15A), kinases (CABC1, CCT2, RPL41), transcriptional and translational regulators (SFRS2, TUFM, ZBTB4), signal transducers (FLNA), control of cell growth and proliferation (RPS6), angiogenesis promoting factors (ITGB1), and others (SLC25A19, NCKAP1, BST1, DBH, FZD7, NACA, MTHFD2). Furthermore, we applied a candidate gene approach and tested the role of resistance mechanisms towards established anti-cancer drugs for ART resistance. By using transfected or knockout cell models we found that the tumor suppressor p16(INK4A) and the anti-oxidant protein, catalase, conferred resistance towards ART, while the oncogene HPV-E6 conferred sensitivity towards ART. The tumor suppressor p53 and its downstream protein, p21, as well as the anti-oxidant manganese-dependent superoxide dismutase did not affect cellular response to ART. In conclusion, our pharmacogenomic approach revealed that response of tumor cells towards ART is multi-factorial and is determined by gene expression associated with either ART sensitivity or resistance. At least some of the functional groups of genes (e.g. angiogenesis promoting factors, cell growth and proliferation-associated genes signal transducers and kinases) are also implicated in clinical responsiveness of tumors towards chemotherapy. It merits further investigation, whether ART is responsive in clinically refractory tumors and whether the genes identified in the present study also determine clinical responsiveness towards ART.

Seo M, Park M, Yook Y, et al.
IL-18 gene expression pattern in exogenously treated AML cells.
BMB Rep. 2008; 41(6):461-5 [PubMed] Related Publications
IL-18 production may enhance immune system defense against KG-1 cells ; NB4 cells, which are associated with good prognosis, do not produce IL-18. In this study, we treated KG-1 cells with IL-18 and used microarray technology to assess subsequent effects on gene expression. In UniGene-array of 7488 human genes, expression of 57 genes, including stress related genes, increased at least 2-fold, whereas expression of 48 genes decreased at least 2-fold. Following exogenous exposure of KG-1 cells to IL-18, expression of CRYGC, NF(kappa)BIA and NACA gene were monitored. The latter is a transcriptional coactivator potentiating c-Jun-mediated transcription. NF(kappa)BIA is an inhibitor of NF(kappa)B, and affects growth regulation, apoptosis and hypoxic stress. Studies, such as this one, are beginning to clarify the differences between cells associated with good and bad cancer prognoses, which may ultimately assist in medical treatment for acute myeloid leukemia.

Zhong X, Ran YL, Lou JN, et al.
Construction of human liver cancer vascular endothelium cDNA expression library and screening of the endothelium-associated antigen genes.
World J Gastroenterol. 2004; 10(10):1402-8 [PubMed] Free Access to Full Article Related Publications
AIM: To gain tumor endothelium associated antigen genes from human liver cancer vascular endothelial cells (HLCVECs) cDNA expression library, so as to find some new possible targets for the diagnosis and therapy of liver tumor.
METHODS: HLCVECs were isolated and purified from a fresh hepatocellular carcinoma tissue sample, and were cultured and proliferated in vitro. A cDNA expression library was constructed with the mRNA extracted from HLCVECs. Anti-sera were prepared from immunized BALB/c mice through subcutaneous injection with high dose of fixed HLCVECs, and were then tested for their specificity against HLCVECs and angiogenic effects in vitro, such as inhibiting proliferation and inducing apoptosis of tumor endothelial cells, using immunocytochemistry, immunofluorescence, cell cycle analysis and MTT assays, etc. The identified xenogeneic sera from immunized mice were employed to screen the library of HLCVECs by modified serological analyses of recombinant cDNA expression libraries (SEREX). The positive clones were sequenced and analyzed by bio-informatics.
RESULTS: The primary cDNA library consisted of 2 x 10(6) recombinants. Thirty-six positive clones were obtained from 6 x 10(5) independent clones by immunoscreening. Bio-informatics analysis of cDNA sequences indicated that 36 positive clones represented 18 different genes. Among them, 3 were new genes previously unreported, 2 of which were hypothetical genes. The other 15 were already known ones. Series analysis of gene expression (SAGE) database showed that ERP70, GRP58, GAPDH, SSB, S100A6, BMP-6, DVS27, HSP70 and NAC alpha in these genes were associated with endothelium and angiogenesis, but their effects on HLCVECs were still unclear. GAPDH, S100A6, BMP-6 and hsp70 were identified by SEREX in other tumor cDNA expression libraries.
CONCLUSION: By screening of HLCVECs cDNA expression library using sera from immunized mice with HLCVECs, the functional genes associated with tumor endothelium or angiogenesis were identified. The modified SEREX, xenogeneic functional serum screening, was demonstrated to be effective for isolation and identification of antigen genes of tumor endothelium, and also for other tumor cell antigen genes. These antigen genes obtained in this study could be a valuable resource for basic and clinical studies of tumor angiogenesis, thus facilitating the development of anti- angiogenesis targeting therapy of tumors.

Hämmerle K, Shayan P, Niemeyer CM, Flotho C
Expression analysis of alpha-NAC and ANX2 in juvenile myelomonocytic leukemia using SMART polymerase chain reaction and "virtual Northern" hybridization.
Cancer Genet Cytogenet. 2003; 142(2):149-52 [PubMed] Related Publications
Juvenile myelomonocytic leukemia (JMML) is a malignant hematopoietic disease of early childhood with both myeloproliferative and myelodysplastic features. We had previously identified the genes for the alpha-chain of the nascent polypeptide-associated complex (NACA) and annexin II (ANX2) as potentially involved in the pathophysiology of JMML. Now we used SMART cDNA synthesis and subsequent "virtual Northern" blot to analyze differential expression of NACA and ANX2 genes in various hematologic cell lines and compared the data to those obtained by standard Northern analyses. The results show that SMART cDNA reproduces the expression profile found in mRNA. Dilution experiments showed that analyses using as little as 0.5 ng of total RNA led to reliable results. After validating the technique, we used virtual Northern blots to analyze expression of NACA and ANX2 in progenitor cultures of nine children with JMML and five healthy individuals. We found no consistent pattern of differential expression between patients and healthy donors. We conclude that aberrant regulation of NACA or ANX2 does not play a relevant role in JMML pathogenesis.

Baghdoyan S, Dubreuil P, Eberlé F, Gomez S
Capture of cytokine-responsive genes (NACA and RBM3) using a gene trap approach.
Blood. 2000; 95(12):3750-7 [PubMed] Related Publications
We have developed a gene trap approach to select specific cytokine receptor/ligand responsive genes in the cell line TF-1. This cell line exhibits a dependency on granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) and responds to interleukin-5 (IL-5). In an attempt to detect genes modulated by one of these factors, cells were infected with the Rosabetageo retrovirus in the presence of GM-CSF, IL-3, or IL-5 and clones were selected for retroviral integration on the basis of G418 resistance. Housekeeping and cytokine-regulated trapped genes were then differentiated on the basis of G418 resistance versus sensitivity in the presence of the different cytokines. To determine the reliability of this screen, DNA sequences upstream of the proviral integration site were identified by 5' rapid amplification of DNA ends polymerase chain reaction (RACE PCR) from selected GM-CSF-treated and -infected clones. Comparison of the sequences with those in the Genbank database revealed that 2 sequences correspond to known genes: NACA and RBM3. NACA was recently defined as a coactivator of c-jun-mediated transcription factors in osteoblasts, and RBM3 as a protein from the heterogeneous nuclear ribonucleoprotein family. Data from transcriptional analysis of these 2 genes in TF-1 cells showed a specific up-regulation by GM-CSF. Both transcripts were also found to be up-regulated in purified CD34(+) cells, suggesting their involvement in proliferative processes during hematopoiesis. Interestingly, down-regulation was observed during monocytic differentiation of TF-1 cells, suggesting their extinction could contribute to monocytic lineage development. This study demonstrates that this gene trap approach is a useful method for identifying novel, specific cytokine-responsive genes that are involved in the regulation of hematopoiesis. (Blood. 2000;95:3750-3757)

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Cite this page: Cotterill SJ. NACA, Cancer Genetics Web: Accessed:

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