NACA (gene) explained

Nascent-polypeptide-associated complex alpha polypeptide, also known as NACA, is a protein which in humans is encoded by the NACA gene.^{[1] [2] [3]}

Function

NACA prevents short recently synthesized (i.e., nascent) ribosome-associated polypeptides from inappropriate interactions with cytosolic proteins. NACA binds nascent-polypeptide domains emerging from ribosomes unless it contains a signal peptide which is fully exposed. Depletion of NACA from ribosomes carrying nascent polypeptides allows the signal recognition particle (SRP) to crosslink to polypeptides regardless of whether or not they contain signal peptides or not. In the absence of NACA, proteins lacking signal peptides can be mis-translocated into the endoplasmic reticulum.^{[2] [4]}

The NACA protein is expressed in bone during development and acts as a transcriptional coactivator in conjunction with acidic activators.^[3]

Interactions

NACA has been shown to interact with BTF3, FADD,^[5] C-jun,^[6] and 3 members of taxilin family.^[7]

Further reading

• Wiedmann B, Sakai H, Davis TA, Wiedmann M . A protein complex required for signal-sequence-specific sorting and translocation. . Nature . 370 . 6489 . 434–40 . 1994 . 8047162 . 10.1038/370434a0 . 1994Natur.370..434W . 4353902 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Yotov WV, St-Arnaud R . Mapping of the human gene for the alpha-NAC/1.9.2 (NACA/1.9.2) transcriptional coactivator to Chromosome 12q23-24.1. . Mamm. Genome . 7 . 2 . 163–4 . 1996 . 8835540 . 10.1007/BF03035343 . 33088429 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Yotov WV, Moreau A, St-Arnaud R . The alpha chain of the nascent polypeptide-associated complex functions as a transcriptional coactivator. . Mol. Cell. Biol. . 18 . 3 . 1303–11 . 1998 . 9488445 . 10.1128/MCB.18.3.1303. 108843 .
• Moreau A, Yotov WV, Glorieux FH, St-Arnaud R . Bone-specific expression of the alpha chain of the nascent polypeptide-associated complex, a coactivator potentiating c-Jun-mediated transcription. . Mol. Cell. Biol. . 18 . 3 . 1312–21 . 1998 . 9488446 . 10.1128/MCB.18.3.1312. 108844 .
• Munz B, Wiedmann M, Lochmüller H, Werner S . Cloning of novel injury-regulated genes. Implications for an important role of the muscle-specific protein skNAC in muscle repair. . J. Biol. Chem. . 274 . 19 . 13305–10 . 1999 . 10224091 . 10.1074/jbc.274.19.13305 . free .
• Beatrix B, Sakai H, Wiedmann M . The alpha and beta subunit of the nascent polypeptide-associated complex have distinct functions. . J. Biol. Chem. . 275 . 48 . 37838–45 . 2001 . 10982809 . 10.1074/jbc.M006368200 . free .
• Zhang QH, Ye M, Wu XY, etal . Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells. . Genome Res. . 10 . 10 . 1546–60 . 2001 . 11042152 . 10.1101/gr.140200 . 310934 .
• Sims RJ, Weihe EK, Zhu L, etal . m-Bop, a repressor protein essential for cardiogenesis, interacts with skNAC, a heart- and muscle-specific transcription factor. . J. Biol. Chem. . 277 . 29 . 26524–9 . 2002 . 12011100 . 10.1074/jbc.M204121200 . free .
• Kim SH, Shim KS, Lubec G . Human brain nascent polypeptide-associated complex alpha subunit is decreased in patients with Alzheimer' s disease and Down syndrome. . J. Investig. Med. . 50 . 4 . 293–301 . 2002 . 12109594 . .
• Behrends U, Jandl T, Golbeck A, etal . Novel products of the HUD, HUC, NNP-1 and alpha-internexin genes identified by autologous antibody screening of a pediatric neuroblastoma library. . Int. J. Cancer . 100 . 6 . 669–77 . 2002 . 12209604 . 10.1002/ijc.10550 . 35369661 . free .
• Mossabeb R, Seiberler S, Mittermann I, etal . Characterization of a novel isoform of alpha-nascent polypeptide-associated complex as IgE-defined autoantigen. . J. Invest. Dermatol. . 119 . 4 . 820–9 . 2002 . 12406326 . 10.1046/j.1523-1747.2002.00518.x . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Stilo R, Liguoro D, di Jeso B, etal . The alpha-chain of the nascent polypeptide-associated complex binds to and regulates FADD function. . Biochem. Biophys. Res. Commun. . 303 . 4 . 1034–41 . 2003 . 12684039 . 10.1016/S0006-291X(03)00487-X .
• Papachristou DJ, Batistatou A, Sykiotis GP, etal . Activation of the JNK-AP-1 signal transduction pathway is associated with pathogenesis and progression of human osteosarcomas. . Bone . 32 . 4 . 364–71 . 2003 . 12689679 . 10.1016/S8756-3282(03)00026-7 .
• 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. . 142 . 2 . 149–52 . 2003 . 12699894 . 10.1016/S0165-4608(02)00841-5 .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Al-Shanti N, Steward CG, Garland RJ, Rowbottom AW . Investigation of alpha nascent polypeptide-associated complex functions in a human CD8(+) T cell ex vivo expansion model using antisense oligonucleotides. . Immunology . 112 . 3 . 397–403 . 2004 . 15196207 . 10.1111/j.1365-2567.2004.01893.x . 1782496 .
• Ballif BA, Villén J, Beausoleil SA, etal . Phosphoproteomic analysis of the developing mouse brain. . Mol. Cell. Proteomics . 3 . 11 . 1093–101 . 2005 . 15345747 . 10.1074/mcp.M400085-MCP200 . free .

Notes and References

1. Web site: Entrez Gene: NACA nascent-polypeptide-associated complex alpha polypeptide.
2. Wiedmann B, Sakai H, Davis TA, Wiedmann M . A protein complex required for signal-sequence-specific sorting and translocation . Nature . 370 . 6489 . 434–40 . August 1994 . 8047162 . 10.1038/370434a0 . 1994Natur.370..434W . 4353902 .
3. Yotov WV, St-Arnaud R . Mapping of the human gene for the alpha-NAC/1.9.2 (NACA/1.9.2) transcriptional coactivator to Chromosome 12q23-24.1 . Mamm. Genome . 7 . 2 . 163–4 . February 1996 . 8835540 . 10.1007/BF03035343 . 33088429 . dead . https://web.archive.org/web/20000916192630/http://link.springer-ny.com/link/service/journals/00335/bibs/7n2p163.html . 2000-09-16 .
4. Rospert S, Dubaquié Y, Gautschi M . Nascent-polypeptide-associated complex . Cell. Mol. Life Sci. . 59 . 10 . 1632–9 . October 2002 . 12475173 . 10.1007/PL00012490 . 8874233 .
5. Stilo R, Liguoro D, di Jeso B, Leonardi A, Vito P . The alpha-chain of the nascent polypeptide-associated complex binds to and regulates FADD function . Biochem. Biophys. Res. Commun. . 303 . 4 . 1034–41 . April 2003 . 12684039 . 10.1016/S0006-291X(03)00487-X.
6. Moreau A, Yotov WV, Glorieux FH, St-Arnaud R . Bone-specific expression of the alpha chain of the nascent polypeptide-associated complex, a coactivator potentiating c-Jun-mediated transcription . Mol. Cell. Biol. . 18 . 3 . 1312–21 . March 1998 . 9488446 . 108844 . 10.1128/MCB.18.3.1312.
7. Yoshida K, Nogami S, Satoh S, Tanaka-Nakadate S, Hiraishi H, Terano A, Shirataki H . Interaction of the taxilin family with the nascent polypeptide-associated complex that is involved in the transcriptional and translational processes . Genes Cells . 10 . 5 . 465–76 . May 2005 . 15836775 . 10.1111/j.1365-2443.2005.00848.x . 19426810 . free .