Nascent polypeptide-associated complex subunit alpha (NACA)

The protein contains 215 amino acids for an estimated molecular weight of 23384 Da.

 

Prevents inappropriate targeting of non-secretory polypeptides to the endoplasmic reticulum (ER). Binds to nascent polypeptide chains as they emerge from the ribosome and blocks their interaction with the signal recognition particle (SRP), which normally targets nascent secretory peptides to the ER. Also reduces the inherent affinity of ribosomes for protein translocation sites in the ER membrane (M sites). May act as a specific coactivator for JUN, binding to DNA and stabilizing the interaction of JUN homodimers with target gene promoters. (updated: March 4, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 48%
Model score: 44

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The reference OMIM entry for this protein is 601234

Nascent polypeptide-associated complex, alpha polypeptide; naca skeletal muscle naca, included; sknac, included

CLONING

Wiedmann et al. (1994) purified the heterodimeric nascent polypeptide-associated complex (NAC) from bovine cytosol and determined that it contains Naca, which migrated at an apparent molecular mass of about 33 kD, and Btf3b (602542), which migrated at an apparent molecular mass of about 21 kD. Using peptide sequences from the purified proteins, they cloned human NACA and BTF3B. Yotov and St-Arnaud (1996) cloned a splice variant of mouse Naca, which they called Sknac, from a skeletal muscle cDNA library. The deduced protein contains 2,187 amino acids. Sknac contains a large in-frame insertion of a proline-rich sequence encoded by Naca exon 3. The first 23 residues and last 192 residues of Naca and Sknac are identical. Both Naca and Sknac have a C-terminal putative nuclear localization signal and calcium-binding EF-hand motif. Northern blot analysis detected a 0.9-kb Naca transcript in all mouse tissues examined, and a 7.0-kb Sknac transcript in skeletal muscle, with weaker expression in heart only. Western blot analysis detected Naca at an apparent molecular mass of 35 kD in mouse osteoblastic cells, embryonal carcinoma cells, undifferentiated C1C12 myoblasts, and differentiated C2C12 myotubes. Sknac was detected at an apparent molecular mass of 220 kD in differentiated C2C12 myotubes only. Li et al. (2009) stated that orthologs of NACA are found in all eukaryotes; however, they found orthologs of the muscle-specific exon 3 in vertebrates only. The deduced human SKNAC protein contains 2,078 amino acids. The first 23 N-terminal amino acids of SKNAC are identical to the N terminus of the deduced 215-amino acid NACA protein. In SKNAC, the N-terminal domain is followed by a 1,863- amino acid domain containing 18 repeats of a 23-amino acid proline- rich sequence. The C terminus of SKNAC is identical to the remainder of the NACA protein. In zebrafish embryos, Li et al. (2009) found ubiquitous Naca expression, but Sknac was expressed in skeletal and cardiac muscle only. In situ hybridization of zebrafish embryos showed Sknac expression increased significantly during somitogenesis and myogenesis. Epitope-tagged Sknac localized to the cytosol at all stages of muscle development, while epitope-tagged Naca was expressed in the nucleus and translocated to the cytosol during differentiation of myotubes into myofibers.

GENE STRUCTURE

Li et al. (2009) determined that the NACA gene contains 9 exons. Exon 3 is very large and encodes the proline-rich repeat region of the striated muscle isoform of NACA. Introns 2 and 5 contain Alu repeats.

MAPPING

Yotov and St-Arnaud (1996) used somatic cell hybrids and fluorescence in situ hybridization to assign the NACA gene to chromosome 12q23-q24.1.

GENE FUNCTION

Wiedmann et al. (1994) showed that NAC bound ubiquitously to nascent polypeptides unless a signal peptide was fully exposed. NAC did not bind to fully emerged signal peptides. In the absence of NAC, the signal recognition particle (SRP; see 604857) interacted with polypeptides even in the absence of a signal peptide and allowed mistargeting of the protein to the SRP receptor (see 600867) at the endoplasmic reticulum membrane. Readdition of purified NAC prevented mistranslocation. Yotov and St-Arnaud (1996) stated that the NACA protein is specifically expressed in bone during development and acts as a transcriptional coactivator in conjunction with acidic activators. Mossabeb et al. (2002) showed that an 86- ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601234 was added.

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed