NRAP

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Protein-coding gene in the species Homo sapiens

title: "NRAP" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public description: "Protein-coding gene in the species Homo sapiens" topic_path: "uncategorized" source: "https://en.wikipedia.org/wiki/NRAP" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Protein-coding gene in the species Homo sapiens ::

Nebulin-related-anchoring protein (N-RAP) is a protein that in humans is encoded by the NRAP gene. N-RAP is a muscle-specific isoform belonging to the nebulin family of proteins. This family is composed of 5 members: N-RAP, nebulin, nebulette, LASP-1 and LASP-2. N-RAP is involved in both myofibrillar myogenesis during development and cell-cell connections in mature muscle.

Structure

N-RAP is a 197 kDa protein composed of 1730 amino acids. As a member of the nebulin family of proteins, N-RAP is characterized by 35 amino acid stretches of ‘‘nebulin repeats’’, which are actin binding domains containing a conserved SDxxYK motif. Like nebulin, groups of seven single repeats within N-RAP form “super repeats”, which incorporate a single conserved motif WLKGIGW at the end of the third repeat. A unique feature of NRAP relative to nebulin is its N-terminal cysteine-rich LIM domain, a feature shared with LASP-1 and LASP-2.

Function

An important role has been implicated for N-RAP in myofibrilar organization during cardiomyocyte development. It is clear that NRAP is critical for normal α-actinin-dependent organization of myofibrils in cardiomyocytes, as knock-down of N-RAP protein levels causes myofbrillar disassembly in embryonic cardiomyocytes. Specifically, studies suggest that NRAP super repeats may be an essential scaffold for organizing alpha-actinin and actin into sarcomereic I-Z-I complexes in premyofibrils, and dynamic imaging studies have shown that N-RAP departs from the I-Z-I complexes upon completion of actin thin filament assembly. In adult cardiac muscle, N-RAP colocalizes to intercalated discs, where it functions to anchor terminal actin filaments to the sarcolemma. It has been suggested that its role in adult muscle is force transduction from the sarcomere to the extracellular matrix.

Clinical significance

Though no known direct link exists between N-RAP mutations and human cardiomyopathies, N-RAP has been shown to be significantly upregulated in murine models of dilated cardiomyopathy. This has been hypothesized to be an adaptive response to correct for disorganized actin thin filament architecture at intercalated disc junctions in cardiomyocytes during dilated cardiomyopathy.

References

References

  1. (July 2003). "Genomic organization, alternative splicing, and expression of human and mouse N-RAP, a nebulin-related LIM protein of striated muscle". Cell Motility and the Cytoskeleton.
  2. (May 1999). "Molecular interactions of N-RAP, a nebulin-related protein of striated muscle myotendon junctions and intercalated disks". Biochemistry.
  3. "Entrez Gene: NRAP nebulin-related anchoring protein".
  4. (January 2011). "The Nebulin family: an actin support group". Trends in Cell Biology.
  5. "Nebulin-related-anchoring protein". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
  6. (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research.
  7. (May 1991). "Evidence that nebulin is a protein-ruler in muscle thin filaments". FEBS Letters.
  8. (April 1995). "The complete primary structure of human nebulin and its correlation to muscle structure". Journal of Molecular Biology.
  9. (August 2006). "Targeted disruption of N-RAP gene function by RNA interference: a role for N-RAP in myofibril organization". Cell Motility and the Cytoskeleton.
  10. (January 2004). "N-RAP scaffolds I-Z-I assembly during myofibrillogenesis in cultured chick cardiomyocytes". Journal of Cell Science.
  11. (July 2009). "Myofibril assembly visualized by imaging N-RAP, alpha-actinin, and actin in living cardiomyocytes". Experimental Cell Research.
  12. (May 2005). "N-RAP expression during mouse heart development". Developmental Dynamics.
  13. (1997). "Complete cDNA sequence and tissue localization of N-RAP, a novel nebulin-related protein of striated muscle". Cell Motility and the Cytoskeleton.
  14. (January 1998). "Myofibril degeneration caused by tropomodulin overexpression leads to dilated cardiomyopathy in juvenile mice". The Journal of Clinical Investigation.
  15. (May 2001). "Alterations at the intercalated disk associated with the absence of muscle LIM protein". The Journal of Cell Biology.

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