NRAP

Protein-coding gene in the species Homo sapiens

NRAP

Identifiers
Aliases| NRAP, N-RAP, nebulin related anchoring protein
External IDs| OMIM: 602873; MGI: 1098765; HomoloGene: 4499; GeneCards: NRAP; OMA:NRAP - orthologs
| Gene location (Human)

Chr.| Chromosome 10 (human)[1]

Band| 10q25.3| Start| 113,588,714 bp[1]
End| 113,664,070 bp[1]
| Gene location (Mouse)

Chr.| Chromosome 19 (mouse)[2]

Band| 19 D2|19 51.8 cM| Start| 56,308,467 bp[2]
End| 56,378,469 bp[2]
| RNA expression pattern

Bgee| | Human| Mouse (ortholog)

|

| Top expressed in

* Skeletal muscle tissue of rectus abdominis

* muscle of thigh

* glutes

* gastrocnemius muscle

* apex of heart

* body of tongue

* Skeletal muscle tissue of biceps brachii

* triceps brachii muscle

* thoracic diaphragm

* ventricle of the heart

| Top expressed in

* ankle

* muscle of thigh

* soleus muscle

* temporal muscle

* triceps brachii muscle

* plantaris muscle

* extensor digitorum longus muscle

* tibialis anterior muscle

* medial head of gastrocnemius muscle

* digastric muscle

More reference expression data
BioGPS| |

More reference expression data
| Gene ontology

Molecular function|

* actin binding
* metal ion binding
* muscle alpha-actinin binding
* protein binding
* actin filament binding

Cellular component|

* fascia adherens
* muscle tendon junction
* Z discdkac

Biological process|

* biological process
* cardiac muscle thin filament assembly

Sources:Amigo / QuickGO
| Orthologs

Species| Human| Mouse
Entrez| |

4892

18175

Ensembl| |

ENSG00000197893

ENSMUSG00000049134

UniProt| |

Q86VF7

Q80XB4

RefSeq (mRNA)| |

NM_001261463
NM_006175
NM_198060
NM_001322945

NM_001286552
NM_008733
NM_198059

RefSeq (protein)| |

NP_001248392
NP_001309874
NP_006166
NP_932326

| NP_001273481
NP_032759
NP_932307
NP_001390105
NP_001390107

NP_001390109
NP_001390113
NP_001390114
NP_001390115
NP_001390116
NP_001390117
NP_001390119
NP_001390120
NP_001390121
NP_001390122
NP_001390123
NP_001390124
NP_001390125

Location (UCSC)| Chr 10: 113.59 – 113.66 Mb| Chr 19: 56.31 – 56.38 Mb
PubMed search| [3]| [4]
Wikidata
| View/Edit Human| View/Edit Mouse

|

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.[5][6][7][8]

## Structure

[edit]

N-RAP is a 197 kDa protein composed of 1730 amino acids.[9][10] 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.[11] 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.[12] 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.[8]

## Function

[edit]

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.[13] 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,[14] and dynamic imaging studies have shown that N-RAP departs from the I-Z-I complexes upon completion of actin thin filament assembly.[15] In adult cardiac muscle, N-RAP colocalizes to intercalated discs,[16] 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.[17]

## Clinical significance

[edit]

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.[18][19] 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

[edit]

1. ^ a b c GRCh38: Ensembl release 89: ENSG00000197893 - Ensembl, May 2017
2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000049134 - Ensembl, May 2017
3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. ^ Mohiddin SA, Lu S, Cardoso JP, Carroll S, Jha S, Horowits R, et al. (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. 55 (3): 200–212\. doi:10.1002/cm.10123. PMID 12789664.
6. ^ Luo G, Herrera AH, Horowits R (May 1999). "Molecular interactions of N-RAP, a nebulin-related protein of striated muscle myotendon junctions and intercalated disks". Biochemistry. 38 (19): 6135–43\. doi:10.1021/bi982395t. PMID 10320340.
7. ^ "Entrez Gene: NRAP nebulin-related anchoring protein".
8. ^ a b Pappas CT, Bliss KT, Zieseniss A, Gregorio CC (January 2011). "The Nebulin family: an actin support group". Trends in Cell Biology. 21 (1): 29–37\. doi:10.1016/j.tcb.2010.09.005. PMC 3014390. PMID 20951588.
9. ^ "Nebulin-related-anchoring protein". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
10. ^ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, et al. (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–1053\. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
11. ^ Labeit S, Gibson T, Lakey A, Leonard K, Zeviani M, Knight P, et al. (May 1991). "Evidence that nebulin is a protein-ruler in muscle thin filaments". FEBS Letters. 282 (2): 313–316\. Bibcode:1991FEBSL.282..313L. doi:10.1016/0014-5793(91)80503-u. PMID 2037050.
12. ^ Labeit S, Kolmerer B (April 1995). "The complete primary structure of human nebulin and its correlation to muscle structure". Journal of Molecular Biology. 248 (2): 308–315\. doi:10.1016/s0022-2836(95)80052-2. PMID 7739042.
13. ^ Dhume A, Lu S, Horowits R (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. 63 (8): 493–511\. doi:10.1002/cm.20141. PMID 16767749.
14. ^ Carroll S, Lu S, Herrera AH, Horowits R (January 2004). "N-RAP scaffolds I-Z-I assembly during myofibrillogenesis in cultured chick cardiomyocytes". Journal of Cell Science. 117 (Pt 1): 105–114\. doi:10.1242/jcs.00847. PMID 14657273.
15. ^ Manisastry SM, Zaal KJ, Horowits R (July 2009). "Myofibril assembly visualized by imaging N-RAP, alpha-actinin, and actin in living cardiomyocytes". Experimental Cell Research. 315 (12): 2126–2139\. doi:10.1016/j.yexcr.2009.02.006. PMC 2742992. PMID 19233165.
16. ^ Lu S, Borst DE, Horowits R (May 2005). "N-RAP expression during mouse heart development". Developmental Dynamics. 233 (1): 201–212\. doi:10.1002/dvdy.20314. PMID 15765519. S2CID 22925166.
17. ^ Luo G, Zhang JQ, Nguyen TP, Herrera AH, Paterson B, Horowits R (1997). "Complete cDNA sequence and tissue localization of N-RAP, a novel nebulin-related protein of striated muscle". Cell Motility and the Cytoskeleton. 38 (1): 75–90\. doi:10.1002/(SICI)1097-0169(1997)38:1<75::AID-CM7>3.0.CO;2-G. PMID 9295142.
18. ^ Sussman MA, Welch S, Cambon N, Klevitsky R, Hewett TE, Price R, et al. (January 1998). "Myofibril degeneration caused by tropomodulin overexpression leads to dilated cardiomyopathy in juvenile mice". The Journal of Clinical Investigation. 101 (1): 51–61\. doi:10.1172/JCI1167. PMC 508539. PMID 9421465.
19. ^ Ehler E, Horowits R, Zuppinger C, Price RL, Perriard E, Leu M, et al. (May 2001). "Alterations at the intercalated disk associated with the absence of muscle LIM protein". The Journal of Cell Biology. 153 (4): 763–772\. doi:10.1083/jcb.153.4.763. PMC 2192386. PMID 11352937.

## Further reading

[edit]

* Lanfranchi G, Muraro T, Caldara F, Pacchioni B, Pallavicini A, Pandolfo D, et al. (January 1996). "Identification of 4370 expressed sequence tags from a 3'-end-specific cDNA library of human skeletal muscle by DNA sequencing and filter hybridization". Genome Research. 6 (1): 35–42\. doi:10.1101/gr.6.1.35. PMID 8681137.
* Luo G, Zhang JQ, Nguyen TP, Herrera AH, Paterson B, Horowits R (1997). "Complete cDNA sequence and tissue localization of N-RAP, a novel nebulin-related protein of striated muscle". Cell Motility and the Cytoskeleton. 38 (1): 75–90\. doi:10.1002/(SICI)1097-0169(1997)38:1<75::AID-CM7>3.0.CO;2-G. PMID 9295142.
* Luo G, Leroy E, Kozak CA, Polymeropoulos MH, Horowits R (October 1997). "Mapping of the gene (NRAP) encoding N-RAP in the mouse and human genomes". Genomics. 45 (1): 229–232\. doi:10.1006/geno.1997.4917. PMID 9339382.
* Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–1795\. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
* Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, et al. (March 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research. 11 (3): 422–435\. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
* Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, et al. (October 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research. 14 (10B): 2136–2144\. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
* Witt SH, Granzier H, Witt CC, Labeit S (Jul 2005). "MURF-1 and MURF-2 target a specific subset of myofibrillar proteins redundantly: towards understanding MURF-dependent muscle ubiquitination". Journal of Molecular Biology. 350 (4): 713–22\. doi:10.1016/j.jmb.2005.05.021. PMID 15967462.
* Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, et al. (January 2006). "The LIFEdb database in 2006". Nucleic Acids Research. 34 (Database issue): D415 – D418. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.
* "Mass spectrometry characterization of human NRAP". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB)..Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, et al. (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–1053\. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.