NF-kappa-B-activating protein

NKAP
Identifiers
Aliases	NKAP, NFKB activating protein, MRXSHD
External IDs	OMIM: 300766; MGI: 1914300; GeneCards: NKAP
Gene location (Human)
Chr.	X chromosome (human)
End	119,943,751 bp
Gene location (Mouse)
Chr.	X chromosome (mouse)
End	36,414,399 bp
RNA expression pattern
	Top expressed in
	Achilles tendon; ; sural nerve; ; gonad; ; monocyte; ; buccal mucosa cell; ; gastrocnemius muscle; ; C1 segment; ; muscle of thigh; ; right adrenal cortex; ; left adrenal gland;
	Top expressed in
	aortic valve; ; otic placode; ; ascending aorta; ; fossa; ; otic vesicle; ; substantia nigra; ; external carotid artery; ; internal carotid artery; ; condyle; ; supraoptic nucleus;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	chromatin DNA binding; protein binding; RNA binding; chromatin binding;
Cellular component	nucleus; nucleoplasm; cytosol;
Biological process	Notch signaling pathway; stem cell population maintenance; hematopoietic stem cell proliferation; hemopoiesis; granulocyte differentiation; negative regulation of transcription by RNA polymerase II; T cell differentiation in thymus; positive regulation of alpha-beta T cell differentiation; regulation of transcription, DNA-templated; transcription, DNA-templated; positive regulation of protein targeting to mitochondrion; negative regulation of transcription, DNA-templated;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	79576
	67050
	ENSG00000101882
	ENSMUSG00000016409
	Q8N5F7
	Q9D0F4
	NM_024528
	NM_025937
	NP_078804
	NP_080213
	Wikidata
View/Edit Human	View/Edit Mouse

NF-kappa-B-activating protein is a protein that in humans is encoded by the NKAP gene.^[5]^[6] NKAP is a nuclear protein that is essential for T cell maturation.^[7]^[8] NKAP physically associates with histone deacetylase 3 (HDAC3).^[9] NKAP has also been identified as an RNA-binding protein that localizes to nuclear speckles and associates with RNA-binding and splicing factors, with evidence supporting a role in pre-mRNA splicing and RNA processing.^[10] NKAP is also required for normal hematopoiesis and the maintenance of hematopoietic progenitor cells; loss of NKAP can induce cellular senescence or cell death.^[11] The interaction between NKAP and HDAC3 is required for hematopoietic stem cell maintenance and survival.^[12] Pathogenic variants in NKAP have been associated with an X-linked neurodevelopmental disorder, Hackmann–Di Donato syndrome.^[13] NKAP variants have additionally been associated with congenital heart defects, with the p.Arg330Cys variant reported to alter NKAP nuclear localization and impair its interaction with HDAC3.^[14]

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000101882 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000016409 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Chen D, Li Z, Yang Q, Zhang J, Zhai Z, Shu HB (Oct 2003). "Identification of a nuclear protein that promotes NF-kappaB activation". Biochem Biophys Res Commun. 310 (3): 720–4. Bibcode:2003BBRC..310..720C. doi:10.1016/j.bbrc.2003.09.074. PMID 14550261.
↑ "Entrez Gene: NKAP NF-kappaB activating protein".
↑ Hsu FC, Pajerowski AG, Nelson-Holte M, Sundsbak R, Shapiro VS (2011). "NKAP is required for T cell maturation and acquisition of functional competency". J Exp Med. 208 (6): 1291–1304. doi:10.1084/jem.20101874. PMC 3173250. PMID 21624937.
↑ Dash B, Shapiro MJ, Chung JY, Romero Arocha S, Shapiro VS (2018). "Treg-specific deletion of NKAP results in severe, systemic autoimmunity due to peripheral loss of Tregs". J Autoimmun. 89: 139–148. doi:10.1016/j.jaut.2017.12.013. PMC 6205721. PMID 29366602.
↑ Dash B, Shapiro MJ, Thapa P, Arocha SR, Chung JY, Schwab AD, McCue SA, Rajcula MJ, Shapiro VS (2019). "The Interaction between NKAP and HDAC3 Is Critical for T Cell Maturation". ImmunoHorizons. 3 (8): 352–367. doi:10.4049/immunohorizons.1900052. PMC 7409817. PMID 31387873.
↑ Burgute BD, Peche VS, Steckelberg AL, Glöckner G, Gaßen B, Gehring NH, Noegel AA (2014). "NKAP is a novel RS-related protein that interacts with RNA and RNA binding proteins". Nucleic Acids Res. 42 (5): 3177–3193. doi:10.1093/nar/gkt1311. PMC 3950704. PMID 24353314.
↑ Shapiro MJ, Anderson J, Lehrke MJ, Chen M, Nelson Holte M, Shapiro VS (2019). "NKAP Regulates Senescence and Cell Death Pathways in Hematopoietic Progenitors". Front Cell Dev Biol. 7 214. doi:10.3389/fcell.2019.00214. PMC 6783958. PMID 31632967.
↑ Shapiro MJ, Lehrke MJ, Chung JY, Romero Arocha S, Shapiro VS (2019). "NKAP Must Associate with HDAC3 to Regulate Hematopoietic Stem Cell Maintenance and Survival". J Immunol. 202 (8): 2287–2295. doi:10.4049/jimmunol.1800862. PMC 6456368. PMID 30804042.
↑ Fiordaliso SK, et al. (2019). "Missense Mutations in NKAP Cause a Disorder of Transcriptional Regulation Characterized by Marfanoid Habitus and Cognitive Impairment". Am J Hum Genet. 105 (5): 987–995. doi:10.1016/j.ajhg.2019.09.009. PMC 6848994. PMID 31587868.
↑ Xu X, Gao C, Ye F, Peng A, Xu J, Jin K, Zhang J, Ye Y, Yang Y, Zhang X, Shen S, Jin F (2024). "From phenotype to mechanism: Prenatal spectrum of NKAP mutation-related disorder and its pathogenesis inducing congenital heart disease". J Cell Mol Med. 28 (8) e18305. doi:10.1111/jcmm.18305. PMC 11034370. PMID 38647244.

Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. Bibcode:2004NaGen..36...40O. doi:10.1038/ng1285. PMID 14702039.
Ghiorzo P, Mantelli M, Gargiulo S, et al. (2004). "Inverse correlation between p16INK4A expression and NF-kappaB activation in melanoma progression". Hum. Pathol. 35 (8): 1029–37. doi:10.1016/j.humpath.2004.02.017. PMID 15297971.
Beausoleil SA, Jedrychowski M, Schwartz D, et al. (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. Bibcode:2004PNAS..10112130B. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
Ballif BA, Villén J, Beausoleil SA, et al. (2005). "Phosphoproteomic analysis of the developing mouse brain". Mol. Cell. Proteomics. 3 (11): 1093–101. doi:10.1074/mcp.M400085-MCP200. PMID 15345747.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Gevaert K, Staes A, Van Damme J, et al. (2006). "Global phosphoproteome analysis on human HepG2 hepatocytes using reversed-phase diagonal LC". Proteomics. 5 (14): 3589–99. doi:10.1002/pmic.200401217. PMID 16097034. S2CID 895879.
Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
Olsen JV, Blagoev B, Gnad F, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983.
Zhande R, Karsan A (2007). "Erythropoietin promotes survival of primary human endothelial cells through PI3K-dependent, NF-kappaB-independent upregulation of Bcl-xL". Am. J. Physiol. Heart Circ. Physiol. 292 (5): H2467–74. doi:10.1152/ajpheart.00649.2006. PMID 17237249. S2CID 15775587.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000101882 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000016409 – 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] Chen D, Li Z, Yang Q, Zhang J, Zhai Z, Shu HB (Oct 2003). "Identification of a nuclear protein that promotes NF-kappaB activation". Biochem Biophys Res Commun. 310 (3): 720–4. Bibcode:2003BBRC..310..720C. doi:10.1016/j.bbrc.2003.09.074. PMID 14550261.

[6] "Entrez Gene: NKAP NF-kappaB activating protein".

[7] Hsu FC, Pajerowski AG, Nelson-Holte M, Sundsbak R, Shapiro VS (2011). "NKAP is required for T cell maturation and acquisition of functional competency". J Exp Med. 208 (6): 1291–1304. doi:10.1084/jem.20101874. PMC 3173250. PMID 21624937.

[8] Dash B, Shapiro MJ, Chung JY, Romero Arocha S, Shapiro VS (2018). "Treg-specific deletion of NKAP results in severe, systemic autoimmunity due to peripheral loss of Tregs". J Autoimmun. 89: 139–148. doi:10.1016/j.jaut.2017.12.013. PMC 6205721. PMID 29366602.

[9] Dash B, Shapiro MJ, Thapa P, Arocha SR, Chung JY, Schwab AD, McCue SA, Rajcula MJ, Shapiro VS (2019). "The Interaction between NKAP and HDAC3 Is Critical for T Cell Maturation". ImmunoHorizons. 3 (8): 352–367. doi:10.4049/immunohorizons.1900052. PMC 7409817. PMID 31387873.

[10] Burgute BD, Peche VS, Steckelberg AL, Glöckner G, Gaßen B, Gehring NH, Noegel AA (2014). "NKAP is a novel RS-related protein that interacts with RNA and RNA binding proteins". Nucleic Acids Res. 42 (5): 3177–3193. doi:10.1093/nar/gkt1311. PMC 3950704. PMID 24353314.

[11] Shapiro MJ, Anderson J, Lehrke MJ, Chen M, Nelson Holte M, Shapiro VS (2019). "NKAP Regulates Senescence and Cell Death Pathways in Hematopoietic Progenitors". Front Cell Dev Biol. 7 214. doi:10.3389/fcell.2019.00214. PMC 6783958. PMID 31632967.

[12] Shapiro MJ, Lehrke MJ, Chung JY, Romero Arocha S, Shapiro VS (2019). "NKAP Must Associate with HDAC3 to Regulate Hematopoietic Stem Cell Maintenance and Survival". J Immunol. 202 (8): 2287–2295. doi:10.4049/jimmunol.1800862. PMC 6456368. PMID 30804042.

[13] Fiordaliso SK, et al. (2019). "Missense Mutations in NKAP Cause a Disorder of Transcriptional Regulation Characterized by Marfanoid Habitus and Cognitive Impairment". Am J Hum Genet. 105 (5): 987–995. doi:10.1016/j.ajhg.2019.09.009. PMC 6848994. PMID 31587868.

[14] Xu X, Gao C, Ye F, Peng A, Xu J, Jin K, Zhang J, Ye Y, Yang Y, Zhang X, Shen S, Jin F (2024). "From phenotype to mechanism: Prenatal spectrum of NKAP mutation-related disorder and its pathogenesis inducing congenital heart disease". J Cell Mol Med. 28 (8) e18305. doi:10.1111/jcmm.18305. PMC 11034370. PMID 38647244.

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References

Further reading