NKAPD1 (NF-kappa-B-activating protein domain containing 1) is a protein, which in humans, is encoded by the gene NKAPD1. This protein is also commonly referred to as C11ORF57 (Chromosome 11 Open Reading Frame 57).
Gene The NKAPD1 gene is found on human chromosome 11 at locus 11q23.1 with plus strand orientation. The exact location is 112,074,086 to 112,085,150, spanning a total of 11,065 base pairs, including introns.
It can be transcribed into 7 different transcript variants resulting in 4 different isoforms of the protein. The longest mRNA transcript contains a total of 6 exons.
Gene neighborhood The human NKAPD1 gene is closely surrounded by the following genes on chromosome 11.
DLAT PIH1D2 TIMM8B SDHD
Gene expression The human NKAPD1 gene is ubiquitously expressed at moderate levels in various normal tissues throughout the body, with higher expression in the brain and thyroid.
Protein
Transcripts The longest protein isoform produced by the human NKAPD1 gene is known as isoform a and it is 293 amino acids long. This particular protein isoform has a predicted molecular weight around 34 kDa. +Transcript Variants and Protein Isoforms of NKAPD1 Transcript VariantIsoformmRNA Accession #mRNA Length Protein Accession #Protein LengthNotes1isoform aNM_018195.43686 ntNP_060665.3293 aaLongest isoform and mRNA2isoform aNM_001082969.2 3128 ntNP_001076438.1293 aaDifferent in 5’ UTR3isoform bNM_001082970.2 3683 ntNP_001076439.1292 aaAlternate splice site in 3’ coding region4N/ANR_103469.23727 ntN/AN/ANon-coding RNA5isoform bNM_001301017.23125 ntNP_001287946.1292 aaAlternate splice site at 5’ end of last exon6isoform cNM_001301019.23169 ntNP_001287948.1264 aaAlternate exons 1 and 2, uses alternate start codon 7isoform dNM_001301021.23166 ntNP_001287950.1 263 aaAlternate exons 1 and 2
Domains The human NKAPD1 protein contains one domain called the NKAP (NF-kappa-B-activating protein) domain. It also has a lysine rich region directly following the NKAP domain.
Structure Secondary structure predictions suggest that the NKAPD1 protein consists mainly of alpha helices. Predicted three-dimensional structures showed mostly coils with a few small regions of alpha helices.
Post-translational modifications The human NKAPD1 protein is predicted to undergo SUMOylation at several different lysines as well as phosphorylation, acetylation, and N-myristoylation at different amino acids.
Homology and evolution
Orthologs Orthologs to the human NKAPD1 gene can be found in all vertebrates through sharks, rays, and lampreys, however it is not found in any invertebrates. This gene is shown to be very highly conserved in mammals.
Evolution When compared to fibrinogen alpha and cytochrome c, the human NKAPD1 gene seems to be evolving at a fairly moderate rate.
Interacting proteins There were 8 proteins found to have potential interactions with the human NKAPD1 protein. The table below shows the possible relationships between these proteins and the human NKAPD1 protein. +Table of NKAPD1 Interacting Proteins (Organized by Score)NameFull NameBasisScoreFunctionTissue ExpressionSubcellular LocalizationCSNK2A1casein kinase 2 alpha 1Experimental/Biochemical Data0.615Regulates numerous cellular processesUbiquitousnucleusPNNpininCo-Expression, Experimental/Biochemical Data0.570Component of multiprotein exon junction complexUbiquitousnucleusDHX8DEAH-box helicase 8Experimental/Biochemical Data0.563facilitates nuclear export of spliced mRNAUbiquitousnucleusC9orf78Chromosome 9 open reading frame 78Co-Expression, Experimental/Biochemical Data0.541regulation of telomere assembly and telomere lengthUbiquitousnucleusRP9RP9 pre-mRNA splicing factorCo-Expression, Experimental/Biochemical Data0.527Target protein for PM1 kinase, B-cell proliferationUbiquitousnucleus, vesicles, and cytosolCSNK2A2casein kinase 2 alpha 2Co-Expression, Experimental/Biochemical Data0.505Regulates numerous cellular processestestesnucleusSREK1IP1SREK1 interacting protein 1Co-Expression, Experimental/Biochemical Data0.502Possible splicing regulator related to cell survivalUbiquitousnucleusSYF2SYF2 pre-mRNA splicing factor Co-Expression, Experimental/Biochemical Data0.482component of spliceosome, pre-mRNA splicingUbiquitousnucleus
Clinical significance Preliminary findings in three published studies suggest that deletion of the NKAPD1 gene, both complete and partial, are associated with the development of paraganglioma, a rare tumor of the head and neck. This research suggest that these deletions often occur hand-in-hand with deletions of several other nearby genes as well, most prominently SDHD, DLAT, PIHD2, and TIMM8B.
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