NKAPD1
| NKAPD1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | NKAPD1, C11orf57, chromosome 11 open reading frame 57, NKAP domain containing 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | MGI: 2143205; HomoloGene: 41233; GeneCards: NKAPD1; OMA:NKAPD1 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
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).[5]
Gene
[edit]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.[5][6]
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. [6]
Gene neighborhood
[edit]The human NKAPD1 gene is closely surrounded by the following genes on chromosome 11.[7]
- DLAT
- PIH1D2
- TIMM8B
- SDHD
Gene expression
[edit]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.[6][8]
Protein
[edit]Transcripts
[edit]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.[5] [6]
| Transcript Variant | Isoform | mRNA Accession # | mRNA Length | Protein Accession # | Protein Length | Notes |
|---|---|---|---|---|---|---|
| 1 | isoform a | NM_018195.4 | 3686 nt | NP_060665.3 | 293 aa | Longest isoform and mRNA |
| 2 | isoform a | NM_001082969.2 | 3128 nt | NP_001076438.1 | 293 aa | Different in 5’ UTR |
| 3 | isoform b | NM_001082970.2 | 3683 nt | NP_001076439.1 | 292 aa | Alternate splice site in 3’ coding region |
| 4 | N/A | NR_103469.2 | 3727 nt | N/A | N/A | Non-coding RNA |
| 5 | isoform b | NM_001301017.2 | 3125 nt | NP_001287946.1 | 292 aa | Alternate splice site at 5’ end of last exon |
| 6 | isoform c | NM_001301019.2 | 3169 nt | NP_001287948.1 | 264 aa | Alternate exons 1 and 2, uses alternate start codon |
| 7 | isoform d | NM_001301021.2 | 3166 nt | NP_001287950.1 | 263 aa | Alternate exons 1 and 2 |
Domains
[edit]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.[9][10]
Structure
[edit]Secondary structure predictions suggest that the NKAPD1 protein consists mainly of alpha helices.[13] Predicted three-dimensional structures showed mostly coils with a few small regions of alpha helices. [11]
Post-translational modifications
[edit]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. [10]
Homology and evolution
[edit]Orthologs
[edit]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.[6][14]
Evolution
[edit]When compared to fibrinogen alpha and cytochrome c, the human NKAPD1 gene seems to be evolving at a fairly moderate rate. [6][15][16]
Interacting proteins
[edit]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.[17]
| Name | Full Name | Basis | Score | Function | Tissue Expression | Subcellular Localization |
|---|---|---|---|---|---|---|
| CSNK2A1 | casein kinase 2 alpha 1 | Experimental/Biochemical Data | 0.615 | Regulates numerous cellular processes | Ubiquitous | nucleus |
| PNN | pinin | Co-Expression, Experimental/Biochemical Data | 0.570 | Component of multiprotein exon junction complex | Ubiquitous | nucleus |
| DHX8 | DEAH-box helicase 8 | Experimental/Biochemical Data | 0.563 | facilitates nuclear export of spliced mRNA | Ubiquitous | nucleus |
| C9orf78 | Chromosome 9 open reading frame 78 | Co-Expression, Experimental/Biochemical Data | 0.541 | regulation of telomere assembly and telomere length | Ubiquitous | nucleus |
| RP9 | RP9 pre-mRNA splicing factor | Co-Expression, Experimental/Biochemical Data | 0.527 | Target protein for PM1 kinase, B-cell proliferation | Ubiquitous | nucleus, vesicles, and cytosol |
| CSNK2A2 | casein kinase 2 alpha 2 | Co-Expression, Experimental/Biochemical Data | 0.505 | Regulates numerous cellular processes | testes | nucleus |
| SREK1IP1 | SREK1 interacting protein 1 | Co-Expression, Experimental/Biochemical Data | 0.502 | Possible splicing regulator related to cell survival | Ubiquitous | nucleus |
| SYF2 | SYF2 pre-mRNA splicing factor | Co-Expression, Experimental/Biochemical Data | 0.482 | component of spliceosome, pre-mRNA splicing | Ubiquitous | nucleus |
Clinical significance
[edit]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.[18][19][20]
References
[edit]- ^ a b c GRCh38: Ensembl release 89: ENSG00000150776 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000059820 – 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.
- ^ a b c "GeneCards". Retrieved December 17, 2023.
- ^ a b c d e f g h "NKAPD1 NKAP domain containing 1 [ Homo sapiens (human) ]". NCBI Gene. Retrieved December 17, 2023.
- ^ "UCSC Genome Browser". Retrieved December 15, 2023.
- ^ "c11orf57 GEO Profiles". NCBI GEO. Retrieved December 15, 2023.
- ^ "uncharacterized protein NKAPD1 isoform a [Homo sapiens]". NCBI Protein. Retrieved December 15, 2023.
- ^ a b "Motif Scan". MyHits Motif Scan. Retrieved December 10, 2023.
- ^ a b "AlphaFold Protein Structure Database". Retrieved December 4, 2023.
- ^ "iCn3D". NCBI. Retrieved December 4, 2023.
- ^ "I-TASSER". Zhang Lab. Retrieved December 4, 2023.
- ^ "EMBOSS Needle". EMBL-EBI. Retrieved December 17, 2023.
- ^ a b "FGA fibrinogen alpha chain [ Homo sapiens (human) ]". NCBI Gene. Retrieved December 17, 2023.
- ^ a b "CYCS cytochrome c, somatic [ Homo sapiens (human) ]". NCBI Gene. Retrieved December 17, 2023.
- ^ a b "STRING-DB". STRING. Retrieved December 17, 2023.
- ^ Cadiñanos J, Llorente JL, de la Rosa J, Villameytide JA, Illán R, Durán NS, et al. (August 2011). "Novel germline SDHD deletion associated with an unusual sympathetic head and neck paraganglioma". Head & Neck. 33 (8): 1233–1240. doi:10.1002/hed.21384. PMID 20310044. S2CID 24385357.
- ^ Bayley JP, Weiss MM, Grimbergen A, van Brussel BT, Hes FJ, Jansen JC, et al. (September 2009). "Molecular characterization of novel germline deletions affecting SDHD and SDHC in pheochromocytoma and paraganglioma patients". Endocrine-Related Cancer. 16 (3): 929–937. doi:10.1677/ERC-09-0084. PMID 19546167.
- ^ Hoekstra AS, van den Ende B, Julià XP, van Breemen L, Scheurwater K, Tops CM, et al. (April 2017). "Simple and rapid characterization of novel large germline deletions in SDHB, SDHC and SDHD-related paraganglioma". Clinical Genetics. 91 (4): 536–544. doi:10.1111/cge.12843. hdl:1887/116006. PMID 27485256.