CCDC92, or Limkain beta-2, is a protein which in humans is encoded by the CCDC92 gene. It is likely involved in DNA repair or reduction/oxidation reactions. The gene ubiquitously found in humans and is highly conserved across animals.GeneCards page for CCDC92NCBI GEO Profile of CCDC92 for experiment GDS596 https://www.ncbi.nlm.nih.gov/geoprofiles/4697540
The CCDC92 gene is located at cytogenic location 12q24.31 and is 36,576 bases long with nine exonsNCBI Gene entry for CCDC92 which codes for a 331 amino-acid long protein.
Protein The protein CCDC92 (Accession Number: NP_079416) is found in the nucleusPSORT2 k-NN prediction for CCDC92 in humans. It has one domain, coiled-coil domain 92, from amino acids 23-82, which has no known function. The protein is rich in histidine and glutamic acid, and is deficient in phenylalanine. It has a molecular weight of 37kDal, a PI of 9.3, and has no charged domains, hydrophobic domains, or transmembrane domains. CCDC92 has conserved predicted phosphorylation sites at S211, S325, T21, T52, T122, Y130 and conserved glycosylation sites at S183 and T244.
Sequence mtsphfssyd egpldvsmaa tnlenqlhsa qknllflqre hastlkglhs eirrlqqhct dltyeltvks seqtgdgtsk sselkkrcee leaqlkvken enaellkele qknamitvle ntikerekky leelkakshk ltllsseleq rastiaylts qlhaakkklm sssgtsdasp sgspvlasyk pappkdklpe tprrrmkksl saplhpefee vyrfgaesrk lllrepvdam pdptpfllar esaevhlike rplvippias drsgeqhspa rekphkahvg vahrihhatp pqaqpevktl avdqvnggkv vrkhsgtdrt v
Structure There is a large alpha helical section near the start of the protein which extends to near the midpoint of the protein, then two smaller helical sections are near the end (see conceptual translation below).
The tertiary structure of CCDC92 was predicted using I-TASSER and is shown to the right. I-TASSER has moderate confidence in the reliability of this structure (C-Score of -1.61). This structure is remarkably similar to that of an antiparallel domain in the protein PcsB in Streptococcus pneumoniae. This protein is involved in cleaving the cell wall, however the antiparallel domain's function is unknown.
Expression
In humans, CCDC92 is expressed ubiquitously at a medium to high level (shown right). In dogs and mice, it is expressed ubiquitously, however at significantly lower levels.NCBI GEO Profile for CCDC92 in experiment GDS3142NCBI GEO Profile of CCDC92 for experiment GDS4164.
Orthologs CCDC92 has orthologs as far back as an acorn worm,NCBI BLAST query for Homo sapiens CCDC92 (Accession Number NP_079416) which diverged from humans 750 million years ago.Time Tree query for Homo sapiens and Saccoglossus kowalevskii comparison The most highly conserved domain is the coiled-coil domain 92, which is amino acids 23-83 in humans.NCBI accession number NP_079416 This region has no known functions and is not present in any other gene.
CCDC92 shares a 54% similarity with the protein SPPG_05228 in the fungus Spizellomyces punctatus. Spizellomyces punctatus has an 8 amino acid stretch (LKGLHSEI) which matches perfectly with the coil-coiled domain 92 of the human variant. This sequence is present in primarily proteins which are involved in reduction/oxidation reactions, and some bind to DNA.NCBI BLAST query for sequence "LKGLHSEI" TaxonCommon nameDivergence dateAccession #LengthIdentitySimilarityHomo sapiensHuman0 myaNP_079416331 aa100%100%Pan paniscusBonobo6.6 myaXP_003812138331 aa99%100%Mus musculusHouse mouse90.9 myaNP_659068314 aa87%92%Ceratotherium simum simumWhite rhino97.5 myaXP_014642670314 aa90%94%Orycteropus aferAardvark105.0 myaXP_007936428276 aa69%76%Meleagris gallapavoWild turkey320.5 myaXP_010718371315 aa86%92%Alligator mississippiensisAmerican Alligator320.5 myaKQL90045338 aa86%91%Python bivittatusBurmese python320.5 myaXP_007424723335 aa84%91%Xenopus tropicalisWestern clawed frog355.7 myaXP_012821424357 aa76%87%Salmo salarAtlantic salmon429.6 myaNP_001167260332 aa71%83%Callorhinchus miliiAustralian ghostshark482.9 myaXP_007905974320 aa72%83%Danio rerioZebrafish429.6 myaNP_001032794349 aa62%74%Saccoglossus kowalevskiiAcorn worm747.8 myaXP_002731228316 aa34%55%Spizellomyces punctatusSpizellomycetales1302.5 myaKNC99855363 aa40%54%
Function The precise function of CCDC92 is not definitively known. However, based on interacting proteins, conserved sequences, and subcellular localization (nucleus), it can be discerned that a likely function of CCDC92 is DNA repair.
Interacting Proteins Interacting ProteinProtein FunctionCEP164DNA UV repairCHGBUnknownUCH37DNA repair, recombination; breaks Lys-48 linked chainsRPN9Regulatory Subunit for ATP degradation of ubiquitinated proteinsaspSAttaches glutamate to tRNAppsAPhosphorylates pyruvate to phosphoenolpyruvateASPP2Regulates apoptosisTRIM27Mediates formation of Lys-48 linked polyubiquitin chainsELAVL1RNA-binding protein that increases stability; involved in embryonic stem cell differentiation European Bioinformatics Institute PSICQUIC View Query for CCDC92
Clinical significance
In large B-cell Lymphona Lines, CCDC92 expression is increased in the presence of a histone deacetylase inhibitor (Panobinostat) or a hypomethylating agent (Decitabine).NCBI GEO Profile of CCDC92 for experiment GDS4006 https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS4006:ILMN_1731107 It is further increased when these two drugs are combined and increase expression by up to 10 percentiles. In leukemia cell line, CCDC92 expression is also increased in the presence of a tyrosine-kinase inhibitor, ImantinibNCBI GEO Profile of CCDC92 for experiment GDS3049 https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS3049:218175_at
These two changes could be significant if CCDC92 is involved in repairing damaged oncogenes. If that was the case, any of the pharmaceuticals which increased CCDC92 expression could be used to introduce more of it into the body to find damaged DNA sequences and repair them.
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