| CCDC92 | |
| Altnames: | Limkain beta-2 |
| Uniprot: | Q53HC0 |
| Chromosome: | 12 |
| Arm: | q |
| Band: | 24.31 |
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.[1] [2]
The CCDC92 gene is located at cytogenic location 12q24.31 and is 36,576 bases long with nine exons[3] which codes for a 331 amino-acid long protein.
The protein CCDC92 (Accession Number: NP_079416) is found in the nucleus[4] 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[5] and conserved glycosylation sites at S183 and T244.[6]
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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.
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.[7] [8]
CCDC92 has orthologs as far back as an acorn worm,[9] which diverged from humans 750 million years ago.[10] The most highly conserved domain is the coiled-coil domain 92, which is amino acids 23-83 in humans.[11] 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.[12]
| Taxon | Common name | Divergence date | Accession # | Length | Identity | Similarity | |
| Homo sapiens | Human | 0 mya | NP_079416 | 331 aa | 100% | 100% | |
| Pan paniscus | Bonobo | 6.6 mya | XP_003812138 | 331 aa | 99% | 100% | |
| Mus musculus | House mouse | 90.9 mya | NP_659068 | 314 aa | 87% | 92% | |
| Ceratotherium simum simum | White rhino | 97.5 mya | XP_014642670 | 314 aa | 90% | 94% | |
| Orycteropus afer | Aardvark | 105.0 mya | XP_007936428 | 276 aa | 69% | 76% | |
| Meleagris gallapavo | Wild turkey | 320.5 mya | XP_010718371 | 315 aa | 86% | 92% | |
| Alligator mississippiensis | American Alligator | 320.5 mya | KQL90045 | 338 aa | 86% | 91% | |
| Python bivittatus | Burmese python | 320.5 mya | XP_007424723 | 335 aa | 84% | 91% | |
| Xenopus tropicalis | Western clawed frog | 355.7 mya | XP_012821424 | 357 aa | 76% | 87% | |
| Salmo salar | Atlantic salmon | 429.6 mya | NP_001167260 | 332 aa | 71% | 83% | |
| Callorhinchus milii | Australian ghostshark | 482.9 mya | XP_007905974 | 320 aa | 72% | 83% | |
| Danio rerio | Zebrafish | 429.6 mya | NP_001032794 | 349 aa | 62% | 74% | |
| Saccoglossus kowalevskii | Acorn worm | 747.8 mya | XP_002731228 | 316 aa | 34% | 55% | |
| Spizellomyces punctatus | Spizellomycetales | 1302.5 mya | KNC99855 | 363 aa | 40% | 54% |
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 Protein | Protein Function | |
| CEP164 | DNA UV repair | |
| CHGB | Unknown | |
| UCH37 | DNA repair, recombination; breaks Lys-48 linked chains | |
| RPN9 | Regulatory Subunit for ATP degradation of ubiquitinated proteins | |
| aspS | Attaches glutamate to tRNA | |
| ppsA | Phosphorylates pyruvate to phosphoenolpyruvate | |
| ASPP2 | Regulates apoptosis | |
| TRIM27 | Mediates formation of Lys-48 linked polyubiquitin chains | |
| ELAVL1 | RNA-binding protein that increases stability; involved in embryonic stem cell differentiation |
In large B-cell Lymphona Lines, CCDC92 expression is increased in the presence of a histone deacetylase inhibitor (Panobinostat) or a hypomethylating agent (Decitabine).[14] 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, Imantinib[15]
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.