CCDC92

Last updated
CCDC92
Identifiers
Symbol?
Alt. namesLimkain beta-2
UniProt Q53HC0
Other data
Locus Chr. 12 q24.31{{{LocusSupplementaryData}}}
Search for
Structures Swiss-model
Domains InterPro

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]

Contents

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.

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]

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).

Predicted tertiary structure (I-TASSER) Tertiary Structure of CCDC92.jpg
Predicted tertiary structure (I-TASSER)

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

GEO Profile of CCDC92 expression in humans. The blue dots indicate the percentile at which the protein was expressed in that tissue compared with all other proteins. Human GEO Profile.png
GEO Profile of CCDC92 expression in humans. The blue dots indicate the percentile at which the protein was expressed in that tissue compared with all other proteins.

In humans, CCDC92 is expressed ubiquitously at a medium to high level (shown right). [2] In dogs and mice, it is expressed ubiquitously, however at significantly lower levels. [7] [8]

Orthologs

Adjusted amino acid changes per 100 (m) against millions of years since the species diverged from humans determines how quickly the protein changes. Fibrinogen and Cytochrome C are given as a reference. Molecular Clock of CCDC92.png
Adjusted amino acid changes per 100 (m) against millions of years since the species diverged from humans determines how quickly the protein changes. Fibrinogen and Cytochrome C are given as a reference.

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. [9] 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]

TaxonCommon nameDivergence dateAccession #LengthIdentitySimilarity
Homo 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 Function
CEP164DNA UV repair
CHGBUnknown
UCH37DNA repair, recombination; breaks Lys-48 linked chains
RPN9Regulatory Subunit for ATP degradation of ubiquitinated proteins
aspSAttaches glutamate to tRNA
ppsAPhosphorylates pyruvate to phosphoenolpyruvate
ASPP2Regulates apoptosis
TRIM27Mediates formation of Lys-48 linked polyubiquitin chains
ELAVL1RNA-binding protein that increases stability; involved in embryonic stem cell differentiation

[13]

Clinical significance

GEO Profile of GDS4006. Observes the effect of a histone deacetylase inhibitor and a hypomethylating agent on CCDC92 levels. GEO GDS4006 CCDC92.png
GEO Profile of GDS4006. Observes the effect of a histone deacetylase inhibitor and a hypomethylating agent on CCDC92 levels.
GEO profile of CCDC92 for experiment GDS3049. Observes expression levels in the presence and absence of a tyrosine kinase inhibitor (Imantinib) GEO Profile of CCDC92 GDS3049.png
GEO profile of CCDC92 for experiment GDS3049. Observes expression levels in the presence and absence of a tyrosine kinase inhibitor (Imantinib)

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.

Related Research Articles

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References

  1. ↑ GeneCards page for CCDC92
  2. 1 2 NCBI GEO Profile of CCDC92 for experiment GDS596 https://www.ncbi.nlm.nih.gov/geoprofiles/4697540
  3. ↑ NCBI Gene entry for CCDC92
  4. ↑ PSORT2 k-NN prediction for CCDC92
  5. ↑ Blom N, Gammeltoft S, Brunak S (December 1999). "Sequence and structure-based prediction of eukaryotic protein phosphorylation sites". Journal of Molecular Biology. 294 (5): 1351–62. doi:10.1006/jmbi.1999.3310. PMID   10600390.
  6. ↑ Steentoft C, Vakhrushev SY, Joshi HJ, Kong Y, Vester-Christensen MB, Schjoldager KT, Lavrsen K, Dabelsteen S, Pedersen NB, Marcos-Silva L, Gupta R, Bennett EP, Mandel U, Brunak S, Wandall HH, Levery SB, Clausen H (May 2013). "Precision mapping of the human O-GalNAc glycoproteome through SimpleCell technology". The EMBO Journal. 32 (10): 1478–88. doi:10.1038/emboj.2013.79. PMC   3655468 . PMID   23584533.
  7. ↑ NCBI GEO Profile for CCDC92 in experiment GDS3142
  8. ↑ NCBI GEO Profile of CCDC92 for experiment GDS4164.
  9. 1 2 NCBI BLAST query for Homo sapiens CCDC92 (Accession Number NP_079416)
  10. ↑ Time Tree query for Homo sapiens and Saccoglossus kowalevskii comparison
  11. ↑ NCBI accession number NP_079416
  12. ↑ NCBI BLAST query for sequence "LKGLHSEI"
  13. ↑ European Bioinformatics Institute PSICQUIC View Query for CCDC92
  14. ↑ NCBI GEO Profile of CCDC92 for experiment GDS4006 https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS4006:ILMN_1731107
  15. ↑ NCBI GEO Profile of CCDC92 for experiment GDS3049 https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS3049:218175_at

Sources

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