Biology:CDV3 (gene)

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Short description: Human protein-coding gene


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example


Protein CDV3 homolog also known as carnitine deficiency-associated gene expressed in ventricle 3 is a protein that in humans is encoded by the CDV3 gene.

CDV3 is a biomarker for hepatocellular carcinoma.[1] CDV3 has been considered as a potential target for gene therapy. Related gene families include plasma proteins and predicted intracellular proteins.[2]

Gene

Aliases

The CDV3 protein is also commonly known as tyrosine-phosphorylated protein 36 (TPP36). TPP36 isoforms have been found to be substrates of Abl tyrosine kinase.[3]

Locus

The CDV3 gene is on chromosome 3 (3q22.1).

Chromosome location of CDV3 from NCBI Gene.[4]

Exons

There were variations in the listed number of exons in CDV3 between genetic databases. The number of exons vary based on the isoform in question, with most transcript isoforms having 5 exons.[4]

Span

The exons of human CDV3 gene's longest transcript isoform span 16,711 bp.[5]

Transcripts

Isoforms

CDV3 has seven isoforms,[4] and more are continuously added to databases as they are discovered. Currently there are isoforms a-f.

Protein

Molecular weight: 27.3 kD

Protein length: 258 aa

Isoelectric point: 5.89[6]

Motifs

A SAPS analysis[7] on the human CDV3 protein sequence found one uncharged cluster segment from 28-75 aa. There were no signs of high scoring hydrophobic segments. One high scoring transmembrane segment was found from 28-55 aa. CDV3 was found to have significant maximal spacing from 27-76 aa.

Repeats

The following repetitive structures were found for the protein.

Aligned matching blocks:

[45-52]  AGAAGGGA

[66-73]  AGAAGPGA

with superset:

  [32-36]   AGAAG

  [45-49]   AGAAG

  [  66- 70]   AGAAG

______________________________

[134-137]   MEKS

[213-216]   MEKS

______________________________

Simple tandem repeat:

[31-43]   AAGAA_GSAGGSSG

[44-54]   AAGAAGGGAGA

Predicted Motifs

PROSITE found several potential motifs in CDV3.[8] 

Motif Predicted Site (Base Pair Location)
Alanine-rich region: 28-77
Glycine-rich region: 33-72
Predicted protein kinase C (PKC) phosphorylation sites 25-27, 107-109, 178-180, 179-181, 201-203, 207-209
Casein kinase ii phosphorylation site 79-82, 107-110, 207-210
Tyrosine kinase phosphorylation site 237-244

Predicted Secondary Structure

Conceptual translation of the longest CDV3 isoform annotated with CDV3's predicted secondary structure and conserved amino acids.

The following programs were used to develop this figure: JPred, CFSSP, and GOR4. The majority of the CDV3 structure is hypothesized to be alpha helices and random coil.

Predicted 3D Structure

The 3D structure of CDV3 was predicted through amino acid submission to the Zhang Lab and their I-TASSER program.

Predicted CDV3 3D structure from I-TASSER.

Gene regulation

Promoter

There are currently six different predicted promoters based on supporting transcripts. The following promoters were found using Genomatix . Promoter GXP_141972 was chosen for further analysis because of the large number of supporting transcripts, and it was found to be conserved in 14 of 14 orth. loci.  

Promoter Name Coordinates Size # of Supporting Transcripts
GXP_141970 133585623 - 133586723 1101 1
GXP_141972 133572563 - 133574180 1618 12
GXP_141973 133587952 - 133589052 1101 1
GXP_6749779 133573434 - 133574748 1315 13
GXP_7542845 133569573 – 133574748 1101 *
GXP_7542846 133583006 - 133584149 1144 *

*No transcript assigned.

Expression patterns

CDV3 is ubiquitously expressed, and at relatively high levels, in all tissues examined in the humans. Higher expression existed in certain diseases.

Gene profile

Various experiments showing expression of CDV3 demonstrated different patterns of tissue expression; however, it is concluded that the gene is expressed ubiquitously throughout all tissue types with more expression within tissues involved in the immune system and skeletal muscle tissue.[4]

HPA RNA-seq Normal Tissue Expression from NCBI Gene entry on CDV3.

The expression of CDV3 generally decreases throughout fetal development, but expression levels remain high.

Tissue-specific circular RNA induction during human fetal development from NCBI Gene entry on CDV3.
RNA sequencing of total RNA from 20 human tissues from NCBI Gene entry on CDV3.
Illumina bodyMap2 transcriptome from NCBI Gene entry on CDV3.

Protein Level Regulation

A conceptual translation was made from NCBI reference sequence NM_017548.4. Amino acids conserved in at least 70% of vertebrate orthologous proteins are bolded (seen in the section below).

A conceptual translation showing predicted sites of CDV3 protein regulation.

Evolution

Orthologs

The following orthologs were found through the NCBI database.[4] The date of divergence between species and Homo sapies was determined using TimeTree. The sequence identity and similarity were found using BLAST.

Genus and Species Common Name Taxonomic Group Date of Divergence (Median Time) Accession Number Sequence Length (aa) Sequence Identity Sequence Similar
Homo sapiens Human Mammalia 0 Q9UKY7 258 100 100
Macaca mulatta Rhesus macaque Mammalia 28.1 AFH33110 257 98 98
Callithrix jacchus Common marmoset Mammalia 42.6 JAB08658 257 98 98
Castor canadensis American beaver Mammalia 88 JAV41819 265 89 89
Mus musculus House mouse Mammalia 89.8 Q4VAA2.2 281 73 79
Lonchura striata domestica Society finch Bird 320 OWK55384 248 62 74
Xenopus laevis African clawed frog Amphibia 353 NP_001080515 240 58 73
Electrophorus electricus Electric eel Fish 432 XP_026860127 230 55 74
Oryzias melastigma Marine Medaka Fish 432 XP_024136300 230 50 63
Danio rerio Zebrafish Fish 432 NP_997886 236 48 59

Paralogs

No human paralogs were found for CDV3 GeneCards and GenesLikeMe databases through the Weizmann Institute of Science. There were not any other relevant sources when the Google Search was conducted.

Phylogenetic tree

A phylogenetic tree was developed from the species listed in the table above using "One Click Mode" on Phylogeny.fr.

Phylogenetic tree of species with CDV3 orthologs using Phylogeny.fr

Interacting proteins

Interacting Protein Sources Supporting the Interaction Function Common Tissues
MYC IntAct,[9] mentha[10] Family of regular genes and proto-oncongenes; code for transcription factors; persistently expressed in cancer Uterus, cervix, leukemia, carcinoma
EWSR1 mentha,[10] BioGRID[11] EWS RNA-binding protein 1; EWS protein function is not fully understood Brain, lymph, placenta, carcinoma, colon, cervix, liver, ubiquitous
RBM3 mentha,[10] BioGRID[11] RNA binding motif (RNP1, RNA recognition motif) protein 3 Placenta, carcinoma, T-cell, cervix, liver, colon
U2AF2 mentha,[10] BioGRID[11] U2 small nuclear RNA auxiliary factor 2; necessary for splicing; non-snRNP protein Lymph, carcinoma, colon, lymphoblast, cervix, T-cell, liver
ELAVL1 mentha,[10] BioGRID[11] ELAV like RNA binding protein 1; stabilizes ARE-containing mRNAs; associated with several diseases and cancer Intestine, cervix, lymphoblast, carcinoma, T-cell, colon, brain, muscle, thymus, ubiquitous
Pr55 (Gag) mentha,[10] BioGRID,[11] NCBI[12] Many diverse functions such as assembly and virion maturation; vital to HIV life cycle; cellular biotinylated CDV3 mouse homolog was found to be incorporated into this particle
PIAS2 NCBI[4] Encodes inhibitor of activated STAT family; aids in sumoylation of target proteins

Clinical significance

As earlier in the article, CDV3 has been found to be expressed in patients with various cancers and HIV. CDV3 has also been found to interact with Pr55 in the HIV retrovirus. Without further testing in expression, it is hard to determine how levels alter depending on disease state or the role this gene plays in these illnesses.

References

  1. ↑ "The potential value of CDV3 in the prognosis evaluation in Hepatocellular carcinoma". Genes & Diseases 5 (2): 167–171. June 2018. doi:10.1016/j.gendis.2018.01.003. PMID 30258946. 
  2. ↑ "Tissue expression of CDV3". The Human Protein Atlas. https://www.proteinatlas.org/ENSG00000091527. 
  3. ↑ "Molecular cloning and characterization of TPP36 and its isoform TPP32, novel substrates of Abl tyrosine kinase". FEBS Letters 537 (1–3): 203–9. February 2003. doi:10.1016/S0014-5793(03)00127-3. PMID 12606058. 
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 "CDV3 CDV3 homolog [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/55573. 
  5. ↑ "Nucleotide Links for Gene (Select 55573) - Nucleotide - NCBI". https://www.ncbi.nlm.nih.gov/nuccore?LinkName=gene_nuccore&from_uid=55573. 
  6. ↑ "IPC - Isoelectric Point Calculator". Biology Direct 11 (1): 55. October 2016. doi:10.1186/s13062-016-0159-9. PMID 27769290. 
  7. ↑ "SAPS < Sequence Statistics < EMBL-EBI". https://www.ebi.ac.uk/Tools/seqstats/saps/. 
  8. ↑ Figure 4—figure supplement 2. Additional analysis of BioID hits.. doi:10.7554/elife.20882.011. 
  9. ↑ "interaction_id:EBI-3962281". https://www.ebi.ac.uk/intact/interaction/EBI-3962281. 
  10. ↑ 10.0 10.1 10.2 10.3 10.4 10.5 "Results - mentha: the interactome browser". https://mentha.uniroma2.it/result.php#CDV3. 
  11. ↑ 11.0 11.1 11.2 11.3 11.4 "CDV3 Result Summary | BioGRID". https://thebiogrid.org/120726/summary/homo-sapiens/cdv3.html. 
  12. ↑ "CDV3 CDV3 homolog [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=DetailsSearch&Term=55573#HIV-1-interactions. 



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