Protein CDV3 homolog also known as carnitine deficiency-associated gene expressed in ventricle 3 is a protein that in humans is encoded by the CDV3gene.
CDV3 is a biomarker for hepatocellular carcinoma.[4] CDV3 has been considered as a potential target for gene therapy. Related gene families include plasma proteins and predicted intracellular proteins.[5]
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.[6]
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.[7]
Span
The exons of human CDV3 gene's longest transcript isoform span 16,711 bp.[8]
Transcripts
Isoforms
CDV3 has seven isoforms,[7] and more are continuously added to databases as they are discovered. Currently there are isoforms a-f.
A SAPS analysis[10] 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.[11]
Motif
Predicted Site (Base Pair Location)
Alanine-rich region: 28-77
Glycine-rich region: 33-72
Predicted protein kinase C (PKC) phosphorylation sites
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 GenomatixArchived 2001-02-24 at the Wayback Machine. 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.[7]
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.[7] 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
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
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.
^Tsuchiya K, Kawano Y, Kojima T, Nagata K, Takao T, Okada M, Shinohara H, Maki K, Toyama-Sorimachi N, Miyasaka N, Watanabe M, Karasuyama H (February 2003). "Molecular cloning and characterization of TPP36 and its isoform TPP32, novel substrates of Abl tyrosine kinase". FEBS Letters. 537 (1–3): 203–9. Bibcode:2003FEBSL.537..203T. doi:10.1016/S0014-5793(03)00127-3. PMID12606058. S2CID46575427.
