Coiled-coil domain containing 74a

Coiled-coil domain containing 74A is a protein that in humans is encoded by the CCDC74A gene.^[3] The protein is most highly expressed in the testis and may play a role in developmental pathways.^[4] The gene has undergone duplication in the primate lineage within the last 9 million years, and its only true ortholog is found in Pan troglodytes.

CCDC74A
Identifiers
Aliases	CCDC74A, coiled-coil domain containing 74A
External IDs	GeneCards: CCDC74A; OMA:CCDC74A - orthologs
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2q21.1 Start 131,527,675 bp[1] End 131,533,666 bp[1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right uterine tube right testis left testis olfactory zone of nasal mucosa pituitary gland right adrenal gland left adrenal cortex right adrenal cortex anterior pituitary ventricular zone n/a More reference expression data BioGPS n/a
Orthologs Species Human Mouse Entrez 90557 n/a Ensembl ENSG00000163040 n/a UniProt Q96AQ1 n/a RefSeq (mRNA) NM_001258304 NM_001258305 NM_001258306 NM_138770 NM_001349041 NM_001349042 NM_001349043 NM_001349044 NM_001349045 NM_001349046 NM_001349047 n/a RefSeq (protein) NP_001245233 NP_001245234 NP_001245235 NP_620125 NP_001335970 NP_001335971 NP_001335972 NP_001335973 NP_001335974 NP_001335975 NP_001335976 n/a Location (UCSC) Chr 2: 131.53 – 131.53 Mb n/a PubMed search [2] n/a
Wikidata
View/Edit Human

Gene

The gene locus is located on the long arm of chromosome 2 at 2q21.1, and spans 5991 base pairs.^[5] A common alternative alias is LOC90557.^[6]

Transcript

The mRNA encoding the largest peptide product, isoform 6, contains 8 exons and 9 introns. It is 1842bps in length. Altogether, 11 protein isoforms have been characterized as a result of alternative splicing.^[7]

Protein

The longest CCDC74A peptide product, isoform 6, is 420 amino acids in length.^[8] This protein has a predicted molecular weight of 45.9kD and a predicted isoelectric point of 10.65.^[9] The entire length of the protein is evenly enriched in lysine and arginine residues. The protein contains 2 eukaryotic coiled-coil domains of unknown function, CCDC92 and CCDC74C.^[10] Its predicted localization is to the nucleus, but the protein may shuttle between the nucleus and the cytoplasm due to the presence of both a nuclear localization signal and a nuclear export signal.^[11]

Secondary structure

This diagram summarizes the locations of predicted alpha helix secondary structures for the human protein CCDC74A.

Predicted secondary structure for CCDC74A consists of 4 alpha helix regions, which are summarized in the table below and the diagram to the right.^[12]

Structure	Start	End
Alpha Helix 1	47	81
Alpha Helix 2	315	330
Alpha Helix 3	371	378
Alpha Helix 4	384	417

This diagram summarizes the conserved domains, signal peptides, and predicted post-translational modifications for the human protein CCDC74A.

Post-translational modification

A threonine residue (T395) which is highly conserved across Animalia orthologs may serve as a phosphorylation site by PKG kinase.^[13] Additionally, SUMOylation, methylation, and acetylation sites are predicted within highly conserved regions and may play a part in regulation.^[14][15] These predicted post-translational modifications and conserved domains are summarized in the diagram to the right.

Homology

In humans, CCDC74A has one important paralog, CCDC74B. Gene duplication is estimated to have occurred approximately 7 million years ago (MYA). As such, the only true ortholog of CCDC74A is found in Pan troglodytes, and is not found in Gorilla gorilla. However, distant orthologs prior to gene duplication are conserved in species that diverged from humans between 92-797 MYA. This includes species as distant as Cnidaria, but excludes Porifera or species outside of the kingdom Animalia.

Function

CCDC74A localization, expression, and interactions suggest that the protein may play a role in the expression of genes related to developmental and differentiation pathways, particularly during spermatogenesis.

Expression

The protein has been found most highly expressed in the testes and trachea. It is also expressed at moderate levels in the lung, brain, prostate, spinal cord, bone marrow, ovary, thymus, and thyroid gland.^[16]

Interactions

Consistent with predicted post-translational methylation, CCDC74A has been shown to interact with the lysine demethylase KDM1A through a yeast 2-hybrid assay.^[17] Additionally, through a yeast 2-hybrid assay, CCDC74A has been shown to interact with the lymphocyte activation molecule associated protein SH2D1A.^[18]

Clinical significance

In a study on androgen-independent prostate cancer, knockout of CCDC74A in androgen-dependent prostate cancer inhibited cell proliferation.^[19] Experiments in genital fibroblast cells have shown that CCDC74A expression significantly increases upon exposure to dihydrotestosterone.^[20]