C19Orf81

C19Orf81 is a protein which in humans is encoded by the gene C19Orf81. It is a rarely expressed protein found mainly in the testes, cerebellum and cerebral cortex.

Aliases
Other names for C19Orf81 include chromosome 19 open reading frame 81 and C9J6K1.

Gene
The gene C19Orf81 is found on chromosome 19 at site 19q13.33 from and is 9862 base pairs in length. It runs in the positive direction. 5 exons compose the 761 base pair (bp) coding sequence of the gene. One isoform gene exists for C19Orf81 that is 951 bp in length (XM_054320844.1).

mRNA expression
Tissue expression of C19Orf81 mRNA is found in the testes. mRNA expression may be regulated by the KMT2D transcription factor, a histone methyltransferase, due to a decrease in C19Orf81 expression when KMT2D is down regulated.

Protein
The protein, C19Orf81, is 198 amino acids in length and has a molecular weight of 22.4 kDa. It contains one domain of unknown function, DUF4732, that spans from Gly23 to Leu181. Using DeepLoc 2.0, C19Orf81 has cytoplasm and nuclear localization. Predicted post-translational modifications (PTMs) of the protein, shown below, could indicate intercellular location and activity.



Post-translational modifications
PTMs predicted using Motif Scan and DTU Health Tec bioinformatic tools.

Phosphorylation
Casein kinase 2 (CK2): Thr31, Thr86, Thr93

Protein kinase C (PKC): Ser46, Ser111, Ser116, Ser154

Casein kinases, specifically CK2, have been shown to play a role in major cell events such as survival metabolism, growth, protein synthesis, proliferation and DNA repair. In an oncogenic setting, CK2 promotes the cancer cell’s growth due to its interference with apoptotic pathways. CK2 also plays a role in spermatogenesis and germ cell growth.

Amidation
An amidation site on C19Orf81 is positioned at Arg129 in the snippet ARGG. Amidation of a protein is and important modification necessary for signaling and protein interactions.

Structure
Secondary structure prediction by CFSSP method displays multiple α-helices and a few β-sheets. A similar pattern seen in the tertiary structure of C19Orf81 by AlphaFold, is shown below

Function
Given C19Orf81’s appearance in early stage spermatogonia cells and lower levels in other stages of spermatogenesis, as shown by expression summaries from the Human Protein Atlas, phosphorylation by CK2 could indicate a role for C19Orf81 in spermatogonial stem cell differentiation and growth.

Phylogeny


Based on data found in the NCBI database and using NCBI BLAST, C19Orf81 has orthologs in all vertebrates except birds.

Orthologs
Below is a table of ortholog genes of the human C19Orf81 gene found by using NCBI Blast. Sequence similarities were calculated using Emboss Needle Alignment Tool and median date of divergence (million years ago) was retrieved from TimeTree