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= PPP1R14B = Protein Phosphatase 1 Regulatory Inhibitor 14B is a protein encoded by the PPP1R14B gene. The function of the PPP1R14B protein is an inhibitor of PPP1CA. It has over 50-fold higher inhibitory activity when phosphorylated.

Gene
The PPP1R14B gene's aliases are Phospholipase C-beta-3 Neighboring Gene Protein, PLCB3N, PNG, SOM172, and PHI-1. PPP1R14B is located on the cytogenic band 11q13.1. It's orientation is on the minus strand with FKBP2 and PLCB3 as neighboring genes. It has a total of 4 exons and has a size of 2,463 bases.

Proteins
The PPP1R14B protein has a molecular weight (MW) of 15.9 kdal and a pI of 4.75. The N-terminus of the PPP1R14B protein is glycine-rich. There is one domain identified in the PPP1R14B protein and it is the PP1-Inhibitor. There is a negative charge cluster from amino acid 84 to 107 with 0 positive, 13 negative, and 11 neutral amino acids. This negative charge cluster is located near the middle of the PP1-Inhibitor.

Structure
The proposed secondary structure and tertiary structure of PPP1R14B from Chou and Fasman, and Phyre 2 show similar results. The N-terminus of PPP1R14B is proposed to have no secondary or tertiary structure. This correlates with the glycine-rich portion of the N-terminus in PPP1R14B. PPP1R14B has no known transmembrane helices.

Promoter
The promoter for PPP1R14B is called hg 38 promoter. It runs through the PPP1R14B gene and helps to promote neighboring genes as well. The hg 38 promoter is 16,668 base pairs and contains many transcription factor binding sites, DNase clusters, and one CpG island that is associated with the PPP1R14B gene. DNase Clusters 25, 92 and 95 were black, indicating that these regions are highly hypersensitive regions. They all had a cluster score of 1000 and had a genomic size of 350, 550, and 750 respectively. The CpG island was CpG Island 143 with a genomic size of 1569.

Expression Pattern
The PPP1R14B protein is ubiquitously expressed in most tissues. The image from NCBI shows the expression levels of PPP1R14B in normal tissues.

Protein Level Regulation
Utilizing the Group Based Prediction system, phosphorylation sites were identified on the PPP1R14B protein sequence. Some sites were experimented and confirmed by the data given by the NCBI page of PPP1R14B protein. These phosphorylation sites can change the conformation of the PPP1R14B protein, as well as help regulate and maintain protein activity and function. The inhibitory activity of the PP1-Inhibitor is increased 50-fold when phosphorylated.

Predicted glycation sites were identified utilizing the NetGlycate program. The positions that were predicted to be glycation sites were positions 114, 140, 146, and 147. All these scores were above the threshold of zero at values of 0.768, 0.717, 0.821, 0.846 respectively. Glycation is a common form of post-translational modification and is required for the function of a mature protein.

Glycosylation sites were predicted on the PPP1R14B sequence. The positions exceeded the 0.5 threshold of the NetOGlyc program. The values were 0.57 for position 22, 0.56 for position 26 and 0.51 for position 108. Glycosylation plays an important role in protein structure, function and stability.

Phosphorylation sites were predicted using the NetPhos server. 7 phosphorylation sites were predicted, some with specific kinases to phosphorylate the specific positions. The threonine on position 6 specified the kinase CKI, the serine at 21 was unspecified, the serine at 32 specified cdk5 and p38MAPK, the threonine at 57 specifies PKC, the serine at 105 specifies CKII, the serine at 142 specifies PKC and cdc2, and the threonine at 143 specifies PKC and p38MAPK.

The cleavage site between position 36 and 37 was identified on TatP 1.0 server. There is a potential Tat signal, but no Tat motif was found. Cleavage sites can be used to restore natural protein sequences, or inactivate a protein. YinYang sites were identified with the YinOYang 1.2 Server. The YinYang sites identified above can be O-GlcNAcylated and phosphorylated at different times in the cell.

Homology
The closest ortholog to the PPP1R14B in humans are Mammalia. The most distant ortholog is the Fresh-water polyp which is a Hydrozoa with a date of divergence of 824 MYA. THe sequence identity is 27.3% and the sequence similarity is 39.4%. From the Date of Divergence vs. Corrected Divergence graph, it can be seen that the evolution of the PPP1R14B gene is relatively slow.

Clinical Significance
PPP1R14B is known to help patients with cardiac dysfunction, mainly due to the domain within PPP1R14B, PP1-Inhibitor.