PPP1R16B Gene

HGNC Family	Ankyrin repeat domain containing (ANKRD), Protein phosphatase 1 regulatory subunits (PPP1R)
Name	protein phosphatase 1, regulatory subunit 16B
Description	The protein encoded by this gene is membrane-associated and contains five ankyrin repeats, a protein phosphatase-1-interacting domain, and a carboxy-terminal CAAX box domain. Synthesis of the encoded protein is inhibited by transforming growth factor beta-1. The protein may bind to the membrane through its CAAX box domain and may act as a signaling molecule through interaction with protein phosphatase-1. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar processing to generate mature protein. [provided by RefSeq, Sep 2015]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPPP1R16B, also known as TIMAP (TGF‑β‑inhibited membrane‑associated protein), was originally identified as a gene highly expressed in endothelial and hematopoietic cells with a domain architecture comprising five ankyrin repeats, a PP1‑interacting motif, and a C‑terminal CAAX box that targets the protein to membranes. Its expression is tightly regulated by TGF‑β1, and TIMAP is post‑translationally modified by prenylation and various kinase activities. These features earmark TIMAP as a regulatory/targeting subunit for protein phosphatase 1 (PP1), and its preferential interaction with the PP1 catalytic β‑isoform establishes it as a member of the myosin phosphatase targeting (MYPT) protein family, suggesting a significant role in cellular signaling in vascular endothelium."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn endothelial cells, TIMAP is central to maintaining barrier integrity and modulating the cytoskeletal dynamics that underpin cell adhesion and permeability. It acts as a modulator of PP1 activity, where its phosphorylation status—regulated by kinases including PKA, GSK3β, and PKC—affects its inhibitory potency towards substrates such as phospho‑ERM proteins and myosin light chain 2. TIMAP depletion, or its altered phosphorylation, leads to impaired endothelial barrier function, reduced proliferation, enhanced apoptosis, and aberrations in angiogenic sprouting. These findings underscore a barrier‑protective role where TIMAP’s regulation of PP1 substrates is critical for controlling cell contractility and intercellular junctions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond barrier regulation, TIMAP influences broader signaling pathways that govern endothelial cell proliferation, survival, and differentiation. Its interaction with PTEN modulates Akt phosphorylation, thereby affecting angiogenic responses, while its binding to eEF1A1 is implicated in the regulation of cell attachment and spreading. TIMAP also associates with merlin to control its phosphorylation state and subcellular localization, impacting cell migration and wound healing. Moreover, by regulating the phosphorylation state of endothelin‑converting enzyme‑1 (ECE‑1), TIMAP indirectly modulates endothelin‑1 secretion and the resultant angiogenic phenotype. Intriguingly, TIMAP expression is not limited to the endothelium; in neuronal cells, its downregulation and translocation from the plasma membrane to the nucleus appear to influence the differentiation process."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "12"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wangsen Cao, Subhendra N Mattagajasingh, Hangxue Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TIMAP, a novel CAAX box protein regulated by TGF-beta1 and expressed in endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00442.2001"}], "href": "https://doi.org/10.1152/ajpcell.00442.2001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12055102"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12055102"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Csilla Csortos, Istvan Czikora, Natalia V Bogatcheva, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TIMAP is a positive regulator of pulmonary endothelial barrier function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Lung Cell Mol Physiol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajplung.00325.2007"}], "href": "https://doi.org/10.1152/ajplung.00325.2007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18586956"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18586956"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Anita Boratkó, Csilla Csortos "}, {"type": "b", "children": [{"type": "t", "text": "TIMAP, the versatile protein phosphatase 1 regulator in endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "IUBMB Life (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/iub.1695"}], "href": "https://doi.org/10.1002/iub.1695"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29140585"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29140585"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "István Czikora, Kyung-mi Kim, Anita Kása, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of the effect of TIMAP phosphorylation on its interaction with protein phosphatase 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochimie (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biochi.2011.03.011"}], "href": "https://doi.org/10.1016/j.biochi.2011.03.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21466834"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21466834"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Christophe Poirier, Boris A Gorshkov, Marina A Zemskova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TIMAP protects endothelial barrier from LPS-induced vascular leakage and is down-regulated by LPS."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Respir Physiol Neurobiol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.resp.2011.08.012"}], "href": "https://doi.org/10.1016/j.resp.2011.08.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21907835"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21907835"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Xin Wang, Marya Obeidat, Laiji Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TIMAP inhibits endothelial myosin light chain phosphatase by competing with MYPT1 for the catalytic protein phosphatase 1 subunit PP1cβ."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA118.006075"}], "href": "https://doi.org/10.1074/jbc.RA118.006075"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31315927"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31315927"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Marya Obeidat, Laiji Li, Barbara J Ballermann "}, {"type": "b", "children": [{"type": "t", "text": "TIMAP promotes angiogenesis by suppressing PTEN-mediated Akt inhibition in human glomerular endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Renal Physiol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajprenal.00070.2014"}], "href": "https://doi.org/10.1152/ajprenal.00070.2014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25007873"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25007873"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Anita Boratkó, Margit Péter, Zsófia Thalwieser, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Elongation factor-1A1 is a novel substrate of the protein phosphatase 1-TIMAP complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biochem Cell Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biocel.2015.10.021"}], "href": "https://doi.org/10.1016/j.biocel.2015.10.021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26497934"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26497934"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Anita Boratkó, Zoltán Veréb, Goran Petrovski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TIMAP-protein phosphatase 1-complex controls endothelin-1 production via ECE-1 dephosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biochem Cell Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biocel.2016.01.016"}], "href": "https://doi.org/10.1016/j.biocel.2016.01.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26806547"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26806547"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Anita Boratkó, Margit Péter, Csilla Csortos "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of merlin by protein phosphatase 1-TIMAP and EBP50 in endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biochem Cell Biol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biocel.2016.11.010"}], "href": "https://doi.org/10.1016/j.biocel.2016.11.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27871951"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27871951"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Anita Boratkó, Csilla Csortos "}, {"type": "b", "children": [{"type": "t", "text": "PKC mediated phosphorylation of TIMAP regulates PP1c activity and endothelial barrier function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Cell Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2016.12.001"}], "href": "https://doi.org/10.1016/j.bbamcr.2016.12.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27939168"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27939168"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Márton Fonódi, Zsófia Thalwieser, Csilla Csortos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TIMAP, a Regulatory Subunit of Protein Phosphatase 1, Inhibits In Vitro Neuronal Differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms242417360"}], "href": "https://doi.org/10.3390/ijms242417360"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38139189"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38139189"}]}]}]}
Synonyms	ANKRD4, TIMAP
Proteins	PP16B_HUMAN
NCBI Gene ID	26051
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PPP1R16B has 5,981 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 113 datasets.

Click the + buttons to view associations for PPP1R16B from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PPP1R16B Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by PPP1R16B gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PPP1R16B gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of PPP1R16B gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of PPP1R16B gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of PPP1R16B gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of PPP1R16B gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PPP1R16B gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of PPP1R16B gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PPP1R16B gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PPP1R16B gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of PPP1R16B gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PPP1R16B gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of PPP1R16B gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PPP1R16B gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PPP1R16B gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PPP1R16B gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of PPP1R16B gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing PPP1R16B protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PPP1R16B gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PPP1R16B protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PPP1R16B protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with PPP1R16B protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with PPP1R16B protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of PPP1R16B gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PPP1R16B gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PPP1R16B gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PPP1R16B gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with PPP1R16B gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by PPP1R16B gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with PPP1R16B gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with PPP1R16B gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with PPP1R16B gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with PPP1R16B gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PPP1R16B gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at PPP1R16B gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PPP1R16B gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PPP1R16B gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing PPP1R16B from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with PPP1R16B gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with PPP1R16B gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.