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    PPP1R16B protein phosphatase 1 regulatory subunit 16B [ Homo sapiens (human) ]

    Gene ID: 26051, updated on 10-Dec-2024

    Summary

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    Official Symbol
    PPP1R16Bprovided by HGNC
    Official Full Name
    protein phosphatase 1 regulatory subunit 16Bprovided by HGNC
    Primary source
    HGNC:HGNC:15850
    See related
    Ensembl:ENSG00000101445 MIM:613275; AllianceGenome:HGNC:15850
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    TIMAP; ANKRD4
    Summary
    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]
    Expression
    Broad expression in lymph node (RPKM 19.5), brain (RPKM 18.4) and 18 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See PPP1R16B in Genome Data Viewer
    Location:
    20q11.23
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 20 NC_000020.11 (38805697..38923024)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 20 NC_060944.1 (40535804..40653075)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 20 NC_000020.10 (37434340..37551667)

    Chromosome 20 - NC_000020.11Genomic Context describing neighboring genes Neighboring gene RN7SK pseudogene 173 Neighboring gene actin related protein 5 Neighboring gene uncharacterized LOC124904902 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:37408141-37408805 Neighboring gene H3K27ac hESC enhancer GRCh37_chr20:37409138-37409638 Neighboring gene H3K27ac hESC enhancer GRCh37_chr20:37409639-37410139 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:37410633-37411244 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:37411245-37411854 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:37432653-37433515 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:37433516-37434377 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:37434958-37435796 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12905 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17862 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17863 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:37446609-37447156 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr20:37447157-37447704 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17864 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17865 Neighboring gene Sharpr-MPRA regulatory region 4490 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17866 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17867 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17868 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17869 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17870 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17871 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:37499114-37499684 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17872 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17873 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17874 Neighboring gene RNA, 7SL, cytoplasmic 116, pseudogene Neighboring gene H3K27ac hESC enhancer GRCh37_chr20:37515241-37515741 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:37521809-37522767 Neighboring gene MPRA-validated peak4213 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:37536633-37537132 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:37548997-37549868 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12907 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17875 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17876 Neighboring gene family with sequence similarity 83 member D Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12908 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17877 Neighboring gene DEAH-box helicase 35 Neighboring gene nucleophosmin 1 pseudogene 19

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. TIMAP, the versatile protein phosphatase 1 regulator in endothelial cells. Boratkó A, et al. IUBMB Life, 2017 Dec. PMID 29140585
    2. TIMAP, a Regulatory Subunit of Protein Phosphatase 1, Inhibits In Vitro Neuronal Differentiation. Fonódi M, et al. Int J Mol Sci, 2023 Dec 11. PMID 38139189, Free PMC Article
    3. PKC mediated phosphorylation of TIMAP regulates PP1c activity and endothelial barrier function. Boratkó A, et al. Biochim Biophys Acta Mol Cell Res, 2017 Feb. PMID 27939168
    4. Regulation of merlin by protein phosphatase 1-TIMAP and EBP50 in endothelial cells. Boratkó A, et al. Int J Biochem Cell Biol, 2017 Jan. PMID 27871951
    5. The role of LR-TIMAP/PP1c complex in the occurrence and development of no-reflow. Quan X, et al. EBioMedicine, 2021 Mar. PMID 33639401, Free PMC Article

    See all (36) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. TIMAP, a Regulatory Subunit of Protein Phosphatase 1, Inhibits In Vitro Neuronal Differentiation.
      Title: TIMAP, a Regulatory Subunit of Protein Phosphatase 1, Inhibits In Vitro Neuronal Differentiation.
    2. The role of LR-TIMAP/PP1c complex in the occurrence and development of no-reflow.
      Title: The role of LR-TIMAP/PP1c complex in the occurrence and development of no-reflow.
    3. The TIMAP inhibits myosin phosphatase activity in ECs by competing with MYPT1 for PP1cbeta and blocking the PP1cbeta active site.
      Title: TIMAP inhibits endothelial myosin light chain phosphatase by competing with MYPT1 for the catalytic protein phosphatase 1 subunit PP1cβ.
    4. TIMAP is the versatile protein phosphatase 1 regulator in endothelial cells. (Review)
      Title: TIMAP, the versatile protein phosphatase 1 regulator in endothelial cells.
    5. NF2 localizes in nucleus when Ser518 is not phosphorylated, while phosphorylated form is present in cytoplasm and plasma membrane. Data suggest that binding of NF2 to TIMAP and EBP50 is critical in nuclear localization of NF2. (NF2 = neurofibromin 2; TIMAP = TGF-beta-inhibited membrane-associated protein; EBP50 = Ezrin-Radixin-Mosein binding phosphoprotein 50)
      Title: Regulation of merlin by protein phosphatase 1-TIMAP and EBP50 in endothelial cells.
    6. phosphorylation of TIMAP on Ser331 by PKC represents a new mechanism of endothelial barrier regulation, through the inhibition of phospho-ERM dephosphorylation
      Title: PKC mediated phosphorylation of TIMAP regulates PP1c activity and endothelial barrier function.
    7. Results indicate that PKC-phosphorylated ECE-1 is a TIMAP-PP1c substrate and this phosphatase complex has an important role in endothelin-1 production of EC through the regulation of ECE-1 activity.
      Title: TIMAP-protein phosphatase 1-complex controls endothelin-1 production via ECE-1 dephosphorylation.
    8. ROCK phosphorylated eEF1A1 is a novel substrate for TIMAP-PP1 underlining the complex regulatory role of TIMAP in the endothelium.
      Title: Elongation factor-1A1 is a novel substrate of the protein phosphatase 1-TIMAP complex.
    9. TIMAP promotes angiogenesis by suppressing PTEN-mediated Akt inhibition in human glomerular endothelial cells.
      Title: TIMAP promotes angiogenesis by suppressing PTEN-mediated Akt inhibition in human glomerular endothelial cells.
    10. These data confirmed the barrier-protective role of TIMAP
      Title: TIMAP protects endothelial barrier from LPS-induced vascular leakage and is down-regulated by LPS.
    Submit: New GeneRIF Correction See all GeneRIFs (13)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Biological insights from 108 schizophrenia-associated genetic loci.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • KIAA0823

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables enzyme inhibitor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables myosin phosphatase regulator activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein phosphatase regulator activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein phosphatase regulator activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in establishment of endothelial barrier IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in establishment of endothelial barrier IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of endothelial cell proliferation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of filopodium assembly ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of sprouting angiogenesis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in cell projection IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nuclear speck IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in perinuclear region of cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    protein phosphatase 1 regulatory inhibitor subunit 16B
    Names
    CAAX box protein TIMAP
    TGF-beta-inhibited membrane-associated protein
    ankyrin repeat domain protein 4
    ankyrin repeat domain-containing protein 4
    hTIMAP
    protein phosphatase 1, regulatory (inhibitor) subunit 16B

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001172735.3 → NP_001166206.1  protein phosphatase 1 regulatory inhibitor subunit 16B isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an in-frame exon in the coding region, as compared to variant 1. The resulting isoform (2) lacks an internal segment, as compared to isoform 1. This isoform (2) may undergo similar processing as isoform 1.
      Source sequence(s)
      AB177855, BC152467, HY125679
      Consensus CDS
      CCDS54462.1
      UniProtKB/Swiss-Prot
      Q96T49
      Related
      ENSP00000362428.1, ENST00000373331.2
      Conserved Domains (3) summary
      cd00204
      Location:71 → 184
      ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...
      pfam12796
      Location:72 → 164
      Ank_2; Ankyrin repeats (3 copies)
      sd00045
      Location:71 → 98
      ANK; ANK repeat [structural motif]

    2. NM_015568.4 → NP_056383.1  protein phosphatase 1 regulatory inhibitor subunit 16B isoform 1 precursor

      See identical proteins and their annotated locations for NP_056383.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AB020630, AB177855, BC152467, HY125679
      Consensus CDS
      CCDS13309.1
      UniProtKB/Swiss-Prot
      A2RRR6, E9PFS8, O94912, Q5W9G4, Q96T49, Q9NQG4
      Related
      ENSP00000299824.1, ENST00000299824.6
      Conserved Domains (3) summary
      cd00204
      Location:71 → 184
      ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...
      sd00045
      Location:71 → 98
      ANK; ANK repeat [structural motif]
      cl26073
      Location:71 → 301
      Ank_2; Ankyrin repeats (3 copies)

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000020.11 Reference GRCh38.p14 Primary Assembly

      Range
      38805697..38923024
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011528768.4 → XP_011527070.1  protein phosphatase 1 regulatory inhibitor subunit 16B isoform X1

      Conserved Domains (5) summary
      cd00204
      Location:99 → 286
      ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...
      pfam12796
      Location:109 → 263
      Ank_2; Ankyrin repeats (3 copies)
      pfam13637
      Location:87 → 125
      Ank_4; Ankyrin repeats (many copies)
      pfam13857
      Location:252 → 305
      Ank_5; Ankyrin repeats (many copies)
      sd00045
      Location:104 → 135
      ANK; ANK repeat [structural motif]

    2. XM_047440086.1 → XP_047296042.1  protein phosphatase 1 regulatory inhibitor subunit 16B isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060944.1 Alternate T2T-CHM13v2.0

      Range
      40535804..40653075
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054323326.1 → XP_054179301.1  protein phosphatase 1 regulatory inhibitor subunit 16B isoform X1

    2. XM_054323327.1 → XP_054179302.1  protein phosphatase 1 regulatory inhibitor subunit 16B isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q96T49.1 GenPept UniProtKB/Swiss-Prot:Q96T49

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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