PP16B_BOVIN
ID PP16B_BOVIN Reviewed; 568 AA.
AC Q95N27;
DT 13-AUG-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Protein phosphatase 1 regulatory inhibitor subunit 16B;
DE AltName: Full=CAAX box protein TIMAP;
DE AltName: Full=TGF-beta-inhibited membrane-associated protein;
DE Short=bTIMAP;
DE Flags: Precursor;
GN Name=PPP1R16B;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], INDUCTION BY TGFB1, AND SUBCELLULAR LOCATION.
RX PubMed=12055102; DOI=10.1152/ajpcell.00442.2001;
RA Cao W., Mattagajasingh S.N., Xu H., Kim K., Fierlbeck W., Deng J.,
RA Lowenstein C.J., Ballermann B.J.;
RT "TIMAP, a novel CAAX box protein regulated by TGF-beta1 and expressed in
RT endothelial cells.";
RL Am. J. Physiol. 283:C327-C337(2002).
RN [2]
RP FUNCTION, PHOSPHORYLATION AT SER-333 AND SER-337, AND MUTAGENESIS OF
RP VAL-64; PHE-66; SER-333 AND SER-337.
RX PubMed=17609201; DOI=10.1074/jbc.m703532200;
RA Li L., Kozlowski K., Wegner B., Rashid T., Yeung T., Holmes C.,
RA Ballermann B.J.;
RT "Phosphorylation of TIMAP by glycogen synthase kinase-3beta activates its
RT associated protein phosphatase 1.";
RL J. Biol. Chem. 282:25960-25969(2007).
RN [3]
RP INDUCTION BY LPS.
RX PubMed=21907835; DOI=10.1016/j.resp.2011.08.012;
RA Poirier C., Gorshkov B.A., Zemskova M.A., Bogatcheva N.V., Verin A.D.;
RT "TIMAP protects endothelial barrier from LPS-induced vascular leakage and
RT is down-regulated by LPS.";
RL Respir. Physiol. Neurobiol. 179:334-337(2011).
RN [4]
RP FUNCTION, AND INTERACTION WITH ECE1.
RX PubMed=26806547; DOI=10.1016/j.biocel.2016.01.016;
RA Boratko A., Vereb Z., Petrovski G., Csortos C.;
RT "TIMAP-protein phosphatase 1-complex controls endothelin-1 production via
RT ECE-1 dephosphorylation.";
RL Int. J. Biochem. Cell Biol. 73:11-18(2016).
CC -!- FUNCTION: Regulator of protein phosphatase 1 (PP1) that acts as a
CC positive regulator of pulmonary endothelial cell (EC) barrier function.
CC Protects the endothelial barrier from lipopolysaccharide (LPS)-induced
CC vascular leakage (By similarity). Involved in the regulation of the
CC PI3K/AKT signaling pathway (By similarity). Involved in the regulation
CC of angiogenesis and endothelial cell proliferation through the control
CC of ECE1 dephosphorylation, trafficking and activity (PubMed:26806547).
CC Involved in the regulation of endothelial cell filopodia extension
CC (PubMed:17609201). May be a downstream target for TGF-beta1 signaling
CC cascade in endothelial cells (By similarity). Involved in PKA-mediated
CC moesin dephosphorylation which is important in EC barrier protection
CC against thrombin stimulation. Promotes the interaction of PPP1CA with
CC RPSA/LAMR1 and in turn facilitates the dephosphorylation of RPSA/LAMR1
CC (By similarity). Involved in the dephosphorylation of EEF1A1 (By
CC similarity). {ECO:0000250|UniProtKB:Q96T49,
CC ECO:0000269|PubMed:17609201, ECO:0000269|PubMed:26806547}.
CC -!- SUBUNIT: Interacts with PPP1CA, PPP1CB and MSN. Interacts (via its
CC fourth ankyrin repeat) with the mature dimeric form of RPSA/LAMR1.
CC Interacts with EEF1A1 (By similarity). Interacts with PTEN (By
CC similarity). Interacts with ECE1 (PubMed:26806547).
CC {ECO:0000250|UniProtKB:Q96T49, ECO:0000269|PubMed:26806547}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12055102}. Cell
CC membrane {ECO:0000305}; Lipid-anchor {ECO:0000305}. Nucleus
CC {ECO:0000250|UniProtKB:Q96T49}. Cell projection
CC {ECO:0000250|UniProtKB:Q96T49}. Note=Colocalizes with RPSA/LAMR1 in the
CC cell membrane (By similarity). Localizes to the perinuclear region
CC (PubMed:12055102). Colocalizes with PTEN at the tip of EC projections
CC (By similarity). {ECO:0000250|UniProtKB:Q96T49,
CC ECO:0000269|PubMed:12055102}.
CC -!- INDUCTION: Inhibited by TGF-beta1 (PubMed:12055102). Down-regulated by
CC LPS (PubMed:21907835). {ECO:0000269|PubMed:12055102,
CC ECO:0000269|PubMed:21907835}.
CC -!- PTM: Phosphorylated by PKA and, after PKA priming, by GSK3B.
CC Phosphorylation by GSK3B reduces its association with PP1C and enhances
CC PP1C activity. Dephosphorylation by its associated PP1C results in
CC enhanced association with PP1C, but reduced PP1C activity.
CC {ECO:0000269|PubMed:17609201}.
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DR EMBL; AF362909; AAK52795.1; -; mRNA.
DR RefSeq; NP_777249.1; NM_174824.2.
DR RefSeq; XP_005214553.1; XM_005214496.3.
DR AlphaFoldDB; Q95N27; -.
DR SMR; Q95N27; -.
DR STRING; 9913.ENSBTAP00000000858; -.
DR iPTMnet; Q95N27; -.
DR PaxDb; Q95N27; -.
DR PRIDE; Q95N27; -.
DR Ensembl; ENSBTAT00000000858; ENSBTAP00000000858; ENSBTAG00000000653.
DR GeneID; 282091; -.
DR KEGG; bta:282091; -.
DR CTD; 26051; -.
DR VEuPathDB; HostDB:ENSBTAG00000000653; -.
DR VGNC; VGNC:33231; PPP1R16B.
DR eggNOG; KOG0505; Eukaryota.
DR GeneTree; ENSGT00940000154090; -.
DR HOGENOM; CLU_000134_54_2_1; -.
DR InParanoid; Q95N27; -.
DR OMA; ISPDLCN; -.
DR OrthoDB; 564568at2759; -.
DR TreeFam; TF316803; -.
DR Proteomes; UP000009136; Chromosome 13.
DR Bgee; ENSBTAG00000000653; Expressed in prefrontal cortex and 101 other tissues.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-SubCell.
DR GO; GO:0016607; C:nuclear speck; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0017020; F:myosin phosphatase regulator activity; IBA:GO_Central.
DR GO; GO:0008157; F:protein phosphatase 1 binding; IBA:GO_Central.
DR GO; GO:0019888; F:protein phosphatase regulator activity; IBA:GO_Central.
DR GO; GO:0061028; P:establishment of endothelial barrier; IBA:GO_Central.
DR GO; GO:1902309; P:negative regulation of peptidyl-serine dephosphorylation; IEA:Ensembl.
DR GO; GO:1903589; P:positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis; IEA:Ensembl.
DR GO; GO:0035307; P:positive regulation of protein dephosphorylation; IEA:Ensembl.
DR GO; GO:0051489; P:regulation of filopodium assembly; IMP:UniProtKB.
DR GO; GO:0014066; P:regulation of phosphatidylinositol 3-kinase signaling; IEA:Ensembl.
DR GO; GO:0035304; P:regulation of protein dephosphorylation; IBA:GO_Central.
DR GO; GO:1903670; P:regulation of sprouting angiogenesis; IMP:UniProtKB.
DR Gene3D; 1.25.40.20; -; 2.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR017417; Pase-1_reg_su_16AB.
DR Pfam; PF12796; Ank_2; 2.
DR PIRSF; PIRSF038159; PP1_16AB_vert; 1.
DR SMART; SM00248; ANK; 5.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 4.
PE 1: Evidence at protein level;
KW ANK repeat; Cell membrane; Cell projection; Coiled coil; Lipoprotein;
KW Membrane; Methylation; Nucleus; Palmitate; Phosphoprotein; Prenylation;
KW Reference proteome; Repeat.
FT CHAIN 1..565
FT /note="Protein phosphatase 1 regulatory inhibitor subunit
FT 16B"
FT /id="PRO_0000067042"
FT PROPEP 566..568
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000396709"
FT REPEAT 100..129
FT /note="ANK 1"
FT REPEAT 133..162
FT /note="ANK 2"
FT REPEAT 228..257
FT /note="ANK 3"
FT REPEAT 261..290
FT /note="ANK 4"
FT REPEAT 531..560
FT /note="ANK 5"
FT REGION 327..346
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 373..404
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 504..525
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 15..55
FT /evidence="ECO:0000255"
FT COMPBIAS 382..404
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 69
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VHQ3"
FT MOD_RES 333
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:17609201"
FT MOD_RES 337
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:17609201"
FT MOD_RES 350
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96T49"
FT MOD_RES 477
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96T49"
FT MOD_RES 565
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250|UniProtKB:Q923M0"
FT LIPID 564
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q923M0"
FT LIPID 565
FT /note="S-farnesyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q923M0"
FT MUTAGEN 64
FT /note="V->A: Hyperphosphorylation, loss of PPP1CA-binding
FT and PP1C phosphatase activity; when associated with A-66."
FT /evidence="ECO:0000269|PubMed:17609201"
FT MUTAGEN 66
FT /note="F->A: Hyperphosphorylation, loss of PPP1CA-binding
FT and PP1C phosphatase activity; when associated with A-64."
FT /evidence="ECO:0000269|PubMed:17609201"
FT MUTAGEN 333
FT /note="S->A: Loss of GSK3B-mediated phosphorylation but no
FT effect on PKA-mediated phosphorylation. Loss of GSK3B-
FT mediated phosphorylation but no effect on PKA-mediated
FT phosphorylation; when associated with A-337."
FT /evidence="ECO:0000269|PubMed:17609201"
FT MUTAGEN 337
FT /note="S->A: Loss of GSK3B-mediated phosphorylation but no
FT effect on PKA-mediated phosphorylation. Loss of GSK3B-
FT mediated phosphorylation but no effect on PKA-mediated
FT phosphorylation; when associated with A-333."
FT /evidence="ECO:0000269|PubMed:17609201"
SQ SEQUENCE 568 AA; 63643 MW; 61C10899462B0334 CRC64;
MASHVDLLTE LQLLEKVPTL ERLRAAQKRR AQQLKKWAQY EQDLQHRKRK HERKRSTGGR
RKKVSFEASV ALLEASLRND AEEVRYFLKN KVSPDLCNED GLTALHQCCI DNFEEIVKLL
LSHGANVNAK DNELWTPLHA AATCGHINLV KILVQYGADL LAVNSDGNMP YDLCEDEPTL
DVIETCMAYQ GITQEKINEM RAAPEQQMIS DIHCMIAAGQ DLDWVDAQGA TLLHIAGANG
YLRAAELLLD HGVRVDVKDW DGWEPLHAAA FWGQMQMAEL LVSHGASLSA RTSMDEMPID
LCEEEEFKVL LLELKHKHDV IMKSQLRHKS SLSRRTSSAG SRGKVVRRAS LSDRTNLYRK
EYEGEAILWQ QRSASEDQRN STYNGDIRET RTDQENKDPN PRLEKPVLLS EFPTKIPHSD
MDMPVENGLR APVSTYQYAL CNGDVWKVHE VPDYSMAYGN PGVADATPSW SGYKEQSPQT
LLELKRQRAA AKLLSHPFLS THLGSGVSRT GEGSSEGKAP LIGGRTSPYS SNGTSVYYTV
TSGDPPLLKF KAPIEEMEEK VHGCCRIS
