PALS1_MOUSE
ID PALS1_MOUSE Reviewed; 675 AA.
AC Q9JLB2;
DT 10-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Protein PALS1 {ECO:0000305};
DE AltName: Full=MAGUK p55 subfamily member 5;
DE AltName: Full=Protein associated with Lin-7 1 {ECO:0000303|PubMed:10753959, ECO:0000303|PubMed:11927608};
GN Name=Pals1 {ECO:0000303|PubMed:10753959, ECO:0000312|MGI:MGI:1927339};
GN Synonyms=Mpp5 {ECO:0000312|MGI:MGI:1927339};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF GLU-207; LEU-208; LEU-212;
RP HIS-216; LEU-221; HIS-224; ASP-225 AND VAL-227, TISSUE SPECIFICITY,
RP SUBCELLULAR LOCATION, AND INTERACTION WITH LIN7C.
RC TISSUE=Embryo;
RX PubMed=10753959; DOI=10.1074/jbc.275.15.11425;
RA Kamberov E., Makarova O., Roh M., Liu A., Karnak D., Straight S.,
RA Margolis B.;
RT "Molecular cloning and characterization of Pals, proteins associated with
RT mLin-7.";
RL J. Biol. Chem. 275:11425-11431(2000).
RN [2]
RP INTERACTION WITH PATJ, DOMAIN, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP LEU-150 AND VAL-154.
RX PubMed=11927608; DOI=10.1083/jcb.200109010;
RA Roh M.H., Makarova O., Liu C.-J., Shin K., Lee S., Laurinec S., Goyal M.,
RA Wiggins R., Margolis B.;
RT "The Maguk protein, Pals1, functions as an adapter, linking mammalian
RT homologues of Crumbs and Discs Lost.";
RL J. Cell Biol. 157:161-172(2002).
RN [3]
RP INTERACTION WITH CRB3 AND PATJ.
RX PubMed=12527193; DOI=10.1016/s0378111902010843;
RA Makarova O., Roh M.H., Liu C.-J., Laurinec S., Margolis B.;
RT "Mammalian Crumbs3 is a small transmembrane protein linked to protein
RT associated with Lin-7 (Pals1).";
RL Gene 302:21-29(2003).
RN [4]
RP INTERACTION WITH PARD6B.
RX PubMed=12545177; DOI=10.1038/ncb923;
RA Hurd T.W., Gao L., Roh M.H., Macara I.G., Margolis B.;
RT "Direct interaction of two polarity complexes implicated in epithelial
RT tight junction assembly.";
RL Nat. Cell Biol. 5:137-142(2003).
RN [5]
RP MUTAGENESIS OF HIS-32; ARG-33; GLU-34; ALA-36; VAL-37; ASP-38; CYS-39 AND
RP PRO-40, SUBCELLULAR LOCATION, AND INTERACTION WITH PARD6B.
RX PubMed=15140881; DOI=10.1074/jbc.m401930200;
RA Wang Q., Hurd T.W., Margolis B.;
RT "Tight junction protein Par6 interacts with an evolutionarily conserved
RT region in the amino terminus of PALS1/stardust.";
RL J. Biol. Chem. 279:30715-30721(2004).
RN [6]
RP INTERACTION WITH MPDZ.
RX PubMed=15316081; DOI=10.1242/jcs.01301;
RA van de Pavert S.A., Kantardzhieva A., Malysheva A., Meuleman J.,
RA Versteeg I., Levelt C., Klooster J., Geiger S., Seeliger M.W., Rashbass P.,
RA Le Bivic A., Wijnholds J.;
RT "Crumbs homologue 1 is required for maintenance of photoreceptor cell
RT polarization and adhesion during light exposure.";
RL J. Cell Sci. 117:4169-4177(2004).
RN [7]
RP FUNCTION, INTERACTION WITH SC6A1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AND DOMAIN.
RX PubMed=15234345; DOI=10.1016/j.mcn.2004.03.006;
RA McHugh E.M., Zhu W., Milgram S., Mager S.;
RT "The GABA transporter GAT1 and the MAGUK protein Pals1: interaction, uptake
RT modulation, and coexpression in the brain.";
RL Mol. Cell. Neurosci. 26:406-417(2004).
RN [8]
RP INTERACTION WITH EZR, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=15677456; DOI=10.1074/jbc.m411941200;
RA Cao X., Ding X., Guo Z., Zhou R., Wang F., Long F., Wu F., Bi F., Wang Q.,
RA Fan D., Forte J.G., Teng M., Yao X.;
RT "PALS1 specifies the localization of Ezrin to the apical membrane of
RT gastric parietal cells.";
RL J. Biol. Chem. 280:13584-13592(2005).
RN [9]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=15558731; DOI=10.1002/cne.20367;
RA Stoehr H., Molday L.L., Molday R.S., Weber B.H.F., Biedermann B.,
RA Reichenbach A., Kraemer F.;
RT "Membrane-associated guanylate kinase proteins MPP4 and MPP5 associate with
RT Veli3 at distinct intercellular junctions of the neurosensory retina.";
RL J. Comp. Neurol. 481:31-41(2005).
RN [10]
RP IDENTIFICATION IN A COMPLEX WITH MPP3 AND CRB1.
RX PubMed=16519681; DOI=10.1111/j.1742-4658.2006.05140.x;
RA Kantardzhieva A., Alexeeva S., Versteeg I., Wijnholds J.;
RT "MPP3 is recruited to the MPP5 protein scaffold at the retinal outer
RT limiting membrane.";
RL FEBS J. 273:1152-1165(2006).
RN [11]
RP DEVELOPMENTAL STAGE.
RX PubMed=17920587; DOI=10.1016/j.yexcr.2007.08.025;
RA Gosens I., Sessa A., den Hollander A.I., Letteboer S.J.F., Belloni V.,
RA Arends M.L., Le Bivic A., Cremers F.P.M., Broccoli V., Roepman R.;
RT "FERM protein EPB41L5 is a novel member of the mammalian CRB-MPP5 polarity
RT complex.";
RL Exp. Cell Res. 313:3959-3970(2007).
RN [12]
RP FUNCTION, DOMAIN, AND MUTAGENESIS OF LEU-379.
RX PubMed=17182851; DOI=10.1091/mbc.e06-07-0651;
RA Wang Q., Chen X.W., Margolis B.;
RT "PALS1 regulates E-cadherin trafficking in mammalian epithelial cells.";
RL Mol. Biol. Cell 18:874-885(2007).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [14]
RP FUNCTION, INTERACTION WITH WWTR1, AND SUBCELLULAR LOCATION.
RX PubMed=21145499; DOI=10.1016/j.devcel.2010.11.012;
RA Varelas X., Samavarchi-Tehrani P., Narimatsu M., Weiss A., Cockburn K.,
RA Larsen B.G., Rossant J., Wrana J.L.;
RT "The Crumbs complex couples cell density sensing to Hippo-dependent control
RT of the TGF-beta-SMAD pathway.";
RL Dev. Cell 19:831-844(2010).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=20237282; DOI=10.1523/jneurosci.5185-09.2010;
RA Ozcelik M., Cotter L., Jacob C., Pereira J.A., Relvas J.B., Suter U.,
RA Tricaud N.;
RT "Pals1 is a major regulator of the epithelial-like polarization and the
RT extension of the myelin sheath in peripheral nerves.";
RL J. Neurosci. 30:4120-4131(2010).
RN [16]
RP FUNCTION, INTERACTION WITH PATJ AND CRB2, DEVELOPMENTAL STAGE, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=20399730; DOI=10.1016/j.neuron.2010.03.019;
RA Kim S., Lehtinen M.K., Sessa A., Zappaterra M.W., Cho S.H., Gonzalez D.,
RA Boggan B., Austin C.A., Wijnholds J., Gambello M.J., Malicki J.,
RA LaMantia A.S., Broccoli V., Walsh C.A.;
RT "The apical complex couples cell fate and cell survival to cerebral
RT cortical development.";
RL Neuron 66:69-84(2010).
RN [17]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=22398208; DOI=10.1093/hmg/dds091;
RA Cho S.H., Kim J.Y., Simons D.L., Song J.Y., Le J.H., Swindell E.C.,
RA Jamrich M., Wu S.M., Kim S.;
RT "Genetic ablation of Pals1 in retinal progenitor cells models the retinal
RT pathology of Leber congenital amaurosis.";
RL Hum. Mol. Genet. 21:2663-2676(2012).
RN [18]
RP TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=23893895; DOI=10.1002/glia.22545;
RA Dudok J.J., Sanz A.S., Lundvig D.M., Sothilingam V., Garcia Garrido M.,
RA Klooster J., Seeliger M.W., Wijnholds J.;
RT "MPP3 regulates levels of PALS1 and adhesion between photoreceptors and
RT Mueller cells.";
RL Glia 61:1629-1644(2013).
RN [19]
RP DEVELOPMENTAL STAGE.
RX PubMed=23001562; DOI=10.1093/hmg/dds398;
RA Alves C.H., Sanz A.S., Park B., Pellissier L.P., Tanimoto N., Beck S.C.,
RA Huber G., Murtaza M., Richard F., Sridevi Gurubaran I., Garcia Garrido M.,
RA Levelt C.N., Rashbass P., Le Bivic A., Seeliger M.W., Wijnholds J.;
RT "Loss of CRB2 in the mouse retina mimics human retinitis pigmentosa due to
RT mutations in the CRB1 gene.";
RL Hum. Mol. Genet. 22:35-50(2013).
RN [20]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=26404741; DOI=10.1038/srep14504;
RA Paniagua A.E., Herranz-Martin S., Jimeno D., Jimeno A.M., Lopez-Benito S.,
RA Carlos Arevalo J., Velasco A., Aijon J., Lillo C.;
RT "CRB2 completes a fully expressed Crumbs complex in the Retinal Pigment
RT Epithelium.";
RL Sci. Rep. 5:14504-14504(2015).
RN [21]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=26657772; DOI=10.1242/dev.124180;
RA Park J.Y., Hughes L.J., Moon U.Y., Park R., Kim S.B., Tran K., Lee J.S.,
RA Cho S.H., Kim S.;
RT "The apical complex protein Pals1 is required to maintain cerebellar
RT progenitor cells in a proliferative state.";
RL Development 143:133-146(2016).
RN [22]
RP TISSUE SPECIFICITY, AND INTERACTION WITH CDH5.
RX PubMed=27466317; DOI=10.1091/mbc.e16-02-0127;
RA Brinkmann B.F., Steinbacher T., Hartmann C., Kummer D., Pajonczyk D.,
RA Mirzapourshafiyi F., Nakayama M., Weide T., Gerke V., Ebnet K.;
RT "VE-cadherin interacts with cell polarity protein Pals1 to regulate
RT vascular lumen formation.";
RL Mol. Biol. Cell 27:2811-2821(2016).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 123-180.
RX PubMed=15241471; DOI=10.1038/sj.emboj.7600294;
RA Li Y., Karnak D., Demeler B., Margolis B., Lavie A.;
RT "Structural basis for L27 domain-mediated assembly of signaling and cell
RT polarity complexes.";
RL EMBO J. 23:2723-2733(2004).
RN [24]
RP STRUCTURE BY NMR OF 236-335.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the PDZ domain of PALS1 protein.";
RL Submitted (FEB-2005) to the PDB data bank.
CC -!- FUNCTION: Plays a role in tight junction biogenesis and in the
CC establishment of cell polarity in epithelial cells (By similarity).
CC Also involved in adherens junction biogenesis by ensuring correct
CC localization of the exocyst complex protein EXOC4/SEC8 which allows
CC trafficking of adherens junction structural component CDH1 to the cell
CC surface (PubMed:17182851, PubMed:20237282). Plays a role through its
CC interaction with CDH5 in vascular lumen formation and endothelial
CC membrane polarity (By similarity). Required during embryonic and
CC postnatal retinal development (PubMed:22398208). Required for the
CC maintenance of cerebellar progenitor cells in an undifferentiated
CC proliferative state, preventing premature differentiation, and is
CC required for cerebellar histogenesis, fissure formation, cerebellar
CC layer organization and cortical development (PubMed:20399730,
CC PubMed:26404741). Plays a role in neuronal progenitor cell survival,
CC potentially via promotion of mTOR signaling (PubMed:20399730). Plays a
CC role in the radial and longitudinal extension of the myelin sheath in
CC Schwann cells (PubMed:20237282). May modulate SC6A1/GAT1-mediated GABA
CC uptake by stabilizing the transporter (PubMed:15234345). May play a
CC role in the T-cell receptor-mediated activation of NF-kappa-B (By
CC similarity). Required for localization of EZR to the apical membrane of
CC parietal cells and may play a role in the dynamic remodeling of the
CC apical cytoskeleton (PubMed:15677456). Required for the normal
CC polarized localization of the vesicular marker STX4 (PubMed:20237282).
CC Required for the correct trafficking of the myelin proteins PMP22 and
CC MAG (By similarity). Involved in promoting phosphorylation and
CC cytoplasmic retention of transcriptional coactivators YAP1 and
CC WWTR1/TAZ which leads to suppression of TGFB1-dependent transcription
CC of target genes such as CCN2/CTGF, SERPINE1/PAI1, SNAI1/SNAIL1 and
CC SMAD7 (PubMed:21145499). {ECO:0000250|UniProtKB:B4F7E7,
CC ECO:0000250|UniProtKB:Q8N3R9, ECO:0000269|PubMed:15234345,
CC ECO:0000269|PubMed:15677456, ECO:0000269|PubMed:17182851,
CC ECO:0000269|PubMed:20237282, ECO:0000269|PubMed:20399730,
CC ECO:0000269|PubMed:21145499, ECO:0000269|PubMed:22398208,
CC ECO:0000269|PubMed:26404741, ECO:0000269|PubMed:26657772}.
CC -!- SUBUNIT: Heterodimer with MPP1 (By similarity). Forms a heterotrimeric
CC complex composed of PALS1, LIN7B and PATJ; the N-terminal L27 domain of
CC PALS1 interacts with the L27 domain of PATJ and the C-terminal L27
CC domain of PALS1 interacts with the L27 domain of LIN7B (By similarity).
CC Component of a complex composed of PALS1, CRB1 and MPP4 (By
CC similarity). Component of a complex whose core is composed of ARHGAP17,
CC AMOT, PALS1, PATJ and PARD3/PAR3 (By similarity). Component of a
CC complex composed of PALS1, CRB1 and EPB41L5 (By similarity). Within the
CC complex, interacts (via HOOK domain) with EPB41L5 (via FERM domain),
CC and interacts with CRB1 (via intracellular domain) (By similarity).
CC Component of a complex composed of PALS1, MPP3 and CRB1; PALS1 acts as
CC a bridging protein between MPP3 (via guanylate kinase-like domain) and
CC CRB1 (PubMed:16519681). Component of a complex composed of CRB3, PALS1
CC and PATJ (By similarity). Interacts (via PDZ domain) with PATJ (via N-
CC terminus) (PubMed:11927608, PubMed:12527193, PubMed:20399730).
CC Interacts with EZR (PubMed:15677456). Interacts (via PDZ domain) with
CC CRB1 (via C-terminal ERLI motif) (By similarity). While the PDZ domain
CC is sufficient for interaction with CRB1, the adjacent SH3 and guanylate
CC kinase-like domains are likely to contribute to a high affinity
CC interaction (By similarity). Interacts with WWTR1/TAZ (via WW domain)
CC (PubMed:21145499). Interacts with MPP7 (By similarity). Interacts (via
CC PDZ domain) with CRB3 (via C-terminus) (PubMed:12527193). Interacts
CC with LIN7C (PubMed:10753959). Interacts with MPDZ (PubMed:15316081).
CC Interacts with PARD6B (PubMed:12545177, PubMed:15140881). Interacts
CC with SC6A1 (PubMed:15234345). Interacts with CDH5; the interaction
CC promotes PALS1 localization to cell junctions and is required for CDH5-
CC mediated vascular lumen formation and endothelial cell
CC (PubMed:27466317). Interacts with NPHP1 (via coiled coil and SH3
CC domains) (By similarity). Interacts with NPHP4 (By similarity).
CC Interacts with CRB2 (PubMed:20399730). {ECO:0000250|UniProtKB:E2QY99,
CC ECO:0000250|UniProtKB:Q8N3R9, ECO:0000269|PubMed:10753959,
CC ECO:0000269|PubMed:11927608, ECO:0000269|PubMed:12527193,
CC ECO:0000269|PubMed:12545177, ECO:0000269|PubMed:15140881,
CC ECO:0000269|PubMed:15234345, ECO:0000269|PubMed:15316081,
CC ECO:0000269|PubMed:15677456, ECO:0000269|PubMed:16519681,
CC ECO:0000269|PubMed:20399730, ECO:0000269|PubMed:21145499,
CC ECO:0000269|PubMed:27466317}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus {ECO:0000250|UniProtKB:Q8N3R9}.
CC Cell membrane; Peripheral membrane protein. Endomembrane system;
CC Peripheral membrane protein. Cell junction, tight junction
CC {ECO:0000269|PubMed:21145499}. Cell junction, adherens junction
CC {ECO:0000250|UniProtKB:Q8N3R9}. Cell projection, axon
CC {ECO:0000269|PubMed:15234345}. Perikaryon
CC {ECO:0000269|PubMed:15234345}. Apical cell membrane
CC {ECO:0000269|PubMed:26404741, ECO:0000269|PubMed:26657772}.
CC Note=Localized to the tight junctions of epithelial cells
CC (PubMed:10753959, PubMed:11927608, PubMed:15140881, PubMed:15677456).
CC Localized to the Golgi apparatus in T lymphocytes (By similarity).
CC Localized to a subset of intracellular vesicles (PubMed:15234345).
CC Localized to the Purkinje cell body and axon (PubMed:15234345).
CC Localized to intercellular junctions in vascular endothelial cells (By
CC similarity). Localized to Schmidt-Lanterman incisures, the adaxonal
CC domain, and the inner part of paranodal loops in myelinating Schwann
CC cells of the sciatic nerve (PubMed:20237282). Localized to apical
CC membrane domains of the outer limiting membrane (OLM) junctions in the
CC retina (PubMed:15558731). Colocalizes with CRB1 at the OLM, apical to
CC the adherens junction (By similarity). Colocalizes with MPP1 in the
CC retina at the OLM (By similarity). Colocalizes with MPP3 to the
CC subapical region of adherens junctions in the retina OLM (By
CC similarity). {ECO:0000250|UniProtKB:Q8N3R9,
CC ECO:0000269|PubMed:10753959, ECO:0000269|PubMed:11927608,
CC ECO:0000269|PubMed:15140881, ECO:0000269|PubMed:15234345,
CC ECO:0000269|PubMed:15558731, ECO:0000269|PubMed:15677456,
CC ECO:0000269|PubMed:20237282}.
CC -!- TISSUE SPECIFICITY: Expressed in the retinal pigment epithelium (at
CC protein level) (PubMed:15558731, PubMed:22398208, PubMed:23893895,
CC PubMed:26404741). Expressed in the vascular plexus of the retina (at
CC protein level) (PubMed:27466317). In the brain, expressed in the
CC dentate gyrus of hippocampus, striatum and cerebellum (at protein
CC level) (PubMed:15234345, PubMed:26404741). Expressed in the sciatic
CC nerve (at protein level) (PubMed:20237282). Expressed in the kidney
CC nephron (at protein level) (PubMed:10753959, PubMed:15558731).
CC Expressed in the lung, and heart (PubMed:10753959, PubMed:15558731).
CC Expressed in placenta, brain, skeletal muscles, pancreas and liver
CC (PubMed:10753959). {ECO:0000269|PubMed:10753959,
CC ECO:0000269|PubMed:15234345, ECO:0000269|PubMed:15558731,
CC ECO:0000269|PubMed:20237282, ECO:0000269|PubMed:22398208,
CC ECO:0000269|PubMed:23893895, ECO:0000269|PubMed:26404741,
CC ECO:0000269|PubMed:27466317}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the developing sciatic nerve, with
CC increasing expression from newborn to postnatal day 20, and decreasing
CC expression at postnatal day 60 (P60) (at protein level)
CC (PubMed:20237282). Expressed in the developing neural tube, optic
CC vesicle, branchial arches and kidney at 10.5 dpc (PubMed:17920587).
CC Expressed in the ventricular layers of the developing neural tube along
CC the entire cranial-caudal length, including the anterior forebrain and
CC the posterior spinal cord at 11.5 dpc (PubMed:17920587). Highly
CC expressed in cortical progenitor cells at 12 dpc, expression decreases
CC during neurogenesis but weak expression is still present at birth
CC (PubMed:20399730). Expressed in the developing brain at 15.5 dpc in the
CC upper rhombic lip, ventricular zone, and external granule layer (EGL)
CC (at protein level) (PubMed:26657772). At birth expressed in the
CC ventricular apical lining cells, proliferating external granule layer
CC and Purkinje cell layer (PCL), with expression remaining abundant in
CC the EGL and weakly evident in the PCL at P6 (at protein level)
CC (PubMed:26657772). Expressed at P8 in the EGL, cerebellar granule
CC neuron precursors, Bergmann glia, Pcna-positive progenitor cells in the
CC white matter, and weakly in Pax6-positive postmitotic granule neurons
CC (at protein level) (PubMed:26657772). Expressed weakly throughout the
CC retina between 12.5 dpc and 14.5 dpc, becoming enriched in progenitors
CC at the outer neuroblastic layer at 14.5 dpc (PubMed:22398208).
CC Expressed in the retinal layer of the optic vesicle, and weakly
CC expressed in the retinal pigment epithelium at 12.5 dpc
CC (PubMed:17920587). Localized to the apical edge of the retina between
CC 12.5 and 16.5 dpc (PubMed:22398208). Expressed in the internal
CC endodermal layer and in the developing saccules of the lung at 11.5 dpc
CC (PubMed:17920587). Expressed at the outer limiting membrane of the
CC retina at 18.5 dpc and 3 months of age (PubMed:23001562).
CC {ECO:0000269|PubMed:17920587, ECO:0000269|PubMed:20237282,
CC ECO:0000269|PubMed:20399730, ECO:0000269|PubMed:22398208,
CC ECO:0000269|PubMed:23001562, ECO:0000269|PubMed:26657772}.
CC -!- DOMAIN: The L27 domain 1 functions in targeting to the tight junctions
CC by binding to and stabilizing PATJ. {ECO:0000269|PubMed:11927608,
CC ECO:0000269|PubMed:17182851}.
CC -!- DOMAIN: The PDZ domain binds to the C-terminus of SC6A1.
CC {ECO:0000269|PubMed:15234345}.
CC -!- DISRUPTION PHENOTYPE: Conditional knockout in the retina results in
CC mice which are viable, fertile, and morphologically normal apart from
CC microphthalmia with severe defects in visual response
CC (PubMed:22398208). From 13.5 days post-conception (dpc) retinas show
CC variable morphology, including retinal folding, variable thickness and
CC disorganization (PubMed:22398208). Postnatally the retinal lamina is
CC thinner, and disorganized, with a shortening or absence of the inner
CC and outer segments of photoreceptor cells (PubMed:22398208). By
CC postnatal day 60 retinas are completely or partially devoid of the
CC outer nuclear layers and photoreceptor layer, and feature a reduced
CC number of photoreceptor cells, disrupted cell polarity and impaired
CC distribution of retinal neurons (PubMed:22398208). Retinal distribution
CC of Par3 and the Crb polarity complex proteins Crbs and Patj is
CC disrupted (PubMed:22398208). Mature mice show aberrant proliferation
CC and apoptosis of retinal epithelia with significantly reduced or
CC undetectable a- and b-waves in electroretinogram-measured dark-adapted
CC response (PubMed:22398208). Conditional knockout in cerebellum
CC proliferating progenitors at 13.5 dpc results in mislocalization of
CC apical polarity complex proteins such as Crb proteins, Pard3, and Prkci
CC at 15.5 dpc (PubMed:26657772). Following cerebellum conditional
CC knockout there is an increase in migration and premature
CC differentiation of Pax2-positive ventricular zone cells at 17.5 dpc,
CC resulting in a reduced number of glial cell progenitors
CC (PubMed:26657772). Conditional knockout in cerebellum results in
CC stunted cerebellum growth and indistinct vermis foliation at birth,
CC there is also an evident reduction of Bergmann glia, oligodendrocyte,
CC astrocyte and GABAergic interneuron progenitors (PubMed:26657772).
CC Conditional knockout in cerebellum shows compromised Purkinje cell
CC migration and formation failure of Purkinje cell plate to contain both
CC Bergmann glia and Purkinje cells, possibly as a result of abnormal
CC Reln-Dab1 signaling at P6 (PubMed:26657772). Conditional knockout in
CC cerebellum results in poorly layered, smaller lobes, severe defects in
CC fissure formation and a reduced number of cerebellar granule neurons
CC and GABAergic interneurons from P8 to P21 (PubMed:26657772).
CC Conditional knockout in the cortex results in mice surviving to
CC adulthood, with lower body weight but exhibit irregular movements with
CC disrupted stride and gait, reduced exploratory initiative, reduced
CC locomotor behavior and swim in circles (PubMed:20399730). Reduced
CC cortical size and disrupted morphology at 12 and 14 dpc resulting in
CC the absence of the cortex postnatally lacking virtually all cortical
CC neurons, additionally extreme thinning of the lateral cortex is
CC observed (PubMed:20399730). Reduced proliferation of cortical
CC progenitor cells and increased cell death of postmitotic neurons in the
CC developing medial cortex and ventral zone from 10.5 dpc, additionally
CC mislocalization and reduced abundance of Crb2 and Prkci is evident
CC (PubMed:20399730). RNAi-mediated knockdown in the sciatic nerve results
CC in mislocalization of Exoc4/Sec8 and Stx4 in Schwann cells and thinning
CC and shortening of Schwann cells as a result of a reduction in the
CC myelinated fiber diameter caused by fewer myelin turns
CC (PubMed:20237282). Conditional knockout of both Mpp3 and Pals1 in the
CC retina results in an increase in retinal degeneration that becomes
CC evident at one month of age (PubMed:23893895).
CC {ECO:0000269|PubMed:20237282, ECO:0000269|PubMed:20399730,
CC ECO:0000269|PubMed:22398208, ECO:0000269|PubMed:23893895,
CC ECO:0000269|PubMed:26657772}.
CC -!- SIMILARITY: Belongs to the MAGUK family. {ECO:0000305}.
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DR EMBL; AF199008; AAF63789.1; -; mRNA.
DR CCDS; CCDS26001.1; -.
DR RefSeq; NP_062525.1; NM_019579.3.
DR RefSeq; XP_006516160.1; XM_006516097.3.
DR PDB; 1VA8; NMR; -; A=236-335.
DR PDB; 1VF6; X-ray; 2.10 A; C/D=123-180.
DR PDBsum; 1VA8; -.
DR PDBsum; 1VF6; -.
DR AlphaFoldDB; Q9JLB2; -.
DR BMRB; Q9JLB2; -.
DR SMR; Q9JLB2; -.
DR BioGRID; 207851; 10.
DR CORUM; Q9JLB2; -.
DR IntAct; Q9JLB2; 3.
DR MINT; Q9JLB2; -.
DR STRING; 10090.ENSMUSP00000080683; -.
DR iPTMnet; Q9JLB2; -.
DR PhosphoSitePlus; Q9JLB2; -.
DR jPOST; Q9JLB2; -.
DR MaxQB; Q9JLB2; -.
DR PaxDb; Q9JLB2; -.
DR PRIDE; Q9JLB2; -.
DR ProteomicsDB; 295587; -.
DR Antibodypedia; 20; 355 antibodies from 38 providers.
DR DNASU; 56217; -.
DR Ensembl; ENSMUST00000082024; ENSMUSP00000080683; ENSMUSG00000021112.
DR GeneID; 56217; -.
DR KEGG; mmu:56217; -.
DR UCSC; uc007nzg.2; mouse.
DR CTD; 64398; -.
DR MGI; MGI:1927339; Pals1.
DR VEuPathDB; HostDB:ENSMUSG00000021112; -.
DR eggNOG; KOG0609; Eukaryota.
DR GeneTree; ENSGT00940000156087; -.
DR HOGENOM; CLU_001715_5_4_1; -.
DR InParanoid; Q9JLB2; -.
DR OMA; LKHIQHV; -.
DR OrthoDB; 531106at2759; -.
DR PhylomeDB; Q9JLB2; -.
DR TreeFam; TF314263; -.
DR BioGRID-ORCS; 56217; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Mpp5; mouse.
DR EvolutionaryTrace; Q9JLB2; -.
DR PRO; PR:Q9JLB2; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q9JLB2; protein.
DR Bgee; ENSMUSG00000021112; Expressed in dorsal pancreas and 252 other tissues.
DR ExpressionAtlas; Q9JLB2; baseline and differential.
DR Genevisible; Q9JLB2; MM.
DR GO; GO:0005912; C:adherens junction; IDA:UniProtKB.
DR GO; GO:0045177; C:apical part of cell; IDA:MGI.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0005923; C:bicellular tight junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005911; C:cell-cell junction; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; ISS:MGI.
DR GO; GO:0043219; C:lateral loop; IDA:BHF-UCL.
DR GO; GO:0035749; C:myelin sheath adaxonal region; IDA:BHF-UCL.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0043220; C:Schmidt-Lanterman incisure; IDA:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004385; F:guanylate kinase activity; ISS:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0021954; P:central nervous system neuron development; IMP:UniProtKB.
DR GO; GO:0021987; P:cerebral cortex development; IMP:UniProtKB.
DR GO; GO:0045197; P:establishment or maintenance of epithelial cell apical/basal polarity; IBA:GO_Central.
DR GO; GO:0016332; P:establishment or maintenance of polarity of embryonic epithelium; IBA:GO_Central.
DR GO; GO:0010467; P:gene expression; IMP:MGI.
DR GO; GO:0048699; P:generation of neurons; IBA:GO_Central.
DR GO; GO:0002011; P:morphogenesis of an epithelial sheet; ISO:MGI.
DR GO; GO:0032288; P:myelin assembly; ISO:MGI.
DR GO; GO:0032287; P:peripheral nervous system myelin maintenance; IMP:BHF-UCL.
DR GO; GO:0007009; P:plasma membrane organization; IMP:MGI.
DR GO; GO:0008104; P:protein localization; IMP:MGI.
DR GO; GO:0035750; P:protein localization to myelin sheath abaxonal region; IMP:BHF-UCL.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISO:MGI.
DR GO; GO:0017015; P:regulation of transforming growth factor beta receptor signaling pathway; IMP:UniProtKB.
DR CDD; cd12036; SH3_MPP5; 1.
DR Gene3D; 2.30.42.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR008145; GK/Ca_channel_bsu.
DR InterPro; IPR008144; Guanylate_kin-like_dom.
DR InterPro; IPR020590; Guanylate_kinase_CS.
DR InterPro; IPR014775; L27_C.
DR InterPro; IPR004172; L27_dom.
DR InterPro; IPR036892; L27_dom_sf.
DR InterPro; IPR015145; L27_N.
DR InterPro; IPR035601; MPP5_SH3.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF00625; Guanylate_kin; 1.
DR Pfam; PF02828; L27; 1.
DR Pfam; PF09060; L27_N; 1.
DR Pfam; PF00595; PDZ; 1.
DR Pfam; PF07653; SH3_2; 1.
DR SMART; SM00072; GuKc; 1.
DR SMART; SM00569; L27; 2.
DR SMART; SM00228; PDZ; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF101288; SSF101288; 2.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00856; GUANYLATE_KINASE_1; 1.
DR PROSITE; PS50052; GUANYLATE_KINASE_2; 1.
DR PROSITE; PS51022; L27; 2.
DR PROSITE; PS50106; PDZ; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell junction; Cell membrane; Cell projection;
KW Golgi apparatus; Membrane; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Repeat; SH3 domain; Tight junction.
FT CHAIN 1..675
FT /note="Protein PALS1"
FT /id="PRO_0000094581"
FT DOMAIN 120..177
FT /note="L27 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00365"
FT DOMAIN 179..235
FT /note="L27 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00365"
FT DOMAIN 256..336
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 345..417
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 479..660
FT /note="Guanylate kinase-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00100"
FT REGION 1..345
FT /note="Required for the correct localization of PALS1 and
FT PATJ at cell-cell contacts and the normal formation of
FT tight junctions and adherens junctions"
FT /evidence="ECO:0000269|PubMed:17182851"
FT REGION 21..140
FT /note="Interaction with PARD6B"
FT /evidence="ECO:0000269|PubMed:15140881"
FT REGION 51..79
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 181..243
FT /note="Interaction with LIN7C"
FT /evidence="ECO:0000269|PubMed:10753959"
FT COMPBIAS 57..79
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 486..493
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00100"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N3R9"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 83
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N3R9"
FT MOD_RES 84
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N3R9"
FT MUTAGEN 32
FT /note="H->A: No effect on interaction with PARD6B."
FT /evidence="ECO:0000269|PubMed:15140881"
FT MUTAGEN 33
FT /note="R->A: No effect on interaction with PARD6B."
FT /evidence="ECO:0000269|PubMed:15140881"
FT MUTAGEN 34
FT /note="E->A: No effect on interaction with PARD6B."
FT /evidence="ECO:0000269|PubMed:15140881"
FT MUTAGEN 36
FT /note="A->G: No effect on interaction with PARD6B."
FT /evidence="ECO:0000269|PubMed:15140881"
FT MUTAGEN 37
FT /note="V->G: Prevents interaction with PARD6B. Does not
FT affect localization to the tight junctions."
FT /evidence="ECO:0000269|PubMed:15140881"
FT MUTAGEN 37
FT /note="V->I: No effect on interaction with PARD6B."
FT /evidence="ECO:0000269|PubMed:15140881"
FT MUTAGEN 38
FT /note="D->A: Prevents interaction with PARD6B."
FT /evidence="ECO:0000269|PubMed:15140881"
FT MUTAGEN 38
FT /note="D->E: No effect on interaction with PARD6B."
FT /evidence="ECO:0000269|PubMed:15140881"
FT MUTAGEN 39
FT /note="C->A: No effect on interaction with PARD6B."
FT /evidence="ECO:0000269|PubMed:15140881"
FT MUTAGEN 40
FT /note="P->A: No effect on interaction with PARD6B."
FT /evidence="ECO:0000269|PubMed:15140881"
FT MUTAGEN 150
FT /note="L->G: No effect on PARD6B interaction. Prevents
FT interaction with PATJ; when associated with G-154."
FT /evidence="ECO:0000269|PubMed:11927608"
FT MUTAGEN 154
FT /note="V->G: No effect on PARD6B interaction. Prevents
FT interaction with PATJ; when associated with G-150."
FT /evidence="ECO:0000269|PubMed:11927608"
FT MUTAGEN 207
FT /note="E->Q: No effect on interaction with LIN7C."
FT /evidence="ECO:0000269|PubMed:10753959"
FT MUTAGEN 208
FT /note="L->G: Prevents interaction with LIN7C."
FT /evidence="ECO:0000269|PubMed:10753959"
FT MUTAGEN 212
FT /note="L->G: Prevents interaction with LIN7C."
FT /evidence="ECO:0000269|PubMed:10753959"
FT MUTAGEN 216
FT /note="H->N: No effect on interaction with LIN7C."
FT /evidence="ECO:0000269|PubMed:10753959"
FT MUTAGEN 221
FT /note="L->G: Partially prevents interaction with LIN7C."
FT /evidence="ECO:0000269|PubMed:10753959"
FT MUTAGEN 224
FT /note="H->N: Partially prevents interaction with LIN7C."
FT /evidence="ECO:0000269|PubMed:10753959"
FT MUTAGEN 225
FT /note="D->N: Prevents interaction with LIN7C."
FT /evidence="ECO:0000269|PubMed:10753959"
FT MUTAGEN 227
FT /note="V->G: Prevents interaction with LIN7C."
FT /evidence="ECO:0000269|PubMed:10753959"
FT MUTAGEN 379
FT /note="L->P: Failure to restore localization of PALS1 and
FT PATJ to cell-cell contacts and to restore tight junction
FT and adherens junction formation in cells where PALS1 has
FT been knocked down."
FT /evidence="ECO:0000269|PubMed:17182851"
FT HELIX 123..135
FT /evidence="ECO:0007829|PDB:1VF6"
FT HELIX 141..155
FT /evidence="ECO:0007829|PDB:1VF6"
FT HELIX 157..169
FT /evidence="ECO:0007829|PDB:1VF6"
FT STRAND 247..249
FT /evidence="ECO:0007829|PDB:1VA8"
FT STRAND 255..261
FT /evidence="ECO:0007829|PDB:1VA8"
FT STRAND 269..273
FT /evidence="ECO:0007829|PDB:1VA8"
FT STRAND 275..283
FT /evidence="ECO:0007829|PDB:1VA8"
FT HELIX 288..292
FT /evidence="ECO:0007829|PDB:1VA8"
FT STRAND 300..304
FT /evidence="ECO:0007829|PDB:1VA8"
FT HELIX 314..323
FT /evidence="ECO:0007829|PDB:1VA8"
FT STRAND 326..333
FT /evidence="ECO:0007829|PDB:1VA8"
SQ SEQUENCE 675 AA; 77229 MW; 66670F919F18063B CRC64;
MTTSYMNGHV TEESDSGIKN LDLASPEEYP KHREMAVDCP GDLGTRMMPV RRSAQLERIR
QQQEDMRRRR EEEGKKQELD LNSSMRLKKL AQIPPKTGID NPIFDTEEGI VLESPHYAVN
ILDVEDLFSS LKHIQHTLVD SQSQEDISLL LQLVQNRDFQ NAFKIHNAVT VHMSKASPPF
PLIANVQDLV QEVQTVLKPV HQKEGQELTA LLNAPHIQAL LLAHDKVAEQ EMQLEPITDE
RVYESIGHYG GETVKIVRIE KARDIPLGAT VRNEMDSVII SRIVKGGAAE KSGLLHEGDE
VLEINGIEIR GKDVNEVFDL LSDMHGTLTF VLIPSQQIKP PPAKETVIHV KAHFDYDPSD
DPYVPCRELG LSFQKGDILH VISQEDPNWW QAYREGDEDN QPLAGLVPGK SFQQQREAMK
QTIEEDKEPE KSGKLWCAKK NKKKRKKVLY NANKNDDYDN EEILTYEEMS LYHQPANRKR
PIILIGPQNC GQNELRQRLM NKEKDRFASA VPHTTRNRRD HEVAGRDYHF VSRQAFEADI
AAGKFIEHGE FEKNLYGTSI DSVRQVINSG KICLLSLRTQ SLKTLRNSDL KPYIIFIAPP
SQERLRALLA KEGKNPKPEE LREIIEKTRE MEQNNGHYFD TAIVNSDLDK AYQELLRLIN
KLDTEPQWVP STWLR
