SCRIB_HUMAN
ID SCRIB_HUMAN Reviewed; 1630 AA.
AC Q14160; Q6P496; Q7Z5D1; Q8WWV8; Q96C69; Q96GG1;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 5.
DT 03-AUG-2022, entry version 217.
DE RecName: Full=Protein scribble homolog;
DE Short=Scribble;
DE Short=hScrib;
DE AltName: Full=Protein LAP4;
GN Name=SCRIB; Synonyms=CRIB1, KIAA0147, LAP4, SCRB1, VARTUL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH LPP, SUBCELLULAR
RP LOCATION, MUTAGENESIS OF 738-LEU--GLY-739; 872-LEU--GLY-873;
RP 1014-LEU--GLY-1015 AND 1111-LEU--GLY-1112, AND VARIANT LEU-422.
RX PubMed=15649318; DOI=10.1186/1471-2121-6-1;
RA Petit M.M.R., Meulemans S.M.P., Alen P., Ayoubi T.A.Y., Jansen E.,
RA Van de Ven W.J.M.;
RT "The tumor suppressor Scrib interacts with the zyxin-related protein LPP,
RT which shuttles between cell adhesion sites and the nucleus.";
RL BMC Cell Biol. 6:1-1(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LEU-422, SUBCELLULAR
RP LOCATION, MUTAGENESIS OF PRO-305, AND TISSUE SPECIFICITY.
RX PubMed=15806148; DOI=10.1038/sj.onc.1208632;
RA Navarro C., Nola S., Audebert S., Santoni M.-J., Arsanto J.-P.,
RA Ginestier C., Marchetto S., Jacquemier J., Isnardon D., Le Bivic A.,
RA Birnbaum D., Borg J.-P.;
RT "Junctional recruitment of mammalian Scribble relies on E-cadherin
RT engagement.";
RL Oncogene 24:4330-4339(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT LEU-422.
RA Petit M.M.R., Alen P., Meulemans S.M.P., Van de Wouwer E., Ayoubi T.A.Y.,
RA Van de Ven W.J.M., Jansen E.;
RT "The human Scrib N1 variant encoded by the SCRIB gene contains 13 leucine-
RT rich repeats and 4 PDZ domains.";
RL Submitted (JUL-2008) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LEU-422.
RC TISSUE=Bone marrow, and Brain;
RX PubMed=8590280; DOI=10.1093/dnares/2.4.167;
RA Nagase T., Seki N., Tanaka A., Ishikawa K., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. IV. The
RT coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 2:167-174(1995).
RN [5]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [6]
RP SEQUENCE REVISION.
RA Ohara O., Nagase T., Kikuno R., Nomura N.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 799-1630 (ISOFORM 1), AND
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1206-1630 (ISOFORM 3).
RC TISSUE=Lung carcinoma, and Neuroblastoma;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP INTERACTION WITH UBE3A AND HPV E6, UBIQUITINATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=11027293; DOI=10.1128/mcb.20.21.8244-8253.2000;
RA Nakagawa S., Huibregtse J.M.;
RT "Human scribble (Vartul) is targeted for ubiquitin-mediated degradation by
RT the high-risk papillomavirus E6 proteins and the E6AP ubiquitin-protein
RT ligase.";
RL Mol. Cell. Biol. 20:8244-8253(2000).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1220, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=15144186; DOI=10.1021/ac035352d;
RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA Peters E.C.;
RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from
RT human T cells using immobilized metal affinity chromatography and tandem
RT mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [11]
RP FUNCTION, INTERACTION WITH ARHGEF7 AND GIT1, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF PRO-305.
RX PubMed=15182672; DOI=10.1016/j.cub.2004.05.051;
RA Audebert S., Navarro C., Nourry C., Chasserot-Golaz S., Lecine P.,
RA Bellaiche Y., Dupont J.-L., Premont R.T., Sempere C., Strub J.-M.,
RA Van Dorsselaer A., Vitale N., Borg J.-P.;
RT "Mammalian Scribble forms a tight complex with the betaPIX exchange
RT factor.";
RL Curr. Biol. 14:987-995(2004).
RN [12]
RP FUNCTION, AND INTERACTION WITH TSHR.
RX PubMed=15775968; DOI=10.1038/sj.emboj.7600616;
RA Lahuna O., Quellari M., Achard C., Nola S., Meduri G., Navarro C.,
RA Vitale N., Borg J.-P., Misrahi M.;
RT "Thyrotropin receptor trafficking relies on the hScrib-betaPIX-GIT1-ARF6
RT pathway.";
RL EMBO J. 24:1364-1374(2005).
RN [13]
RP INTERACTION WITH TJP2.
RX PubMed=15975580; DOI=10.1016/j.febslet.2005.05.062;
RA Metais J.-Y., Navarro C., Santoni M.-J., Audebert S., Borg J.-P.;
RT "hScrib interacts with ZO-2 at the cell-cell junctions of epithelial
RT cells.";
RL FEBS Lett. 579:3725-3730(2005).
RN [14]
RP INTERACTION WITH TRIP6.
RX PubMed=16137684; DOI=10.1016/j.febslet.2005.08.012;
RA Petit M.M.R., Crombez K.R.M.O., Vervenne H.B.V.K., Weyns N.,
RA Van de Ven W.J.M.;
RT "The tumor suppressor Scrib selectively interacts with specific members of
RT the zyxin family of proteins.";
RL FEBS Lett. 579:5061-5068(2005).
RN [15]
RP FUNCTION IN CELL ADHESION.
RX PubMed=16344308; DOI=10.1083/jcb.200506094;
RA Qin Y., Capaldo C., Gumbiner B.M., Macara I.G.;
RT "The mammalian Scribble polarity protein regulates epithelial cell adhesion
RT and migration through E-cadherin.";
RL J. Cell Biol. 171:1061-1071(2005).
RN [16]
RP FUNCTION IN CELL PROLIFERATION, AND SUBCELLULAR LOCATION.
RX PubMed=16965391; DOI=10.1111/j.1349-7006.2006.00315.x;
RA Nagasaka K., Nakagawa S., Yano T., Takizawa S., Matsumoto Y., Tsuruga T.,
RA Nakagawa K., Minaguchi T., Oda K., Hiraike-Wada O., Ooishi H., Yasugi T.,
RA Taketani Y.;
RT "Human homolog of Drosophila tumor suppressor Scribble negatively regulates
RT cell-cycle progression from G1 to S phase by localizing at the basolateral
RT membrane in epithelial cells.";
RL Cancer Sci. 97:1217-1225(2006).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-853; SER-1306; SER-1309 AND
RP SER-1378, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [18]
RP INTERACTION WITH APC, AND SUBCELLULAR LOCATION.
RX PubMed=16611247; DOI=10.1111/j.1365-2443.2006.00954.x;
RA Takizawa S., Nagasaka K., Nakagawa S., Yano T., Nakagawa K., Yasugi T.,
RA Takeuchi T., Kanda T., Huibregtse J.M., Akiyama T., Taketani Y.;
RT "Human scribble, a novel tumor suppressor identified as a target of high-
RT risk HPV E6 for ubiquitin-mediated degradation, interacts with adenomatous
RT polyposis coli.";
RL Genes Cells 11:453-464(2006).
RN [19]
RP FUNCTION IN APOPTOSIS, SUBCELLULAR LOCATION, AND MUTAGENESIS OF PRO-305.
RX PubMed=19041750; DOI=10.1016/j.cell.2008.09.045;
RA Zhan L., Rosenberg A., Bergami K.C., Yu M., Xuan Z., Jaffe A.B., Allred C.,
RA Muthuswamy S.K.;
RT "Deregulation of scribble promotes mammary tumorigenesis and reveals a role
RT for cell polarity in carcinoma.";
RL Cell 135:865-878(2008).
RN [20]
RP FUNCTION IN CELL MIGRATION, AND INTERACTION WITH PAK1 AND PAK2.
RX PubMed=18716323; DOI=10.1093/hmg/ddn248;
RA Nola S., Sebbagh M., Marchetto S., Osmani N., Nourry C., Audebert S.,
RA Navarro C., Rachel R., Montcouquiol M., Sans N., Etienne-Manneville S.,
RA Borg J.-P., Santoni M.-J.;
RT "Scrib regulates PAK activity during the cell migration process.";
RL Hum. Mol. Genet. 17:3552-3565(2008).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1475 AND SER-1566, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [22]
RP FUNCTION.
RX PubMed=18641685; DOI=10.1038/onc.2008.219;
RA Dow L.E., Elsum I.A., King C.L., Kinross K.M., Richardson H.E.,
RA Humbert P.O.;
RT "Loss of human Scribble cooperates with H-Ras to promote cell invasion
RT through deregulation of MAPK signalling.";
RL Oncogene 27:5988-6001(2008).
RN [23]
RP INTERACTION WITH TICK-BORNE ENCEPHALITIS VIRUS RNA-DIRECTED RNA POLYMERASE
RP NS5.
RX PubMed=18042258; DOI=10.1111/j.1462-5822.2007.01076.x;
RA Werme K., Wigerius M., Johansson M.;
RT "Tick-borne encephalitis virus NS5 associates with membrane protein
RT scribble and impairs interferon-stimulated JAK-STAT signalling.";
RL Cell. Microbiol. 10:696-712(2008).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-826; SER-939; SER-1223;
RP SER-1232; SER-1306; SER-1309; THR-1342; SER-1348; SER-1437; SER-1547 AND
RP SER-1566, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [26]
RP INTERACTION WITH MCC.
RX PubMed=19555689; DOI=10.1016/j.febslet.2009.06.034;
RA Arnaud C., Sebbagh M., Nola S., Audebert S., Bidaut G., Hermant A.,
RA Gayet O., Dusetti N.J., Ollendorff V., Santoni M.J., Borg J.P., Lecine P.;
RT "MCC, a new interacting protein for Scrib, is required for cell migration
RT in epithelial cells.";
RL FEBS Lett. 583:2326-2332(2009).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1348 AND SER-1448, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-826; SER-1220; THR-1342;
RP SER-1348; SER-1475; SER-1547 AND SER-1566, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-826; SER-835; SER-853;
RP SER-939; SER-1140; SER-1220; SER-1232; THR-1342; SER-1348; SER-1378;
RP SER-1448; SER-1475; SER-1486 AND SER-1566, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [30]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [31]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-688; THR-689; SER-1220;
RP SER-1309 AND SER-1378, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [32]
RP INTERACTION WITH MCC, AND SUBCELLULAR LOCATION.
RX PubMed=22480440; DOI=10.1016/j.bbamcr.2012.03.011;
RA Pangon L., Van Kralingen C., Abas M., Daly R.J., Musgrove E.A.,
RA Kohonen-Corish M.R.;
RT "The PDZ-binding motif of MCC is phosphorylated at position -1 and controls
RT lamellipodia formation in colon epithelial cells.";
RL Biochim. Biophys. Acta 1823:1058-1067(2012).
RN [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37; THR-378; THR-475;
RP SER-504; SER-708; SER-853; SER-875; SER-1140; SER-1220; SER-1223; SER-1226;
RP SER-1232; SER-1276; SER-1279; SER-1306; SER-1309; SER-1348; SER-1378;
RP SER-1448; SER-1475; SER-1486; SER-1508; SER-1541; SER-1561 AND SER-1566,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [34]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-504; SER-764; SER-853;
RP SER-1140; SER-1220; SER-1295; SER-1298; SER-1306; SER-1309; SER-1378;
RP SER-1445; SER-1448; SER-1486; SER-1508; THR-1545 AND SER-1566, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [35]
RP FUNCTION, SUBCELLULAR LOCATION, PALMITOYLATION, AND MUTAGENESIS OF CYS-4;
RP CYS-10; CYS-22 AND PRO-305.
RX PubMed=27380321; DOI=10.1038/nchembio.2119;
RA Chen B., Zheng B., DeRan M., Jarugumilli G.K., Fu J., Brooks Y.S., Wu X.;
RT "ZDHHC7-mediated S-palmitoylation of Scribble regulates cell polarity.";
RL Nat. Chem. Biol. 12:686-693(2016).
RN [36]
RP INTERACTION WITH DLG5; STK4 AND LATS1, AND SUBCELLULAR LOCATION.
RX PubMed=28169360; DOI=10.1038/srep42125;
RA Liu J., Li J., Li P., Wang Y., Liang Z., Jiang Y., Li J., Feng C., Wang R.,
RA Chen H., Zhou C., Zhang J., Yang J., Liu P.;
RT "Loss of DLG5 promotes breast cancer malignancy by inhibiting the Hippo
RT signaling pathway.";
RL Sci. Rep. 7:42125-42125(2017).
RN [37]
RP STRUCTURE BY NMR OF 718-814; 860-951 AND 1096-1193.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the first, second and fourth PDZ domain of human
RT scribble (KIAA0147 protein).";
RL Submitted (NOV-2005) to the PDB data bank.
RN [38]
RP VARIANTS NTD SER-454 AND GLN-1535, AND CHARACTERIZATION OF VARIANTS NTD
RP SER-454 AND GLN-1535.
RX PubMed=22095531; DOI=10.1002/humu.21662;
RA Robinson A., Escuin S., Doudney K., Vekemans M., Stevenson R.E.,
RA Greene N.D., Copp A.J., Stanier P.;
RT "Mutations in the planar cell polarity genes CELSR1 and SCRIB are
RT associated with the severe neural tube defect craniorachischisis.";
RL Hum. Mutat. 33:440-447(2012).
CC -!- FUNCTION: Scaffold protein involved in different aspects of polarized
CC cell differentiation regulating epithelial and neuronal morphogenesis
CC and T-cell polarization (PubMed:15182672, PubMed:16344308,
CC PubMed:19041750, PubMed:18716323, PubMed:18641685, PubMed:16965391,
CC PubMed:27380321). Via its interaction with CRTAM, required for the late
CC phase polarization of a subset of CD4+ T-cells, which in turn regulates
CC TCR-mediated proliferation and IFNG and IL22 production (By
CC similarity). Most probably functions in the establishment of apico-
CC basal cell polarity (PubMed:16344308, PubMed:19041750). May function in
CC cell proliferation regulating progression from G1 to S phase and as a
CC positive regulator of apoptosis for instance during acinar
CC morphogenesis of the mammary epithelium (PubMed:16965391,
CC PubMed:19041750). May also function in cell migration and adhesion and
CC hence regulate cell invasion through MAPK signaling (PubMed:18716323,
CC PubMed:18641685). May play a role in exocytosis and in the targeting of
CC synaptic vesicles to synapses (PubMed:15182672). Functions as an
CC activator of Rac GTPase activity. {ECO:0000250|UniProtKB:Q80U72,
CC ECO:0000269|PubMed:15182672, ECO:0000269|PubMed:16344308,
CC ECO:0000269|PubMed:16965391, ECO:0000269|PubMed:18641685,
CC ECO:0000269|PubMed:18716323, ECO:0000269|PubMed:19041750,
CC ECO:0000269|PubMed:27380321}.
CC -!- SUBUNIT: Interacts with UBE3A (PubMed:11027293). Interacts with PAK1
CC and PAK2 (PubMed:18716323). Interacts (via PDZ domains) with VANGL2 (By
CC similarity). Interacts (via PDZ domains) with LPP and TRIP6; the
CC interaction is direct (PubMed:15649318, PubMed:16137684). Interacts
CC (via PDZ domains) with TJP2 (PubMed:15975580). Interacts (via PDZ
CC domains) with APC; may mediate APC targeting to adherens junctions of
CC epithelial cells (PubMed:16611247). Interacts (via PDZ domains) with
CC TSHR; regulates TSHR trafficking and function (PubMed:15775968).
CC Interacts with ARHGEF7 and GIT1; interacts directly with ARHGEF7
CC (PubMed:15182672). Interacts with CTNNB1 (By similarity). Interacts
CC with MAPK12 (By similarity). Interacts (via PDZ domains 1 and 3) with
CC MCC (PubMed:19555689, PubMed:22480440). Interacts with DLG5
CC (PubMed:28169360). Interacts with STK4/MST1 and LATS1 in the presence
CC of DLG5 (PubMed:28169360). Interacts (via PDZ domain 3) with CRTAM (via
CC PDZ-binding motif); the interaction promotes CRTAM and SCRIB
CC polarization in a subset of CD4+ T-cells (By similarity).
CC {ECO:0000250|UniProtKB:Q80U72, ECO:0000269|PubMed:11027293,
CC ECO:0000269|PubMed:15182672, ECO:0000269|PubMed:15649318,
CC ECO:0000269|PubMed:15775968, ECO:0000269|PubMed:15975580,
CC ECO:0000269|PubMed:16137684, ECO:0000269|PubMed:16611247,
CC ECO:0000269|PubMed:18716323, ECO:0000269|PubMed:19555689,
CC ECO:0000269|PubMed:22480440, ECO:0000269|PubMed:28169360}.
CC -!- SUBUNIT: (Microbial infection) Interacts (via fourth PDZ domain) with
CC tick-borne encephalitis virus RNA-directed RNA polymerase NS5; this
CC interaction targets viral NS5 to the cell membrane periphery and
CC nucleus and prevents STAT1 phosphorylation, and thus, the activation of
CC the JAK-STAT signaling pathway (PubMed:18042258). Interacts with HPV E6
CC (PubMed:11027293). {ECO:0000269|PubMed:11027293,
CC ECO:0000269|PubMed:18042258}.
CC -!- INTERACTION:
CC Q14160; Q9P0K1: ADAM22; NbExp=3; IntAct=EBI-357345, EBI-1567236;
CC Q14160; P25100: ADRA1D; NbExp=19; IntAct=EBI-357345, EBI-489993;
CC Q14160; P25054: APC; NbExp=5; IntAct=EBI-357345, EBI-727707;
CC Q14160; Q5VV41: ARHGEF16; NbExp=2; IntAct=EBI-357345, EBI-1057448;
CC Q14160; Q14155: ARHGEF7; NbExp=11; IntAct=EBI-357345, EBI-717515;
CC Q14160; P20020: ATP2B1; NbExp=2; IntAct=EBI-357345, EBI-5279998;
CC Q14160; Q01814: ATP2B2; NbExp=2; IntAct=EBI-357345, EBI-1174243;
CC Q14160; P34998: CRHR1; NbExp=3; IntAct=EBI-357345, EBI-3870393;
CC Q14160; Q9UQB3: CTNND2; NbExp=2; IntAct=EBI-357345, EBI-7266482;
CC Q14160; Q9NS75: CYSLTR2; NbExp=3; IntAct=EBI-357345, EBI-3843579;
CC Q14160; O00429: DNM1L; NbExp=2; IntAct=EBI-357345, EBI-724571;
CC Q14160; P0C2L3: FAM163B; NbExp=3; IntAct=EBI-357345, EBI-11793223;
CC Q14160; Q7L8L6: FASTKD5; NbExp=2; IntAct=EBI-357345, EBI-747570;
CC Q14160; Q14CM0: FRMPD4; NbExp=2; IntAct=EBI-357345, EBI-311279;
CC Q14160; P33402: GUCY1A2; NbExp=6; IntAct=EBI-357345, EBI-6911715;
CC Q14160; P22460: KCNA5; NbExp=2; IntAct=EBI-357345, EBI-6426121;
CC Q14160; Q14500: KCNJ12; NbExp=2; IntAct=EBI-357345, EBI-11794596;
CC Q14160; P63252: KCNJ2; NbExp=2; IntAct=EBI-357345, EBI-703457;
CC Q14160; P48050: KCNJ4; NbExp=2; IntAct=EBI-357345, EBI-706117;
CC Q14160; P53778: MAPK12; NbExp=6; IntAct=EBI-357345, EBI-602406;
CC Q14160; P27361: MAPK3; NbExp=2; IntAct=EBI-357345, EBI-73995;
CC Q14160; P23508: MCC; NbExp=14; IntAct=EBI-357345, EBI-307531;
CC Q14160; Q7Z628: NET1; NbExp=2; IntAct=EBI-357345, EBI-2511306;
CC Q14160; Q96DL1: NXPE2; NbExp=2; IntAct=EBI-357345, EBI-11791121;
CC Q14160; O60346: PHLPP1; NbExp=2; IntAct=EBI-357345, EBI-2511516;
CC Q14160; Q99569: PKP4; NbExp=4; IntAct=EBI-357345, EBI-726447;
CC Q14160; Q15311: RALBP1; NbExp=2; IntAct=EBI-357345, EBI-749285;
CC Q14160; Q15418: RPS6KA1; NbExp=3; IntAct=EBI-357345, EBI-963034;
CC Q14160; Q15349: RPS6KA2; NbExp=9; IntAct=EBI-357345, EBI-1384149;
CC Q14160; A6NIM6: SLC15A5; NbExp=2; IntAct=EBI-357345, EBI-11792220;
CC Q14160; P48065: SLC6A12; NbExp=2; IntAct=EBI-357345, EBI-3843589;
CC Q14160; Q9C0D5: TANC1; NbExp=4; IntAct=EBI-357345, EBI-11023211;
CC Q14160; P16473: TSHR; NbExp=3; IntAct=EBI-357345, EBI-13939599;
CC Q14160; Q14D04: VEPH1; NbExp=2; IntAct=EBI-357345, EBI-1043669;
CC Q14160; A6NIX2: WTIP; NbExp=2; IntAct=EBI-357345, EBI-20730502;
CC Q14160; Q9GZV5: WWTR1; NbExp=3; IntAct=EBI-357345, EBI-747743;
CC Q14160; P46937: YAP1; NbExp=2; IntAct=EBI-357345, EBI-1044059;
CC Q14160; B7Z2Y1; NbExp=3; IntAct=EBI-357345, EBI-11791049;
CC Q14160; P03126: E6; Xeno; NbExp=8; IntAct=EBI-357345, EBI-1177242;
CC Q14160; P06427: E6; Xeno; NbExp=3; IntAct=EBI-357345, EBI-11737184;
CC Q14160; P06463: E6; Xeno; NbExp=4; IntAct=EBI-357345, EBI-1186926;
CC Q14160; P24835: E6; Xeno; NbExp=2; IntAct=EBI-357345, EBI-11793707;
CC Q14160; Q9QXA3: Fat1; Xeno; NbExp=5; IntAct=EBI-357345, EBI-6980218;
CC Q14160; P0C213: tax; Xeno; NbExp=2; IntAct=EBI-357345, EBI-11793850;
CC Q14160; P0C222: tax; Xeno; NbExp=2; IntAct=EBI-357345, EBI-11794384;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:28169360};
CC Peripheral membrane protein. Cell junction
CC {ECO:0000269|PubMed:27380321}. Cell junction, adherens junction. Cell
CC projection, lamellipodium. Cytoplasm. Postsynapse
CC {ECO:0000269|PubMed:15182672}. Presynapse
CC {ECO:0000269|PubMed:15182672}. Note=Targeting to cell-cell junctions
CC which is CDH1-dependent is required for the pro-apoptotic activity. In
CC a subset of CD4+ T-cells, colocalizes with CRTAM at the immunological
CC synapse during the late phase of T-cell activation (By similarity).
CC {ECO:0000250|UniProtKB:Q80U72}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q14160-1; Sequence=Displayed;
CC Name=2; Synonyms=Variant N1;
CC IsoId=Q14160-2; Sequence=VSP_010906;
CC Name=3;
CC IsoId=Q14160-3; Sequence=VSP_010908;
CC -!- TISSUE SPECIFICITY: Expressed in kidney, skeletal muscles, liver, lung,
CC breast, intestine, placenta and skin mainly in epithelial cells (at
CC protein level). {ECO:0000269|PubMed:15806148}.
CC -!- PTM: Ubiquitinated; targeted for UBE3A-dependent multiubiquitination in
CC the presence of high-risk HPV E6 proteins and degraded.
CC {ECO:0000269|PubMed:11027293}.
CC -!- PTM: Palmitoylated (PubMed:27380321). Could be depalmitoylated by
CC LYPLA1 and/or LYPLA2 (PubMed:27380321). Palmitoylation of SCRIB by
CC ZDHHC7 is required for its localization to cell-cell junctions,
CC function in the establishement of epithelial cell polarity and the
CC regulation of downstream signaling pathways important for epithelial
CC cell differentiation (PubMed:27380321). {ECO:0000269|PubMed:27380321}.
CC -!- DISEASE: Neural tube defects (NTD) [MIM:182940]: Congenital
CC malformations of the central nervous system and adjacent structures
CC related to defective neural tube closure during the first trimester of
CC pregnancy. Failure of neural tube closure can occur at any level of the
CC embryonic axis. Common NTD forms include anencephaly, myelomeningocele
CC and spina bifida, which result from the failure of fusion in the
CC cranial and spinal region of the neural tube. NTDs have a
CC multifactorial etiology encompassing both genetic and environmental
CC components. {ECO:0000269|PubMed:22095531}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the LAP (LRR and PDZ) protein family.
CC {ECO:0000305}.
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DR EMBL; AF240677; AAP88017.1; -; mRNA.
DR EMBL; AY062238; AAL38976.1; -; mRNA.
DR EMBL; AF271734; AAP88018.2; -; mRNA.
DR EMBL; D63481; BAA09768.3; -; mRNA.
DR EMBL; AC105219; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF458881; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC009490; AAH09490.2; -; mRNA.
DR EMBL; BC014632; AAH14632.2; -; mRNA.
DR CCDS; CCDS6411.1; -. [Q14160-1]
DR CCDS; CCDS6412.1; -. [Q14160-3]
DR RefSeq; NP_056171.3; NM_015356.4.
DR RefSeq; NP_874365.3; NM_182706.4.
DR PDB; 1UJU; NMR; -; A=1096-1193.
DR PDB; 1WHA; NMR; -; A=860-951.
DR PDB; 1X5Q; NMR; -; A=718-814.
DR PDB; 2W4F; X-ray; 1.30 A; A=725-815.
DR PDB; 4WYT; X-ray; 2.60 A; A=992-1203.
DR PDB; 4WYU; X-ray; 2.50 A; A/B=992-1203.
DR PDB; 5VWC; X-ray; 1.91 A; A=725-815.
DR PDB; 5VWI; X-ray; 1.75 A; A/B=1002-1092.
DR PDB; 5VWK; X-ray; 2.35 A; A/B/C/D=700-816.
DR PDB; 6EEY; X-ray; 1.15 A; A=1098-1189.
DR PDB; 6ESP; NMR; -; A=719-829.
DR PDB; 6MS1; X-ray; 1.35 A; A/B=722-815.
DR PDB; 6MTU; X-ray; 2.14 A; A/B=700-816.
DR PDB; 6MTV; X-ray; 2.60 A; A/B=700-816.
DR PDB; 6MYE; X-ray; 1.10 A; A=725-815.
DR PDB; 6MYF; X-ray; 1.60 A; A=725-815.
DR PDB; 6XA6; X-ray; 1.95 A; A/B=1002-1092.
DR PDB; 6XA7; X-ray; 2.50 A; A/B/C/D=860-950.
DR PDB; 6XA8; X-ray; 2.20 A; A/B=700-816.
DR PDB; 7JO7; X-ray; 2.44 A; A/B/C/D=860-950.
DR PDB; 7QTO; X-ray; 3.50 A; A/B=700-816.
DR PDB; 7QTP; X-ray; 1.90 A; A=700-816.
DR PDB; 7QTU; X-ray; 2.84 A; A/B/E/G=1002-1092.
DR PDBsum; 1UJU; -.
DR PDBsum; 1WHA; -.
DR PDBsum; 1X5Q; -.
DR PDBsum; 2W4F; -.
DR PDBsum; 4WYT; -.
DR PDBsum; 4WYU; -.
DR PDBsum; 5VWC; -.
DR PDBsum; 5VWI; -.
DR PDBsum; 5VWK; -.
DR PDBsum; 6EEY; -.
DR PDBsum; 6ESP; -.
DR PDBsum; 6MS1; -.
DR PDBsum; 6MTU; -.
DR PDBsum; 6MTV; -.
DR PDBsum; 6MYE; -.
DR PDBsum; 6MYF; -.
DR PDBsum; 6XA6; -.
DR PDBsum; 6XA7; -.
DR PDBsum; 6XA8; -.
DR PDBsum; 7JO7; -.
DR PDBsum; 7QTO; -.
DR PDBsum; 7QTP; -.
DR PDBsum; 7QTU; -.
DR AlphaFoldDB; Q14160; -.
DR SMR; Q14160; -.
DR BioGRID; 117060; 221.
DR ComplexPortal; CPX-6168; Scribble cell polarity complex, DLG1-LLGL2-SCRIB variant.
DR ComplexPortal; CPX-6184; Scribble cell polarity complex, DLG2-LLGL2-SCRIB variant.
DR ComplexPortal; CPX-6185; Scribble cell polarity complex, DLG3-LLGL2-SCRIB variant.
DR ComplexPortal; CPX-6186; Scribble cell polarity complex, DLG4-LLGL2-SCRIB variant.
DR ComplexPortal; CPX-6187; Scribble cell polarity complex, DLG5-LLGL2-SCRIB variant.
DR ComplexPortal; CPX-6188; Scribble cell polarity complex, DLG5-LLGL1-SCRIB variant.
DR ComplexPortal; CPX-6189; Scribble cell polarity complex, DLG4-LLGL1-SCRIB variant.
DR ComplexPortal; CPX-6190; Scribble cell polarity complex, DLG3-LLGL1-SCRIB variant.
DR ComplexPortal; CPX-6191; Scribble cell polarity complex, DLG2-LLGL1-SCRIB variant.
DR ComplexPortal; CPX-6192; Scribble cell polarity complex, DLG1-LLGL1-SCRIB variant.
DR CORUM; Q14160; -.
DR DIP; DIP-31259N; -.
DR ELM; Q14160; -.
DR IntAct; Q14160; 195.
DR MINT; Q14160; -.
DR STRING; 9606.ENSP00000349486; -.
DR MoonDB; Q14160; Predicted.
DR GlyGen; Q14160; 1 site, 2 O-linked glycans (1 site).
DR iPTMnet; Q14160; -.
DR PhosphoSitePlus; Q14160; -.
DR SwissPalm; Q14160; -.
DR BioMuta; SCRIB; -.
DR DMDM; 261260101; -.
DR EPD; Q14160; -.
DR jPOST; Q14160; -.
DR MassIVE; Q14160; -.
DR MaxQB; Q14160; -.
DR PaxDb; Q14160; -.
DR PeptideAtlas; Q14160; -.
DR PRIDE; Q14160; -.
DR ProteomicsDB; 59873; -. [Q14160-1]
DR ProteomicsDB; 59874; -. [Q14160-2]
DR ProteomicsDB; 59875; -. [Q14160-3]
DR Antibodypedia; 43533; 135 antibodies from 27 providers.
DR DNASU; 23513; -.
DR Ensembl; ENST00000320476.7; ENSP00000322938.3; ENSG00000180900.20. [Q14160-1]
DR Ensembl; ENST00000356994.7; ENSP00000349486.2; ENSG00000180900.20. [Q14160-3]
DR Ensembl; ENST00000377533.7; ENSP00000366756.3; ENSG00000180900.20. [Q14160-2]
DR Ensembl; ENST00000611528.2; ENSP00000479898.1; ENSG00000274287.4. [Q14160-2]
DR Ensembl; ENST00000612204.4; ENSP00000484041.1; ENSG00000274287.4. [Q14160-3]
DR Ensembl; ENST00000622455.4; ENSP00000482406.1; ENSG00000274287.4. [Q14160-1]
DR GeneID; 23513; -.
DR KEGG; hsa:23513; -.
DR MANE-Select; ENST00000356994.7; ENSP00000349486.2; NM_182706.5; NP_874365.3. [Q14160-3]
DR UCSC; uc003yzo.1; human. [Q14160-1]
DR CTD; 23513; -.
DR DisGeNET; 23513; -.
DR GeneCards; SCRIB; -.
DR HGNC; HGNC:30377; SCRIB.
DR HPA; ENSG00000180900; Tissue enhanced (esophagus).
DR MalaCards; SCRIB; -.
DR MIM; 182940; phenotype.
DR MIM; 607733; gene.
DR neXtProt; NX_Q14160; -.
DR OpenTargets; ENSG00000180900; -.
DR PharmGKB; PA134936275; -.
DR VEuPathDB; HostDB:ENSG00000180900; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000154025; -.
DR HOGENOM; CLU_000288_18_20_1; -.
DR InParanoid; Q14160; -.
DR OrthoDB; 284114at2759; -.
DR PhylomeDB; Q14160; -.
DR TreeFam; TF351429; -.
DR PathwayCommons; Q14160; -.
DR Reactome; R-HSA-4608870; Asymmetric localization of PCP proteins.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013406; RHOQ GTPase cycle.
DR Reactome; R-HSA-9013409; RHOJ GTPase cycle.
DR Reactome; R-HSA-9696264; RND3 GTPase cycle.
DR Reactome; R-HSA-9696270; RND2 GTPase cycle.
DR SignaLink; Q14160; -.
DR SIGNOR; Q14160; -.
DR BioGRID-ORCS; 23513; 31 hits in 1076 CRISPR screens.
DR ChiTaRS; SCRIB; human.
DR EvolutionaryTrace; Q14160; -.
DR GeneWiki; SCRIB; -.
DR GenomeRNAi; 23513; -.
DR Pharos; Q14160; Tbio.
DR PRO; PR:Q14160; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q14160; protein.
DR Bgee; ENSG00000180900; Expressed in lower esophagus mucosa and 91 other tissues.
DR ExpressionAtlas; Q14160; baseline and differential.
DR Genevisible; Q14160; HS.
DR GO; GO:0005912; C:adherens junction; IDA:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; IBA:GO_Central.
DR GO; GO:0030054; C:cell junction; IDA:HPA.
DR GO; GO:0044291; C:cell-cell contact zone; IEA:Ensembl.
DR GO; GO:0005911; C:cell-cell junction; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0099147; C:extrinsic component of postsynaptic density membrane; IEA:Ensembl.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0001772; C:immunological synapse; ISS:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0035748; C:myelin sheath abaxonal region; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IBA:GO_Central.
DR GO; GO:0098793; C:presynapse; IEA:UniProtKB-SubCell.
DR GO; GO:0034750; C:Scrib-APC-beta-catenin complex; IDA:BHF-UCL.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0090630; P:activation of GTPase activity; IMP:UniProtKB.
DR GO; GO:0060561; P:apoptotic process involved in morphogenesis; IMP:UniProtKB.
DR GO; GO:0043615; P:astrocyte cell migration; IEA:Ensembl.
DR GO; GO:0060088; P:auditory receptor cell stereocilium organization; IEA:Ensembl.
DR GO; GO:0016477; P:cell migration; IMP:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; IDA:UniProtKB.
DR GO; GO:0098609; P:cell-cell adhesion; IGI:UniProtKB.
DR GO; GO:0021747; P:cochlear nucleus development; IEA:Ensembl.
DR GO; GO:0035089; P:establishment of apical/basal cell polarity; IMP:UniProtKB.
DR GO; GO:0001768; P:establishment of T cell polarity; ISS:UniProtKB.
DR GO; GO:0045197; P:establishment or maintenance of epithelial cell apical/basal polarity; IBA:GO_Central.
DR GO; GO:0060603; P:mammary gland duct morphogenesis; ISS:UniProtKB.
DR GO; GO:0046007; P:negative regulation of activated T cell proliferation; ISS:UniProtKB.
DR GO; GO:0045930; P:negative regulation of mitotic cell cycle; IDA:UniProtKB.
DR GO; GO:0001843; P:neural tube closure; IMP:UniProtKB.
DR GO; GO:0098968; P:neurotransmitter receptor transport postsynaptic membrane to endosome; IBA:GO_Central.
DR GO; GO:0098887; P:neurotransmitter receptor transport, endosome to postsynaptic membrane; IBA:GO_Central.
DR GO; GO:0030859; P:polarized epithelial cell differentiation; IMP:UniProtKB.
DR GO; GO:0050918; P:positive chemotaxis; IMP:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; ISS:UniProtKB.
DR GO; GO:0001921; P:positive regulation of receptor recycling; IMP:UniProtKB.
DR GO; GO:0036342; P:post-anal tail morphogenesis; IEA:Ensembl.
DR GO; GO:0071896; P:protein localization to adherens junction; IMP:BHF-UCL.
DR GO; GO:0043113; P:receptor clustering; IBA:GO_Central.
DR GO; GO:0097120; P:receptor localization to synapse; IBA:GO_Central.
DR GO; GO:0099149; P:regulation of postsynaptic neurotransmitter receptor internalization; IEA:Ensembl.
DR GO; GO:0048488; P:synaptic vesicle endocytosis; IEA:Ensembl.
DR GO; GO:0016080; P:synaptic vesicle targeting; IEA:Ensembl.
DR GO; GO:0042060; P:wound healing; IEA:Ensembl.
DR Gene3D; 2.30.42.10; -; 4.
DR Gene3D; 3.80.10.10; -; 4.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR Pfam; PF13855; LRR_8; 2.
DR Pfam; PF00595; PDZ; 4.
DR SMART; SM00369; LRR_TYP; 11.
DR SMART; SM00228; PDZ; 4.
DR SUPFAM; SSF50156; SSF50156; 4.
DR PROSITE; PS51450; LRR; 13.
DR PROSITE; PS50106; PDZ; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell junction; Cell membrane;
KW Cell projection; Coiled coil; Cytoplasm; Developmental protein;
KW Differentiation; Disease variant; Host-virus interaction;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus;
KW Inhibition of host STAT1 by virus; Inhibition of host STAT2 by virus;
KW Leucine-rich repeat; Lipoprotein; Membrane; Palmitate; Phosphoprotein;
KW Reference proteome; Repeat; Synapse; Ubl conjugation; Viral immunoevasion.
FT CHAIN 1..1630
FT /note="Protein scribble homolog"
FT /id="PRO_0000188303"
FT REPEAT 37..58
FT /note="LRR 1"
FT REPEAT 60..81
FT /note="LRR 2"
FT REPEAT 83..104
FT /note="LRR 3"
FT REPEAT 106..127
FT /note="LRR 4"
FT REPEAT 129..150
FT /note="LRR 5"
FT REPEAT 152..174
FT /note="LRR 6"
FT REPEAT 175..197
FT /note="LRR 7"
FT REPEAT 198..219
FT /note="LRR 8"
FT REPEAT 221..243
FT /note="LRR 9"
FT REPEAT 244..265
FT /note="LRR 10"
FT REPEAT 267..288
FT /note="LRR 11"
FT REPEAT 290..312
FT /note="LRR 12"
FT REPEAT 313..334
FT /note="LRR 13"
FT REPEAT 336..357
FT /note="LRR 14"
FT REPEAT 359..381
FT /note="LRR 15"
FT REPEAT 382..402
FT /note="LRR 16"
FT DOMAIN 728..815
FT /note="PDZ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 862..950
FT /note="PDZ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 1004..1093
FT /note="PDZ 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 1100..1194
FT /note="PDZ 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 1..818
FT /note="Sufficient for targeting to adherens junction and to
FT inhibit cell proliferation"
FT REGION 417..440
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 459..606
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 628..702
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 717..1229
FT /note="Interaction with ARHGEF7"
FT /evidence="ECO:0000269|PubMed:15182672"
FT REGION 827..853
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1105..1117
FT /note="Interaction with tick-borne encephalitis virus RNA-
FT directed RNA polymerase NS5"
FT /evidence="ECO:0000269|PubMed:18042258"
FT REGION 1227..1246
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1277..1489
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1520..1630
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 458..474
FT /evidence="ECO:0000255"
FT COILED 656..701
FT /evidence="ECO:0000255"
FT COILED 1379..1419
FT /evidence="ECO:0000255"
FT COMPBIAS 423..440
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 460..492
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 520..534
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 565..588
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 664..692
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1333..1347
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1380..1402
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1439..1453
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 37
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 378
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 475
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 504
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 688
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 689
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 708
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 764
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 826
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231"
FT MOD_RES 835
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 853
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 875
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 939
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 1140
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 1220
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:15144186,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 1223
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1226
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1232
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 1276
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1279
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1295
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1298
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1306
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 1309
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 1342
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231"
FT MOD_RES 1348
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 1378
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 1437
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1445
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1448
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 1475
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1486
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 1508
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 1541
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1545
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1547
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 1561
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1566
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..81
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_010906"
FT VAR_SEQ 1565
FT /note="L -> LPLSGKKFDYRAFAALPSSRPVYDIQ (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_010908"
FT VARIANT 422
FT /note="P -> L (in dbSNP:rs6558394)"
FT /evidence="ECO:0000269|PubMed:15649318,
FT ECO:0000269|PubMed:15806148, ECO:0000269|PubMed:8590280,
FT ECO:0000269|Ref.3"
FT /id="VAR_019429"
FT VARIANT 454
FT /note="P -> S (in NTD; protein interactions not affected by
FT the mutation; shows reduced protein localization to the
FT cell membrane; dbSNP:rs1302482009)"
FT /evidence="ECO:0000269|PubMed:22095531"
FT /id="VAR_067219"
FT VARIANT 1535
FT /note="R -> Q (in NTD; protein interactions not affected by
FT the mutation; shows reduced protein localization to the
FT cell membrane; dbSNP:rs782428100)"
FT /evidence="ECO:0000269|PubMed:22095531"
FT /id="VAR_067220"
FT MUTAGEN 4
FT /note="C->S: Loss of palmitoylation. Loss of
FT palmitoylation, localization to cell-cell junctions and
FT function in epithelial cell polarization and signaling
FT pathways regulation; when associated with S-10."
FT /evidence="ECO:0000269|PubMed:27380321"
FT MUTAGEN 10
FT /note="C->S: Loss of palmitoylation. Loss of
FT palmitoylation, localization to cell-cell junctions and
FT function in epithelial cell polarization and signaling
FT pathways regulation; when associated with S-4."
FT /evidence="ECO:0000269|PubMed:27380321"
FT MUTAGEN 22
FT /note="C->S: No effect on palmitoylation."
FT /evidence="ECO:0000269|PubMed:27380321"
FT MUTAGEN 305
FT /note="P->L: Decreased palmitoylation. Loss of localization
FT at the plasma membrane. Loss of targeting to cell-cell
FT junctions. Alters interaction with TJP2. Loss of pro-
FT apoptotic function. Loss of function in epithelial cell
FT polarization and signaling pathways regulation."
FT /evidence="ECO:0000269|PubMed:15182672,
FT ECO:0000269|PubMed:15806148, ECO:0000269|PubMed:19041750,
FT ECO:0000269|PubMed:27380321"
FT MUTAGEN 738..739
FT /note="LG->AE: Alters interaction with LPP."
FT /evidence="ECO:0000269|PubMed:15649318"
FT MUTAGEN 738
FT /note="L->R: Loss of anti-proliferative activity."
FT MUTAGEN 872..873
FT /note="LG->AE: Alters interaction with LPP."
FT /evidence="ECO:0000269|PubMed:15649318"
FT MUTAGEN 1014..1015
FT /note="LG->AE: Loss of interaction with LPP and TRIP6."
FT /evidence="ECO:0000269|PubMed:15649318"
FT MUTAGEN 1111..1112
FT /note="LG->AE: Alters interaction with LPP."
FT /evidence="ECO:0000269|PubMed:15649318"
FT CONFLICT 1489
FT /note="E -> K (in Ref. 2; AAL38976)"
FT /evidence="ECO:0000305"
FT STRAND 725..732
FT /evidence="ECO:0007829|PDB:6MYE"
FT STRAND 734..736
FT /evidence="ECO:0007829|PDB:6XA8"
FT STRAND 740..744
FT /evidence="ECO:0007829|PDB:6MYE"
FT STRAND 751..754
FT /evidence="ECO:0007829|PDB:5VWC"
FT STRAND 757..763
FT /evidence="ECO:0007829|PDB:6MYE"
FT STRAND 765..767
FT /evidence="ECO:0007829|PDB:6ESP"
FT HELIX 768..772
FT /evidence="ECO:0007829|PDB:6MYE"
FT STRAND 779..783
FT /evidence="ECO:0007829|PDB:6MYE"
FT HELIX 793..801
FT /evidence="ECO:0007829|PDB:6MYE"
FT STRAND 805..814
FT /evidence="ECO:0007829|PDB:6MYE"
FT STRAND 815..818
FT /evidence="ECO:0007829|PDB:6ESP"
FT HELIX 820..823
FT /evidence="ECO:0007829|PDB:6ESP"
FT STRAND 860..866
FT /evidence="ECO:0007829|PDB:7JO7"
FT STRAND 875..877
FT /evidence="ECO:0007829|PDB:7JO7"
FT STRAND 893..896
FT /evidence="ECO:0007829|PDB:7JO7"
FT HELIX 902..905
FT /evidence="ECO:0007829|PDB:7JO7"
FT STRAND 914..918
FT /evidence="ECO:0007829|PDB:7JO7"
FT HELIX 928..936
FT /evidence="ECO:0007829|PDB:7JO7"
FT STRAND 940..947
FT /evidence="ECO:0007829|PDB:7JO7"
FT STRAND 997..1000
FT /evidence="ECO:0007829|PDB:4WYU"
FT STRAND 1002..1008
FT /evidence="ECO:0007829|PDB:5VWI"
FT STRAND 1010..1012
FT /evidence="ECO:0007829|PDB:4WYU"
FT STRAND 1016..1020
FT /evidence="ECO:0007829|PDB:5VWI"
FT STRAND 1022..1024
FT /evidence="ECO:0007829|PDB:4WYT"
FT TURN 1027..1030
FT /evidence="ECO:0007829|PDB:4WYU"
FT STRAND 1031..1033
FT /evidence="ECO:0007829|PDB:4WYU"
FT STRAND 1036..1041
FT /evidence="ECO:0007829|PDB:5VWI"
FT HELIX 1046..1049
FT /evidence="ECO:0007829|PDB:5VWI"
FT STRAND 1057..1061
FT /evidence="ECO:0007829|PDB:5VWI"
FT HELIX 1071..1078
FT /evidence="ECO:0007829|PDB:5VWI"
FT STRAND 1080..1090
FT /evidence="ECO:0007829|PDB:5VWI"
FT STRAND 1099..1104
FT /evidence="ECO:0007829|PDB:6EEY"
FT STRAND 1113..1117
FT /evidence="ECO:0007829|PDB:6EEY"
FT STRAND 1119..1122
FT /evidence="ECO:0007829|PDB:1UJU"
FT STRAND 1126..1128
FT /evidence="ECO:0007829|PDB:4WYT"
FT HELIX 1129..1131
FT /evidence="ECO:0007829|PDB:6EEY"
FT STRAND 1134..1139
FT /evidence="ECO:0007829|PDB:6EEY"
FT STRAND 1141..1143
FT /evidence="ECO:0007829|PDB:4WYT"
FT HELIX 1144..1148
FT /evidence="ECO:0007829|PDB:6EEY"
FT STRAND 1156..1160
FT /evidence="ECO:0007829|PDB:6EEY"
FT HELIX 1170..1177
FT /evidence="ECO:0007829|PDB:6EEY"
FT STRAND 1181..1189
FT /evidence="ECO:0007829|PDB:6EEY"
SQ SEQUENCE 1630 AA; 174915 MW; 9CF28E3510E8BDB4 CRC64;
MLKCIPLWRC NRHVESVDKR HCSLQAVPEE IYRYSRSLEE LLLDANQLRE LPKPFFRLLN
LRKLGLSDNE IQRLPPEVAN FMQLVELDVS RNDIPEIPES IKFCKALEIA DFSGNPLSRL
PDGFTQLRSL AHLALNDVSL QALPGDVGNL ANLVTLELRE NLLKSLPASL SFLVKLEQLD
LGGNDLEVLP DTLGALPNLR ELWLDRNQLS ALPPELGNLR RLVCLDVSEN RLEELPAELG
GLVLLTDLLL SQNLLRRLPD GIGQLKQLSI LKVDQNRLCE VTEAIGDCEN LSELILTENL
LMALPRSLGK LTKLTNLNVD RNHLEALPPE IGGCVALSVL SLRDNRLAVL PPELAHTTEL
HVLDVAGNRL QSLPFALTHL NLKALWLAEN QAQPMLRFQT EDDARTGEKV LTCYLLPQQP
PPSLEDAGQQ GSLSETWSDA PPSRVSVIQF LEAPIGDEDA EEAAAEKRGL QRRATPHPSE
LKVMKRSIEG RRSEACPCQP DSGSPLPAEE EKRLSAESGL SEDSRPSAST VSEAEPEGPS
AEAQGGSQQE ATTAGGEEDA EEDYQEPTVH FAEDALLPGD DREIEEGQPE APWTLPGGRQ
RLIRKDTPHY KKHFKISKLP QPEAVVALLQ GMQPDGEGPV APGGWHNGPH APWAPRAQKE
EEEEEEGSPQ EEEEEEEEEN RAEEEEASTE EEDKEGAVVS APSVKGVSFD QANNLLIEPA
RIEEEELTLT ILRQTGGLGI SIAGGKGSTP YKGDDEGIFI SRVSEEGPAA RAGVRVGDKL
LEVNGVALQG AEHHEAVEAL RGAGTAVQMR VWRERMVEPE NAVTITPLRP EDDYSPRERR
GGGLRLPLLP PESPGPLRQR HVACLARSER GLGFSIAGGK GSTPYRAGDA GIFVSRIAEG
GAAHRAGTLQ VGDRVLSING VDVTEARHDH AVSLLTAASP TIALLLEREA GGPLPPSPLP
HSSPPTAAVA TTSITTATPG VPGLPSLAPS LLAAALEGPY PVEEIRLPRA GGPLGLSIVG
GSDHSSHPFG VQEPGVFISK VLPRGLAARS GLRVGDRILA VNGQDVRDAT HQEAVSALLR
PCLELSLLVR RDPAPPGLRE LCIQKAPGER LGISIRGGAR GHAGNPRDPT DEGIFISKVS
PTGAAGRDGR LRVGLRLLEV NQQSLLGLTH GEAVQLLRSV GDTLTVLVCD GFEASTDAAL
EVSPGVIANP FAAGIGHRNS LESISSIDRE LSPEGPGKEK ELPGQTLHWG PEATEAAGRG
LQPLKLDYRA LAAVPSAGSV QRVPSGAAGG KMAESPCSPS GQQPPSPPSP DELPANVKQA
YRAFAAVPTS HPPEDAPAQP PTPGPAASPE QLSFRERQKY FELEVRVPQA EGPPKRVSLV
GADDLRKMQE EEARKLQQKR AQMLREAAEA GAEARLALDG ETLGEEEQED EQPPWASPSP
TSRQSPASPP PLGGGAPVRT AKAERRHQER LRVQSPEPPA PERALSPAEL RALEAEKRAL
WRAARMKSLE QDALRAQMVL SRSQEGRGTR GPLERLAEAP SPAPTPSPTP VEDLGPQTST
SPGRLSPDFA EELRSLEPSP SPGPQEEDGE VALVLLGRPS PGAVGPEDVA LCSSRRPVRP
GRRGLGPVPS
