NISCH_MOUSE
ID NISCH_MOUSE Reviewed; 1593 AA.
AC Q80TM9; Q2YDV7; Q8C354; Q8C4X9; Q8CBH0; Q91XW6; Q99LG6; Q9EPW8; Q9WUM6;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 02-SEP-2008, sequence version 2.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Nischarin;
DE AltName: Full=Imidazoline receptor 1;
DE Short=I-1;
DE Short=IR1;
DE AltName: Full=Imidazoline receptor I-1-like protein;
DE AltName: Full=Imidazoline-1 receptor;
DE Short=I1R;
GN Name=Nisch; Synonyms=Kiaa0975;
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] (ISOFORM 3), FUNCTION, INTERACTION WITH ITGA5,
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RC STRAIN=ICR; TISSUE=Brain;
RX PubMed=11121431; DOI=10.1083/jcb.151.6.1141;
RA Alahari S.K., Lee J.W., Juliano R.L.;
RT "Nischarin, a novel protein that interacts with the integrin alpha5 subunit
RT and inhibits cell migration.";
RL J. Cell Biol. 151:1141-1154(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=12693553; DOI=10.1093/dnares/10.1.35;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S.,
RA Nakajima D., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: II.
RT The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:35-48(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4; 5 AND 7).
RC STRAIN=C57BL/6J; TISSUE=Cerebellum, and Lung;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 215-1593 (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Colon, and Mammary tumor;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1238-1593 (ISOFORM 1).
RC TISSUE=Carcinoma;
RA Bailey T.L., Smith D.R., McGaugh B.D., Mitchell J.;
RL Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1386-1593 (ISOFORM 1).
RC TISSUE=Lung;
RA Cain D., Carter J., McLean W., Robbins L.;
RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP FUNCTION.
RX PubMed=12915132; DOI=10.1016/s0014-4827(03)00233-7;
RA Alahari S.K.;
RT "Nischarin inhibits Rac induced migration and invasion of epithelial cells
RT by affecting signaling cascades involving PAK.";
RL Exp. Cell Res. 288:415-424(2003).
RN [9]
RP INTERACTION WITH ITGA5.
RX PubMed=14535848; DOI=10.1042/bj20030411;
RA Alahari S.K., Nasrallah H.;
RT "A membrane proximal region of the integrin alpha5 subunit is important for
RT its interaction with nischarin.";
RL Biochem. J. 377:449-457(2004).
RN [10]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH ITGA5 AND PAK1, INTERACTION WITH
RP PAK1, AND SUBCELLULAR LOCATION.
RX PubMed=15229651; DOI=10.1038/sj.emboj.7600291;
RA Alahari S.K., Reddig P.J., Juliano R.L.;
RT "The integrin-binding protein Nischarin regulates cell migration by
RT inhibiting PAK.";
RL EMBO J. 23:2777-2788(2004).
RN [11]
RP FUNCTION, INTERACTION WITH RAC1, AND SUBCELLULAR LOCATION.
RX PubMed=16002401; DOI=10.1074/jbc.m502546200;
RA Reddig P.J., Xu D., Juliano R.L.;
RT "Regulation of p21-activated kinase-independent Rac1 signal transduction by
RT Nischarin.";
RL J. Biol. Chem. 280:30994-31002(2005).
RN [12]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16678176; DOI=10.1016/j.febslet.2006.04.058;
RA Zhang J., Abdel-Rahman A.A.;
RT "Nischarin as a functional imidazoline (I1) receptor.";
RL FEBS Lett. 580:3070-3074(2006).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-543, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [14]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH LIMK1 AND PAK1, AND INTERACTION
RP WITH LIMK1 AND LIMK2.
RX PubMed=18332102; DOI=10.1128/mcb.01832-07;
RA Ding Y., Milosavljevic T., Alahari S.K.;
RT "Nischarin inhibits LIM kinase to regulate cofilin phosphorylation and cell
RT invasion.";
RL Mol. Cell. Biol. 28:3742-3756(2008).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-543; SER-545; SER-548 AND
RP THR-1371, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Lung, Pancreas, Spleen, and Testis;
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).
CC -!- FUNCTION: Acts either as the functional imidazoline-1 receptor (I1R)
CC candidate or as a membrane-associated mediator of the I1R signaling.
CC Binds numerous imidazoline ligands that induces initiation of cell-
CC signaling cascades triggering to cell survival, growth and migration.
CC Its activation by the agonist rilmenidine induces an increase in
CC phosphorylation of mitogen-activated protein kinases MAPK1 and MAPK3 in
CC rostral ventrolateral medulla (RVLM) neurons that exhibited
CC rilmenidine-evoked hypotension (By similarity). Blocking its activation
CC with efaroxan abolished rilmenidine-induced mitogen-activated protein
CC kinase phosphorylation in RVLM neurons (By similarity). Acts as a
CC modulator of Rac-regulated signal transduction pathways. Suppresses
CC Rac1-stimulated cell migration by interacting with PAK1 and inhibiting
CC its kinase activity. Also blocks Pak-independent Rac signaling by
CC interacting with RAC1 and inhibiting Rac1-stimulated NF-kB response
CC element and cyclin D1 promoter activation. Inhibits also LIMK1 kinase
CC activity by reducing LIMK1 'Tyr-508' phosphorylation. Inhibits Rac-
CC induced cell migration and invasion in breast and colon epithelial
CC cells. Inhibits lamellipodia formation, when overexpressed. Plays a
CC role in protection against apoptosis (By similarity). Involved in
CC association with IRS4 in the enhancement of insulin activation of MAPK1
CC and MAPK3 (By similarity). When overexpressed, induces a redistribution
CC of cell surface ITGA5 integrin to intracellular endosomal structures
CC (By similarity). {ECO:0000250, ECO:0000269|PubMed:11121431,
CC ECO:0000269|PubMed:12915132, ECO:0000269|PubMed:15229651,
CC ECO:0000269|PubMed:16002401, ECO:0000269|PubMed:16678176,
CC ECO:0000269|PubMed:18332102}.
CC -!- SUBUNIT: Homooligomer (By similarity). Interacts with GRB2 (By
CC similarity). Interacts with PIK3R1; probably associates with the PI3-
CC kinase complex (By similarity). Interacts with IRS4 (By similarity).
CC Found in a complex with ITGA5 and PAK1. Found in a complex with LIMK1
CC and PAK1. Interacts with ITGA5 (via cytoplasmic domain); this
CC interaction is direct. Interacts with PAK1 (via kinase domain); this
CC interaction is direct and is increased upon activation of PAK1.
CC Interacts with LIMK1 (via PDZ and kinase domain); this interaction is
CC direct. Interacts with LIMK2; this interaction depends on LIMK2
CC activity. Interacts with RAC1 (activated state). Interacts with STK11;
CC this interaction may increase STK11 activity (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}. Cytoplasm
CC {ECO:0000269|PubMed:11121431, ECO:0000269|PubMed:15229651,
CC ECO:0000269|PubMed:16002401, ECO:0000269|PubMed:16678176}. Early
CC endosome {ECO:0000250}. Recycling endosome {ECO:0000250}. Note=Enriched
CC in the early/sorting and recycling endosomes (By similarity).
CC Colocalized in early/sorting endosomes with EEA1 and SNX2 and in
CC recycling endosomes with transferrin receptor (By similarity).
CC Colocalized with MAPK1 and MAPK3 in RVLM neurons (By similarity).
CC Detected in the perinuclear region partially associated with punctate
CC structures. Colocalizes with PAK1 in cytoplasm, vesicular structures in
CC the perinuclear area and membrane ruffles. Colocalizes with RAC1 in the
CC cytoplasm and vesicles structures. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1;
CC IsoId=Q80TM9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q80TM9-2; Sequence=VSP_035141;
CC Name=3;
CC IsoId=Q80TM9-3; Sequence=VSP_035136;
CC Name=4;
CC IsoId=Q80TM9-4; Sequence=VSP_035142, VSP_035143;
CC Name=5;
CC IsoId=Q80TM9-5; Sequence=VSP_035139, VSP_035140;
CC Name=6;
CC IsoId=Q80TM9-6; Sequence=VSP_035144, VSP_035145;
CC Name=7;
CC IsoId=Q80TM9-7; Sequence=VSP_035137, VSP_035138;
CC -!- TISSUE SPECIFICITY: Highly expressed in brain and kidney. Moderately
CC expressed in heart, liver, lung and skeletal muscle. Not detected in
CC spleen and testis. {ECO:0000269|PubMed:11121431}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryo at 7 day dpc onwards.
CC {ECO:0000269|PubMed:11121431}.
CC -!- DOMAIN: Both the presence of the PX domain and the coiled coil region
CC are necessary for its endosomal targeting. {ECO:0000250}.
CC -!- MISCELLANEOUS: 'Nischarin' means 'slowness of motion' in classic
CC Sanskrit.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH03270.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAI08365.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAK52087.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC65694.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF315344; AAG42100.1; -; mRNA.
DR EMBL; AK122412; BAC65694.1; ALT_INIT; mRNA.
DR EMBL; AK036043; BAC29286.1; -; mRNA.
DR EMBL; AK080441; BAC37917.1; -; mRNA.
DR EMBL; AK086880; BAC39757.1; -; mRNA.
DR EMBL; AC108416; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC154446; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC003270; AAH03270.1; ALT_INIT; mRNA.
DR EMBL; BC108364; AAI08365.1; ALT_FRAME; mRNA.
DR EMBL; AY032852; AAK52087.1; ALT_INIT; mRNA.
DR EMBL; AF144133; AAD31521.1; -; mRNA.
DR CCDS; CCDS36853.1; -. [Q80TM9-1]
DR CCDS; CCDS84107.1; -. [Q80TM9-6]
DR RefSeq; NP_073147.2; NM_022656.2. [Q80TM9-1]
DR AlphaFoldDB; Q80TM9; -.
DR SMR; Q80TM9; -.
DR BioGRID; 211089; 3.
DR IntAct; Q80TM9; 3.
DR STRING; 10090.ENSMUSP00000022469; -.
DR iPTMnet; Q80TM9; -.
DR PhosphoSitePlus; Q80TM9; -.
DR EPD; Q80TM9; -.
DR jPOST; Q80TM9; -.
DR MaxQB; Q80TM9; -.
DR PaxDb; Q80TM9; -.
DR PeptideAtlas; Q80TM9; -.
DR PRIDE; Q80TM9; -.
DR ProteomicsDB; 293557; -. [Q80TM9-1]
DR ProteomicsDB; 293558; -. [Q80TM9-2]
DR ProteomicsDB; 293559; -. [Q80TM9-3]
DR ProteomicsDB; 293560; -. [Q80TM9-4]
DR ProteomicsDB; 293561; -. [Q80TM9-5]
DR ProteomicsDB; 293562; -. [Q80TM9-6]
DR ProteomicsDB; 293563; -. [Q80TM9-7]
DR Antibodypedia; 14512; 109 antibodies from 25 providers.
DR DNASU; 64652; -.
DR Ensembl; ENSMUST00000022469; ENSMUSP00000022469; ENSMUSG00000021910. [Q80TM9-1]
DR Ensembl; ENSMUST00000164989; ENSMUSP00000126982; ENSMUSG00000021910. [Q80TM9-5]
DR Ensembl; ENSMUST00000165981; ENSMUSP00000130210; ENSMUSG00000021910. [Q80TM9-4]
DR Ensembl; ENSMUST00000168206; ENSMUSP00000132842; ENSMUSG00000021910. [Q80TM9-3]
DR Ensembl; ENSMUST00000171735; ENSMUSP00000127132; ENSMUSG00000021910. [Q80TM9-7]
DR Ensembl; ENSMUST00000172142; ENSMUSP00000132413; ENSMUSG00000021910. [Q80TM9-6]
DR GeneID; 64652; -.
DR KEGG; mmu:64652; -.
DR UCSC; uc007swy.1; mouse. [Q80TM9-1]
DR UCSC; uc007sxa.1; mouse. [Q80TM9-6]
DR UCSC; uc007sxb.1; mouse. [Q80TM9-4]
DR UCSC; uc007sxc.1; mouse. [Q80TM9-7]
DR CTD; 11188; -.
DR MGI; MGI:1928323; Nisch.
DR VEuPathDB; HostDB:ENSMUSG00000021910; -.
DR eggNOG; KOG1259; Eukaryota.
DR GeneTree; ENSGT00940000156494; -.
DR HOGENOM; CLU_252294_0_0_1; -.
DR InParanoid; Q80TM9; -.
DR OMA; PIDKDFY; -.
DR OrthoDB; 320361at2759; -.
DR PhylomeDB; Q80TM9; -.
DR TreeFam; TF320547; -.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR Reactome; R-MMU-9696264; RND3 GTPase cycle.
DR Reactome; R-MMU-9696270; RND2 GTPase cycle.
DR BioGRID-ORCS; 64652; 7 hits in 71 CRISPR screens.
DR ChiTaRS; Nisch; mouse.
DR PRO; PR:Q80TM9; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q80TM9; protein.
DR Bgee; ENSMUSG00000021910; Expressed in internal carotid artery and 266 other tissues.
DR ExpressionAtlas; Q80TM9; baseline and differential.
DR Genevisible; Q80TM9; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0045171; C:intercellular bridge; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0015630; C:microtubule cytoskeleton; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0005178; F:integrin binding; IDA:MGI.
DR GO; GO:0035091; F:phosphatidylinositol binding; IEA:InterPro.
DR GO; GO:0019901; F:protein kinase binding; IBA:GO_Central.
DR GO; GO:0030036; P:actin cytoskeleton organization; IDA:MGI.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0006006; P:glucose metabolic process; ISO:MGI.
DR GO; GO:0030336; P:negative regulation of cell migration; IDA:MGI.
DR GO; GO:0048243; P:norepinephrine secretion; ISO:MGI.
DR GO; GO:0016601; P:Rac protein signal transduction; IDA:MGI.
DR GO; GO:0008217; P:regulation of blood pressure; ISO:MGI.
DR GO; GO:0032228; P:regulation of synaptic transmission, GABAergic; ISO:MGI.
DR CDD; cd06875; PX_IRAS; 1.
DR Gene3D; 3.30.1520.10; -; 1.
DR Gene3D; 3.80.10.10; -; 2.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR025875; Leu-rich_rpt_4.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR037904; Nischarin_PX.
DR InterPro; IPR001683; PX_dom.
DR InterPro; IPR036871; PX_dom_sf.
DR Pfam; PF12799; LRR_4; 1.
DR Pfam; PF00787; PX; 1.
DR SMART; SM00312; PX; 1.
DR SUPFAM; SSF64268; SSF64268; 1.
DR PROSITE; PS51450; LRR; 6.
DR PROSITE; PS50195; PX; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; Cell membrane; Coiled coil; Cytoplasm;
KW Endosome; Leucine-rich repeat; Membrane; Phosphoprotein; Receptor;
KW Reference proteome; Repeat.
FT CHAIN 1..1593
FT /note="Nischarin"
FT /id="PRO_0000348266"
FT DOMAIN 12..122
FT /note="PX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00147"
FT REPEAT 290..311
FT /note="LRR 1"
FT REPEAT 313..334
FT /note="LRR 2"
FT REPEAT 335..356
FT /note="LRR 3"
FT REPEAT 358..379
FT /note="LRR 4"
FT REPEAT 380..401
FT /note="LRR 5"
FT REPEAT 405..426
FT /note="LRR 6"
FT REPEAT 1081..1086
FT /note="1"
FT REPEAT 1087..1092
FT /note="2"
FT REPEAT 1093..1098
FT /note="3"
FT REPEAT 1099..1104
FT /note="4"
FT REPEAT 1105..1110
FT /note="5"
FT REPEAT 1111..1116
FT /note="6"
FT REPEAT 1123..1128
FT /note="7"
FT REPEAT 1129..1134
FT /note="8"
FT REPEAT 1135..1140
FT /note="9"
FT REPEAT 1141..1146
FT /note="10"
FT REGION 1..134
FT /note="Necessary for binding to phosphoinositide-3-P; not
FT sufficient for targeting to endosomes"
FT /evidence="ECO:0000250"
FT REGION 121..695
FT /note="Necessary for homooligomerization and targeting to
FT endosomes"
FT /evidence="ECO:0000250"
FT REGION 246..869
FT /note="Interaction with PAK1"
FT /evidence="ECO:0000269|PubMed:15229651"
FT REGION 466..499
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 629..687
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 661..869
FT /note="Interaction with LIMK"
FT REGION 709..807
FT /note="Interaction with ITGA5"
FT REGION 1016..1185
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1081..1146
FT /note="10 X 6 AA tandem repeat of A-E-A-P-A-A"
FT COILED 624..694
FT /evidence="ECO:0000255"
FT COMPBIAS 636..652
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 662..687
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1016..1035
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1161..1177
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 543
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 545
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 548
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1371
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1373
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2I1"
FT VAR_SEQ 1..245
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11121431"
FT /id="VSP_035136"
FT VAR_SEQ 122..153
FT /note="EVNGVTAALAEELFEKGEQLLGAGEVFAIRPL -> VSSFGALCFAYEPTAT
FT KAVGLGFEETQTGPWP (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_035137"
FT VAR_SEQ 154..1593
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_035138"
FT VAR_SEQ 332..334
FT /note="HLY -> ATS (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_035139"
FT VAR_SEQ 335..1593
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_035140"
FT VAR_SEQ 348..500
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12693553"
FT /id="VSP_035141"
FT VAR_SEQ 437..472
FT /note="ICLDDVATTEKELDTVEVLKAIQKAKDVKSKLSNTE -> VSPRSSSRAQRD
FT WQGKPSLSAKADRGKAVHSVLVFF (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_035142"
FT VAR_SEQ 473..1593
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_035143"
FT VAR_SEQ 513..516
FT /note="MFVQ -> LGDE (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_035144"
FT VAR_SEQ 517..1593
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_035145"
FT CONFLICT 607
FT /note="R -> P (in Ref. 2; BAC65694)"
FT /evidence="ECO:0000305"
FT CONFLICT 1123..1128
FT /note="Missing (in Ref. 2; BAC65694)"
FT /evidence="ECO:0000305"
FT CONFLICT 1172
FT /note="R -> RGPAPAG (in Ref. 1; AAG42100)"
FT /evidence="ECO:0000305"
FT CONFLICT 1518
FT /note="A -> G (in Ref. 6; AAK52087)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1593 AA; 175012 MW; 90B407A165A4C1F8 CRC64;
MAAATLSFGP EREAEPAKEA RVVGSELVDT YTVYVIQVTD GNHEWTIKHR YSDFHDLHEK
LVAERKIDKS LLPPKKIIGK NSRSLVEKRE RDLEVYLQTL LTTFPDVAPR VLAHFLHFHL
YEVNGVTAAL AEELFEKGEQ LLGAGEVFAI RPLQLYAITE QLQQGKPTCA SGDAKTDLGH
ILDFTCRLKY LKVSGTEGPF GTSNIKEQLL PFDLSIFKSL HQVEISHCDA KHIRGLVTSK
PTLATMSVRF SATSMKEVLA PEASEFDEWE PEGTATLGGP VTAIIPTWQA LTTLDLSHNS
ICEIDESVKL IPKIEYLDLS HNGLRVVDNL QHLYNLVHLD LSYNKLSSLE GVHTKLGNVK
TLNLAGNFLE SLSGLHKLYS LVNVDLRDNR IEQLDEVKSI GSLPCLERLT LLNNPLSIIP
DYRTKVLSQF GERASEICLD DVATTEKELD TVEVLKAIQK AKDVKSKLSN TEKKAGEDFR
LPPAPCIRPG GSPPAAPASA SLPQPILSNQ GIMFVQEEAL ASSLSSTDSL PPEDHRPIAR
ACSDSLESIP AGQVASDDLR DVPGAVGGVS PDHAEPEVQV VPGSGQIIFL PFTCIGYTAT
NQDFIQRLST LIRQAIERQL PAWIEAANQR EEAHGEQGEE EEEEEEEEDV AENRYFEMGP
PDAEEEEGSG QGEEDEEDED EEAEEERLAL EWALGADEDF LLEHIRILKV LWCFLIHVQG
SIRQFAACLV LTDFGIAVFE IPHQESRGSS QHILSSLRFV FCFPHGDLTE FGFLMPELCL
VLKVRHSENT LFIISDAANL HEFHADLRSC FAPQHMAMLC SPILYGSHTT LQEFLRQLLT
FYKVAGGSQE RSQGCFPVYL VYSDKRMVQT PAGDYSGNIE WASCTLCSAV RRSCCAPSEA
VKSAAIPYWL LLTSQHLNVI KADFNPMPNR GTHNCRNRNS FKLSRVPLST VLLDPTRSCT
QPRGAFADGH VLELLVGYRF VTAIFVLPHE KFHFLRVYNQ LRASLQDLKT VVISKNPSAK
PRNQPAKSRA SAEQRLQETP ADAPAPAAVP PTASAPAPAE ALAPDLAPVQ APGEDRGLTS
AEAPAAAEAP AAAEAPAAAE APAAAEAPAA AEAPAAAEAP APAEAPAAAE APAAAEAPAA
AEAPAAAEAP ASAEAPAPNQ APAPARGPAP ARGPAPAGGP APAEALAQAE VPAQYPSERL
IQSTSEENQI PSHLPVCPSL QHIARLRGRA IIDLFHNSIA EVENEELRHL LWSSVVFYQT
PGLEVTACVL LSSKAVYFIL HDGLRRYFSE PLQDFWHQKN TDYNNSPFHV SQCFVLKLSD
LQSVNVGLFD QYFRLTGSSP TQVVTCLTRD SYLTHCFLQH LMLVLSSLER TPSPEPVDKD
FYSEFGDKNT GKMENYELIH SSRVKFTYPS EEEVGDLTYI VAQKMADPAK NPALSILLYI
QAFQVVTPHL GRGRGPLRPK TLLLTSAEIF LLDEDYIHYP LPEFAKEPPQ RDRYRLDDGR
RVRDLDRVLM GYYPYPQALT LVFDDTQGHD LMGSVTLDHF GEMPGGPGRV GQGREVQWQV
FVPSAESREK LISLLARQWE ALCGRELPVE LTG
