NISCH_HUMAN
ID NISCH_HUMAN Reviewed; 1504 AA.
AC Q9Y2I1; C9J245; Q6PGP3; Q6PIB4; Q7L8M3; Q7Z2X6; Q9UES6; Q9UEU4; Q9UFW3;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Nischarin;
DE AltName: Full=Imidazoline receptor 1;
DE Short=I-1;
DE Short=IR1;
DE AltName: Full=Imidazoline receptor antisera-selected protein;
DE Short=hIRAS;
DE AltName: Full=Imidazoline-1 receptor;
DE Short=I1R;
DE AltName: Full=Imidazoline-1 receptor candidate protein;
DE Short=I-1 receptor candidate protein;
DE Short=I1R candidate protein;
GN Name=NISCH; Synonyms=IRAS, KIAA0975;
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), FUNCTION, SUBCELLULAR LOCATION, AND
RP VARIANTS ILE-299 AND VAL-1056.
RX PubMed=10882231; DOI=10.1089/10445490050043290;
RA Piletz J.E., Ivanov T.R., Sharp J.D., Ernsberger P., Chang C.-H.,
RA Pickard R.T., Gold G., Roth B., Zhu H., Jones J.C., Baldwin J., Reis D.J.;
RT "Imidazoline receptor antisera-selected (IRAS) cDNA: cloning and
RT characterization.";
RL DNA Cell Biol. 19:319-329(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3 AND 4), FUNCTION, TISSUE
RP SPECIFICITY, AND VARIANT ILE-299.
RX PubMed=15028621; DOI=10.1196/annals.1304.056;
RA Piletz J.E., Deleersnijder W., Roth B.L., Ernsberger P., Zhu H.,
RA Ziegler D.;
RT "IRAS splice variants.";
RL Ann. N. Y. Acad. Sci. 1009:419-426(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS ILE-299
RP AND VAL-1056.
RC TISSUE=Brain;
RX PubMed=10231032; DOI=10.1093/dnares/6.1.63;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:63-70(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS ILE-299
RP AND VAL-1056.
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT VAL-1056.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS ILE-299 AND
RP VAL-1056.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS ILE-299
RP AND VAL-1056.
RC TISSUE=Eye, PNS, and Testis;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 469-1063 (ISOFORM 1), TISSUE SPECIFICITY, AND
RP VARIANT VAL-1056.
RC TISSUE=Hippocampus;
RX PubMed=9851558; DOI=10.1016/s0165-1838(98)00094-0;
RA Ivanov T.R., Jones J.C., Dontenwill M., Bousquet P., Piletz J.E.;
RT "Characterization of a partial cDNA clone detected by imidazoline receptor-
RT selective antisera.";
RL J. Auton. Nerv. Syst. 72:98-110(1998).
RN [10]
RP INTERACTION WITH GRB2; IRS4 AND PIK3R1, AND SUBCELLULAR LOCATION.
RX PubMed=11912194; DOI=10.1074/jbc.m111838200;
RA Sano H., Liu S.C.H., Lane W.S., Piletz J.E., Lienhard G.E.;
RT "Insulin receptor substrate 4 associates with the protein IRAS.";
RL J. Biol. Chem. 277:19439-19447(2002).
RN [11]
RP FUNCTION.
RX PubMed=15028619; DOI=10.1196/annals.1304.054;
RA Dontenwill M., Piletz J.E., Chen M., Baldwin J., Pascal G., Ronde P.,
RA Dupuy L., Greney H., Takeda K., Bousquetd P.;
RT "IRAS is an anti-apoptotic protein.";
RL Ann. N. Y. Acad. Sci. 1009:400-412(2003).
RN [12]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=12868002; DOI=10.1038/sj.cdd.4401275;
RA Dontenwill M., Pascal G., Piletz J.E., Chen M., Baldwin J., Ronde P.,
RA Dupuy L., Urosevic D., Greney H., Takeda K., Bousquet P.;
RT "IRAS, the human homologue of Nischarin, prolongs survival of transfected
RT PC12 cells.";
RL Cell Death Differ. 10:933-935(2003).
RN [13]
RP FUNCTION, SUBUNIT, INTERACTION WITH ITGA5, MUTAGENESIS OF ARG-49 AND
RP TYR-50, AND SUBCELLULAR LOCATION.
RX PubMed=15475348; DOI=10.1074/jbc.m411315200;
RA Lim K.-P., Hong W.;
RT "Human Nischarin/imidazoline receptor antisera-selected protein is targeted
RT to the endosomes by a combined action of a PX domain and a coiled-coil
RT region.";
RL J. Biol. Chem. 279:54770-54782(2004).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1284, AND IDENTIFICATION BY
RP MASS 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 [16]
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 [17]
RP INTERACTION WITH STK11, AND SUBCELLULAR LOCATION.
RX PubMed=23572524; DOI=10.1074/jbc.m112.418103;
RA Jain P., Baranwal S., Dong S., Struckhoff A.P., Worthylake R.A.,
RA Alahari S.K.;
RT "Integrin-binding protein nischarin interacts with tumor suppressor liver
RT kinase B1 (LKB1) to regulate cell migration of breast epithelial cells.";
RL J. Biol. Chem. 288:15495-15509(2013).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1022 AND SER-1284, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [19]
RP X-RAY CRYSTALLOGRAPHY (2.27 ANGSTROMS) OF 18-124.
RG Structural genomics consortium (SGC);
RT "Crystal structure of nischarin PX-domain.";
RL Submitted (OCT-2010) to the PDB data bank.
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 (By
CC similarity). Suppresses Rac1-stimulated cell migration by interacting
CC with PAK1 and inhibiting its kinase activity (By similarity). Also
CC blocks Pak-independent Rac signaling by interacting with RAC1 and
CC inhibiting Rac1-stimulated NF-kB response element and cyclin D1
CC promoter activation (By similarity). Inhibits also LIMK1 kinase
CC activity by reducing LIMK1 'Tyr-508' phosphorylation (By similarity).
CC Inhibits Rac-induced cell migration and invasion in breast and colon
CC epithelial cells (By similarity). Inhibits lamellipodia formation, when
CC overexpressed (By similarity). Plays a role in protection against
CC apoptosis. Involved in association with IRS4 in the enhancement of
CC insulin activation of MAPK1 and MAPK3. When overexpressed, induces a
CC redistribution of cell surface ITGA5 integrin to intracellular
CC endosomal structures. {ECO:0000250, ECO:0000269|PubMed:10882231,
CC ECO:0000269|PubMed:12868002, ECO:0000269|PubMed:15028619,
CC ECO:0000269|PubMed:15028621, ECO:0000269|PubMed:15475348}.
CC -!- SUBUNIT: Homooligomer. Interacts with GRB2. Interacts with PIK3R1;
CC probably associates with the PI3-kinase complex. Interacts with IRS4.
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 (By
CC similarity). Interacts with LIMK1 (via PDZ and kinase domain); this
CC interaction is direct (By similarity). Interacts with LIMK2; this
CC interaction depends on LIMK2 activity (By similarity). Interacts with
CC RAC1 (activated state) (By similarity). Interacts with STK11; this
CC interaction may increase STK11 activity. {ECO:0000250,
CC ECO:0000269|PubMed:11912194, ECO:0000269|PubMed:15475348,
CC ECO:0000269|PubMed:23572524}.
CC -!- INTERACTION:
CC Q9Y2I1; Q9Y2I1: NISCH; NbExp=2; IntAct=EBI-2688731, EBI-2688731;
CC Q9Y2I1; P51151: RAB9A; NbExp=8; IntAct=EBI-2688731, EBI-4401353;
CC Q9Y2I1; P61107: Rab14; Xeno; NbExp=9; IntAct=EBI-2688731, EBI-917845;
CC Q9Y2I1; P05714: Rab4a; Xeno; NbExp=3; IntAct=EBI-2688731, EBI-9029299;
CC -!- SUBCELLULAR LOCATION: Cell membrane. Cytoplasm. Early endosome.
CC Recycling endosome. Note=Enriched in the early/sorting and recycling
CC endosomes. Colocalized in early/sorting endosomes with EEA1 and SNX2
CC and in recycling endosomes with transferrin receptor. Detected in the
CC perinuclear region partially associated with punctate structures (By
CC similarity). Colocalizes with PAK1 in cytoplasm, vesicular structures
CC in the perinuclear area and membrane ruffles (By similarity).
CC Colocalizes with RAC1 in the cytoplasm and vesicles structures (By
CC similarity). Colocalized with MAPK1 and MAPK3 in RVLM neurons (By
CC similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=IRAS-1, IRAS-M;
CC IsoId=Q9Y2I1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y2I1-2; Sequence=VSP_035131;
CC Name=3; Synonyms=IRAS-L;
CC IsoId=Q9Y2I1-3; Sequence=VSP_035132, VSP_035135;
CC Name=4; Synonyms=IRAS-S;
CC IsoId=Q9Y2I1-4; Sequence=VSP_035133, VSP_035134;
CC -!- TISSUE SPECIFICITY: Isoform 1, isoform 3 and isoform 4 are expressed in
CC brain. Isoform 1 is expressed in endocrine tissues.
CC {ECO:0000269|PubMed:15028621, ECO:0000269|PubMed:9851558}.
CC -!- DOMAIN: Both the presence of the PX domain and the coiled coil region
CC are necessary for its endosomal targeting.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA76819.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF082516; AAC33104.1; -; mRNA.
DR EMBL; AB023192; BAA76819.1; ALT_INIT; mRNA.
DR EMBL; AK291398; BAF84087.1; -; mRNA.
DR EMBL; AL117432; CAB55920.1; -; mRNA.
DR EMBL; AC006208; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471055; EAW65229.1; -; Genomic_DNA.
DR EMBL; BC038102; AAH38102.1; -; mRNA.
DR EMBL; BC054494; AAH54494.1; -; mRNA.
DR EMBL; BC056900; AAH56900.1; -; mRNA.
DR EMBL; AF058290; AAC33321.1; -; mRNA.
DR CCDS; CCDS33767.1; -. [Q9Y2I1-1]
DR CCDS; CCDS63651.1; -. [Q9Y2I1-4]
DR CCDS; CCDS63652.1; -. [Q9Y2I1-3]
DR PIR; T17230; T17230.
DR RefSeq; NP_001263222.1; NM_001276293.1.
DR RefSeq; NP_001263223.1; NM_001276294.1. [Q9Y2I1-4]
DR RefSeq; NP_009115.2; NM_007184.3. [Q9Y2I1-1]
DR PDB; 3P0C; X-ray; 2.27 A; A/B=18-124.
DR PDBsum; 3P0C; -.
DR AlphaFoldDB; Q9Y2I1; -.
DR SMR; Q9Y2I1; -.
DR BioGRID; 116358; 158.
DR IntAct; Q9Y2I1; 41.
DR MINT; Q9Y2I1; -.
DR STRING; 9606.ENSP00000339958; -.
DR BindingDB; Q9Y2I1; -.
DR ChEMBL; CHEMBL3923; -.
DR DrugBank; DB08838; Agmatine.
DR DrugBank; DB09242; Moxonidine.
DR DrugBank; DB15133; Tepotinib.
DR DrugBank; DB00697; Tizanidine.
DR DrugCentral; Q9Y2I1; -.
DR iPTMnet; Q9Y2I1; -.
DR PhosphoSitePlus; Q9Y2I1; -.
DR BioMuta; NISCH; -.
DR DMDM; 296439287; -.
DR EPD; Q9Y2I1; -.
DR jPOST; Q9Y2I1; -.
DR MassIVE; Q9Y2I1; -.
DR MaxQB; Q9Y2I1; -.
DR PaxDb; Q9Y2I1; -.
DR PeptideAtlas; Q9Y2I1; -.
DR PRIDE; Q9Y2I1; -.
DR ProteomicsDB; 85789; -. [Q9Y2I1-1]
DR ProteomicsDB; 85790; -. [Q9Y2I1-2]
DR ProteomicsDB; 85791; -. [Q9Y2I1-3]
DR ProteomicsDB; 85792; -. [Q9Y2I1-4]
DR Antibodypedia; 14512; 109 antibodies from 25 providers.
DR DNASU; 11188; -.
DR Ensembl; ENST00000345716.9; ENSP00000339958.4; ENSG00000010322.16. [Q9Y2I1-1]
DR Ensembl; ENST00000420808.2; ENSP00000392484.2; ENSG00000010322.16. [Q9Y2I1-4]
DR Ensembl; ENST00000479054.5; ENSP00000418232.1; ENSG00000010322.16. [Q9Y2I1-1]
DR GeneID; 11188; -.
DR KEGG; hsa:11188; -.
DR MANE-Select; ENST00000345716.9; ENSP00000339958.4; NM_007184.4; NP_009115.3.
DR UCSC; uc003ded.5; human. [Q9Y2I1-1]
DR CTD; 11188; -.
DR DisGeNET; 11188; -.
DR GeneCards; NISCH; -.
DR HGNC; HGNC:18006; NISCH.
DR HPA; ENSG00000010322; Low tissue specificity.
DR MIM; 615507; gene.
DR neXtProt; NX_Q9Y2I1; -.
DR OpenTargets; ENSG00000010322; -.
DR PharmGKB; PA31635; -.
DR VEuPathDB; HostDB:ENSG00000010322; -.
DR eggNOG; KOG1259; Eukaryota.
DR GeneTree; ENSGT00940000156494; -.
DR HOGENOM; CLU_252294_0_0_1; -.
DR InParanoid; Q9Y2I1; -.
DR OMA; PIDKDFY; -.
DR OrthoDB; 320361at2759; -.
DR PhylomeDB; Q9Y2I1; -.
DR TreeFam; TF320547; -.
DR PathwayCommons; Q9Y2I1; -.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9696264; RND3 GTPase cycle.
DR Reactome; R-HSA-9696270; RND2 GTPase cycle.
DR SignaLink; Q9Y2I1; -.
DR BioGRID-ORCS; 11188; 64 hits in 1088 CRISPR screens.
DR ChiTaRS; NISCH; human.
DR GeneWiki; NISCH; -.
DR GenomeRNAi; 11188; -.
DR Pharos; Q9Y2I1; Tclin.
DR PRO; PR:Q9Y2I1; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9Y2I1; protein.
DR Bgee; ENSG00000010322; Expressed in middle temporal gyrus and 203 other tissues.
DR ExpressionAtlas; Q9Y2I1; baseline and differential.
DR Genevisible; Q9Y2I1; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:BHF-UCL.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0045171; C:intercellular bridge; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005178; F:integrin binding; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0030336; P:negative regulation of cell migration; IEA:Ensembl.
DR GO; GO:0016601; P:Rac protein signal transduction; IEA:Ensembl.
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; IPR032675; LRR_dom_sf.
DR InterPro; IPR037904; Nischarin_PX.
DR InterPro; IPR001683; PX_dom.
DR InterPro; IPR036871; PX_dom_sf.
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 3D-structure; Acetylation; Alternative splicing; Apoptosis; Cell membrane;
KW Coiled coil; Cytoplasm; Endosome; Leucine-rich repeat; Membrane;
KW Phosphoprotein; Receptor; Reference proteome; Repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..1504
FT /note="Nischarin"
FT /id="PRO_0000348265"
FT DOMAIN 11..121
FT /note="PX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00147"
FT REPEAT 288..309
FT /note="LRR 1"
FT REPEAT 311..332
FT /note="LRR 2"
FT REPEAT 333..354
FT /note="LRR 3"
FT REPEAT 356..377
FT /note="LRR 4"
FT REPEAT 378..399
FT /note="LRR 5"
FT REPEAT 403..424
FT /note="LRR 6"
FT REGION 2..133
FT /note="Necessary for binding to phosphoinositide-3-P; not
FT sufficient for targeting to endosomes"
FT REGION 120..695
FT /note="Necessary for homooligomerization and targeting to
FT endosomes"
FT REGION 245..869
FT /note="Interaction with PAK1"
FT /evidence="ECO:0000250"
FT REGION 463..501
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 524..547
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 554..573
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 628..687
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 660..869
FT /note="Interaction with LIMK"
FT /evidence="ECO:0000250"
FT REGION 709..807
FT /note="Interaction with ITGA5"
FT /evidence="ECO:0000250"
FT REGION 1016..1104
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 634..695
FT /evidence="ECO:0000255"
FT COMPBIAS 463..477
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 483..501
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 633..651
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 661..687
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 541
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80TM9"
FT MOD_RES 543
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80TM9"
FT MOD_RES 546
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80TM9"
FT MOD_RES 1022
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1282
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q80TM9"
FT MOD_RES 1284
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..511
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_035131"
FT VAR_SEQ 511..583
FT /note="IMFVQEEALASSLSSTDSLTPEHQPIAQGCSDSLESIPAGQAASDDLRDVPG
FT AVGGASPEHAEPEVQVVPGSG -> NRVCTLLLVEPHSPAWAPWLGWGWGRGASTCFQQ
FT GTQGGGQCLLQAGPRGGTHGRGAWPDASCCLLGEDSQLL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15028621"
FT /id="VSP_035132"
FT VAR_SEQ 512..515
FT /note="MFVQ -> LGDE (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15028621"
FT /id="VSP_035133"
FT VAR_SEQ 516..1504
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15028621"
FT /id="VSP_035134"
FT VAR_SEQ 584..1504
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15028621"
FT /id="VSP_035135"
FT VARIANT 299
FT /note="V -> I (in dbSNP:rs9856575)"
FT /evidence="ECO:0000269|PubMed:10231032,
FT ECO:0000269|PubMed:10882231, ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15028621, ECO:0000269|PubMed:15489334,
FT ECO:0000269|Ref.7"
FT /id="VAR_046130"
FT VARIANT 1056
FT /note="A -> V (in dbSNP:rs887515)"
FT /evidence="ECO:0000269|PubMed:10231032,
FT ECO:0000269|PubMed:10882231, ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17974005,
FT ECO:0000269|PubMed:9851558, ECO:0000269|Ref.7"
FT /id="VAR_046131"
FT MUTAGEN 49
FT /note="R->A: Inhibits targeting to endosomes."
FT /evidence="ECO:0000269|PubMed:15475348"
FT MUTAGEN 50
FT /note="Y->A: Inhibits targeting to endosomes."
FT /evidence="ECO:0000269|PubMed:15475348"
FT CONFLICT 927
FT /note="M -> I (in Ref. 8; AAH56900)"
FT /evidence="ECO:0000305"
FT CONFLICT 1023
FT /note="P -> A (in Ref. 3; BAA76819)"
FT /evidence="ECO:0000305"
FT CONFLICT 1123
FT /note="S -> P (in Ref. 8; AAH38102)"
FT /evidence="ECO:0000305"
FT CONFLICT 1382
FT /note="L -> F (in Ref. 8; AAH54494)"
FT /evidence="ECO:0000305"
FT STRAND 18..25
FT /evidence="ECO:0007829|PDB:3P0C"
FT STRAND 27..30
FT /evidence="ECO:0007829|PDB:3P0C"
FT STRAND 32..38
FT /evidence="ECO:0007829|PDB:3P0C"
FT STRAND 43..49
FT /evidence="ECO:0007829|PDB:3P0C"
FT HELIX 50..62
FT /evidence="ECO:0007829|PDB:3P0C"
FT HELIX 85..101
FT /evidence="ECO:0007829|PDB:3P0C"
FT STRAND 105..107
FT /evidence="ECO:0007829|PDB:3P0C"
FT HELIX 109..116
FT /evidence="ECO:0007829|PDB:3P0C"
SQ SEQUENCE 1504 AA; 166629 MW; 7761C7DA1FDC4E53 CRC64;
MATARTFGPE REAEPAKEAR VVGSELVDTY TVYIIQVTDG SHEWTVKHRY SDFHDLHEKL
VAERKIDKNL LPPKKIIGKN SRSLVEKREK DLEVYLQKLL AAFPGVTPRV LAHFLHFHFY
EINGITAALA EELFEKGEQL LGAGEVFAIG PLQLYAVTEQ LQQGKPTCAS GDAKTDLGHI
LDFTCRLKYL KVSGTEGPFG TSNIQEQLLP FDLSIFKSLH QVEISHCDAK HIRGLVASKP
TLATLSVRFS ATSMKEVLVP EASEFDEWEP EGTTLEGPVT AVIPTWQALT TLDLSHNSVS
EIDESVKLIP KIEFLDLSHN GLLVVDNLQH LYNLVHLDLS YNKLSSLEGL HTKLGNIKTL
NLAGNLLESL SGLHKLYSLV NLDLRDNRIE QMEEVRSIGS LPCLEHVSLL NNPLSIIPDY
RTKVLAQFGE RASEVCLDDT VTTEKELDTV EVLKAIQKAK EVKSKLSNPE KKGGEDSRLS
AAPCIRPSSS PPTVAPASAS LPQPILSNQG IMFVQEEALA SSLSSTDSLT PEHQPIAQGC
SDSLESIPAG QAASDDLRDV PGAVGGASPE HAEPEVQVVP GSGQIIFLPF TCIGYTATNQ
DFIQRLSTLI RQAIERQLPA WIEAANQREE GQGEQGEEED EEEEEEEDVA ENRYFEMGPP
DVEEEEGGGQ GEEEEEEEED EEAEEERLAL EWALGADEDF LLEHIRILKV LWCFLIHVQG
SIRQFAACLV LTDFGIAVFE IPHQESRGSS QHILSSLRFV FCFPHGDLTE FGFLMPELCL
VLKVRHSENT LFIISDAANL HEFHADLRSC FAPQHMAMLC SPILYGSHTS LQEFLRQLLT
FYKVAGGCQE RSQGCFPVYL VYSDKRMVQT AAGDYSGNIE WASCTLCSAV RRSCCAPSEA
VKSAAIPYWL LLTPQHLNVI KADFNPMPNR GTHNCRNRNS FKLSRVPLST VLLDPTRSCT
QPRGAFADGH VLELLVGYRF VTAIFVLPHE KFHFLRVYNQ LRASLQDLKT VVIAKTPGTG
GSPQGSFADG QPAERRASND QRPQEVPAEA LAPAPAEVPA PAPAAASASG PAKTPAPAEA
STSALVPEET PVEAPAPPPA EAPAQYPSEH LIQATSEENQ IPSHLPACPS LRHVASLRGS
AIIELFHSSI AEVENEELRH LMWSSVVFYQ TPGLEVTACV LLSTKAVYFV LHDGLRRYFS
EPLQDFWHQK NTDYNNSPFH ISQCFVLKLS DLQSVNVGLF DQHFRLTGST PMQVVTCLTR
DSYLTHCFLQ HLMVVLSSLE RTPSPEPVDK DFYSEFGNKT TGKMENYELI HSSRVKFTYP
SEEEIGDLTF TVAQKMAEPE KAPALSILLY VQAFQVGMPP PGCCRGPLRP KTLLLTSSEI
FLLDEDCVHY PLPEFAKEPP QRDRYRLDDG RRVRDLDRVL MGYQTYPQAL TLVFDDVQGH
DLMGSVTLDH FGEVPGGPAR ASQGREVQWQ VFVPSAESRE KLISLLARQW EALCGRELPV
ELTG
