NISCH_RAT
ID NISCH_RAT Reviewed; 1502 AA.
AC Q4G017;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 02-SEP-2008, sequence version 2.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Nischarin;
DE AltName: Full=Imidazoline receptor 1;
DE Short=I-1;
DE Short=IR1;
DE AltName: Full=Imidazoline-1 receptor;
DE Short=I1R;
GN Name=Nisch;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1287-1502.
RC TISSUE=Spleen;
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 [3]
RP FUNCTION.
RX PubMed=11274989; DOI=10.1016/s0014-2999(01)00834-2;
RA Zhang J., El-Mas M.M., Abdel-Rahman A.A.;
RT "Imidazoline I(1) receptor-induced activation of phosphatidylcholine-
RT specific phospholipase C elicits mitogen-activated protein kinase
RT phosphorylation in PC12 cells.";
RL Eur. J. Pharmacol. 415:117-125(2001).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15901801; DOI=10.1124/jpet.105.087510;
RA Zhang J., Abdel-Rahman A.A.;
RT "Mitogen-activated protein kinase phosphorylation in the rostral
RT ventrolateral medulla plays a key role in imidazoline (I1)-receptor-
RT mediated hypotension.";
RL J. Pharmacol. Exp. Ther. 314:945-952(2005).
RN [5]
RP FUNCTION.
RX PubMed=17254010; DOI=10.1111/j.1471-4159.2006.04413.x;
RA Sun Z., Chang C.-H., Ernsberger P.;
RT "Identification of IRAS/Nischarin as an I1-imidazoline receptor in PC12 rat
RT pheochromocytoma cells.";
RL J. Neurochem. 101:99-108(2007).
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17940198; DOI=10.1124/jpet.107.129049;
RA Zhang J., Abdel-Rahman A.A.;
RT "Inhibition of nischarin expression attenuates rilmenidine-evoked
RT hypotension and phosphorylated extracellular signal-regulated kinase 1/2
RT production in the rostral ventrolateral medulla of rats.";
RL J. Pharmacol. Exp. Ther. 324:72-78(2008).
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. Blocking its activation with efaroxan
CC abolished rilmenidine-induced mitogen-activated protein kinase
CC phosphorylation in RVLM neurons. Acts as a modulator of Rac-regulated
CC signal transduction pathways (By similarity). Suppresses Rac1-
CC stimulated cell migration by interacting with PAK1 and inhibiting its
CC kinase activity (By similarity). Also blocks Pak-independent Rac
CC signaling by interacting with RAC1 and inhibiting Rac1-stimulated NF-kB
CC response element and cyclin D1 promoter activation (By similarity).
CC Inhibits also LIMK1 kinase activity by reducing LIMK1 'Tyr-508'
CC phosphorylation (By similarity). Inhibits Rac-induced cell migration
CC and invasion in breast and colon epithelial cells (By similarity).
CC Inhibits lamellipodia formation, when overexpressed (By similarity).
CC Plays a role in protection against apoptosis (By similarity). Involved
CC in association with IRS4 in the enhancement of insulin activation of
CC MAPK1 and MAPK3 (By similarity). When overexpressed, induces a
CC redistribution of cell surface ITGA5 integrin to intracellular
CC endosomal structures (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:11274989, ECO:0000269|PubMed:15901801,
CC ECO:0000269|PubMed:17254010, ECO:0000269|PubMed:17940198}.
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.
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) (By similarity).
CC Interacts with STK11; this interaction may increase STK11 activity (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}. Cytoplasm
CC {ECO:0000250}. Early endosome {ECO:0000250}. Recycling endosome
CC {ECO:0000250}. 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.
CC Colocalizes with PAK1 in cytoplasm, vesicular structures in the
CC perinuclear area and membrane ruffles. Colocalizes with RAC1 in the
CC cytoplasm and vesicles structures (By similarity). Colocalized with
CC MAPK1 and MAPK3 in RVLM neurons. {ECO:0000250,
CC ECO:0000269|PubMed:15901801, ECO:0000269|PubMed:17940198}.
CC -!- DOMAIN: Both the presence of the PX domain and the coiled coil region
CC are necessary for its endosomal targeting. {ECO:0000250}.
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DR EMBL; AABR03100261; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC098837; AAH98837.1; -; mRNA.
DR AlphaFoldDB; Q4G017; -.
DR SMR; Q4G017; -.
DR IntAct; Q4G017; 3.
DR MINT; Q4G017; -.
DR STRING; 10116.ENSRNOP00000032758; -.
DR BindingDB; Q4G017; -.
DR ChEMBL; CHEMBL5221; -.
DR DrugCentral; Q4G017; -.
DR iPTMnet; Q4G017; -.
DR PhosphoSitePlus; Q4G017; -.
DR jPOST; Q4G017; -.
DR PaxDb; Q4G017; -.
DR PRIDE; Q4G017; -.
DR UCSC; RGD:1306950; rat.
DR RGD; 1306950; Nisch.
DR VEuPathDB; HostDB:ENSRNOG00000018823; -.
DR eggNOG; KOG1259; Eukaryota.
DR HOGENOM; CLU_252294_0_0_1; -.
DR InParanoid; Q4G017; -.
DR OMA; PIDKDFY; -.
DR Reactome; R-RNO-9013149; RAC1 GTPase cycle.
DR Reactome; R-RNO-9696264; RND3 GTPase cycle.
DR Reactome; R-RNO-9696270; RND2 GTPase cycle.
DR PRO; PR:Q4G017; -.
DR Proteomes; UP000002494; Chromosome 16.
DR Bgee; ENSRNOG00000018823; Expressed in frontal cortex and 19 other tissues.
DR Genevisible; Q4G017; RN.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0005178; F:integrin binding; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0006006; P:glucose metabolic process; IMP:RGD.
DR GO; GO:0030336; P:negative regulation of cell migration; ISO:RGD.
DR GO; GO:0048243; P:norepinephrine secretion; IMP:RGD.
DR GO; GO:0016601; P:Rac protein signal transduction; ISO:RGD.
DR GO; GO:0008217; P:regulation of blood pressure; IMP:RGD.
DR GO; GO:0032228; P:regulation of synaptic transmission, GABAergic; IMP:RGD.
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; IPR003591; Leu-rich_rpt_typical-subtyp.
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; SM00369; LRR_TYP; 4.
DR SMART; SM00312; PX; 1.
DR SUPFAM; SSF64268; SSF64268; 1.
DR PROSITE; PS51450; LRR; 6.
DR PROSITE; PS50195; PX; 1.
PE 2: Evidence at transcript level;
KW Apoptosis; Cell membrane; Coiled coil; Cytoplasm; Endosome;
KW Leucine-rich repeat; Membrane; Phosphoprotein; Receptor;
KW Reference proteome; Repeat.
FT CHAIN 1..1502
FT /note="Nischarin"
FT /id="PRO_0000348267"
FT DOMAIN 12..122
FT /note="PX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00147"
FT REPEAT 289..310
FT /note="LRR 1"
FT REPEAT 312..333
FT /note="LRR 2"
FT REPEAT 334..355
FT /note="LRR 3"
FT REPEAT 357..378
FT /note="LRR 4"
FT REPEAT 379..400
FT /note="LRR 5"
FT REPEAT 404..425
FT /note="LRR 6"
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..693
FT /note="Necessary for homooligomerization and targeting to
FT endosomes"
FT /evidence="ECO:0000250"
FT REGION 246..867
FT /note="Interaction with PAK1"
FT /evidence="ECO:0000250"
FT REGION 481..501
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 524..549
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 628..684
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 659..867
FT /note="Interaction with LIMK"
FT /evidence="ECO:0000250"
FT REGION 707..805
FT /note="Interaction with ITGA5"
FT /evidence="ECO:0000250"
FT REGION 1014..1101
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 623..692
FT /evidence="ECO:0000255"
FT COMPBIAS 635..650
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 660..684
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 542
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80TM9"
FT MOD_RES 544
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80TM9"
FT MOD_RES 547
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80TM9"
FT MOD_RES 1280
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q80TM9"
FT MOD_RES 1282
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2I1"
SQ SEQUENCE 1502 AA; 166503 MW; E89025E32450ECF8 CRC64;
MAAATLSFGP EREAEPAKEA RVVGSELVDT YTVYVIQVTD GNHEWTIKHR YSDFHDLHEK
LVAERKIDKT LLPPKKIIGK NSRSLVEKRE KDLEVYLQTL LKTFPDVAPR VLAHFLHFHL
YEINGVTAAL AEELFEKGEQ LLGAGEVFAI RPLQLYAITE QLQQGKPTCA SGDAKTDLGH
ILDFTCRLKY LKVSGTEGPF GTSNIREQLL PFDLSIFKSL HQVEMSHCDA KHVRGLVTSK
PTLATMSVRF SAASMKEVLV PEASEFDEWE PEGTTLGGPV TAVIPTWQAL TTLDLSHNSI
SEIDESVKLI PKIEYLDLSH NGVLVVDNLQ HLYNLVHLDL SYNKLSSLEG VHTKLGNVKT
LNLAGNFLER LSGLHKLYSL VNLDLRDNRI EQLDEVKSIG NLPCLEHVAL LNNPLSIIPD
YRTKVLSQFG ERASEICLDD VATTEKELDT VEVLKAIQKA KDVKSKLSST EKKVGEDFRL
PTAPCIRPSS SPPTAVPTSA SLPQPILSNQ GIMFVQEEAL ASSLSSTDSL PPDDRPIAQA
CSNSMGSLPT GQVAAEDLRD LPGAVGGVSP DHAEPEVQVV PGSGQIIFLP FTCIGYTATN
QDFIQRLSTL IRQAIERQLP AWIEAANQRE EAHGEQGEEE EEEEEEDVAE SRYFEMGPPD
AEEEEGSGQG EEDEEDEDEE AEEERLALEW ALGADEDFLL EHIRILKVLW CFLIHVQGSI
RQFAACLVLT DFGIAVFEIP HQESRGSSQH ILSSLRFVFC FPHGDLTEFG FLMPELCLVL
KVRHSENTLF IISDAANLHE FHADLRSCFA PQHMAMLCSP ILYGSHTSLQ EFLRQLLTFY
KVAGGSQERS QGCFPVYLVY SDKRMVQTAA GDYSGNIEWA SCTLCSAVRR SCCAPSEAVK
SAAIPYWLLL TSQHLNVIKA DFNPMPSRGT HNCRNRNSFK LSRVPLSTVL LDPTRSCTQP
RGAFADGHVL ELLVGYRFVT AIFVLPHEKF HFLRVYNQLR ASLKDLKTVV IAKNPSARPR
TQGPLAGGQP AKSRVSAEQR LQETPAEAPA PAPAAAESAA EAPAAAEASA PAGAPAPAGA
PAPAGAPAGA QAPAPAQAEV PAQYPSERLI QSTSEENQIP SHLPVCPSLQ HIARLRGRAI
IDLFHSSIAE VENEELRHLL WSSVVFYQTP GLEVTACVLL STKAVYFILH DGLRRYFSEP
LQDFWHQKNT DYNNSPFHIS QCFVLKLSDL QSVNVGLFDQ YFRLTGSSPT QVVTCLTRDS
YLTHCFLQHL MLVLSSLERT PSPEPIDKDF YSEFGDKNTG KMENYELIHS SRVKFTYPSE
EEVGDLTYVV AQKMADPAKN PALSILLYIQ AFQVITPQLG RGRGPLRPKT LLLTSAEIFL
LDEDYIHYPL PEFAKEPPQR DRYRLDDGRR VRDLDRVLMG YNPYPQALTL VFDDTQGHDL
MGSVTLDHFG EMPGGPGRAG QGREVQWQVF VPSAESREKL ISLLARQWEA LCGRELPVEL
TG
