Q4G017 · NISCH_RAT
- ProteinNischarin
- GeneNisch
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1502 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
Function
function
Acts either as the functional imidazoline-1 receptor (I1R) candidate or as a membrane-associated mediator of the I1R signaling. Binds numerous imidazoline ligands that induces initiation of cell-signaling cascades triggering to cell survival, growth and migration. Its activation by the agonist rilmenidine induces an increase in phosphorylation of mitogen-activated protein kinases MAPK1 and MAPK3 in rostral ventrolateral medulla (RVLM) neurons that exhibited rilmenidine-evoked hypotension. Blocking its activation with efaroxan abolished rilmenidine-induced mitogen-activated protein kinase phosphorylation in RVLM neurons. Acts as a modulator of Rac-regulated signal transduction pathways (By similarity).
Suppresses Rac1-stimulated cell migration by interacting with PAK1 and inhibiting its kinase activity (By similarity).
Also blocks Pak-independent Rac signaling by interacting with RAC1 and inhibiting Rac1-stimulated NF-kB response element and cyclin D1 promoter activation (By similarity).
Inhibits also LIMK1 kinase activity by reducing LIMK1 'Tyr-508' phosphorylation (By similarity).
Inhibits Rac-induced cell migration and invasion in breast and colon epithelial cells (By similarity).
Inhibits lamellipodia formation, when overexpressed (By similarity).
Plays a role in protection against apoptosis (By similarity).
Involved in association with IRS4 in the enhancement of insulin activation of MAPK1 and MAPK3 (By similarity).
When overexpressed, induces a redistribution of cell surface ITGA5 integrin to intracellular endosomal structures (By similarity).
Suppresses Rac1-stimulated cell migration by interacting with PAK1 and inhibiting its kinase activity (By similarity).
Also blocks Pak-independent Rac signaling by interacting with RAC1 and inhibiting Rac1-stimulated NF-kB response element and cyclin D1 promoter activation (By similarity).
Inhibits also LIMK1 kinase activity by reducing LIMK1 'Tyr-508' phosphorylation (By similarity).
Inhibits Rac-induced cell migration and invasion in breast and colon epithelial cells (By similarity).
Inhibits lamellipodia formation, when overexpressed (By similarity).
Plays a role in protection against apoptosis (By similarity).
Involved in association with IRS4 in the enhancement of insulin activation of MAPK1 and MAPK3 (By similarity).
When overexpressed, induces a redistribution of cell surface ITGA5 integrin to intracellular endosomal structures (By similarity).
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | early endosome | |
Cellular Component | plasma membrane | |
Cellular Component | recycling endosome | |
Molecular Function | alpha-tubulin binding | |
Molecular Function | dynein heavy chain binding | |
Molecular Function | identical protein binding | |
Molecular Function | integrin binding | |
Molecular Function | phosphatidylinositol binding | |
Biological Process | actin cytoskeleton organization | |
Biological Process | apoptotic process | |
Biological Process | glucose metabolic process | |
Biological Process | negative regulation of cell migration | |
Biological Process | norepinephrine secretion | |
Biological Process | outer dynein arm assembly | |
Biological Process | Rac protein signal transduction | |
Biological Process | regulation of blood pressure | |
Biological Process | regulation of synaptic transmission, GABAergic |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameNischarin
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionQ4G017
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Enriched in the early/sorting and recycling endosomes. Colocalized in early/sorting endosomes with EEA1 and SNX2 and in recycling endosomes with transferrin receptor. Detected in the perinuclear region partially associated with punctate structures. Colocalizes with PAK1 in cytoplasm, vesicular structures in the perinuclear area and membrane ruffles. Colocalizes with RAC1 in the cytoplasm and vesicles structures (By similarity).
Colocalized with MAPK1 and MAPK3 in RVLM neurons
Colocalized with MAPK1 and MAPK3 in RVLM neurons
Keywords
- Cellular component
Phenotypes & Variants
Chemistry
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000348267 | 1-1502 | Nischarin | |||
Sequence: MAAATLSFGPEREAEPAKEARVVGSELVDTYTVYVIQVTDGNHEWTIKHRYSDFHDLHEKLVAERKIDKTLLPPKKIIGKNSRSLVEKREKDLEVYLQTLLKTFPDVAPRVLAHFLHFHLYEINGVTAALAEELFEKGEQLLGAGEVFAIRPLQLYAITEQLQQGKPTCASGDAKTDLGHILDFTCRLKYLKVSGTEGPFGTSNIREQLLPFDLSIFKSLHQVEMSHCDAKHVRGLVTSKPTLATMSVRFSAASMKEVLVPEASEFDEWEPEGTTLGGPVTAVIPTWQALTTLDLSHNSISEIDESVKLIPKIEYLDLSHNGVLVVDNLQHLYNLVHLDLSYNKLSSLEGVHTKLGNVKTLNLAGNFLERLSGLHKLYSLVNLDLRDNRIEQLDEVKSIGNLPCLEHVALLNNPLSIIPDYRTKVLSQFGERASEICLDDVATTEKELDTVEVLKAIQKAKDVKSKLSSTEKKVGEDFRLPTAPCIRPSSSPPTAVPTSASLPQPILSNQGIMFVQEEALASSLSSTDSLPPDDRPIAQACSNSMGSLPTGQVAAEDLRDLPGAVGGVSPDHAEPEVQVVPGSGQIIFLPFTCIGYTATNQDFIQRLSTLIRQAIERQLPAWIEAANQREEAHGEQGEEEEEEEEEDVAESRYFEMGPPDAEEEEGSGQGEEDEEDEDEEAEEERLALEWALGADEDFLLEHIRILKVLWCFLIHVQGSIRQFAACLVLTDFGIAVFEIPHQESRGSSQHILSSLRFVFCFPHGDLTEFGFLMPELCLVLKVRHSENTLFIISDAANLHEFHADLRSCFAPQHMAMLCSPILYGSHTSLQEFLRQLLTFYKVAGGSQERSQGCFPVYLVYSDKRMVQTAAGDYSGNIEWASCTLCSAVRRSCCAPSEAVKSAAIPYWLLLTSQHLNVIKADFNPMPSRGTHNCRNRNSFKLSRVPLSTVLLDPTRSCTQPRGAFADGHVLELLVGYRFVTAIFVLPHEKFHFLRVYNQLRASLKDLKTVVIAKNPSARPRTQGPLAGGQPAKSRVSAEQRLQETPAEAPAPAPAAAESAAEAPAAAEASAPAGAPAPAGAPAPAGAPAGAQAPAPAQAEVPAQYPSERLIQSTSEENQIPSHLPVCPSLQHIARLRGRAIIDLFHSSIAEVENEELRHLLWSSVVFYQTPGLEVTACVLLSTKAVYFILHDGLRRYFSEPLQDFWHQKNTDYNNSPFHISQCFVLKLSDLQSVNVGLFDQYFRLTGSSPTQVVTCLTRDSYLTHCFLQHLMLVLSSLERTPSPEPIDKDFYSEFGDKNTGKMENYELIHSSRVKFTYPSEEEVGDLTYVVAQKMADPAKNPALSILLYIQAFQVITPQLGRGRGPLRPKTLLLTSAEIFLLDEDYIHYPLPEFAKEPPQRDRYRLDDGRRVRDLDRVLMGYNPYPQALTLVFDDTQGHDLMGSVTLDHFGEMPGGPGRAGQGREVQWQVFVPSAESREKLISLLARQWEALCGRELPVELTG | ||||||
Modified residue | 542 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 544 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 547 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1280 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 1282 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
Homooligomer. Interacts with GRB2. Interacts with PIK3R1; probably associates with the PI3-kinase complex. Interacts with IRS4. Found in a complex with ITGA5 and PAK1. Found in a complex with LIMK1 and PAK1. Interacts with ITGA5 (via cytoplasmic domain); this interaction is direct. Interacts with PAK1 (via kinase domain); this interaction is direct and is increased upon activation of PAK1. Interacts with LIMK1 (via PDZ and kinase domain); this interaction is direct. Interacts with LIMK2; this interaction depends on LIMK2 activity. Interacts with RAC1 (activated state) (By similarity).
Interacts with STK11; this interaction may increase STK11 activity (By similarity).
Interacts with STK11; this interaction may increase STK11 activity (By similarity).
Protein-protein interaction databases
Chemistry
Structure
Family & Domains
Features
Showing features for region, domain, repeat, coiled coil, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-134 | Necessary for binding to phosphoinositide-3-P; not sufficient for targeting to endosomes | ||||
Sequence: MAAATLSFGPEREAEPAKEARVVGSELVDTYTVYVIQVTDGNHEWTIKHRYSDFHDLHEKLVAERKIDKTLLPPKKIIGKNSRSLVEKREKDLEVYLQTLLKTFPDVAPRVLAHFLHFHLYEINGVTAALAEEL | ||||||
Domain | 12-122 | PX | ||||
Sequence: REAEPAKEARVVGSELVDTYTVYVIQVTDGNHEWTIKHRYSDFHDLHEKLVAERKIDKTLLPPKKIIGKNSRSLVEKREKDLEVYLQTLLKTFPDVAPRVLAHFLHFHLYE | ||||||
Region | 121-693 | Necessary for homooligomerization and targeting to endosomes | ||||
Sequence: YEINGVTAALAEELFEKGEQLLGAGEVFAIRPLQLYAITEQLQQGKPTCASGDAKTDLGHILDFTCRLKYLKVSGTEGPFGTSNIREQLLPFDLSIFKSLHQVEMSHCDAKHVRGLVTSKPTLATMSVRFSAASMKEVLVPEASEFDEWEPEGTTLGGPVTAVIPTWQALTTLDLSHNSISEIDESVKLIPKIEYLDLSHNGVLVVDNLQHLYNLVHLDLSYNKLSSLEGVHTKLGNVKTLNLAGNFLERLSGLHKLYSLVNLDLRDNRIEQLDEVKSIGNLPCLEHVALLNNPLSIIPDYRTKVLSQFGERASEICLDDVATTEKELDTVEVLKAIQKAKDVKSKLSSTEKKVGEDFRLPTAPCIRPSSSPPTAVPTSASLPQPILSNQGIMFVQEEALASSLSSTDSLPPDDRPIAQACSNSMGSLPTGQVAAEDLRDLPGAVGGVSPDHAEPEVQVVPGSGQIIFLPFTCIGYTATNQDFIQRLSTLIRQAIERQLPAWIEAANQREEAHGEQGEEEEEEEEEDVAESRYFEMGPPDAEEEEGSGQGEEDEEDEDEEAEEERLALEWALG | ||||||
Region | 246-867 | Interaction with PAK1 | ||||
Sequence: MSVRFSAASMKEVLVPEASEFDEWEPEGTTLGGPVTAVIPTWQALTTLDLSHNSISEIDESVKLIPKIEYLDLSHNGVLVVDNLQHLYNLVHLDLSYNKLSSLEGVHTKLGNVKTLNLAGNFLERLSGLHKLYSLVNLDLRDNRIEQLDEVKSIGNLPCLEHVALLNNPLSIIPDYRTKVLSQFGERASEICLDDVATTEKELDTVEVLKAIQKAKDVKSKLSSTEKKVGEDFRLPTAPCIRPSSSPPTAVPTSASLPQPILSNQGIMFVQEEALASSLSSTDSLPPDDRPIAQACSNSMGSLPTGQVAAEDLRDLPGAVGGVSPDHAEPEVQVVPGSGQIIFLPFTCIGYTATNQDFIQRLSTLIRQAIERQLPAWIEAANQREEAHGEQGEEEEEEEEEDVAESRYFEMGPPDAEEEEGSGQGEEDEEDEDEEAEEERLALEWALGADEDFLLEHIRILKVLWCFLIHVQGSIRQFAACLVLTDFGIAVFEIPHQESRGSSQHILSSLRFVFCFPHGDLTEFGFLMPELCLVLKVRHSENTLFIISDAANLHEFHADLRSCFAPQHMAMLCSPILYGSHTSLQEFLRQLLTFYKVAGGSQERSQGCFPVYLVYSDKRMVQ | ||||||
Repeat | 289-310 | LRR 1 | ||||
Sequence: ALTTLDLSHNSISEIDESVKLI | ||||||
Repeat | 312-333 | LRR 2 | ||||
Sequence: KIEYLDLSHNGVLVVDNLQHLY | ||||||
Repeat | 334-355 | LRR 3 | ||||
Sequence: NLVHLDLSYNKLSSLEGVHTKL | ||||||
Repeat | 357-378 | LRR 4 | ||||
Sequence: NVKTLNLAGNFLERLSGLHKLY | ||||||
Repeat | 379-400 | LRR 5 | ||||
Sequence: SLVNLDLRDNRIEQLDEVKSIG | ||||||
Repeat | 404-425 | LRR 6 | ||||
Sequence: CLEHVALLNNPLSIIPDYRTKV | ||||||
Region | 481-501 | Disordered | ||||
Sequence: PTAPCIRPSSSPPTAVPTSAS | ||||||
Region | 524-549 | Disordered | ||||
Sequence: LSSTDSLPPDDRPIAQACSNSMGSLP | ||||||
Coiled coil | 623-692 | |||||
Sequence: IEAANQREEAHGEQGEEEEEEEEEDVAESRYFEMGPPDAEEEEGSGQGEEDEEDEDEEAEEERLALEWAL | ||||||
Region | 628-684 | Disordered | ||||
Sequence: QREEAHGEQGEEEEEEEEEDVAESRYFEMGPPDAEEEEGSGQGEEDEEDEDEEAEEE | ||||||
Compositional bias | 635-650 | Acidic residues | ||||
Sequence: EQGEEEEEEEEEDVAE | ||||||
Region | 659-867 | Interaction with LIMK | ||||
Sequence: PDAEEEEGSGQGEEDEEDEDEEAEEERLALEWALGADEDFLLEHIRILKVLWCFLIHVQGSIRQFAACLVLTDFGIAVFEIPHQESRGSSQHILSSLRFVFCFPHGDLTEFGFLMPELCLVLKVRHSENTLFIISDAANLHEFHADLRSCFAPQHMAMLCSPILYGSHTSLQEFLRQLLTFYKVAGGSQERSQGCFPVYLVYSDKRMVQ | ||||||
Compositional bias | 660-684 | Acidic residues | ||||
Sequence: DAEEEEGSGQGEEDEEDEDEEAEEE | ||||||
Region | 707-805 | Interaction with ITGA5 | ||||
Sequence: KVLWCFLIHVQGSIRQFAACLVLTDFGIAVFEIPHQESRGSSQHILSSLRFVFCFPHGDLTEFGFLMPELCLVLKVRHSENTLFIISDAANLHEFHADL | ||||||
Region | 1014-1101 | Disordered | ||||
Sequence: NPSARPRTQGPLAGGQPAKSRVSAEQRLQETPAEAPAPAPAAAESAAEAPAAAEASAPAGAPAPAGAPAPAGAPAGAQAPAPAQAEVP |
Domain
Both the presence of the PX domain and the coiled coil region are necessary for its endosomal targeting.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,502
- Mass (Da)166,503
- Last updated2008-09-02 v2
- ChecksumE89025E32450ECF8
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A8I6AMT4 | A0A8I6AMT4_RAT | Nisch | 1624 | ||
A0A8I6ATD2 | A0A8I6ATD2_RAT | Nisch | 516 | ||
A0A8I5ZTG9 | A0A8I5ZTG9_RAT | Nisch | 1646 | ||
A0A8L2QGU1 | A0A8L2QGU1_RAT | Nisch | 1495 |
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 635-650 | Acidic residues | ||||
Sequence: EQGEEEEEEEEEDVAE | ||||||
Compositional bias | 660-684 | Acidic residues | ||||
Sequence: DAEEEEGSGQGEEDEEDEDEEAEEE |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AABR03100261 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC098837 EMBL· GenBank· DDBJ | AAH98837.1 EMBL· GenBank· DDBJ | mRNA |