NISCH

Protein identityUniProt · HPA

UniProt accession

Q9Y2I1

Gene

NISCH

Ensembl

ENSG00000010322

Chromosome

3

Canonical length

1504 aa

Protein class

FDA approved drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Vesicles,Microtubules,Cytokinetic bridge,Cytosol

Quaternary structure

Homooligomer

OverviewNCBI Gene

This gene encodes a nonadrenergic imidazoline-1 receptor protein that localizes to the cytosol and anchors to the inner layer of the plasma membrane. The orthologous mouse protein has been shown to influence cytoskeletal organization and cell migration by binding to alpha-5-beta-1 integrin. In humans, this protein has been shown to bind to the adapter insulin receptor substrate 4 (IRS4) to mediate translocation of alpha-5 integrin from the cell membrane to endosomes. Expression of this protein was reduced in human breast cancers while its overexpression reduced tumor growth and metastasis; possibly by limiting the expression of alpha-5 integrin. In human cardiac tissue, this gene was found to affect cell growth and death while in neural tissue it affected neuronal growth and differentiation. Alternative splicing results in multiple transcript variants encoding differerent isoforms. Some isoforms lack the expected C-terminal domains of a functional imidazoline receptor. [provided by RefSeq, Jan 2013]

Canonical amino-acid sequenceUniProt

1504 residues, UniProt reviewed canonical sequence.

>Q9Y2I1|NISCH
     1  MATARTFGPE REAEPAKEAR VVGSELVDTY TVYIIQVTDG SHEWTVKHRY SDFHDLHEKL
    61  VAERKIDKNL LPPKKIIGKN SRSLVEKREK DLEVYLQKLL AAFPGVTPRV LAHFLHFHFY
   121  EINGITAALA EELFEKGEQL LGAGEVFAIG PLQLYAVTEQ LQQGKPTCAS GDAKTDLGHI
   181  LDFTCRLKYL KVSGTEGPFG TSNIQEQLLP FDLSIFKSLH QVEISHCDAK HIRGLVASKP
   241  TLATLSVRFS ATSMKEVLVP EASEFDEWEP EGTTLEGPVT AVIPTWQALT TLDLSHNSVS
   301  EIDESVKLIP KIEFLDLSHN GLLVVDNLQH LYNLVHLDLS YNKLSSLEGL HTKLGNIKTL
   361  NLAGNLLESL SGLHKLYSLV NLDLRDNRIE QMEEVRSIGS LPCLEHVSLL NNPLSIIPDY
   421  RTKVLAQFGE RASEVCLDDT VTTEKELDTV EVLKAIQKAK EVKSKLSNPE KKGGEDSRLS
   481  AAPCIRPSSS PPTVAPASAS LPQPILSNQG IMFVQEEALA SSLSSTDSLT PEHQPIAQGC
   541  SDSLESIPAG QAASDDLRDV PGAVGGASPE HAEPEVQVVP GSGQIIFLPF TCIGYTATNQ
   601  DFIQRLSTLI RQAIERQLPA WIEAANQREE GQGEQGEEED EEEEEEEDVA ENRYFEMGPP
   661  DVEEEEGGGQ GEEEEEEEED EEAEEERLAL EWALGADEDF LLEHIRILKV LWCFLIHVQG
   721  SIRQFAACLV LTDFGIAVFE IPHQESRGSS QHILSSLRFV FCFPHGDLTE FGFLMPELCL
   781  VLKVRHSENT LFIISDAANL HEFHADLRSC FAPQHMAMLC SPILYGSHTS LQEFLRQLLT
   841  FYKVAGGCQE RSQGCFPVYL VYSDKRMVQT AAGDYSGNIE WASCTLCSAV RRSCCAPSEA
   901  VKSAAIPYWL LLTPQHLNVI KADFNPMPNR GTHNCRNRNS FKLSRVPLST VLLDPTRSCT
   961  QPRGAFADGH VLELLVGYRF VTAIFVLPHE KFHFLRVYNQ LRASLQDLKT VVIAKTPGTG
  1021  GSPQGSFADG QPAERRASND QRPQEVPAEA LAPAPAEVPA PAPAAASASG PAKTPAPAEA
  1081  STSALVPEET PVEAPAPPPA EAPAQYPSEH LIQATSEENQ IPSHLPACPS LRHVASLRGS
  1141  AIIELFHSSI AEVENEELRH LMWSSVVFYQ TPGLEVTACV LLSTKAVYFV LHDGLRRYFS
  1201  EPLQDFWHQK NTDYNNSPFH ISQCFVLKLS DLQSVNVGLF DQHFRLTGST PMQVVTCLTR
  1261  DSYLTHCFLQ HLMVVLSSLE RTPSPEPVDK DFYSEFGNKT TGKMENYELI HSSRVKFTYP
  1321  SEEEIGDLTF TVAQKMAEPE KAPALSILLY VQAFQVGMPP PGCCRGPLRP KTLLLTSSEI
  1381  FLLDEDCVHY PLPEFAKEPP QRDRYRLDDG RRVRDLDRVL MGYQTYPQAL TLVFDDVQGH
  1441  DLMGSVTLDH FGEVPGGPAR ASQGREVQWQ VFVPSAESRE KLISLLARQW EALCGRELPV
  1501  ELTG

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NISCH can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.36

Highest tissue expression

276 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NISCH.

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 259 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Lynch syndrome 1
• Breast-ovarian cancer, familial, susceptibility to, 1

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.28

gnomAD pLI

0.99

gnomAD missense Z

2.3

DepMap mean gene effect

-0.36

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• actin cytoskeleton organization
• apoptotic process
• negative regulation of cell migration
• Rac protein signal transduction

Molecular functions

• identical protein binding
• integrin binding
• phosphatidylinositol binding

Cellular components

• cytoplasm
• cytosol
• early endosome
• intercellular bridge
• membrane
• microtubule cytoskeleton
• nucleoplasm
• plasma membrane
• recycling endosome

Protein domainsUniProt · Pfam · InterPro

• Leucine-rich repeat
• Phox homology
• Leucine-rich repeat domain superfamily
• PX domain superfamily
• PLEKHM2, PH domain-like
• PX domain
• PLEKHM2 PH domain-like
• Nischarin, PX domain
• Nischarin, C-terminal PH domain
• Nischarin, C-terminal PH domain

KeywordsUniProt

• Acetylation
• Apoptosis
• Cell membrane
• Coiled coil
• Cytoplasm
• Endosome
• Leucine-rich repeat
• Membrane
• Phosphoprotein
• Receptor
• Repeat

InteractionsUniProt · HPA

Protein binding partners of NISCH in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• GRB2
• IRS4
• ITGA5
• LIMK1
• LIMK2
• PAK1
• PIK3R1
• RAC1
• STK11
• RAB9A