Seroatlas · Human Serome Atlas

NOTCH3

Neurogenic locus notch homolog protein 3

Also known as: CADASIL, CASIL, NOTC3_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q9UM47
Gene: NOTCH3
Ensembl: ENSG00000074181
Chromosome: 19
Canonical length: 2321 aa
Protein class: Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins
Subcellular location: Nucleoplasm,Plasma membrane

OverviewNCBI Gene

This gene encodes the third discovered human homologue of the Drosophilia melanogaster type I membrane protein notch. In Drosophilia, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signalling pathway that plays a key role in neural development. Homologues of the notch-ligands have also been identified in human, but precise interactions between these ligands and the human notch homologues remains to be determined. Mutations in NOTCH3 have been identified as the underlying cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

2321 residues, UniProt reviewed canonical sequence.

>Q9UM47|NOTCH3
     1  MGPGARGRRR RRRPMSPPPP PPPVRALPLL LLLAGPGAAA PPCLDGSPCA NGGRCTQLPS
    61  REAACLCPPG WVGERCQLED PCHSGPCAGR GVCQSSVVAG TARFSCRCPR GFRGPDCSLP
   121  DPCLSSPCAH GARCSVGPDG RFLCSCPPGY QGRSCRSDVD ECRVGEPCRH GGTCLNTPGS
   181  FRCQCPAGYT GPLCENPAVP CAPSPCRNGG TCRQSGDLTY DCACLPGFEG QNCEVNVDDC
   241  PGHRCLNGGT CVDGVNTYNC QCPPEWTGQF CTEDVDECQL QPNACHNGGT CFNTLGGHSC
   301  VCVNGWTGES CSQNIDDCAT AVCFHGATCH DRVASFYCAC PMGKTGLLCH LDDACVSNPC
   361  HEDAICDTNP VNGRAICTCP PGFTGGACDQ DVDECSIGAN PCEHLGRCVN TQGSFLCQCG
   421  RGYTGPRCET DVNECLSGPC RNQATCLDRI GQFTCICMAG FTGTYCEVDI DECQSSPCVN
   481  GGVCKDRVNG FSCTCPSGFS GSTCQLDVDE CASTPCRNGA KCVDQPDGYE CRCAEGFEGT
   541  LCDRNVDDCS PDPCHHGRCV DGIASFSCAC APGYTGTRCE SQVDECRSQP CRHGGKCLDL
   601  VDKYLCRCPS GTTGVNCEVN IDDCASNPCT FGVCRDGINR YDCVCQPGFT GPLCNVEINE
   661  CASSPCGEGG SCVDGENGFR CLCPPGSLPP LCLPPSHPCA HEPCSHGICY DAPGGFRCVC
   721  EPGWSGPRCS QSLARDACES QPCRAGGTCS SDGMGFHCTC PPGVQGRQCE LLSPCTPNPC
   781  EHGGRCESAP GQLPVCSCPQ GWQGPRCQQD VDECAGPAPC GPHGICTNLA GSFSCTCHGG
   841  YTGPSCDQDI NDCDPNPCLN GGSCQDGVGS FSCSCLPGFA GPRCARDVDE CLSNPCGPGT
   901  CTDHVASFTC TCPPGYGGFH CEQDLPDCSP SSCFNGGTCV DGVNSFSCLC RPGYTGAHCQ
   961  HEADPCLSRP CLHGGVCSAA HPGFRCTCLE SFTGPQCQTL VDWCSRQPCQ NGGRCVQTGA
  1021  YCLCPPGWSG RLCDIRSLPC REAAAQIGVR LEQLCQAGGQ CVDEDSSHYC VCPEGRTGSH
  1081  CEQEVDPCLA QPCQHGGTCR GYMGGYMCEC LPGYNGDNCE DDVDECASQP CQHGGSCIDL
  1141  VARYLCSCPP GTLGVLCEIN EDDCGPGPPL DSGPRCLHNG TCVDLVGGFR CTCPPGYTGL
  1201  RCEADINECR SGACHAAHTR DCLQDPGGGF RCLCHAGFSG PRCQTVLSPC ESQPCQHGGQ
  1261  CRPSPGPGGG LTFTCHCAQP FWGPRCERVA RSCRELQCPV GVPCQQTPRG PRCACPPGLS
  1321  GPSCRSFPGS PPGASNASCA AAPCLHGGSC RPAPLAPFFR CACAQGWTGP RCEAPAAAPE
  1381  VSEEPRCPRA ACQAKRGDQR CDRECNSPGC GWDGGDCSLS VGDPWRQCEA LQCWRLFNNS
  1441  RCDPACSSPA CLYDNFDCHA GGRERTCNPV YEKYCADHFA DGRCDQGCNT EECGWDGLDC
  1501  ASEVPALLAR GVLVLTVLLP PEELLRSSAD FLQRLSAILR TSLRFRLDAH GQAMVFPYHR
  1561  PSPGSEPRAR RELAPEVIGS VVMLEIDNRL CLQSPENDHC FPDAQSAADY LGALSAVERL
  1621  DFPYPLRDVR GEPLEPPEPS VPLLPLLVAG AVLLLVILVL GVMVARRKRE HSTLWFPEGF
  1681  SLHKDVASGH KGRREPVGQD ALGMKNMAKG ESLMGEVATD WMDTECPEAK RLKVEEPGMG
  1741  AEEAVDCRQW TQHHLVAADI RVAPAMALTP PQGDADADGM DVNVRGPDGF TPLMLASFCG
  1801  GALEPMPTEE DEADDTSASI ISDLICQGAQ LGARTDRTGE TALHLAARYA RADAAKRLLD
  1861  AGADTNAQDH SGRTPLHTAV TADAQGVFQI LIRNRSTDLD ARMADGSTAL ILAARLAVEG
  1921  MVEELIASHA DVNAVDELGK SALHWAAAVN NVEATLALLK NGANKDMQDS KEETPLFLAA
  1981  REGSYEAAKL LLDHFANREI TDHLDRLPRD VAQERLHQDI VRLLDQPSGP RSPPGPHGLG
  2041  PLLCPPGAFL PGLKAAQSGS KKSRRPPGKA GLGPQGPRGR GKKLTLACPG PLADSSVTLS
  2101  PVDSLDSPRP FGGPPASPGG FPLEGPYAAA TATAVSLAQL GGPGRAGLGR QPPGGCVLSL
  2161  GLLNPVAVPL DWARLPPPAP PGPSFLLPLA PGPQLLNPGT PVSPQERPPP YLAVPGHGEE
  2221  YPAAGAHSSP PKARFLRVPS EHPYLTPSPE SPEHWASPSP PSLSDWSEST PSPATATGAM
  2281  ATTTGALPAQ PLPLSVPSSL AQAQTQLGPQ PEVTPKRQVL A

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NOTCH3 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: 1
Mean surface accessibility (rSASA): 0.42
Highest tissue expression: 201 nTPM

Expression across tissuesHPA

Tissue

blood vessel: 201 nTPM
adipose tissue: 82 nTPM
skin: 79 nTPM
esophagus: 72 nTPM
placenta: 56 nTPM
vagina: 53 nTPM

Single-cell type

vascular smooth muscle cells: 532 nCPM
pericytes: 498 nCPM
esophageal suprabasal cells: 165 nCPM
myosatellite cells: 146 nCPM
suprabasal keratinocytes: 127 nCPM
esophageal apical cells: 127 nCPM

Immune cell

plasmacytoid DC: 0.4 nTPM
basophil: 0.2 nTPM
neutrophil: 0.1 nTPM
classical monocyte: 0 nTPM
eosinophil: 0 nTPM
gdT-cell: 0 nTPM

Brain region

cerebral cortex: 40 nTPM
thalamus: 37 nTPM
midbrain: 34 nTPM
amygdala: 33 nTPM
pons: 32 nTPM
basal ganglia: 28 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NOTCH3.

Disease | AllUniProt

Conditions NOTCH3 is implicated in, by any mechanism.

Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, 1 (CADASIL1) MIM:125310
Cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1 (CARASIL1) MIM:621295
Myofibromatosis, infantile 2 (IMF2) MIM:615293
Lateral meningocele syndrome (LMNS) MIM:130720
Lipodystrophy, familial partial, 1 (FPLD1) MIM:608600

Disease | GeneticClinVar

319 pathogenic / likely-pathogenic of 2,072 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1
NOTCH3-related disorder
Lateral meningocele syndrome
Myofibromatosis, infantile, 2
Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy

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): 0.32
gnomAD pLI: 0.41
gnomAD missense Z: 3.53
DepMap mean gene effect: -0.02
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of NOTCH3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads NOTCH3 as an antibody target. Whether an autoantibody or antibody against NOTCH3 could matter depends on whether native NOTCH3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

NOTCH3 is annotated at the cell surface, where native NOTCH3 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label NOTCH3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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