Seroatlas · Human Serome Atlas

NOTCH1

Neurogenic locus notch homolog protein 1

Also known as: NOTC1_HUMAN, TAN1

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

Protein identityUniProt · HPA

UniProt accession: P46531
Gene: NOTCH1
Ensembl: ENSG00000148400
Chromosome: 9
Canonical length: 2555 aa
Protein class: Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted membrane proteins, Transporters
Subcellular location: Nucleoplasm

OverviewNCBI Gene

This gene encodes a member of the NOTCH family of proteins. Members of this Type I transmembrane protein family share structural characteristics including an extracellular domain consisting of multiple epidermal growth factor-like (EGF) repeats, and an intracellular domain consisting of multiple different domain types. Notch signaling is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells through binding of Notch family receptors to their cognate ligands. The encoded preproprotein is proteolytically processed in the trans-Golgi network to generate two polypeptide chains that heterodimerize to form the mature cell-surface receptor. This receptor plays a role in the development of numerous cell and tissue types. Mutations in this gene are associated with aortic valve disease, Adams-Oliver syndrome, T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and head and neck squamous cell carcinoma. [provided by RefSeq, Jan 2016]

Canonical amino-acid sequenceUniProt

2555 residues, UniProt reviewed canonical sequence.

>P46531|NOTCH1
     1  MPPLLAPLLC LALLPALAAR GPRCSQPGET CLNGGKCEAA NGTEACVCGG AFVGPRCQDP
    61  NPCLSTPCKN AGTCHVVDRR GVADYACSCA LGFSGPLCLT PLDNACLTNP CRNGGTCDLL
   121  TLTEYKCRCP PGWSGKSCQQ ADPCASNPCA NGGQCLPFEA SYICHCPPSF HGPTCRQDVN
   181  ECGQKPGLCR HGGTCHNEVG SYRCVCRATH TGPNCERPYV PCSPSPCQNG GTCRPTGDVT
   241  HECACLPGFT GQNCEENIDD CPGNNCKNGG ACVDGVNTYN CRCPPEWTGQ YCTEDVDECQ
   301  LMPNACQNGG TCHNTHGGYN CVCVNGWTGE DCSENIDDCA SAACFHGATC HDRVASFYCE
   361  CPHGRTGLLC HLNDACISNP CNEGSNCDTN PVNGKAICTC PSGYTGPACS QDVDECSLGA
   421  NPCEHAGKCI NTLGSFECQC LQGYTGPRCE IDVNECVSNP CQNDATCLDQ IGEFQCICMP
   481  GYEGVHCEVN TDECASSPCL HNGRCLDKIN EFQCECPTGF TGHLCQYDVD ECASTPCKNG
   541  AKCLDGPNTY TCVCTEGYTG THCEVDIDEC DPDPCHYGSC KDGVATFTCL CRPGYTGHHC
   601  ETNINECSSQ PCRHGGTCQD RDNAYLCFCL KGTTGPNCEI NLDDCASSPC DSGTCLDKID
   661  GYECACEPGY TGSMCNINID ECAGNPCHNG GTCEDGINGF TCRCPEGYHD PTCLSEVNEC
   721  NSNPCVHGAC RDSLNGYKCD CDPGWSGTNC DINNNECESN PCVNGGTCKD MTSGYVCTCR
   781  EGFSGPNCQT NINECASNPC LNQGTCIDDV AGYKCNCLLP YTGATCEVVL APCAPSPCRN
   841  GGECRQSEDY ESFSCVCPTG WQGQTCEVDI NECVLSPCRH GASCQNTHGG YRCHCQAGYS
   901  GRNCETDIDD CRPNPCHNGG SCTDGINTAF CDCLPGFRGT FCEEDINECA SDPCRNGANC
   961  TDCVDSYTCT CPAGFSGIHC ENNTPDCTES SCFNGGTCVD GINSFTCLCP PGFTGSYCQH
  1021  DVNECDSQPC LHGGTCQDGC GSYRCTCPQG YTGPNCQNLV HWCDSSPCKN GGKCWQTHTQ
  1081  YRCECPSGWT GLYCDVPSVS CEVAAQRQGV DVARLCQHGG LCVDAGNTHH CRCQAGYTGS
  1141  YCEDLVDECS PSPCQNGATC TDYLGGYSCK CVAGYHGVNC SEEIDECLSH PCQNGGTCLD
  1201  LPNTYKCSCP RGTQGVHCEI NVDDCNPPVD PVSRSPKCFN NGTCVDQVGG YSCTCPPGFV
  1261  GERCEGDVNE CLSNPCDARG TQNCVQRVND FHCECRAGHT GRRCESVING CKGKPCKNGG
  1321  TCAVASNTAR GFICKCPAGF EGATCENDAR TCGSLRCLNG GTCISGPRSP TCLCLGPFTG
  1381  PECQFPASSP CLGGNPCYNQ GTCEPTSESP FYRCLCPAKF NGLLCHILDY SFGGGAGRDI
  1441  PPPLIEEACE LPECQEDAGN KVCSLQCNNH ACGWDGGDCS LNFNDPWKNC TQSLQCWKYF
  1501  SDGHCDSQCN SAGCLFDGFD CQRAEGQCNP LYDQYCKDHF SDGHCDQGCN SAECEWDGLD
  1561  CAEHVPERLA AGTLVVVVLM PPEQLRNSSF HFLRELSRVL HTNVVFKRDA HGQQMIFPYY
  1621  GREEELRKHP IKRAAEGWAA PDALLGQVKA SLLPGGSEGG RRRRELDPMD VRGSIVYLEI
  1681  DNRQCVQASS QCFQSATDVA AFLGALASLG SLNIPYKIEA VQSETVEPPP PAQLHFMYVA
  1741  AAAFVLLFFV GCGVLLSRKR RRQHGQLWFP EGFKVSEASK KKRREPLGED SVGLKPLKNA
  1801  SDGALMDDNQ NEWGDEDLET KKFRFEEPVV LPDLDDQTDH RQWTQQHLDA ADLRMSAMAP
  1861  TPPQGEVDAD CMDVNVRGPD GFTPLMIASC SGGGLETGNS EEEEDAPAVI SDFIYQGASL
  1921  HNQTDRTGET ALHLAARYSR SDAAKRLLEA SADANIQDNM GRTPLHAAVS ADAQGVFQIL
  1981  IRNRATDLDA RMHDGTTPLI LAARLAVEGM LEDLINSHAD VNAVDDLGKS ALHWAAAVNN
  2041  VDAAVVLLKN GANKDMQNNR EETPLFLAAR EGSYETAKVL LDHFANRDIT DHMDRLPRDI
  2101  AQERMHHDIV RLLDEYNLVR SPQLHGAPLG GTPTLSPPLC SPNGYLGSLK PGVQGKKVRK
  2161  PSSKGLACGS KEAKDLKARR KKSQDGKGCL LDSSGMLSPV DSLESPHGYL SDVASPPLLP
  2221  SPFQQSPSVP LNHLPGMPDT HLGIGHLNVA AKPEMAALGG GGRLAFETGP PRLSHLPVAS
  2281  GTSTVLGSSS GGALNFTVGG STSLNGQCEW LSRLQSGMVP NQYNPLRGSV APGPLSTQAP
  2341  SLQHGMVGPL HSSLAASALS QMMSYQGLPS TRLATQPHLV QTQQVQPQNL QMQQQNLQPA
  2401  NIQQQQSLQP PPPPPQPHLG VSSAASGHLG RSFLSGEPSQ ADVQPLGPSS LAVHTILPQE
  2461  SPALPTSLPS SLVPPVTAAQ FLTPPSQHSY SSPVDNTPSH QLQVPEHPFL TPSPESPDQW
  2521  SSSSPHSNVS DWSEGVSSPP TSMQSQIARI PEAFK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NOTCH1 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): 0.38
Highest tissue expression: 19 nTPM

Expression across tissuesHPA

Tissue

skin: 19 nTPM
colon: 15 nTPM
lung: 14 nTPM
adipose tissue: 14 nTPM
spleen: 14 nTPM
esophagus: 12 nTPM

Single-cell type

neutrophils: 214 nCPM
lymphatic endothelial cells: 93 nCPM
müller glia: 84 nCPM
vascular endothelial cells: 83 nCPM
astrocytes: 77 nCPM
thymocytes: 75 nCPM

Immune cell

neutrophil: 2.3 nTPM
NK-cell: 0.7 nTPM
eosinophil: 0.6 nTPM
memory CD8 T-cell: 0.5 nTPM
total PBMC: 0.5 nTPM
classical monocyte: 0.4 nTPM

Brain region

basal ganglia: 55 nTPM
thalamus: 51 nTPM
white matter: 50 nTPM
medulla oblongata: 50 nTPM
cerebellum: 47 nTPM
midbrain: 47 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NOTCH1.

Disease | AllUniProt

Conditions NOTCH1 is implicated in, by any mechanism.

Aortic valve disease 1 (AOVD1) MIM:109730
Adams-Oliver syndrome 5 (AOS5) MIM:616028

Disease | GeneticClinVar

170 pathogenic / likely-pathogenic of 4,644 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Adams-Oliver syndrome 5
Aortic valve disease 1
NOTCH1-related disorder
Familial thoracic aortic aneurysm and aortic dissection
Abnormal heart morphology

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): 0.1
gnomAD pLI: 1
gnomAD missense Z: 3.45
DepMap mean gene effect: -0.03
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% 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 NOTCH1 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 NOTCH1 as an antibody target. Whether an autoantibody or antibody against NOTCH1 could matter depends on whether native NOTCH1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

NOTCH1 is annotated at the cell surface, where native NOTCH1 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 NOTCH1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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