Entity Details

Primary name NOTC2_HUMAN
Entity type UniProt
Source Source Link

Details

AccessionQ04721
EntryNameNOTC2_HUMAN
FullNameNeurogenic locus notch homolog protein 2
TaxID9606
Evidenceevidence at protein level
Length2471
SequenceStatuscomplete
DateCreated2002-03-27
DateModified2021-06-02

Ontological Relatives

GenesNOTCH2

GO terms

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GOName
GO:0000122 negative regulation of transcription by RNA polymerase II
GO:0000139 Golgi membrane
GO:0001701 in utero embryonic development
GO:0001709 cell fate determination
GO:0001947 heart looping
GO:0002011 morphogenesis of an epithelial sheet
GO:0002315 marginal zone B cell differentiation
GO:0002437 inflammatory response to antigenic stimulus
GO:0003162 atrioventricular node development
GO:0003184 pulmonary valve morphogenesis
GO:0005509 calcium ion binding
GO:0005576 extracellular region
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005789 endoplasmic reticulum membrane
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0005929 cilium
GO:0006367 transcription initiation from RNA polymerase II promoter
GO:0006915 apoptotic process
GO:0006959 humoral immune response
GO:0007219 Notch signaling pathway
GO:0007275 multicellular organism development
GO:0007399 nervous system development
GO:0007411 axon guidance
GO:0009887 animal organ morphogenesis
GO:0009986 cell surface
GO:0010629 negative regulation of gene expression
GO:0010838 positive regulation of keratinocyte proliferation
GO:0016020 membrane
GO:0019827 stem cell population maintenance
GO:0019899 enzyme binding
GO:0030097 hemopoiesis
GO:0030326 embryonic limb morphogenesis
GO:0030513 positive regulation of BMP signaling pathway
GO:0035264 multicellular organism growth
GO:0035622 intrahepatic bile duct development
GO:0038023 signaling receptor activity
GO:0042060 wound healing
GO:0042742 defense response to bacterium
GO:0043011 myeloid dendritic cell differentiation
GO:0043065 positive regulation of apoptotic process
GO:0043066 negative regulation of apoptotic process
GO:0043235 receptor complex
GO:0045672 positive regulation of osteoclast differentiation
GO:0045967 negative regulation of growth rate
GO:0046579 positive regulation of Ras protein signal transduction
GO:0046849 bone remodeling
GO:0051059 NF-kappaB binding
GO:0060413 atrial septum morphogenesis
GO:0060674 placenta blood vessel development
GO:0061073 ciliary body morphogenesis
GO:0061314 Notch signaling involved in heart development
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0070986 left/right axis specification
GO:0072014 proximal tubule development
GO:0072015 glomerular visceral epithelial cell development
GO:0072104 glomerular capillary formation
GO:0072574 hepatocyte proliferation
GO:1990705 cholangiocyte proliferation
GO:2000249 regulation of actin cytoskeleton reorganization
GO:2001204 regulation of osteoclast development

Subcellular Location

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Subcellular Location
Cell membrane
Cytoplasm
Nucleus

Domains

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DomainNameCategoryType
IPR000152 EGF-type aspartate/asparagine hydroxylation sitePTMPTM
IPR000742 EGF-like domainDomainDomain
IPR000800 Notch domainDomainDomain
IPR001881 EGF-like calcium-binding domainDomainDomain
IPR002110 Ankyrin repeatRepeatRepeat
IPR008297 NotchFamilyFamily
IPR009030 Growth factor receptor cysteine-rich domain superfamilyFamilyHomologous superfamily
IPR010660 Notch, NOD domainDomainDomain
IPR011656 Notch, NODP domainDomainDomain
IPR013032 EGF-like, conserved siteSiteConserved site
IPR018097 EGF-like calcium-binding, conserved siteSiteConserved site
IPR020683 Ankyrin repeat-containing domainDomainDomain
IPR022336 Neurogenic locus Notch 2FamilyFamily
IPR024600 Domain of unknown function DUF3454, notchDomainDomain
IPR035993 Notch-like domain superfamilyFamilyHomologous superfamily
IPR036770 Ankyrin repeat-containing domain superfamilyFamilyHomologous superfamily

Diseases

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Disease IDSourceNameDescription
610205 OMIMAlagille syndrome 2 (ALGS2)A form of Alagille syndrome, an autosomal dominant multisystem disorder. It is clinically defined by hepatic bile duct paucity and cholestasis in association with cardiac, skeletal, and ophthalmologic manifestations. There are characteristic facial features and less frequent clinical involvement of the renal and vascular systems. The disease is caused by variants affecting the gene represented in this entry.
102500 OMIMHajdu-Cheney syndrome (HJCYS)A rare, autosomal dominant skeletal disorder characterized by the association of facial anomalies, acro-osteolysis, general osteoporosis, insufficient ossification of the skull, and periodontal disease (premature loss of permanent teeth). Other features include cleft palate, congenital heart defects, polycystic kidneys, orthopedic problems and anomalies of the genitalia, intestines and eyes. The disease is caused by variants affecting the gene represented in this entry. NOTCH2 nonsense and frameshift mutations associated with Hajdu-Cheney syndrome cluster to the last coding exon of the gene. Mutant mRNA products escape nonsense-mediated decay and the resulting truncated NOTCH2 proteins act in a gain-of-function manner (PubMed:21378989). The pathological mechanism at cellular level involves disruption of a high affinity degron recognized by FBXW7 at the C-terminus, loss of interaction with FBXW7, reduced ubiquitination and degradation, and increased NOTCH2 levels. Bone marrow cells derived from HJCYS patients have an enhanced capacity of osteoclastogenesis due to sustained NOTCH2 activity (PubMed:29149593).

Interactions

36 interactions

InteractorPartnerSourcesPublicationsLink
NOTC2_HUMANSMAD1_HUMANBioGRID, HPRD, MINT15231748 details
NOTC2_HUMANCRKL_HUMANBioGRID, IntAct18654987 details
NOTC2_HUMANANR28_HUMANBioGRID, IntAct23414517 24255178 details
NOTC2_HUMANCYTM_HUMANBioGRID, MINT25640309 details
NOTC2_HUMANESIP1_HUMANBioGRID, MINT25640309 details
NOTC2_HUMANLRAT2_HUMANBioGRID, MINT25640309 details
NOTC2_HUMANI13R2_HUMANBioGRID, MINT25640309 details
NOTC2_HUMANIL24_HUMANBioGRID, MINT25640309 details
NOTC2_HUMANITIH5_HUMANBioGRID, MINT25640309 details
NOTC2_HUMANKLK5_HUMANBioGRID, MINT25640309 details
NOTC2_HUMANMTA3_HUMANBioGRID, MINT25640309 details
NOTC2_HUMANHOP2_HUMANBioGRID, MINT25640309 details
NOTC2_HUMANST14_HUMANBioGRID, MINT25640309 details
NOTC2_HUMANSUH_HUMANBioGRID, HPRD, IntAct, MINT25609649 26186194 26496610 28514442 9032325 details
NOTC2_HUMANCCR2_HUMANBioGRID, MINT28298427 details
NOTC2_HUMANGSK3B_HUMANBioGRID, HPRD12794074 details
NOTC2_HUMANJAG1_HUMANBioGRID, HPRD10551863 10958687 11346656 details
NOTC2_HUMANDLL1_HUMANBioGRID, HPRD10958687 11346656 9244302 details
NOTC2_HUMANMAML1_HUMANBioGRID, HPRD11101851 details
NOTC2_HUMANJAG2_HUMANBioGRID, HPRD10958687 details
NOTC2_HUMANMYOC_HUMANBioGRID, HPRD16289162 details
NOTC2_HUMANEGFL7_HUMANBioGRID19503073 details
NOTC2_HUMANDTX3_HUMANBioGRID31854042 details
NOTC2_HUMANSHAN3_HUMANMINT21653829 details
NOTC2_HUMANCNTN1_HUMANBioGRID, HPRD14567914 details
NOTC2_HUMANCASR_HUMANBioGRID17573339 details
NOTC2_HUMANST7_HUMANBioGRID29395067 details
NOTC2_HUMANSMAP2_HUMANBioGRID29395067 details
NOTC2_HUMANDTX3L_HUMANBioGRID31854042 details
NOTC2_HUMANLFNG_HUMANHPRD11346656 details
NOTC2_HUMANMFNG_HUMANHPRD11346656 details
NOTC2_HUMANDTX1_HUMANHPRD9244302 details
NOTC2_HUMANPSN1_HUMANHPRD11518718 details
NOTC2_HUMANPSN2_HUMANHPRD11518718 details
NOTC2_HUMANMAML2_HUMANHPRD12370315 details
NOTC2_HUMANMAML3_HUMANHPRD12370315 details