Q9QW30 · NOTC2_RAT

  • Protein
    Neurogenic locus notch homolog protein 2
  • Gene
    Notch2
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs (By similarity).
Involved in bone remodeling and homeostasis. In collaboration with RELA/p65 enhances NFATc1 promoter activity and positively regulates RANKL-induced osteoclast differentiation. Positively regulates self-renewal of liver cancer cells (By similarity).

Features

Showing features for site.

124712004006008001,0001,2001,4001,6001,8002,0002,2002,400
TypeIDPosition(s)Description
Site614Essential for O-xylosylation

GO annotations

all annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular Componentcell surface
Cellular Componentcilium
Cellular Componentcytosol
Cellular Componentextracellular region
Cellular Componentglutamatergic synapse
Cellular Componentnucleus
Cellular Componentplasma membrane
Cellular Componentpostsynaptic density membrane
Cellular Componentreceptor complex
Molecular Functioncalcium ion binding
Molecular Functioncis-regulatory region sequence-specific DNA binding
Molecular FunctionDNA-binding transcription activator activity, RNA polymerase II-specific
Molecular Functionenzyme binding
Molecular FunctionNF-kappaB binding
Molecular Functiontransmembrane signaling receptor activity
Biological Processanimal organ morphogenesis
Biological Processapoptotic process
Biological Processatrial septum morphogenesis
Biological ProcessBMP signaling pathway
Biological Processbone remodeling
Biological Processcell fate determination
Biological Processcell population proliferation
Biological Processcellular response to tumor cell
Biological Processcholangiocyte proliferation
Biological Processciliary body morphogenesis
Biological Processdefense response to bacterium
Biological Processdetermination of left/right symmetry
Biological Processembryonic limb morphogenesis
Biological Processglial cell differentiation
Biological Processglomerular capillary formation
Biological Processheart looping
Biological Processhepatocyte proliferation
Biological Processhumoral immune response
Biological Processin utero embryonic development
Biological Processinflammatory response to antigenic stimulus
Biological Processintracellular signal transduction
Biological Processintrahepatic bile duct development
Biological Processleft/right axis specification
Biological Processliver development
Biological Processliver morphogenesis
Biological Processmarginal zone B cell differentiation
Biological Processmorphogenesis of an epithelial sheet
Biological Processmulticellular organism growth
Biological Processmyeloid dendritic cell differentiation
Biological Processnegative regulation of gene expression
Biological Processnegative regulation of transcription by RNA polymerase II
Biological ProcessNotch signaling pathway
Biological Processplacenta blood vessel development
Biological Processplacenta development
Biological Processpodocyte development
Biological Processpositive regulation of apoptotic process
Biological Processpositive regulation of BMP signaling pathway
Biological Processpositive regulation of cell population proliferation
Biological Processpositive regulation of ERK1 and ERK2 cascade
Biological Processpositive regulation of keratinocyte proliferation
Biological Processpositive regulation of miRNA transcription
Biological Processpositive regulation of neuroblast proliferation
Biological Processpositive regulation of osteoclast differentiation
Biological Processpositive regulation of Ras protein signal transduction
Biological Processpositive regulation of smooth muscle cell differentiation
Biological Processpositive regulation of transcription by RNA polymerase II
Biological Processproximal tubule development
Biological Processpulmonary valve morphogenesis
Biological Processregulation of osteoclast development
Biological Processregulation of transcription by RNA polymerase II
Biological Processtissue regeneration
Biological Processwound healing

Keywords

Names & Taxonomy

Protein names

Gene names

    • Name
      Notch2

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus

Accessions

  • Primary accession
    Q9QW30

Proteomes

Organism-specific databases

Subcellular Location

Notch 2 extracellular truncation

Cell membrane
; Single-pass type I membrane protein

Notch 2 intracellular domain

Nucleus
Cytoplasm
Note: Following proteolytical processing NICD is translocated to the nucleus. Retained at the cytoplasm by TCIM.

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain26-1677Extracellular
Transmembrane1678-1698Helical
Topological domain1699-2471Cytoplasmic

Keywords

Phenotypes & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis2078Permits Notch2 inhibitory activity upon G-CSF action on myeloid cells.
Mutagenesis2090No effect.

PTM/Processing

Features

Showing features for signal, chain, disulfide bond, glycosylation, modified residue.

TypeIDPosition(s)Description
Signal1-25
ChainPRO_000000768926-2471Neurogenic locus notch homolog protein 2
Disulfide bond28↔41
Disulfide bond35↔51
Glycosylation46N-linked (GlcNAc...) asparagine
Disulfide bond53↔62
Disulfide bond68↔79
Disulfide bond73↔90
Disulfide bond92↔101
Disulfide bond109↔121
Disulfide bond115↔131
Disulfide bond133↔142
Disulfide bond148↔159
Disulfide bond153↔168
Glycosylation155N-linked (GlcNAc...) asparagine
Disulfide bond170↔179
Disulfide bond186↔198
Disulfide bond192↔207
Disulfide bond209↔218
Disulfide bond225↔236
Disulfide bond230↔246
Disulfide bond248↔257
Disulfide bond264↔275
Disulfide bond269↔284
Disulfide bond286↔295
Disulfide bond302↔315
Disulfide bond309↔324
Disulfide bond326↔335
Disulfide bond342↔353
Disulfide bond347↔362
Disulfide bond364↔373
Disulfide bond379↔390
Disulfide bond384↔401
Disulfide bond403↔412
Disulfide bond419↔433
Disulfide bond427↔442
Disulfide bond444↔453
Disulfide bond460↔471
Disulfide bond465↔480
Disulfide bond482↔491
Disulfide bond498↔509
Disulfide bond503↔518
Disulfide bond520↔529
Disulfide bond536↔547
Disulfide bond541↔556
Disulfide bond558↔567
Disulfide bond574↔584
Disulfide bond579↔593
Disulfide bond595↔604
Disulfide bond611↔622
Glycosylation613O-linked (Glc...) serine; alternate
Glycosylation613O-linked (Xyl...) serine; alternate
Disulfide bond616↔631
Disulfide bond633↔642
Disulfide bond649↔659
Disulfide bond654↔668
Disulfide bond670↔679
Disulfide bond686↔697
Disulfide bond691↔706
Disulfide bond708↔717
Disulfide bond724↔734
Disulfide bond729↔743
Glycosylation733N-linked (GlcNAc...) asparagine
Disulfide bond745↔754
Disulfide bond761↔772
Disulfide bond766↔781
Disulfide bond783↔792
Disulfide bond799↔810
Disulfide bond804↔819
Disulfide bond821↔830
Disulfide bond837↔848
Disulfide bond842↔859
Disulfide bond861↔870
Disulfide bond877↔888
Disulfide bond882↔897
Disulfide bond899↔908
Disulfide bond915↔926
Disulfide bond920↔935
Disulfide bond937↔946
Disulfide bond953↔964
Disulfide bond958↔973
Disulfide bond975↔984
Disulfide bond991↔1002
Disulfide bond996↔1011
Disulfide bond1013↔1022
Disulfide bond1029↔1040
Disulfide bond1034↔1049
Disulfide bond1051↔1060
Disulfide bond1067↔1078
Disulfide bond1072↔1087
Disulfide bond1089↔1098
Glycosylation1102N-linked (GlcNAc...) asparagine
Disulfide bond1105↔1126
Disulfide bond1120↔1135
Disulfide bond1137↔1146
Disulfide bond1153↔1164
Disulfide bond1158↔1173
Disulfide bond1175↔1184
Disulfide bond1191↔1202
Disulfide bond1196↔1211
Disulfide bond1213↔1222
Disulfide bond1229↔1241
Disulfide bond1235↔1250
Disulfide bond1252↔1261
Disulfide bond1268↔1281
Disulfide bond1273↔1290
Disulfide bond1292↔1301
Disulfide bond1308↔1319
Disulfide bond1313↔1331
Disulfide bond1333↔1342
Disulfide bond1378↔1389
Disulfide bond1383↔1400
Disulfide bond1402↔1411
Disulfide bond1425↔1448
Disulfide bond1430↔1443
Disulfide bond1439↔1455
Glycosylation1465N-linked (GlcNAc...) asparagine
Disulfide bond1466↔1489
Disulfide bond1472↔1484
Disulfide bond1480↔1496
Disulfide bond1503↔1527
Disulfide bond1509↔1522
Disulfide bond1518↔1534
Disulfide bond1632↔1639
ChainPRO_00000076901666-2471Notch 2 extracellular truncation
ChainPRO_00000076911697-2471Notch 2 intracellular domain
Modified residue1716Phosphothreonine
Modified residue1779Phosphoserine
Modified residue1802Phosphothreonine
Modified residue1804Phosphoserine
Modified residue1808Phosphothreonine
Modified residue1842Phosphoserine
Modified residue1845Phosphoserine
Modified residue2070Phosphoserine
Modified residue2078Phosphoserine
Modified residue2081Phosphoserine
Modified residue2097Phosphothreonine

Post-translational modification

Synthesized in the endoplasmic reticulum as an inactive form which is proteolytically cleaved by a furin-like convertase in the trans-Golgi network before it reaches the plasma membrane to yield an active, ligand-accessible form. Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC) (By similarity).
Following ligand binding, it is cleaved by TNF-alpha converting enzyme (TACE) to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT) (By similarity).
This fragment is then cleaved by presenilin dependent gamma-secretase to release a notch-derived peptide containing the intracellular domain (NICD) from the membrane (By similarity).
Phosphorylated. G-CSF treatment of myeloid cells specifically promotes Ser-2078 phosphorylation, which inactivates Notch2 and permits differentiation.
Hydroxylated by HIF1AN.
Can be either O-glucosylated or O-xylosylated at Ser-613 by POGLUT1.
Phosphorylated by GSK3. GSK3-mediated phosphorylation is necessary for NOTCH2 recognition by FBXW7, ubiquitination and degradation via the ubiquitin proteasome pathway.

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Highly expressed in the spleen and choroid plexus in the brain. Expressed in postnatal central nervous system (CNS) germinal zones and, in early postnatal life, within numerous cells throughout the CNS. It is more highly localized to ventricular germinal zones. Also found in the heart, liver and kidney.

Developmental stage

Expressed in the brain during 14 dpc and 17 dpc.

Interaction

Subunit

Heterodimer of a C-terminal fragment N(TM) and an N-terminal fragment N(EC) which are probably linked by disulfide bonds (By similarity).
Interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH2. Interacts with RELA/p65 (By similarity).
Interacts with HIF1AN. Interacts (via ANK repeats) with TCIM, the interaction inhibits the nuclear translocation of NOTCH2 N2ICD (By similarity).
Interacts with CUL1, RBX1, SKP1 and FBXW7 that are SCF(FBXW7) E3 ubiquitin-protein ligase complex components.Interacts with MINAR1; this interaction increases MINAR1 stability and function (By similarity).
Interacts with MDK; this interaction mediates a nuclear accumulation of NOTCH2 and therefore activation of NOTCH2 signaling leading to interaction between HES1 and STAT3 (By similarity).
Interacts with MINAR2 (By similarity).

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for domain, repeat, region, compositional bias.

TypeIDPosition(s)Description
Domain26-63EGF-like 1
Domain64-102EGF-like 2
Domain105-143EGF-like 3
Domain144-180EGF-like 4
Domain182-219EGF-like 5; calcium-binding
Domain221-258EGF-like 6
Domain260-296EGF-like 7; calcium-binding
Domain298-336EGF-like 8; calcium-binding
Domain338-374EGF-like 9; calcium-binding
Domain375-413EGF-like 10
Domain415-454EGF-like 11; calcium-binding
Domain456-492EGF-like 12; calcium-binding
Domain494-530EGF-like 13; calcium-binding
Domain532-568EGF-like 14; calcium-binding
Domain570-605EGF-like 15; calcium-binding
Domain607-643EGF-like 16; calcium-binding
Domain645-680EGF-like 17; calcium-binding
Domain682-718EGF-like 18; calcium-binding
Domain720-755EGF-like 19
Domain757-793EGF-like 20; calcium-binding
Domain795-831EGF-like 21; calcium-binding
Domain833-871EGF-like 22
Domain873-909EGF-like 23; calcium-binding
Domain911-947EGF-like 24; calcium-binding
Domain949-985EGF-like 25; calcium-binding
Domain987-1023EGF-like 26; calcium-binding
Domain1025-1061EGF-like 27; calcium-binding
Domain1063-1099EGF-like 28
Domain1101-1147EGF-like 29
Domain1149-1185EGF-like 30; calcium-binding
Domain1187-1223EGF-like 31; calcium-binding
Domain1225-1262EGF-like 32; calcium-binding
Domain1264-1302EGF-like 33
Domain1304-1343EGF-like 34
Domain1374-1412EGF-like 35
Repeat1425-1465LNR 1
Region1425-1677Negative regulatory region (NRR)
Repeat1466-1502LNR 2
Repeat1503-1544LNR 3
Region1751-1788Disordered
Compositional bias1760-1788Basic and acidic residues
Region1794-1813Disordered
Repeat1827-1871ANK 1
Repeat1876-1905ANK 2
Repeat1909-1939ANK 3
Repeat1943-1972ANK 4
Repeat1976-2005ANK 5
Repeat2009-2038ANK 6
Region2097-2116Disordered
Region2380-2471Disordered
Compositional bias2384-2402Polar residues
Compositional bias2419-2447Polar residues

Sequence similarities

Belongs to the NOTCH family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    2,471
  • Mass (Da)
    265,370
  • Last updated
    2000-05-01 v1
  • Checksum
    7D5C8E18DDE95FE8
MPALRPAALRALLWLWLCGAGPAHALQCRGGQEPCVNEGTCVTYHNGTGYCRCPEGFLGEYCQHRDPCEKNRCQNGGTCVTQAMLGKATCRCAPGFTGEDCQYSTSHPCFVSRPCQNGGTCHMLSWDTYECTCQVGFTGKQCQWTDVCLSHPCENGSTCSSVANQFSCRCPAGITGQKCDADINECDIPGRCQHGGTCLNLPGSYRCQCPQRFTGQHCDSPYVPCAPSPCVNGGTCRQTGDFTSECHCLPGFEGSNCERNIDDCPNHKCQNGGVCVDGVNTYNCRCPPQWTGQFCTEDVDECLLQPNACQNGGTCTNRNGGYGCVCVNGWSGDDCSENIDDCAFASCTPGSTCIDRVASFSCLCPEGKAGLLCHLDDACISNPCHKGALCDTNPLNGQYICTCPQAYKGADCTEDVDECAMANSNPCEHAGKCVNTDGAFHCECLKGYAGPRCEMDINECHSDPCQNDATCLDKIGGFTCLCMPGFKGVHCELEVNECQSNPCVNNGQCVDKVNRFQCLCPPGFTGPVCQIDIDDCSSTPCLNGAKCIDHPNGYECQCATGFTGTLCDENIDNCDPDPCHHGQCQDGIDSYTCICNPGYMGAICSDQIDECYSSPCLNDGRCIDLVNGYQCNCQPGTSGLNCEINFDDCASNPCLHGACVDGINRYSCVCSPGFTGQRCNIDIDECASNPCRKDATCINDVNGFRCMCPEGPHHPSCYSQVNECLSSPCIHGNCTGGLSGYKCLCDAGWVGINCEVDKNECLSNPCQNGGTCNNLVNGYRCTCKKGFKGYNCQVNIDECASNPCLNQGTCLDDVSGYTCHCMLPYTGKNCQTVLAPCSPNPCENAAVCKEAPNFESFTCLCAPGWQGQRCTVDVDECVSKPCMNNGICHNTQGSYMCECPPGFSGMDCEEDINDCLANPCQNGGSCVDKVNTFSCLCLPGFVGDKCQTDMNECLSEPCKNGGTCSDYVNSYTCTCPAGFHGVHCENNIDECTESSCFNGGTCVDGINSFSCLCPVGFTGPFCLHDINECSSNPCLNSGTCVDGLGTYRCTCPLGYTGKNCQTLVNLCSPSPCKNKGTCAQEKARPRCLCPPGWDGAYCDVLNVSCKAAALQKGVPVEHLCQHSGICINAGNTHHCQCPLGYTGSYCEEQLDECASNPCQHGATCSDFIGGYRCECVPGYQGVNCEYEVDECQNQPCQNGGTCIDLVNHFKCSCPPGTRGLLCEENIDDCAGAPHCLNGGQCVDRIGGYSCRCLPGFAGERCEGDINECLSNPCSSEGSLDCIQLKNNYQCVCRSAFTGRHCETFLDVCPQKPCLNGGTCAVASNVPDGFICRCPPGFSGARCQSSCGQVKCRRGEQCVHTASGPHCFCPNHKDCESGCASNPCQHGGTCYPQRQPPYYSCRCSPPFWGSHCESYTAPTSTPPATCLSQYCADKARDGICDEACNSHACQWDGGDCSLTMEDPWANCTSSLRCWEYINNQCDELCNTAECLFDNFECQRNSKTCKYDKYCADHFKDNHCDKGCNNEECGWDGLDCAADQPENLAEGILVIVVLLPPEQLLQDSRSFLRALGTLLHTNLRIKQDSQGALMVYPYYGEKSAAMKKQKVARRSLPDEQEQEIIGSKVFLEIDNRQCVQDSDQCFKNTDAAAALLASHAIQGTLSYPLVSVVSESEDPRNTPLLYLLAVAVVIILFLILLGVIMAKRKRKHGFLWLPEGFTLRRDSSNHKRREPVGQDAVGLKNLSVQVSEANLIGSTTSEHWGDDEGPQPKKAKAEDDEALLSEDDPVDRRPWTQQHLEAADIRRTPSLALTPPQAEQEVDVLDVNVRGPDGCTPLMLASLRGGSSDLSDEDEDAEDSSANIITDLVYQGASLQAQTDRTGEMALHLAARYSRADAAKRLLDAGADANAQDNMGRCPLHAAVAADAQGVFQILIRNRVTDLDARMNDGTTPLILAARLAVEGMVAELINCQADVNAVDDHGKSALHWAAAVNNVEATLLLLKNGANRDMQDNKEETPLFLAAREGSYEAAKILLDHFANRDITDHMDRLPRDVARDRMHHDIVRLLDEYNVTPSPPGTVLTSALSPVLCGPNRSFLSLKHTPMGKKARRPNTKSTMPTSLPNLAKEAKDVKGSRRKKCLNEKVQLSESSVTLSPVDSLESPHTYVSDATSSPMITSPGILQASPTPLLAAAPAAPVHAQHALSFSNLHEMQPLRPGASTVLPSVSQLLSHHHIVPPGSGSAGSLGRLHSVPVPSDWMNRVEMSETQYSEMFGMVLAPAEGTHPGMAAPQSRAPEGKPIPTQREPLPPIVTFQLIPKGSLAQAAGAPQTQSGCPPAVAGPLPSMYQIPEMARLPSVAFPPTMMPQQEGQVAQTIVPTYHPFPASVGKYPTPPSQHSYASSNAAERTPNHGGHLQGEHPYLTPSPESPDQWSSSSPHSASDWSDVTTSPTPGGGGGGQRGPGTHMSEPPHSNMQVYA

Computationally mapped potential isoform sequences

There are 4 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A8I6B3I0A0A8I6B3I0_RATNotch22450
A0A8I6GM47A0A8I6GM47_RATNotch22421
G3V8G9G3V8G9_RATNotch22471
A0A1W2Q619A0A1W2Q619_RATNotch279

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias1760-1788Basic and acidic residues
Compositional bias2384-2402Polar residues
Compositional bias2419-2447Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
M93661
EMBL· GenBank· DDBJ
AAK13558.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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