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0NOTC2_HUMAN*   SwissProt (?) | Description Local Annotation Link Reference
General Information
NameNOTCH2
DescriptionNeurogenic locus notch homolog protein 2 precursor (notch 2) (hn2) .
SpeciesHomo sapiens (NCBI taxonomy ID: 9606)
GO0009986 cell surface (IDA)
0005887 integral to plasma membrane (IDA)
0005634 nucleus (IDA)
0003706 ligand-regulated transcription factor activity (TAS)
0005515 protein binding (NAS)
0046982 protein heterodimerization activity (NAS)
0004872 receptor activity (NAS)
0006916 anti-apoptosis (TAS)
0007050 cell cycle arrest (IDA)
0001709 cell fate determination (TAS)
0016049 cell growth (IDA)
0030097 hemopoiesis (TAS)
0006917 induction of apoptosis (TAS)
0008285 negative regulation of cell proliferation (IDA)
0007399 neurogenesis (NAS)
0007219 Notch signaling pathway (ISS)
0046579 positive regulation of Ras protein signal t... (IDA)
0006355 regulation of transcription, DNA-dependent (TAS)
0019827 stem cell maintenance (TAS)

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schematic display of those terms with internal associations, click the node and browse the corresponding GO term
Domain Architecture (Details)
InterPro domains unassigned to SynO:
The ankyrin repeat is one of the most common protein-protein interaction motifs in nature. Ankyrin repeats are tandemly repeated modules of about 33 amino acids. They occur in a large number of functionally diverse proteins mainly from eukaryotes. The few known examples from prokaryotes and viruses may be the result of horizontal gene transfers . The repeat has been found in proteins of diverse function such as transcriptional initiators.ell-cycle regulators.ytoskeletal.on transporters and signal transducers. The ankyrin fold appears to be defined by its structure rather than its function since there is no specific sequence or structure which is universally recognised by it. The conserved fold of the ankyrin repeat unit is known from several crystal and solution structures . Each repeat folds into a helix-loop-helix structure with a beta-hairpin/loop region projecting out from the helices at a 90o angle. The repeats stack together to form an L-shaped structure .
  IPR002110:Ankyrin
NOTCH signalling plays a fundamental role during a great number of developmental processes in multicellular animals . NOD (NOTCH protein domain) represents a region present in many NOTCH proteins and NOTCH homologues in multiple species such as 0.OTCH2 and NOTCH3.IN12.C1 and TAN1. Role of NOD domain remains to be elucidated.
  IPR010660:Notch, NOD region
NOTCH signalling plays a fundamental role during a great number of developmental processes in multicellular animals . NOD and NODP represent a region present in many NOTCH proteins and NOTCH homologs in multiple species such as NOTCH2 and NOTCH3.IN12.C1 and TAN1. The role of the NOD and NODP domains remains to be elucidated.
  IPR011656:Notch, NODP region
The Notch domain is also called the DSL domain or the Lin-12/Notch repeat (LNR). The LNR region is present only in Notch related proteins C-terminal to EGF repeats. The lin-12/Notch proteinsact as transmembrane receptors for intercellular signals that specify cell fates during animaldevelopment. In response to a ligand.roteolytic cleavages release the intracellular domain ofNotch.hich then gains access to the nucleus and acts as a transcriptional co-activator . TheLNR region is supposed to negatively regulate the Lin-12/Notch proteins activity. It is a triplicationof an around 35-40 amino acids module present on the extracellular part of the protein . Eachmodule contains six cysteine residues engaged in three disulphide bonds and three conserved aspartateand asparagine residues . The biochemical characterization of a recombinantly expressed LIN-12.1module from the human Notch1 receptor indicate that the disulphide bonds are formed between the firstand fifth.econd and fourth.nd third and sixth cysteines. The formation of this particular disulphideisomer is favored by the presence of Ca2+.hich is also required to maintain the structural integrityof the rLIN-12.1 module. The conserved aspartate and asparagine residues are likely to be important forCa2+ binding.nd thereby contribute to the native fold.
  IPR000800:Notch region
A sequence of about forty amino-acid residues found in epidermal growth factor (EGF) has been shown .o be present in a large number of membrane-bound and extracellular.ostly animal.roteins. Many of these proteins require calcium for their biological function and a calcium-binding site has been found at the N-terminus of some EGF-like domains . Calcium-binding may be crucial for numerous protein-protein interactions.For human coagulation factor IX it has been shown that the calcium-ligands form a pentagonal bipyramid. The first.hird and fourth conserved negatively charged or polar residues are side chain ligands. The latter is possibly hydroxylated (see aspartic acid and asparagine hydroxylation site) . A conserved aromatic residue.s well as the second conserved negative residue.re thought to be involved in stabilizing the calcium-binding site.As in non-calcium binding EGF-like domains.here are six conserved cysteines and the structure of both types is very similar as calcium-binding induces only strictly local structural changes .
  IPR001881:EGF-like calcium-binding
A sequence of about forty amino-acid residues found in epidermal growth factor (EGF) has been shown .o be present in a large number of membrane-bound and extracellular.ostly animal.roteins. Many of these proteins require calcium for their biological function and a calcium-binding site has been found at the N-terminus of some EGF-like domains . Calcium-binding may be crucial for numerous protein-protein interactions.For human coagulation factor IX it has been shown that the calcium-ligands form a pentagonal bipyramid. The first.hird and fourth conserved negatively charged or polar residues are side chain ligands. The latter is possibly hydroxylated (see aspartic acid and asparagine hydroxylation site) . A conserved aromatic residue.s well as the second conserved negative residue.re thought to be involved in stabilizing the calcium-binding site.As in non-calcium binding EGF-like domains.here are six conserved cysteines and the structure of both types is very similar as calcium-binding induces only strictly local structural changes .
  IPR013091:EGF calcium-binding
A sequence of about thirty to forty amino-acid residues long found in the sequence of epidermal growth factor (EGF)has been shown to be present.n a moreor less conserved form.n a large number of other.ostly animal proteins. The list of proteins currently known tocontain one or more copies of an EGF-like pattern is large and varied. The functional significance of EGF domains inwhat appear to be unrelated proteins is not yet clear. However. common feature is that these repeats are found inthe extracellular domain of membrane-bound proteins or in proteins known to be secreted (exception: prostaglandinG/H synthase). The EGF domain includes six cysteine residues which have been shown (in EGF) to be involved in disulphidebonds. The main structure is a two-stranded beta-sheet followed by a loop to a C-terminal short two-stranded sheet.Subdomains between the conserved cysteines vary in length.
  IPR006209:EGF-like
Epidermal growth factors and transforming growth factors belong to a general class of proteins that share a repeat pattern involving a number of conserved Cys residues. Growth factors are involved in cell recognition and division . The repeating pattern.specially of cysteines (the so-called EGF repeat).s thought to be important to the 3D structure of the proteins.nd hence its recognition by receptors and other molecules. The type 1 EGF signature includes six conserved cysteines believed to be involved in disulphide bond formation. The EGF motif is found frequently in nature.articularly in extracellular proteins.
  IPR006210:EGF
EGF-like repeats occur in coagulation factors.otch and xotch proteins.rotein Z.rokinases.lasminogen factors and the lin-12 protein . The repeat pattern is EGF-like in the sense that it does not share the exact Cys spacings of the type I EGF motif. The primary structures of many of the superfamily members contain regions that are dominated by multiple EGF-like repeats: these have been linked to some physiological role.hough the precise nature of this role is as yet unclear.The type II EGF-like signature is found in a variety of proteins having different functions and from a variety of sources.
  IPR001438:EGF-like, type 2
Notch is a membrane-bound transcription factor that regulates many cellular processes.specially in development. In response to ligand binding.ts intracellular domain is released by two proteases. The released intracellular domain enters the nucleus and interacts with a DNA-bound protein to activate transcription. The extracellular domain of notch and related proteins contains up to 36 EGF-like domains.ollowed by three notch (DSL) domains. The intracellular domain contains six ankyrin repeats and a carboxyl-terminal extension that includes a PEST region (rich in proline.lutamine.erine.nd threonine). Caenorhabditis elegans proteins lin-12 and glp1 are similar but have fewer EGF repeats.For additional information please see .
  IPR008297:Notch
IPR002110:ANK 
Evalue:-50.3565483093262 
Location:1820-2068IPR010660:NOD 
Evalue:-32.7212448120117 
Location:1539-1595IPR011656:NODP 
Evalue:-26.6989707946777 
Location:1617-1677IPR000800:NL 
Evalue:-17.0268721464003 
Location:1418-1456IPR001881:EGF_CA 
Evalue:-13.7695510786217 
Location:873-909IPR001881:EGF_CA 
Evalue:-13.4814860601221 
Location:456-492IPR001881:EGF_CA 
Evalue:-12.7212463990472 
Location:1025-1061IPR001881:EGF_CA 
Evalue:-12.4202164033832 
Location:182-219IPR001881:EGF_CA 
Evalue:-11.6197887582884 
Location:532-568IPR001881:EGF_CA 
Evalue:-11.5850266520292 
Location:494-530IPR001881:EGF_CA 
Evalue:-11.568636235841 
Location:1187-1223IPR001881:EGF_CA 
Evalue:-11.431798275933 
Location:911-947IPR001881:EGF_CA 
Evalue:-11.397940008672 
Location:415-454IPR001881:EGF_CA 
Evalue:-11.1938200260161 
Location:949-985IPR001881:EGF_CA 
Evalue:-11.0861861476163 
Location:757-793IPR001881:EGF_CA 
Evalue:-10.8860566476932 
Location:1149-1185IPR006209:EGF 
Evalue:-10.795880317688 
Location:799-830IPR001881:EGF_CA 
Evalue:-10.6382721639824 
Location:987-1023IPR000800:Notch 
Evalue:-10.508638381958 
Location:1498-1535IPR006209:EGF 
Evalue:-10.3010301589966 
Location:649-679IPR006209:EGF 
Evalue:-9.85387229919434 
Location:837-870IPR001881:EGF_CA 
Evalue:-9.85387196432176 
Location:607-643IPR001881:EGF_CA 
Evalue:-9.85387196432176 
Location:682-718IPR000800:NL 
Evalue:-9.72124639904717 
Location:1459-1497IPR001881:EGF_CA 
Evalue:-9.63827216398241 
Location:1225-1262IPR006209:EGF 
Evalue:-9.24412536621094 
Location:1308-1342IPR006209:EGF 
Evalue:-8.37675094604492 
Location:109-142IPR006209:EGF 
Evalue:-8.35654735565185 
Location:68-101IPR006209:EGF 
Evalue:-8.30980396270752 
Location:264-295IPR006209:EGF 
Evalue:-7.76955127716064 
Location:574-604IPR006209:EGF 
Evalue:-7.45593214035034 
Location:1067-1098IPR006209:EGF 
Evalue:-7.36653137207031 
Location:148-179IPR013091:EGF_CA 
Evalue:-7.20760822296143 
Location:298-335IPR006209:EGF 
Evalue:-7.07058095932007 
Location:379-412IPR006209:EGF 
Evalue:-6.85387182235718 
Location:225-257IPR006209:EGF 
Evalue:-6.74472761154175 
Location:1118-1146IPR006209:EGF 
Evalue:-6.65757751464844 
Location:1378-1411IPR006209:EGF 
Evalue:-6.63827228546143 
Location:724-754IPR001881:EGF_CA 
Evalue:-6.09691001300806 
Location:338-374IPR006209:EGF 
Evalue:-3.60206007957458 
Location:28-62IPR006209:EGF 
Evalue:-2.72124648094177 
Location:1268-1301IPR002110:ANK 
Evalue:0 
Location:2381-2435
SequencesProtein: NOTC2_HUMAN (2471 aa)
mRNA: NM_024408
Local Annotation
Synapse Ontology
A process that increases long-term neuronal synaptic plasticity, the ability of neuronal synapses to change long-term as circumstances require. Long-term neuronal synaptic plasticity generally involves increase or decrease in actual synapse numbers.
sdb:0039 positive regulation of long-term neuronal synaptic plasticity  (Evidence:keywords)
A process that increases short-term neuronal synaptic plasticity, the ability of neuronal synapses to change in the short-term as circumstances require. Short-term neuronal synaptic plasticity generally involves increasing or decreasing synaptic sensitivity.
sdb:0043 positive regulation of short-term neuronal synaptic plasticity  (Evidence:keywords)
the mechanism by which the restiong potential is held.
sdb:0288 maintain membrane potential  (Evidence:keywords)
KO assignmentK02599
  Level 3 annotation:
    Notch
  Level 2 annotation:
    Notch signaling pathway
    Dorso-ventral axis formation
Loci Structure (Details)Loci index, Chromosomal location, Length, Possible relational loci clusterExon1: 1714 residues, 120255700-120260840Exon2: 34 residues, 120261810-120261908Exon3: 51 residues, 120262551-120262699Exon4: 102 residues, 120263457-120263759Exon5: 58 residues, 120264374-120264543Exon6: 34 residues, 120265858-120265955Exon7: 72 residues, 120266381-120266592Exon8: 49 residues, 120266781-120266924Exon9: 118 residues, 120267782-120268130Exon10: 170 residues, 120269450-120269956Exon11: 39 residues, 120270644-120270757Exon12: 81 residues, 120273121-120273358Exon13: 46 residues, 120279617-120279750Exon14: 63 residues, 120281427-120281612Exon15: 53 residues, 120282002-120282156Exon16: 69 residues, 120284700-120284902Exon17: 78 residues, 120285671-120285900Exon18: 53 residues, 120292559-120292712Exon19: 42 residues, 120293152-120293272Exon20: 40 residues, 120294869-120294983Exon21: 50 residues, 120297688-120297834Exon22: 66 residues, 120299185-120299378Exon23: 39 residues, 120303537-120303648Exon24: 80 residues, 120307719-120307953Exon25: 40 residues, 120309598-120309712Exon26: 40 residues, 120310521-120310635Exon27: 65 residues, 120311578-120311767Exon28: 54 residues, 120312222-120312378Exon29: 80 residues, 120313656-120313890Exon30: 43 residues, 120331105-120331228Exon31: 114 residues, 120341142-120341478Exon32: 88 residues, 120349474-120349734Exon33: 29 residues, 120374051-120374133Exon34: 111 residues, 120413470-120413799Exon35: 2 residues, -Jump to NOTC2_HUMAN  
Tune and view alternative isoforms
Loci Cluster (Details)Loci: 2544 120056032-120088359 ~-32K 2308(PHGDH)(+)Loci: 3825 120092527-120113041 ~-21K 2310(HMGCS2)(-)Loci: 3826 120255700-120413799 ~-158K 2313(NOTCH2)(-)Loci: 2543 119759295-119767172 ~-8K 2303(HSD3B2)(+)Link out to UCSC