P46530
SS
Gene name |
notch1a (notch) |
Protein name |
Neurogenic locus notch homolog protein 1 |
Names |
Notch 1 [Cleaved into: Notch 1 extracellular truncation , NEXT; Notch 1 intracellular domain , NICD] |
Species |
Danio rerio (Zebrafish) (Brachydanio rerio) |
KEGG Pathway |
dre:30718 |
EC number |
|
Protein Class |
|
Descriptions
NOTCH1 is a neurogenic locus notch homolog protein 1 and belongs to the NOTCH family of proteins that regulate cell growth, proliferation, differentiation and apoptosis in both embryonic and adult tissues. The negative regulatory region (NRR) of NOTCH1 contains three Lin12/Notch repeats (LNR-A, LNR-B, and LNR-C). The LNR-C hydrophobic residues pack against the heterodimerization (HD) domain core. In addition, the LNR-B, the linker between LNR-A and LNR-B, and the C-terminus of LNR-A wrap around the HD domain, thus masking the metalloprotease site (S2) and preventing exposure to receptor activation. For the activation of NOTCH1, the LNR-A, LNR-AB linker, and LNR-B must be removed.
Autoinhibitory domains (AIDs)
Target domain |
1562-1718 (HD domain) |
Relief mechanism |
Cleavage |
Assay |
|
Accessory elements
No accessory elements
References
- Gordon WR et al. (2007) "Structural basis for autoinhibition of Notch", Nature structural & molecular biology, 14, 295-300
- Tiyanont K et al. (2011) "Evidence for increased exposure of the Notch1 metalloprotease cleavage site upon conversion to an activated conformation", Structure (London, England : 1993), 19, 546-54
- Gordon WR et al. (2009) "Structure of the Notch1-negative regulatory region: implications for normal activation and pathogenic signaling in T-ALL", Blood, 113, 4381-90
Autoinhibited structure
Activated structure
1 structures for P46530
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-P46530-F1 | Predicted | AlphaFoldDB |
No variants for P46530
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for P46530 | |||||
No associated diseases with P46530
5 regional properties for P46530
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain | 588 - 912 | IPR002073 |
| domain | GAF domain | 217 - 380 | IPR003018-1 |
| domain | GAF domain | 402 - 568 | IPR003018-2 |
| domain | HD/PDEase domain | 661 - 839 | IPR003607 |
| conserved_site | 3'5'-cyclic nucleotide phosphodiesterase, conserved site | 704 - 715 | IPR023174 |
2 GO annotations of cellular component
| Name | Definition |
|---|---|
| nucleus | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
3 GO annotations of molecular function
| Name | Definition |
|---|---|
| calcium ion binding | Binding to a calcium ion (Ca2+). |
| Notch binding | Binding to a Notch (N) protein, a surface receptor. |
| signaling receptor activity | Receiving a signal and transmitting it in the cell to initiate a change in cell activity. A signal is a physical entity or change in state that is used to transfer information in order to trigger a response. |
26 GO annotations of biological process
| Name | Definition |
|---|---|
| angiogenesis | Blood vessel formation when new vessels emerge from the proliferation of pre-existing blood vessels. |
| anterior/posterior pattern specification | The regionalization process in which specific areas of cell differentiation are determined along the anterior-posterior axis. The anterior-posterior axis is defined by a line that runs from the head or mouth of an organism to the tail or opposite end of the organism. |
| cilium assembly | The assembly of a cilium, a specialized eukaryotic organelle that consists of a filiform extrusion of the cell surface. Each cilium is bounded by an extrusion of the cytoplasmic membrane, and contains a regular longitudinal array of microtubules, anchored basally in a centriole. |
| determination of left/right symmetry | The establishment of an organism's body plan or part of an organism with respect to the left and right halves. The pattern can either be symmetric, such that the halves are mirror images, or asymmetric where the pattern deviates from this symmetry. |
| dorsal aorta development | The progression of the dorsal aorta over time, from its initial formation to the mature structure. The dorsal aorta is a blood vessel in a single-pass circulatory system that carries oxygenated blood from the gills to the rest of the body. In a single-pass circulatory system blood passes once through the heart to supply the body once. |
| exocrine pancreas development | The process whose specific outcome is the progression of the exocrine pancreas over time, from its formation to the mature structure. The exocrine pancreas produces and store zymogens of digestive enzymes, such as chymotrypsinogen and trypsinogen in the acinar cells. |
| generation of neurons | The process in which nerve cells are generated. This includes the production of neuroblasts and their differentiation into neurons. |
| habenula development | The progression of the habenula over time from its initial formation until its mature state. The habenula is the group of nuclei that makes up the stalk of the pineal gland. |
| hematopoietic progenitor cell differentiation | The process in which precursor cell type acquires the specialized features of a hematopoietic progenitor cell, a class of cell types including myeloid progenitor cells and lymphoid progenitor cells. |
| hematopoietic stem cell differentiation | The process in which a relatively unspecialized cell acquires specialized features of a hematopoietic stem cell. A stem cell is a cell that retains the ability to divide and proliferate throughout life to provide progenitor cells that can differentiate into specialized cells. |
| hypochord development | The process whose specific outcome is the progression of the hypochord over time, from its formation to the mature structure. The hypochord is a transient rod-like structure in the embryos of fish, lampreys and amphibians that is located immediately ventral to the notochord. The hypochord may play a role in positioning the dorsal aorta. |
| negative regulation of neurogenesis | Any process that stops, prevents, or reduces the frequency, rate or extent of neurogenesis, the generation of cells within the nervous system. |
| neural plate development | The process whose specific outcome is the progression of the neural plate over time, from its formation to the mature structure. The neural plate is a flat, thickened layer of ectodermal cells. The underlying dorsal mesoderm signals the ectodermal cells above it to elongate into columnar neural plate cells. The neural plate subsequently develops into the neural tube, which gives rise to the central nervous system. |
| Notch signaling involved in heart development | The series of molecular signals initiated by binding of an extracellular ligand to a Notch receptor on the surface of the target cell and contributing to the progression of the heart over time. |
| Notch signaling pathway | The series of molecular signals initiated by an extracellular ligand binding to the receptor Notch on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. |
| pancreas development | The process whose specific outcome is the progression of the pancreas over time, from its formation to the mature structure. The pancreas is an endoderm derived structure that produces precursors of digestive enzymes and blood glucose regulating hormones. |
| peripheral nervous system neuron axonogenesis | Generation of a long process from a neuron whose cell body resides in the peripheral nervous system. The axon carries action potential from the cell body towards target cells. |
| positive regulation of mesodermal cell fate specification | Any process that activates or increases the frequency, rate or extent of mesoderm cell fate specification. |
| regulation of DNA-templated transcription | Any process that modulates the frequency, rate or extent of cellular DNA-templated transcription. |
| regulation of endodermal cell fate specification | Any process that mediates the specification of a cell into an endoderm cell. |
| regulation of non-canonical NF-kappaB signal transduction | Any process that modulates the frequency, rate or extent of NIK/NF-kappaB signaling. |
| regulation of receptor-mediated endocytosis | Any process that modulates the frequency, rate or extent of receptor mediated endocytosis, the uptake of external materials by cells, utilizing receptors to ensure specificity of transport. |
| somatic motor neuron differentiation | The process in which neuroepithelial cells in the neural tube acquire specialized structural and/or functional features of somatic motor neurons. Somatic motor neurons innervate skeletal muscle targets and are responsible for transmission of motor impulses from the brain to the periphery. Differentiation includes the processes involved in commitment of a cell to a specific fate. |
| somitogenesis | The formation of mesodermal clusters that are arranged segmentally along the anterior posterior axis of an embryo. |
| spinal cord radial glial cell differentiation | The process in which neuroepithelial cells in the ventral neural tube acquire specialized structural and/or functional features of radial glial cells. Radial cell precursors differentiate into both neuronal cell types and mature radial glial cells. Mature radial glial cells regulate the axon growth and pathfinding processes that occur during white matter patterning of the developing spinal cord. Differentiation includes the processes involved in commitment of a cell to a specific fate. |
| ventral spinal cord interneuron differentiation | The process in which neuroepithelial cells in the neural tube acquire specialized structural and/or functional features of ventral spinal cord interneurons. Ventral spinal cord interneurons are cells located in the ventral portion of the spinal cord that transmit signals between sensory and motor neurons and are required for reflexive responses. Differentiation includes the processes involved in commitment of a cell to a specific fate. |
13 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q868Z9 | Ppn | Papilin | Drosophila melanogaster (Fruit fly) | SS |
| Q04721 | NOTCH2 | Neurogenic locus notch homolog protein 2 | Homo sapiens (Human) | EV |
| P21941 | MATN1 | Cartilage matrix protein | Homo sapiens (Human) | PR |
| P46531 | NOTCH1 | Neurogenic locus notch homolog protein 1 | Homo sapiens (Human) | EV |
| Q6GUQ1 | Egfl8 | Epidermal growth factor-like protein 8 | Mus musculus (Mouse) | PR |
| Q91V88 | Npnt | Nephronectin | Mus musculus (Mouse) | PR |
| O35516 | Notch2 | Neurogenic locus notch homolog protein 2 | Mus musculus (Mouse) | SS |
| P51942 | Matn1 | Cartilage matrix protein | Mus musculus (Mouse) | PR |
| Q01705 | Notch1 | Neurogenic locus notch homolog protein 1 | Mus musculus (Mouse) | SS |
| Q9QW30 | Notch2 | Neurogenic locus notch homolog protein 2 | Rattus norvegicus (Rat) | SS |
| Q07008 | Notch1 | Neurogenic locus notch homolog protein 1 | Rattus norvegicus (Rat) | SS |
| P13508 | glp-1 | Protein glp-1 | Caenorhabditis elegans | EV |
| A2RUV0 | notch1 | Neurogenic locus notch homolog protein 1 | Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MNRFLVKLTL | LTAASLATVA | QGQRCSEYCQ | NGGICEYKPS | GEASCRCPAD | FVGAQCQFPN |
| 70 | 80 | 90 | 100 | 110 | 120 |
| PCNPSPCRNG | GVCRPQMQGN | EVGVKCDCVL | GFSDRLCLTP | VNHACMNSPC | RNGGTCSLLT |
| 130 | 140 | 150 | 160 | 170 | 180 |
| LDTFTCRCQP | GWSGKTCQLA | DPCASNPCAN | GGQCSAFESH | YICTCPPNFH | GQTCRQDVNE |
| 190 | 200 | 210 | 220 | 230 | 240 |
| CAVSPSPCRN | GGTCINEVGS | YLCRCPPEYT | GPHCQRLYQP | CLPSPCRSGG | TCVQTSDTTH |
| 250 | 260 | 270 | 280 | 290 | 300 |
| TCSCLPGFTG | QTCEHNVDDC | TQHACENGGP | CIDGINTYNC | HCDKHWTGQY | CTEDVDECEL |
| 310 | 320 | 330 | 340 | 350 | 360 |
| SPNACQNGGT | CHNTIGGFHC | VCVNGWTGDD | CSENIDDCAS | AACSHGATCH | DRVASFFCEC |
| 370 | 380 | 390 | 400 | 410 | 420 |
| PHGRTGLLCH | LDDACISNPC | QKGSNCDTNP | VSGKAICTCP | PGYTGSACNQ | DIDECSLGAN |
| 430 | 440 | 450 | 460 | 470 | 480 |
| PCEHGGRCLN | TKGSFQCKCL | QGYEGPRCEM | DVNECKSNPC | QNDATCLDQI | GGFHCICMPG |
| 490 | 500 | 510 | 520 | 530 | 540 |
| YEGVFCQINS | DDCASQPCLN | GKCIDKINSF | HCECPKGFSG | SLCQVDVDEC | ASTPCKNGAK |
| 550 | 560 | 570 | 580 | 590 | 600 |
| CTDGPNKYTC | ECTPGFSGIH | CELDINECAS | SPCHYGVCRD | GVASFTCDCR | PGYTGRLCET |
| 610 | 620 | 630 | 640 | 650 | 660 |
| NINECLSQPC | RNGGTCQDRE | NAYICTCPKG | TTGVNCEINI | DDCKRKPCDY | GKCIDKINGY |
| 670 | 680 | 690 | 700 | 710 | 720 |
| ECVCEPGYSG | SMCNINIDDC | ALNPCHNGGT | CIDGVNSFTC | LCPDGFRDAT | CLSQHNECSS |
| 730 | 740 | 750 | 760 | 770 | 780 |
| NPCIHGSCLD | QINSYRCVCE | AGWMGRNCDI | NINECLSNPC | VNGGTCKDMT | SGYLCTCRAG |
| 790 | 800 | 810 | 820 | 830 | 840 |
| FSGPNCQMNI | NECASNPCLN | QGSCIDDVAG | FKCNCMLPYT | GEVCENVLAP | CSPRPCKNGG |
| 850 | 860 | 870 | 880 | 890 | 900 |
| VCRESEDFQS | FSCNCPAGWQ | GQTCEVDINE | CVRNPCTNGG | VCENLRGGFQ | CRCNPGFTGA |
| 910 | 920 | 930 | 940 | 950 | 960 |
| LCENDIDDCE | PNPCSNGGVC | QDRVNGFVCV | CLAGFRGERC | AEDIDECVSA | PCRNGGNCTD |
| 970 | 980 | 990 | 1000 | 1010 | 1020 |
| CVNSYTCSCP | AGFSGINCEI | NTPDCTESSC | FNGGTCVDGI | SSFSCVCLPG | FTGNYCQHDV |
| 1030 | 1040 | 1050 | 1060 | 1070 | 1080 |
| NECDSRPCQN | GGSCQDGYGT | YKCTCPHGYT | GLNCQSLVRW | CDSSPCKNGG | SCWQQGASFT |
| 1090 | 1100 | 1110 | 1120 | 1130 | 1140 |
| CQCASGWTGI | YCDVPSVSCE | VAARQQGVSV | AVLCRHAGQC | VDAGNTHLCR | CQAGYTGSYC |
| 1150 | 1160 | 1170 | 1180 | 1190 | 1200 |
| QEQVDECQPN | PCQNGATCTD | YLGGYSCECV | PGYHGMNCSK | EINECLSQPC | QNGGTCIDLV |
| 1210 | 1220 | 1230 | 1240 | 1250 | 1260 |
| NTYKCSCPRG | TQGVHCEIDI | DDCSPSVDPL | TGEPRCFNGG | RCVDRVGGYG | CVCPAGFVGE |
| 1270 | 1280 | 1290 | 1300 | 1310 | 1320 |
| RCEGDVNECL | SDPCDPSGSY | NCVQLINDFR | CECRTGYTGK | RCETVFNGCK | DTPCKNGGTC |
| 1330 | 1340 | 1350 | 1360 | 1370 | 1380 |
| AVASNTKHGY | ICKCQPGYSG | SSCEYDSQSC | GSLRCRNGAT | CVSGHLSPRC | LCAPGFSGHE |
| 1390 | 1400 | 1410 | 1420 | 1430 | 1440 |
| CQTRMDSPCL | VNPCYNGGTC | QPISDAPFYR | CSCPANFNGL | LCHILDYSFS | GGQGRDIAPP |
| 1450 | 1460 | 1470 | 1480 | 1490 | 1500 |
| VEVEIRCEIA | QCEGRGGNAI | CDTQCNNHAC | GWDGGDCSLN | FDDPWQNCSA | ALQCWRYFND |
| 1510 | 1520 | 1530 | 1540 | 1550 | 1560 |
| GKCDEQCATA | GCLYDGFDCQ | RLEGQCNPLY | DQYCRDHYAD | GHCDQGCNNA | ECEWDGLDCA |
| 1570 | 1580 | 1590 | 1600 | 1610 | 1620 |
| DDVPQKLAVG | SLVLVVHIPP | DELRNRSSSF | LRELSSLLHT | NVVFRRDANG | EALIFPYYGS |
| 1630 | 1640 | 1650 | 1660 | 1670 | 1680 |
| EHELSKHKRS | DWTDPGQLMQ | RARRSLTSFL | KPRTRRELDH | MEVKGSIVYL | EIDNRQCFQQ |
| 1690 | 1700 | 1710 | 1720 | 1730 | 1740 |
| SDECFQSATD | VAAFLGALAS | SGNLNVPYII | EAVTSEGGPP | KTGEMYPMFL | VLLALAVLAL |
| 1750 | 1760 | 1770 | 1780 | 1790 | 1800 |
| AAVGVVVSRK | RKREHGQLWF | PEGFKVNEPK | KKRREPVGED | SVGLKPLKNS | DSSLMDEQLS |
| 1810 | 1820 | 1830 | 1840 | 1850 | 1860 |
| EWAEDDTNKR | FRFEGQSILE | MSGQLDHRQW | TQQHLDAADL | RLNSMAPTPP | QGQIENDCMD |
| 1870 | 1880 | 1890 | 1900 | 1910 | 1920 |
| VNVRGPDGFT | PLMIASCSGG | GLENENGEAE | EDPSADVITD | FIYHGANLHN | QTDRTGETAL |
| 1930 | 1940 | 1950 | 1960 | 1970 | 1980 |
| HLAARYARSD | AAKRLLESCA | DANVQDNMGR | TPLHAAVAAD | AQGVFQILIR | NRATDLDARM |
| 1990 | 2000 | 2010 | 2020 | 2030 | 2040 |
| HDGTTPLILA | TRLAVEGMVE | ELINCHADPN | AVDDSGKSAL | HWAAAVNNVD | AAVVLLKNGA |
| 2050 | 2060 | 2070 | 2080 | 2090 | 2100 |
| NKDLQNNKEE | TPLFLAAREG | SYETAKVLLD | HLANRDIADH | LDQLPRDIAH | ERMHHDIVRL |
| 2110 | 2120 | 2130 | 2140 | 2150 | 2160 |
| LEEYNLVRSP | PLPLSPPLCC | PNTYLGIKPS | PGNNNNTAKK | TRKPGGKGVG | GKDSGKDIRT |
| 2170 | 2180 | 2190 | 2200 | 2210 | 2220 |
| KKKKSGDGKN | GGIMEVGVLS | PVDSLESPHG | YLSDVSSPPM | MTSPFQQSPP | ISLNQLQGLA |
| 2230 | 2240 | 2250 | 2260 | 2270 | 2280 |
| DSHMGGALQG | LGKPFDSAPR | LSHLPVANNV | GGAQAGACDW | LQRVQQQQQQ | QQQQQQAGML |
| 2290 | 2300 | 2310 | 2320 | 2330 | 2340 |
| MPTMLSATNM | PQVMGYPTMQ | SSHLGAPSHM | IAHQNMAPMQ | HQNISHHFLG | DLSGLDLQSS |
| 2350 | 2360 | 2370 | 2380 | 2390 | 2400 |
| SGHAPIQTIL | PQDSQRMAPP | ISSTQFLTPP | SQHSYSNPMD | NTPNHQQVPD | HPFLTPSAGS |
| 2410 | 2420 | 2430 | |||
| PDQWSSSSPH | SNLSDWSEGI | SSPPTSMQMN | HIPEAFK |