notch-2 (Drosophila) homolog protein (NOTCH2)

Function: - functions as a receptor for membrane-bound ligands Jagged1, Jagged2 & delta1 to regulate cell-fate determination - upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBP-J kappa & activates genes of the enhancer of split locus - affects implementation of differentiation, proliferation & apoptotic programs (putative) - 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) & a N-terminal fragment N(EC) - following ligand binding, it is cleaved by TNF-alpha converting enzyme (TACE) to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT) - this fragment is then cleaved by presenilin dependent gamma-secretase to release a notch-derived peptide containing the intracellular domain (NICD) from the membrane (putative) - phosphorylated (putative) - heterodimer of a C-terminal fragment N(TM) & an N-terminal fragment N(EC) which are probably linked by disulfide bonds (putative) - interacts with MAML1, MAML2 & MAML3 which act as transcriptional coactivators for NOTCH2 Structure: - belongs to the NOTCH family - contains 6 ANK repeats - contains 35 EGF-like domains - contains 3 LNR (lin/notch) repeats Compartment: - cell membrane; single-pass type 1 membrane protein - notch 2 intracellular domain: nucleus - following proteolytical processing NICD is translocated to the nucleus Expression: - expressed in the brain, heart, kidney, lung, skeletal muscle & liver Pathology: - defects in NOTCH2 are the cause of Alagille syndrome type 2

General

ankyrin repeat domain protein (ANKRD) glycoprotein notch (Drosophila) homolog protein phosphoprotein

Properties

SIZE: entity length = 2471 aa MW = 265 kD COMPARTMENT: cell nucleus cellular membrane MOTIF: signal sequence {1-25} EGF domain {26-1412} (35) Notch/Lin12 repeat {1425-1544} (3) cysteine residue {C1503} MODIFICATION: cysteine residue {C1527} cysteine residue {C1509} MODIFICATION: cysteine residue {C1522} cysteine residue {C1518} MODIFICATION: cysteine residue {C1534} cysteine residue {C1522} MODIFICATION: cysteine residue {C1509} cysteine residue {C1527} MODIFICATION: cysteine residue {C1503} cysteine residue {C1534} MODIFICATION: cysteine residue {C1518} cysteine residue {C1632} MODIFICATION: cysteine residue {C1639} cysteine residue {C1639} MODIFICATION: cysteine residue {C1632} transmembrane domain ankyrin repeat NAME: ankyrin repeat (6) transmembrane domain {1678-1698} Thr phosphorylation site {T1716} Ser phosphorylation site {S1778} Thr phosphorylation site {T1802} Ser phosphorylation site {S1804} Thr phosphorylation site {T1808} ankyrin repeat NAME: ankyrin repeat SITE: 1827-1871 MOTIF: Ser phosphorylation site {S1841} Ser phosphorylation site {S1842} Ser phosphorylation site {S1845} ankyrin repeat NAME: ankyrin repeat SITE: 1876-1905 ankyrin repeat NAME: ankyrin repeat SITE: 1909-1939 ankyrin repeat NAME: ankyrin repeat SITE: 1943-1972 ankyrin repeat NAME: ankyrin repeat SITE: 1976-2005 ankyrin repeat NAME: ankyrin repeat SITE: 2009-2038 Ser phosphorylation site {S2070} Thr phosphorylation site {T2074} Ser phosphorylation site {S2078} Ser phosphorylation site {S2081} Thr phosphorylation site {T2097} serine-rich region {2426-2429} MOTIF: serine residue (SEVERAL)

Database Correlations

OMIM correlations MORBIDMAP 600275 UniProt Q04721 PFAM correlations Entrez Gene 4853 Kegg hsa:4853