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Details on Person UniProt:Q14511 NEDD9
| Class:Id | ReferenceGeneProduct:69960 |
|---|---|
| _chainChangeLog | chain:1-834 added on Sat February 7 2015;chain:1- added on Sat February 7 2015 |
| _displayName | UniProt:Q14511 NEDD9 |
| _timestamp | 2025-08-15 21:43:49 |
| chain | chain:1-834 chain:1- |
| checksum | C54DEC36C8C8E9E6 |
| comment | FUNCTION Scaffolding protein which plays a central coordinating role for tyrosine-kinase-based signaling related to cell adhesion (PubMed:24574519). As a focal adhesion protein, plays a role in embryonic fibroblast migration (By similarity). May play an important role in integrin beta-1 or B cell antigen receptor (BCR) mediated signaling in B- and T-cells. Integrin beta-1 stimulation leads to recruitment of various proteins including CRKL and SHPTP2 to the tyrosine phosphorylated form (PubMed:9020138). Promotes adhesion and migration of lymphocytes; as a result required for the correct migration of lymphocytes to the spleen and other secondary lymphoid organs (PubMed:17174122). Plays a role in the organization of T-cell F-actin cortical cytoskeleton and the centralization of T-cell receptor microclusters at the immunological synapse (By similarity). Negatively regulates cilia outgrowth in polarized cysts (By similarity). Modulates cilia disassembly via activation of AURKA-mediated phosphorylation of HDAC6 and subsequent deacetylation of alpha-tubulin (PubMed:17604723). Positively regulates RANKL-induced osteoclastogenesis (By similarity). Required for the maintenance of hippocampal dendritic spines in the dentate gyrus and CA1 regions, thereby involved in spatial learning and memory (By similarity).SUBUNIT Homodimer (PubMed:10502414, PubMed:9584194). Forms heterodimers with BCAR1/p130cas (PubMed:10502414). Forms complexes with PTK2B/RAFTK, adapter protein CRKL and LYN kinase (PubMed:9020138). Part of a complex composed of NEDD9, AURKA and CTTN; within the complex NEDD9 acts as a scaffold protein and is required for complex formation (PubMed:24574519). Part of a ternary complex composed of SMAD3, ITCH/AIP4 and NEDD9/HEF1; within the complex NEDD9/HEF1 interacts (via N-terminus) with ITCH/AIP4 (via WW domains); the complex mediates ubiquitination and proteasomal degradation of NEDD9/HEF1 (PubMed:15051726). Interacts with SMAD3; the interaction promotes NEDD9 ubiquitination and proteasomal degradation (PubMed:24574519). Interacts with ID2 (PubMed:10502414). Interacts with CTTN (via N-terminus) (PubMed:24574519). Interacts with MICAL (PubMed:11827972). Interacts with TXNL4/DIM1 (PubMed:11054566). Interacts with BCAR3 (via Ras-GEF domain) (PubMed:19103205). Interacts with SH2D3C isoform 1 and isoform 2 (By similarity). Interacts with ECT2 (PubMed:16394104). Interacts with PTPN11/SHP-2 (via SH2 domains); the interaction is enhanced when NEDD9/CAS-L is tyrosine phosphorylated (PubMed:19275884). Interacts (via C-terminus) with PLK1 (via polo box domains) (PubMed:29191835). Interacts with NKX2-5 (PubMed:29899023). Interacts with SMAD3; the interaction is inhibited by oxidation of NEDD9 (PubMed:15051726, PubMed:29899023). Interacts with NEDD9/HEF1; interaction is induced by CXCL12 promotion of ABL-mediated phosphorylation of NEDD9/HEF1 (PubMed:22810897). Interacts (via SH3 domain) with PTK2/FAK (PubMed:8668148, PubMed:8879209, PubMed:9360983). Interacts with FYN; in the presence of PTK2 (PubMed:9360983). Interacts with INPPL1/SHIP2 (By similarity).INTERACTION Expressed in B-cells (at protein level) (PubMed:9020138). Expressed in the respiratory epithelium of the main bronchi to the bronchioles in the lungs (at protein level) (PubMed:9584194). High levels detected in kidney, lung, and placenta (PubMed:9584194). Expressed in lymphocytes (PubMed:9497377).DEVELOPMENTAL STAGE initially expressed in the fetus (at protein level).INDUCTION Induced by oxidant stress in pulmonary artery endothelial cells.DOMAIN Contains a central domain containing multiple potential SH2-binding sites and a C-terminal domain containing a divergent helix-loop-helix (HLH) motif (PubMed:10502414). The SH2-binding sites putatively bind CRKL SH2 domains (PubMed:9020138). The HLH motif confers specific interaction with the HLH protein ID2 (PubMed:10502414). It is absolutely required for the induction of pseudohyphal growth in yeast and mediates homodimerization and heterodimerization with BCAR1/p130cas (PubMed:10502414, PubMed:8668148).PTM Cell cycle-regulated processing produces four isoforms: p115, p105, p65, and p55. Isoform p115 arises from p105 phosphorylation and appears later in the cell cycle. Isoform p55 arises from p105 as a result of cleavage at a caspase cleavage-related site and it appears specifically at mitosis. The p65 isoform is poorly detected.PTM Polyubiquitinated by ITCH/AIP4, leading to proteasomal degradation.PTM PTK2/FAK1 phosphorylates the protein at the YDYVHL motif (conserved among all cas proteins) following integrin stimulation (PubMed:9360983). The SRC family kinases (FYN, SRC, LCK and CRK) are recruited to the phosphorylated sites and can phosphorylate other tyrosine residues (PubMed:9020138). Ligation of either integrin beta-1 or B-cell antigen receptor on tonsillar B-cells and B-cell lines promotes tyrosine phosphorylation and both integrin and BCR-mediated tyrosine phosphorylation requires an intact actin network (PubMed:9020138). Phosphorylation is required to recruit NEDD9 to T-cell receptor microclusters at the periphery of newly formed immunological synapses (By similarity). In fibroblasts transformation with oncogene v-ABL results in an increase in tyrosine phosphorylation. Transiently phosphorylated following CD3 cross-linking and this phosphorylated form binds to CRKL and C3G (PubMed:9497377). A mutant lacking the SH3 domain is phosphorylated upon CD3 cross-linking but not upon integrin beta-1 cross-linking (PubMed:9497377). Tyrosine phosphorylation occurs upon stimulation of the G-protein coupled C1a calcitonin receptor. Calcitonin-stimulated tyrosine phosphorylation is mediated by calcium- and protein kinase C-dependent mechanisms and requires the integrity of the actin cytoskeleton. Phosphorylation at Ser-369 induces proteasomal degradation (PubMed:19539609). Phosphorylated by LYN (PubMed:9020138). Phosphorylation at Ser-780 by CSNK1D or CSNK1E, or phosphorylation of Thr-804 by CSNK1E enhances the interaction of NEDD9 with PLK1 (PubMed:29191835).SIMILARITY Belongs to the CAS family. |
| description | recommendedName: fullName evidence="31"Enhancer of filamentation 1 shortName evidence="31"hEF1 alternativeName: fullName evidence="30"CRK-associated substrate-related protein shortName evidence="30"CAS-L shortName evidence="26"CasL alternativeName: fullName evidence="33"Cas scaffolding protein family member 2 shortName evidence="33"CASS2 alternativeName: fullName evidence="33"Neural precursor cell expressed developmentally down-regulated protein 9 shortName evidence="33"NEDD-9 alternativeName: fullName evidence="25"Renal carcinoma antigen NY-REN-12 alternativeName: fullName evidence="29"p105 component recommendedName: Enhancer of filamentation 1 p55 /component |
| geneName | NEDD9 CASL |
| identifier | Q14511 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing Cell adhesion Cell cycle Cell division Cell junction Cell membrane Cell projection Cytoplasm Cytoskeleton Golgi apparatus Growth regulation Membrane Mitosis Nucleus Phosphoprotein Proteomics identification Reference proteome SH3 domain Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9841277] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 |
| name | NEDD9 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8991156] ENSEMBL:ENSG00000111859 NEDD9 [Homo sapiens] |
| secondaryIdentifier | CASL_HUMAN A8K9G7 A8MSJ9 G5E9Y9 Q5T9R4 Q5XKI0 |
| sequenceLength | 834 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:8975475] UniProt:Q14511-1 NEDD9 [Homo sapiens] [ReferenceIsoform:8975476] UniProt:Q14511-2 NEDD9 [Homo sapiens] [ReferenceIsoform:8975477] UniProt:Q14511-3 NEDD9 [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:201571] NEDD9 [cytosol] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:Q14511 NEDD9 (69960)
