UniProt:Q9Y2J4 AMOTL2

chain
  • chain:1-779
checksum 665BE69FD7757CEF
comment
  • FUNCTION Regulates the translocation of phosphorylated SRC to peripheral cell-matrix adhesion sites. Required for proper architecture of actin filaments. Plays a role in coupling actin fibers to cell junctions in endothelial cells and is therefore required for correct endothelial cell morphology via facilitating transcellular transmission of mechanical force resulting in endothelial cell elongation (By similarity). Required for the anchoring of radial actin fibers to CDH1 junction complexes at the cell membrane which facilitates organization of radial actin fiber structure and cellular response to contractile forces (PubMed:28842668). This contributes to maintenance of cell area, size, shape, epithelial sheet organization and trophectoderm cell properties that facilitate blastocyst zona hatching (PubMed:28842668). Inhibits the Wnt/beta-catenin signaling pathway, probably by recruiting CTNNB1 to recycling endosomes and hence preventing its translocation to the nucleus. Participates in angiogenesis. Activates the Hippo signaling pathway in response to cell contact inhibition via interaction with and ubiquitination by Crumbs complex-bound WWP1 (PubMed:34404733). Ubiquitinated AMOTL2 then interacts with LATS2 which in turn phosphorylates YAP1, excluding it from the nucleus and localizing it to the cytoplasm and tight junctions, therefore ultimately repressing YAP1-driven transcription of target genes (PubMed:17293535, PubMed:21205866, PubMed:26598551). Acts to inhibit WWTR1/TAZ transcriptional coactivator activity via sequestering WWTR1/TAZ in the cytoplasm and at tight junctions (PubMed:23911299). Regulates the size and protein composition of the podosome cortex and core at myofibril neuromuscular junctions (PubMed:23525008). Selectively promotes FGF-induced MAPK activation through SRC (PubMed:17293535). May play a role in the polarity, proliferation and migration of endothelial cells.SUBUNIT Part of a complex composed of AMOTL2, MAGI1 and CDH5, within the complex AMOTL2 acts as a scaffold protein for the interaction of MAGI1 with CDH5 (By similarity). The complex is required for coupling actin fibers to cell junctions in endothelial cells (By similarity). Within the complex AMOTL2 (via its N-terminus) interacts with CDH5 (By similarity). Interacts (via N-terminus) with MAGI1 (By similarity). Interacts (via N-terminus) with ACTB; the interaction facilitates binding of cell junction complexes to actin fibers in endothelial cells (By similarity). Interacts with CDH1; the interaction may facilitate binding of radial actin fibers to cell junction complexes (PubMed:28842668). Interacts with SRC (PubMed:17293535). Interacts with YAP1; the interaction is required for ubiquitination of AMOTL2 and localization of YAP1 to tight junctions (PubMed:21205866, PubMed:26598551). Interacts with WWP1; the interaction facilitates WWP1 interaction with the Crumbs complex and subsequent WWP1 translocation to the plasma membrane (PubMed:34404733). WWP1 interaction with the Crumbs complex promotes WWP1 monoubiquitination of AMOTL2 which subsequently activates the Hippo signaling pathway (PubMed:34404733). When ubiquitinated interacts with LATS2 (via UBA domain); the interaction promotes LATS2 phosphorylation of YAP1 (PubMed:26598551). Interacts (via PPXY motif) with WWTR1/TAZ (via WW domain); the interaction promotes WWTR1/TAZ localization to the cytoplasm and thereby inhibition of its transcriptional properties (PubMed:23911299). Interacts with PHLDB2; interaction may facilitate PHLDB2 localization to the myotube podosome cortex that surrounds the core (PubMed:23525008).SUBCELLULAR LOCATION Expressed in the trophectoderm of the blastocyst at 5 dpc (at protein level).PTM Monoubiquitinated at Lys-347 and Lys-408 by Crumbs complex-bound WWP1 (PubMed:34404733). De-ubiquitinated at Lys-347 and Lys-408 by USP9X; the interaction may be promoted by cell contact inhibition (PubMed:26598551, PubMed:34404733). Deubiquitination of AMOTL2 negatively regulates Hippo signaling activation (PubMed:26598551).PTM Phosphorylation at Tyr-107 is necessary for efficient binding to SRC and synergistically functioning with SRC to activate the downstream MAPK pathway.SIMILARITY Belongs to the angiomotin family.SEQUENCE CAUTION Truncated N-terminus.SEQUENCE CAUTION Extended N-terminus.SEQUENCE CAUTION Extended N-terminus.
created [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53
crossReference
databaseName UniProt
dbId 218498
description
  • recommendedName: fullName evidence="22"Angiomotin-like protein 2 alternativeName: fullName evidence="24"Leman coiled-coil protein shortName evidence="24"LCCP
displayName UniProt:Q9Y2J4 AMOTL2
geneName
  • AMOTL2
  • KIAA0989
identifier Q9Y2J4
isSequenceChanged false
keyword
  • Alternative splicing
  • Cell junction
  • Cell projection
  • Coiled coil
  • Cytoplasm
  • Endosome
  • Isopeptide bond
  • Phosphoprotein
  • Proteomics identification
  • Reference proteome
  • Ubl conjugation
  • Wnt signaling pathway
modified [InstanceEdit:9983091] Weiser, Joel, 2026-02-20
moleculeType Protein
name
  • AMOTL2
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • AMOL2_HUMAN
  • A8K6F1
  • B7Z5Q1
  • E9PHW3
  • Q53EP1
  • Q96F99
  • Q9UKB4
sequenceLength 779
species [Species:48887] Homo sapiens
stId uniprot:Q9Y2J4
url http://purl.uniprot.org/uniprot/Q9Y2J4
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