Adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1), or DCC-interacting protein 13-alpha (DIP13alpha), is a protein that in humans is encoded by the APPL1 gene. [5] [6] [7] APPL1 contains several key interactory domains: pleckstrin homology (PH) domain, phosphotyrosine-binding (PTB) domain and Bin–Amphiphysin–Rvs (BAR) domain. [8]
APPL1 is an adaptor protein localized to a subset of Rab5-positive ("early") endosomes, where it recruits other binding partners and regulates vesicle trafficking and endosomal signalling. APPL1 is enriched at very early endosomes which are negative for EEA1, indicating that APPL1 affects the earliest stages of endosomal traffic before EEA1 takes over. This is in line with observations that APPL1 and EEA1 compete for Rab5 binding. APPL1 affects the speed of internalization of key endosomal cargo (eg. EGF receptor) which is dependent on Rab5 activation. [8]
PTB domain of APPL1 regulates many cell signalling events in specific endosomal compartments - sometimes termed the "signalling endosomes". This includes lysophosphatidic acid (LPA)-induced signaling (together with interacting protein GIPC1). Additional roles for APPL1 were pinpointed to the nucleus where APPL1 can localize once dissociated from endosomes. [8]
| Mouse Mutant Alleles for Appl1 | ||
|---|---|---|
| Marker Symbol for Mouse Gene. This symbol is assigned to the genomic locus by the MGI | Appl1 | |
| Mutant Mouse Embryonic Stem Cell Clones. These are the known targeted mutations for this gene in a mouse. | Appl1tm1a(KOMP)Wtsi | |
| Example structure of targeted conditional mutant allele for this gene | ||
 | ||
| These Mutant ES Cells can be studied directly or used to generate mice with this gene knocked out. Study of these mice can shed light on the function of Appl1: see Knockout mouse | ||
APPL1 has been shown to interact with Deleted in Colorectal Cancer, [9] AKT2, [5] but also Rab5, Rab21, OCRL and almost 30 other proteins. [8]
The low-density lipoprotein receptor gene family codes for a class of structurally related cell surface receptors that fulfill diverse biological functions in different organs, tissues, and cell types. The role that is most commonly associated with this evolutionarily ancient family is cholesterol homeostasis. In humans, excess cholesterol in the blood is captured by low-density lipoprotein (LDL) and removed by the liver via endocytosis of the LDL receptor. Recent evidence indicates that the members of the LDL receptor gene family are active in the cell signalling pathways between specialized cells in many, if not all, multicellular organisms.
Cbl is a mammalian gene encoding the protein CBL which is an E3 ubiquitin-protein ligase involved in cell signalling and protein ubiquitination. Mutations to this gene have been implicated in a number of human cancers, particularly acute myeloid leukaemia.
AKT2, also known as RAC-beta serine/threonine-protein kinase, is an enzyme that in humans is encoded by the AKT2 gene. It influences metabolite storage as part of the insulin signal transduction pathway.
Ras-related protein Rab-11A is a protein that in humans is encoded by the RAB11A gene.
Hepatocyte growth factor-regulated tyrosine kinase substrate is an enzyme that in humans is encoded by the HGS gene.
Amyloid beta A4 precursor protein-binding family A member 1 is a protein that in humans is encoded by the APBA1 gene.
Signal transducing adapter molecule 1 is a protein that in humans is encoded by the STAM gene.
Syntaxin-6 is a protein that in humans is encoded by the STX6 gene.
STAM-binding protein is a protein that in humans is encoded by the STAMBP gene.
Amyloid beta A4 precursor protein-binding family A member 2 is a protein that in humans is encoded by the APBA2 gene.
Low-density lipoprotein receptor adapter protein 1 is a protein that in humans is encoded by the LDLRAP1 gene.
SHC-transforming protein 3 is a protein that in humans is encoded by the SHC3 gene.
Integrin beta-1-binding protein 1 is a protein that in humans is encoded by the ITGB1BP1 gene.
Syntaxin-12 is a protein that in humans is encoded by the STX12 gene.
SH2B adapter protein 2 is a protein that in humans is encoded by the SH2B2 gene.
Rab11 family-interacting protein 5 is a protein that in humans is encoded by the RAB11FIP5 gene.
Vacuolar protein sorting-associated protein 28 homolog is a protein that in humans is encoded by the VPS28 gene.
Ras-related protein Rab-22A is a protein that in humans is encoded by the RAB22A gene.
Zinc finger FYVE domain-containing protein 16 is a protein that in humans is encoded by the ZFYVE16 gene.
DCC-interacting protein 13-beta is a protein that in humans is encoded by the APPL2 gene.
PDB gallery | |
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