Adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1), or DCC-interacting protein 13-alpha (DIP13alpha), is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''APPL1''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
APPL1 contains several key interactory domains:
pleckstrin homology (PH) domain,
phosphotyrosine-binding (PTB) domain and
Bin–Amphiphysin–Rvs (BAR) domain.
Function
APPL1 is an
adaptor protein localized to a subset of
Rab5-positive ("early")
endosome
Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can ...
s, where it recruits other binding partners and regulates
vesicle trafficking and endosomal
signalling
In signal processing, a signal is a function that conveys information about a phenomenon. Any quantity that can vary over space or time can be used as a signal to share messages between observers. The ''IEEE Transactions on Signal Processing'' ...
. 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 EGF may refer to:
* E.G.F., a Gabonese company
* East Grand Forks, Minnesota, a city
* East Garforth railway station in England
* Epidermal growth factor
* Equity Group Foundation, a Kenyan charity
* European Gendarmerie Force, a military unit of ...
) which is dependent on Rab5 activation.
PTB domain of APPL1 regulates many cell signalling events in specific endosomal compartments - sometimes termed the "signalling endosomes". This includes
lysophosphatidic acid
Lysophosphatidic acid (LPA) is a phospholipid derivative that can act as a signaling molecule.
Function
LPA acts as a potent mitogen due to its activation of three high-affinity G-protein-coupled receptors called LPAR1, LPAR2, and LPAR3 (also kn ...
(LPA)-induced signaling (together with interacting protein
GIPC1
GIPC PDZ domain containing family, member 1 (GIPC1) is a protein that in humans is encoded by the ''GIPC1'' gene. GIPC was originally identified as it binds specifically to the C terminus of RGS-GAIP, a protein involved in the regulation of G prot ...
). Additional roles for APPL1 were pinpointed to the
nucleus
Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to:
*Atomic nucleus, the very dense central region of an atom
*Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA
Nucle ...
where APPL1 can localize once dissociated from endosomes.
Mutant studies
Interactions
APPL1 has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with
Deleted in Colorectal Cancer
Netrin receptor DCC, also known as DCC, or colorectal cancer suppressor is a protein which in humans is encoded by the ''DCC'' gene. DCC has long been implicated in colorectal cancer and its previous name was ''Deleted in colorectal carcinoma''. ...
,
AKT2
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.
Function
This gene is a putative o ...
,
but also
Rab5,
Rab21
Ras-related protein Rab-21 is a protein that in humans is encoded by the ''RAB21'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' ...
,
OCRL
Inositol polyphosphate 5-phosphatase OCRL-1, also known as Lowe oculocerebrorenal syndrome protein, is an enzyme encoded by the ''OCRL'' gene located on the X chromosome in humans.
This gene encodes an inositol polyphosphate 5-phosphatase. The ...
and almost 30 other proteins.
References
Further reading
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External links
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