APPL1: Polycystic Ovarian Syndrome Database

Gene Information

Gene Symbol

APPL1

Aliases

APPL, DIP13alpha, MODY14

Entrez Gene ID

26060

Gene Name

Adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1

Chromosomal Location

3p14.3

HGNC ID

HGNC:24035

Summary

The protein encoded by this gene has been shown to be involved in the regulation of cell proliferation, and in the crosstalk between the adiponectin signalling and insulin signalling pathways. The encoded protein binds many other proteins, including RAB5A, DCC, AKT2, PIK3CA, adiponectin receptors, and proteins of the NuRD/MeCP1 complex. This protein is found associated with endosomal membranes, but can be released by EGF and translocated to the nucleus. [provided by RefSeq, Jul 2008]

RefSeq DNA

NG_047003.1

RefSeq mRNA

NM_012096.3

e!Ensembl

Gene	ENSG00000157500
Transcript	ENST00000650354, ENST00000288266, ENST00000495803, ENST00000444459
Protein	ENSP00000498115, ENSP00000288266, ENSP00000419644, ENSP00000406095

Gene Ontology (GO)

Show/Hide all(35 )

GO ID	Ontology	Function	Evidence	Reference
GO:0006606	Biological process	Protein import into nucleus	IDA	26583432
GO:0007165	Biological process	Signal transduction	TAS	10490823
GO:0007179	Biological process	Transforming growth factor beta receptor signaling pathway	IMP	26583432
GO:0008283	Biological process	Cell proliferation	IDA	15016378
GO:0008286	Biological process	Insulin receptor signaling pathway	IBA	21873635
GO:0008286	Biological process	Insulin receptor signaling pathway	IMP	26073777
GO:0008286	Biological process	Insulin receptor signaling pathway	TAS	17848569
GO:0023052	Biological process	Signaling	IBA	21873635
GO:0033211	Biological process	Adiponectin-activated signaling pathway	IMP	19661063
GO:0046324	Biological process	Regulation of glucose import	IMP	17848569
GO:0046326	Biological process	Positive regulation of glucose import	IMP	24879834
GO:0048023	Biological process	Positive regulation of melanin biosynthetic process	IMP	21291857
GO:1903076	Biological process	Regulation of protein localization to plasma membrane	IMP	17848569
GO:0005634	Cellular component	Nucleus	IDA	15016378, 18034774, 19433865, 26583432
GO:0005737	Cellular component	Cytoplasm	IDA	19433865, 19661063, 21291857
GO:0005768	Cellular component	Endosome	IDA	26583432
GO:0005769	Cellular component	Early endosome	IDA	21645192
GO:0005829	Cellular component	Cytosol	IDA	17848569
GO:0005886	Cellular component	Plasma membrane	IDA	18034774
GO:0010008	Cellular component	Endosome membrane	IBA	21873635
GO:0010008	Cellular component	Endosome membrane	IDA	15016378
GO:0012506	Cellular component	Vesicle membrane	IDA	17848569
GO:0016020	Cellular component	Membrane	IDA	18034774
GO:0031410	Cellular component	Cytoplasmic vesicle	IDA	18034774
GO:0070062	Cellular component	Extracellular exosome	HDA	18570454, 19056867
GO:0097708	Cellular component	Intracellular vesicle	IDA	21291857
GO:0001786	Molecular function	Phosphatidylserine binding	IDA	18034774
GO:0005515	Molecular function	Protein binding	IPI	10490823, 12011067, 15016378, 16189514, 16273093, 16622416, 17030088, 17581628, 18034774, 19433865, 19661063, 21233288, 21291857, 21645192, 23414517, 23752268, 25241761, 25416956, 25814554, 26583432, 29568061
GO:0035091	Molecular function	Phosphatidylinositol binding	IDA	18034774
GO:0042802	Molecular function	Identical protein binding	IPI	17502098, 17581628, 25416956
GO:0042803	Molecular function	Protein homodimerization activity	IDA	18034774
GO:0043422	Molecular function	Protein kinase B binding	IBA	21873635
GO:0043422	Molecular function	Protein kinase B binding	IPI	17848569
GO:0044877	Molecular function	Protein-containing complex binding	IPI	15016378
GO:0048487	Molecular function	Beta-tubulin binding	IDA	26583432

Protein Information

Protein Name

DCC-interacting protein 13-alpha, AKT2 interactor, adapter protein containing PH domain, PTB domain and leucine zipper motif 1, adaptor protein containing pH domain, PTB domain and leucine zipper motif 1, adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 1, dip13-alpha, signaling adaptor protein DIP13alpha

Function

Multifunctional adapter protein that binds to various membrane receptors, nuclear factors and signaling proteins to regulate many processes, such as cell proliferation, immune response, endosomal trafficking and cell metabolism (PubMed:26583432, PubMed:15016378, PubMed:26073777, PubMed:19661063, PubMed:10490823). Regulates signaling pathway leading to cell proliferation through interaction with RAB5A and subunits of the NuRD/MeCP1 complex (PubMed:15016378). Functions as a positive regulator of innate immune response via activation of AKT1 signaling pathway by forming a complex with APPL1 and PIK3R1 (By similarity). Inhibits Fc-gamma receptor-mediated phagocytosis through PI3K/Akt signaling in macrophages (By similarity). Regulates TLR4 signaling in activated macrophages (By similarity). Involved in trafficking of the TGFBR1 from the endosomes to the nucleus via microtubules in a TRAF6-dependent manner (PubMed:26583432). Plays a role in cell metabolism by regulating adiponecting and insulin signaling pathways (PubMed:26073777, PubMed:19661063, PubMed:24879834). Required for fibroblast migration through HGF cell signaling (By similarity). Positive regulator of beta-catenin/TCF-dependent transcription through direct interaction with RUVBL2/reptin resulting in the relief of RUVBL2-mediated repression of beta-catenin/TCF target genes by modulating the interactions within the beta-catenin-reptin-HDAC complex (PubMed:19433865).

Refseq Proteins

NP_036228.1

UniProt

Q9UKG1

PDB

2EJ8, 2ELA, 2ELB, 2Q12, 2Q13, 2Z0N, 2Z0O, 5C5B

Pfam

Pfam Accession	Pfam ID
PF00169	PH
PF00640	PID