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APPL2 adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 2 [ Homo sapiens (human) ]

Gene ID: 55198, updated on 17-Jun-2019

Summary

Official Symbol
APPL2provided by HGNC
Official Full Name
adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 2provided by HGNC
Primary source
HGNC:HGNC:18242
See related
Ensembl:ENSG00000136044 MIM:606231
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
DIP13B
Summary
The protein encoded by this gene is one of two effectors of the small GTPase RAB5A/Rab5, which are involved in a signal transduction pathway. Both effectors contain an N-terminal Bin/Amphiphysin/Rvs (BAR) domain, a central pleckstrin homology (PH) domain, and a C-terminal phosphotyrosine binding (PTB) domain, and they bind the Rab5 through the BAR domain. They are associated with endosomal membranes and can be translocated to the nucleus in response to the EGF stimulus. They interact with the NuRD/MeCP1 complex (nucleosome remodeling and deacetylase /methyl-CpG-binding protein 1 complex) and are required for efficient cell proliferation. A chromosomal aberration t(12;22)(q24.1;q13.3) involving this gene and the PSAP2 gene results in 22q13.3 deletion syndrome, also known as Phelan-McDermid syndrome. [provided by RefSeq, Oct 2011]
Expression
Ubiquitous expression in colon (RPKM 10.8), small intestine (RPKM 10.3) and 25 other tissues See more
Orthologs

Genomic context

See APPL2 in Genome Data Viewer
Location:
12q23.3
Exon count:
24
Annotation release Status Assembly Chr Location
109.20190607 current GRCh38.p13 (GCF_000001405.39) 12 NC_000012.12 (105173297..105236230, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (105567075..105630008, complement)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC414300 Neighboring gene WASH complex subunit 4 Neighboring gene uncharacterized LOC105369953 Neighboring gene renal clear cell carcinoma-associated transcript 198 Neighboring gene chromosome 12 open reading frame 75

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • FLJ10659

Gene Ontology Provided by GOA

Function Evidence Code Pubs
phosphatidylinositol binding IDA
Inferred from Direct Assay
more info
PubMed 
phosphatidylserine binding IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein homodimerization activity IDA
Inferred from Direct Assay
more info
PubMed 
protein-containing complex binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
adiponectin-activated signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
 
cell cycle IEA
Inferred from Electronic Annotation
more info
 
cell proliferation IDA
Inferred from Direct Assay
more info
PubMed 
cellular response to hepatocyte growth factor stimulus ISS
Inferred from Sequence or Structural Similarity
more info
 
cold acclimation ISS
Inferred from Sequence or Structural Similarity
more info
 
diet induced thermogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
glucose homeostasis IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of cellular response to insulin stimulus ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of cytokine production involved in inflammatory response ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of fatty acid oxidation ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of glucose import IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of glucose import ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of neural precursor cell proliferation ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of neurogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of Fc-gamma receptor signaling pathway involved in phagocytosis ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of cold-induced thermogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of macropinocytosis ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of phagocytosis, engulfment ISS
Inferred from Sequence or Structural Similarity
more info
 
protein homotetramerization IDA
Inferred from Direct Assay
more info
PubMed 
protein import into nucleus IDA
Inferred from Direct Assay
more info
PubMed 
regulation of fibroblast migration ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of innate immune response ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of toll-like receptor 4 signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
 
signal transduction TAS
Traceable Author Statement
more info
PubMed 
signaling IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
transforming growth factor beta receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
cytoplasmic vesicle IDA
Inferred from Direct Assay
more info
PubMed 
early endosome membrane IEA
Inferred from Electronic Annotation
more info
 
early phagosome ISS
Inferred from Sequence or Structural Similarity
more info
 
early phagosome membrane ISS
Inferred from Sequence or Structural Similarity
more info
 
endosome IDA
Inferred from Direct Assay
more info
PubMed 
endosome membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
endosome membrane IDA
Inferred from Direct Assay
more info
PubMed 
extracellular exosome HDA PubMed 
macropinosome ISS
Inferred from Sequence or Structural Similarity
more info
 
membrane IDA
Inferred from Direct Assay
more info
PubMed 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
ruffle ISS
Inferred from Sequence or Structural Similarity
more info
 
ruffle membrane ISS
Inferred from Sequence or Structural Similarity
more info
 
vesicle IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
DCC-interacting protein 13-beta
Names
DIP13 beta
adapter protein containing PH domain, PTB domain and leucine zipper motif 2
adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 2

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_030419.1 RefSeqGene

    Range
    5001..67934
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001251904.1NP_001238833.1  DCC-interacting protein 13-beta isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) has an additional in-frame segment in the coding region, compared to variant 1. The resulting isoform 2 is longer than isoform 1.
    Source sequence(s)
    AK297100, AY113704, BC028008
    Consensus CDS
    CCDS58276.1
    UniProtKB/Swiss-Prot
    Q8NEU8
    Related
    ENSP00000446917.1, ENST00000551662.5
    Conserved Domains (4) summary
    cd07632
    Location:20240
    BAR_APPL2; The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing 2
    cd13158
    Location:488621
    PTB_APPL; Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif (APPL; also called DCC-interacting protein (DIP)-13alpha) Phosphotyrosine-binding (PTB) domain
    cd13247
    Location:258382
    BAR-PH_APPL; Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif Bin1/amphiphysin/Rvs167 (BAR)-Pleckstrin homology (PH) domain
    pfam00169
    Location:284381
    PH; PH domain
  2. NM_001251905.1NP_001238834.1  DCC-interacting protein 13-beta isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' exon, which results in a downstream AUG start codon, compared to variant 1. The resulting isoform (3) has a shorter N-terminus, compared to isoform 1.
    Source sequence(s)
    AK296610, BC028008, DN993818
    Consensus CDS
    CCDS58275.1
    UniProtKB/Swiss-Prot
    Q8NEU8
    Related
    ENSP00000444472.2, ENST00000539978.6
    Conserved Domains (4) summary
    cd13158
    Location:439572
    PTB_APPL; Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif (APPL; also called DCC-interacting protein (DIP)-13alpha) Phosphotyrosine-binding (PTB) domain
    cd13247
    Location:209333
    BAR-PH_APPL; Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif Bin1/amphiphysin/Rvs167 (BAR)-Pleckstrin homology (PH) domain
    pfam00169
    Location:235332
    PH; PH domain
    cl12013
    Location:1191
    BAR; The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects membrane curvature
  3. NM_018171.4NP_060641.2  DCC-interacting protein 13-beta isoform 1

    See identical proteins and their annotated locations for NP_060641.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the predominant isoform (1).
    Source sequence(s)
    AY113704, BC028008
    Consensus CDS
    CCDS9101.1
    UniProtKB/Swiss-Prot
    Q8NEU8
    Related
    ENSP00000258530.3, ENST00000258530.8
    Conserved Domains (4) summary
    cd07632
    Location:20234
    BAR_APPL2; The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing 2
    cd13158
    Location:482615
    PTB_APPL; Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif (APPL; also called DCC-interacting protein (DIP)-13alpha) Phosphotyrosine-binding (PTB) domain
    cd13247
    Location:252376
    BAR-PH_APPL; Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif Bin1/amphiphysin/Rvs167 (BAR)-Pleckstrin homology (PH) domain
    pfam00169
    Location:278375
    PH; PH domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p13 Primary Assembly

    Range
    105173297..105236230 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017019554.1XP_016875043.1  DCC-interacting protein 13-beta isoform X6

  2. XM_006719472.1XP_006719535.1  DCC-interacting protein 13-beta isoform X4

    Conserved Domains (4) summary
    cd07632
    Location:20240
    BAR_APPL2; The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing 2
    cd13247
    Location:258382
    BAR-PH_APPL; Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif Bin1/amphiphysin/Rvs167 (BAR)-Pleckstrin homology (PH) domain
    pfam00169
    Location:284381
    PH; PH domain
    cl17171
    Location:488563
    PH-like; Pleckstrin homology-like domain
  3. XM_011538532.3XP_011536834.1  DCC-interacting protein 13-beta isoform X3

    See identical proteins and their annotated locations for XP_011536834.1

    Conserved Domains (4) summary
    cd13158
    Location:445578
    PTB_APPL; Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif (APPL; also called DCC-interacting protein (DIP)-13alpha) Phosphotyrosine-binding (PTB) domain
    cd13247
    Location:215339
    BAR-PH_APPL; Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif Bin1/amphiphysin/Rvs167 (BAR)-Pleckstrin homology (PH) domain
    pfam00169
    Location:241338
    PH; PH domain
    cl12013
    Location:1197
    BAR; The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects membrane curvature
  4. XM_017019553.2XP_016875042.1  DCC-interacting protein 13-beta isoform X5

    UniProtKB/Swiss-Prot
    Q8NEU8
    Conserved Domains (4) summary
    cd13158
    Location:439572
    PTB_APPL; Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif (APPL; also called DCC-interacting protein (DIP)-13alpha) Phosphotyrosine-binding (PTB) domain
    cd13247
    Location:209333
    BAR-PH_APPL; Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif Bin1/amphiphysin/Rvs167 (BAR)-Pleckstrin homology (PH) domain
    pfam00169
    Location:235332
    PH; PH domain
    cl12013
    Location:1191
    BAR; The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects membrane curvature
  5. XM_011538531.3XP_011536833.1  DCC-interacting protein 13-beta isoform X3

    See identical proteins and their annotated locations for XP_011536833.1

    Conserved Domains (4) summary
    cd13158
    Location:445578
    PTB_APPL; Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif (APPL; also called DCC-interacting protein (DIP)-13alpha) Phosphotyrosine-binding (PTB) domain
    cd13247
    Location:215339
    BAR-PH_APPL; Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif Bin1/amphiphysin/Rvs167 (BAR)-Pleckstrin homology (PH) domain
    pfam00169
    Location:241338
    PH; PH domain
    cl12013
    Location:1197
    BAR; The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects membrane curvature
  6. XM_017019552.2XP_016875041.1  DCC-interacting protein 13-beta isoform X5

    UniProtKB/Swiss-Prot
    Q8NEU8
    Conserved Domains (4) summary
    cd13158
    Location:439572
    PTB_APPL; Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif (APPL; also called DCC-interacting protein (DIP)-13alpha) Phosphotyrosine-binding (PTB) domain
    cd13247
    Location:209333
    BAR-PH_APPL; Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif Bin1/amphiphysin/Rvs167 (BAR)-Pleckstrin homology (PH) domain
    pfam00169
    Location:235332
    PH; PH domain
    cl12013
    Location:1191
    BAR; The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects membrane curvature
  7. XM_011538530.3XP_011536832.1  DCC-interacting protein 13-beta isoform X1

    Conserved Domains (4) summary
    cd07632
    Location:7227
    BAR_APPL2; The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing 2
    cd13158
    Location:475608
    PTB_APPL; Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif (APPL; also called DCC-interacting protein (DIP)-13alpha) Phosphotyrosine-binding (PTB) domain
    cd13247
    Location:245369
    BAR-PH_APPL; Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif Bin1/amphiphysin/Rvs167 (BAR)-Pleckstrin homology (PH) domain
    pfam00169
    Location:271368
    PH; PH domain
  8. XM_017019551.2XP_016875040.1  DCC-interacting protein 13-beta isoform X2

RNA

  1. XR_001748796.1 RNA Sequence

    Related
    ENST00000547439.5
  2. XR_001748795.1 RNA Sequence

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