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

Gene ID: 55198, updated on 15-Sep-2022

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; AllianceGenome:HGNC:18242
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
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Genomic context

See APPL2 in Genome Data Viewer
Location:
12q23.3
Exon count:
23
Annotation release Status Assembly Chr Location
110 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (105173300..105236174, complement)
110 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (105135121..105197990, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (105567078..105629952, complement)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC414300 Neighboring gene WASH complex subunit 4 Neighboring gene C12orf75 antisense RNA 1 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 Functions

What'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
enables identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables phosphatidylinositol binding IDA
Inferred from Direct Assay
more info
PubMed 
enables phosphatidylserine binding IDA
Inferred from Direct Assay
more info
PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables protein homodimerization activity IDA
Inferred from Direct Assay
more info
PubMed 
enables protein-containing complex binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
involved_in adiponectin-activated signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in cell cycle IEA
Inferred from Electronic Annotation
more info
 
involved_in cellular response to hepatocyte growth factor stimulus ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in cold acclimation ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in diet induced thermogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in glucose homeostasis IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in negative regulation of cellular response to insulin stimulus ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in negative regulation of cytokine production involved in inflammatory response ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in negative regulation of fatty acid oxidation ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in negative regulation of glucose import IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in negative regulation of glucose import ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in negative regulation of neural precursor cell proliferation ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in negative regulation of neurogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in positive regulation of Fc-gamma receptor signaling pathway involved in phagocytosis ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in positive regulation of cold-induced thermogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in positive regulation of macropinocytosis ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in positive regulation of phagocytosis, engulfment ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in protein homotetramerization IDA
Inferred from Direct Assay
more info
PubMed 
involved_in protein import into nucleus IDA
Inferred from Direct Assay
more info
PubMed 
involved_in regulation of G1/S transition of mitotic cell cycle IDA
Inferred from Direct Assay
more info
PubMed 
involved_in regulation of fibroblast migration ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in regulation of innate immune response ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in regulation of toll-like receptor 4 signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in signal transduction TAS
Traceable Author Statement
more info
PubMed 
involved_in signaling IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
involved_in transforming growth factor beta receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
located_in cytoplasmic vesicle IDA
Inferred from Direct Assay
more info
PubMed 
located_in early endosome membrane IEA
Inferred from Electronic Annotation
more info
 
located_in early phagosome ISS
Inferred from Sequence or Structural Similarity
more info
 
located_in early phagosome membrane ISS
Inferred from Sequence or Structural Similarity
more info
 
located_in endosome IDA
Inferred from Direct Assay
more info
PubMed 
is_active_in endosome membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
located_in endosome membrane IDA
Inferred from Direct Assay
more info
PubMed 
located_in extracellular exosome HDA PubMed 
located_in macropinosome ISS
Inferred from Sequence or Structural Similarity
more info
 
located_in membrane IDA
Inferred from Direct Assay
more info
PubMed 
located_in nucleus IDA
Inferred from Direct Assay
more info
PubMed 
located_in plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
located_in ruffle ISS
Inferred from Sequence or Structural Similarity
more info
 
located_in ruffle membrane ISS
Inferred from Sequence or Structural Similarity
more info
 
located_in 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)

NEW Try the new Transcript table

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_030419.2 RefSeqGene

    Range
    5000..67874
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001251904.2NP_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)
    AC016257, AC078874
    Consensus CDS
    CCDS58276.1
    UniProtKB/Swiss-Prot
    Q8NEU8
    Related
    ENSP00000446917.1, ENST00000551662.5
    Conserved Domains (3) 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
  2. NM_001251905.2NP_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)
    AC016257, AC078874
    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_018171.5NP_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)
    AC016257, AC078874
    Consensus CDS
    CCDS9101.1
    UniProtKB/Swiss-Prot
    Q8NEU8, Q9NVL2
    Related
    ENSP00000258530.3, ENST00000258530.8
    Conserved Domains (3) 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

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 110 details...Open this link in a new tab

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    105173300..105236174 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017019554.2XP_016875043.1  DCC-interacting protein 13-beta isoform X5

  2. XM_006719472.2XP_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_017019551.3XP_016875040.1  DCC-interacting protein 13-beta isoform X2

  4. XM_047429065.1XP_047285021.1  DCC-interacting protein 13-beta isoform X8

  5. XM_011538532.4XP_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
  6. XM_047429062.1XP_047285018.1  DCC-interacting protein 13-beta isoform X3

  7. XM_011538531.4XP_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
  8. XM_047429064.1XP_047285020.1  DCC-interacting protein 13-beta isoform X7

  9. XM_047429063.1XP_047285019.1  DCC-interacting protein 13-beta isoform X6

  10. XM_011538530.4XP_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
  11. XM_047429066.1XP_047285022.1  DCC-interacting protein 13-beta isoform X9

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    105135121..105197990 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)