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Aliases for PHLDA3 Gene

Aliases for PHLDA3 Gene

  • Pleckstrin Homology Like Domain Family A Member 3 2 3 5
  • Pleckstrin Homology-Like Domain, Family A, Member 2 2 3
  • TDAG51/Ipl Homolog 1 3 4
  • TIH1 3 4
  • Pleckstrin Homology-Like Domain, Family A, Member 3 2
  • Pleckstrin Homology-Like Domain Family A Member 3 3

External Ids for PHLDA3 Gene

Previous GeneCards Identifiers for PHLDA3 Gene

  • GC01M199137
  • GC01M196871
  • GC01M197901
  • GC01M198722
  • GC01M198166
  • GC01M199701
  • GC01M172600

Summaries for PHLDA3 Gene

GeneCards Summary for PHLDA3 Gene

PHLDA3 (Pleckstrin Homology Like Domain Family A Member 3) is a Protein Coding gene. Among its related pathways are DNA Damage and PI3K / Akt Signaling. Gene Ontology (GO) annotations related to this gene include phosphatidylinositol-4,5-bisphosphate binding and phosphatidylinositol-3-phosphate binding. An important paralog of this gene is PHLDA1.

UniProtKB/Swiss-Prot for PHLDA3 Gene

  • p53/TP53-regulated repressor of Akt/AKT1 signaling. Represses AKT1 by preventing AKT1-binding to membrane lipids, thereby inhibiting AKT1 translocation to the cellular membrane and activation. Contributes to p53/TP53-dependent apoptosis by repressing AKT1 activity. Its direct transcription regulation by p53/TP53 may explain how p53/TP53 can negatively regulate AKT1. May act as a tumor suppressor.

Additional gene information for PHLDA3 Gene

No data available for Entrez Gene Summary , CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for PHLDA3 Gene

Genomics for PHLDA3 Gene

GeneHancer (GH) Regulatory Elements for PHLDA3 Gene

Promoters and enhancers for PHLDA3 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH01I201465 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE dbSUPER 557.8 +1.6 1614 5.2 PKNOX1 ZFP64 SIN3A ZNF2 ZBTB7B GLIS2 ZNF213 SP3 SP5 MXD4 PHLDA3 ENSG00000224818 GC01P201469
GH01I201488 Promoter/Enhancer 2.1 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 11.4 -23.9 -23873 9.1 PKNOX1 FOXA2 ARID4B SIN3A BRCA1 YY1 ZNF143 ATF7 FOS DEK CSRP1 GC01P201494 GC01M201488 ENSG00000224818 NAV1 PHLDA3 LAD1 RPS10P7 LMOD1
GH01I201435 Enhancer 1.4 Ensembl ENCODE dbSUPER 12.3 +33.3 33268 0.9 HDGF CLOCK SMAD1 ARNT ZFP64 NEUROD1 SIN3A FEZF1 ZNF2 ZBTB7B IPO9 IPO9-AS1 ENSG00000224818 ENSG00000235121 CAMSAP2 RNPEP ENSG00000273478 DDX59 PHLDA3 LAD1
GH01I201530 Enhancer 1.5 FANTOM5 Ensembl ENCODE dbSUPER 11.3 -62.2 -62231 2.8 HDAC1 PKNOX1 CLOCK ATF1 RB1 ZSCAN4 SIN3A ZNF2 RAD21 GLIS2 NAV1 CSRP1 ENSG00000224536 PHLDA3 ENSG00000224818 RNU6-501P ENSG00000235121 ENSG00000236390 RPS10P7 GC01P201537
GH01I201709 Enhancer 1.7 FANTOM5 Ensembl ENCODE dbSUPER 9.6 -244.1 -244105 8.7 HDGF PKNOX1 NEUROD1 SIN3A ZNF2 ZBTB7B ZNF143 ZNF548 FOS KLF13 NAV1 MIR1231 RPS27P8 ENSG00000236390 CSRP1 ENSG00000224536 PHLDA3 ENSG00000224818 ARL8A MIR5191
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around PHLDA3 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the PHLDA3 gene promoter:

Genomic Locations for PHLDA3 Gene

Genomic Locations for PHLDA3 Gene
chr1:201,464,383-201,469,237
(GRCh38/hg38)
Size:
4,855 bases
Orientation:
Minus strand
chr1:201,434,620-201,438,365
(GRCh37/hg19)

Genomic View for PHLDA3 Gene

Genes around PHLDA3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PHLDA3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PHLDA3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PHLDA3 Gene

Proteins for PHLDA3 Gene

  • Protein details for PHLDA3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y5J5-PHLA3_HUMAN
    Recommended name:
    Pleckstrin homology-like domain family A member 3
    Protein Accession:
    Q9Y5J5
    Secondary Accessions:
    • B2R5A4
    • Q53HD6
    • Q8NBW9

    Protein attributes for PHLDA3 Gene

    Size:
    127 amino acids
    Molecular mass:
    13891 Da
    Quaternary structure:
    No Data Available
    Miscellaneous:
    • PHLDA3 genomic locus is frequently observed in primary lung cancers, suggesting a role in tumor suppression.

neXtProt entry for PHLDA3 Gene

Post-translational modifications for PHLDA3 Gene

No Post-translational modifications

Other Protein References for PHLDA3 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for PHLDA3 Gene

Domains & Families for PHLDA3 Gene

Gene Families for PHLDA3 Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for PHLDA3 Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for PHLDA3 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q9Y5J5

UniProtKB/Swiss-Prot:

PHLA3_HUMAN :
  • The PH domain binds phosphoinositides with a broad specificity. It competes with the PH domain of AKT1 and directly interferes with AKT1 binding to phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3), preventing AKT1 association to membrane lipids and subsequent activation of AKT1 signaling.
  • Belongs to the PHLDA3 family.
Domain:
  • The PH domain binds phosphoinositides with a broad specificity. It competes with the PH domain of AKT1 and directly interferes with AKT1 binding to phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3), preventing AKT1 association to membrane lipids and subsequent activation of AKT1 signaling.
Family:
  • Belongs to the PHLDA3 family.
genes like me logo Genes that share domains with PHLDA3: view

Function for PHLDA3 Gene

Molecular function for PHLDA3 Gene

GENATLAS Biochemistry:
pleckstrin homology domain,family A,member 3,TDAG51/Ip1 homology 1 (TIH1),putatively involved in FAS (APT1) expression and apoptosis
UniProtKB/Swiss-Prot Function:
p53/TP53-regulated repressor of Akt/AKT1 signaling. Represses AKT1 by preventing AKT1-binding to membrane lipids, thereby inhibiting AKT1 translocation to the cellular membrane and activation. Contributes to p53/TP53-dependent apoptosis by repressing AKT1 activity. Its direct transcription regulation by p53/TP53 may explain how p53/TP53 can negatively regulate AKT1. May act as a tumor suppressor.
UniProtKB/Swiss-Prot Induction:
By p53/TP53; expression is directly activated by TP53. TP53 phosphorylation on Ser-15 is required to activate the PHLDA3 promoter.

Phenotypes From GWAS Catalog for PHLDA3 Gene

Gene Ontology (GO) - Molecular Function for PHLDA3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005546 phosphatidylinositol-4,5-bisphosphate binding IDA 19203586
GO:0005547 phosphatidylinositol-3,4,5-trisphosphate binding IDA 19203586
GO:0010314 phosphatidylinositol-5-phosphate binding IDA 19203586
GO:0032266 phosphatidylinositol-3-phosphate binding IDA 19203586
GO:0043325 phosphatidylinositol-3,4-bisphosphate binding IDA 19203586
genes like me logo Genes that share ontologies with PHLDA3: view
genes like me logo Genes that share phenotypes with PHLDA3: view

Animal Models for PHLDA3 Gene

MGI Knock Outs for PHLDA3:

Animal Model Products

miRNA for PHLDA3 Gene

miRTarBase miRNAs that target PHLDA3

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for PHLDA3 Gene

Localization for PHLDA3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for PHLDA3 Gene

Cytoplasm. Membrane; Peripheral membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PHLDA3 gene
Compartment Confidence
plasma membrane 5
extracellular 5
cytosol 2
mitochondrion 1
nucleus 1

Gene Ontology (GO) - Cellular Components for PHLDA3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005886 plasma membrane IDA 19203586
GO:0016020 membrane IEA --
GO:0070062 extracellular exosome IDA,HDA 23376485
genes like me logo Genes that share ontologies with PHLDA3: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for PHLDA3 Gene

Pathways & Interactions for PHLDA3 Gene

genes like me logo Genes that share pathways with PHLDA3: view

Pathways by source for PHLDA3 Gene

3 Cell Signaling Technology pathways for PHLDA3 Gene

Interacting Proteins for PHLDA3 Gene

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)
http://version10.5.string-db.org/api/image/networkList?limit=0&targetmode=proteins&caller_identity=gene_cards&network_flavor=evidence&identifiers=9606.ENSP00000356278%0d%0a9606.ENSP00000318297%0d%0a9606.ENSP00000215587%0d%0a9606.ENSP00000402515%0d%0a9606.ENSP00000313420%0d%0a9606.ENSP00000005386%0d%0a
Selected Interacting proteins: ENSP00000356278 Q9Y5J5-PHLA3_HUMAN for PHLDA3 Gene via STRING IID

Gene Ontology (GO) - Biological Process for PHLDA3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006915 apoptotic process IEA --
GO:0009653 anatomical structure morphogenesis TAS 10594239
GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator IDA 19203586
GO:0043065 positive regulation of apoptotic process IDA 19203586
GO:0051898 negative regulation of protein kinase B signaling IDA 19203586
genes like me logo Genes that share ontologies with PHLDA3: view

No data available for SIGNOR curated interactions for PHLDA3 Gene

Drugs & Compounds for PHLDA3 Gene

No Compound Related Data Available

Transcripts for PHLDA3 Gene

Unigene Clusters for PHLDA3 Gene

Pleckstrin homology-like domain, family A, member 3:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for PHLDA3 Gene

ExUns: 1 ^ 2a · 2b · 2c ^ 3 ^ 4 ^ 5a · 5b · 5c
SP1: -
SP2: -
SP3: - -
SP4:

Relevant External Links for PHLDA3 Gene

GeneLoc Exon Structure for
PHLDA3
ECgene alternative splicing isoforms for
PHLDA3

Expression for PHLDA3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for PHLDA3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for PHLDA3 Gene

This gene is overexpressed in Bone (13.6), Nasopharynx (8.9), Frontal cortex (8.9), Esophagus (7.7), and Prostate (6.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for PHLDA3 Gene



NURSA nuclear receptor signaling pathways regulating expression of PHLDA3 Gene:

PHLDA3

SOURCE GeneReport for Unigene cluster for PHLDA3 Gene:

Hs.268557

mRNA Expression by UniProt/SwissProt for PHLDA3 Gene:

Q9Y5J5-PHLA3_HUMAN
Tissue specificity: Widely expressed with lowest expression in liver and spleen.

Evidence on tissue expression from TISSUES for PHLDA3 Gene

  • Skin(4.6)
  • Nervous system(4.4)
genes like me logo Genes that share expression patterns with PHLDA3: view

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for PHLDA3 Gene

Orthologs for PHLDA3 Gene

This gene was present in the common ancestor of chordates.

Orthologs for PHLDA3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia PHLDA3 33 34
  • 100 (n)
mouse
(Mus musculus)
Mammalia Phlda3 33 16 34
  • 94.4 (n)
rat
(Rattus norvegicus)
Mammalia Phlda3 33
  • 94.4 (n)
oppossum
(Monodelphis domestica)
Mammalia PHLDA3 34
  • 93 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia PHLDA3 34
  • 87 (a)
OneToOne
chicken
(Gallus gallus)
Aves LOC100859283 33
  • 80.73 (n)
PHLDA3 34
  • 70 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia PHLDA3 34
  • 55 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.20873 33
zebrafish
(Danio rerio)
Actinopterygii phlda3 33 34
  • 61.11 (n)
Species where no ortholog for PHLDA3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • cow (Bos Taurus)
  • dog (Canis familiaris)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for PHLDA3 Gene

ENSEMBL:
Gene Tree for PHLDA3 (if available)
TreeFam:
Gene Tree for PHLDA3 (if available)

Paralogs for PHLDA3 Gene

Paralogs for PHLDA3 Gene

(2) SIMAP similar genes for PHLDA3 Gene using alignment to 1 proteins:

genes like me logo Genes that share paralogs with PHLDA3: view

Variants for PHLDA3 Gene

Sequence variations from dbSNP and Humsavar for PHLDA3 Gene

SNP ID Clin Chr 01 pos Variation AA Info Type
rs1000190306 -- 201,469,285(-) C/T upstream_transcript_variant
rs1000342724 -- 201,464,266(-) T/C downstream_transcript_variant
rs1000774888 -- 201,470,842(-) C/G upstream_transcript_variant
rs1000776142 -- 201,464,535(-) G/A/C 3_prime_UTR_variant, genic_downstream_transcript_variant
rs1000904953 -- 201,468,166(-) A/G intron_variant

Structural Variations from Database of Genomic Variants (DGV) for PHLDA3 Gene

Variant ID Type Subtype PubMed ID
nsv947466 CNV duplication 23825009
nsv832326 CNV loss 17160897
nsv832315 CNV loss 17160897
nsv548997 CNV gain 21841781
nsv470776 CNV gain 18288195
nsv467961 CNV gain 19166990

Variation tolerance for PHLDA3 Gene

Residual Variation Intolerance Score: 67.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.87; 48.40% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PHLDA3 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
PHLDA3

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PHLDA3 Gene

Disorders for PHLDA3 Gene

Additional Disease Information for PHLDA3

No disorders were found for PHLDA3 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for PHLDA3 Gene

Publications for PHLDA3 Gene

  1. PH domain-only protein PHLDA3 is a p53-regulated repressor of Akt. (PMID: 19203586) Kawase T … Taya Y (Cell 2009) 3 4 58
  2. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4 58
  3. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4 58
  4. A novel pleckstrin homology-related gene family defined by Ipl/Tssc3, TDAG51, and Tih1: tissue-specific expression, chromosomal location, and parental imprinting. (PMID: 10594239) Frank D … Tycko B (Mammalian genome : official journal of the International Mammalian Genome Society 1999) 3 4 58
  5. Low PHLDA3 expression in oesophageal squamous cell carcinomas is associated with poor prognosis. (PMID: 25667479) Muroi H … Kato H (Anticancer research 2015) 3 58

Products for PHLDA3 Gene

Sources for PHLDA3 Gene

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