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Q9Y5J5

- PHLA3_HUMAN

UniProt

Q9Y5J5 - PHLA3_HUMAN

Protein

Pleckstrin homology-like domain family A member 3

Gene

PHLDA3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. Functioni

    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.1 Publication

    GO - Molecular functioni

    1. phosphatidylinositol-3,4,5-trisphosphate binding Source: UniProtKB
    2. phosphatidylinositol-3,4-bisphosphate binding Source: UniProtKB
    3. phosphatidylinositol-3,5-bisphosphate binding Source: UniProtKB
    4. phosphatidylinositol-3-phosphate binding Source: UniProtKB
    5. phosphatidylinositol-4,5-bisphosphate binding Source: UniProtKB
    6. phosphatidylinositol-5-phosphate binding Source: UniProtKB

    GO - Biological processi

    1. anatomical structure morphogenesis Source: ProtInc
    2. intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: UniProtKB
    3. negative regulation of protein kinase B signaling Source: UniProtKB
    4. positive regulation of apoptotic process Source: UniProtKB

    Keywords - Biological processi

    Apoptosis

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Pleckstrin homology-like domain family A member 3
    Alternative name(s):
    TDAG51/Ipl homolog 1
    Gene namesi
    Name:PHLDA3
    Synonyms:TIH1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:8934. PHLDA3.

    Subcellular locationi

    Cytoplasm 1 Publication. Membrane 1 Publication; Peripheral membrane protein 1 Publication

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. extracellular vesicular exosome Source: UniProt
    3. plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Membrane

    Pathology & Biotechi

    Keywords - Diseasei

    Tumor suppressor

    Organism-specific databases

    PharmGKBiPA33275.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 127127Pleckstrin homology-like domain family A member 3PRO_0000053902Add
    BLAST

    Proteomic databases

    MaxQBiQ9Y5J5.
    PaxDbiQ9Y5J5.
    PRIDEiQ9Y5J5.

    PTM databases

    PhosphoSiteiQ9Y5J5.

    Expressioni

    Tissue specificityi

    Widely expressed with lowest expression in liver and spleen.1 Publication

    Inductioni

    By p53/TP53; expression is directly activated by TP53. TP53 phosphorylation on 'Ser-15' is required to activate the PHLDA3 promoter.2 Publications

    Gene expression databases

    BgeeiQ9Y5J5.
    CleanExiHS_PHLDA3.
    GenevestigatoriQ9Y5J5.

    Organism-specific databases

    HPAiHPA027601.

    Interactioni

    Protein-protein interaction databases

    BioGridi117145. 24 interactions.
    IntActiQ9Y5J5. 1 interaction.
    STRINGi9606.ENSP00000356278.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9Y5J5.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini8 – 127120PHAdd
    BLAST

    Domaini

    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.

    Sequence similaritiesi

    Belongs to the PHLDA3 family.Curated
    Contains 1 PH domain.Curated

    Phylogenomic databases

    eggNOGiNOG40478.
    HOGENOMiHOG000115528.
    HOVERGENiHBG052730.
    InParanoidiQ9Y5J5.
    OMAiESTERHI.
    OrthoDBiEOG7NKKM7.
    PhylomeDBiQ9Y5J5.
    TreeFamiTF332320.

    Family and domain databases

    Gene3Di2.30.29.30. 1 hit.
    InterProiIPR001849. PH_domain.
    IPR011993. PH_like_dom.
    [Graphical view]
    SMARTiSM00233. PH. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9Y5J5-1 [UniParc]FASTAAdd to Basket

    « Hide

    MTAAATATVL KEGVLEKRSG GLLQLWKRKR CVLTERGLQL FEAKGTGGRP    50
    KELSFARIKA VECVESTGRH IYFTLVTEGG GEIDFRCPLE DPGWNAQITL 100
    GLVKFKNQQA IQTVRARQSL GTGTLVS 127
    Length:127
    Mass (Da):13,891
    Last modified:November 1, 1999 - v1
    Checksum:i35014547F840D115
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti8 – 81T → A in BAD96364. 1 PublicationCurated
    Sequence conflicti88 – 881P → L in BAC11454. (PubMed:14702039)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti28 – 281R → Q.
    Corresponds to variant rs35383942 [ dbSNP | Ensembl ].
    VAR_050515

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF151100 mRNA. Translation: AAD42081.1.
    AK075179 mRNA. Translation: BAC11454.1.
    AK312115 mRNA. Translation: BAG35051.1.
    AK222644 mRNA. Translation: BAD96364.1.
    CH471067 Genomic DNA. Translation: EAW91369.1.
    BC014390 mRNA. Translation: AAH14390.1.
    BC068273 mRNA. Translation: AAH68273.1.
    CCDSiCCDS1412.1.
    RefSeqiNP_036528.1. NM_012396.3.
    UniGeneiHs.268557.

    Genome annotation databases

    EnsembliENST00000367309; ENSP00000356278; ENSG00000174307.
    ENST00000367311; ENSP00000356280; ENSG00000174307.
    GeneIDi23612.
    KEGGihsa:23612.
    UCSCiuc001gwq.4. human.

    Polymorphism databases

    DMDMi74735291.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF151100 mRNA. Translation: AAD42081.1 .
    AK075179 mRNA. Translation: BAC11454.1 .
    AK312115 mRNA. Translation: BAG35051.1 .
    AK222644 mRNA. Translation: BAD96364.1 .
    CH471067 Genomic DNA. Translation: EAW91369.1 .
    BC014390 mRNA. Translation: AAH14390.1 .
    BC068273 mRNA. Translation: AAH68273.1 .
    CCDSi CCDS1412.1.
    RefSeqi NP_036528.1. NM_012396.3.
    UniGenei Hs.268557.

    3D structure databases

    ProteinModelPortali Q9Y5J5.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 117145. 24 interactions.
    IntActi Q9Y5J5. 1 interaction.
    STRINGi 9606.ENSP00000356278.

    PTM databases

    PhosphoSitei Q9Y5J5.

    Polymorphism databases

    DMDMi 74735291.

    Proteomic databases

    MaxQBi Q9Y5J5.
    PaxDbi Q9Y5J5.
    PRIDEi Q9Y5J5.

    Protocols and materials databases

    DNASUi 23612.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000367309 ; ENSP00000356278 ; ENSG00000174307 .
    ENST00000367311 ; ENSP00000356280 ; ENSG00000174307 .
    GeneIDi 23612.
    KEGGi hsa:23612.
    UCSCi uc001gwq.4. human.

    Organism-specific databases

    CTDi 23612.
    GeneCardsi GC01M201434.
    HGNCi HGNC:8934. PHLDA3.
    HPAi HPA027601.
    MIMi 607054. gene.
    neXtProti NX_Q9Y5J5.
    PharmGKBi PA33275.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG40478.
    HOGENOMi HOG000115528.
    HOVERGENi HBG052730.
    InParanoidi Q9Y5J5.
    OMAi ESTERHI.
    OrthoDBi EOG7NKKM7.
    PhylomeDBi Q9Y5J5.
    TreeFami TF332320.

    Miscellaneous databases

    GenomeRNAii 23612.
    NextBioi 46318.
    PROi Q9Y5J5.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q9Y5J5.
    CleanExi HS_PHLDA3.
    Genevestigatori Q9Y5J5.

    Family and domain databases

    Gene3Di 2.30.29.30. 1 hit.
    InterProi IPR001849. PH_domain.
    IPR011993. PH_like_dom.
    [Graphical view ]
    SMARTi SM00233. PH. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "A novel pleckstrin homology-related gene family defined by Ipl/Tssc3, TDAG51, and Tih1: tissue-specific expression, chromosomal location, and parental imprinting."
      Frank D., Mendelsohn C.L., Ciccone E., Svensson K., Ohlsson R., Tycko B.
      Mamm. Genome 10:1150-1159(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
    2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Placenta and Thalamus.
    3. Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
      Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Cerebellum.
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Brain and Skin.
    6. "A p53-dominant transcriptional response to cisplatin in testicular germ cell tumor-derived human embryonal carcinoma."
      Kerley-Hamilton J.S., Pike A.M., Li N., DiRenzo J., Spinella M.J.
      Oncogene 24:6090-6100(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION BY TP53.
    7. Cited for: FUNCTION, PHOSPHOINOSITIDE-BINDING, SUBCELLULAR LOCATION, INDUCTION BY TP53.
    8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiPHLA3_HUMAN
    AccessioniPrimary (citable) accession number: Q9Y5J5
    Secondary accession number(s): B2R5A4, Q53HD6, Q8NBW9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 20, 2005
    Last sequence update: November 1, 1999
    Last modified: October 1, 2014
    This is version 105 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Miscellaneous

    PHLDA3 genomic locus is frequently observed in primary lung cancers, suggesting a role in tumor suppression.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3