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Protein

Pleckstrin homology-like domain family A member 3

Gene

PHLDA3

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

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
Complete GO annotation...

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: UniProtKB
  3. plasma membrane Source: UniProtKB
Complete GO annotation...

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.
GeneTreeiENSGT00440000039564.
HOGENOMiHOG000115528.
HOVERGENiHBG052730.
InParanoidiQ9Y5J5.
OMAiVRARHSC.
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

        10         20         30         40         50
MTAAATATVL KEGVLEKRSG GLLQLWKRKR CVLTERGLQL FEAKGTGGRP
60 70 80 90 100
KELSFARIKA VECVESTGRH IYFTLVTEGG GEIDFRCPLE DPGWNAQITL
110 120
GLVKFKNQQA IQTVRARQSL GTGTLVS
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

ProteinModelPortaliQ9Y5J5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

PTM databases

PhosphoSiteiQ9Y5J5.

Polymorphism databases

DMDMi74735291.

Proteomic databases

MaxQBiQ9Y5J5.
PaxDbiQ9Y5J5.
PRIDEiQ9Y5J5.

Protocols and materials databases

DNASUi23612.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi23612.
GeneCardsiGC01M201434.
HGNCiHGNC:8934. PHLDA3.
HPAiHPA027601.
MIMi607054. gene.
neXtProtiNX_Q9Y5J5.
PharmGKBiPA33275.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG40478.
GeneTreeiENSGT00440000039564.
HOGENOMiHOG000115528.
HOVERGENiHBG052730.
InParanoidiQ9Y5J5.
OMAiVRARHSC.
OrthoDBiEOG7NKKM7.
PhylomeDBiQ9Y5J5.
TreeFamiTF332320.

Miscellaneous databases

ChiTaRSiPHLDA3. human.
GenomeRNAii23612.
NextBioi46318.
PROiQ9Y5J5.
SOURCEiSearch...

Gene expression databases

BgeeiQ9Y5J5.
CleanExiHS_PHLDA3.
GenevestigatoriQ9Y5J5.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: January 7, 2015
This is version 108 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.