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Q9Y5J5 (PHLA3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Pleckstrin homology-like domain family A member 3
Alternative name(s):
TDAG51/Ipl homolog 1
Gene names
Name:PHLDA3
Synonyms:TIH1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length127 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.7

Subcellular location

Cytoplasm. Membrane; Peripheral membrane protein Ref.7.

Tissue specificity

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

Induction

By p53/TP53; expression is directly activated by TP53. TP53 phosphorylation on 'Ser-15' is required to activate the PHLDA3 promoter. Ref.6 Ref.7

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.

Miscellaneous

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

Sequence similarities

Belongs to the PHLDA3 family.

Contains 1 PH domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 127127Pleckstrin homology-like domain family A member 3
PRO_0000053902

Regions

Domain8 – 127120PH

Natural variations

Natural variant281R → Q.
Corresponds to variant rs35383942 [ dbSNP | Ensembl ].
VAR_050515

Experimental info

Sequence conflict81T → A in BAD96364. Ref.3
Sequence conflict881P → L in BAC11454. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q9Y5J5 [UniParc].

Last modified November 1, 1999. Version 1.
Checksum: 35014547F840D115

FASTA12713,891
        10         20         30         40         50         60 
MTAAATATVL KEGVLEKRSG GLLQLWKRKR CVLTERGLQL FEAKGTGGRP KELSFARIKA 

        70         80         90        100        110        120 
VECVESTGRH IYFTLVTEGG GEIDFRCPLE DPGWNAQITL GLVKFKNQQA IQTVRARQSL 


GTGTLVS 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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]"PH domain-only protein PHLDA3 is a p53-regulated repressor of Akt."
Kawase T., Ohki R., Shibata T., Tsutsumi S., Kamimura N., Inazawa J., Ohta T., Ichikawa H., Aburatani H., Tashiro F., Taya Y.
Cell 136:535-550(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHOINOSITIDE-BINDING, SUBCELLULAR LOCATION, INDUCTION BY TP53.
[8]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_036528.1. NM_012396.3.
UniGeneHs.268557.

3D structure databases

ProteinModelPortalQ9Y5J5.
SMRQ9Y5J5. Positions 10-102.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117145. 24 interactions.
IntActQ9Y5J5. 1 interaction.
STRING9606.ENSP00000356278.

PTM databases

PhosphoSiteQ9Y5J5.

Polymorphism databases

DMDM74735291.

Proteomic databases

PaxDbQ9Y5J5.
PRIDEQ9Y5J5.

Protocols and materials databases

DNASU23612.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000367309; ENSP00000356278; ENSG00000174307.
ENST00000367311; ENSP00000356280; ENSG00000174307.
GeneID23612.
KEGGhsa:23612.
UCSCuc001gwq.4. human.

Organism-specific databases

CTD23612.
GeneCardsGC01M201434.
HGNCHGNC:8934. PHLDA3.
HPAHPA027601.
MIM607054. gene.
neXtProtNX_Q9Y5J5.
PharmGKBPA33275.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG40478.
HOGENOMHOG000115528.
HOVERGENHBG052730.
InParanoidQ9Y5J5.
OMAESTERHI.
OrthoDBEOG7NKKM7.
PhylomeDBQ9Y5J5.
TreeFamTF332320.

Gene expression databases

BgeeQ9Y5J5.
CleanExHS_PHLDA3.
GenevestigatorQ9Y5J5.

Family and domain databases

Gene3D2.30.29.30. 1 hit.
InterProIPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
[Graphical view]
SMARTSM00233. PH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi23612.
NextBio46318.
PROQ9Y5J5.
SOURCESearch...

Entry information

Entry namePHLA3_HUMAN
AccessionPrimary (citable) accession number: Q9Y5J5
Secondary accession number(s): B2R5A4, Q53HD6, Q8NBW9
Entry history
Integrated into UniProtKB/Swiss-Prot: December 20, 2005
Last sequence update: November 1, 1999
Last modified: April 16, 2014
This is version 100 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM