Q9Y5J5 (PHLA3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pleckstrin homology-like domain family A member 3

Alternative name(s):
TDAG51/Ipl homolog 1

Gene names

Name:	PHLDA3
Synonyms:	TIH1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	127 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Polymorphism
Disease	Tumor suppressor
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	anatomical structure morphogenesis Traceable author statement Ref.1. Source: ProtInc induction of apoptosis Inferred from direct assay Ref.7. Source: UniProtKB intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Inferred from direct assay Ref.7. Source: UniProtKB negative regulation of protein kinase B signaling cascade Inferred from direct assay Ref.7. Source: UniProtKB
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell intracellular membrane-bounded organelle Inferred from direct assay. Source: HPA plasma membrane Inferred from direct assay Ref.7. Source: UniProtKB
Molecular_function	phosphatidylinositol-3,4,5-trisphosphate binding Inferred from direct assay Ref.7. Source: UniProtKB phosphatidylinositol-3,4-bisphosphate binding Inferred from direct assay Ref.7. Source: UniProtKB phosphatidylinositol-3,5-bisphosphate binding Inferred from direct assay Ref.7. Source: UniProtKB phosphatidylinositol-3-phosphate binding Inferred from direct assay Ref.7. Source: UniProtKB phosphatidylinositol-4,5-bisphosphate binding Inferred from direct assay Ref.7. Source: UniProtKB phosphatidylinositol-5-phosphate binding Inferred from direct assay Ref.7. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 127	127	Pleckstrin homology-like domain family A member 3		PRO_0000053902
Regions
	Domain	8 – 127	120	PH
Natural variations
	Natural variant	28	1	R → Q. Corresponds to variant rs35383942 [ dbSNP | Ensembl ].		VAR_050515
Experimental info
	Sequence conflict	8	1	T → A in BAD96364. Ref.3
	Sequence conflict	88	1	P → L in BAC11454. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9Y5J5 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 35014547F840D115	FASTA	127	13,891
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
IPI	IPI00329599.
RefSeq	NP_036528.1. NM_012396.3.
UniGene	Hs.268557.
3D structure databases
ProteinModelPortal	Q9Y5J5.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y5J5. 1 interaction.
STRING	9606.ENSP00000356278.
PTM databases
PhosphoSite	Q9Y5J5.
Polymorphism databases
DMDM	74735291.
Proteomic databases
PaxDb	Q9Y5J5.
PRIDE	Q9Y5J5.
Protocols and materials databases
DNASU	23612.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000367309; ENSP00000356278; ENSG00000174307. ENST00000367311; ENSP00000356280; ENSG00000174307.
GeneID	23612.
KEGG	hsa:23612.
UCSC	uc001gwq.3. human.
Organism-specific databases
CTD	23612.
GeneCards	GC01M201434.
HGNC	HGNC:8934. PHLDA3.
HPA	HPA027601.
MIM	607054. gene.
neXtProt	NX_Q9Y5J5.
PharmGKB	PA33275.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG40478.
HOGENOM	HOG000115528.
HOVERGEN	HBG052730.
InParanoid	Q9Y5J5.
OMA	ESTERHI.
OrthoDB	EOG4FR0T0.
PhylomeDB	Q9Y5J5.
Gene expression databases
Bgee	Q9Y5J5.
CleanEx	HS_PHLDA3.
Genevestigator	Q9Y5J5.
GermOnline	ENSG00000174307. Homo sapiens.
Family and domain databases
Gene3D	2.30.29.30. 1 hit.
InterPro	IPR011993. PH_like_dom. IPR001849. Pleckstrin_homology. [Graphical view]
SMART	SM00233. PH. 1 hit. [Graphical view]
PROSITE	PS50003. PH_DOMAIN. False negative. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	23612.
NextBio	46318.
SOURCE	Search...

Entry information

Entry name

PHLA3_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.