Reviewed, UniProtKB/Swiss-Prot Q9Y5J5 (PHLA3_HUMAN)

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) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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 directs transcription regulation by p53/TP53 may explain how p53/TP53 can negatively regulate AKT1. May acts 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 p53/TP53. p53/TP53 phosphorylation on 'Ser-15' is required to activate the PHLDA3 promoter. Ref.7 Ref.6
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-triphosphate (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
Gene Ontology (GO)
Biological process	DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis Ref.7 Inferred from direct assay. Source: UniProtKB anatomical structure morphogenesis Ref.1 Traceable author statement. Source: ProtInc apoptosis Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of protein kinase B signaling cascade Ref.7 Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Ref.7 Inferred from direct assay. Source: UniProtKB
Molecular function	identical protein binding Inferred from physical interaction. Source: IntAct phosphatidylinositol 3-phosphate binding Ref.7 Inferred from direct assay. Source: UniProtKB phosphatidylinositol-3,4,5-trisphosphate binding Ref.7 Inferred from direct assay. Source: UniProtKB phosphatidylinositol-3,4-bisphosphate binding Ref.7 Inferred from direct assay. Source: UniProtKB phosphatidylinositol-3,5-bisphosphate binding Ref.7 Inferred from direct assay. Source: UniProtKB phosphatidylinositol-4,5-bisphosphate binding Ref.7 Inferred from direct assay. Source: UniProtKB phosphatidylinositol-5-phosphate binding Ref.7 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		1	EBI-1055859,EBI-1055859
AHSA1	O95433	1	EBI-1055859,EBI-448610
ATP5L	O75964	1	EBI-1055859,EBI-1044001
CCDC47	Q96A33	1	EBI-1055859,EBI-720151
EFTUD2	Q15029	1	EBI-1055859,EBI-357897
HEATR2	Q86Y56	1	EBI-1055859,EBI-719966
HNRNPM	P52272	1	EBI-1055859,EBI-486809
IPO4	Q8TEX9	1	EBI-1055859,EBI-395967
LRPPRC	P42704	1	EBI-1055859,EBI-1050853
MMS19	Q96T76	1	EBI-1055859,EBI-1044169
NUP205	Q92621	1	EBI-1055859,EBI-1045046
NUP93	Q8N1F7	1	EBI-1055859,EBI-1042703
PDCD6IP	Q8WUM4	1	EBI-1055859,EBI-310624
PDXDC1	Q6P996	1	EBI-1055859,EBI-1049813
RARS2	Q5T160	1	EBI-1055859,EBI-1050546
SLC25A12	O75746	1	EBI-1055859,EBI-1047585
SSR4	P51571	1	EBI-1055859,EBI-1054539
TNPO3	Q9Y5L0	1	EBI-1055859,EBI-1042571
TTC27	Q6P3X3	1	EBI-1055859,EBI-1057046
UNC45A	Q9H3U1	1	EBI-1055859,EBI-1048763
XPO4	Q9C0E2	1	EBI-1055859,EBI-1044855
XPO5	Q9HAV4	1	EBI-1055859,EBI-517949
ZW10	O43264	1	EBI-1055859,EBI-1001217

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: dbSNP rs35383942.		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)
	Q9Y5J5-1 [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: 10594239] [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: 14702039] [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: 15489334] [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: 15940259] [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: 19203586] [Abstract] Cited for: FUNCTION, PHOSPHOINOSITIDE-BINDING, SUBCELLULAR LOCATION, INDUCTION BY TP53.

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.
UniGene	Hs.268557
3D structure databases
SMR	Q9Y5J5. Positions 5-98.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y5J5. 98 interactions.
STRING	Q9Y5J5.
Proteomic databases
PRIDE	Q9Y5J5.
Genome annotation databases
Ensembl	ENST00000367309; ENSP00000356278; ENSG00000174307; Homo sapiens. [Genome view] ENST00000367311; ENSP00000356280; ENSG00000174307; Homo sapiens. [Genome view]
GeneID	23612.
KEGG	hsa:23612.
UCSC	uc001gwq.1. human.
Organism-specific databases
CTD	23612.
GeneCards	GC01M199701.
H-InvDB	HIX0001459.
HGNC	HGNC:8934. PHLDA3.
MIM	607054. gene.
PharmGKB	PA33275.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG20417.
HOGENOM	HBG713670.
HOVERGEN	Q9Y5J5.
InParanoid	Q9Y5J5.
OMA	FRGPLED.
OrthoDB	EOG91ZHXC.
PhylomeDB	Q9Y5J5.
Gene expression databases
ArrayExpress	Q9Y5J5.
Bgee	Q9Y5J5.
CleanEx	HS_PHLDA3.
Genevestigator	Q9Y5J5.
GermOnline	ENSG00000174307. Homo sapiens.
Family and domain databases
InterPro	IPR001849. Pleckstrin_homology. [Graphical view]
SMART	SM00233. PH. 1 hit. [Graphical view]
PROSITE	PS50003. PH_DOMAIN. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
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:	January 19, 2010
This is version 64 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.