Q53GA4 (PHLA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pleckstrin homology-like domain family A member 2

Alternative name(s):
Beckwith-Wiedemann syndrome chromosomal region 1 candidate gene C protein
Imprinted in placenta and liver protein
Tumor-suppressing STF cDNA 3 protein
Tumor-suppressing subchromosomal transferable fragment candidate gene 3 protein
p17-Beckwith-Wiedemann region 1 C
Short name=p17-BWR1C

Gene names

Name:	PHLDA2
Synonyms:	BWR1C, HLDA2, IPL, TSSC3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	152 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays a role in regulating placenta growth. May act via its PH domain that competes with other PH domain-containing proteins, thereby preventing their binding to membrane lipids By similarity.
Subcellular location	Cytoplasm By similarity. Membrane; Peripheral membrane protein By similarity Ref.10.
Tissue specificity	Expressed in placenta and adult prostate gland. In placenta, it is present in all cells of the villous cytotrophoblast. The protein is absent in cells from hydatidiform moles. Hydatidiform mole is a gestation characterized by abnormal development of both fetus and trophoblast. The majority of hydatidiform moles are associated with an excess of paternal to maternal genomes and are likely to result from the abnormal expression of imprinted genes (at protein level). Expressed at low levels in adult liver and lung, and fetal liver. Expressed in adult brain and neuroblastoma, medullablastoma and glioblastoma cell lines. Ref.2 Ref.7 Ref.8 Ref.9 Ref.10
Induction	Maternal PHLDA2 allele is activated, while paternal Phlda2 is repressed due to genomic imprinting. Down-regulated by hypoxia. Although highly similar to PHLDA3 protein, it is not regulated by p53/TP53. Ref.11 Ref.14 Ref.17
Domain	The PH domain binds phosphoinositides with a broad specificity. It may compete with the PH domain of some other proteins, thereby interfering with their binding to phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-triphosphate (PIP3) By similarity.
Miscellaneous	The PHLDA2 locus is imprinted. Loss of imprinting results in overexpression. Imprinting is dependent on RNAi machinery.
Sequence similarities	Belongs to the PHLDA2 family. Contains 1 PH domain.

Ontologies

Keywords
Cellular component	Cytoplasm Membrane
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	apoptotic process Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 152	152	Pleckstrin homology-like domain family A member 2		PRO_0000053900
Regions
	Domain	7 – 99	93	PH
	Compositional bias	126 – 133	8	Poly-Ala
Amino acid modifications
	Modified residue	3	1	Phosphoserine Ref.15
	Modified residue	42	1	Phosphoserine Ref.12 Ref.15 Ref.16 Ref.18
	Modified residue	135	1	Phosphoserine Ref.18
	Modified residue	138	1	Phosphoserine Ref.18
	Modified residue	141	1	Phosphoserine Ref.15 Ref.18
	Modified residue	144	1	Phosphoserine Ref.15 Ref.16
	Modified residue	151	1	Phosphothreonine Ref.16
Experimental info
	Sequence conflict	24	1	W → R in BAD96747. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Q53GA4 [UniParc]. Last modified December 20, 2005. Version 2. Checksum: 3A1168CBB859FC3B	FASTA	152	17,092
	10 20 30 40 50 60 MKSPDEVLRE GELEKRSDSL FQLWKKKRGV LTSDRLSLFP ASPRARPKEL RFHSILKVDC 70 80 90 100 110 120 VERTGKYVYF TIVTTDHKEI DFRCAGESCW NAAIALALID FQNRRALQDF RSRQERTAPA 130 140 150 APAEDAVAAA AAAPSEPSEP SRPSPQPKPR TP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A 2.5-Mb transcript map of a tumor-suppressing subchromosomal transferable fragment from 11p15.5, and isolation and sequence analysis of three novel genes." Hu R.-J., Lee M.P., Connors T.D., Johnson L.A., Burn T.C., Su K., Landes G.M., Feinberg A.P. Genomics 46:9-17(1997) [PubMed: 9403053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The IPL gene on chromosome 11p15.5 is imprinted in humans and mice and is similar to TDAG51, implicated in Fas expression and apoptosis." Qian N., Frank D., O'Keefe D., Dao D., Zhao L., Yuan L., Wang Q., Keating M., Walsh C., Tycko B. Hum. Mol. Genet. 6:2021-2029(1997) [PubMed: 9328465] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[3]	"Transcriptional map of 170-kb region at chromosome 11p15.5: identification and mutational analysis of the BWR1A gene reveals the presence of mutations in tumor samples." Schwienbacher C., Sabbioni S., Campi M., Veronese A., Bernardi G., Menegatti A., Hatada I., Mukai T., Ohashi H., Barbanti-Brodano G., Croce C.M., Negrini M. Proc. Natl. Acad. Sci. U.S.A. 95:3873-3878(1998) [PubMed: 9520460] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	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: Umbilical vein.
[6]	"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: Skin.
[7]	"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: TISSUE SPECIFICITY.
[8]	"Retention of imprinting of the human apoptosis-related gene TSSC3 in human brain tumors." Mueller S., van den Boom D., Zirkel D., Koester H., Berthold F., Schwab M., Westphal M., Zumkeller W. Hum. Mol. Genet. 9:757-763(2000) [PubMed: 10749982] [Abstract] Cited for: TISSUE SPECIFICITY.
[9]	"The product of the imprinted gene IPL marks human villous cytotrophoblast and is lost in complete hydatidiform mole." Saxena A., Frank D., Panichkul P., Van den Veyver I.B., Tycko B., Thaker H. Placenta 24:835-842(2003) [PubMed: 13129680] [Abstract] Cited for: TISSUE SPECIFICITY.
[10]	"Immunohistochemistry for the imprinted gene product IPL/PHLDA2 for facilitating the differential diagnosis of complete hydatidiform mole." Thaker H.M., Berlin A., Tycko B., Goldstein D.P., Berkowitz R.S., Castrillon D.H., Genest D.R. J. Reprod. Med. 49:630-636(2004) [PubMed: 15457853] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[11]	"Complete hydatidiform mole retaining a chromosome 11 of maternal origin: molecular genetic analysis of a case." Fisher R.A., Nucci M.R., Thaker H.M., Weremowicz S., Genest D.R., Castrillon D.H. Mod. Pathol. 17:1155-1160(2004) [PubMed: 15314611] [Abstract] Cited for: INDUCTION, IMPRINTING.
[12]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"Upregulation of PHLDA2 in Dicer knockdown HEK293 cells." Tang K.-F., Wang Y., Wang P., Chen M., Chen Y., Hu H.-D., Hu P., Wang B., Yang W., Ren H. Biochim. Biophys. Acta 1770:820-825(2007) [PubMed: 17303335] [Abstract] Cited for: IMPRINTING.
[14]	"Hypoxia regulates the expression of PHLDA2 in primary term human trophoblasts." Kim H.-S., Roh C.-R., Chen B., Tycko B., Nelson D.M., Sadovsky Y. Placenta 28:77-84(2007) [PubMed: 16584773] [Abstract] Cited for: INDUCTION.
[15]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3; SER-42; SER-141 AND SER-144, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[16]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42; SER-144 AND THR-151, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[17]	"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: LACK OF INDUCTION BY TP53.
[18]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42; SER-135; SER-138 AND SER-141, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF019953 mRNA. Translation: AAC51912.1. AF001294 mRNA. Translation: AAB86680.1. AF035444 mRNA. Translation: AAC17458.1. CR407664 mRNA. Translation: CAG28592.1. AK223027 mRNA. Translation: BAD96747.1. BC005034 mRNA. Translation: AAH05034.1.
IPI	IPI00019551.
RefSeq	NP_003302.1. NM_003311.3.
UniGene	Hs.154036.
3D structure databases
ProteinModelPortal	Q53GA4.
SMR	Q53GA4. Positions 4-98.
ModBase	Search...
Protein-protein interaction databases
STRING	Q53GA4.
PTM databases
PhosphoSite	Q53GA4.
Polymorphism databases
DMDM	84029394.
Proteomic databases
PRIDE	Q53GA4.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000314222; ENSP00000319231; ENSG00000181649.
GeneID	7262.
KEGG	hsa:7262.
UCSC	uc001lxa.1. human.
Organism-specific databases
CTD	7262.
GeneCards	GC11M002949.
H-InvDB	HIX0009369.
HGNC	HGNC:12385. PHLDA2.
HPA	HPA003994.
MIM	602131. gene.
neXtProt	NX_Q53GA4.
PharmGKB	PA37053.
GenAtlas	Search...
Phylogenomic databases
eggNOG	maNOG21061.
GeneTree	ENSGT00440000039564.
HOGENOM	HBG713670.
HOVERGEN	HBG052730.
InParanoid	Q53GA4.
OMA	RKEIDFR.
OrthoDB	EOG4FR0T0.
PhylomeDB	Q53GA4.
Gene expression databases
ArrayExpress	Q53GA4.
Bgee	Q53GA4.
CleanEx	HS_PHLDA2.
Genevestigator	Q53GA4.
GermOnline	ENSG00000181649. Homo sapiens.
Family and domain databases
InterPro	IPR011993. PH_type. IPR001849. Pleckstrin_homology. [Graphical view]
Gene3D	G3DSA:2.30.29.30. PH_type. 1 hit.
SMART	SM00233. PH. 1 hit. [Graphical view]
PROSITE	PS50003. PH_DOMAIN. False negative. [Graphical view]
ProtoNet	Search...
Other
NextBio	28391.
SOURCE	Search...

Entry information

Entry name

PHLA2_HUMAN

Accession

Primary (citable) accession number: Q53GA4
Secondary accession number(s): O00496

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 20, 2005
Last sequence update:	December 20, 2005
Last modified:	January 25, 2012
This is version 60 of the entry and version 2 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.