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Q53GA4 (PHLA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 78. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length152 AA.
Sequence statusComplete.
Protein existenceEvidence 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.13 Ref.16

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-trisphosphate (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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 152152Pleckstrin homology-like domain family A member 2
PRO_0000053900

Regions

Domain7 – 9993PH
Compositional bias126 – 1338Poly-Ala

Amino acid modifications

Modified residue31Phosphoserine Ref.14
Modified residue421Phosphoserine Ref.15 Ref.18
Modified residue1411Phosphoserine Ref.14
Modified residue1441Phosphoserine Ref.14 Ref.15
Modified residue1511Phosphothreonine Ref.15

Experimental info

Sequence conflict241W → R in BAD96747. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Q53GA4 [UniParc].

Last modified December 20, 2005. Version 2.
Checksum: 3A1168CBB859FC3B

FASTA15217,092
        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 

« Hide

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: INDUCTION, IMPRINTING.
[12]"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] [Europe PMC] [Abstract]
Cited for: IMPRINTING.
[13]"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] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[14]"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3; SER-141 AND SER-144, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[15]"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42; SER-144 AND THR-151, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[16]"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: LACK OF INDUCTION BY TP53.
[17]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[19]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+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.
RefSeqNP_003302.1. NM_003311.3.
UniGeneHs.154036.

3D structure databases

ProteinModelPortalQ53GA4.
SMRQ53GA4. Positions 2-97.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113113. 1 interaction.
STRING9606.ENSP00000319231.

PTM databases

PhosphoSiteQ53GA4.

Polymorphism databases

DMDM84029394.

Proteomic databases

PaxDbQ53GA4.
PRIDEQ53GA4.

Protocols and materials databases

DNASU7262.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000314222; ENSP00000319231; ENSG00000181649.
GeneID7262.
KEGGhsa:7262.
UCSCuc001lxa.1. human.

Organism-specific databases

CTD7262.
GeneCardsGC11M002949.
HGNCHGNC:12385. PHLDA2.
HPAHPA003994.
MIM602131. gene.
neXtProtNX_Q53GA4.
PharmGKBPA37053.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG47789.
HOGENOMHOG000115528.
HOVERGENHBG052730.
InParanoidQ53GA4.
OMAKKVDCVE.
OrthoDBEOG7NKKM7.
PhylomeDBQ53GA4.
TreeFamTF332320.

Gene expression databases

BgeeQ53GA4.
CleanExHS_PHLDA2.
GenevestigatorQ53GA4.

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

GeneWikiPHLDA2.
GenomeRNAi7262.
NextBio28391.
PROQ53GA4.
SOURCESearch...

Entry information

Entry namePHLA2_HUMAN
AccessionPrimary (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: March 19, 2014
This is version 78 of the entry and version 2 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 chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM