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Q9HB21 (PKHA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 108. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Pleckstrin homology domain-containing family A member 1

Short name=PH domain-containing family A member 1
Alternative name(s):
Tandem PH domain-containing protein 1
Short name=TAPP-1
Gene names
Name:PLEKHA1
Synonyms:TAPP1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length404 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Binds specifically to phosphatidylinositol 3,4-diphosphate (PtdIns3,4P2), but not to other phosphoinositides. May recruit other proteins to the plasma membrane. Ref.1 Ref.8 Ref.12

Subunit structure

Interacts with MPDZ and PTPN13. Ref.6 Ref.8

Subcellular location

Cytoplasm. Cell membrane; Peripheral membrane protein. Nucleus. Note: Locates to the plasma membrane after treatments that stimulate the production of PtdIns3,4P2. Ref.6 Ref.7

Tissue specificity

Highly expressed in skeletal muscle, thymus, pancreas, placenta and lung. Detected at low levels in brain, heart, peripheral blood leukocytes, testis, ovary, spinal cord, thyroid, kidney, liver, small intestine and colon. Ref.1 Ref.7

Domain

Binds to membranes enriched in PtdIns3,4P2 via the C-terminal PH domain.

Sequence similarities

Contains 2 PH domains.

Ontologies

Keywords
   Cellular componentCell membrane
Cytoplasm
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
   LigandLipid-binding
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processB cell receptor signaling pathway

Inferred from direct assay Ref.7. Source: UniProtKB

Leydig cell differentiation

Inferred from electronic annotation. Source: Ensembl

androgen metabolic process

Inferred from electronic annotation. Source: Ensembl

cellular response to hydrogen peroxide

Inferred from direct assay Ref.8. Source: UniProtKB

establishment of protein localization

Inferred from direct assay Ref.8. Source: UniProtKB

estrogen metabolic process

Inferred from electronic annotation. Source: Ensembl

face morphogenesis

Inferred from electronic annotation. Source: Ensembl

luteinization

Inferred from electronic annotation. Source: Ensembl

multicellular organism growth

Inferred from electronic annotation. Source: Ensembl

negative regulation of protein kinase B signaling

Inferred from mutant phenotype Ref.8. Source: UniProtKB

palate development

Inferred from electronic annotation. Source: Ensembl

phosphatidylinositol 3-kinase signaling

Inferred from direct assay Ref.7. Source: UniProtKB

platelet-derived growth factor receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

post-embryonic development

Inferred from electronic annotation. Source: Ensembl

ruffle organization

Inferred from direct assay PubMed 15485858. Source: UniProtKB

skeletal system morphogenesis

Inferred from electronic annotation. Source: Ensembl

spermatogenesis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from direct assay Ref.7Ref.8. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

nucleus

Inferred from direct assay. Source: HPA

plasma membrane

Inferred from direct assay Ref.7Ref.8. Source: UniProtKB

ruffle membrane

Inferred from direct assay Ref.7. Source: UniProtKB

   Molecular_functionPDZ domain binding

Inferred from physical interaction Ref.6Ref.8PubMed 15485858. Source: UniProtKB

phosphatidylinositol-3,4-bisphosphate binding

Inferred from direct assay Ref.1PubMed 17823121. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.6PubMed 18654987. Source: IntAct

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9HB21-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9HB21-2)

The sequence of this isoform differs from the canonical sequence as follows:
     301-404: EHPPGPSESK...DDASLPVSDV → MRQARRLSNPCIQRYTSRAGECSTYVGSHANVPS
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 404404Pleckstrin homology domain-containing family A member 1
PRO_0000053873

Regions

Domain7 – 112106PH 1
Domain191 – 28999PH 2

Amino acid modifications

Modified residue3621Phosphoserine Ref.9

Natural variations

Alternative sequence301 – 404104EHPPG…PVSDV → MRQARRLSNPCIQRYTSRAG ECSTYVGSHANVPS in isoform 2.
VSP_043091
Natural variant3201T → A. Ref.1 Ref.4
Corresponds to variant rs1045216 [ dbSNP | Ensembl ].
VAR_024562

Experimental info

Mutagenesis281R → L: No effect on phosphatidylinositide binding. Ref.1
Mutagenesis203 – 2053AVM → GGG: Abolishes phosphatidylinositide binding. Ref.12
Mutagenesis203 – 2053AVM → GLV: Binds both PtdIns3,4P2 and PtdIns3,4,5P3. Ref.12
Mutagenesis203 – 2042AV → GG: Binds both PtdIns3,4P2 and PtdIns3,4,5P3. Ref.12
Mutagenesis2031A → G: Binds both PtdIns3,4P2 and PtdIns3,4,5P3. Ref.12
Mutagenesis2041V → L: No effect. Ref.12
Mutagenesis2051M → V: No effect. Ref.12
Mutagenesis2071N → T: No effect. Ref.12
Mutagenesis2111R → L: Abolishes phosphatidylinositide binding. Ref.1

Secondary structure

...................... 404
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 29, 2004. Version 2.
Checksum: 6855CD58E1A80F8A

FASTA40445,553
        10         20         30         40         50         60 
MPYVDRQNRI CGFLDIEENE NSGKFLRRYF ILDTREDSFV WYMDNPQNLP SGSSRVGAIK 

        70         80         90        100        110        120 
LTYISKVSDA TKLRPKAEFC FVMNAGMRKY FLQANDQQDL VEWVNVLNKA IKITVPKQSD 

       130        140        150        160        170        180 
SQPNSDNLSR HGECGKKQVS YRTDIVGGVP IITPTQKEEV NECGESIDRN NLKRSQSHLP 

       190        200        210        220        230        240 
YFTPKPPQDS AVIKAGYCVK QGAVMKNWKR RYFQLDENTI GYFKSELEKE PLRVIPLKEV 

       250        260        270        280        290        300 
HKVQECKQSD IMMRDNLFEI VTTSRTFYVQ ADSPEEMHSW IKAVSGAIVA QRGPGRSASS 

       310        320        330        340        350        360 
EHPPGPSESK HAFRPTNAAT ATSHSTASRS NSLVSTFTME KRGFYESLAK VKPGNFKVQT 

       370        380        390        400 
VSPREPASKV TEQALLRPQS KNGPQEKDCD LVDLDDASLP VSDV 

« Hide

Isoform 2 [UniParc].

Checksum: 34B9D858E2993FDE
Show »

FASTA33438,113

References

« Hide 'large scale' references
[1]"Identification of pleckstrin-homology-domain-containing proteins with novel phosphoinositide-binding specificities."
Dowler S.J., Currie R.A., Campbell D.G., Deak M., Kular G., Downes C.P., Alessi D.R.
Biochem. J. 351:19-31(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, MUTAGENESIS OF ARG-28 AND ARG-211, TISSUE SPECIFICITY, VARIANT ALA-320.
[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] (ISOFORM 2).
Tissue: Testis.
[3]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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 (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ALA-320.
[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] (ISOFORM 1).
Tissue: Colon and Testis.
[6]"Evidence that the tandem-pleckstrin-homology-domain-containing protein TAPP1 interacts with Ptd(3,4)P2 and the multi-PDZ-domain-containing protein MUPP1 in vivo."
Kimber W.A., Trinkle-Mulcahy L., Cheung P.C.F., Deak M., Marsden L.J., Kieloch A., Watt S., Javier R.T., Gray A., Downes C.P., Lucocq J.M., Alessi D.R.
Biochem. J. 361:525-536(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MPDZ, SUBCELLULAR LOCATION.
[7]"TAPP1 and TAPP2 are targets of phosphatidylinositol 3-kinase signaling in B cells: sustained plasma membrane recruitment triggered by the B-cell antigen receptor."
Marshall A.J., Krahn A.K., Ma K., Duronio V., Hou S.
Mol. Cell. Biol. 22:5479-5491(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[8]"Interaction of the protein tyrosine phosphatase PTPL1 with the PtdIns(3,4)P2-binding adaptor protein TAPP1."
Kimber W.A., Deak M., Prescott A.R., Alessi D.R.
Biochem. J. 376:525-535(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PTPN13, FUNCTION.
[9]"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-362, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[11]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Crystal structure of the phosphatidylinositol 3,4-bisphosphate-binding pleckstrin homology (PH) domain of tandem PH-domain-containing protein 1 (TAPP1): molecular basis of lipid specificity."
Thomas C.C., Dowler S.J., Deak M., Alessi D.R., van Aalten D.M.F.
Biochem. J. 358:287-294(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 190-292, FUNCTION, MUTAGENESIS OF ALA-203; VAL-204; MET-205 AND ASN-207.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF286160 mRNA. Translation: AAG15197.1.
AK057463 mRNA. Translation: BAG51917.1.
BX664700, BX842242 Genomic DNA. Translation: CAI23597.1.
CH471066 Genomic DNA. Translation: EAW49315.1.
CH471066 Genomic DNA. Translation: EAW49316.1.
CH471066 Genomic DNA. Translation: EAW49318.1.
CH471066 Genomic DNA. Translation: EAW49319.1.
BC001136 mRNA. Translation: AAH01136.1.
BC042458 mRNA. Translation: AAH42458.1.
CCDSCCDS55730.1. [Q9HB21-2]
CCDS7629.1. [Q9HB21-1]
RefSeqNP_001001974.1. NM_001001974.2. [Q9HB21-1]
NP_001182537.1. NM_001195608.1. [Q9HB21-2]
NP_067635.2. NM_021622.4. [Q9HB21-1]
XP_005270073.1. XM_005270016.1. [Q9HB21-1]
XP_005270074.1. XM_005270017.1. [Q9HB21-1]
XP_005270075.1. XM_005270018.1. [Q9HB21-1]
XP_005270078.1. XM_005270021.2. [Q9HB21-2]
UniGeneHs.643512.
Hs.738826.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1EAZX-ray1.40A182-303[»]
ProteinModelPortalQ9HB21.
SMRQ9HB21. Positions 1-112, 155-292.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121880. 8 interactions.
IntActQ9HB21. 5 interactions.
MINTMINT-275100.
STRING9606.ENSP00000357986.

PTM databases

PhosphoSiteQ9HB21.

Polymorphism databases

DMDM48474647.

Proteomic databases

MaxQBQ9HB21.
PaxDbQ9HB21.
PRIDEQ9HB21.

Protocols and materials databases

DNASU59338.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000368990; ENSP00000357986; ENSG00000107679. [Q9HB21-1]
ENST00000392799; ENSP00000376547; ENSG00000107679. [Q9HB21-1]
ENST00000433307; ENSP00000394416; ENSG00000107679. [Q9HB21-1]
ENST00000538022; ENSP00000438608; ENSG00000107679. [Q9HB21-2]
GeneID59338.
KEGGhsa:59338.
UCSCuc001lge.2. human. [Q9HB21-1]
uc001lgf.2. human. [Q9HB21-2]

Organism-specific databases

CTD59338.
GeneCardsGC10P124124.
HGNCHGNC:14335. PLEKHA1.
HPAHPA002043.
MIM607772. gene.
neXtProtNX_Q9HB21.
PharmGKBPA33401.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG45745.
HOGENOMHOG000116175.
HOVERGENHBG053612.
InParanoidQ9HB21.
OrthoDBEOG7VMP5J.
PhylomeDBQ9HB21.
TreeFamTF329516.

Gene expression databases

ArrayExpressQ9HB21.
BgeeQ9HB21.
CleanExHS_PLEKHA1.
GenevestigatorQ9HB21.

Family and domain databases

Gene3D2.30.29.30. 2 hits.
InterProIPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
[Graphical view]
PfamPF00169. PH. 2 hits.
[Graphical view]
SMARTSM00233. PH. 2 hits.
[Graphical view]
PROSITEPS50003. PH_DOMAIN. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPLEKHA1. human.
EvolutionaryTraceQ9HB21.
GeneWikiPLEKHA1.
GenomeRNAi59338.
NextBio65210.
PROQ9HB21.
SOURCESearch...

Entry information

Entry namePKHA1_HUMAN
AccessionPrimary (citable) accession number: Q9HB21
Secondary accession number(s): B3KQ55, D3DRE2, Q9BVK0
Entry history
Integrated into UniProtKB/Swiss-Prot: March 29, 2004
Last sequence update: March 29, 2004
Last modified: July 9, 2014
This is version 108 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 10

Human chromosome 10: entries, gene names and cross-references to MIM