Q9HB21 (PKHA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	404 AA.
Sequence status	Complete.
Protein existence	Evidence 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 component	Cell membrane Cytoplasm Membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat
Ligand	Lipid-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell receptor signaling pathway Inferred from direct assay Ref.7. Source: UniProtKB Leydig cell differentiation Inferred from electronic annotation. Source: Compara androgen metabolic process Inferred from electronic annotation. Source: Compara 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: Compara face morphogenesis Inferred from electronic annotation. Source: Compara luteinization Inferred from electronic annotation. Source: Compara multicellular organism growth Inferred from electronic annotation. Source: Compara negative regulation of protein kinase B signaling cascade Inferred from mutant phenotype Ref.8. Source: UniProtKB palate development Inferred from electronic annotation. Source: Compara phosphatidylinositol 3-kinase cascade Inferred from direct assay Ref.7. Source: UniProtKB platelet-derived growth factor receptor signaling pathway Inferred from electronic annotation. Source: Compara post-embryonic development Inferred from electronic annotation. Source: Compara ruffle organization Inferred from direct assay PubMed 15485858. Source: UniProtKB skeletal system morphogenesis Inferred from electronic annotation. Source: Compara spermatogenesis Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from direct assay Ref.7Ref.8. Source: UniProtKB nucleus Inferred from direct assay. Source: HPA ruffle membrane Inferred from direct assay Ref.7. Source: UniProtKB
Molecular_function	phosphatidylinositol-3,4-bisphosphate binding Inferred from direct assay Ref.1PubMed 17823121. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SH3BP4	Q9P0V3	2	EBI-2652984,EBI-1049513

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 404

404

Pleckstrin homology domain-containing family A member 1

PRO_0000053873

Regions

Domain

7 – 112

106

PH 1

Domain

191 – 289

99

PH 2

Amino acid modifications

Modified residue

362

1

Phosphoserine Ref.9

Natural variations

Alternative sequence

301 – 404

104

EHPPG…PVSDV → MRQARRLSNPCIQRYTSRAG ECSTYVGSHANVPS in isoform 2.

VSP_043091

Natural variant

320

1

T → A. Ref.1 Ref.4
Corresponds to variant rs1045216 [ dbSNP | Ensembl ].

VAR_024562

Experimental info

Mutagenesis

28

1

R → L: No effect on phosphatidylinositide binding. Ref.1

Mutagenesis

203 – 205

3

AVM → GGG: Abolishes phosphatidylinositide binding. Ref.12

Mutagenesis

203 – 205

3

AVM → GLV: Binds both PtdIns3,4P2 and PtdIns3,4,5P3. Ref.12

Mutagenesis

203 – 204

2

AV → GG: Binds both PtdIns3,4P2 and PtdIns3,4,5P3. Ref.12

Mutagenesis

203

1

A → G: Binds both PtdIns3,4P2 and PtdIns3,4,5P3. Ref.12

Mutagenesis

204

1

V → L: No effect. Ref.12

Mutagenesis

205

1

M → V: No effect. Ref.12

Mutagenesis

207

1

N → T: No effect. Ref.12

Mutagenesis

211

1

R → L: Abolishes phosphatidylinositide binding. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

404

Helix Strand Turn

Details...

Beta strand

193 – 201

9

Turn

203 – 205

3

Beta strand

208 – 215

8

Beta strand

217 – 225

9

Beta strand

232 – 236

5

Helix

237 – 239

3

Beta strand

242 – 245

4

Helix

249 – 252

4

Beta strand

255 – 261

7

Beta strand

266 – 270

5

Helix

274 – 290

17

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 29, 2004. Version 2. Checksum: 6855CD58E1A80F8A	FASTA	404	45,553
	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
	Isoform 2 [UniParc]. Checksum: 34B9D858E2993FDE	FASTA	334	38,113
	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 MRQARRLSNP CIQRYTSRAG ECSTYVGSHA NVPS

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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, MASS SPECTROMETRY. 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.

IPI

IPI00306354.
IPI00646101.

RefSeq

NP_001001974.1. NM_001001974.2.
NP_001182537.1. NM_001195608.1.
NP_067635.2. NM_021622.4.

UniGene

Hs.643512.
Hs.738826.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EAZ	X-ray	1.40	A	182-303	[»]

ProteinModelPortal

Q9HB21.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9HB21. 3 interactions.

MINT

MINT-275100.

STRING

9606.ENSP00000357986.

PTM databases

PhosphoSite

Q9HB21.

Polymorphism databases

DMDM

48474647.

Proteomic databases

PaxDb

Q9HB21.

PRIDE

Q9HB21.

Protocols and materials databases

DNASU

59338.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000368990; ENSP00000357986; ENSG00000107679.
ENST00000409427; ENSP00000386800; ENSG00000107679.
ENST00000433307; ENSP00000394416; ENSG00000107679.
ENST00000538022; ENSP00000438608; ENSG00000107679.

GeneID

59338.

KEGG

hsa:59338.

UCSC

uc001lge.2. human.
uc001lgf.2. human.

Organism-specific databases

CTD

59338.

GeneCards

GC10P124124.

HGNC

HGNC:14335. PLEKHA1.

HPA

HPA002043.

MIM

607772. gene.

neXtProt

NX_Q9HB21.

PharmGKB

PA33401.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG45745.

HOGENOM

HOG000116175.

HOVERGEN

HBG053612.

InParanoid

Q9HB21.

OMA

NPCIQRS.

OrthoDB

EOG4MPHQF.

PhylomeDB

Q9HB21.

Enzyme and pathway databases

Pathway_Interaction_DB

pi3kcipathway. Class I PI3K signaling events.

Gene expression databases

ArrayExpress

Q9HB21.

Bgee

Q9HB21.

CleanEx

HS_PLEKHA1.

Genevestigator

Q9HB21.

GermOnline

ENSG00000107679. Homo sapiens.

Family and domain databases

Gene3D

2.30.29.30. 2 hits.

InterPro

IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
[Graphical view]

Pfam

PF00169. PH. 2 hits.
[Graphical view]

SMART

SM00233. PH. 2 hits.
[Graphical view]

PROSITE

PS50003. PH_DOMAIN. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

PLEKHA1. human.

EvolutionaryTrace

Q9HB21.

GenomeRNAi

59338.

NextBio

65210.

SOURCE

Search...

Entry information

Entry name

PKHA1_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 96 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.