P08567 (PLEK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pleckstrin

Alternative name(s):
Platelet 47 kDa protein
Short name=p47

Gene names

Name:	PLEK
Synonyms:	P47

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	350 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Major protein kinase C substrate of platelets.
Sequence similarities	Contains 1 DEP domain. Contains 2 PH domains.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Domain	Repeat
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	actin cytoskeleton reorganization Inferred from direct assay PubMed 10497244. Source: BHF-UCL cortical actin cytoskeleton organization Inferred from direct assay PubMed 10497244. Source: BHF-UCL hematopoietic progenitor cell differentiation Inferred from expression pattern Ref.2. Source: BHF-UCL integrin-mediated signaling pathway Inferred from direct assay PubMed 10995449. Source: BHF-UCL negative regulation of G-protein coupled receptor protein signaling pathway Inferred from direct assay PubMed 7782310. Source: BHF-UCL negative regulation of calcium-mediated signaling Non-traceable author statement PubMed 8999861. Source: BHF-UCL negative regulation of inositol phosphate biosynthetic process Inferred from direct assay PubMed 7559487PubMed 7782310. Source: BHF-UCL phosphatidylinositol metabolic process Inferred from direct assay PubMed 7559487. Source: BHF-UCL phospholipase C-inhibiting G-protein coupled receptor signaling pathway Inferred from direct assay PubMed 7782310. Source: BHF-UCL platelet aggregation Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of actin filament bundle assembly Inferred from direct assay PubMed 10497244. Source: BHF-UCL positive regulation of actin filament depolymerization Inferred from direct assay PubMed 10497244. Source: BHF-UCL positive regulation of inositol-polyphosphate 5-phosphatase activity Inferred from direct assay PubMed 8999861. Source: BHF-UCL positive regulation of integrin activation Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of platelet activation Inferred from sequence or structural similarity. Source: BHF-UCL protein kinase C signaling cascade Inferred from sequence or structural similarity. Source: BHF-UCL protein secretion by platelet Inferred from sequence or structural similarity. Source: BHF-UCL regulation of cell diameter Inferred from direct assay PubMed 10995449. Source: BHF-UCL ruffle organization Inferred from direct assay PubMed 10497244. Source: BHF-UCL thrombin receptor signaling pathway Inferred from direct assay PubMed 7782310. Source: BHF-UCL vesicle docking involved in exocytosis Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular_component	cytosol Traceable author statement. Source: Reactome extracellular region Traceable author statement. Source: Reactome ruffle membrane Inferred from direct assay PubMed 9060471. Source: BHF-UCL
Molecular_function	phosphatidylinositol-3,4-bisphosphate binding Inferred from direct assay PubMed 15698571. Source: BHF-UCL protein homodimerization activity Inferred from direct assay PubMed 8694752. Source: BHF-UCL protein kinase C binding Inferred from direct assay Ref.8. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SDPR	O95810	4	EBI-2565501,EBI-742141

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 350

350

Pleckstrin

PRO_0000053859

Regions

Domain

4 – 101

98

PH 1

Domain

136 – 221

86

DEP

Domain

244 – 347

104

PH 2

Amino acid modifications

Modified residue

64

1

N6-acetyllysine Ref.10

Modified residue

113

1

Phosphoserine; by PKC Ref.8

Modified residue

117

1

Phosphoserine; by PKC Ref.8 Ref.9

Natural variations

Natural variant

5

1

R → W.
Corresponds to variant rs17035364 [ dbSNP | Ensembl ].

VAR_027797

Natural variant

92

1

W → R.

VAR_005524

Natural variant

97

1

K → N. Ref.1 Ref.2
Corresponds to variant rs3816281 [ dbSNP | Ensembl ].

VAR_027798

Natural variant

108

1

K → Q.
Corresponds to variant rs34515106 [ dbSNP | Ensembl ].

VAR_056666

Natural variant

340

1

R → K. Ref.1 Ref.2 Ref.3 Ref.7
Corresponds to variant rs1063479 [ dbSNP | Ensembl ].

VAR_027799

Experimental info

Sequence conflict

284

1

E → G in CAG46876. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

350

Helix Strand Turn

Details...

Beta strand

6 – 19

14

Beta strand

22 – 29

8

Beta strand

32 – 38

7

Beta strand

45 – 52

8

Beta strand

55 – 58

4

Beta strand

65 – 73

9

Turn

74 – 76

3

Beta strand

77 – 82

6

Helix

86 – 103

18

Helix

126 – 133

8

Beta strand

135 – 140

6

Beta strand

143 – 147

5

Beta strand

155 – 157

3

Helix

158 – 167

10

Beta strand

168 – 170

3

Helix

174 – 187

14

Beta strand

189 – 194

6

Helix

195 – 200

6

Beta strand

215 – 218

4

Beta strand

220 – 222

3

Beta strand

226 – 228

3

Helix

239 – 241

3

Beta strand

245 – 254

10

Turn

256 – 258

3

Beta strand

261 – 269

9

Turn

270 – 273

4

Beta strand

274 – 278

5

Beta strand

280 – 282

3

Beta strand

287 – 291

5

Beta strand

296 – 300

5

Beta strand

306 – 308

3

Beta strand

313 – 318

6

Beta strand

324 – 328

5

Helix

332 – 346

15

Sequences

	Sequence		Length	Mass (Da)
	P08567 [UniParc]. Last modified January 11, 2011. Version 3. Checksum: 2E292CB18B533261	FASTA	350	40,125
	10 20 30 40 50 60 MEPKRIREGY LVKKGSVFNT WKPMWVVLLE DGIEFYKKKS DNSPKGMIPL KGSTLTSPCQ 70 80 90 100 110 120 DFGKRMFVFK ITTTKQQDHF FQAAFLEERD AWVRDIKKAI KCIEGGQKFA RKSTRRSIRL 130 140 150 160 170 180 PETIDLGALY LSMKDTEKGI KELNLEKDKK IFNHCFTGNC VIDWLVSNQS VRNRQEGLMI 190 200 210 220 230 240 ASSLLNEGYL QPAGDMSKSA VDGTAENPFL DNPDAFYYFP DSGFFCEENS SDDDVILKEE 250 260 270 280 290 300 FRGVIIKQGC LLKQGHRRKN WKVRKFILRE DPAYLHYYDP AGAEDPLGAI HLRGCVVTSV 310 320 330 340 350 ESNSNGRKSE EENLFEIITA DEVHYFLQAA TPKERTEWIR AIQMASRTGK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and expression of the major protein kinase C substrate of platelets." Tyers M., Rachubinski R.A., McCaw M.L., Varrichio A.M., Shorr R.G.L., Haslam R.J., Harley C.B. Nature 333:470-473(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ASN-97 AND LYS-340.
[2]	"Molecular analysis of pleckstrin: the major protein kinase C substrate of platelets." Tyers M., Haslam R.J., Rachubinski R.A., Harley C.B. J. Cell. Biochem. 40:133-145(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ASN-97 AND LYS-340.
[3]	"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 (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LYS-340.
[4]	"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]. Tissue: Spleen.
[5]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	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].
[7]	"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], VARIANT LYS-340. Tissue: Lymph.
[8]	"Phosphorylation of human pleckstrin on Ser-113 and Ser-117 by protein kinase C." Craig K.L., Harley C.B. Biochem. J. 314:937-942(1996) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-113 AND SER-117.
[9]	"Phosphorylation analysis of primary human T lymphocytes using sequential IMAC and titanium oxide enrichment." Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J. J. Proteome Res. 7:5167-5176(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-117, MASS SPECTROMETRY. Tissue: T-cell.
[10]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-64, MASS SPECTROMETRY.
[11]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]	"Solution structure of a pleckstrin-homology domain." Yoon H.S., Hajduk P.J., Petros A.M., Olejniczak E.T., Meadows R.P., Fesik S.W. Nature 369:672-675(1994) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 1-105.
[13]	"Structure and dynamics of the human pleckstrin DEP domain: distinct molecular features of a novel DEP domain subfamily." Civera C., Simon B., Stier G., Sattler M., Macias M.J. Proteins 58:354-366(2005) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 121-223.
[14]	"Solution structure of the DEP domain and of the C-terminal PH domain of human pleckstrin." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 116-350.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X07743 mRNA. Translation: CAA30564.1.
CR542056 mRNA. Translation: CAG46853.1.
CR542079 mRNA. Translation: CAG46876.1.
AK313756 mRNA. Translation: BAG36495.1.
AC015969 Genomic DNA. Translation: AAX93121.1.
CH471053 Genomic DNA. Translation: EAW99876.1.
BC018549 mRNA. Translation: AAH18549.1.

IPI

IPI00306311.

PIR

S00755.

RefSeq

NP_002655.2. NM_002664.2.

UniGene

Hs.468840.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1PLS	NMR	-	A	1-105	[»]
1W4M	NMR	-	A	121-223	[»]
1X05	NMR	-	A	235-350	[»]
1XX0	NMR	-	A	234-350	[»]
1ZM0	X-ray	2.10	A/B	240-350	[»]
2CSO	NMR	-	A	116-229	[»]
2I5C	X-ray	1.75	A/B/C	243-347	[»]
2I5F	X-ray	1.35	A	243-347	[»]

ProteinModelPortal

P08567.

SMR

P08567. Positions 1-105, 118-230, 234-350.

ModBase

Search...

Protein-protein interaction databases

IntAct

P08567. 8 interactions.

MINT

MINT-8216753.

STRING

9606.ENSP00000234313.

PTM databases

PhosphoSite

P08567.

Polymorphism databases

DMDM

84028239.

2D gel databases

OGP

P08567.

Proteomic databases

PaxDb

P08567.

PRIDE

P08567.

Protocols and materials databases

DNASU

5341.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000234313; ENSP00000234313; ENSG00000115956.

GeneID

5341.

KEGG

hsa:5341.

UCSC

uc002sen.4. human.

Organism-specific databases

CTD

5341.

GeneCards

GC02P068504.

H-InvDB

HIX0002122.

HGNC

HGNC:9070. PLEK.

HPA

HPA031838.

MIM

173570. gene.

neXtProt

NX_P08567.

PharmGKB

PA33400.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG44162.

HOGENOM

HOG000294078.

HOVERGEN

HBG001361.

InParanoid

P08567.

OMA

YYFADSG.

OrthoDB

EOG4N5VX3.

PhylomeDB

P08567.

Enzyme and pathway databases

Reactome

REACT_604. Hemostasis.

Gene expression databases

Bgee

P08567.

CleanEx

HS_PLEK.

Genevestigator

P08567.

GermOnline

ENSG00000115956. Homo sapiens.

Family and domain databases

Gene3D

1.10.10.10. 1 hit.
2.30.29.30. 2 hits.

InterPro

IPR000591. DEP_dom.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]

Pfam

PF00610. DEP. 1 hit.
PF00169. PH. 2 hits.
[Graphical view]

SMART

SM00049. DEP. 1 hit.
SM00233. PH. 2 hits.
[Graphical view]

PROSITE

PS50186. DEP. 1 hit.
PS50003. PH_DOMAIN. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P08567.

GenomeRNAi

5341.

NextBio

20702.

SOURCE

Search...

Entry information

Entry name

PLEK_HUMAN

Accession

Primary (citable) accession number: P08567
Secondary accession number(s): B2R9E8 , Q53SU8, Q6FGM8, Q6FGQ1, Q8WV81

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	January 11, 2011
Last modified:	May 29, 2013
This is version 147 of the entry and version 3 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.