Reviewed, UniProtKB/Swiss-Prot O15530 (PDPK1_HUMAN)

Names and origin

Protein names

Recommended name:
    3-phosphoinositide-dependent protein kinase 1
      Short name(s)=hPDK1
    EC=2.7.11.1

Gene names

Name:	PDPK1
Synonyms:	PDK1

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	556 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Phosphorylates and activates not only PKB/AKT, but also PKA, PKC-zeta, RPS6KA1 and RPS6KB1. May play a general role in signaling processes and in development By similarity. Isoform 3 is catalytically inactive.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subcellular location	Cytoplasm. Membrane; Peripheral membrane protein. Note= Membrane-associated after cell stimulation leading to its translocation. Tyrosine phosphorylation seems to occur only at the plasma membrane.
Tissue specificity	Appears to be expressed ubiquitously.
Post-translational modification	Phosphorylated on tyrosine and serine/threonine. Phosphorylation on Ser-241 in the activation loop is required for full activity. PDK1 itself can autophosphorylate Ser-241, leading to its own activation.
Sequence similarities	Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PDK1 subfamily. Contains 1 PH domain. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	actin cytoskeleton organization and biogenesis Traceable author statement. Source: ProtInc insulin receptor signaling pathway Traceable author statement. Source: ProtInc intracellular signaling cascade Inferred from direct assay. Source: MGI protein amino acid phosphorylation Ref.2 Traceable author statement. Source: ProtInc
Cellular component	cytosol Inferred from Experiment. Source: Reactome plasma membrane Ref.5 Inferred from direct assay. Source: UniProtKB
Molecular function	3-phosphoinositide-dependent protein kinase activity Ref.2 Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O15530-1)

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: O15530-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-50: Missing.

Isoform 3 (identifier: O15530-3)

The sequence of this isoform differs from the canonical sequence as follows:
     238-263: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Chain

1 – 556

556

3-phosphoinositide-dependent protein kinase 1

Regions

Domain

82 – 342

261

Protein kinase

Domain

459 – 550

92

PH

Nucleotide binding

88 – 96

9

ATP By similarity

Compositional bias

389 – 398

10

Poly-Ser

Sites

Active site

205

1

Proton acceptor By similarity

Binding site

111

1

ATP By similarity

Amino acid modifications

Modified residue

9

1

Phosphotyrosine

Modified residue

25

1

Phosphoserine

Modified residue

241

1

Phosphoserine; by autocatalysis

Modified residue

245

1

Phosphothreonine

Modified residue

373

1

Phosphotyrosine

Modified residue

376

1

Phosphotyrosine

Modified residue

393

1

Phosphoserine

Modified residue

396

1

Phosphoserine

Modified residue

410

1

Phosphoserine

Natural variations

Alternative sequence

1 – 50

50

Missing in isoform 2.

Alternative sequence

238 – 263

26

Missing in isoform 3.

Experimental info

Mutagenesis

9

1

Y → F: Slight reduction in pervanadate-stimulated tyrosine phosphorylation

Mutagenesis

25

1

S → A: No effect

Mutagenesis

241

1

S → A: No activation

Mutagenesis

277

1

A → V: 3-fold increase in kinase activity

Mutagenesis

373

1

Y → F: Reduction in basal activity

Mutagenesis

376

1

Y → F: Reduction in basal activity

Mutagenesis

393

1

S → A: No effect

Mutagenesis

396

1

S → A: No effect

Mutagenesis

410

1

S → A: No effect

Mutagenesis

474

1

R → A: No PDGF-dependent translocation to the membrane

Secondary structure

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556

Helix Strand Turn

Details...

Helix

79 – 81

3

Beta strand

82 – 90

9

Beta strand

95 – 101

7

Turn

102 – 104

3

Beta strand

107 – 114

8

Helix

115 – 120

6

Helix

124 – 136

13

Beta strand

145 – 150

6

Beta strand

152 – 159

8

Helix

167 – 174

8

Helix

179 – 198

20

Turn

208 – 210

3

Beta strand

211 – 213

3

Beta strand

219 – 221

3

Helix

246 – 248

3

Helix

251 – 255

5

Helix

261 – 277

17

Helix

287 – 295

9

Helix

307 – 314

8

Helix

321 – 323

3

Helix

328 – 330

3

Helix

333 – 337

5

Helix

340 – 342

3

Helix

350 – 352

3

Helix

412 – 415

4

Beta strand

416 – 420

5

Beta strand

423 – 426

4

Helix

432 – 445

14

Helix

449 – 451

3

Turn

452 – 454

3

Beta strand

457 – 467

11

Beta strand

470 – 479

10

Turn

480 – 482

3

Beta strand

483 – 488

6

Turn

489 – 492

4

Beta strand

493 – 498

6

Beta strand

505 – 518

14

Beta strand

521 – 526

6

Helix

532 – 547

16

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: ED8C0306DC4D0653	FASTA	556	63,152
	10 20 30 40 50 60 MARTTSQLYD AVPIQSSVVL CSCPSPSMVR TQTESSTPPG IPGGSRQGPA MDGTAAEPRP 70 80 90 100 110 120 GAGSLQHAQP PPQPRKKRPE DFKFGKILGE GSFSTVVLAR ELATSREYAI KILEKRHIIK 130 140 150 160 170 180 ENKVPYVTRE RDVMSRLDHP FFVKLYFTFQ DDEKLYFGLS YAKNGELLKY IRKIGSFDET 190 200 210 220 230 240 CTRFYTAEIV SALEYLHGKG IIHRDLKPEN ILLNEDMHIQ ITDFGTAKVL SPESKQARAN 250 260 270 280 290 300 SFVGTAQYVS PELLTEKSAC KSSDLWALGC IIYQLVAGLP PFRAGNEYLI FQKIIKLEYD 310 320 330 340 350 360 FPEKFFPKAR DLVEKLLVLD ATKRLGCEEM EGYGPLKAHP FFESVTWENL HQQTPPKLTA 370 380 390 400 410 420 YLPAMSEDDE DCYGNYDNLL SQFGCMQVSS SSSSHSLSAS DTGLPQRSGS NIEQYIHDLD 430 440 450 460 470 480 SNSFELDLQF SEDEKRLLLE KQAGGNPWHQ FVENNLILKM GPVDKRKGLF ARRRQLLLTE 490 500 510 520 530 540 GPHLYYVDPV NKVLKGEIPW SQELRPEAKN FKTFFVHTPN RTYYLMDPSG NAHKWCRKIQ 550 EVWRQRYQSH PDAAVQ
	Isoform 2 [UniParc]. Checksum: 22D376B8A13FD3F3		506	58,035
	10 20 30 40 50 60 MDGTAAEPRP GAGSLQHAQP PPQPRKKRPE DFKFGKILGE GSFSTVVLAR ELATSREYAI 70 80 90 100 110 120 KILEKRHIIK ENKVPYVTRE RDVMSRLDHP FFVKLYFTFQ DDEKLYFGLS YAKNGELLKY 130 140 150 160 170 180 IRKIGSFDET CTRFYTAEIV SALEYLHGKG IIHRDLKPEN ILLNEDMHIQ ITDFGTAKVL 190 200 210 220 230 240 SPESKQARAN SFVGTAQYVS PELLTEKSAC KSSDLWALGC IIYQLVAGLP PFRAGNEYLI 250 260 270 280 290 300 FQKIIKLEYD FPEKFFPKAR DLVEKLLVLD ATKRLGCEEM EGYGPLKAHP FFESVTWENL 310 320 330 340 350 360 HQQTPPKLTA YLPAMSEDDE DCYGNYDNLL SQFGCMQVSS SSSSHSLSAS DTGLPQRSGS 370 380 390 400 410 420 NIEQYIHDLD SNSFELDLQF SEDEKRLLLE KQAGGNPWHQ FVENNLILKM GPVDKRKGLF 430 440 450 460 470 480 ARRRQLLLTE GPHLYYVDPV NKVLKGEIPW SQELRPEAKN FKTFFVHTPN RTYYLMDPSG 490 500 NAHKWCRKIQ EVWRQRYQSH PDAAVQ
	Isoform 3 [UniParc]. Checksum: CEAF882CBD3EB1F2		530	60,396
	10 20 30 40 50 60 MARTTSQLYD AVPIQSSVVL CSCPSPSMVR TQTESSTPPG IPGGSRQGPA MDGTAAEPRP 70 80 90 100 110 120 GAGSLQHAQP PPQPRKKRPE DFKFGKILGE GSFSTVVLAR ELATSREYAI KILEKRHIIK 130 140 150 160 170 180 ENKVPYVTRE RDVMSRLDHP FFVKLYFTFQ DDEKLYFGLS YAKNGELLKY IRKIGSFDET 190 200 210 220 230 240 CTRFYTAEIV SALEYLHGKG IIHRDLKPEN ILLNEDMHIQ ITDFGTAKVL SPESKQADLW 250 260 270 280 290 300 ALGCIIYQLV AGLPPFRAGN EYLIFQKIIK LEYDFPEKFF PKARDLVEKL LVLDATKRLG 310 320 330 340 350 360 CEEMEGYGPL KAHPFFESVT WENLHQQTPP KLTAYLPAMS EDDEDCYGNY DNLLSQFGCM 370 380 390 400 410 420 QVSSSSSSHS LSASDTGLPQ RSGSNIEQYI HDLDSNSFEL DLQFSEDEKR LLLEKQAGGN 430 440 450 460 470 480 PWHQFVENNL ILKMGPVDKR KGLFARRRQL LLTEGPHLYY VDPVNKVLKG EIPWSQELRP 490 500 510 520 530 EAKNFKTFFV HTPNRTYYLM DPSGNAHKWC RKIQEVWRQR YQSHPDAAVQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase B alpha." Alessi D.R., James S.R., Downes C.P., Holmes A.B., Gaffney P.R.J., Reese C.B., Cohen P. Curr. Biol. 7:261-269(1997) [PubMed: 9094314] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"3-phosphoinositide-dependent protein kinase-1 (PDK1): structural and functional homology with the Drosophila DSTPK61 kinase." Alessi D.R., Deak M., Casamayor A., Caudwell F.B., Morrice N.A., Norman D.G., Gaffney P.R.J., Reese C.B., MacDougall C.N., Harbison D., Ashworth A., Bownes M. Curr. Biol. 7:776-789(1997) [PubMed: 9368760] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Protein kinase B kinases that mediate phosphatidylinositol 3,4,5-trisphosphate-dependent activation of protein kinase B." Stephens L.R., Anderson K.E., Stokoe D., Erdjument-Bromage H., Painter G.F., Holmes A.B., Gaffney P.R.J., Reese C.B., McCormick F., Tempst P., Coadwell W.J., Hawkins P.T. Science 279:710-714(1998) [PubMed: 9445477] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3). Tissue: Myeloid.
[4]	"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] (ISOFORM 1). Tissue: Kidney.
[5]	"Translocation of PDK-1 to the plasma membrane is important in allowing PDK-1 to activate protein kinase B." Anderson K.E., Coadwell W.J., Stephens L.R., Hawkins P.T. Curr. Biol. 8:684-691(1998) [PubMed: 9637919] [Abstract] Cited for: MUTAGENESIS OF ARG-474, ALTERNATIVE SPLICING.
[6]	"Phosphorylation of Ser-241 is essential for the activity of 3-phosphoinositide-dependent protein kinase-1: identification of five sites of phosphorylation in vivo." Casamayor A., Morrice N.A., Alessi D.R. Biochem. J. 342:287-292(1999) [PubMed: 10455013] [Abstract] Cited for: PHOSPHORYLATION AT SER-25; SER-241; SER-393; SER-396 AND SER-410, MUTAGENESIS OF SER-25; SER-241; SER-393; SER-396 AND SER-410.
[7]	"A PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 kinase signals that regulate diapause in Caenorhabditis elegans." Paradis S., Ailion M., Toker A., Thomas J.H., Ruvkun G. Genes Dev. 13:1438-1452(1999) [PubMed: 10364160] [Abstract] Cited for: MUTAGENESIS OF ALA-277.
[8]	"Identification of tyrosine phosphorylation sites on 3-phosphoinositide-dependent protein kinase-1 (PDK1) and their role in regulating kinase activity." Park J., Hill M.M., Hess D., Brazil D.P., Hofsteenge J., Hemmings B.A. J. Biol. Chem. 276:37459-37471(2001) [PubMed: 11481331] [Abstract] Cited for: PHOSPHORYLATION AT TYR-9; SER-241; TYR-373 AND TYR-376, MUTAGENESIS OF TYR-9; TYR-373 AND TYR-376.
[9]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A.,