Q13153 (PAK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase PAK 1
EC=2.7.11.1

Alternative name(s):
Alpha-PAK
p21-activated kinase 1
Short name=PAK-1
p65-PAK

Gene names

Name:

PAK1

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

General annotation (Comments)

Function	Protein kinase involved in intracellular signaling pathways downstream of integrins and receptor-type kinases that plays an important role in cytoskeleton dynamics, in cell adhesion, migration, proliferation, apoptosis, mitosis, and in vesicle-mediated transport processes. Can directly phosphorylate BAD and protects cells against apoptosis. Activated by interaction with CDC42 and RAC1. Functions as GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway. Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases. Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes. Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton. Plays a role in the regulation of insulin secretion in response to elevated glucose levels. Part of a ternary complex that contains PAK1, DVL1 and MUSK that is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ). Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2. Phosphorylates MYL9/MLC2. Phosphorylates RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1 translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1 binding to BCL2. Phosphorylates SNAI1 at 'Ser-246' promoting its transcriptional repressor activity by increasing its accumulation in the nucleus. Ref.1 Ref.2 Ref.6 Ref.8 Ref.10 Ref.12 Ref.14 Ref.15 Ref.16 Ref.18 Ref.19 Ref.20 Ref.22 Ref.23 Ref.24 Ref.31
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.6 Ref.10 Ref.35
Cofactor	Magnesium.
Enzyme regulation	Phosphorylation of Thr-84 by OXSR1 inhibits activation By similarity. Activated by binding small G proteins. Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, and enables activation by phosphorylation of Thr-423. Ref.6 Ref.11 Ref.13 Ref.34
Subunit structure	Homodimer in its autoinhibited state. Active as monomer. Component of cytoplasmic complexes, which also contains PXN, ARHGEF6 and GIT1. Interacts with NISCH By similarity. Interacts with DVL1; mediates the formation of a DVL1, MUSK and PAK1 ternary complex involved in AChR clustering By similarity. Binds to the caspase-cleaved p110 isoform of CDC2L1 and CDC2L2, p110C, but not the full-length proteins. Interacts with ARHGEF7. Interacts tightly with GTP-bound but not GDP-bound CDC42/P21 and RAC1. Probably found in a ternary complex composed of DSCAM, PAK1 and RAC1. Interacts with DSCAM (via cytoplasmic domain); the interaction is direct and enhanced in presence of RAC1. Interacts with SCRIB. Interacts with PDPK1. Interacts (via kinase domain) with RAF1. Interacts with NCK1 and NCK2. Interacts with TBCB. Interacts with CRIPAK. Interacts with BRSK2. Interacts with SNAI1. Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.16 Ref.17 Ref.18 Ref.20 Ref.22 Ref.25 Ref.26 Ref.31 Ref.33 Ref.35
Subcellular location	Cytoplasm. Cell junction › focal adhesion. Cell membrane. Note: Recruited to the cell membrane by interaction with CDC42 and RAC1. Recruited to focal adhesions upon activation. Ref.6 Ref.16
Post-translational modification	Autophosphorylated in trans, meaning that in a dimer, one kinase molecule phosphorylates the other one. Activated by autophosphorylation at Thr-423 in response to a conformation change, triggered by interaction with GTP-bound CDC42 or RAC1. Activated by phosphorylation at Thr-423 by BRSK2 and by PDPK1. Phosphorylated by JAK2 in response to PRL; this increases PAK1 kinase activity. Phosphorylated at Ser-21 by PKB/AKT; this reduces interaction with NCK1 and association with focal adhesion sites. Ref.6 Ref.10 Ref.11 Ref.16 Ref.23 Ref.24 Ref.31 Ref.35
Sequence similarities	Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily. Contains 1 CRIB domain. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Apoptosis Exocytosis
Cellular component	Cell junction Cell membrane Cytoplasm Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Allosteric enzyme Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	T cell costimulation Traceable author statement. Source: Reactome T cell receptor signaling pathway Traceable author statement. Source: Reactome actin cytoskeleton reorganization Inferred from direct assay Ref.2. Source: UniProtKB apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW axon guidance Traceable author statement. Source: Reactome branching morphogenesis of an epithelial tube Inferred from mutant phenotype PubMed 20457839. Source: UniProtKB cellular response to insulin stimulus Inferred from electronic annotation. Source: Compara cellular response to stress Inferred from electronic annotation. Source: Compara dendrite development Inferred from electronic annotation. Source: Compara exocytosis Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of cell proliferation involved in contact inhibition Inferred from mutant phenotype PubMed 12912914. Source: UniProtKB neuromuscular junction development Inferred from electronic annotation. Source: Compara positive regulation of JUN kinase activity Inferred from mutant phenotype Ref.1. Source: UniProtKB positive regulation of intracellular estrogen receptor signaling pathway Inferred from direct assay Ref.22. Source: UniProtKB positive regulation of peptidyl-serine phosphorylation Inferred from direct assay PubMed 19667065. Source: UniProtKB positive regulation of stress fiber assembly Inferred from mutant phenotype PubMed 11864573. Source: UniProtKB protein autophosphorylation Inferred from direct assay Ref.1. Source: UniProtKB receptor clustering Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from electronic annotation. Source: Compara wound healing Inferred from mutant phenotype PubMed 12912914. Source: UniProtKB
Cellular_component	Golgi apparatus Inferred from direct assay. Source: HPA Z disc Inferred from sequence or structural similarity. Source: UniProtKB axon Inferred from sequence or structural similarity. Source: UniProtKB cytosol Traceable author statement. Source: Reactome dendrite Inferred from sequence or structural similarity. Source: UniProtKB focal adhesion Inferred from electronic annotation. Source: UniProtKB-SubCell growth cone Inferred from electronic annotation. Source: Compara intercalated disc Inferred from sequence or structural similarity. Source: UniProtKB nuclear membrane Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from direct assay Ref.22. Source: HGNC protein complex Inferred from direct assay PubMed 11864573. Source: UniProtKB ruffle Inferred from direct assay PubMed 12912914. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from direct assay Ref.22PubMed 19667065. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		4	EBI-1307,EBI-1307
CDC42	P60953	5	EBI-1307,EBI-81752
CDK11B	P21127	3	EBI-1307,EBI-1298
CRIPAK	Q8N1N5	6	EBI-1307,EBI-1205846
LIMK1	P53667	5	EBI-1307,EBI-444403
RAC1	P63000	8	EBI-1307,EBI-413628
RHOU	Q7L0Q8	2	EBI-1019502,EBI-1638043

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q13153-1)

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: Q13153-2)

Also known as: PAK1B;

The sequence of this isoform differs from the canonical sequence as follows:
     518-545: HQFLKIAKPLSSLTPLIAAAKEATKNNH → VRKLRFQVFSNFSMIAASIPEDCQAPLQPHSTDCCS

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 545

545

Serine/threonine-protein kinase PAK 1

PRO_0000086460

Regions

Domain

75 – 88

14

CRIB

Domain

270 – 521

252

Protein kinase

Nucleotide binding

276 – 284

9

ATP

Nucleotide binding

345 – 347

3

ATP

Region

70 – 140

71

Autoregulatory region

Region

75 – 105

31

GTPase-binding

Region

132 – 270

139

Interaction with CRIPAK

Sites

Active site

389

1

Proton acceptor

Binding site

299

1

ATP

Amino acid modifications

Modified residue

21

1

Phosphoserine; by PKB and autocatalysis Ref.16 Ref.24

Modified residue

57

1

Phosphoserine; by autocatalysis Ref.24

Modified residue

84

1

Phosphothreonine; by OXSR1 By similarity

Modified residue

131

1

Phosphotyrosine Ref.24

Modified residue

142

1

Phosphotyrosine Ref.24

Modified residue

144

1

Phosphoserine Ref.30

Modified residue

149

1

Phosphoserine Ref.30

Modified residue

153

1

Phosphotyrosine; by JAK2 Ref.23 Ref.24

Modified residue

174

1

Phosphoserine Ref.24 Ref.30

Modified residue

185

1

Phosphothreonine Ref.24

Modified residue

199

1

Phosphoserine; by autocatalysis By similarity

Modified residue

201

1

Phosphotyrosine; by JAK2 Ref.23

Modified residue

204

1

Phosphoserine Ref.28

Modified residue

212

1

Phosphothreonine Ref.21 Ref.24 Ref.28

Modified residue

219

1

Phosphothreonine Ref.28

Modified residue

220

1

Phosphoserine Ref.28

Modified residue

223

1

Phosphoserine Ref.30

Modified residue

225

1

Phosphothreonine By similarity

Modified residue

230

1

Phosphothreonine Ref.27 Ref.28 Ref.30

Modified residue

285

1

Phosphotyrosine; by JAK2 Ref.23 Ref.24

Modified residue

423

1

Phosphothreonine; by autocatalysis, BRSK2 and PDPK1 Ref.10 Ref.11 Ref.31 Ref.35

Natural variations

Alternative sequence

518 – 545

28

HQFLK…TKNNH → VRKLRFQVFSNFSMIAASIP EDCQAPLQPHSTDCCS in isoform 2.

VSP_017507

Natural variant

515

1

L → V.
Corresponds to variant rs35345144 [ dbSNP | Ensembl ].

VAR_051654

Experimental info

Mutagenesis

83

1

H → L: Abolishes interaction with CDC42, leading to strongly decreased activity; when associated with L-86. Ref.7 Ref.10

Mutagenesis

86

1

H → L: Abolishes interaction with CDC42, leading to strongly decreased activity; when associated with L-83. Ref.7 Ref.10

Mutagenesis

107

1

L → F: Abolishes autoinhibition, leading to constitutive kinase activity. Ref.10

Mutagenesis

299

1

K → R: Strongly decreases activity. Abolishes kinase activity; when associated with N-389. Ref.35

Mutagenesis

389

1

D → N: Abolishes kinase activity; when associated with R-299. Ref.35

Mutagenesis

393

1

D → A: Abolishes autophosphorylation at Thr-423.

Mutagenesis

423

1

T → A: Decreases CDC42-stimulated activity and autophosphorylation. Ref.10

Mutagenesis

423

1

T → E: Constitutive kinase activity. Ref.10

Sequence conflict

26

1

A → V in AAA65441. Ref.2

Sequence conflict

26

1

A → V in AAC24716. Ref.3

Sequence conflict

237

1

R → L in AAC50590. Ref.1

Sequence conflict

379

1

F → S in AAC50590. Ref.1

Sequence conflict

503

1

E → D in AAA65441. Ref.2

Secondary structure

1

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545

Helix Strand Turn

Details...

Beta strand

79 – 87

9

Turn

91 – 94

4

Beta strand

195 – 198

4

Beta strand

214 – 219

6

Helix

250 – 260

11

Beta strand

261 – 264

4

Helix

266 – 268

3

Beta strand

274 – 279

6

Beta strand

282 – 289

8

Turn

290 – 292

3

Beta strand

295 – 302

8

Helix

303 – 305

3

Helix

309 – 321

13

Beta strand

330 – 336

7

Beta strand

339 – 345

7

Helix

352 – 358

7

Helix

363 – 382

20

Helix

392 – 394

3

Beta strand

395 – 397

3

Beta strand

403 – 405

3

Beta strand

416 – 418

3

Helix

428 – 430

3

Helix

433 – 437

5

Helix

444 – 459

16

Turn

463 – 466

4

Helix

469 – 479

11

Helix

487 – 489

3

Helix

492 – 501

10

Turn

506 – 508

3

Helix

512 – 515

4

Helix

519 – 523

5

Helix

527 – 530

4

Helix

531 – 540

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 7, 2006. Version 2. Checksum: 1A95CD5F2195CD7B	FASTA	545	60,647
	10 20 30 40 50 60 MSNNGLDIQD KPPAPPMRNT STMIGAGSKD AGTLNHGSKP LPPNPEEKKK KDRFYRSILP 70 80 90 100 110 120 GDKTNKKKEK ERPEISLPSD FEHTIHVGFD AVTGEFTGMP EQWARLLQTS NITKSEQKKN 130 140 150 160 170 180 PQAVLDVLEF YNSKKTSNSQ KYMSFTDKSA EDYNSSNALN VKAVSETPAV PPVSEDEDDD 190 200 210 220 230 240 DDDATPPPVI APRPEHTKSV YTRSVIEPLP VTPTRDVATS PISPTENNTT PPDALTRNTE 250 260 270 280 290 300 KQKKKPKMSD EEILEKLRSI VSVGDPKKKY TRFEKIGQGA SGTVYTAMDV ATGQEVAIKQ 310 320 330 340 350 360 MNLQQQPKKE LIINEILVMR ENKNPNIVNY LDSYLVGDEL WVVMEYLAGG SLTDVVTETC 370 380 390 400 410 420 MDEGQIAAVC RECLQALEFL HSNQVIHRDI KSDNILLGMD GSVKLTDFGF CAQITPEQSK 430 440 450 460 470 480 RSTMVGTPYW MAPEVVTRKA YGPKVDIWSL GIMAIEMIEG EPPYLNENPL RALYLIATNG 490 500 510 520 530 540 TPELQNPEKL SAIFRDFLNR CLEMDVEKRG SAKELLQHQF LKIAKPLSSL TPLIAAAKEA TKNNH
	Isoform 2 (PAK1B) [UniParc]. Checksum: 6A3BB134DD2A82A8	FASTA	553	61,632
	10 20 30 40 50 60 MSNNGLDIQD KPPAPPMRNT STMIGAGSKD AGTLNHGSKP LPPNPEEKKK KDRFYRSILP 70 80 90 100 110 120 GDKTNKKKEK ERPEISLPSD FEHTIHVGFD AVTGEFTGMP EQWARLLQTS NITKSEQKKN 130 140 150 160 170 180 PQAVLDVLEF YNSKKTSNSQ KYMSFTDKSA EDYNSSNALN VKAVSETPAV PPVSEDEDDD 190 200 210 220 230 240 DDDATPPPVI APRPEHTKSV YTRSVIEPLP VTPTRDVATS PISPTENNTT PPDALTRNTE 250 260 270 280 290 300 KQKKKPKMSD EEILEKLRSI VSVGDPKKKY TRFEKIGQGA SGTVYTAMDV ATGQEVAIKQ 310 320 330 340 350 360 MNLQQQPKKE LIINEILVMR ENKNPNIVNY LDSYLVGDEL WVVMEYLAGG SLTDVVTETC 370 380 390 400 410 420 MDEGQIAAVC RECLQALEFL HSNQVIHRDI KSDNILLGMD GSVKLTDFGF CAQITPEQSK 430 440 450 460 470 480 RSTMVGTPYW MAPEVVTRKA YGPKVDIWSL GIMAIEMIEG EPPYLNENPL RALYLIATNG 490 500 510 520 530 540 TPELQNPEKL SAIFRDFLNR CLEMDVEKRG SAKELLQVRK LRFQVFSNFS MIAASIPEDC 550 QAPLQPHSTD CCS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human Ste20 homologue hPAK1 links GTPases to the JNK MAP kinase pathway." Brown J.L., Stowers L., Baer M., Trejo J., Coughlin S., Chant J. Curr. Biol. 6:598-605(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION. Tissue: Placenta.
[2]	"Human p21-activated kinase (Pak1) regulates actin organization in mammalian cells." Sells M.A., Knaus U.G., Bagrodia S., Ambrose D.M., Bokoch G.M., Chernoff J. Curr. Biol. 7:202-210(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION.
[3]	"Human PAK1B." Reid T., Aspenstroem P., Bertoglio J. Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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).
[6]	"Expression of constitutively active alpha-PAK reveals effects of the kinase on actin and focal complexes." Manser E., Huang H.Y., Loo T.H., Chen X.Q., Dong J.M., Leung T., Lim L. Mol. Cell. Biol. 17:1129-1143(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, ENZYME REGULATION, SUBCELLULAR LOCATION.
[7]	"Differential effects of PAK1-activating mutations reveal activity-dependent and -independent effects on cytoskeletal regulation." Frost J.A., Khokhlatchev A., Stippec S., White M.A., Cobb M.H. J. Biol. Chem. 273:28191-28198(1998) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF HIS-83 AND HIS-86.
[8]	"A conserved negative regulatory region in alphaPAK: inhibition of PAK kinases reveals their morphological roles downstream of Cdc42 and Rac1." Zhao Z.S., Manser E., Chen X.Q., Chong C., Leung T., Lim L. Mol. Cell. Biol. 18:2153-2163(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, AUTOREGULATORY DOMAIN.
[9]	"Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck." Braverman L.E., Quilliam L.A. J. Biol. Chem. 274:5542-5549(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NCK1 AND NCK2.
[10]	"Identification of a central phosphorylation site in p21-activated kinase regulating autoinhibition and kinase activity." Zenke F.T., King C.C., Bohl B.P., Bokoch G.M. J. Biol. Chem. 274:32565-32573(1999) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, AUTOREGULATORY REGION, FUNCTION, INTERACTION WITH CDC42, PHOSPHORYLATION AT THR-423, MUTAGENESIS OF HIS-83; HIS-86; LEU-107 AND THR-423.
[11]	"p21-activated kinase (PAK1) is phosphorylated and activated by 3-phosphoinositide-dependent kinase-1 (PDK1)." King C.C., Gardiner E.M., Zenke F.T., Bohl B.P., Newton A.C., Hemmings B.A., Bokoch G.M. J. Biol. Chem. 275:41201-41209(2000) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-423 BY PDPK1, INTERACTION WITH PDPK1, ENZYME REGULATION.
[12]	"Interaction between active Pak1 and Raf-1 is necessary for phosphorylation and activation of Raf-1." Zang M., Hayne C., Luo Z. J. Biol. Chem. 277:4395-4405(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF RAF1, INTERACTION WITH RAF1.
[13]	"Pak1 kinase homodimers are autoinhibited in trans and dissociated upon activation by Cdc42 and Rac1." Parrini M.C., Lei M., Harrison S.C., Mayer B.J. Mol. Cell 9:73-83(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT, ENZYME REGULATION.
[14]	"The C-terminal kinase domain of the p34cdc2-related PITSLRE protein kinase (p110C) associates with p21-activated kinase 1 and inhibits its activity during anoikis." Chen S., Yin X., Zhu X., Yan J., Ji S., Chen C., Cai M., Zhang S., Zong H., Hu Y., Yuan Z., Shen Z., Gu J. J. Biol. Chem. 278:20029-20036(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CDC2L1 AND CDC2L2.
[15]	"PAK1 phosphorylation of MEK1 regulates fibronectin-stimulated MAPK activation." Slack-Davis J.K., Eblen S.T., Zecevic M., Boerner S.A., Tarcsafalvi A., Diaz H.B., Marshall M.S., Weber M.J., Parsons J.T., Catling A.D. J. Cell Biol. 162:281-291(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[16]	"Akt phosphorylation of serine 21 on Pak1 modulates Nck binding and cell migration." Zhou G.L., Zhuo Y., King C.C., Fryer B.H., Bokoch G.M., Field J. Mol. Cell. Biol. 23:8058-8069(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-21, MASS SPECTROMETRY, FUNCTION, INTERACTION WITH NCK1, SUBCELLULAR LOCATION.
[17]	"The Down syndrome cell adhesion molecule (DSCAM) interacts with and activates Pak." Li W., Guan K.L. J. Biol. Chem. 279:32824-32831(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DSCAM.
[18]	"Pak1 phosphorylation of snail, a master regulator of epithelial-to-mesenchyme transition, modulates snail's subcellular localization and functions." Yang Z., Rayala S., Nguyen D., Vadlamudi R.K., Chen S., Kumar R. Cancer Res. 65:3179-3184(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH SNAI1.
[19]	"Integrin engagement differentially modulates epithelial cell motility by RhoA/ROCK and PAK1." Zhou H., Kramer R.H. J. Biol. Chem. 280:10624-10635(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[20]	"p21-activated kinase 1 regulates microtubule dynamics by phosphorylating tubulin cofactor B." Vadlamudi R.K., Barnes C.J., Rayala S., Li F., Balasenthil S., Marcus S., Goodson H.V., Sahin A.A., Kumar R. Mol. Cell. Biol. 25:3726-3736(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH TBCB.
[21]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-212, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[22]	"CRIPak, a novel endogenous Pak1 inhibitor." Talukder A.H., Meng Q., Kumar R. Oncogene 25:1311-1319(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CRIPAK.
[23]	"JAK2 tyrosine kinase phosphorylates PAK1 and regulates PAK1 activity and functions." Rider L., Shatrova A., Feener E.P., Webb L., Diakonova M. J. Biol. Chem. 282:30985-30996(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT TYR-153; TYR-201 AND TYR-285, MASS SPECTROMETRY.
[24]	"Identification of phosphorylation sites in betaPIX and PAK1." Mayhew M.W., Jeffery E.D., Sherman N.E., Nelson K., Polefrone J.M., Pratt S.J., Shabanowitz J., Parsons J.T., Fox J.W., Hunt D.F., Horwitz A.F. J. Cell Sci. 120:3911-3918(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT SER-21; SER-57; TYR-131; TYR-142; TYR-153; SER-174; THR-185; THR-212 AND TYR-285, MASS SPECTROMETRY.
[25]	"Affixin activates Rac1 via betaPIX in C2C12 myoblast." Matsuda C., Kameyama K., Suzuki A., Mishima W., Yamaji S., Okamoto H., Nishino I., Hayashi Y.K. FEBS Lett. 582:1189-1196(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RAC1 AND CDC42.
[26]	"Scrib regulates PAK activity during the cell migration process." Nola S., Sebbagh M., Marchetto S., Osmani N., Nourry C., Audebert S., Navarro C., Rachel R., Montcouquiol M., Sans N., Etienne-Manneville S., Borg J.-P., Santoni M.-J. Hum. Mol. Genet. 17:3552-3565(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SCRIB.
[27]	"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 THR-230, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[28]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-204; THR-212; THR-219; SER-220 AND THR-230, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[29]	"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].
[30]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-144; SER-149; SER-174; SER-223 AND THR-230, MASS SPECTROMETRY.
[31]	"Synapses of amphids defective (SAD-A) kinase promotes glucose-stimulated insulin secretion through activation of p21-activated kinase (PAK1) in pancreatic beta-Cells." Nie J., Sun C., Faruque O., Ye G., Li J., Liang Q., Chang Z., Yang W., Han X., Shi Y. J. Biol. Chem. 287:26435-26444(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH BRSK2, PHOSPHORYLATION AT THR-423.
[32]	"Structure of PAK1 in an autoinhibited conformation reveals a multistage activation switch." Lei M., Lu W., Meng W., Parrini M.C., Eck M.J., Mayer B.J., Harrison S.C. Cell 102:387-397(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 70-545.
[33]	"Structural analysis of the SH3 domain of beta-PIX and its interaction with alpha-p21 activated kinase (PAK)." Mott H.R., Nietlispach D., Evetts K.A., Owen D. Biochemistry 44:10977-10983(2005) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 183-204 IN COMPLEX WITH ARHGEF7, INTERACTION WITH ARHGEF7.
[34]	"The active conformation of the PAK1 kinase domain." Lei M., Robinson M.A., Harrison S.C. Structure 13:769-778(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 249-545, ENZYME REGULATION.
[35]	"Structural insights into the autoactivation mechanism of p21-activated protein kinase." Wang J., Wu J.W., Wang Z.X. Structure 19:1752-1761(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 248-545 OF MUTANT ARG-299 IN COMPLEX WITH ATP ANALOG AMP-PNP, MUTAGENESIS OF LYS-299 AND ASP-389, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, SUBUNIT, PHOSPHORYLATION AT THR-423.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U51120 mRNA. Translation: AAC50590.1.
U24152 mRNA. Translation: AAA65441.1.
AF071884 mRNA. Translation: AAC24716.1.
AP000486 Genomic DNA. No translation available.
AP003680 Genomic DNA. No translation available.
BC109299 mRNA. Translation: AAI09300.1.

IPI

IPI00289746.
IPI00656138.

PIR

G01773.

RefSeq

NP_001122092.1. NM_001128620.1.
NP_002567.3. NM_002576.4.

UniGene

Hs.435714.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1F3M	X-ray	2.30	A/B	70-149	[»]
			C/D	249-545	[»]
1YHV	X-ray	1.80	A	249-545	[»]
1YHW	X-ray	1.80	A	249-545	[»]
1ZSG	NMR	-	B	183-204	[»]
2HY8	X-ray	2.00	1	249-545	[»]
2QME	X-ray	1.75	I	74-109	[»]
3DVP	X-ray	2.50	C/D	212-221	[»]
3FXZ	X-ray	1.64	A	249-545	[»]
3FY0	X-ray	2.35	A	249-545	[»]
3Q4Z	X-ray	1.89	A/B	248-545	[»]
3Q52	X-ray	1.80	A	248-545	[»]
3Q53	X-ray	2.09	A	248-545	[»]
4DAW	X-ray	2.00	A	249-545	[»]

ProteinModelPortal

Q13153.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31016N.

IntAct

Q13153. 34 interactions.

MINT

MINT-92897.

STRING

9606.ENSP00000278568.

PTM databases

PhosphoSite

Q13153.

Polymorphism databases

DMDM

90111767.

Proteomic databases

PaxDb

Q13153.

PRIDE

Q13153.

Protocols and materials databases

DNASU

5058.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000278568; ENSP00000278568; ENSG00000149269.
ENST00000356341; ENSP00000348696; ENSG00000149269.

GeneID

5058.

KEGG

hsa:5058.

UCSC

uc001oyg.4. human.
uc001oyh.4. human.

Organism-specific databases

CTD

5058.

GeneCards

GC11M077033.

HGNC

HGNC:8590. PAK1.

HPA

CAB005312.
HPA003565.

MIM

602590. gene.

neXtProt

NX_Q13153.

PharmGKB

PA32917.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000234202.

HOVERGEN

HBG108518.

KO

K04409.

OMA

TPTRDVA.

OrthoDB

EOG45DWP5.

Enzyme and pathway databases

BRENDA

2.7.11.1. 2681.

Pathway_Interaction_DB

angiopoietinreceptor_pathway. Angiopoietin receptor Tie2-mediated signaling.
aurora_a_pathway. Aurora A signaling.
epha2_fwdpathway. EPHA2 forward signaling.
ephbfwdpathway. EPHB forward signaling.
p38alphabetapathway. Regulation of p38-alpha and p38-beta.
s1p_s1p2_pathway. S1P2 pathway.
met_pathway. Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.

Reactome

REACT_111045. Developmental Biology.
REACT_111155. Cell-Cell communication.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q13153.

Bgee

Q13153.

CleanEx

HS_PAK1.

Genevestigator

Q13153.

GermOnline

ENSG00000149269. Homo sapiens.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000095. PAK_box_Rho-bd.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

PF00786. PBD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]

SMART

SM00285. PBD. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS50108. CRIB. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q13153.

ChEMBL

CHEMBL4600.

ChiTaRS

PAK1. human.

EvolutionaryTrace

Q13153.

GenomeRNAi

5058.

NextBio

19488.

SOURCE

Search...

Entry information

Entry name

PAK1_HUMAN

Accession

Primary (citable) accession number: Q13153
Secondary accession number(s): O75561 , Q13567, Q32M53, Q32M54, Q86W79

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	March 7, 2006
Last modified:	May 1, 2013
This is version 151 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.