Reviewed, UniProtKB/Swiss-Prot Q13153 (PAK1_HUMAN)

Names and origin

Protein names

Recommended name:
    Serine/threonine-protein kinase PAK 1
    EC=2.7.11.1
Alternative name(s):
    p21-activated kinase 1
      Short name=PAK-1
    p65-PAK
    Alpha-PAK

Gene names

Name:

PAK1

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

General annotation (Comments)

Function	The activated kinase acts on a variety of targets. Likely to be the GTPase effector that links the Rho-related GTPases to the JNK MAP kinase pathway. Activated by CDC42 and RAC1. Involved in dissolution of stress fibers and reorganization of focal complexes. Involved in regulation of microtubule biogenesis through phosphorylation of TBCB. Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium.
Enzyme regulation	Activated by binding small G proteins. Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, enables phosphorylation of Thr-423 and allows the kinase domain to adopt an active structure. Also activated by binding to GTP-bound CDC42, independent of the phosphorylation state of Thr-423. Phosphorylation of Thr-84 by OXSR1 inhibits this activation By similarity.
Subunit structure	Homodimer in its autoinhibited state. Active as monomer. Interacts tightly with GTP-bound but not GDP-bound CDC42/P21 and RAC1. Binds to the caspase-cleaved p110 isoform of CDC2L1 and CDC2L2, p110C, but not the full-length proteins. Component of cytoplasmic complexes, which also contain PXN, ARHGEF6 and GIT1. Interacts with ARHGEF7. Also interacts with CRIPAK. Interacts with NISCH By similarity.
Subcellular location	Cytoplasm. Cell junction › focal adhesion. Note= Recruited to focal adhesions upon activation.
Post-translational modification	Autophosphorylated when activated by CDC42/p21 and RAC1.
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
Cellular component	Cell junction Cytoplasm
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Allosteric enzyme
Gene Ontology (GO)
Biological process	ER-nuclear signaling pathway Ref.13 Traceable author statement. Source: HGNC apoptosis Inferred from electronic annotation. Source: UniProtKB-KW cytoskeleton organization Ref.13 Traceable author statement. Source: HGNC positive regulation of JNK activity Ref.1 Inferred from mutant phenotype. Source: UniProtKB protein amino acid autophosphorylation Ref.1 Inferred from direct assay. Source: UniProtKB
Cellular component	Golgi apparatus Inferred from direct assay. Source: HPA cell junction Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro collagen binding Inferred from physical interaction. Source: UniProtKB protein serine/threonine kinase activity Ref.13 Traceable author statement. Source: HGNC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDC2L1	P21127	2	EBI-1307,EBI-1298
CDC42	P60953	2	EBI-1307,EBI-81752
CRIPAK	Q8N1N5	5	EBI-1307,EBI-1205846
RAC1	P63000	3	EBI-1307,EBI-413628
RHOU	Q7L0Q8	1	EBI-1019502,EBI-1638043
RHOU	Q7L0Q8	1	EBI-1307,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 By similarity

Region

70 – 140

71

Autoregulatory region

Region

75 – 105

31

GTPase-binding By similarity

Region

132 – 270

139

Interaction with CRIPAK

Sites

Active site

389

1

Proton acceptor

Binding site

299

1

ATP By similarity

Amino acid modifications

Modified residue

21

1

Phosphoserine; by autocatalysis By similarity

Modified residue

57

1

Phosphoserine; by autocatalysis By similarity

Modified residue

84

1

Phosphothreonine; by OXSR1 By similarity

Modified residue

144

1

Phosphoserine; by autocatalysis By similarity

Modified residue

149

1

Phosphoserine; by autocatalysis By similarity

Modified residue

199

1

Phosphoserine; by autocatalysis By similarity

Modified residue

204

1

Phosphoserine; by autocatalysis By similarity

Modified residue

212

1

Phosphothreonine

Modified residue

220

1

Phosphoserine By similarity

Modified residue

223

1

Phosphoserine By similarity

Modified residue

225

1

Phosphothreonine By similarity

Modified residue

230

1

Phosphothreonine

Modified residue

423

1

Phosphothreonine; by autocatalysis Probable

Natural variations

Alternative sequence

518 – 545

28

HQFLK…TKNNH → VRKLRFQVFSNFSMIAASIP EDCQAPLQPHSTDCCS in isoform 2.

VSP_017507

Experimental info

Mutagenesis

83

1

H → L: Decreases activity; when associated with L-86

Mutagenesis

86

1

H → L: Decreases activity; when associated with L-83

Mutagenesis

107

1

L → F: Constitutively active

Mutagenesis

423

1

T → A: Decreases CDC42-stimulated activity and autophosphorylation

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

80 – 90

11

Turn

91 – 94

4

Beta strand

95 – 98

4

Helix

101 – 108

8

Helix

114 – 119

6

Helix

121 – 135

15

Beta strand

195 – 198

4

Helix

252 – 257

6

Turn

258 – 260

3

Helix

266 – 269

4

Beta strand

275 – 279

5

Beta strand

282 – 289

8

Turn

290 – 292

3

Beta strand

295 – 300

6

Helix

309 – 319

11

Beta strand

330 – 334

5

Beta strand

341 – 345

5

Beta strand

349 – 351

3

Helix

352 – 358

7

Helix

363 – 382

20

Helix

392 – 394

3

Beta strand

395 – 397

3

Beta strand

403 – 405

3

Beta strand

408 – 410

3

Helix

433 – 436

4

Helix

444 – 459

16

Turn

463 – 466

4

Helix

469 – 478

10

Helix

487 – 489

3

Helix

492 – 501

10

Turn

506 – 508

3

Helix

512 – 515

4

Helix

519 – 523

5

Helix

527 – 529

3

Helix

531 – 539

9

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		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: 8805275] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). 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: 9395435] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[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]	"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).
[5]	"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: 9032240] [Abstract] Cited for: ENZYME REGULATION, SUBCELLULAR LOCATION. </