Skip Header

 
Contribute Send feedback

Reviewed, UniProtKB/Swiss-Prot Q13153 (PAK1_HUMAN)

Last modified November 25, 2008. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length545 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence 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 junctionfocal 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.

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 545545Serine/threonine-protein kinase PAK 1
PRO_0000086460

Regions

Domain75 – 8814CRIB
Domain270 – 521252Protein kinase
Nucleotide binding276 – 2849ATP By similarity
Region70 – 14071Autoregulatory region
Region75 – 10531GTPase-binding By similarity
Region132 – 270139Interaction with CRIPAK

Sites

Active site3891Proton acceptor
Binding site2991ATP By similarity

Amino acid modifications

Modified residue211Phosphoserine; by autocatalysis By similarity
Modified residue571Phosphoserine; by autocatalysis By similarity
Modified residue841Phosphothreonine; by OXSR1 By similarity
Modified residue1441Phosphoserine; by autocatalysis By similarity
Modified residue1491Phosphoserine; by autocatalysis By similarity
Modified residue1991Phosphoserine; by autocatalysis By similarity
Modified residue2041Phosphoserine; by autocatalysis By similarity
Modified residue2121Phosphothreonine
Modified residue2201Phosphoserine By similarity
Modified residue2231Phosphoserine By similarity
Modified residue2251Phosphothreonine By similarity
Modified residue2301Phosphothreonine
Modified residue4231Phosphothreonine; by autocatalysis Probable

Natural variations

Alternative sequence518 – 54528HQFLK…TKNNH → VRKLRFQVFSNFSMIAASIP EDCQAPLQPHSTDCCS in isoform 2.
VSP_017507

Experimental info

Mutagenesis831H → L: Decreases activity; when associated with L-86
Mutagenesis861H → L: Decreases activity; when associated with L-83
Mutagenesis1071L → F: Constitutively active
Mutagenesis4231T → A: Decreases CDC42-stimulated activity and autophosphorylation
Sequence conflict261A → V in AAA65441. Ref.2
Sequence conflict261A → V in AAC24716. Ref.3
Sequence conflict2371R → L in AAC50590. Ref.1
Sequence conflict3791F → S in AAC50590. Ref.1
Sequence conflict5031E → D in AAA65441. Ref.2

Secondary structure

................................................................. 545
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 7, 2006. Version 2.
Checksum: 1A95CD5F2195CD7B

FASTA54560,647
        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 

« Hide

Isoform 2 (PAK1B) [UniParc].

Checksum: 6A3BB134DD2A82A8
Show »

55361,632

References

« Hide '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. </