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Q13153 (PAK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 164. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

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

Protein attributes

Sequence length545 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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. In podocytes, promotes NR3C2 nuclear localization. Required for atypical chemokine receptor ACKR2-induced phosphorylation of LIMK1 and cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3, maybe through CFL1 phosphorylation and inactivation. Ref.1 Ref.2 Ref.6 Ref.8 Ref.10 Ref.12 Ref.14 Ref.15 Ref.16 Ref.18 Ref.19 Ref.21 Ref.23 Ref.24 Ref.25 Ref.33 Ref.36

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. Ref.6 Ref.10 Ref.40

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.39

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 ofCDC2L1 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. Interacts with CIB1 isoform 2. Interacts with CIB1 (via N-terminal region); the interaction is direct, promotes PAK1 activity and occurs in a calcium-dependent manner. Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.16 Ref.17 Ref.18 Ref.20 Ref.21 Ref.23 Ref.26 Ref.27 Ref.33 Ref.35 Ref.38 Ref.40

Subcellular location

Cytoplasm. Cell junctionfocal adhesion. Cell membrane. Cell projectionruffle membrane. Note: Recruited to the cell membrane by interaction with CDC42 and RAC1. Recruited to focal adhesions upon activation. Colocalized with CIB1 within membrane ruffles during cell spreading upon readhesion to fibronectin. Ref.6 Ref.16 Ref.20

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.24 Ref.25 Ref.33 Ref.36 Ref.40

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 processApoptosis
Exocytosis
   Cellular componentCell junction
Cell membrane
Cell projection
Cytoplasm
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Allosteric enzyme
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processFc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

Fc-gamma receptor signaling pathway involved in phagocytosis

Traceable author statement. Source: Reactome

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

axonogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

branching morphogenesis of an epithelial tube

Inferred from mutant phenotype PubMed 20457839. Source: UniProtKB

cellular response to insulin stimulus

Inferred from electronic annotation. Source: Ensembl

dendrite development

Inferred from electronic annotation. Source: Ensembl

exocytosis

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Traceable author statement. Source: Reactome

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: Ensembl

neuron projection morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

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.23. Source: UniProtKB

positive regulation of peptidyl-serine phosphorylation

Inferred from direct assay PubMed 19667065. Source: UniProtKB

positive regulation of protein phosphorylation

Inferred from mutant phenotype Ref.36. 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

protein phosphorylation

Inferred from direct assay PubMed 9852149. Source: UniProtKB

receptor clustering

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

signal transduction by phosphorylation

Inferred from Biological aspect of Ancestor. Source: GOC

wound healing

Inferred from mutant phenotype PubMed 12912914. Source: UniProtKB

   Cellular_componentZ disc

Inferred from sequence or structural similarity. Source: UniProtKB

axon

Inferred from sequence or structural similarity. Source: UniProtKB

cell-cell junction

Inferred from direct assay PubMed 12912914. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.23. Source: HGNC

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: Ensembl

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.23. Source: HGNC

protein complex

Inferred from direct assay PubMed 11864573. Source: UniProtKB

ruffle

Inferred from direct assay PubMed 12912914. Source: UniProtKB

ruffle membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

collagen binding

Inferred from physical interaction PubMed 12189148. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 14521508PubMed 15350535. Source: IntAct

protein kinase activity

Inferred from direct assay Ref.1PubMed 9852149. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from direct assay Ref.23PubMed 19667065. Source: UniProtKB

receptor signaling protein serine/threonine kinase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

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

Initiator methionine11Removed Ref.34
Chain2 – 545544Serine/threonine-protein kinase PAK 1
PRO_0000086460

Regions

Domain75 – 8814CRIB
Domain270 – 521252Protein kinase
Nucleotide binding276 – 2849ATP
Nucleotide binding345 – 3473ATP
Region70 – 14071Autoregulatory region
Region75 – 10531GTPase-binding
Region132 – 270139Interaction with CRIPAK

Sites

Active site3891Proton acceptor
Binding site2991ATP

Amino acid modifications

Modified residue21N-acetylserine Ref.34
Modified residue211Phosphoserine; by PKB and autocatalysis Ref.16 Ref.25
Modified residue571Phosphoserine; by autocatalysis Ref.25
Modified residue841Phosphothreonine; by OXSR1 By similarity
Modified residue1311Phosphotyrosine Ref.25
Modified residue1421Phosphotyrosine Ref.25
Modified residue1441Phosphoserine Ref.32
Modified residue1491Phosphoserine Ref.32
Modified residue1531Phosphotyrosine; by JAK2 Ref.24 Ref.25
Modified residue1741Phosphoserine Ref.25 Ref.32
Modified residue1851Phosphothreonine Ref.25
Modified residue1991Phosphoserine; by autocatalysis By similarity
Modified residue2011Phosphotyrosine; by JAK2 Ref.24
Modified residue2041Phosphoserine Ref.30
Modified residue2121Phosphothreonine Ref.22 Ref.25 Ref.30
Modified residue2191Phosphothreonine Ref.30
Modified residue2201Phosphoserine Ref.30
Modified residue2231Phosphoserine Ref.32
Modified residue2301Phosphothreonine Ref.28 Ref.30 Ref.32
Modified residue2851Phosphotyrosine; by JAK2 Ref.24 Ref.25
Modified residue4231Phosphothreonine; by autocatalysis, BRSK2 and PDPK1 Ref.10 Ref.11 Ref.33 Ref.40

Natural variations

Alternative sequence518 – 54528HQFLK…TKNNH → VRKLRFQVFSNFSMIAASIP EDCQAPLQPHSTDCCS in isoform 2.
VSP_017507
Natural variant5151L → V.
Corresponds to variant rs35345144 [ dbSNP | Ensembl ].
VAR_051654

Experimental info

Mutagenesis831H → L: Abolishes interaction with CDC42, leading to strongly decreased activity; when associated with L-86. Ref.7 Ref.10
Mutagenesis861H → L: Abolishes interaction with CDC42, leading to strongly decreased activity; when associated with L-83. Ref.7 Ref.10
Mutagenesis1071L → F: Abolishes autoinhibition, leading to constitutive kinase activity. Ref.10
Mutagenesis2991K → R: Strongly decreases activity. Abolishes kinase activity; when associated with N-389. Ref.40
Mutagenesis3891D → N: Abolishes kinase activity; when associated with R-299. Ref.40
Mutagenesis3931D → A: Abolishes autophosphorylation at Thr-423.
Mutagenesis4231T → A: Decreases CDC42-stimulated activity and autophosphorylation. Ref.10
Mutagenesis4231T → E: Constitutive kinase activity. Ref.10
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 »

FASTA55361,632

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] [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. expand/collapse author list , 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, IDENTIFICATION BY 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]"Essential role of CIB1 in regulating PAK1 activation and cell migration."
Leisner T.M., Liu M., Jaffer Z.M., Chernoff J., Parise L.V.
J. Cell Biol. 170:465-476(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CIB1, SUBCELLULAR LOCATION.
[21]"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.
[22]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[23]"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.
[24]"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, IDENTIFICATION BY MASS SPECTROMETRY.
[25]"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, IDENTIFICATION BY MASS SPECTROMETRY.
[26]"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.
[27]"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.
[28]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[29]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[30]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[31]"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].
[32]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[33]"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.
[34]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[35]"A novel splice variant of calcium and integrin-binding protein 1 mediates protein kinase D2-stimulated tumour growth by regulating angiogenesis."
Armacki M., Joodi G., Nimmagadda S.C., de Kimpe L., Pusapati G.V., Vandoninck S., Van Lint J., Illing A., Seufferlein T.
Oncogene 33:1167-1180(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CIB1 ISOFORM 2.
Tissue: Brain.
[36]"Beta-arrestin-dependent activation of the cofilin pathway is required for the scavenging activity of the atypical chemokine receptor D6."
Borroni E.M., Cancellieri C., Vacchini A., Benureau Y., Lagane B., Bachelerie F., Arenzana-Seisdedos F., Mizuno K., Mantovani A., Bonecchi R., Locati M.
Sci. Signal. 6:RA30-RA30(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION.
[37]"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.
[38]"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.
[39]"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.
[40]"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.

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.
CCDSCCDS44687.1. [Q13153-2]
CCDS8250.1. [Q13153-1]
PIRG01773.
RefSeqNP_001122092.1. NM_001128620.1. [Q13153-2]
NP_002567.3. NM_002576.4. [Q13153-1]
XP_005274082.1. XM_005274025.1. [Q13153-1]
XP_006718636.1. XM_006718573.1. [Q13153-1]
XP_006718637.1. XM_006718574.1. [Q13153-1]
XP_006718638.1. XM_006718575.1. [Q13153-1]
XP_006718639.1. XM_006718576.1. [Q13153-1]
UniGeneHs.435714.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1F3MX-ray2.30A/B70-149[»]
C/D249-545[»]
1YHVX-ray1.80A249-545[»]
1YHWX-ray1.80A249-545[»]
1ZSGNMR-B183-204[»]
2HY8X-ray2.001249-545[»]
2QMEX-ray1.75I74-109[»]
3DVPX-ray2.50C/D212-221[»]
3FXZX-ray1.64A249-545[»]
3FY0X-ray2.35A249-545[»]
3Q4ZX-ray1.89A/B248-545[»]
3Q52X-ray1.80A248-545[»]
3Q53X-ray2.09A248-545[»]
4DAWX-ray2.00A249-545[»]
4EQCX-ray2.01A249-545[»]
4O0RX-ray2.40A/B249-545[»]
4O0TX-ray2.60A/B249-545[»]
ProteinModelPortalQ13153.
SMRQ13153. Positions 78-147, 249-541.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111095. 93 interactions.
DIPDIP-31016N.
IntActQ13153. 45 interactions.
MINTMINT-92897.
STRING9606.ENSP00000278568.

Chemistry

BindingDBQ13153.
ChEMBLCHEMBL4600.
GuidetoPHARMACOLOGY2133.

PTM databases

PhosphoSiteQ13153.

Polymorphism databases

DMDM90111767.

Proteomic databases

MaxQBQ13153.
PaxDbQ13153.
PRIDEQ13153.

Protocols and materials databases

DNASU5058.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000278568; ENSP00000278568; ENSG00000149269. [Q13153-2]
ENST00000356341; ENSP00000348696; ENSG00000149269. [Q13153-1]
GeneID5058.
KEGGhsa:5058.
UCSCuc001oyg.4. human. [Q13153-2]
uc001oyh.4. human. [Q13153-1]

Organism-specific databases

CTD5058.
GeneCardsGC11M077033.
HGNCHGNC:8590. PAK1.
HPACAB005312.
HPA003565.
MIM602590. gene.
neXtProtNX_Q13153.
PharmGKBPA32917.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000234202.
HOVERGENHBG108518.
KOK04409.
OMAAGTLNHG.
OrthoDBEOG7CK36J.
PhylomeDBQ13153.
TreeFamTF105351.

Enzyme and pathway databases

BRENDA2.7.11.1. 2681.
ReactomeREACT_111045. Developmental Biology.
REACT_111155. Cell-Cell communication.
REACT_6900. Immune System.
SignaLinkQ13153.

Gene expression databases

ArrayExpressQ13153.
BgeeQ13153.
CleanExHS_PAK1.
GenevestigatorQ13153.

Family and domain databases

Gene3D3.90.810.10. 1 hit.
InterProIPR000095. CRIB_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00786. PBD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00285. PBD. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS50108. CRIB. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPAK1. human.
EvolutionaryTraceQ13153.
GeneWikiPAK1.
GenomeRNAi5058.
NextBio19488.
PROQ13153.
SOURCESearch...

Entry information

Entry namePAK1_HUMAN
AccessionPrimary (citable) accession number: Q13153
Secondary accession number(s): O75561 expand/collapse secondary AC list , Q13567, Q32M53, Q32M54, Q86W79
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: March 7, 2006
Last modified: July 9, 2014
This is version 164 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM