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Q13153

- PAK1_HUMAN

UniProt

Q13153 - PAK1_HUMAN

Protein

Serine/threonine-protein kinase PAK 1

Gene

PAK1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 166 (01 Oct 2014)
      Sequence version 2 (07 Mar 2006)
      Previous versions | rss
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    Functioni

    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.17 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.3 Publications

    Cofactori

    Magnesium.

    Enzyme regulationi

    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.By similarity4 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei299 – 2991ATP
    Active sitei389 – 3891Proton acceptor

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi276 – 2849ATP
    Nucleotide bindingi345 – 3473ATP

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. collagen binding Source: UniProtKB
    3. protein binding Source: IntAct
    4. protein kinase activity Source: UniProtKB
    5. protein serine/threonine kinase activity Source: UniProtKB

    GO - Biological processi

    1. actin cytoskeleton reorganization Source: UniProtKB
    2. apoptotic process Source: UniProtKB-KW
    3. axon guidance Source: Reactome
    4. branching morphogenesis of an epithelial tube Source: UniProtKB
    5. cellular response to insulin stimulus Source: Ensembl
    6. dendrite development Source: Ensembl
    7. exocytosis Source: UniProtKB-KW
    8. Fc-epsilon receptor signaling pathway Source: Reactome
    9. Fc-gamma receptor signaling pathway involved in phagocytosis Source: Reactome
    10. innate immune response Source: Reactome
    11. negative regulation of cell proliferation involved in contact inhibition Source: UniProtKB
    12. neuromuscular junction development Source: Ensembl
    13. neuron projection morphogenesis Source: UniProtKB
    14. positive regulation of intracellular estrogen receptor signaling pathway Source: UniProtKB
    15. positive regulation of JUN kinase activity Source: UniProtKB
    16. positive regulation of peptidyl-serine phosphorylation Source: UniProtKB
    17. positive regulation of protein phosphorylation Source: UniProtKB
    18. positive regulation of stress fiber assembly Source: UniProtKB
    19. protein autophosphorylation Source: UniProtKB
    20. protein phosphorylation Source: UniProtKB
    21. receptor clustering Source: Ensembl
    22. response to hypoxia Source: Ensembl
    23. T cell costimulation Source: Reactome
    24. T cell receptor signaling pathway Source: Reactome
    25. wound healing Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Apoptosis, Exocytosis

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.11.1. 2681.
    ReactomeiREACT_12623. Generation of second messenger molecules.
    REACT_160086. Regulation of actin dynamics for phagocytic cup formation.
    REACT_163701. FCERI mediated MAPK activation.
    REACT_19226. Activation of Rac.
    REACT_19236. Sema3A PAK dependent Axon repulsion.
    REACT_19238. CD28 dependent Vav1 pathway.
    REACT_22272. Signal transduction by L1.
    REACT_25299. DSCAM interactions.
    SignaLinkiQ13153.

    Names & Taxonomyi

    Protein namesi
    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 namesi
    Name:PAK1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:8590. PAK1.

    Subcellular locationi

    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.

    GO - Cellular componenti

    1. axon Source: UniProtKB
    2. cell-cell junction Source: UniProtKB
    3. cytoplasm Source: HGNC
    4. cytosol Source: Reactome
    5. dendrite Source: UniProtKB
    6. focal adhesion Source: UniProtKB-SubCell
    7. growth cone Source: Ensembl
    8. intercalated disc Source: UniProtKB
    9. nuclear membrane Source: UniProtKB
    10. plasma membrane Source: HGNC
    11. protein complex Source: UniProtKB
    12. ruffle Source: UniProtKB
    13. ruffle membrane Source: UniProtKB-SubCell
    14. Z disc Source: UniProtKB

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Cell projection, Cytoplasm, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi83 – 831H → L: Abolishes interaction with CDC42, leading to strongly decreased activity; when associated with L-86. 2 Publications
    Mutagenesisi86 – 861H → L: Abolishes interaction with CDC42, leading to strongly decreased activity; when associated with L-83. 2 Publications
    Mutagenesisi107 – 1071L → F: Abolishes autoinhibition, leading to constitutive kinase activity. 1 Publication
    Mutagenesisi299 – 2991K → R: Strongly decreases activity. Abolishes kinase activity; when associated with N-389. 1 Publication
    Mutagenesisi389 – 3891D → N: Abolishes kinase activity; when associated with R-299. 1 Publication
    Mutagenesisi393 – 3931D → A: Abolishes autophosphorylation at Thr-423.
    Mutagenesisi423 – 4231T → A: Decreases CDC42-stimulated activity and autophosphorylation. 1 Publication
    Mutagenesisi423 – 4231T → E: Constitutive kinase activity. 1 Publication

    Organism-specific databases

    PharmGKBiPA32917.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed1 Publication
    Chaini2 – 545544Serine/threonine-protein kinase PAK 1PRO_0000086460Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylserine1 Publication
    Modified residuei21 – 211Phosphoserine; by PKB and autocatalysis3 Publications
    Modified residuei57 – 571Phosphoserine; by autocatalysis2 Publications
    Modified residuei84 – 841Phosphothreonine; by OXSR1By similarity
    Modified residuei131 – 1311Phosphotyrosine2 Publications
    Modified residuei142 – 1421Phosphotyrosine2 Publications
    Modified residuei144 – 1441Phosphoserine2 Publications
    Modified residuei149 – 1491Phosphoserine2 Publications
    Modified residuei153 – 1531Phosphotyrosine; by JAK23 Publications
    Modified residuei174 – 1741Phosphoserine3 Publications
    Modified residuei185 – 1851Phosphothreonine2 Publications
    Modified residuei199 – 1991Phosphoserine; by autocatalysisBy similarity
    Modified residuei201 – 2011Phosphotyrosine; by JAK22 Publications
    Modified residuei204 – 2041Phosphoserine2 Publications
    Modified residuei212 – 2121Phosphothreonine4 Publications
    Modified residuei219 – 2191Phosphothreonine2 Publications
    Modified residuei220 – 2201Phosphoserine2 Publications
    Modified residuei223 – 2231Phosphoserine2 Publications
    Modified residuei230 – 2301Phosphothreonine4 Publications
    Modified residuei285 – 2851Phosphotyrosine; by JAK23 Publications
    Modified residuei423 – 4231Phosphothreonine; by autocatalysis, BRSK2 and PDPK15 Publications

    Post-translational modificationi

    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.12 Publications

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    MaxQBiQ13153.
    PaxDbiQ13153.
    PRIDEiQ13153.

    PTM databases

    PhosphoSiteiQ13153.

    Expressioni

    Gene expression databases

    ArrayExpressiQ13153.
    BgeeiQ13153.
    CleanExiHS_PAK1.
    GenevestigatoriQ13153.

    Organism-specific databases

    HPAiCAB005312.
    HPA003565.

    Interactioni

    Subunit structurei

    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. 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.By similarity18 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ARHGEF7Q141557EBI-1307,EBI-717515
    CDC42P609537EBI-1307,EBI-81752
    Cdc42P607663EBI-1307,EBI-81763From a different organism.
    CDK11BP211274EBI-1307,EBI-1298
    CRIPAKQ8N1N56EBI-1307,EBI-1205846
    GIT1Q9Y2X72EBI-1307,EBI-466061
    LIMK1P536675EBI-1307,EBI-444403
    RAC1P6300016EBI-1307,EBI-413628
    Rac1P630013EBI-1307,EBI-413646From a different organism.
    RHOUQ7L0Q82EBI-1019502,EBI-1638043

    Protein-protein interaction databases

    BioGridi111095. 60 interactions.
    DIPiDIP-31016N.
    IntActiQ13153. 45 interactions.
    MINTiMINT-92897.
    STRINGi9606.ENSP00000278568.

    Structurei

    Secondary structure

    1
    545
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi79 – 879
    Turni91 – 944
    Beta strandi95 – 984
    Helixi101 – 1088
    Helixi114 – 1196
    Helixi121 – 13515
    Beta strandi195 – 1984
    Beta strandi214 – 2196
    Helixi250 – 26011
    Beta strandi261 – 2644
    Helixi266 – 2683
    Beta strandi274 – 2796
    Beta strandi282 – 2898
    Turni290 – 2923
    Beta strandi295 – 3028
    Helixi303 – 3053
    Helixi309 – 32113
    Beta strandi330 – 3367
    Beta strandi339 – 3457
    Beta strandi349 – 3513
    Helixi352 – 3587
    Helixi363 – 38220
    Helixi392 – 3943
    Beta strandi395 – 3973
    Beta strandi403 – 4053
    Beta strandi408 – 4103
    Beta strandi416 – 4183
    Helixi428 – 4303
    Helixi433 – 4375
    Helixi444 – 45916
    Turni463 – 4664
    Helixi469 – 47911
    Helixi487 – 4893
    Helixi492 – 50110
    Turni506 – 5083
    Helixi512 – 5154
    Helixi519 – 5235
    Helixi527 – 5304
    Helixi531 – 54010

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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[»]
    ProteinModelPortaliQ13153.
    SMRiQ13153. Positions 78-147, 249-541.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ13153.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini75 – 8814CRIBPROSITE-ProRule annotationAdd
    BLAST
    Domaini270 – 521252Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni70 – 14071Autoregulatory regionAdd
    BLAST
    Regioni75 – 10531GTPase-bindingAdd
    BLAST
    Regioni132 – 270139Interaction with CRIPAKAdd
    BLAST

    Sequence similaritiesi

    Contains 1 CRIB domain.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000234202.
    HOVERGENiHBG108518.
    KOiK04409.
    OMAiAGTLNHG.
    OrthoDBiEOG7CK36J.
    PhylomeDBiQ13153.
    TreeFamiTF105351.

    Family and domain databases

    Gene3Di3.90.810.10. 1 hit.
    InterProiIPR000095. 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]
    PfamiPF00786. PBD. 1 hit.
    PF00069. Pkinase. 1 hit.
    [Graphical view]
    SMARTiSM00285. PBD. 1 hit.
    SM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS50108. CRIB. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q13153-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MSNNGLDIQD KPPAPPMRNT STMIGAGSKD AGTLNHGSKP LPPNPEEKKK    50
    KDRFYRSILP GDKTNKKKEK ERPEISLPSD FEHTIHVGFD AVTGEFTGMP 100
    EQWARLLQTS NITKSEQKKN PQAVLDVLEF YNSKKTSNSQ KYMSFTDKSA 150
    EDYNSSNALN VKAVSETPAV PPVSEDEDDD DDDATPPPVI APRPEHTKSV 200
    YTRSVIEPLP VTPTRDVATS PISPTENNTT PPDALTRNTE KQKKKPKMSD 250
    EEILEKLRSI VSVGDPKKKY TRFEKIGQGA SGTVYTAMDV ATGQEVAIKQ 300
    MNLQQQPKKE LIINEILVMR ENKNPNIVNY LDSYLVGDEL WVVMEYLAGG 350
    SLTDVVTETC MDEGQIAAVC RECLQALEFL HSNQVIHRDI KSDNILLGMD 400
    GSVKLTDFGF CAQITPEQSK RSTMVGTPYW MAPEVVTRKA YGPKVDIWSL 450
    GIMAIEMIEG EPPYLNENPL RALYLIATNG TPELQNPEKL SAIFRDFLNR 500
    CLEMDVEKRG SAKELLQHQF LKIAKPLSSL TPLIAAAKEA TKNNH 545
    Length:545
    Mass (Da):60,647
    Last modified:March 7, 2006 - v2
    Checksum:i1A95CD5F2195CD7B
    GO
    Isoform 2 (identifier: Q13153-2) [UniParc]FASTAAdd to Basket

    Also known as: PAK1B

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

    Show »
    Length:553
    Mass (Da):61,632
    Checksum:i6A3BB134DD2A82A8
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti26 – 261A → V in AAA65441. (PubMed:9395435)Curated
    Sequence conflicti26 – 261A → V in AAC24716. 1 PublicationCurated
    Sequence conflicti237 – 2371R → L in AAC50590. (PubMed:8805275)Curated
    Sequence conflicti379 – 3791F → S in AAC50590. (PubMed:8805275)Curated
    Sequence conflicti503 – 5031E → D in AAA65441. (PubMed:9395435)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti515 – 5151L → V.
    Corresponds to variant rs35345144 [ dbSNP | Ensembl ].
    VAR_051654

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei518 – 54528HQFLK…TKNNH → VRKLRFQVFSNFSMIAASIP EDCQAPLQPHSTDCCS in isoform 2. 1 PublicationVSP_017507Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS44687.1. [Q13153-2]
    CCDS8250.1. [Q13153-1]
    PIRiG01773.
    RefSeqiNP_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]
    UniGeneiHs.435714.

    Genome annotation databases

    EnsembliENST00000278568; ENSP00000278568; ENSG00000149269. [Q13153-2]
    ENST00000356341; ENSP00000348696; ENSG00000149269. [Q13153-1]
    GeneIDi5058.
    KEGGihsa:5058.
    UCSCiuc001oyg.4. human. [Q13153-2]
    uc001oyh.4. human. [Q13153-1]

    Polymorphism databases

    DMDMi90111767.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS44687.1. [Q13153-2 ]
    CCDS8250.1. [Q13153-1 ]
    PIRi G01773.
    RefSeqi NP_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 ]
    UniGenei Hs.435714.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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 [» ]
    4EQC X-ray 2.01 A 249-545 [» ]
    4O0R X-ray 2.40 A/B 249-545 [» ]
    4O0T X-ray 2.60 A/B 249-545 [» ]
    ProteinModelPortali Q13153.
    SMRi Q13153. Positions 78-147, 249-541.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111095. 60 interactions.
    DIPi DIP-31016N.
    IntActi Q13153. 45 interactions.
    MINTi MINT-92897.
    STRINGi 9606.ENSP00000278568.

    Chemistry

    BindingDBi Q13153.
    ChEMBLi CHEMBL4600.
    GuidetoPHARMACOLOGYi 2133.

    PTM databases

    PhosphoSitei Q13153.

    Polymorphism databases

    DMDMi 90111767.

    Proteomic databases

    MaxQBi Q13153.
    PaxDbi Q13153.
    PRIDEi Q13153.

    Protocols and materials databases

    DNASUi 5058.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000278568 ; ENSP00000278568 ; ENSG00000149269 . [Q13153-2 ]
    ENST00000356341 ; ENSP00000348696 ; ENSG00000149269 . [Q13153-1 ]
    GeneIDi 5058.
    KEGGi hsa:5058.
    UCSCi uc001oyg.4. human. [Q13153-2 ]
    uc001oyh.4. human. [Q13153-1 ]

    Organism-specific databases

    CTDi 5058.
    GeneCardsi GC11M077033.
    HGNCi HGNC:8590. PAK1.
    HPAi CAB005312.
    HPA003565.
    MIMi 602590. gene.
    neXtProti NX_Q13153.
    PharmGKBi PA32917.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000234202.
    HOVERGENi HBG108518.
    KOi K04409.
    OMAi AGTLNHG.
    OrthoDBi EOG7CK36J.
    PhylomeDBi Q13153.
    TreeFami TF105351.

    Enzyme and pathway databases

    BRENDAi 2.7.11.1. 2681.
    Reactomei REACT_12623. Generation of second messenger molecules.
    REACT_160086. Regulation of actin dynamics for phagocytic cup formation.
    REACT_163701. FCERI mediated MAPK activation.
    REACT_19226. Activation of Rac.
    REACT_19236. Sema3A PAK dependent Axon repulsion.
    REACT_19238. CD28 dependent Vav1 pathway.
    REACT_22272. Signal transduction by L1.
    REACT_25299. DSCAM interactions.
    SignaLinki Q13153.

    Miscellaneous databases

    ChiTaRSi PAK1. human.
    EvolutionaryTracei Q13153.
    GeneWikii PAK1.
    GenomeRNAii 5058.
    NextBioi 19488.
    PROi Q13153.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q13153.
    Bgeei Q13153.
    CleanExi HS_PAK1.
    Genevestigatori Q13153.

    Family and domain databases

    Gene3Di 3.90.810.10. 1 hit.
    InterProi IPR000095. 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 ]
    Pfami PF00786. PBD. 1 hit.
    PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SMARTi SM00285. PBD. 1 hit.
    SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS50108. CRIB. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. 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. 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. 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. Cited for: INTERACTION WITH RAC1 AND CDC42.
    27. Cited for: INTERACTION WITH SCRIB.
    28. 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. 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. 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.

    Entry informationi

    Entry nameiPAK1_HUMAN
    AccessioniPrimary (citable) accession number: Q13153
    Secondary accession number(s): O75561
    , Q13567, Q32M53, Q32M54, Q86W79
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: March 7, 2006
    Last modified: October 1, 2014
    This is version 166 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Allosteric enzyme, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 11
      Human chromosome 11: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3