Human Gene PAK1 (ENST00000356341.8_8) from GENCODE V47lift37
  Description: p21 (RAC1) activated kinase 1, transcript variant 2 (from RefSeq NM_002576.5)
Gencode Transcript: ENST00000356341.8_8
Gencode Gene: ENSG00000149269.10_14
Transcript (Including UTRs)
   Position: hg19 chr11:77,033,062-77,185,139 Size: 152,078 Total Exon Count: 15 Strand: -
Coding Region
   Position: hg19 chr11:77,034,319-77,103,565 Size: 69,247 Coding Exon Count: 14 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr11:77,033,062-77,185,139)mRNA (may differ from genome)Protein (545 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
HGNCMalacardsMGIOMIMPubMedReactome
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: PAK1_HUMAN
DESCRIPTION: RecName: Full=Serine/threonine-protein kinase PAK 1; EC=2.7.11.1; AltName: Full=Alpha-PAK; AltName: Full=p21-activated kinase 1; Short=PAK-1; AltName: Full=p65-PAK;
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. DVL1 and PAK1 form a ternary complex with MUSK which 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.
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). Phosphorylation at Thr-423 by PDPK1 results in its activation.
SUBUNIT: 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). Interacts with DVL1; mediates the formation of a DVL1, MUSK and PAK1 ternary complex involved in AChR clustering (By similarity). 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. Interaction with NCK1 and NCK2.
INTERACTION: P60953:CDC42; NbExp=4; IntAct=EBI-1307, EBI-81752; P21127:CDK11B; NbExp=3; IntAct=EBI-1307, EBI-1298; Q8N1N5:CRIPAK; NbExp=6; IntAct=EBI-1307, EBI-1205846; P53667:LIMK1; NbExp=5; IntAct=EBI-1307, EBI-444403; P63000:RAC1; NbExp=7; IntAct=EBI-1307, EBI-413628; Q7L0Q8:RHOU; NbExp=2; IntAct=EBI-1019502, EBI-1638043;
SUBCELLULAR LOCATION: Cytoplasm. Cell junction, focal adhesion. Note=Recruited to focal adhesions upon activation.
PTM: Autophosphorylated when activated by CDC42/p21 and RAC1. Phosphorylation at Thr-423 by PDPK1 results in its activation.
SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.
SIMILARITY: Contains 1 CRIB domain.
SIMILARITY: Contains 1 protein kinase domain.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/PAK1ID41633ch11q13.html";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: PAK1
Diseases sorted by gene-association score: thymic neuroendocrine tumor (4), breast cancer (3), renal cell carcinoma (2)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 81.62 RPKM in Brain - Frontal Cortex (BA9)
Total median expression: 925.50 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -244.00564-0.433 Picture PostScript Text
3' UTR -362.401257-0.288 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
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

Pfam Domains:
PF00069 - Protein kinase domain
PF00786 - P21-Rho-binding domain
PF07714 - Protein tyrosine and serine/threonine kinase
PF17667 - Fungal protein kinase

SCOP Domains:
56112 - Protein kinase-like (PK-like)

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1F3M - X-ray MuPIT 1YHV - X-ray MuPIT 1YHW - X-ray MuPIT 1ZSG - NMR MuPIT 2HY8 - X-ray MuPIT 2QME - X-ray MuPIT 3DVP - X-ray 3FXZ - X-ray MuPIT 3FY0 - X-ray MuPIT 3Q4Z - X-ray MuPIT 3Q52 - X-ray MuPIT 3Q53 - X-ray MuPIT 4DAW - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q13153
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologGenome BrowserGenome Browser
Gene DetailsGene Details  Gene DetailsGene Details
Gene SorterGene Sorter  Gene SorterGene Sorter
 RGDEnsembl WormBaseSGD
    Protein SequenceProtein Sequence
    AlignmentAlignment

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0003824 catalytic activity
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0005515 protein binding
GO:0005518 collagen binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0019901 protein kinase binding
GO:0042802 identical protein binding
GO:0048365 Rac GTPase binding

Biological Process:
GO:0001666 response to hypoxia
GO:0001934 positive regulation of protein phosphorylation
GO:0002223 stimulatory C-type lectin receptor signaling pathway
GO:0006468 protein phosphorylation
GO:0006887 exocytosis
GO:0006915 apoptotic process
GO:0007266 Rho protein signal transduction
GO:0007346 regulation of mitotic cell cycle
GO:0008152 metabolic process
GO:0008284 positive regulation of cell proliferation
GO:0010033 response to organic substance
GO:0010763 positive regulation of fibroblast migration
GO:0016310 phosphorylation
GO:0021549 cerebellum development
GO:0030010 establishment of cell polarity
GO:0030335 positive regulation of cell migration
GO:0031116 positive regulation of microtubule polymerization
GO:0031295 T cell costimulation
GO:0031532 actin cytoskeleton reorganization
GO:0032147 activation of protein kinase activity
GO:0032869 cellular response to insulin stimulus
GO:0032956 regulation of actin cytoskeleton organization
GO:0033138 positive regulation of peptidyl-serine phosphorylation
GO:0033148 positive regulation of intracellular estrogen receptor signaling pathway
GO:0038095 Fc-epsilon receptor signaling pathway
GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis
GO:0042060 wound healing
GO:0042981 regulation of apoptotic process
GO:0043507 positive regulation of JUN kinase activity
GO:0045773 positive regulation of axon extension
GO:0046777 protein autophosphorylation
GO:0048012 hepatocyte growth factor receptor signaling pathway
GO:0048013 ephrin receptor signaling pathway
GO:0048754 branching morphogenesis of an epithelial tube
GO:0048812 neuron projection morphogenesis
GO:0050770 regulation of axonogenesis
GO:0050852 T cell receptor signaling pathway
GO:0051496 positive regulation of stress fiber assembly
GO:0060244 negative regulation of cell proliferation involved in contact inhibition
GO:0061052 negative regulation of cell growth involved in cardiac muscle cell development
GO:0090314 positive regulation of protein targeting to membrane
GO:1904707 positive regulation of vascular smooth muscle cell proliferation
GO:1904754 positive regulation of vascular associated smooth muscle cell migration
GO:2001275 positive regulation of glucose import in response to insulin stimulus
GO:0000165 MAPK cascade

Cellular Component:
GO:0001726 ruffle
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0005911 cell-cell junction
GO:0005925 focal adhesion
GO:0014704 intercalated disc
GO:0016020 membrane
GO:0030018 Z disc
GO:0030027 lamellipodium
GO:0030054 cell junction
GO:0030424 axon
GO:0030425 dendrite
GO:0031965 nuclear membrane
GO:0032587 ruffle membrane
GO:0032991 macromolecular complex
GO:0042995 cell projection
GO:0071437 invadopodium
GO:0031941 filamentous actin


-  Descriptions from all associated GenBank mRNAs
  LF213743 - JP 2014500723-A/21246: Polycomb-Associated Non-Coding RNAs.
LF384290 - JP 2014500723-A/191793: Polycomb-Associated Non-Coding RNAs.
AK055228 - Homo sapiens cDNA FLJ30666 fis, clone FCBBF1000627, highly similar to Serine/threonine-protein kinase PAK 1 (EC 2.7.11.1).
BC050377 - Homo sapiens p21/Cdc42/Rac1-activated kinase 1 (STE20 homolog, yeast), mRNA (cDNA clone IMAGE:5763796).
BC109298 - Homo sapiens p21/Cdc42/Rac1-activated kinase 1 (STE20 homolog, yeast), mRNA (cDNA clone IMAGE:40034481).
BC109299 - Homo sapiens p21 protein (Cdc42/Rac)-activated kinase 1, mRNA (cDNA clone MGC:130001 IMAGE:40034484), complete cds.
AK293098 - Homo sapiens cDNA FLJ77226 complete cds, highly similar to Homo sapiens p21 activated kinase 1B (PAK1B) mRNA.
U24152 - Homo sapiens p21-activated protein kinase (Pak1) mRNA, complete cds.
AK296006 - Homo sapiens cDNA FLJ51645 complete cds, highly similar to Serine/threonine-protein kinase P>AK 1 (EC 2.7.11.1).
AF071884 - Homo sapiens p21 activated kinase 1B (PAK1B) mRNA, complete cds.
U51120 - Human protein kinase PAK1 mRNA, complete cds.
EU832767 - Synthetic construct Homo sapiens clone HAIB:100067796; DKFZo008A1033 p21/Cdc42/Rac1-activated kinase 1 (STE20 homolog, yeast) protein (PAK1) gene, encodes complete protein.
KJ891750 - Synthetic construct Homo sapiens clone ccsbBroadEn_01144 PAK1 gene, encodes complete protein.
GQ129310 - Synthetic construct Homo sapiens clone HAIB:100068457; DKFZo004A1034 p21/Cdc42/Rac1-activated kinase 1 (STE20 homolog, yeast) protein (PAK1) gene, partial cds.
MA619867 - JP 2018138019-A/191793: Polycomb-Associated Non-Coding RNAs.
MA449320 - JP 2018138019-A/21246: Polycomb-Associated Non-Coding RNAs.
JD521721 - Sequence 502745 from Patent EP1572962.
LF369039 - JP 2014500723-A/176542: Polycomb-Associated Non-Coding RNAs.
JD154006 - Sequence 135030 from Patent EP1572962.
JD101135 - Sequence 82159 from Patent EP1572962.
JD042501 - Sequence 23525 from Patent EP1572962.
JD037729 - Sequence 18753 from Patent EP1572962.
AK295344 - Homo sapiens cDNA FLJ51644 complete cds, highly similar to Serine/threonine-protein kinase P>AK 1 (EC 2.7.11.1).
LF369037 - JP 2014500723-A/176540: Polycomb-Associated Non-Coding RNAs.
LF369030 - JP 2014500723-A/176533: Polycomb-Associated Non-Coding RNAs.
MA604616 - JP 2018138019-A/176542: Polycomb-Associated Non-Coding RNAs.
MA604614 - JP 2018138019-A/176540: Polycomb-Associated Non-Coding RNAs.
MA604607 - JP 2018138019-A/176533: Polycomb-Associated Non-Coding RNAs.
LF369025 - JP 2014500723-A/176528: Polycomb-Associated Non-Coding RNAs.
LF369021 - JP 2014500723-A/176524: Polycomb-Associated Non-Coding RNAs.
LF369020 - JP 2014500723-A/176523: Polycomb-Associated Non-Coding RNAs.
LF369011 - JP 2014500723-A/176514: Polycomb-Associated Non-Coding RNAs.
JD393655 - Sequence 374679 from Patent EP1572962.
JD402340 - Sequence 383364 from Patent EP1572962.
JD111379 - Sequence 92403 from Patent EP1572962.
JD454619 - Sequence 435643 from Patent EP1572962.
JD385372 - Sequence 366396 from Patent EP1572962.
JD251284 - Sequence 232308 from Patent EP1572962.
JD399179 - Sequence 380203 from Patent EP1572962.
JD391939 - Sequence 372963 from Patent EP1572962.
JD443169 - Sequence 424193 from Patent EP1572962.
JD298118 - Sequence 279142 from Patent EP1572962.
JD205769 - Sequence 186793 from Patent EP1572962.
JD403218 - Sequence 384242 from Patent EP1572962.
MA604602 - JP 2018138019-A/176528: Polycomb-Associated Non-Coding RNAs.
MA604598 - JP 2018138019-A/176524: Polycomb-Associated Non-Coding RNAs.
MA604597 - JP 2018138019-A/176523: Polycomb-Associated Non-Coding RNAs.
MA604588 - JP 2018138019-A/176514: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  BioCarta from NCI Cancer Genome Anatomy Project
h_At1rPathway - Angiotensin II mediated activation of JNK Pathway via Pyk2 dependent signaling
h_fMLPpathway - fMLP induced chemokine gene expression in HMC-1 cells
h_mapkPathway - MAPKinase Signaling Pathway
h_RacCycDPathway - Influence of Ras and Rho proteins on G1 to S Transition
h_cdc42racPathway - Role of PI3K subunit p85 in regulation of Actin Organization and Cell Migration
h_rac1Pathway - Rac 1 cell motility signaling pathway
h_pyk2Pathway - Links between Pyk2 and Map Kinases
h_tnfr1Pathway - TNFR1 Signaling Pathway
h_metPathway - Signaling of Hepatocyte Growth Factor Receptor
h_nkcellsPathway - Ras-Independent pathway in NK cell-mediated cytotoxicity
h_fasPathway - FAS signaling pathway ( CD95 )
h_agrPathway - Agrin in Postsynaptic Differentiation

Reactome (by CSHL, EBI, and GO)

Protein Q13153 (Reactome details) participates in the following event(s):

R-HSA-445072 Interaction of PAK1 with Rac1-GTP
R-HSA-2029456 RAC1 and CDC42 activate PAK1
R-HSA-5669240 FLNA binds PAK1
R-HSA-2029454 Autophosphorylation of PAK1
R-HSA-5669250 PAK1 phosphorylates FLNA
R-HSA-3928619 PAK1 binds RAC1:GTP
R-HSA-5669158 NF2 binds PAK1
R-HSA-430183 NCK binds PAK
R-HSA-389788 Activation of PAKs by RAC1 and CDC42
R-HSA-399930 Activation of PAK by Rac1
R-HSA-3928641 PAK binds RAC and bPIX
R-HSA-428531 Recruitment of PAK to NCK
R-HSA-5357472 PAK1-3 autophosphorylates
R-HSA-5627775 Autophosphorylation of PAK1,2,3
R-HSA-2730856 Autophosphorylation of PAK
R-HSA-2029460 PAK1 phosphorylates LIMK1
R-HSA-5668947 PAK1 phosphorylates myosin phosphatase
R-HSA-376123 DSCAM associates with Rac1-GTP:pPAK1
R-HSA-3928620 PAK1 autophosphorylates
R-HSA-5357483 RAC1 binds PAK1-3
R-HSA-2730889 Recruitment of PAK to the membrane by binding active RAC1
R-HSA-399939 Autophosphorylation of PAK
R-HSA-5357445 PAK1-3 dimer disassociates
R-HSA-5624492 PAK phosphorylates p21 RAF1 on S338
R-HSA-3928625 PAKs autophosphorylate
R-HSA-442832 PAK phosphorylates cortactin
R-HSA-5687086 PAK1,2,3 phosphorylates MAPK6,4
R-HSA-5357477 PAK1-3 phosphorylates VE-cadherin
R-HSA-5668984 PAK1 or PAK2 phosphorylates MYLK
R-HSA-399952 Phosphorylation of LIMK-1 by PAK
R-HSA-451347 Activation of JNK by DSCAM
R-HSA-3928640 PAKs phosphorylate MLC
R-HSA-445144 Signal transduction by L1
R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation
R-HSA-5627123 RHO GTPases activate PAKs
R-HSA-3928662 EPHB-mediated forward signaling
R-HSA-202433 Generation of second messenger molecules
R-HSA-389359 CD28 dependent Vav1 pathway
R-HSA-5687128 MAPK6/MAPK4 signaling
R-HSA-399954 Sema3A PAK dependent Axon repulsion
R-HSA-3928664 Ephrin signaling
R-HSA-428540 Activation of RAC1
R-HSA-373760 L1CAM interactions
R-HSA-2029480 Fcgamma receptor (FCGR) dependent phagocytosis
R-HSA-195258 RHO GTPase Effectors
R-HSA-5218920 VEGFR2 mediated vascular permeability
R-HSA-2871796 FCERI mediated MAPK activation
R-HSA-376172 DSCAM interactions
R-HSA-2682334 EPH-Ephrin signaling
R-HSA-202403 TCR signaling
R-HSA-389356 CD28 co-stimulation
R-HSA-5683057 MAPK family signaling cascades
R-HSA-373755 Semaphorin interactions
R-HSA-5621575 CD209 (DC-SIGN) signaling
R-HSA-376176 Signaling by ROBO receptors
R-HSA-422475 Axon guidance
R-HSA-168249 Innate Immune System
R-HSA-194315 Signaling by Rho GTPases
R-HSA-4420097 VEGFA-VEGFR2 Pathway
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling
R-HSA-373752 Netrin-1 signaling
R-HSA-1280218 Adaptive Immune System
R-HSA-388841 Costimulation by the CD28 family
R-HSA-162582 Signal Transduction
R-HSA-5621481 C-type lectin receptors (CLRs)
R-HSA-1266738 Developmental Biology
R-HSA-168256 Immune System
R-HSA-194138 Signaling by VEGF
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000356341.1, ENST00000356341.2, ENST00000356341.3, ENST00000356341.4, ENST00000356341.5, ENST00000356341.6, ENST00000356341.7, NM_002576, O75561, PAK1 , PAK1_HUMAN, Q13153, Q13567, Q32M53, Q32M54, Q86W79, uc317zmy.1, uc317zmy.2
UCSC ID: ENST00000356341.8_8
RefSeq Accession: NM_002576.5
Protein: Q13153 (aka PAK1_HUMAN)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.