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Protein

Serine/threonine-protein kinase PAK 1

Gene

PAK1

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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. Plays a role in RUFY3-mediated facilitating gastric cancer cells migration and invasion.1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

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-422 (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei298 – 2981ATPPROSITE-ProRule annotation
Active sitei388 – 3881Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi275 – 2839ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Exocytosis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-BTA-202433. Generation of second messenger molecules.
R-BTA-2029482. Regulation of actin dynamics for phagocytic cup formation.
R-BTA-2871796. FCERI mediated MAPK activation.
R-BTA-376172. DSCAM interactions.
R-BTA-389359. CD28 dependent Vav1 pathway.
R-BTA-3928662. EPHB-mediated forward signaling.
R-BTA-3928664. Ephrin signaling.
R-BTA-399954. Sema3A PAK dependent Axon repulsion.
R-BTA-4420097. VEGFA-VEGFR2 Pathway.
R-BTA-445144. Signal transduction by L1.
R-BTA-5218920. VEGFR2 mediated vascular permeability.
R-BTA-5621575. CD209 (DC-SIGN) signaling.
R-BTA-5627123. RHO GTPases activate PAKs.
R-BTA-5687128. MAPK6/MAPK4 signaling.

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
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 29

Subcellular locationi

  • Cytoplasm By similarity
  • Cell junctionfocal adhesion By similarity
  • Cell membrane By similarity
  • Cell projectionruffle membrane By similarity
  • Cell projectioninvadopodium By similarity

  • 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. Colocalizes with RUFY3, F-actin and other core migration components in invadopodia at the cell periphery (By similarity).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 544543Serine/threonine-protein kinase PAK 1PRO_0000286350Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineBy similarity
Modified residuei21 – 211Phosphoserine; by PKB and autocatalysisBy similarity
Modified residuei84 – 841Phosphothreonine; by OXSR1By similarity
Modified residuei115 – 1151PhosphoserineBy similarity
Modified residuei131 – 1311PhosphotyrosineBy similarity
Modified residuei142 – 1421PhosphotyrosineBy similarity
Modified residuei144 – 1441Phosphoserine; by autocatalysisBy similarity
Modified residuei149 – 1491Phosphoserine; by autocatalysisBy similarity
Modified residuei153 – 1531Phosphotyrosine; by JAK2By similarity
Modified residuei174 – 1741PhosphoserineBy similarity
Modified residuei184 – 1841PhosphothreonineBy similarity
Modified residuei198 – 1981Phosphoserine; by autocatalysisBy similarity
Modified residuei200 – 2001Phosphotyrosine; by JAK2By similarity
Modified residuei203 – 2031Phosphoserine; by autocatalysisBy similarity
Modified residuei211 – 2111PhosphothreonineBy similarity
Modified residuei218 – 2181PhosphothreonineBy similarity
Modified residuei219 – 2191PhosphoserineBy similarity
Modified residuei222 – 2221PhosphoserineBy similarity
Modified residuei224 – 2241PhosphothreonineBy similarity
Modified residuei228 – 2281PhosphothreonineBy similarity
Modified residuei229 – 2291PhosphothreonineBy similarity
Modified residuei284 – 2841Phosphotyrosine; by JAK2By similarity
Modified residuei422 – 4221Phosphothreonine; by autocatalysis, BRSK2 and PDPK1By similarity

Post-translational modificationi

Autophosphorylated in trans, meaning that in a dimer, one kinase molecule phosphorylates the other one. Activated by autophosphorylation at Thr-422 in response to a conformation change, triggered by interaction with GTP-bound CDC42 or RAC1. Activated by phosphorylation at Thr-422 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 (By similarity).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiQ08E52.
PeptideAtlasiQ08E52.
PRIDEiQ08E52.

Expressioni

Gene expression databases

BgeeiENSBTAG00000010191.

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 (via N-terminal region); the interaction is direct, promotes PAK1 activity and occurs in a calcium-dependent manner (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ08E52. 1 interaction.
STRINGi9913.ENSBTAP00000013448.

Structurei

3D structure databases

ProteinModelPortaliQ08E52.
SMRiQ08E52. Positions 78-147, 248-540.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini75 – 8814CRIBPROSITE-ProRule annotationAdd
BLAST
Domaini269 – 520252Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni70 – 14071Autoregulatory regionBy similarityAdd
BLAST
Regioni70 – 10536GTPase-bindingBy similarityAdd
BLAST
Regioni132 – 269138Interaction with CRIPAKBy similarityAdd
BLAST

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG0578. Eukaryota.
ENOG410XP4K. LUCA.
GeneTreeiENSGT00840000129718.
HOGENOMiHOG000234202.
HOVERGENiHBG108518.
InParanoidiQ08E52.
KOiK04409.
OMAiAGDKTNK.
OrthoDBiEOG091G04H8.
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.
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]

Sequencei

Sequence statusi: Complete.

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

Q08E52-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSNNGLDIQD KPPAPPMRNT STMIGAGSKD AGTLNHGSKP LPPNPEEKKK
60 70 80 90 100
KDRFYRAILP GDKTNKKKEK ERPEISLPSD FEHTIHVGFD AVTGEFTGMP
110 120 130 140 150
EQWARLLQTS NITKSEQKKN PQAVLDVLEF YNSKKTSNSQ KYMSFTDKSA
160 170 180 190 200
EDYNSSNTLN VKAVSETPAV PPVSEDEDDD DDGTPPPVIA PRPEHTKSVY
210 220 230 240 250
TRSVIEPLPI TPTRDVATSP ISPTENNTTP PDALTRNTEK QKKKPKMSDE
260 270 280 290 300
EILEKLRSIV SVGDPKKKYT RFEKIGQGAS GTVYTAMDVA TGQEVAIKQM
310 320 330 340 350
NLQQQPKKEL IINEILVMRE NKNPNIVNYL DSYLVGDELW VVMEYLAGGS
360 370 380 390 400
LTDVVTETCM DEGQIAAVCR ECLQALEFLH SNQVIHRDIK SDNILLGMDG
410 420 430 440 450
SVKLTDFGFC AQITPEQSKR STMVGTPYWM APEVVTRKAY GPKVDIWSLG
460 470 480 490 500
IMAIEMIEGE PPYLNENPLR ALYLIATNGT PELQNPEKLS AIFRDFLNRC
510 520 530 540
LEMDVEKRGS AKELLQHQFL KIAKPLSSLT PLIAAAKEAT KNNH
Length:544
Mass (Da):60,546
Last modified:October 31, 2006 - v1
Checksum:i92A385B77CD46DBF
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC123416 mRNA. Translation: AAI23417.1.
RefSeqiNP_001070366.1. NM_001076898.1.
XP_010819137.1. XM_010820835.1.
XP_010819138.1. XM_010820836.2.
XP_010819139.1. XM_010820837.1.
XP_015316619.1. XM_015461133.1.
UniGeneiBt.17706.

Genome annotation databases

EnsembliENSBTAT00000013448; ENSBTAP00000013448; ENSBTAG00000010191.
GeneIDi533729.
KEGGibta:533729.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC123416 mRNA. Translation: AAI23417.1.
RefSeqiNP_001070366.1. NM_001076898.1.
XP_010819137.1. XM_010820835.1.
XP_010819138.1. XM_010820836.2.
XP_010819139.1. XM_010820837.1.
XP_015316619.1. XM_015461133.1.
UniGeneiBt.17706.

3D structure databases

ProteinModelPortaliQ08E52.
SMRiQ08E52. Positions 78-147, 248-540.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ08E52. 1 interaction.
STRINGi9913.ENSBTAP00000013448.

Proteomic databases

PaxDbiQ08E52.
PeptideAtlasiQ08E52.
PRIDEiQ08E52.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000013448; ENSBTAP00000013448; ENSBTAG00000010191.
GeneIDi533729.
KEGGibta:533729.

Organism-specific databases

CTDi5058.

Phylogenomic databases

eggNOGiKOG0578. Eukaryota.
ENOG410XP4K. LUCA.
GeneTreeiENSGT00840000129718.
HOGENOMiHOG000234202.
HOVERGENiHBG108518.
InParanoidiQ08E52.
KOiK04409.
OMAiAGDKTNK.
OrthoDBiEOG091G04H8.
TreeFamiTF105351.

Enzyme and pathway databases

ReactomeiR-BTA-202433. Generation of second messenger molecules.
R-BTA-2029482. Regulation of actin dynamics for phagocytic cup formation.
R-BTA-2871796. FCERI mediated MAPK activation.
R-BTA-376172. DSCAM interactions.
R-BTA-389359. CD28 dependent Vav1 pathway.
R-BTA-3928662. EPHB-mediated forward signaling.
R-BTA-3928664. Ephrin signaling.
R-BTA-399954. Sema3A PAK dependent Axon repulsion.
R-BTA-4420097. VEGFA-VEGFR2 Pathway.
R-BTA-445144. Signal transduction by L1.
R-BTA-5218920. VEGFR2 mediated vascular permeability.
R-BTA-5621575. CD209 (DC-SIGN) signaling.
R-BTA-5627123. RHO GTPases activate PAKs.
R-BTA-5687128. MAPK6/MAPK4 signaling.

Gene expression databases

BgeeiENSBTAG00000010191.

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.
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]
ProtoNetiSearch...

Entry informationi

Entry nameiPAK1_BOVIN
AccessioniPrimary (citable) accession number: Q08E52
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: October 31, 2006
Last modified: September 7, 2016
This is version 92 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Allosteric enzyme, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.