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Protein

Serine/threonine-protein kinase PAK 5

Gene

Pak5

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, proliferation or cell survival. Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates the proto-oncogene RAF1 and stimulates its kinase activity. Promotes cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Phosphorylates CTNND1, probably to regulate cytoskeletal organization and cell morphology. Keeps microtubules stable through MARK2 inhibition and destabilizes the F-actin network leading to the disappearance of stress fibers and focal adhesions (By similarity).By similarity1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei478ATPPROSITE-ProRule annotation1
Active sitei568Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi455 – 463ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • protein serine/threonine kinase activity Source: MGI
  • Rac GTPase binding Source: GO_Central

GO - Biological processi

  • actin cytoskeleton organization Source: GO_Central
  • activation of protein kinase activity Source: GO_Central
  • apoptotic process Source: UniProtKB-KW
  • cell growth Source: InterPro
  • cell migration Source: GO_Central
  • learning Source: MGI
  • locomotory behavior Source: MGI
  • memory Source: MGI
  • negative regulation of extrinsic apoptotic signaling pathway Source: MGI
  • regulation of MAPK cascade Source: GO_Central
  • regulation of mitotic cell cycle Source: GO_Central
  • Rho protein signal transduction Source: GO_Central
  • signal transduction by protein phosphorylation Source: GO_Central
  • stress-activated protein kinase signaling cascade Source: GO_Central

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processApoptosis
LigandATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase PAK 5 (EC:2.7.11.1)
Alternative name(s):
p21-activated kinase 5
Short name:
PAK-5
p21-activated kinase 7
Short name:
PAK-7
Gene namesi
Name:Pak5
Synonyms:Pak7
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1920334. Pak7.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice are viable and fertile, and show normal development of brain, eye, pancreas and adrenal gland.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000864781 – 719Serine/threonine-protein kinase PAK 5Add BLAST719

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei41PhosphoserineBy similarity1
Modified residuei78N6-methyllysineBy similarity1
Modified residuei104PhosphoserineCombined sources1
Modified residuei107PhosphothreonineCombined sources1
Modified residuei288PhosphoserineBy similarity1
Modified residuei387PhosphoserineBy similarity1
Modified residuei396PhosphoserineBy similarity1
Modified residuei419PhosphoserineBy similarity1
Modified residuei602PhosphoserineBy similarity1

Post-translational modificationi

Autophosphorylated when activated by CDC42/p21.By similarity

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

MaxQBiQ8C015.
PaxDbiQ8C015.
PRIDEiQ8C015.

PTM databases

iPTMnetiQ8C015.
PhosphoSitePlusiQ8C015.

Expressioni

Tissue specificityi

Highly expressed in brain and eye. Also expressed in adrenal gland, pancreas, prostate and testes. Within the brain, expression is restricted to neurons. Present in brain but not in kidney, lung and spleen (at protein level).1 Publication

Developmental stagei

Expressed in fetal brain.1 Publication

Gene expression databases

BgeeiENSMUSG00000039913.
CleanExiMM_PAK7.
GenevisibleiQ8C015. MM.

Interactioni

Subunit structurei

Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and RAC1. Interacts with MARK2, leading to inhibit MARK2 independently of kinase activity. Interacts with RHOD and RHOH (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000047285.

Structurei

3D structure databases

ProteinModelPortaliQ8C015.
SMRiQ8C015.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini11 – 24CRIBPROSITE-ProRule annotationAdd BLAST14
Domaini449 – 700Protein kinasePROSITE-ProRule annotationAdd BLAST252

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni25 – 448LinkerAdd BLAST424

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi4 – 8Poly-Lys5
Compositional biasi223 – 226Poly-Ser4
Compositional biasi360 – 428Ser-richAdd BLAST69

Domaini

An autoinhibitory domain is present in the N-terminal region of the protein.By similarity

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0578. Eukaryota.
ENOG410XP4K. LUCA.
GeneTreeiENSGT00900000140851.
HOGENOMiHOG000234205.
HOVERGENiHBG108518.
InParanoidiQ8C015.
KOiK05736.
OMAiMRQYRHH.
OrthoDBiEOG091G0OT5.
PhylomeDBiQ8C015.
TreeFamiTF105352.

Family and domain databases

CDDicd01093. CRIB_PAK_like. 1 hit.
Gene3Di3.90.810.10. 1 hit.
InterProiView protein in InterPro
IPR000095. CRIB_dom.
IPR036936. CRIB_dom_sf.
IPR011009. Kinase-like_dom.
IPR028754. PAK5.
IPR033923. PAK_BD.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
PANTHERiPTHR24361:SF183. PTHR24361:SF183. 1 hit.
PfamiView protein in Pfam
PF00786. PBD. 1 hit.
PF00069. Pkinase. 1 hit.
SMARTiView protein in SMART
SM00285. PBD. 1 hit.
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiView protein in PROSITE
PS50108. CRIB. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.

Sequencei

Sequence statusi: Complete.

Q8C015-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MFGKKKKKIE ISGPSNFEHR VHTGFDPQEQ KFTGLPQQWH SLLADTANRP
60 70 80 90 100
KPMVDPSCIT PIQLAPMKTI VRGNKSCKET SINGLLEDFD NISVTRSNSL
110 120 130 140 150
RKESPPTPDQ GAASRIQGHS EENGFITFSQ YSSESDTTAD YTTEKYRDRS
160 170 180 190 200
LYGDDLDLYY KSSHAAKQNG HAMKMKHGDA YYPEMKSLKT DLAGFPVDYH
210 220 230 240 250
THLDSLRKSS EYGDLRWDYQ RASSSSPLDY SFQLTPSRTA GTSRCSKESL
260 270 280 290 300
AYSESDWGPS LDDYDRRPKS SYLHQTSPQP AMRQRSKSGS GLQEPMMPFG
310 320 330 340 350
ASAFKTHPQG HSYNSYTYPR LSEPTMCIPK VDYDRAQMVF SPPLSGSDTY
360 370 380 390 400
PRGPTKLPQS QSKAGYSSGS HQYPSGYHKA SLYHHPSLQT SSQYISTASY
410 420 430 440 450
LSSLSISSST YPPPSWGSSS DQQPSRVSHE QFRAALQLVV SPGDPREYLD
460 470 480 490 500
NFIKIGEGST GIVCIATEKH TGKQVAVKKM DLRKQQRREL LFNEVVIMRD
510 520 530 540 550
YHHDNVVDMY NSYLVGDELW VVMEFLEGGA LTDIVTHTRM NEEQIATVCL
560 570 580 590 600
SVLKALSYLH NQGVIHRDIK SDSILLTSDG RIKLSDFGFC AQVSKEVPKR
610 620 630 640 650
KSLVGTPYWM APEVISRLPY GTEVDIWSLG IMVIEMIDGE PPYFNEPPLQ
660 670 680 690 700
AMRRIRDSLP PRVKDLHKVS SMLRGFLDLM LVREPSQRAT AQELLGHPFL
710
KLAGPPSCIV PLMRQYRHH
Length:719
Mass (Da):80,948
Last modified:March 1, 2003 - v1
Checksum:i5E16D2318C238C8D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti315S → F in AAR37415 (PubMed:14517284).Curated1
Sequence conflicti320R → G in AAR37415 (PubMed:14517284).Curated1
Sequence conflicti454K → R in AAR37415 (PubMed:14517284).Curated1
Sequence conflicti522V → A in AAR37415 (PubMed:14517284).Curated1
Sequence conflicti664K → E in AAR37415 (PubMed:14517284).Curated1
Sequence conflicti687Q → R in AAR37415 (PubMed:14517284).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY487425 mRNA. Translation: AAR37415.1.
AK032593 mRNA. Translation: BAC27939.1.
AK163530 mRNA. Translation: BAE37385.1.
CCDSiCCDS16790.1.
RefSeqiNP_766446.2. NM_172858.2.
XP_006499572.1. XM_006499509.1.
XP_011237833.1. XM_011239531.1.
XP_017173706.1. XM_017318217.1.
XP_017173707.1. XM_017318218.1.
UniGeneiMm.131572.

Genome annotation databases

EnsembliENSMUST00000035264; ENSMUSP00000047285; ENSMUSG00000039913.
ENSMUST00000077200; ENSMUSP00000076440; ENSMUSG00000039913.
GeneIDi241656.
KEGGimmu:241656.
UCSCiuc008moh.1. mouse.

Similar proteinsi

Entry informationi

Entry nameiPAK5_MOUSE
AccessioniPrimary (citable) accession number: Q8C015
Secondary accession number(s): Q3TQJ7, Q6RWS7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 27, 2005
Last sequence update: March 1, 2003
Last modified: October 25, 2017
This is version 130 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families