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Q8BTW9

- PAK4_MOUSE

UniProt

Q8BTW9 - PAK4_MOUSE

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Protein

Serine/threonine-protein kinase PAK 4

Gene

Pak4

Organism
Mus musculus (Mouse)
Status
Reviewed - 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, growth, 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 and inactivates the protein phosphatase SSH1, leading to increased inhibitory phosphorylation of the actin binding/depolymerizing factor cofilin. Decreased cofilin activity may lead to stabilization of actin filaments. Phosphorylates LIMK1, a kinase that also inhibits the activity of cofilin. Phosphorylates integrin beta5/ITGB5 and thus regulates cell motility. Phosphorylates ARHGEF2 and activates the downstream target RHOA that plays a role in the regulation of assembly of focal adhesions and actin stress fibers. Stimulates cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Alternatively, inhibits apoptosis by preventing caspase-8 binding to death domain receptors in a kinase independent manner. Plays a role in cell-cycle progression by controlling levels of the cell-cycle regulatory protein CDKN1A and by phosphorylating RAN.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei352 – 3521ATPPROSITE-ProRule annotation
Active sitei442 – 4421Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi329 – 3379ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. protein serine/threonine kinase activity Source: UniProtKB-KW

GO - Biological processi

  1. apoptotic process Source: UniProtKB-KW
  2. cell cycle Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Cell cycle

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_260744. Activation of Rac.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase PAK 4 (EC:2.7.11.1)
Alternative name(s):
p21-activated kinase 4
Short name:
PAK-4
Gene namesi
Name:Pak4
Synonyms:Kiaa1142
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 7

Organism-specific databases

MGIiMGI:1917834. Pak4.

Subcellular locationi

Cytoplasm
Note: Seems to shuttle between cytoplasmic compartments depending on the activating effector. For example, can be found on the cell periphery after activation of growth-factor or integrin-mediated signaling pathways (By similarity).By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Disruption phenotypei

Mice die at embryonic day 11.5 probably due to a defect in the fetal heart. They show strong defects in neuronal development and axonal outgrowth. Spinal cord motor neurons and interneurons failed to differentiate and migrate to their proper position. Nervous system-specific conditional PAK4 deletion mice display growth retardation and die prematurely.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 593593Serine/threonine-protein kinase PAK 4PRO_0000086475Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei41 – 411PhosphoserineBy similarity
Modified residuei104 – 1041PhosphoserineBy similarity
Modified residuei148 – 1481PhosphoserineBy similarity
Modified residuei181 – 1811Phosphoserine1 Publication
Modified residuei187 – 1871PhosphothreonineBy similarity
Modified residuei195 – 1951PhosphoserineBy similarity
Modified residuei257 – 2571PhosphoserineBy similarity
Modified residuei266 – 2661PhosphoserineBy similarity
Modified residuei293 – 2931PhosphoserineBy similarity
Modified residuei476 – 4761Phosphoserine; by autocatalysis2 Publications

Post-translational modificationi

Autophosphorylated on serine residues when activated by CDC42/p21.By similarity
Phosphorylated on tyrosine residues upon stimulation of FGFR2.4 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ8BTW9.
PaxDbiQ8BTW9.
PRIDEiQ8BTW9.

PTM databases

PhosphoSiteiQ8BTW9.

Expressioni

Gene expression databases

BgeeiQ8BTW9.
CleanExiMM_PAK4.
ExpressionAtlasiQ8BTW9. baseline and differential.
GenevestigatoriQ8BTW9.

Interactioni

Subunit structurei

Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and weakly with RAC1 (By similarity). Interacts with FGFR2 and GRB2.By similarity1 Publication

Protein-protein interaction databases

BioGridi214149. 1 interaction.
IntActiQ8BTW9. 1 interaction.
MINTiMINT-4106515.
STRINGi10090.ENSMUSP00000103918.

Structurei

3D structure databases

ProteinModelPortaliQ8BTW9.
SMRiQ8BTW9. Positions 10-44, 300-593.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini11 – 2414CRIBPROSITE-ProRule annotationAdd
BLAST
Domaini323 – 574252Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni25 – 322298LinkerAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi4 – 74Poly-Lys
Compositional biasi105 – 1084Poly-Pro
Compositional biasi216 – 29883Pro-richAdd
BLAST
Compositional biasi242 – 2465Poly-Ser

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00390000015877.
HOGENOMiHOG000234205.
HOVERGENiHBG108518.
InParanoidiQ8BTW9.
KOiK05734.
OMAiIDPACIT.
OrthoDBiEOG73804D.
PhylomeDBiQ8BTW9.
TreeFamiTF105352.

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.
[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.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8BTW9-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MFGKKKKRVE ISAPSNFEHR VHTGFDQHEQ KFTGLPRQWQ SLIEESARRP
60 70 80 90 100
KPLIDPACIT SIQPGAPKTI VRGSKGAKDG ALTLLLDEFE NMSVTRSNSL
110 120 130 140 150
RRESPPPPAR AHQENGMLEE RAAPARMAPD KAGSRARATG HSEAGSGSGD
160 170 180 190 200
RRRVGPEKRP KSSRDGPGGP QEASRDKRPL SGPDVSTPQP GSLTSGTKLA
210 220 230 240 250
AGRPFNTYPR ADTDHPPRGA QGEPHTMAPN GPSATGLAAP QSSSSSRPPT
260 270 280 290 300
RARGAPSPGV LGPHASEPQL APPARALAAP AVPPAPGPPG PRSPQREPQR
310 320 330 340 350
VSHEQFRAAL QLVVDPGDPR SYLDNFIKIG EGSTGIVCIA TVRSSGKLVA
360 370 380 390 400
VKKMDLRKQQ RRELLFNEVV IMRDYRHENV VEMYNSYLVG DELWVVMEFL
410 420 430 440 450
EGGALTDIVT HTRMNEEQIA AVCLAVLQAL AVLHAQGVIH RDIKSDSILL
460 470 480 490 500
THDGRVKLSD FGFCAQVSKE VPRRKSLVGT PYWMAPELIS RLPYGPEVDI
510 520 530 540 550
WSLGVMVIEM VDGEPPYFNE PPLKAMKMIR DNLPPRLKNL HKASPSLKGF
560 570 580 590
LDRLLVRDPA QRATAAELLK HPFLTKAGPP ASIVPLMRQH RTR
Length:593
Mass (Da):64,623
Last modified:March 1, 2003 - v1
Checksum:i4AFA91DD73D4C6D5
GO

Sequence cautioni

The sequence BAC98108.2 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti5 – 51K → R in AAO61496. (PubMed:12529371)Curated
Sequence conflicti248 – 2481P → L in AAO61496. (PubMed:12529371)Curated
Sequence conflicti564 – 5641T → P in BAB30889. (PubMed:16141072)Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY217016 mRNA. Translation: AAO61496.1.
AK129298 mRNA. Translation: BAC98108.2. Different initiation.
AK017713 mRNA. Translation: BAB30889.1.
AK088512 mRNA. Translation: BAC40396.1.
BC048238 mRNA. Translation: AAH48238.1.
CCDSiCCDS21049.1.
RefSeqiNP_081746.1. NM_027470.3.
XP_006540419.1. XM_006540356.1.
UniGeneiMm.21876.

Genome annotation databases

EnsembliENSMUST00000032823; ENSMUSP00000032823; ENSMUSG00000030602.
ENSMUST00000108283; ENSMUSP00000103918; ENSMUSG00000030602.
GeneIDi70584.
KEGGimmu:70584.
UCSCiuc009fzh.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY217016 mRNA. Translation: AAO61496.1 .
AK129298 mRNA. Translation: BAC98108.2 . Different initiation.
AK017713 mRNA. Translation: BAB30889.1 .
AK088512 mRNA. Translation: BAC40396.1 .
BC048238 mRNA. Translation: AAH48238.1 .
CCDSi CCDS21049.1.
RefSeqi NP_081746.1. NM_027470.3.
XP_006540419.1. XM_006540356.1.
UniGenei Mm.21876.

3D structure databases

ProteinModelPortali Q8BTW9.
SMRi Q8BTW9. Positions 10-44, 300-593.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 214149. 1 interaction.
IntActi Q8BTW9. 1 interaction.
MINTi MINT-4106515.
STRINGi 10090.ENSMUSP00000103918.

PTM databases

PhosphoSitei Q8BTW9.

Proteomic databases

MaxQBi Q8BTW9.
PaxDbi Q8BTW9.
PRIDEi Q8BTW9.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000032823 ; ENSMUSP00000032823 ; ENSMUSG00000030602 .
ENSMUST00000108283 ; ENSMUSP00000103918 ; ENSMUSG00000030602 .
GeneIDi 70584.
KEGGi mmu:70584.
UCSCi uc009fzh.1. mouse.

Organism-specific databases

CTDi 10298.
MGIi MGI:1917834. Pak4.
Rougei Search...

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00390000015877.
HOGENOMi HOG000234205.
HOVERGENi HBG108518.
InParanoidi Q8BTW9.
KOi K05734.
OMAi IDPACIT.
OrthoDBi EOG73804D.
PhylomeDBi Q8BTW9.
TreeFami TF105352.

Enzyme and pathway databases

Reactomei REACT_260744. Activation of Rac.

Miscellaneous databases

ChiTaRSi Pak4. mouse.
NextBioi 331922.
PROi Q8BTW9.
SOURCEi Search...

Gene expression databases

Bgeei Q8BTW9.
CleanExi MM_PAK4.
ExpressionAtlasi Q8BTW9. baseline and differential.
Genevestigatori Q8BTW9.

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.
[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.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "p21-activated protein kinase 4 (PAK4) interacts with the keratinocyte growth factor receptor and participates in keratinocyte growth factor-mediated inhibition of oxidant-induced cell death."
    Lu Y., Pan Z.-Z., Devaux Y., Ray P.
    J. Biol. Chem. 278:10374-10380(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH FGFR2 AND GRB2, PHOSPHORYLATION AT TYROSINE RESIDUES.
    Strain: BALB/c.
  2. "Prediction of the coding sequences of mouse homologues of KIAA gene: III. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
    Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Nagase T., Ohara O., Koga H.
    DNA Res. 10:167-180(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Embryonic tail.
  3. Okazaki N., Kikuno R., Nagase T., Ohara O., Koga H.
    Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: SEQUENCE REVISION.
  4. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: NOD.
    Tissue: Embryo and Thymus.
  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].
    Strain: FVB/N.
    Tissue: Colon.
  6. "Cytoskeletal changes regulated by the PAK4 serine/threonine kinase are mediated by LIM kinase 1 and cofilin."
    Dan C., Kelly A., Bernard O., Minden A.
    J. Biol. Chem. 276:32115-32121(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF LIMK1.
  7. "PAK4 kinase is essential for embryonic viability and for proper neuronal development."
    Qu J., Li X., Novitch B.G., Zheng Y., Kohn M., Xie J.M., Kozinn S., Bronson R., Beg A.A., Minden A.
    Mol. Cell. Biol. 23:7122-7133(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  8. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-476, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Embryonic brain.
  9. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-476, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  10. "The phagosomal proteome in interferon-gamma-activated macrophages."
    Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
    Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  11. "PAK4 is required for regulation of the cell-cycle regulatory protein p21, and for control of cell-cycle progression."
    Nekrasova T., Minden A.
    J. Cell. Biochem. 112:1795-1806(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  12. "A key role for Pak4 in proliferation and differentiation of neural progenitor cells."
    Tian Y., Lei L., Minden A.
    Dev. Biol. 353:206-216(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.

Entry informationi

Entry nameiPAK4_MOUSE
AccessioniPrimary (citable) accession number: Q8BTW9
Secondary accession number(s): Q6ZPX0, Q80Z97, Q9CS71
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: March 1, 2003
Last modified: November 26, 2014
This is version 107 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

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

External Data

Dasty 3