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Q8BTW9 (PAK4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein kinase PAK 4

EC=2.7.11.1
Alternative name(s):
p21-activated kinase 4
Short name=PAK-4
Gene names
Name:Pak4
Synonyms:Kiaa1142
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length593 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6 Ref.11

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Subunit structure

Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and weakly with RAC1 By similarity. Interacts with FGFR2 and GRB2. Ref.1

Subcellular location

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.

Post-translational modification

Autophosphorylated on serine residues when activated by CDC42/p21 By similarity. Ref.1

Phosphorylated on tyrosine residues upon stimulation of FGFR2. Ref.1

Disruption phenotype

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. Ref.7 Ref.12

Sequence similarities

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.

Contains 1 CRIB domain.

Contains 1 protein kinase domain.

Sequence caution

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 593593Serine/threonine-protein kinase PAK 4
PRO_0000086475

Regions

Domain11 – 2414CRIB
Domain323 – 574252Protein kinase
Nucleotide binding329 – 3379ATP By similarity
Region25 – 322298Linker
Compositional bias4 – 74Poly-Lys
Compositional bias105 – 1084Poly-Pro
Compositional bias216 – 29883Pro-rich
Compositional bias242 – 2465Poly-Ser

Sites

Active site4421Proton acceptor By similarity
Binding site3521ATP By similarity

Amino acid modifications

Modified residue411Phosphoserine By similarity
Modified residue1041Phosphoserine By similarity
Modified residue1481Phosphoserine By similarity
Modified residue1811Phosphoserine Ref.1 Ref.10
Modified residue1871Phosphothreonine By similarity
Modified residue1951Phosphoserine By similarity
Modified residue2571Phosphoserine By similarity
Modified residue2661Phosphoserine By similarity
Modified residue2931Phosphoserine By similarity
Modified residue4761Phosphoserine; by autocatalysis Ref.1 Ref.8 Ref.9

Experimental info

Sequence conflict51K → R in AAO61496. Ref.1
Sequence conflict2481P → L in AAO61496. Ref.1
Sequence conflict5641T → P in BAB30889. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Q8BTW9 [UniParc].

Last modified March 1, 2003. Version 1.
Checksum: 4AFA91DD73D4C6D5

FASTA59364,623
        10         20         30         40         50         60 
MFGKKKKRVE ISAPSNFEHR VHTGFDQHEQ KFTGLPRQWQ SLIEESARRP KPLIDPACIT 

        70         80         90        100        110        120 
SIQPGAPKTI VRGSKGAKDG ALTLLLDEFE NMSVTRSNSL RRESPPPPAR AHQENGMLEE 

       130        140        150        160        170        180 
RAAPARMAPD KAGSRARATG HSEAGSGSGD RRRVGPEKRP KSSRDGPGGP QEASRDKRPL 

       190        200        210        220        230        240 
SGPDVSTPQP GSLTSGTKLA AGRPFNTYPR ADTDHPPRGA QGEPHTMAPN GPSATGLAAP 

       250        260        270        280        290        300 
QSSSSSRPPT RARGAPSPGV LGPHASEPQL APPARALAAP AVPPAPGPPG PRSPQREPQR 

       310        320        330        340        350        360 
VSHEQFRAAL QLVVDPGDPR SYLDNFIKIG EGSTGIVCIA TVRSSGKLVA VKKMDLRKQQ 

       370        380        390        400        410        420 
RRELLFNEVV IMRDYRHENV VEMYNSYLVG DELWVVMEFL EGGALTDIVT HTRMNEEQIA 

       430        440        450        460        470        480 
AVCLAVLQAL AVLHAQGVIH RDIKSDSILL THDGRVKLSD FGFCAQVSKE VPRRKSLVGT 

       490        500        510        520        530        540 
PYWMAPELIS RLPYGPEVDI WSLGVMVIEM VDGEPPYFNE PPLKAMKMIR DNLPPRLKNL 

       550        560        570        580        590 
HKASPSLKGF LDRLLVRDPA QRATAAELLK HPFLTKAGPP ASIVPLMRQH RTR 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Phosphoproteomic analysis of the developing mouse brain."
Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.
Mol. Cell. Proteomics 3:1093-1101(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-476, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic brain.
[9]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS21049.1.
RefSeqNP_081746.1. NM_027470.3.
XP_006540419.1. XM_006540356.1.
UniGeneMm.21876.

3D structure databases

ProteinModelPortalQ8BTW9.
SMRQ8BTW9. Positions 10-44, 300-593.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid214149. 1 interaction.
IntActQ8BTW9. 1 interaction.
MINTMINT-4106515.
STRING10090.ENSMUSP00000103918.

PTM databases

PhosphoSiteQ8BTW9.

Proteomic databases

MaxQBQ8BTW9.
PaxDbQ8BTW9.
PRIDEQ8BTW9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000032823; ENSMUSP00000032823; ENSMUSG00000030602.
ENSMUST00000108283; ENSMUSP00000103918; ENSMUSG00000030602.
GeneID70584.
KEGGmmu:70584.
UCSCuc009fzh.1. mouse.

Organism-specific databases

CTD10298.
MGIMGI:1917834. Pak4.
RougeSearch...

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00670000097939.
HOGENOMHOG000234205.
HOVERGENHBG108518.
InParanoidQ8BTW9.
KOK05734.
OMAIDPACIT.
OrthoDBEOG73804D.
PhylomeDBQ8BTW9.
TreeFamTF105352.

Gene expression databases

BgeeQ8BTW9.
CleanExMM_PAK4.
GenevestigatorQ8BTW9.

Family and domain databases

Gene3D3.90.810.10. 1 hit.
InterProIPR000095. CRIB_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
[Graphical view]
PfamPF00786. PBD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00285. PBD. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS50108. CRIB. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPAK4. mouse.
NextBio331922.
PROQ8BTW9.
SOURCESearch...

Entry information

Entry namePAK4_MOUSE
AccessionPrimary (citable) accession number: Q8BTW9
Secondary accession number(s): Q6ZPX0, Q80Z97, Q9CS71
Entry history
Integrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: March 1, 2003
Last modified: July 9, 2014
This is version 104 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot