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Reviewed, UniProtKB/Swiss-Prot Q13177 (PAK2_HUMAN)

Last modified January 19, 2010. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Serine/threonine-protein kinase PAK 2
    EC=2.7.11.1
Alternative name(s):
    p21-activated kinase 2
      Short name=PAK-2
    Gamma-PAK
    PAK65
    S6/H4 kinase
    p58
Cleaved into the following 2 chains:
    1- Recommended name:
            PAK-2p27
                Short name=p27
    2- Recommended name:
            PAK-2p34
                Short name=p34
        Alternative name(s):
            C-t-PAK2
Gene names
Name: PAK2
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length524 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

The activated kinase acts on a variety of targets. Phosphorylates ribosomal protein S6, histone H4 and myelin basic protein. Full length PAK 2 stimulates cell survival and cell growth. The process is, at least in part, mediated by phosphorylation and inhibition of pro-apoptotic BAD. Caspase-activated PAK-2p34 is involved in cell death response, probably involving the JNK signaling pathway. Cleaved PAK-2p34 seems to have a higher activity than the CDC42-activated form. Ref.6 Ref.9 Ref.14

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

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-402 and allows the kinase domain to adopt an active structure By similarity. Following caspase cleavage, autophosphorylted PAK-2p34 is constitutively active.

Subunit structure

Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and RAC1. Interacts with SH3MD4. Interacts with and activated by HIV-1 Nef. PAK-2p34 interacts with ARHGAP10. Interacts with SCRIB. Ref.8 Ref.10 Ref.12 Ref.15

Subcellular location

Serine/threonine-protein kinase PAK 2: Cytoplasm Ref.9 Ref.14 Ref.10.

PAK-2p34: Nucleus. Cytoplasmperinuclear region. Membrane; Lipid-anchor. Note: Interaction with ARHGAP10 probably changes PAK-2p34 location to cytoplasmic perinuclear region. Myristoylation changes PAK-2p34 location to the membrane. Ref.9 Ref.14 Ref.10

Tissue specificity

Ubiquitously expressed. Higher levels seen in skeletal muscle, ovary, thymus and spleen.

Post-translational modification

Full length PAK 2 is autophosphorylated when activated by CDC42/p21. Following cleavage, both peptides, PAK-2p27 and PAK-2p34, become highly autophosphorylated, with PAK-2p27 being phosphorylated on serine and PAK-2p34 on threonine residues, respectively. Autophosphorylation of PAK-2p27 can occur in the absence of any effectors and is dependent on phosphorylation of Thr-402, because PAK-2p27 is acting as an exogenous substrate. Ref.5 Ref.7 Ref.11 Ref.13 Ref.16 Ref.17 Ref.19 Ref.20

During apoptosis proteolytically cleaved by caspase-3 or caspase-3-like proteases to yield active PAK-2p34. Ref.6 Ref.7

Ubiquitinated, leading to its proteosomal degradation. Ref.9

PAK-2p34 is myristoylated.

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.

Ontologies

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 524524Serine/threonine-protein kinase PAK 2
PRO_0000086465
Chain1 – 212212PAK-2p27
PRO_0000304922
Chain213 – 524312PAK-2p34
PRO_0000304923

Regions

Domain74 – 8714CRIB
Domain249 – 499251Protein kinase
Nucleotide binding255 – 2639ATP By similarity
Region69 – 13769Autoregulatory region By similarity
Region69 – 11244GTPase-binding By similarity
Motif245 – 2517Nuclear localization signal

Sites

Active site3671Proton acceptor By similarity
Binding site2781ATP By similarity
Site212 – 2132Cleavage; by caspase-3 or caspase-3-like proteases

Amino acid modifications

Modified residue21Phosphoserine Ref.11
Modified residue381N6-acetyllysine Ref.21
Modified residue551Phosphoserine Ref.20
Modified residue581Phosphoserine Ref.17 Ref.19
Modified residue601Phosphothreonine Ref.16
Modified residue1281N6-acetyllysine Ref.21
Modified residue1391Phosphotyrosine By similarity
Modified residue1411Phosphoserine Ref.11 Ref.13 Ref.17 Ref.19 Ref.20
Modified residue1431Phosphothreonine Ref.11 Ref.20
Modified residue1691Phosphothreonine Ref.17
Modified residue1971Phosphoserine Ref.20
Modified residue4021Phosphothreonine; by autocatalysis Probable
Lipidation2131N-myristoyl glycine Ref.14

Experimental info

Mutagenesis2121D → N: Inhibits caspase-mediated cleavage. Ref.6
Mutagenesis2131G → A: Abolishes myristoylation of PAK-2p34 and membrane location.
Mutagenesis239 – 2435IVSIG → REGRS: Abolishes nuclear export. Ref.9
Mutagenesis246 – 2483KKK → MHE: Greatly inhibits nuclear localization. Ref.9
Mutagenesis2781K → R: Abolishes kinase activity and autophosphorylation. Ref.7
Mutagenesis4021T → A: Abolishes kinase activity and greatly inhibits autophosphorylation of PAK-2p27 and PAK-2p34. Ref.7
Sequence conflict901A → T in AAA75468. Ref.3
Sequence conflict1501F → L in AAA65442. Ref.1
Sequence conflict2251T → P in AAA65442. Ref.1
Sequence conflict2581G → R in AAH69613. Ref.2
Sequence conflict3291G → R in AAA75468. Ref.3
Sequence conflict3381T → TA in AAA65442. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q13177-1 [UniParc].

Last modified April 3, 2007. Version 3.
Checksum: 00A7CD15F93D4180

FASTA52458,043
        10         20         30         40         50         60 
MSDNGELEDK PPAPPVRMSS TIFSTGGKDP LSANHSLKPL PSVPEEKKPR HKIISIFSGT 

        70         80         90        100        110        120 
EKGSKKKEKE RPEISPPSDF EHTIHVGFDA VTGEFTGMPE QWARLLQTSN ITKLEQKKNP 

       130        140        150        160        170        180 
QAVLDVLKFY DSNTVKQKYL SFTPPEKDGF PSGTPALNAK GTEAPAVVTE EEDDDEETAP 

       190        200        210        220        230        240 
PVIAPRPDHT KSIYTRSVID PVPAPVGDSH VDGAAKSLDK QKKKTKMTDE EIMEKLRTIV 

       250        260        270        280        290        300 
SIGDPKKKYT RYEKIGQGAS GTVFTATDVA LGQEVAIKQI NLQKQPKKEL IINEILVMKE 

       310        320        330        340        350        360 
LKNPNIVNFL DSYLVGDELF VVMEYLAGGS LTDVVTETCM DEAQIAAVCR ECLQALEFLH 

       370        380        390        400        410        420 
ANQVIHRDIK SDNVLLGMEG SVKLTDFGFC AQITPEQSKR STMVGTPYWM APEVVTRKAY 

       430        440        450        460        470        480 
GPKVDIWSLG IMAIEMVEGE PPYLNENPLR ALYLIATNGT PELQNPEKLS PIFRDFLNRC 

       490        500        510        520 
LEMDVEKRGS AKELLQHPFL KLAKPLSSLT PLIMAAKEAM KSNR 

« Hide

References

« Hide 'large scale' references
[1]Sells M., Knause U.J., Bagrodia S., Ambrose D., Bokoch G.M., Chernoff J.
Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]"A novel serine kinase activated by rac1/CDC42Hs-dependent autophosphorylation is related to PAK65 and STE20."
Martin G.A., Bollag G., McCormick F., Abo A.
EMBO J. 14:1970-1978(1995) [PubMed: 7744004] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 32-524, PROTEIN SEQUENCE OF 401-417.
Tissue: Placenta.
[4]Erratum
Martin G.A., Bollag G., McCormick F., Abo A.
EMBO J. 14:4385-4385(1995) [PubMed: 7556080] [Abstract]
[5]"Activation of an S6/H4 kinase (PAK 65) from human placenta by intramolecular and intermolecular autophosphorylation."
Benner G.E., Dennis P.B., Masaracchia R.A.
J. Biol. Chem. 270:21121-21128(1995) [PubMed: 7673144] [Abstract]
Cited for: AUTOPHOSPHORYLATION.
[6]"Membrane and morphological changes in apoptotic cells regulated by caspase-mediated activation of PAK2."
Rudel T., Bokoch G.M.
Science 276:1571-1574(1997) [PubMed: 9171063] [Abstract]
Cited for: CASPASE-3 CLEAVAGE AT ASP-512, FUNCTION, MUTAGENESIS OF ASP-212.
[7]"Cleavage and activation of p21-activated protein kinase gamma-PAK by CPP32 (caspase 3). Effects of autophosphorylation on activity."
Walter B.N., Huang Z., Jakobi R., Tuazon P.T., Alnemri E.S., Litwack G., Traugh J.A.
J. Biol. Chem. 273:28733-28739(1998) [PubMed: 9786869] [Abstract]
Cited for: CASPASE-3 CLEAVAGE AT ASP-512, AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-278 AND THR-402.
[8]"Lentivirus Nef specifically activates Pak2."
Arora V.K., Molina R.P., Foster J.L., Blakemore J.L., Chernoff J., Fredericksen B.L., Garcia J.V.
J. Virol. 74:11081-11087(2000) [PubMed: 11070003] [Abstract]
Cited for: INTERACTION WITH HIV-1 NEF.
[9]"Caspase-activated PAK-2 is regulated by subcellular targeting and proteasomal degradation."
Jakobi R., McCarthy C.C., Koeppel M.A., Stringer D.K.
J. Biol. Chem. 278:38675-38685(2003) [PubMed: 12853446] [Abstract]
Cited for: FUNCTION (PAK-2P34), UBIQUITINATION, SUBCELLULAR LOCATION, MUTAGENESIS OF 239-ILE--GLY-243 AND 246-LYS--LYS-248.
[10]"Identification and characterization of PS-GAP as a novel regulator of caspase-activated PAK-2."
Koeppel M.A., McCarthy C.C., Moertl E., Jakobi R.
J. Biol. Chem. 279:53653-53664(2004) [PubMed: 15471851] [Abstract]
Cited for: INTERACTION WITH ARHGAP10, SUBCELLULAR LOCATION.
[11]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed: 17081983] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; SER-141 AND THR-143, MASS SPECTROMETRY.
Tissue: Epithelium.
[12]"Identification of preferred protein interactions by phage-display of the human Src homology-3 proteome."
Kaerkkaeinen S., Hiipakka M., Wang J.-H., Kleino I., Vaehae-Jaakkola M., Renkema G.H., Liss M., Wagner R., Saksela K.
EMBO Rep. 7:186-191(2006) [PubMed: 16374509] [Abstract]
Cited for: INTERACTION WITH SH3MD4.
[13]"A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.
Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-141, MASS SPECTROMETRY.
Tissue: Epithelium.
[14]"Posttranslational myristoylation of caspase-activated p21-activated protein kinase 2 (PAK2) potentiates late apoptotic events."
Vilas G.L., Corvi M.M., Plummer G.J., Seime A.M., Lambkin G.R., Berthiaume L.G.
Proc. Natl. Acad. Sci. U.S.A. 103:6542-6547(2006) [PubMed: 16617111] [Abstract]
Cited for: FUNCTION (PAK-2P34), MYRISTOYLATION AT GLY-213 (PAK-2P34), SUBCELLULAR LOCATION.
[15]"Scrib regulates PAK activity during the cell migration process."
Nola S., Sebbagh M., Marchetto S., Osmani N., Nourry C., Audebert S., Navarro C., Rachel R., Montcouquiol M., Sans N., Etienne-Manneville S., Borg J.-P., Santoni M.-J.
Hum. Mol. Genet. 17:3552-3565(2008) [PubMed: 18716323] [Abstract]
Cited for: INTERACTION WITH SCRIB.
[16]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-60, MASS SPECTROMETRY.
Tissue: Platelet.
[17]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58; SER-141 AND THR-169, MASS SPECTROMETRY.
[18]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[19]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58 AND SER-141, MASS SPECTROMETRY.
[20]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-55; SER-141; THR-143 AND SER-197, MASS SPECTROMETRY.
Tissue: T-cell.
[21]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed: 19608861] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-38 AND LYS-128, MASS SPECTROMETRY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U24153 mRNA. Translation: AAA65442.1.
BC069613 mRNA. Translation: AAH69613.1.
U25975 mRNA. Translation: AAA75468.1.
IPIIPI00419979.
PIRS58682.
RefSeqNP_002568.2.
UniGeneHs.518530

3D structure databases

SMRQ13177. Positions 77-143, 228-519.
ModBaseSearch...

Protein-protein interaction databases

IntActQ13177. 47 interactions.
STRINGQ13177.

PTM databases

PhosphoSiteQ13177.

2-D gel databases

OGPQ13177.

Proteomic databases

PRIDEQ13177.

Genome annotation databases

EnsemblENST00000327134; ENSP00000314067; ENSG00000180370; Homo sapiens. [Genome view]
GeneID5062.
KEGGhsa:5062.
UCSCuc003fwy.2. human.

Organism-specific databases

CTD5062.
GeneCardsGC03P197955.
H-InvDBHIX0030815.
HGNCHGNC:8591. PAK2.
HPACAB007794.
MIM605022. gene.
PharmGKBPA32918.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG08571.
HOGENOMHBG755340.
HOVERGENQ13177.
InParanoidQ13177.
OMANVDGGAK.
OrthoDBEOG96MF4W.
PhylomeDBQ13177.

Enzyme and pathway databases

BRENDA2.7.11.1. 247.
Pathway_Interaction_DBfaspathway. FAS signaling pathway (CD95).
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
p38alphabetapathway. Regulation of p38-alpha and p38-beta.
ReactomeREACT_18266. Axon guidance.
REACT_578. Apoptosis.
REACT_6185. HIV Infection.
REACT_6900. Signaling in Immune system.

Gene expression databases

ArrayExpressQ13177.
BgeeQ13177.
CleanExHS_PAK2.
GenevestigatorQ13177.
GermOnlineENSG00000180370. Homo sapiens.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000095. PAK_box_Rho_bd.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_prot_kinase-like_dom.
IPR015750. Ser/Thr_kinase_Pak-rel.
IPR008271. Ser/Thr_prot_kinase_AS.
IPR002290. Ser/Thr_prot_kinase_dom.
[Graphical view]
PANTHERPTHR22986:SF84. Pak_like. 1 hit.
PfamPF00786. PBD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00285. PBD. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
PROSITEPS50108. CRIB. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio19496.
PMAP-CutDBQ13177.
SOURCESearch...

Entry information

Entry namePAK2_HUMAN
AccessionPrimary (citable) accession number: Q13177
Secondary accession number(s): Q13154, Q6ISC3
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: April 3, 2007
Last modified: January 19, 2010
This is version 109 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents