PAK2_RABIT
ID PAK2_RABIT Reviewed; 524 AA.
AC Q29502;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Serine/threonine-protein kinase PAK 2;
DE EC=2.7.11.1;
DE AltName: Full=Gamma-PAK;
DE AltName: Full=p21-activated kinase 2;
DE Short=PAK-2;
DE AltName: Full=p21-activated protein kinase I;
DE Short=PAKI;
DE Contains:
DE RecName: Full=PAK-2p27;
DE Contains:
DE RecName: Full=PAK-2p34;
GN Name=PAK2;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8626411; DOI=10.1074/jbc.271.11.6206;
RA Jakobi R., Chen C., Tuazon P.T., Traugh J.A.;
RT "Molecular cloning and sequencing of the cytostatic G protein-activated
RT protein kinase PAK I.";
RL J. Biol. Chem. 271:6206-6211(1996).
CC -!- FUNCTION: Serine/threonine protein kinase that plays a role in a
CC variety of different signaling pathways including cytoskeleton
CC regulation, cell motility, cell cycle progression, apoptosis or
CC proliferation. Acts as downstream effector of the small GTPases CDC42
CC and RAC1. Activation by the binding of active CDC42 and RAC1 results in
CC a conformational change and a subsequent autophosphorylation on several
CC serine and/or threonine residues. Full-length PAK2 stimulates cell
CC survival and cell growth. Phosphorylates MAPK4 and MAPK6 and activates
CC the downstream target MAPKAPK5, a regulator of F-actin polymerization
CC and cell migration. Phosphorylates JUN and plays an important role in
CC EGF-induced cell proliferation. Phosphorylates many other substrates
CC including histone H4 to promote assembly of H3.3 and H4 into
CC nucleosomes, BAD, ribosomal protein S6, or MBP. Additionally,
CC associates with ARHGEF7 and GIT1 to perform kinase-independent
CC functions such as spindle orientation control during mitosis. On the
CC other hand, apoptotic stimuli such as DNA damage lead to caspase-
CC mediated cleavage of PAK2, generating PAK-2p34, an active p34 fragment
CC that translocates to the nucleus and promotes cellular apoptosis
CC involving the JNK signaling pathway. Caspase-activated PAK2
CC phosphorylates MKNK1 and reduces cellular translation (By similarity).
CC {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- ACTIVITY REGULATION: Activated by binding small G proteins. Binding of
CC GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers
CC from the autoinhibited dimer, enables phosphorylation of Thr-402 and
CC allows the kinase domain to adopt an active structure. Following
CC caspase cleavage, autophosphorylated PAK-2p34 is constitutively active
CC (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts tightly with GTP-bound but not GDP-bound CDC42/p21
CC and RAC1. Interacts with SH3MD4. Interacts with SCRIB. Interacts with
CC ARHGEF7 and GIT1. PAK-2p34 interacts with ARHGAP10. Interacts with RAC1
CC (By similarity). {ECO:0000250|UniProtKB:Q13177}.
CC -!- INTERACTION:
CC PRO_0000304927; Q6Y5D8: Arhgap10; Xeno; NbExp=3; IntAct=EBI-4406512, EBI-4396535;
CC PRO_0000304927; Q6Y5D8-1: Arhgap10; Xeno; NbExp=4; IntAct=EBI-4406512, EBI-4396677;
CC -!- SUBCELLULAR LOCATION: [Serine/threonine-protein kinase PAK 2]:
CC Cytoplasm {ECO:0000250}. Note=MYO18A mediates the cellular distribution
CC of the PAK2-ARHGEF7-GIT1 complex to the inner surface of the cell
CC membrane. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [PAK-2p34]: Nucleus {ECO:0000250}. Cytoplasm,
CC perinuclear region {ECO:0000250}. Membrane {ECO:0000250}; Lipid-anchor
CC {ECO:0000250}. Note=Interaction with ARHGAP10 probably changes PAK-2p34
CC location to cytoplasmic perinuclear region. {ECO:0000250}.
CC -!- PTM: Full-length PAK2 is autophosphorylated when activated by
CC CDC42/p21. Following cleavage, both peptides, PAK-2p27 and PAK-2p34,
CC become highly autophosphorylated. Autophosphorylation of PAK-2p27 can
CC occur in the absence of any effectors and is dependent on
CC phosphorylation of Thr-402, because PAK-2p27 is acting as an exogenous
CC substrate (By similarity). {ECO:0000250}.
CC -!- PTM: During apoptosis proteolytically cleaved by caspase-3 or caspase-
CC 3-like proteases to yield active PAK-2p34. {ECO:0000250}.
CC -!- PTM: Ubiquitinated, leading to its proteasomal degradation.
CC {ECO:0000250}.
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DR EMBL; U46915; AAC48537.1; -; mRNA.
DR RefSeq; NP_001076225.1; NM_001082756.1.
DR RefSeq; XP_017202139.1; XM_017346650.1.
DR AlphaFoldDB; Q29502; -.
DR SMR; Q29502; -.
DR IntAct; Q29502; 1.
DR STRING; 9986.ENSOCUP00000007111; -.
DR iPTMnet; Q29502; -.
DR Ensembl; ENSOCUT00000008227; ENSOCUP00000007111; ENSOCUG00000008224.
DR GeneID; 100009535; -.
DR KEGG; ocu:100009535; -.
DR CTD; 5062; -.
DR eggNOG; KOG0578; Eukaryota.
DR GeneTree; ENSGT00950000182988; -.
DR HOGENOM; CLU_000288_26_6_1; -.
DR InParanoid; Q29502; -.
DR OMA; IMMMEMA; -.
DR OrthoDB; 757766at2759; -.
DR TreeFam; TF105351; -.
DR BRENDA; 2.7.11.1; 1749.
DR Proteomes; UP000001811; Chromosome 14.
DR Bgee; ENSOCUG00000008224; Expressed in aorta and 16 other tissues.
DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; TAS:Reactome.
DR GO; GO:0030296; F:protein tyrosine kinase activator activity; IEA:Ensembl.
DR GO; GO:0031267; F:small GTPase binding; IEA:Ensembl.
DR GO; GO:0034333; P:adherens junction assembly; IEA:Ensembl.
DR GO; GO:0070830; P:bicellular tight junction assembly; IEA:Ensembl.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0060996; P:dendritic spine development; IEA:Ensembl.
DR GO; GO:0097194; P:execution phase of apoptosis; IMP:UniProtKB.
DR GO; GO:2001271; P:negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis; IEA:Ensembl.
DR GO; GO:0051497; P:negative regulation of stress fiber assembly; IEA:Ensembl.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0046777; P:protein autophosphorylation; IEA:Ensembl.
DR GO; GO:0150105; P:protein localization to cell-cell junction; IEA:Ensembl.
DR CDD; cd01093; CRIB_PAK_like; 1.
DR CDD; cd06655; STKc_PAK2; 1.
DR Gene3D; 3.90.810.10; -; 1.
DR InterPro; IPR000095; CRIB_dom.
DR InterPro; IPR036936; CRIB_dom_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR035065; PAK2.
DR InterPro; IPR033923; PAK_BD.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR035064; STK_PAK2.
DR PANTHER; PTHR45832:SF1; PTHR45832:SF1; 1.
DR Pfam; PF00786; PBD; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00285; PBD; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50108; CRIB; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Acetylation; Allosteric enzyme; ATP-binding; Cytoplasm; Kinase;
KW Lipoprotein; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q13177"
FT CHAIN 2..524
FT /note="Serine/threonine-protein kinase PAK 2"
FT /id="PRO_0000086467"
FT CHAIN 2..212
FT /note="PAK-2p27"
FT /evidence="ECO:0000250"
FT /id="PRO_0000304926"
FT CHAIN 213..524
FT /note="PAK-2p34"
FT /evidence="ECO:0000250"
FT /id="PRO_0000304927"
FT DOMAIN 74..87
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT DOMAIN 249..500
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..81
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 69..137
FT /note="Autoregulatory region"
FT /evidence="ECO:0000250"
FT REGION 69..112
FT /note="GTPase-binding"
FT /evidence="ECO:0000250"
FT REGION 88..248
FT /note="Linker"
FT REGION 169..188
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 204..228
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 245..251
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 61..78
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 213..228
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 368
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 255..263
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 278
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 212..213
FT /note="Cleavage; by caspase-3 or caspase-3-like proteases"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q13177"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13177"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13177"
FT MOD_RES 55
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13177"
FT MOD_RES 58
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13177"
FT MOD_RES 60
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13177"
FT MOD_RES 62
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8CIN4"
FT MOD_RES 64
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13177"
FT MOD_RES 128
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q13177"
FT MOD_RES 134
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13177"
FT MOD_RES 139
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q13177"
FT MOD_RES 141
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13177"
FT MOD_RES 143
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13177"
FT MOD_RES 152
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CIN4"
FT MOD_RES 159
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8CIN4"
FT MOD_RES 169
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13177"
FT MOD_RES 197
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13177"
FT MOD_RES 402
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
SQ SEQUENCE 524 AA; 58028 MW; 397D71020EADFFCA CRC64;
MSDNGELEDK PPAPPVRMSS TIFSTGGKDP LSANHSLKPL PSVPEEKKPR NKIISIFSGT
EKGSKKKEKE RPEISPPSDF EHTIHVGFDA VTGEFTGMPE QWARLLQTSN ITKLEQKKNP
QAVLDVLKFY DSNTVKQKYL SFTPPEKDGF PSGAPALNTK VSETSAVVTE EDDDDEEAAP
PVIAPRPDHT KSIYTRSVID PIPAPVGDSH VDSGAKSSDK QKKKTKMTDE EIMEKLRTIV
SIGDPKKKYT RYEKIGQGAS GTVFTATDVA LGQEVAIKQI NLQKQPKKEL IINEILVMKE
LKNPNIVNFL DSYLVGDELF VVMEYLAGGS LTDVVTETCM DEAQIAAVCR ECLQALEFLH
ANQVIHRDIK SDNVLLGMEG SVKLTDFGFC AQITPEQSKR STMVGTPYWM APEVVTRKAY
GPKVDIWSLG IMAIEMVEGE PPYLNENPLR ALYLIATNGT PELQNPEKLS PIFRDFLNRC
LEMDVEKRGS AKELLQHPFL KLAKPLSSLT PLIMAAKEAM KSNR
