PAK5_RAT
ID PAK5_RAT Reviewed; 718 AA.
AC D4A280;
DT 19-OCT-2011, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=Serine/threonine-protein kinase PAK 5;
DE EC=2.7.11.1;
DE AltName: Full=p21-activated kinase 5;
DE Short=PAK-5;
DE AltName: Full=p21-activated kinase 7;
DE Short=PAK-7;
GN Name=Pak5; Synonyms=Pak7;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP INTERACTION WITH MARK2.
RX PubMed=16014608; DOI=10.1091/mbc.e05-01-0081;
RA Matenia D., Griesshaber B., Li X.Y., Thiessen A., Johne C., Jiao J.,
RA Mandelkow E., Mandelkow E.M.;
RT "PAK5 kinase is an inhibitor of MARK/Par-1, which leads to stable
RT microtubules and dynamic actin.";
RL Mol. Biol. Cell 16:4410-4422(2005).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-104 AND THR-107, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Serine/threonine protein kinase that plays a role in a
CC variety of different signaling pathways including cytoskeleton
CC regulation, cell migration, proliferation or cell survival. Activation
CC by various effectors including growth factor receptors or active CDC42
CC and RAC1 results in a conformational change and a subsequent
CC autophosphorylation on several serine and/or threonine residues.
CC Phosphorylates the proto-oncogene RAF and stimulates its kinase
CC activity. Promotes cell survival by phosphorylating the BCL2 antagonist
CC of cell death BAD. Phosphorylates CTNND1, probably to regulate
CC cytoskeletal organization and cell morphology. Keeps microtubules
CC stable through MARK2 inhibition and destabilizes the F-actin network
CC leading to the disappearance of stress fibers and focal adhesions (By
CC similarity). {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 -!- SUBUNIT: Interacts tightly with GTP-bound but not GDP-bound CDC42/p21
CC and RAC1. Interacts with MARK2, leading to inhibit MARK2 independently
CC of kinase activity. Interacts with RHOD and RHOH (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250}. Cytoplasm
CC {ECO:0000250}. Nucleus {ECO:0000250}. Note=Shuttles between the nucleus
CC and the mitochondria, and mitochondrial localization is essential for
CC the role in cell survival. {ECO:0000250}.
CC -!- DOMAIN: An autoinhibitory domain is present in the N-terminal region of
CC the protein. {ECO:0000250}.
CC -!- PTM: Autophosphorylated when activated by CDC42/p21. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily. {ECO:0000305}.
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DR EMBL; CH473949; EDL80300.1; -; Genomic_DNA.
DR RefSeq; NP_001101251.1; NM_001107781.1.
DR RefSeq; XP_017447245.1; XM_017591756.1.
DR RefSeq; XP_017447246.1; XM_017591757.1.
DR RefSeq; XP_017447247.1; XM_017591758.1.
DR AlphaFoldDB; D4A280; -.
DR SMR; D4A280; -.
DR STRING; 10116.ENSRNOP00000007410; -.
DR iPTMnet; D4A280; -.
DR PhosphoSitePlus; D4A280; -.
DR PaxDb; D4A280; -.
DR PeptideAtlas; D4A280; -.
DR PRIDE; D4A280; -.
DR Ensembl; ENSRNOT00000007410; ENSRNOP00000007410; ENSRNOG00000005509.
DR GeneID; 311450; -.
DR KEGG; rno:311450; -.
DR UCSC; RGD:1312009; rat.
DR CTD; 57144; -.
DR RGD; 1312009; Pak7.
DR eggNOG; KOG0578; Eukaryota.
DR GeneTree; ENSGT00940000158656; -.
DR InParanoid; D4A280; -.
DR OMA; VDYHAHL; -.
DR OrthoDB; 757766at2759; -.
DR PhylomeDB; D4A280; -.
DR TreeFam; TF105352; -.
DR Reactome; R-RNO-9013148; CDC42 GTPase cycle.
DR Reactome; R-RNO-9013149; RAC1 GTPase cycle.
DR Reactome; R-RNO-9013405; RHOD GTPase cycle.
DR Reactome; R-RNO-9013407; RHOH GTPase cycle.
DR PRO; PR:D4A280; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Proteomes; UP000234681; Chromosome 3.
DR Bgee; ENSRNOG00000005509; Expressed in frontal cortex and 1 other tissue.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0045202; C:synapse; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:RGD.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007010; P:cytoskeleton organization; IEA:InterPro.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0007612; P:learning; ISO:RGD.
DR GO; GO:0007626; P:locomotory behavior; ISO:RGD.
DR GO; GO:0007613; P:memory; ISO:RGD.
DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
DR CDD; cd01093; CRIB_PAK_like; 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; IPR028754; PAK5.
DR InterPro; IPR033923; PAK_BD.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR PANTHER; PTHR45832:SF4; PTHR45832:SF4; 1.
DR Pfam; PF00786; PBD; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00285; PBD; 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.
PE 1: Evidence at protein level;
KW Apoptosis; ATP-binding; Cytoplasm; Kinase; Mitochondrion;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..718
FT /note="Serine/threonine-protein kinase PAK 5"
FT /id="PRO_0000413066"
FT DOMAIN 11..24
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT DOMAIN 448..699
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 25..447
FT /note="Linker"
FT /evidence="ECO:0000250"
FT REGION 96..119
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 226..245
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 264..296
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 339..371
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..15
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 271..291
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 352..371
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 567
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 454..462
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 477
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 104
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 107
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 718 AA; 80949 MW; FA48783A5813C508 CRC64;
MFGKKKKKIE ISGPSNFEHR VHTGFDPQEQ KFTGLPQQWH SLLADTANRP KPMVDPSCIT
PIQLAPMKTI VRGNKSCKES SINGLLEDFD NISVTRSNSL RKESPPTPDQ GAASRIQGHS
EENGFITFSQ YSSESDTTTD YTTEKYRDRS LYGDDLDLYY RGSHAAKQNG HAMKMKHGDA
YYPEMKPLKS DLARFPVDYH THLDSLSKAS EYGDLKWDYQ RASSSSPLDY SFQLTPSRTA
GTSRCSKESL AYSESDWGPS FDDYDRRPKS SYLHQTSPQP AMRQRSKSGS GLQEPMMPFG
ASAFKTHPQG HSYNSYTYPR LSEPTMCIPK VDYDRAQMVF SPPLSGSDTY PRGPTKLPQS
QSKVGYSSSS HQYPGYHKAS LYHHPSLQTS SQYISTASYL SSLSISSSTY PPPSWGSSSD
QQPSRVSHEQ FRAALQLVVS PGDPREYLDN FIKIGEGSTG IVCIATEKHT GKQVAVKKMD
LRKQQRRELL FNEVVIMRDY HHDNVVDMYN SYLVGDELWV VMEFLEGGAL TDIVTHTRMN
EEQIATVCLS VLKALSYLHN QGVIHRDIKS DSILLTSDGR IKLSDFGFCA QVSKEVPKRK
SLVGTPYWMA PEVISRLPYG TEVDIWSLGI MVIEMIDGEP PYFNEPPLQA MRRIRDSLPP
RVKDLHKVSS MLRGFLDLML VREPSQRATA QELLGHPFLK LAGPPSCIVP LMRQYRHH
