PAK5_MOUSE
ID PAK5_MOUSE Reviewed; 719 AA.
AC Q8C015; Q3TQJ7; Q6RWS7;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 158.
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 {ECO:0000303|PubMed:11756552};
GN Synonyms=Pak7 {ECO:0000312|MGI:MGI:1920334};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP DISRUPTION PHENOTYPE.
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=14517284; DOI=10.1128/mcb.23.20.7134-7142.2003;
RA Li X., Minden A.;
RT "Targeted disruption of the gene for the PAK5 kinase in mice.";
RL Mol. Cell. Biol. 23:7134-7142(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Corpora quadrigemina, and Olfactory bulb;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP FUNCTION.
RX PubMed=11756552; DOI=10.1128/mcb.22.2.567-577.2002;
RA Dan C., Nath N., Liberto M., Minden A.;
RT "PAK5, a new brain-specific kinase, promotes neurite outgrowth in N1E-115
RT cells.";
RL Mol. Cell. Biol. 22:567-577(2002).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-104 AND THR-107, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-104 AND THR-107, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 RAF1 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, ECO:0000269|PubMed:11756552}.
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 -!- TISSUE SPECIFICITY: Highly expressed in brain and eye. Also expressed
CC in adrenal gland, pancreas, prostate and testes. Within the brain,
CC expression is restricted to neurons. Present in brain but not in
CC kidney, lung and spleen (at protein level).
CC {ECO:0000269|PubMed:14517284}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal brain.
CC {ECO:0000269|PubMed:14517284}.
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 -!- DISRUPTION PHENOTYPE: Mice are viable and fertile, and show normal
CC development of brain, eye, pancreas and adrenal gland.
CC {ECO:0000269|PubMed:14517284}.
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; AY487425; AAR37415.1; -; mRNA.
DR EMBL; AK032593; BAC27939.1; -; mRNA.
DR EMBL; AK163530; BAE37385.1; -; mRNA.
DR CCDS; CCDS16790.1; -.
DR RefSeq; NP_766446.2; NM_172858.2.
DR RefSeq; XP_006499572.1; XM_006499509.1.
DR RefSeq; XP_011237833.1; XM_011239531.1.
DR RefSeq; XP_017173706.1; XM_017318217.1.
DR RefSeq; XP_017173707.1; XM_017318218.1.
DR AlphaFoldDB; Q8C015; -.
DR SMR; Q8C015; -.
DR BioGRID; 232340; 3.
DR IntAct; Q8C015; 4.
DR MINT; Q8C015; -.
DR STRING; 10090.ENSMUSP00000047285; -.
DR iPTMnet; Q8C015; -.
DR PhosphoSitePlus; Q8C015; -.
DR MaxQB; Q8C015; -.
DR PaxDb; Q8C015; -.
DR PRIDE; Q8C015; -.
DR ProteomicsDB; 287941; -.
DR Antibodypedia; 8792; 378 antibodies from 39 providers.
DR DNASU; 241656; -.
DR Ensembl; ENSMUST00000035264; ENSMUSP00000047285; ENSMUSG00000039913.
DR Ensembl; ENSMUST00000077200; ENSMUSP00000076440; ENSMUSG00000039913.
DR GeneID; 241656; -.
DR KEGG; mmu:241656; -.
DR UCSC; uc008moh.1; mouse.
DR CTD; 57144; -.
DR MGI; MGI:1920334; Pak5.
DR VEuPathDB; HostDB:ENSMUSG00000039913; -.
DR eggNOG; KOG0578; Eukaryota.
DR GeneTree; ENSGT00940000158656; -.
DR HOGENOM; CLU_000288_26_6_1; -.
DR InParanoid; Q8C015; -.
DR OMA; VDYHAHL; -.
DR OrthoDB; 757766at2759; -.
DR PhylomeDB; Q8C015; -.
DR TreeFam; TF105352; -.
DR Reactome; R-MMU-9013148; CDC42 GTPase cycle.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR Reactome; R-MMU-9013405; RHOD GTPase cycle.
DR Reactome; R-MMU-9013407; RHOH GTPase cycle.
DR BioGRID-ORCS; 241656; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Pak7; mouse.
DR PRO; PR:Q8C015; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q8C015; protein.
DR Bgee; ENSMUSG00000039913; Expressed in lumbar subsegment of spinal cord and 82 other tissues.
DR Genevisible; Q8C015; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0045202; C:synapse; IDA:SynGO.
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; IDA:MGI.
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; IGI:MGI.
DR GO; GO:0007626; P:locomotory behavior; IGI:MGI.
DR GO; GO:0007613; P:memory; IGI:MGI.
DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IDA:MGI.
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..719
FT /note="Serine/threonine-protein kinase PAK 5"
FT /id="PRO_0000086478"
FT DOMAIN 11..24
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT DOMAIN 449..700
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..28
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 25..448
FT /note="Linker"
FT REGION 96..118
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 253..298
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 339..372
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..372
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 568
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 455..463
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 478
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:16452087,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 107
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16452087,
FT ECO:0007744|PubMed:21183079"
FT CONFLICT 315
FT /note="S -> F (in Ref. 1; AAR37415)"
FT /evidence="ECO:0000305"
FT CONFLICT 320
FT /note="R -> G (in Ref. 1; AAR37415)"
FT /evidence="ECO:0000305"
FT CONFLICT 454
FT /note="K -> R (in Ref. 1; AAR37415)"
FT /evidence="ECO:0000305"
FT CONFLICT 522
FT /note="V -> A (in Ref. 1; AAR37415)"
FT /evidence="ECO:0000305"
FT CONFLICT 664
FT /note="K -> E (in Ref. 1; AAR37415)"
FT /evidence="ECO:0000305"
FT CONFLICT 687
FT /note="Q -> R (in Ref. 1; AAR37415)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 719 AA; 80948 MW; 5E16D2318C238C8D CRC64;
MFGKKKKKIE ISGPSNFEHR VHTGFDPQEQ KFTGLPQQWH SLLADTANRP KPMVDPSCIT
PIQLAPMKTI VRGNKSCKET SINGLLEDFD NISVTRSNSL RKESPPTPDQ GAASRIQGHS
EENGFITFSQ YSSESDTTAD YTTEKYRDRS LYGDDLDLYY KSSHAAKQNG HAMKMKHGDA
YYPEMKSLKT DLAGFPVDYH THLDSLRKSS EYGDLRWDYQ RASSSSPLDY SFQLTPSRTA
GTSRCSKESL AYSESDWGPS LDDYDRRPKS SYLHQTSPQP AMRQRSKSGS GLQEPMMPFG
ASAFKTHPQG HSYNSYTYPR LSEPTMCIPK VDYDRAQMVF SPPLSGSDTY PRGPTKLPQS
QSKAGYSSGS HQYPSGYHKA SLYHHPSLQT SSQYISTASY LSSLSISSST YPPPSWGSSS
DQQPSRVSHE QFRAALQLVV SPGDPREYLD NFIKIGEGST GIVCIATEKH TGKQVAVKKM
DLRKQQRREL LFNEVVIMRD YHHDNVVDMY NSYLVGDELW VVMEFLEGGA LTDIVTHTRM
NEEQIATVCL SVLKALSYLH NQGVIHRDIK SDSILLTSDG RIKLSDFGFC AQVSKEVPKR
KSLVGTPYWM APEVISRLPY GTEVDIWSLG IMVIEMIDGE PPYFNEPPLQ AMRRIRDSLP
PRVKDLHKVS SMLRGFLDLM LVREPSQRAT AQELLGHPFL KLAGPPSCIV PLMRQYRHH
