PAK3_HUMAN
ID PAK3_HUMAN Reviewed; 559 AA.
AC O75914; A8K389; B1GX77; B1GX78; B1GX79; Q5JWX1; Q5JWX2; Q7Z2D6; Q7Z2E4;
AC Q7Z3Z8; Q8WWK5; Q8WX23; Q9P0J8;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 2.
DT 03-AUG-2022, entry version 212.
DE RecName: Full=Serine/threonine-protein kinase PAK 3;
DE EC=2.7.11.1;
DE AltName: Full=Beta-PAK;
DE AltName: Full=Oligophrenin-3;
DE AltName: Full=p21-activated kinase 3;
DE Short=PAK-3;
GN Name=PAK3; Synonyms=OPHN3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND INVOLVEMENT IN XLID30.
RX PubMed=9731525; DOI=10.1038/1675;
RA Allen K.M., Gleeson J.G., Bagrodia S., Partington M.W., Macmillan J.C.,
RA Cerione R.A., Mulley J.C., Walsh C.A.;
RT "PAK3 mutation in nonsyndromic X-linked mental retardation.";
RL Nat. Genet. 20:25-30(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Adrenal gland;
RA Jiang C., Gu J., Fu S., Ren S., Gu Y., Huang Q., Dong H., Yu Y., Fu G.,
RA Wang Y., Chen Z., Han Z.;
RT "A novel gene expressed in the human adrenal gland.";
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=12777533; DOI=10.1093/molbev/msg134;
RA Kitano T., Schwarz C., Nickel B., Paeaebo S.;
RT "Gene diversity patterns at 10 X-chromosomal loci in humans and
RT chimpanzees.";
RL Mol. Biol. Evol. 20:1281-1289(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3 AND 4).
RC TISSUE=Brain;
RX PubMed=18507705; DOI=10.1111/j.1471-4159.2008.05474.x;
RA Kreis P., Rousseau V., Thevenot E., Combeau G., Barnier J.V.;
RT "The four mammalian splice variants encoded by the p21-activated kinase 3
RT gene have different biological properties.";
RL J. Neurochem. 106:1184-1197(2008).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP INTERACTION WITH GIT1 AND GIT2.
RX PubMed=10896954; DOI=10.1074/jbc.275.29.22373;
RA Premont R.T., Claing A., Vitale N., Perry S.J., Lefkowitz R.J.;
RT "The GIT family of ADP-ribosylation factor GTPase-activating proteins.
RT Functional diversity of GIT2 through alternative splicing.";
RL J. Biol. Chem. 275:22373-22380(2000).
RN [9]
RP AUTOPHOSPHORYLATION.
RX PubMed=11278486; DOI=10.1074/jbc.m009316200;
RA Chong C., Tan L., Lim L., Manser E.;
RT "The mechanism of PAK activation. Autophosphorylation events in both
RT regulatory and kinase domains control activity.";
RL J. Biol. Chem. 276:17347-17353(2001).
RN [10]
RP INTERACTION WITH ARHGEF6 AND ARHGEF7.
RX PubMed=11741931; DOI=10.1074/jbc.m107704200;
RA Feng Q., Albeck J.G., Cerione R.A., Yang W.;
RT "Regulation of the Cool/Pix proteins: key binding partners of the Cdc42/Rac
RT targets, the p21-activated kinases.";
RL J. Biol. Chem. 277:5644-5650(2002).
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=12890786; DOI=10.1523/jneurosci.23-17-06914.2003;
RA McPhie D.L., Coopersmith R., Hines-Peralta A., Chen Y., Ivins K.J.,
RA Manly S.P., Kozlowski M.R., Neve K.A., Neve R.L.;
RT "DNA synthesis and neuronal apoptosis caused by familial Alzheimer disease
RT mutants of the amyloid precursor protein are mediated by the p21 activated
RT kinase PAK3.";
RL J. Neurosci. 23:6914-6927(2003).
RN [12]
RP NEDDYLATION.
RX PubMed=20596523; DOI=10.1371/journal.pone.0011332;
RA Del Rincon S.V., Rogers J., Widschwendter M., Sun D., Sieburg H.B.,
RA Spruck C.;
RT "Development and validation of a method for profiling post-translational
RT modification activities using protein microarrays.";
RL PLoS ONE 5:E11332-E11332(2010).
RN [13]
RP FUNCTION IN PHOSPHORYLATION OF MAPK4 AND MAPK6.
RX PubMed=21177870; DOI=10.1074/jbc.m110.181529;
RA Deleris P., Trost M., Topisirovic I., Tanguay P.L., Borden K.L.,
RA Thibault P., Meloche S.;
RT "Activation loop phosphorylation of ERK3/ERK4 by group I p21-activated
RT kinases (PAKs) defines a novel PAK-ERK3/4-MAPK-activated protein kinase 5
RT signaling pathway.";
RL J. Biol. Chem. 286:6470-6478(2011).
RN [14]
RP REVIEW ON FUNCTION.
RX PubMed=19036346; DOI=10.1016/j.cellsig.2008.11.001;
RA Kreis P., Barnier J.V.;
RT "PAK signalling in neuronal physiology.";
RL Cell. Signal. 21:384-393(2009).
RN [15]
RP VARIANT XLID30 CYS-67.
RX PubMed=10946356;
RX DOI=10.1002/1096-8628(20000814)93:4<294::aid-ajmg8>3.0.co;2-f;
RA Bienvenu T., des Portes V., McDonell N., Carrie A., Zemni R., Couvert P.,
RA Ropers H.-H., Moraine C., van Bokhoven H., Fryns J.-P., Allen K.,
RA Walsh C.A., Boue J., Kahn A., Chelly J., Beldjord C.;
RT "Missense mutation in PAK3, R67C, causes X-linked nonspecific mental
RT retardation.";
RL Am. J. Med. Genet. 93:294-298(2000).
RN [16]
RP VARIANT XLID30 GLU-380.
RX PubMed=12884430; DOI=10.1002/ajmg.a.20131;
RA Gedeon A.K., Nelson J., Gecz J., Mulley J.C.;
RT "X-linked mild non-syndromic mental retardation with neuropsychiatric
RT problems and the missense mutation A365E in PAK3.";
RL Am. J. Med. Genet. A 120:509-517(2003).
RN [17]
RP VARIANT [LARGE SCALE ANALYSIS] SER-440.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Serine/threonine protein kinase that plays a role in a
CC variety of different signaling pathways including cytoskeleton
CC regulation, cell migration, or cell cycle regulation. Plays a role in
CC dendrite spine morphogenesis as well as synapse formation and
CC plasticity. Acts as downstream effector of the small GTPases CDC42 and
CC RAC1. Activation by the binding of active CDC42 and RAC1 results in a
CC conformational change and a subsequent autophosphorylation on several
CC serine and/or threonine residues. Phosphorylates MAPK4 and MAPK6 and
CC activates the downstream target MAPKAPK5, a regulator of F-actin
CC polymerization and cell migration. Additionally, phosphorylates
CC TNNI3/troponin I to modulate calcium sensitivity and relaxation
CC kinetics of thin myofilaments. May also be involved in early neuronal
CC development. In hippocampal neurons, necessary for the formation of
CC dendritic spines and excitatory synapses; this function is dependent on
CC kinase activity and may be exerted by the regulation of actomyosin
CC contractility through the phosphorylation of myosin II regulatory light
CC chain (MLC) (By similarity). {ECO:0000250|UniProtKB:Q61036,
CC ECO:0000269|PubMed:21177870}.
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 -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
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-436 and
CC allows the kinase domain to adopt an active structure (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Interacts tightly with GTP-bound but not GDP-bound CDC42/p21
CC and RAC1. Shows highly specific binding to the SH3 domains of
CC phospholipase C-gamma and of adapter protein NCK. Interacts with the C-
CC terminal of APP (By similarity). Interacts with ARHGEF6 and ARHGEF7.
CC Interacts with GIT1 and GIT2 (PubMed:10896954). {ECO:0000250,
CC ECO:0000269|PubMed:10896954, ECO:0000269|PubMed:11741931}.
CC -!- INTERACTION:
CC O75914; P60953-2: CDC42; NbExp=2; IntAct=EBI-3389553, EBI-287394;
CC O75914-2; Q9H4E5: RHOJ; NbExp=3; IntAct=EBI-17483970, EBI-6285694;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=PAK3b;
CC IsoId=O75914-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75914-2; Sequence=VSP_010242;
CC Name=3; Synonyms=PAK3cb;
CC IsoId=O75914-3; Sequence=VSP_041839;
CC Name=4; Synonyms=PAK3c;
CC IsoId=O75914-4; Sequence=VSP_041840;
CC -!- TISSUE SPECIFICITY: Restricted to the nervous system. Highly expressed
CC in postmitotic neurons of the developing and postnatal cerebral cortex
CC and hippocampus. {ECO:0000269|PubMed:12890786}.
CC -!- PTM: Autophosphorylated when activated by CDC42/p21.
CC -!- PTM: Neddylated. {ECO:0000269|PubMed:20596523}.
CC -!- DISEASE: Intellectual developmental disorder, X-linked 30 (XLID30)
CC [MIM:300558]: A disorder characterized by significantly below average
CC general intellectual functioning associated with impairments in
CC adaptive behavior and manifested during the developmental period.
CC Intellectual deficiency is the only primary symptom of non-syndromic X-
CC linked forms, while syndromic intellectual disability presents with
CC associated physical, neurological and/or psychiatric manifestations.
CC {ECO:0000269|PubMed:10946356, ECO:0000269|PubMed:12884430,
CC ECO:0000269|PubMed:9731525}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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; AF068864; AAC36097.1; -; mRNA.
DR EMBL; AF155651; AAF67008.1; -; mRNA.
DR EMBL; AB102659; BAC81128.1; -; mRNA.
DR EMBL; AB102251; BAC80750.1; -; Genomic_DNA.
DR EMBL; AB102252; BAC80751.1; -; Genomic_DNA.
DR EMBL; AB102253; BAC80752.1; -; Genomic_DNA.
DR EMBL; AB102254; BAC80753.1; -; Genomic_DNA.
DR EMBL; AB102255; BAC80754.1; -; Genomic_DNA.
DR EMBL; AB102256; BAC80755.1; -; Genomic_DNA.
DR EMBL; AB102257; BAC80756.1; -; Genomic_DNA.
DR EMBL; AB102258; BAC80757.1; -; Genomic_DNA.
DR EMBL; AB102259; BAC80758.1; -; Genomic_DNA.
DR EMBL; AB102260; BAC80759.1; -; Genomic_DNA.
DR EMBL; AB102261; BAC80760.1; -; Genomic_DNA.
DR EMBL; AB102262; BAC80761.1; -; Genomic_DNA.
DR EMBL; AB102263; BAC80762.1; -; Genomic_DNA.
DR EMBL; AB102264; BAC80763.1; -; Genomic_DNA.
DR EMBL; AB102265; BAC80764.1; -; Genomic_DNA.
DR EMBL; AB102266; BAC80765.1; -; Genomic_DNA.
DR EMBL; AB102267; BAC80766.1; -; Genomic_DNA.
DR EMBL; AB102268; BAC80767.1; -; Genomic_DNA.
DR EMBL; AB102269; BAC80768.1; -; Genomic_DNA.
DR EMBL; AB102270; BAC80769.1; -; Genomic_DNA.
DR EMBL; AB102281; BAC80780.1; -; Genomic_DNA.
DR EMBL; AB102282; BAC80781.1; -; Genomic_DNA.
DR EMBL; AB102283; BAC80782.1; -; Genomic_DNA.
DR EMBL; AB102284; BAC80783.1; -; Genomic_DNA.
DR EMBL; AB102285; BAC80784.1; -; Genomic_DNA.
DR EMBL; AB102286; BAC80785.1; -; Genomic_DNA.
DR EMBL; AB102287; BAC80786.1; -; Genomic_DNA.
DR EMBL; AB102288; BAC80787.1; -; Genomic_DNA.
DR EMBL; AB102289; BAC80788.1; -; Genomic_DNA.
DR EMBL; AB102290; BAC80789.1; -; Genomic_DNA.
DR EMBL; AB102291; BAC80790.1; -; Genomic_DNA.
DR EMBL; AB102292; BAC80791.1; -; Genomic_DNA.
DR EMBL; AB102293; BAC80792.1; -; Genomic_DNA.
DR EMBL; AB102294; BAC80793.1; -; Genomic_DNA.
DR EMBL; AB102295; BAC80794.1; -; Genomic_DNA.
DR EMBL; AB102296; BAC80795.1; -; Genomic_DNA.
DR EMBL; AB102297; BAC80796.1; -; Genomic_DNA.
DR EMBL; AB102298; BAC80797.1; -; Genomic_DNA.
DR EMBL; AB102299; BAC80798.1; -; Genomic_DNA.
DR EMBL; AB102300; BAC80799.1; -; Genomic_DNA.
DR EMBL; AM943850; CAQ16016.1; -; mRNA.
DR EMBL; AM943851; CAQ16017.1; -; mRNA.
DR EMBL; AM943852; CAQ16018.1; -; mRNA.
DR EMBL; AK290504; BAF83193.1; -; mRNA.
DR EMBL; AL356578; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL357774; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL031117; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL117326; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471120; EAX02654.1; -; Genomic_DNA.
DR CCDS; CCDS14554.1; -. [O75914-2]
DR CCDS; CCDS48151.1; -. [O75914-3]
DR CCDS; CCDS48152.1; -. [O75914-4]
DR CCDS; CCDS48153.1; -. [O75914-1]
DR RefSeq; NP_001121638.1; NM_001128166.2. [O75914-2]
DR RefSeq; NP_001121639.1; NM_001128167.2. [O75914-2]
DR RefSeq; NP_001121640.1; NM_001128168.2. [O75914-3]
DR RefSeq; NP_001121644.1; NM_001128172.2. [O75914-4]
DR RefSeq; NP_001121645.1; NM_001128173.2. [O75914-1]
DR RefSeq; NP_001311254.1; NM_001324325.1. [O75914-2]
DR RefSeq; NP_001311255.1; NM_001324326.1. [O75914-2]
DR RefSeq; NP_001311256.1; NM_001324327.1. [O75914-1]
DR RefSeq; NP_001311257.1; NM_001324328.1. [O75914-1]
DR RefSeq; NP_001311258.1; NM_001324329.1. [O75914-1]
DR RefSeq; NP_001311259.1; NM_001324330.1. [O75914-2]
DR RefSeq; NP_001311260.1; NM_001324331.1. [O75914-2]
DR RefSeq; NP_001311261.1; NM_001324332.1. [O75914-2]
DR RefSeq; NP_001311262.1; NM_001324333.1. [O75914-1]
DR RefSeq; NP_001311263.1; NM_001324334.1. [O75914-2]
DR RefSeq; NP_002569.1; NM_002578.4. [O75914-2]
DR RefSeq; XP_016885046.1; XM_017029557.1. [O75914-1]
DR RefSeq; XP_016885050.1; XM_017029561.1. [O75914-2]
DR RefSeq; XP_016885052.1; XM_017029563.1. [O75914-3]
DR PDB; 6FD3; X-ray; 1.52 A; A=261-559.
DR PDBsum; 6FD3; -.
DR AlphaFoldDB; O75914; -.
DR SMR; O75914; -.
DR BioGRID; 111099; 27.
DR IntAct; O75914; 6.
DR MINT; O75914; -.
DR STRING; 9606.ENSP00000353864; -.
DR BindingDB; O75914; -.
DR ChEMBL; CHEMBL2999; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; O75914; -.
DR GuidetoPHARMACOLOGY; 2135; -.
DR GlyGen; O75914; 2 sites.
DR iPTMnet; O75914; -.
DR MetOSite; O75914; -.
DR PhosphoSitePlus; O75914; -.
DR BioMuta; PAK3; -.
DR EPD; O75914; -.
DR jPOST; O75914; -.
DR MassIVE; O75914; -.
DR PaxDb; O75914; -.
DR PeptideAtlas; O75914; -.
DR PRIDE; O75914; -.
DR ProteomicsDB; 50266; -. [O75914-1]
DR ProteomicsDB; 50267; -. [O75914-2]
DR ProteomicsDB; 50268; -. [O75914-3]
DR ProteomicsDB; 50269; -. [O75914-4]
DR Antibodypedia; 29512; 532 antibodies from 37 providers.
DR DNASU; 5063; -.
DR Ensembl; ENST00000262836.6; ENSP00000262836.4; ENSG00000077264.16. [O75914-1]
DR Ensembl; ENST00000360648.8; ENSP00000353864.4; ENSG00000077264.16. [O75914-3]
DR Ensembl; ENST00000372007.10; ENSP00000361077.4; ENSG00000077264.16. [O75914-2]
DR Ensembl; ENST00000372010.5; ENSP00000361080.1; ENSG00000077264.16. [O75914-1]
DR Ensembl; ENST00000417227.5; ENSP00000389172.1; ENSG00000077264.16. [O75914-4]
DR Ensembl; ENST00000425146.5; ENSP00000401982.1; ENSG00000077264.16. [O75914-2]
DR Ensembl; ENST00000446737.5; ENSP00000410853.1; ENSG00000077264.16. [O75914-2]
DR Ensembl; ENST00000518291.5; ENSP00000428921.1; ENSG00000077264.16. [O75914-3]
DR Ensembl; ENST00000519681.5; ENSP00000429113.1; ENSG00000077264.16. [O75914-4]
DR GeneID; 5063; -.
DR KEGG; hsa:5063; -.
DR MANE-Select; ENST00000372007.10; ENSP00000361077.4; NM_002578.5; NP_002569.1. [O75914-2]
DR UCSC; uc004eoz.3; human. [O75914-1]
DR CTD; 5063; -.
DR DisGeNET; 5063; -.
DR GeneCards; PAK3; -.
DR HGNC; HGNC:8592; PAK3.
DR HPA; ENSG00000077264; Tissue enhanced (brain, pancreas).
DR MalaCards; PAK3; -.
DR MIM; 300142; gene.
DR MIM; 300558; phenotype.
DR neXtProt; NX_O75914; -.
DR OpenTargets; ENSG00000077264; -.
DR Orphanet; 777; X-linked non-syndromic intellectual disability.
DR PharmGKB; PA32919; -.
DR VEuPathDB; HostDB:ENSG00000077264; -.
DR eggNOG; KOG0578; Eukaryota.
DR GeneTree; ENSGT00950000182988; -.
DR HOGENOM; CLU_000288_26_6_1; -.
DR InParanoid; O75914; -.
DR OMA; LPEXKSA; -.
DR OrthoDB; 750735at2759; -.
DR PhylomeDB; O75914; -.
DR TreeFam; TF105351; -.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; O75914; -.
DR Reactome; R-HSA-202433; Generation of second messenger molecules.
DR Reactome; R-HSA-389359; CD28 dependent Vav1 pathway.
DR Reactome; R-HSA-3928664; Ephrin signaling.
DR Reactome; R-HSA-399954; Sema3A PAK dependent Axon repulsion.
DR Reactome; R-HSA-428540; Activation of RAC1.
DR Reactome; R-HSA-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-HSA-5621575; CD209 (DC-SIGN) signaling.
DR Reactome; R-HSA-5627123; RHO GTPases activate PAKs.
DR Reactome; R-HSA-5687128; MAPK6/MAPK4 signaling.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013409; RHOJ GTPase cycle.
DR Reactome; R-HSA-9013420; RHOU GTPase cycle.
DR SignaLink; O75914; -.
DR SIGNOR; O75914; -.
DR BioGRID-ORCS; 5063; 12 hits in 731 CRISPR screens.
DR ChiTaRS; PAK3; human.
DR GeneWiki; PAK3; -.
DR GenomeRNAi; 5063; -.
DR Pharos; O75914; Tchem.
DR PRO; PR:O75914; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; O75914; protein.
DR Bgee; ENSG00000077264; Expressed in middle temporal gyrus and 155 other tissues.
DR ExpressionAtlas; O75914; baseline and differential.
DR Genevisible; O75914; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005768; C:endosome; IEA:Ensembl.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004708; F:MAP kinase kinase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion 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; EXP:Reactome.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0031267; F:small GTPase binding; IEA:Ensembl.
DR GO; GO:0007409; P:axonogenesis; ISS:UniProtKB.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0016358; P:dendrite development; ISS:UniProtKB.
DR GO; GO:0060997; P:dendritic spine morphogenesis; ISS:UniProtKB.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; TAS:Reactome.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0061003; P:positive regulation of dendritic spine morphogenesis; IEA:Ensembl.
DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; IEA:Ensembl.
DR GO; GO:0010763; P:positive regulation of fibroblast migration; IEA:Ensembl.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0030833; P:regulation of actin filament polymerization; IDA:UniProtKB.
DR GO; GO:0050770; P:regulation of axonogenesis; IBA:GO_Central.
DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0002223; P:stimulatory C-type lectin receptor signaling pathway; TAS:Reactome.
DR GO; GO:0050808; P:synapse organization; TAS:UniProtKB.
DR CDD; cd01093; CRIB_PAK_like; 1.
DR CDD; cd06656; STKc_PAK3; 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; 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; IPR035063; STK_PAK3.
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 3D-structure; Allosteric enzyme; Alternative splicing; ATP-binding;
KW Cytoplasm; Developmental protein; Disease variant; Intellectual disability;
KW Kinase; Magnesium; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; SH3-binding;
KW Transferase; Ubl conjugation.
FT CHAIN 1..559
FT /note="Serine/threonine-protein kinase PAK 3"
FT /id="PRO_0000086469"
FT DOMAIN 70..83
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT DOMAIN 283..534
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..72
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 65..150
FT /note="Autoregulatory region"
FT /evidence="ECO:0000250"
FT REGION 65..123
FT /note="GTPase-binding"
FT /evidence="ECO:0000250"
FT REGION 84..282
FT /note="Linker"
FT REGION 164..212
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 228..262
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 18..32
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 56..72
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 184..201
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 402
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 289..297
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 312
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62829"
FT MOD_RES 50
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q62829"
FT MOD_RES 154
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q62829"
FT MOD_RES 186
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61036"
FT MOD_RES 436
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q62829"
FT VAR_SEQ 92..107
FT /note="TPDLYGSQMCPGKLPE -> TNSPFQTSRPVTVASSQSEGKM (in
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:18507705"
FT /id="VSP_041840"
FT VAR_SEQ 92
FT /note="T -> TNSPFQTSRPVTVASSQSEGKM (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:18507705"
FT /id="VSP_041839"
FT VAR_SEQ 93..107
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:9731525, ECO:0000303|Ref.2"
FT /id="VSP_010242"
FT VARIANT 67
FT /note="R -> C (in XLID30; dbSNP:rs121434612)"
FT /evidence="ECO:0000269|PubMed:10946356"
FT /id="VAR_023825"
FT VARIANT 380
FT /note="A -> E (in XLID30; dbSNP:rs121434613)"
FT /evidence="ECO:0000269|PubMed:12884430"
FT /id="VAR_023826"
FT VARIANT 440
FT /note="T -> S (in a colorectal adenocarcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_046764"
FT CONFLICT 32
FT /note="S -> F (in Ref. 2; AAF67008)"
FT /evidence="ECO:0000305"
FT CONFLICT 36
FT /note="P -> S (in Ref. 2; AAF67008)"
FT /evidence="ECO:0000305"
FT CONFLICT 73
FT /note="P -> S (in Ref. 2; AAF67008)"
FT /evidence="ECO:0000305"
FT CONFLICT 106..107
FT /note="PE -> SL (in Ref. 2; AAF67008)"
FT /evidence="ECO:0000305"
FT CONFLICT 123
FT /note="T -> P (in Ref. 2; AAF67008)"
FT /evidence="ECO:0000305"
FT CONFLICT 127..130
FT /note="QKKN -> PEEE (in Ref. 2; AAF67008)"
FT /evidence="ECO:0000305"
FT CONFLICT 134..137
FT /note="VLDV -> CSRC (in Ref. 2; AAF67008)"
FT /evidence="ECO:0000305"
FT CONFLICT 146..148
FT /note="TVN -> PVT (in Ref. 2; AAF67008)"
FT /evidence="ECO:0000305"
FT CONFLICT 175
FT /note="T -> P (in Ref. 2; AAF67008)"
FT /evidence="ECO:0000305"
FT HELIX 263..273
FT /evidence="ECO:0007829|PDB:6FD3"
FT STRAND 274..277
FT /evidence="ECO:0007829|PDB:6FD3"
FT HELIX 279..281
FT /evidence="ECO:0007829|PDB:6FD3"
FT STRAND 283..291
FT /evidence="ECO:0007829|PDB:6FD3"
FT STRAND 293..302
FT /evidence="ECO:0007829|PDB:6FD3"
FT TURN 303..305
FT /evidence="ECO:0007829|PDB:6FD3"
FT STRAND 308..315
FT /evidence="ECO:0007829|PDB:6FD3"
FT HELIX 316..318
FT /evidence="ECO:0007829|PDB:6FD3"
FT HELIX 324..334
FT /evidence="ECO:0007829|PDB:6FD3"
FT STRAND 343..349
FT /evidence="ECO:0007829|PDB:6FD3"
FT STRAND 352..358
FT /evidence="ECO:0007829|PDB:6FD3"
FT HELIX 365..371
FT /evidence="ECO:0007829|PDB:6FD3"
FT HELIX 376..395
FT /evidence="ECO:0007829|PDB:6FD3"
FT HELIX 405..407
FT /evidence="ECO:0007829|PDB:6FD3"
FT STRAND 408..410
FT /evidence="ECO:0007829|PDB:6FD3"
FT STRAND 416..418
FT /evidence="ECO:0007829|PDB:6FD3"
FT HELIX 441..443
FT /evidence="ECO:0007829|PDB:6FD3"
FT HELIX 446..449
FT /evidence="ECO:0007829|PDB:6FD3"
FT HELIX 458..472
FT /evidence="ECO:0007829|PDB:6FD3"
FT TURN 476..479
FT /evidence="ECO:0007829|PDB:6FD3"
FT HELIX 482..492
FT /evidence="ECO:0007829|PDB:6FD3"
FT HELIX 500..502
FT /evidence="ECO:0007829|PDB:6FD3"
FT HELIX 505..514
FT /evidence="ECO:0007829|PDB:6FD3"
FT TURN 519..521
FT /evidence="ECO:0007829|PDB:6FD3"
FT HELIX 525..528
FT /evidence="ECO:0007829|PDB:6FD3"
FT HELIX 532..536
FT /evidence="ECO:0007829|PDB:6FD3"
FT HELIX 540..543
FT /evidence="ECO:0007829|PDB:6FD3"
FT HELIX 544..555
FT /evidence="ECO:0007829|PDB:6FD3"
SQ SEQUENCE 559 AA; 62310 MW; BC39AEC6F0A5478B CRC64;
MSDGLDNEEK PPAPPLRMNS NNRDSSALNH SSKPLPMAPE EKNKKARLRS IFPGGGDKTN
KKKEKERPEI SLPSDFEHTI HVGFDAVTGE FTPDLYGSQM CPGKLPEGIP EQWARLLQTS
NITKLEQKKN PQAVLDVLKF YDSKETVNNQ KYMSFTSGDK SAHGYIAAHP SSTKTASEPP
LAPPVSEEED EEEEEEEDEN EPPPVIAPRP EHTKSIYTRS VVESIASPAV PNKEVTPPSA
ENANSSTLYR NTDRQRKKSK MTDEEILEKL RSIVSVGDPK KKYTRFEKIG QGASGTVYTA
LDIATGQEVA IKQMNLQQQP KKELIINEIL VMRENKNPNI VNYLDSYLVG DELWVVMEYL
AGGSLTDVVT ETCMDEGQIA AVCRECLQAL DFLHSNQVIH RDIKSDNILL GMDGSVKLTD
FGFCAQITPE QSKRSTMVGT PYWMAPEVVT RKAYGPKVDI WSLGIMAIEM VEGEPPYLNE
NPLRALYLIA TNGTPELQNP ERLSAVFRDF LNRCLEMDVD RRGSAKELLQ HPFLKLAKPL
SSLTPLIIAA KEAIKNSSR
