PAK4_HUMAN
ID PAK4_HUMAN Reviewed; 591 AA.
AC O96013; B4DGG6; Q8N4E1; Q8NCH5; Q8NDE3; Q9BU33; Q9ULS8;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 222.
DE RecName: Full=Serine/threonine-protein kinase PAK 4;
DE EC=2.7.11.1;
DE AltName: Full=p21-activated kinase 4;
DE Short=PAK-4;
GN Name=PAK4; Synonyms=KIAA1142;
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 1).
RC TISSUE=Lymphoma;
RX PubMed=9822598; DOI=10.1093/emboj/17.22.6527;
RA Abo A., Qu J., Cammarano M.S., Dan C., Fritsch A., Baud V., Belisle B.,
RA Minden A.;
RT "PAK4, a novel effector for Cdc42Hs, is implicated in the reorganization of
RT the actin cytoskeleton and in the formation of filopodia.";
RL EMBO J. 17:6527-6540(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Neuroblastoma;
RA Melnick M.B.;
RL Submitted (MAY-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=10574461; DOI=10.1093/dnares/6.5.329;
RA Hirosawa M., Nagase T., Ishikawa K., Kikuno R., Nomura N., Ohara O.;
RT "Characterization of cDNA clones selected by the GeneMark analysis from
RT size-fractionated cDNA libraries from human brain.";
RL DNA Res. 6:329-336(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 264-591 (ISOFORM 1).
RC TISSUE=Brain, and Teratocarcinoma;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 4).
RC TISSUE=Eye, Pancreas, and Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP FUNCTION IN PHOSPHORYLATION OF BAD.
RX PubMed=11278822; DOI=10.1074/jbc.m011046200;
RA Gnesutta N., Qu J., Minden A.;
RT "The serine/threonine kinase PAK4 prevents caspase activation and protects
RT cells from apoptosis.";
RL J. Biol. Chem. 276:14414-14419(2001).
RN [9]
RP FUNCTION, AND MUTAGENESIS OF SER-445 AND SER-474.
RX PubMed=11313478; DOI=10.1128/mcb.21.10.3523-3533.2001;
RA Qu J., Cammarano M.S., Shi Q., Ha K.C., de Lanerolle P., Minden A.;
RT "Activated PAK4 regulates cell adhesion and anchorage-independent growth.";
RL Mol. Cell. Biol. 21:3523-3533(2001).
RN [10]
RP SUBCELLULAR LOCATION.
RX PubMed=12356872; DOI=10.1083/jcb.200207008;
RA Zhang H., Li Z., Viklund E.K., Stromblad S.;
RT "P21-activated kinase 4 interacts with integrin alpha v beta 5 and
RT regulates alpha v beta 5-mediated cell migration.";
RL J. Cell Biol. 158:1287-1297(2002).
RN [11]
RP FUNCTION.
RX PubMed=14560027; DOI=10.1128/mcb.23.21.7838-7848.2003;
RA Gnesutta N., Minden A.;
RT "Death receptor-induced activation of initiator caspase 8 is antagonized by
RT serine/threonine kinase PAK4.";
RL Mol. Cell. Biol. 23:7838-7848(2003).
RN [12]
RP FUNCTION.
RX PubMed=15660133; DOI=10.1038/sj.emboj.7600543;
RA Soosairajah J., Maiti S., Wiggan O., Sarmiere P., Moussi N., Sarcevic B.,
RA Sampath R., Bamburg J.R., Bernard O.;
RT "Interplay between components of a novel LIM kinase-slingshot phosphatase
RT complex regulates cofilin.";
RL EMBO J. 24:473-486(2005).
RN [13]
RP INTERACTION WITH ARHGEF2.
RX PubMed=15827085; DOI=10.1242/jcs.02313;
RA Callow M.G., Zozulya S., Gishizky M.L., Jallal B., Smeal T.;
RT "PAK4 mediates morphological changes through the regulation of GEF-H1.";
RL J. Cell Sci. 118:1861-1872(2005).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-474, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41; SER-104; SER-148;
RP SER-167; SER-181; SER-258; SER-267; SER-291 AND SER-474, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181 AND SER-474, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41; SER-104; SER-148;
RP SER-167; SER-181; THR-187; SER-195; SER-258; SER-291 AND SER-474, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181 AND SER-474, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [19]
RP FUNCTION IN PHOSPHORYLATION OF ITGB5.
RX PubMed=20507994; DOI=10.1074/jbc.m110.123497;
RA Li Z., Zhang H., Lundin L., Thullberg M., Liu Y., Wang Y.,
RA Claesson-Welsh L., Stromblad S.;
RT "p21-activated kinase 4 phosphorylation of integrin beta5 Ser-759 and Ser-
RT 762 regulates cell migration.";
RL J. Biol. Chem. 285:23699-23710(2010).
RN [20]
RP FUNCTION IN PHOSPHORYLATION OF RAN.
RX PubMed=20805321; DOI=10.1083/jcb.200912056;
RA Bompard G., Rabeharivelo G., Frank M., Cau J., Delsert C., Morin N.;
RT "Subgroup II PAK-mediated phosphorylation regulates Ran activity during
RT mitosis.";
RL J. Cell Biol. 190:807-822(2010).
RN [21]
RP FUNCTION.
RX PubMed=20631255; DOI=10.1091/mbc.e10-05-0429;
RA Wallace S.W., Durgan J., Jin D., Hall A.;
RT "Cdc42 regulates apical junction formation in human bronchial epithelial
RT cells through PAK4 and Par6B.";
RL Mol. Biol. Cell 21:2996-3006(2010).
RN [22]
RP REVIEW.
RX PubMed=11950587; DOI=10.1016/s1357-2725(01)00158-3;
RA Jaffer Z.M., Chernoff J.;
RT "p21-activated kinases: three more join the Pak.";
RL Int. J. Biochem. Cell Biol. 34:713-717(2002).
RN [23]
RP REVIEW ON FUNCTION.
RX PubMed=20070256; DOI=10.1042/bj20091173;
RA Wells C.M., Jones G.E.;
RT "The emerging importance of group II PAKs.";
RL Biochem. J. 425:465-473(2010).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-474, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181 AND SER-474, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41; SER-181; THR-207 AND
RP SER-474, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [28]
RP INTERACTION WITH SH3RF2, UBIQUITINATION, AND PROTEASOMAL DEGRADATION.
RX PubMed=24130170; DOI=10.1093/carcin/bgt338;
RA Kim T.W., Kang Y.K., Park Z.Y., Kim Y.H., Hong S.W., Oh S.J., Sohn H.A.,
RA Yang S.J., Jang Y.J., Lee D.C., Kim S.Y., Yoo H.S., Kim E., Yeom Y.I.,
RA Park K.C.;
RT "SH3RF2 functions as an oncogene by mediating PAK4 protein stability.";
RL Carcinogenesis 35:624-634(2014).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [30]
RP METHYLATION [LARGE SCALE ANALYSIS] AT LYS-78, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [31]
RP METHYLATION.
RX PubMed=30189201; DOI=10.1016/j.jmb.2018.08.028;
RA Weil L.E., Shmidov Y., Kublanovsky M., Morgenstern D., Feldman M.,
RA Bitton R., Levy D.;
RT "Oligomerization and Auto-methylation of the Human Lysine Methyltransferase
RT SETD6.";
RL J. Mol. Biol. 430:4359-4368(2018).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 300-591, AND PHOSPHORYLATION AT
RP SER-474.
RA Eswaran J., Debreczeni J.E., Bunkoczi G., Filippakopoulos P., Das S.,
RA Fedorov O., Sundstrom M., Arrowsmith C., Edwards A., von Delft F.,
RA Knapp S.;
RT "Crystal structure of the human p21-activated kinase 4.";
RL Submitted (JUL-2005) to the PDB data bank.
RN [33]
RP X-RAY CRYSTALLOGRAPHY (2.06 ANGSTROMS) OF 286-591 IN COMPLEX WITH INKA1,
RP FUNCTION, INTERACTION WITH INKA1, AND ACTIVITY REGULATION.
RX PubMed=26607847; DOI=10.1038/ncomms9681;
RA Baskaran Y., Ang K.C., Anekal P.V., Chan W.L., Grimes J.M., Manser E.,
RA Robinson R.C.;
RT "An in cellulo-derived structure of PAK4 in complex with its inhibitor
RT Inka1.";
RL Nat. Commun. 6:8681-8681(2015).
RN [34]
RP VARIANTS [LARGE SCALE ANALYSIS] GLN-135 AND THR-139.
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, growth, proliferation or cell survival.
CC Activation by various effectors including growth factor receptors or
CC active CDC42 and RAC1 results in a conformational change and a
CC subsequent autophosphorylation on several serine and/or threonine
CC residues. Phosphorylates and inactivates the protein phosphatase SSH1,
CC leading to increased inhibitory phosphorylation of the actin
CC binding/depolymerizing factor cofilin. Decreased cofilin activity may
CC lead to stabilization of actin filaments. Phosphorylates LIMK1, a
CC kinase that also inhibits the activity of cofilin. Phosphorylates
CC integrin beta5/ITGB5 and thus regulates cell motility. Phosphorylates
CC ARHGEF2 and activates the downstream target RHOA that plays a role in
CC the regulation of assembly of focal adhesions and actin stress fibers.
CC Stimulates cell survival by phosphorylating the BCL2 antagonist of cell
CC death BAD. Alternatively, inhibits apoptosis by preventing caspase-8
CC binding to death domain receptors in a kinase independent manner. Plays
CC a role in cell-cycle progression by controlling levels of the cell-
CC cycle regulatory protein CDKN1A and by phosphorylating RAN.
CC {ECO:0000269|PubMed:11278822, ECO:0000269|PubMed:11313478,
CC ECO:0000269|PubMed:14560027, ECO:0000269|PubMed:15660133,
CC ECO:0000269|PubMed:20507994, ECO:0000269|PubMed:20631255,
CC ECO:0000269|PubMed:20805321, ECO:0000269|PubMed:26607847}.
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: Inhibited by INKA1; which inhibits the
CC serine/threonine-protein kinase activity by binding PAK4 in a
CC substrate-like manner (PubMed:26607847). {ECO:0000269|PubMed:26607847}.
CC -!- SUBUNIT: Interacts with FGFR2 and GRB2 (By similarity). Interacts
CC tightly with GTP-bound but not GDP-bound CDC42/p21 and weakly with RAC1
CC (PubMed:15827085). Interacts with INKA1 (PubMed:26607847). Interacts
CC with SH3RF2 (PubMed:24130170). {ECO:0000250|UniProtKB:Q8BTW9,
CC ECO:0000269|PubMed:15827085, ECO:0000269|PubMed:24130170,
CC ECO:0000269|PubMed:26607847}.
CC -!- INTERACTION:
CC O96013; P60953: CDC42; NbExp=4; IntAct=EBI-713738, EBI-81752;
CC O96013; Q96EL1: INKA1; NbExp=3; IntAct=EBI-713738, EBI-10285157;
CC O96013; P54274: TERF1; NbExp=2; IntAct=EBI-713738, EBI-710997;
CC O96013; O00401: WASL; NbExp=8; IntAct=EBI-713738, EBI-957615;
CC O96013; P63104: YWHAZ; NbExp=5; IntAct=EBI-713738, EBI-347088;
CC O96013-2; P05067: APP; NbExp=3; IntAct=EBI-21659863, EBI-77613;
CC O96013-2; P37840: SNCA; NbExp=3; IntAct=EBI-21659863, EBI-985879;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12356872}.
CC Note=Seems to shuttle between cytoplasmic compartments depending on the
CC activating effector. For example, can be found on the cell periphery
CC after activation of growth-factor or integrin-mediated signaling
CC pathways. {ECO:0000269|PubMed:12356872}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=O96013-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O96013-2; Sequence=VSP_004892, VSP_004893;
CC Name=3;
CC IsoId=O96013-3; Sequence=VSP_017572;
CC Name=4;
CC IsoId=O96013-4; Sequence=VSP_017573;
CC -!- TISSUE SPECIFICITY: Highest expression in prostate, testis and colon.
CC -!- PTM: Autophosphorylated on serine residues when activated by CDC42/p21
CC (Ref.32). Phosphorylated on tyrosine residues upon stimulation of FGFR2
CC (By similarity). Methylated by SETD6. {ECO:0000250|UniProtKB:Q8BTW9,
CC ECO:0000269|PubMed:30189201, ECO:0000269|Ref.32}.
CC -!- PTM: Polyubiquitinated, leading to its proteasomal degradation.
CC {ECO:0000269|PubMed:24130170}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA86456.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC11166.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AJ011855; CAA09820.1; -; mRNA.
DR EMBL; AF005046; AAD01210.1; -; mRNA.
DR EMBL; AB032968; BAA86456.1; ALT_INIT; mRNA.
DR EMBL; AK074728; BAC11166.1; ALT_INIT; mRNA.
DR EMBL; AK294586; BAG57777.1; -; mRNA.
DR EMBL; AL834236; CAD38914.2; -; mRNA.
DR EMBL; CH471126; EAW56861.1; -; Genomic_DNA.
DR EMBL; BC002921; AAH02921.1; -; mRNA.
DR EMBL; BC011368; AAH11368.1; -; mRNA.
DR EMBL; BC025282; AAH25282.1; -; mRNA.
DR EMBL; BC034511; AAH34511.1; -; mRNA.
DR CCDS; CCDS12528.1; -. [O96013-1]
DR CCDS; CCDS33019.1; -. [O96013-3]
DR RefSeq; NP_001014831.1; NM_001014831.2. [O96013-1]
DR RefSeq; NP_001014832.1; NM_001014832.1. [O96013-1]
DR RefSeq; NP_001014834.1; NM_001014834.2. [O96013-3]
DR RefSeq; NP_001014835.1; NM_001014835.1. [O96013-3]
DR RefSeq; NP_005875.1; NM_005884.3. [O96013-1]
DR RefSeq; XP_011524618.1; XM_011526316.1. [O96013-1]
DR RefSeq; XP_011524619.1; XM_011526317.2. [O96013-1]
DR RefSeq; XP_011524620.1; XM_011526318.2. [O96013-1]
DR RefSeq; XP_011524621.1; XM_011526319.2. [O96013-1]
DR RefSeq; XP_011524622.1; XM_011526320.1. [O96013-3]
DR PDB; 2BVA; X-ray; 2.30 A; A/B=300-591.
DR PDB; 2CDZ; X-ray; 2.30 A; A=291-591.
DR PDB; 2J0I; X-ray; 1.60 A; A=291-591.
DR PDB; 2OV2; X-ray; 2.10 A; I/J/K/L/M/N/O/P=10-44.
DR PDB; 2Q0N; X-ray; 1.75 A; A=291-591.
DR PDB; 2X4Z; X-ray; 2.10 A; A=297-591.
DR PDB; 4APP; X-ray; 2.20 A; A=300-591.
DR PDB; 4FIE; X-ray; 3.11 A; A/B=5-591.
DR PDB; 4FIF; X-ray; 2.60 A; A/B=286-591, C/D=49-56.
DR PDB; 4FIG; X-ray; 3.01 A; A/B=286-591.
DR PDB; 4FIH; X-ray; 1.97 A; A=286-591.
DR PDB; 4FII; X-ray; 2.00 A; A=286-591, B=49-56.
DR PDB; 4FIJ; X-ray; 2.30 A; A=286-591.
DR PDB; 4JDH; X-ray; 2.00 A; A=286-591.
DR PDB; 4JDI; X-ray; 1.85 A; A=286-591.
DR PDB; 4JDJ; X-ray; 2.30 A; A=286-591.
DR PDB; 4JDK; X-ray; 2.40 A; A=286-591.
DR PDB; 4L67; X-ray; 2.80 A; A=300-591, B=36-60.
DR PDB; 4NJD; X-ray; 2.50 A; A=300-591.
DR PDB; 4O0V; X-ray; 2.80 A; A=300-591.
DR PDB; 4O0X; X-ray; 2.48 A; A=300-591.
DR PDB; 4O0Y; X-ray; 2.20 A; A=300-591.
DR PDB; 4XBR; X-ray; 2.94 A; A=278-591.
DR PDB; 4XBU; X-ray; 2.06 A; A=286-591.
DR PDB; 5BMS; X-ray; 2.90 A; A=300-591.
DR PDB; 5I0B; X-ray; 3.09 A; A=300-591.
DR PDB; 5UPK; X-ray; 2.40 A; A=1-45, B=286-591.
DR PDB; 5UPL; X-ray; 3.00 A; A=2-591.
DR PDB; 5VED; X-ray; 2.30 A; A=286-591.
DR PDB; 5VEE; X-ray; 2.50 A; A=286-591.
DR PDB; 5VEF; X-ray; 1.75 A; A=286-591.
DR PDB; 5XVA; X-ray; 1.85 A; A=300-591.
DR PDB; 5XVF; X-ray; 2.65 A; A=300-588.
DR PDB; 5XVG; X-ray; 2.10 A; A=300-591.
DR PDB; 5ZJW; X-ray; 1.80 A; A=300-591.
DR PDB; 6WLX; X-ray; 2.20 A; A=286-591.
DR PDB; 6WLY; X-ray; 1.90 A; A=286-591.
DR PDB; 7CMB; X-ray; 2.59 A; A=300-591.
DR PDB; 7CP3; X-ray; 2.90 A; A=300-591.
DR PDB; 7CP4; X-ray; 2.50 A; A=300-591.
DR PDBsum; 2BVA; -.
DR PDBsum; 2CDZ; -.
DR PDBsum; 2J0I; -.
DR PDBsum; 2OV2; -.
DR PDBsum; 2Q0N; -.
DR PDBsum; 2X4Z; -.
DR PDBsum; 4APP; -.
DR PDBsum; 4FIE; -.
DR PDBsum; 4FIF; -.
DR PDBsum; 4FIG; -.
DR PDBsum; 4FIH; -.
DR PDBsum; 4FII; -.
DR PDBsum; 4FIJ; -.
DR PDBsum; 4JDH; -.
DR PDBsum; 4JDI; -.
DR PDBsum; 4JDJ; -.
DR PDBsum; 4JDK; -.
DR PDBsum; 4L67; -.
DR PDBsum; 4NJD; -.
DR PDBsum; 4O0V; -.
DR PDBsum; 4O0X; -.
DR PDBsum; 4O0Y; -.
DR PDBsum; 4XBR; -.
DR PDBsum; 4XBU; -.
DR PDBsum; 5BMS; -.
DR PDBsum; 5I0B; -.
DR PDBsum; 5UPK; -.
DR PDBsum; 5UPL; -.
DR PDBsum; 5VED; -.
DR PDBsum; 5VEE; -.
DR PDBsum; 5VEF; -.
DR PDBsum; 5XVA; -.
DR PDBsum; 5XVF; -.
DR PDBsum; 5XVG; -.
DR PDBsum; 5ZJW; -.
DR PDBsum; 6WLX; -.
DR PDBsum; 6WLY; -.
DR PDBsum; 7CMB; -.
DR PDBsum; 7CP3; -.
DR PDBsum; 7CP4; -.
DR AlphaFoldDB; O96013; -.
DR SMR; O96013; -.
DR BioGRID; 115586; 129.
DR DIP; DIP-39742N; -.
DR IntAct; O96013; 346.
DR MINT; O96013; -.
DR STRING; 9606.ENSP00000469413; -.
DR BindingDB; O96013; -.
DR ChEMBL; CHEMBL4482; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; O96013; -.
DR GuidetoPHARMACOLOGY; 2136; -.
DR GlyGen; O96013; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O96013; -.
DR MetOSite; O96013; -.
DR PhosphoSitePlus; O96013; -.
DR BioMuta; PAK4; -.
DR EPD; O96013; -.
DR jPOST; O96013; -.
DR MassIVE; O96013; -.
DR MaxQB; O96013; -.
DR PaxDb; O96013; -.
DR PeptideAtlas; O96013; -.
DR PRIDE; O96013; -.
DR ProteomicsDB; 51192; -. [O96013-1]
DR ProteomicsDB; 51193; -. [O96013-2]
DR ProteomicsDB; 51194; -. [O96013-3]
DR ProteomicsDB; 51195; -. [O96013-4]
DR Antibodypedia; 16732; 640 antibodies from 43 providers.
DR CPTC; O96013; 1 antibody.
DR DNASU; 10298; -.
DR Ensembl; ENST00000321944.8; ENSP00000326864.4; ENSG00000130669.17. [O96013-4]
DR Ensembl; ENST00000358301.7; ENSP00000351049.2; ENSG00000130669.17. [O96013-1]
DR Ensembl; ENST00000360442.7; ENSP00000353625.3; ENSG00000130669.17. [O96013-1]
DR Ensembl; ENST00000593690.5; ENSP00000469413.1; ENSG00000130669.17. [O96013-1]
DR Ensembl; ENST00000599386.5; ENSP00000471157.1; ENSG00000130669.17. [O96013-3]
DR Ensembl; ENST00000599470.5; ENSP00000470284.1; ENSG00000130669.17. [O96013-3]
DR GeneID; 10298; -.
DR KEGG; hsa:10298; -.
DR MANE-Select; ENST00000360442.8; ENSP00000353625.3; NM_005884.5; NP_005875.1.
DR UCSC; uc002okj.2; human. [O96013-1]
DR CTD; 10298; -.
DR DisGeNET; 10298; -.
DR GeneCards; PAK4; -.
DR HGNC; HGNC:16059; PAK4.
DR HPA; ENSG00000130669; Low tissue specificity.
DR MIM; 605451; gene.
DR neXtProt; NX_O96013; -.
DR OpenTargets; ENSG00000130669; -.
DR PharmGKB; PA32920; -.
DR VEuPathDB; HostDB:ENSG00000130669; -.
DR eggNOG; KOG0578; Eukaryota.
DR GeneTree; ENSGT00940000159792; -.
DR HOGENOM; CLU_000288_26_6_1; -.
DR InParanoid; O96013; -.
DR OMA; QENGDPQ; -.
DR PhylomeDB; O96013; -.
DR TreeFam; TF105352; -.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; O96013; -.
DR Reactome; R-HSA-428540; Activation of RAC1.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013404; RAC2 GTPase cycle.
DR Reactome; R-HSA-9013406; RHOQ GTPase cycle.
DR Reactome; R-HSA-9013407; RHOH GTPase cycle.
DR Reactome; R-HSA-9013408; RHOG GTPase cycle.
DR Reactome; R-HSA-9013409; RHOJ GTPase cycle.
DR Reactome; R-HSA-9013420; RHOU GTPase cycle.
DR Reactome; R-HSA-9013423; RAC3 GTPase cycle.
DR Reactome; R-HSA-9013424; RHOV GTPase cycle.
DR SignaLink; O96013; -.
DR SIGNOR; O96013; -.
DR BioGRID-ORCS; 10298; 21 hits in 1119 CRISPR screens.
DR ChiTaRS; PAK4; human.
DR EvolutionaryTrace; O96013; -.
DR GeneWiki; PAK4; -.
DR GenomeRNAi; 10298; -.
DR Pharos; O96013; Tchem.
DR PRO; PR:O96013; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; O96013; protein.
DR Bgee; ENSG00000130669; Expressed in type B pancreatic cell and 201 other tissues.
DR ExpressionAtlas; O96013; baseline and differential.
DR Genevisible; O96013; HS.
DR GO; GO:0005912; C:adherens junction; HDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; TAS:ProtInc.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0098641; F:cadherin binding involved in cell-cell adhesion; HDA:BHF-UCL.
DR GO; GO:0004672; F:protein kinase activity; NAS:ProtInc.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; TAS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0016477; P:cell migration; TAS:UniProtKB.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0007010; P:cytoskeleton organization; TAS:UniProtKB.
DR GO; GO:0060996; P:dendritic spine development; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; IMP:BHF-UCL.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0001558; P:regulation of cell growth; TAS:UniProtKB.
DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; TAS:UniProtKB.
DR CDD; cd01093; CRIB_PAK_like; 1.
DR DisProt; DP01184; -.
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 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 3D-structure; Alternative splicing; Apoptosis; ATP-binding; Cell cycle;
KW Cytoplasm; Kinase; Methylation; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Ubl conjugation.
FT CHAIN 1..591
FT /note="Serine/threonine-protein kinase PAK 4"
FT /id="PRO_0000086474"
FT DOMAIN 11..24
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT DOMAIN 321..572
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 25..320
FT /note="Linker"
FT REGION 95..301
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 298..323
FT /note="GEF-interaction domain (GID)"
FT COMPBIAS 146..165
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 236..252
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 274..293
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 440
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 327..335
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:26607847, ECO:0007744|PDB:4XBR,
FT ECO:0007744|PDB:4XBU"
FT BINDING 350
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:26607847, ECO:0007744|PDB:4XBR,
FT ECO:0007744|PDB:4XBU"
FT BINDING 396..398
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:26607847,
FT ECO:0007744|PDB:4XBR, ECO:0007744|PDB:4XBU"
FT BINDING 458..460
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:26607847,
FT ECO:0007744|PDB:4XBR, ECO:0007744|PDB:4XBU"
FT MOD_RES 41
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163"
FT MOD_RES 78
FT /note="N6-methyllysine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 104
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 148
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 167
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 181
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 187
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 195
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 207
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 258
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 267
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 291
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 474
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|Ref.32, ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 69..221
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10574461,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:17974005"
FT /id="VSP_017572"
FT VAR_SEQ 120
FT /note="E -> K (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_004892"
FT VAR_SEQ 121..285
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_004893"
FT VAR_SEQ 132..221
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_017573"
FT VARIANT 135
FT /note="R -> Q (in dbSNP:rs56099436)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040970"
FT VARIANT 139
FT /note="A -> T (in dbSNP:rs35655056)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040971"
FT MUTAGEN 445
FT /note="S->N: Approximately 30-fold increased
FT autophosphorylation (constitutively active mutant)."
FT /evidence="ECO:0000269|PubMed:11313478"
FT MUTAGEN 474
FT /note="S->E: Approximately 3-fold increased
FT autophosphorylation."
FT /evidence="ECO:0000269|PubMed:11313478"
FT STRAND 15..26
FT /evidence="ECO:0007829|PDB:2OV2"
FT TURN 27..30
FT /evidence="ECO:0007829|PDB:2OV2"
FT STRAND 31..34
FT /evidence="ECO:0007829|PDB:2OV2"
FT HELIX 37..39
FT /evidence="ECO:0007829|PDB:2OV2"
FT TURN 40..42
FT /evidence="ECO:0007829|PDB:2OV2"
FT TURN 46..48
FT /evidence="ECO:0007829|PDB:4L67"
FT HELIX 301..311
FT /evidence="ECO:0007829|PDB:2J0I"
FT STRAND 312..315
FT /evidence="ECO:0007829|PDB:4O0Y"
FT HELIX 317..319
FT /evidence="ECO:0007829|PDB:2J0I"
FT STRAND 321..329
FT /evidence="ECO:0007829|PDB:2J0I"
FT STRAND 331..333
FT /evidence="ECO:0007829|PDB:4L67"
FT STRAND 334..340
FT /evidence="ECO:0007829|PDB:2J0I"
FT TURN 341..343
FT /evidence="ECO:0007829|PDB:2J0I"
FT STRAND 346..353
FT /evidence="ECO:0007829|PDB:2J0I"
FT HELIX 354..356
FT /evidence="ECO:0007829|PDB:2Q0N"
FT HELIX 360..362
FT /evidence="ECO:0007829|PDB:2J0I"
FT HELIX 363..369
FT /evidence="ECO:0007829|PDB:2J0I"
FT TURN 370..372
FT /evidence="ECO:0007829|PDB:2J0I"
FT STRAND 381..387
FT /evidence="ECO:0007829|PDB:2J0I"
FT STRAND 390..395
FT /evidence="ECO:0007829|PDB:2J0I"
FT HELIX 403..409
FT /evidence="ECO:0007829|PDB:2J0I"
FT HELIX 414..433
FT /evidence="ECO:0007829|PDB:2J0I"
FT HELIX 443..445
FT /evidence="ECO:0007829|PDB:2J0I"
FT STRAND 446..448
FT /evidence="ECO:0007829|PDB:2J0I"
FT STRAND 454..456
FT /evidence="ECO:0007829|PDB:2J0I"
FT HELIX 459..461
FT /evidence="ECO:0007829|PDB:4FII"
FT STRAND 467..469
FT /evidence="ECO:0007829|PDB:2J0I"
FT STRAND 475..477
FT /evidence="ECO:0007829|PDB:2Q0N"
FT HELIX 479..481
FT /evidence="ECO:0007829|PDB:2J0I"
FT HELIX 484..487
FT /evidence="ECO:0007829|PDB:2J0I"
FT HELIX 495..510
FT /evidence="ECO:0007829|PDB:2J0I"
FT TURN 514..517
FT /evidence="ECO:0007829|PDB:2J0I"
FT HELIX 520..529
FT /evidence="ECO:0007829|PDB:2J0I"
FT HELIX 538..540
FT /evidence="ECO:0007829|PDB:2J0I"
FT HELIX 543..552
FT /evidence="ECO:0007829|PDB:2J0I"
FT TURN 557..559
FT /evidence="ECO:0007829|PDB:2J0I"
FT HELIX 563..566
FT /evidence="ECO:0007829|PDB:2J0I"
FT HELIX 570..574
FT /evidence="ECO:0007829|PDB:2J0I"
FT HELIX 578..581
FT /evidence="ECO:0007829|PDB:2J0I"
FT HELIX 582..584
FT /evidence="ECO:0007829|PDB:2J0I"
FT TURN 586..588
FT /evidence="ECO:0007829|PDB:2J0I"
SQ SEQUENCE 591 AA; 64072 MW; 04C2A5C0B06427D5 CRC64;
MFGKRKKRVE ISAPSNFEHR VHTGFDQHEQ KFTGLPRQWQ SLIEESARRP KPLVDPACIT
SIQPGAPKTI VRGSKGAKDG ALTLLLDEFE NMSVTRSNSL RRDSPPPPAR ARQENGMPEE
PATTARGGPG KAGSRGRFAG HSEAGGGSGD RRRAGPEKRP KSSREGSGGP QESSRDKRPL
SGPDVGTPQP AGLASGAKLA AGRPFNTYPR ADTDHPSRGA QGEPHDVAPN GPSAGGLAIP
QSSSSSSRPP TRARGAPSPG VLGPHASEPQ LAPPACTPAA PAVPGPPGPR SPQREPQRVS
HEQFRAALQL VVDPGDPRSY LDNFIKIGEG STGIVCIATV RSSGKLVAVK KMDLRKQQRR
ELLFNEVVIM RDYQHENVVE MYNSYLVGDE LWVVMEFLEG GALTDIVTHT RMNEEQIAAV
CLAVLQALSV LHAQGVIHRD IKSDSILLTH DGRVKLSDFG FCAQVSKEVP RRKSLVGTPY
WMAPELISRL PYGPEVDIWS LGIMVIEMVD GEPPYFNEPP LKAMKMIRDN LPPRLKNLHK
VSPSLKGFLD RLLVRDPAQR ATAAELLKHP FLAKAGPPAS IVPLMRQNRT R
