KKCC2_HUMAN
ID KKCC2_HUMAN Reviewed; 588 AA.
AC Q96RR4; A8K7Q7; O94883; Q8IUG2; Q8IUG3; Q8N3I4; Q8WY03; Q8WY04; Q8WY05;
AC Q8WY06; Q96RP1; Q96RP2; Q96RR3; Q9BWE9; Q9UER3; Q9UES2; Q9Y5N2;
DT 07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Calcium/calmodulin-dependent protein kinase kinase 2;
DE Short=CaM-KK 2;
DE Short=CaM-kinase kinase 2;
DE Short=CaMKK 2;
DE EC=2.7.11.17;
DE AltName: Full=Calcium/calmodulin-dependent protein kinase kinase beta;
DE Short=CaM-KK beta;
DE Short=CaM-kinase kinase beta;
DE Short=CaMKK beta;
GN Name=CAMKK2; Synonyms=CAMKKB, KIAA0787;
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 [GENOMIC DNA / MRNA] (ISOFORMS 1; 2; 3; 4; 5 AND 6),
RP FUNCTION, AND VARIANT SER-85.
RX PubMed=11395482; DOI=10.1074/jbc.m011720200;
RA Hsu L.-S., Chen G.-D., Lee L.-S., Chi C.-W., Cheng J.-F., Chen J.-Y.;
RT "Human Ca2+/calmodulin-dependent protein kinase kinase beta gene encodes
RT multiple isoforms that display distinct kinase activity.";
RL J. Biol. Chem. 276:31113-31123(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain cortex;
RX PubMed=9822657; DOI=10.1074/jbc.273.48.31880;
RA Anderson K.A., Means R.L., Huang Q.-H., Kemp B.E., Goldstein E.G.,
RA Selbert M.A., Edelman A.M., Fremeau R.T., Means A.R.;
RT "Components of a calmodulin-dependent protein kinase cascade. Molecular
RT cloning, functional characterization and cellular localization of
RT Ca2+/calmodulin-dependent protein kinase kinase beta.";
RL J. Biol. Chem. 273:31880-31889(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND FUNCTION IN PHOSPHORYLATION OF
RP CAMK1D.
RX PubMed=12935886; DOI=10.1016/s0014-5793(03)00817-2;
RA Ishikawa Y., Tokumitsu H., Inuzuka H., Murata-Hori M., Hosoya H.,
RA Kobayashi R.;
RT "Identification and characterization of novel components of a
RT Ca2+/calmodulin-dependent protein kinase cascade in HeLa cells.";
RL FEBS Lett. 550:57-63(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7), AND VARIANT SER-85.
RC TISSUE=Brain;
RX PubMed=9872452; DOI=10.1093/dnares/5.5.277;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XI. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:277-286(1998).
RN [5]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Stomach;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 233-588 (ISOFORM 5), AND VARIANT SER-85.
RC TISSUE=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 [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 117-588 (ISOFORM 2), FUNCTION IN
RP PHOSPHORYLATION OF CAMK1, AND TISSUE SPECIFICITY.
RX PubMed=9662074; DOI=10.1007/bf02258368;
RA Hsu L.-S., Tsou A.-P., Chi C.-W., Lee C.-H., Chen J.-Y.;
RT "Cloning, expression and chromosomal localization of human Ca2+/calmodulin-
RT dependent protein kinase kinase.";
RL J. Biomed. Sci. 5:141-149(1998).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 254-588 (ISOFORM 7).
RC TISSUE=Amygdala;
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 [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 338-533 (ISOFORM 2).
RA Barrow I.K.-P., Boguski M.S., Touchman J.W., Spencer F.;
RT "Full-insert sequence of mapped XREF EST.";
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-495, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-522 (ISOFORM 3), PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-479 (ISOFORM 5), AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [13]
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 [14]
RP FUNCTION, SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION, PHOSPHORYLATION BY
RP PKA, AND INDUCTION OF ISOFORM 1.
RX PubMed=21957496; DOI=10.4161/rna.8.6.16691;
RA Cao W., Sohail M., Liu G., Koumbadinga G.A., Lobo V.G., Xie J.;
RT "Differential effects of PKA-controlled CaMKK2 variants on neuronal
RT differentiation.";
RL RNA Biol. 8:1061-1072(2011).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-114; SER-129; SER-495 AND
RP SER-511, 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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-495, 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 [18]
RP VARIANTS [LARGE SCALE ANALYSIS] ASN-10; SER-85; TYR-123; LEU-127; THR-182
RP AND HIS-492.
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: Calcium/calmodulin-dependent protein kinase belonging to a
CC proposed calcium-triggered signaling cascade involved in a number of
CC cellular processes. Isoform 1, isoform 2 and isoform 3 phosphorylate
CC CAMK1 and CAMK4. Isoform 3 phosphorylates CAMK1D. Isoform 4, isoform 5
CC and isoform 6 lacking part of the calmodulin-binding domain are
CC inactive. Efficiently phosphorylates 5'-AMP-activated protein kinase
CC (AMPK) trimer, including that consisting of PRKAA1, PRKAB1 and PRKAG1.
CC This phosphorylation is stimulated in response to Ca(2+) signals (By
CC similarity). Seems to be involved in hippocampal activation of CREB1
CC (By similarity). May play a role in neurite growth. Isoform 3 may
CC promote neurite elongation, while isoform 1 may promoter neurite
CC branching. {ECO:0000250, ECO:0000269|PubMed:11395482,
CC ECO:0000269|PubMed:12935886, ECO:0000269|PubMed:21957496,
CC ECO:0000269|PubMed:9662074}.
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=2.7.11.17;
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=2.7.11.17;
CC -!- ACTIVITY REGULATION: Activated by Ca(2+)/calmodulin. Binding of
CC calmodulin may relieve intrasteric autoinhibition. Autophosphorylation
CC does not alter activity or regulation by Ca(2+)/calmodulin. In part,
CC activity is independent on Ca(2+)/calmodulin (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Interacts with calmodulin. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21957496}. Cytoplasm
CC {ECO:0000269|PubMed:21957496}. Cell projection, neuron projection
CC {ECO:0000269|PubMed:21957496}. Note=Predominantly nuclear in
CC unstimulated cells, relocalizes into cytoplasm and neurites after
CC forskolin induction. {ECO:0000269|PubMed:21957496}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1; Synonyms=Beta1, CAMKK2+E16;
CC IsoId=Q96RR4-1; Sequence=Displayed;
CC Name=2; Synonyms=Beta2;
CC IsoId=Q96RR4-2; Sequence=VSP_012146, VSP_012147, VSP_012149;
CC Name=3; Synonyms=Beta1delta16, CAMKK2-E16;
CC IsoId=Q96RR4-3; Sequence=VSP_012143, VSP_012144, VSP_012145,
CC VSP_012149;
CC Name=4; Synonyms=Beta1delta14;
CC IsoId=Q96RR4-4; Sequence=VSP_012142;
CC Name=5; Synonyms=Beta1delta14/16, beta-3x;
CC IsoId=Q96RR4-5; Sequence=VSP_012142, VSP_012143, VSP_012144,
CC VSP_012145, VSP_012149;
CC Name=6; Synonyms=Beta2delta14;
CC IsoId=Q96RR4-6; Sequence=VSP_012142, VSP_012146, VSP_012147,
CC VSP_012149;
CC Name=7;
CC IsoId=Q96RR4-7; Sequence=VSP_012148, VSP_012149;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with higher levels in the
CC brain. Intermediate levels are detected in spleen, prostate, thyroid
CC and leukocytes. The lowest level is in lung.
CC {ECO:0000269|PubMed:9662074}.
CC -!- INDUCTION: [Isoform 1]: Up-regulated by PKA pathway.
CC {ECO:0000269|PubMed:21957496}.
CC -!- DOMAIN: The autoinhibitory domain overlaps with the calmodulin binding
CC region and may be involved in intrasteric autoinhibition.
CC -!- DOMAIN: The RP domain (arginine/proline-rich) is involved in the
CC recognition of CAMKI and CAMK4 as substrates. {ECO:0000250}.
CC -!- PTM: Autophosphorylated and phosphorylated by PKA. Each isoform may
CC show a different pattern of phosphorylation.
CC {ECO:0000269|PubMed:21957496}.
CC -!- MISCELLANEOUS: [Isoform 1]: Major isoform.
CC -!- MISCELLANEOUS: [Isoform 2]: Major isoform. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 5]: Inactive. Does not activate CAMK1 and
CC CAMK4. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 6]: Inactive. Does not activate CAMK1 and
CC CAMK4. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC72943.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA34507.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAD38990.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
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DR EMBL; AB081337; BAC19841.1; -; mRNA.
DR EMBL; AF287630; AAK64600.1; -; mRNA.
DR EMBL; AF287631; AAK64601.1; -; mRNA.
DR EMBL; AF321385; AAL37215.1; -; mRNA.
DR EMBL; AF321386; AAL37216.1; -; mRNA.
DR EMBL; AF321387; AAL37217.1; -; mRNA.
DR EMBL; AF321388; AAL37218.1; -; mRNA.
DR EMBL; AF321401; AAK91830.1; -; Genomic_DNA.
DR EMBL; AF321390; AAK91830.1; JOINED; Genomic_DNA.
DR EMBL; AF321391; AAK91830.1; JOINED; Genomic_DNA.
DR EMBL; AF321392; AAK91830.1; JOINED; Genomic_DNA.
DR EMBL; AF321393; AAK91830.1; JOINED; Genomic_DNA.
DR EMBL; AF321394; AAK91830.1; JOINED; Genomic_DNA.
DR EMBL; AF321395; AAK91830.1; JOINED; Genomic_DNA.
DR EMBL; AF321396; AAK91830.1; JOINED; Genomic_DNA.
DR EMBL; AF321397; AAK91830.1; JOINED; Genomic_DNA.
DR EMBL; AF321398; AAK91830.1; JOINED; Genomic_DNA.
DR EMBL; AF321399; AAK91830.1; JOINED; Genomic_DNA.
DR EMBL; AF321400; AAK91830.1; JOINED; Genomic_DNA.
DR EMBL; AF321575; AAK91830.1; JOINED; Genomic_DNA.
DR EMBL; AF321576; AAK91830.1; JOINED; Genomic_DNA.
DR EMBL; AF321577; AAK91830.1; JOINED; Genomic_DNA.
DR EMBL; AF321578; AAK91830.1; JOINED; Genomic_DNA.
DR EMBL; AF321402; AAK91829.1; -; Genomic_DNA.
DR EMBL; AF321390; AAK91829.1; JOINED; Genomic_DNA.
DR EMBL; AF321391; AAK91829.1; JOINED; Genomic_DNA.
DR EMBL; AF321392; AAK91829.1; JOINED; Genomic_DNA.
DR EMBL; AF321393; AAK91829.1; JOINED; Genomic_DNA.
DR EMBL; AF321394; AAK91829.1; JOINED; Genomic_DNA.
DR EMBL; AF321395; AAK91829.1; JOINED; Genomic_DNA.
DR EMBL; AF321396; AAK91829.1; JOINED; Genomic_DNA.
DR EMBL; AF321397; AAK91829.1; JOINED; Genomic_DNA.
DR EMBL; AF321398; AAK91829.1; JOINED; Genomic_DNA.
DR EMBL; AF321399; AAK91829.1; JOINED; Genomic_DNA.
DR EMBL; AF321400; AAK91829.1; JOINED; Genomic_DNA.
DR EMBL; AF321575; AAK91829.1; JOINED; Genomic_DNA.
DR EMBL; AF321576; AAK91829.1; JOINED; Genomic_DNA.
DR EMBL; AF321577; AAK91829.1; JOINED; Genomic_DNA.
DR EMBL; AF321578; AAK91829.1; JOINED; Genomic_DNA.
DR EMBL; AF140507; AAD31507.1; -; mRNA.
DR EMBL; AB081336; BAC19840.1; -; mRNA.
DR EMBL; AB018330; BAA34507.2; ALT_INIT; mRNA.
DR EMBL; AK292072; BAF84761.1; -; mRNA.
DR EMBL; AC069209; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000318; AAH00318.2; -; mRNA.
DR EMBL; BC026060; AAH26060.1; -; mRNA.
DR EMBL; AF101264; AAD04566.1; -; mRNA.
DR EMBL; AL834322; CAD38990.1; ALT_SEQ; mRNA.
DR EMBL; AF091074; AAC72943.1; ALT_INIT; mRNA.
DR CCDS; CCDS44999.1; -. [Q96RR4-2]
DR CCDS; CCDS53837.1; -. [Q96RR4-6]
DR CCDS; CCDS58283.1; -. [Q96RR4-7]
DR CCDS; CCDS9216.1; -. [Q96RR4-1]
DR CCDS; CCDS9217.1; -. [Q96RR4-4]
DR CCDS; CCDS9218.1; -. [Q96RR4-3]
DR CCDS; CCDS9219.1; -. [Q96RR4-5]
DR PIR; JE0191; JE0191.
DR RefSeq; NP_001257414.1; NM_001270485.1. [Q96RR4-1]
DR RefSeq; NP_001257415.1; NM_001270486.1. [Q96RR4-7]
DR RefSeq; NP_006540.3; NM_006549.3. [Q96RR4-1]
DR RefSeq; NP_705719.2; NM_153499.2. [Q96RR4-3]
DR RefSeq; NP_705720.1; NM_153500.1. [Q96RR4-5]
DR RefSeq; NP_757363.1; NM_172214.2. [Q96RR4-2]
DR RefSeq; NP_757364.1; NM_172215.2. [Q96RR4-6]
DR RefSeq; NP_757365.1; NM_172216.1. [Q96RR4-4]
DR RefSeq; NP_757380.1; NM_172226.2. [Q96RR4-3]
DR RefSeq; XP_005253880.1; XM_005253823.1. [Q96RR4-2]
DR RefSeq; XP_005253881.1; XM_005253824.3. [Q96RR4-5]
DR RefSeq; XP_011536065.1; XM_011537763.1. [Q96RR4-7]
DR RefSeq; XP_016874187.1; XM_017018698.1.
DR RefSeq; XP_016874190.1; XM_017018701.1.
DR RefSeq; XP_016874191.1; XM_017018702.1. [Q96RR4-7]
DR RefSeq; XP_016874193.1; XM_017018704.1.
DR PDB; 2ZV2; X-ray; 2.40 A; A=158-448.
DR PDB; 5UY6; X-ray; 1.70 A; A=161-449.
DR PDB; 5UYJ; X-ray; 1.60 A; A=161-449.
DR PDB; 5VT1; X-ray; 1.90 A; A=161-449.
DR PDB; 5YV8; X-ray; 1.93 A; A=158-448.
DR PDB; 5YV9; X-ray; 2.53 A; A=158-448.
DR PDB; 5YVA; X-ray; 2.57 A; A=158-448.
DR PDB; 5YVB; X-ray; 2.02 A; A=158-448.
DR PDB; 5YVC; X-ray; 2.02 A; A=158-448.
DR PDB; 6BKU; X-ray; 2.00 A; A=162-449.
DR PDB; 6BLE; X-ray; 1.90 A; A=161-449.
DR PDB; 6BQL; X-ray; 2.00 A; A=161-449.
DR PDB; 6BQP; X-ray; 1.95 A; A=161-449.
DR PDB; 6BQQ; X-ray; 1.80 A; A=161-449.
DR PDB; 6BRC; X-ray; 2.20 A; A/B=161-449.
DR PDB; 6CMJ; X-ray; 2.40 A; A/B=149-465.
DR PDB; 6EF5; X-ray; 2.44 A; Q/S=508-514.
DR PDB; 6EWW; X-ray; 2.68 A; E/F/G/H=97-104.
DR PDB; 6FEL; X-ray; 2.84 A; E/F/G/H=508-515.
DR PDB; 6Y3O; X-ray; 1.50 A; P=97-104.
DR PDB; 6Y4K; X-ray; 3.00 A; E/F=97-104.
DR PDB; 6Y6B; X-ray; 3.08 A; C/D=97-104.
DR PDB; 6Y8A; X-ray; 1.50 A; P=508-515.
DR PDBsum; 2ZV2; -.
DR PDBsum; 5UY6; -.
DR PDBsum; 5UYJ; -.
DR PDBsum; 5VT1; -.
DR PDBsum; 5YV8; -.
DR PDBsum; 5YV9; -.
DR PDBsum; 5YVA; -.
DR PDBsum; 5YVB; -.
DR PDBsum; 5YVC; -.
DR PDBsum; 6BKU; -.
DR PDBsum; 6BLE; -.
DR PDBsum; 6BQL; -.
DR PDBsum; 6BQP; -.
DR PDBsum; 6BQQ; -.
DR PDBsum; 6BRC; -.
DR PDBsum; 6CMJ; -.
DR PDBsum; 6EF5; -.
DR PDBsum; 6EWW; -.
DR PDBsum; 6FEL; -.
DR PDBsum; 6Y3O; -.
DR PDBsum; 6Y4K; -.
DR PDBsum; 6Y6B; -.
DR PDBsum; 6Y8A; -.
DR AlphaFoldDB; Q96RR4; -.
DR SMR; Q96RR4; -.
DR BioGRID; 115889; 64.
DR IntAct; Q96RR4; 31.
DR STRING; 9606.ENSP00000312741; -.
DR BindingDB; Q96RR4; -.
DR ChEMBL; CHEMBL5284; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q96RR4; -.
DR GuidetoPHARMACOLOGY; 1957; -.
DR GlyGen; Q96RR4; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96RR4; -.
DR PhosphoSitePlus; Q96RR4; -.
DR BioMuta; CAMKK2; -.
DR DMDM; 317373374; -.
DR EPD; Q96RR4; -.
DR jPOST; Q96RR4; -.
DR MassIVE; Q96RR4; -.
DR MaxQB; Q96RR4; -.
DR PaxDb; Q96RR4; -.
DR PeptideAtlas; Q96RR4; -.
DR PRIDE; Q96RR4; -.
DR ProteomicsDB; 78009; -. [Q96RR4-1]
DR ProteomicsDB; 78010; -. [Q96RR4-2]
DR ProteomicsDB; 78011; -. [Q96RR4-3]
DR ProteomicsDB; 78012; -. [Q96RR4-4]
DR ProteomicsDB; 78013; -. [Q96RR4-5]
DR ProteomicsDB; 78014; -. [Q96RR4-6]
DR ProteomicsDB; 78015; -. [Q96RR4-7]
DR Antibodypedia; 19059; 395 antibodies from 35 providers.
DR DNASU; 10645; -.
DR Ensembl; ENST00000324774.9; ENSP00000312741.5; ENSG00000110931.19. [Q96RR4-1]
DR Ensembl; ENST00000337174.7; ENSP00000336634.3; ENSG00000110931.19. [Q96RR4-3]
DR Ensembl; ENST00000347034.6; ENSP00000321230.3; ENSG00000110931.19. [Q96RR4-4]
DR Ensembl; ENST00000392473.2; ENSP00000376265.2; ENSG00000110931.19. [Q96RR4-2]
DR Ensembl; ENST00000392474.6; ENSP00000376266.2; ENSG00000110931.19. [Q96RR4-7]
DR Ensembl; ENST00000402834.8; ENSP00000384591.4; ENSG00000110931.19. [Q96RR4-1]
DR Ensembl; ENST00000404169.8; ENSP00000384600.3; ENSG00000110931.19. [Q96RR4-1]
DR Ensembl; ENST00000412367.6; ENSP00000388368.2; ENSG00000110931.19. [Q96RR4-3]
DR Ensembl; ENST00000446440.6; ENSP00000388273.2; ENSG00000110931.19. [Q96RR4-6]
DR Ensembl; ENST00000538733.5; ENSP00000445944.1; ENSG00000110931.19. [Q96RR4-5]
DR Ensembl; ENST00000652382.1; ENSP00000498824.1; ENSG00000110931.19. [Q96RR4-1]
DR GeneID; 10645; -.
DR KEGG; hsa:10645; -.
DR MANE-Select; ENST00000404169.8; ENSP00000384600.3; NM_001270485.2; NP_001257414.1.
DR UCSC; uc001tzt.4; human. [Q96RR4-1]
DR CTD; 10645; -.
DR DisGeNET; 10645; -.
DR GeneCards; CAMKK2; -.
DR HGNC; HGNC:1470; CAMKK2.
DR HPA; ENSG00000110931; Tissue enhanced (brain).
DR MIM; 615002; gene.
DR neXtProt; NX_Q96RR4; -.
DR OpenTargets; ENSG00000110931; -.
DR PharmGKB; PA26052; -.
DR VEuPathDB; HostDB:ENSG00000110931; -.
DR eggNOG; KOG0585; Eukaryota.
DR GeneTree; ENSGT00940000161828; -.
DR HOGENOM; CLU_000288_63_0_1; -.
DR InParanoid; Q96RR4; -.
DR OMA; NGRCVHP; -.
DR OrthoDB; 856506at2759; -.
DR PhylomeDB; Q96RR4; -.
DR TreeFam; TF313013; -.
DR BRENDA; 2.7.11.17; 2681.
DR PathwayCommons; Q96RR4; -.
DR Reactome; R-HSA-111932; CaMK IV-mediated phosphorylation of CREB.
DR Reactome; R-HSA-442729; CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde.
DR Reactome; R-HSA-9619229; Activation of RAC1 downstream of NMDARs.
DR Reactome; R-HSA-9619483; Activation of AMPK downstream of NMDARs.
DR SignaLink; Q96RR4; -.
DR SIGNOR; Q96RR4; -.
DR BioGRID-ORCS; 10645; 15 hits in 1109 CRISPR screens.
DR ChiTaRS; CAMKK2; human.
DR EvolutionaryTrace; Q96RR4; -.
DR GeneWiki; CAMKK2; -.
DR GenomeRNAi; 10645; -.
DR Pharos; Q96RR4; Tchem.
DR PRO; PR:Q96RR4; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q96RR4; protein.
DR Bgee; ENSG00000110931; Expressed in cerebellar cortex and 200 other tissues.
DR ExpressionAtlas; Q96RR4; baseline and differential.
DR Genevisible; Q96RR4; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0043005; C:neuron projection; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; TAS:UniProtKB.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0004713; F:protein tyrosine kinase activity; TAS:UniProtKB.
DR GO; GO:0032147; P:activation of protein kinase activity; IBA:GO_Central.
DR GO; GO:0019722; P:calcium-mediated signaling; TAS:UniProtKB.
DR GO; GO:0061762; P:CAMKK-AMPK signaling cascade; IMP:ParkinsonsUK-UCL.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; TAS:ParkinsonsUK-UCL.
DR GO; GO:0000165; P:MAPK cascade; TAS:UniProtKB.
DR GO; GO:1903599; P:positive regulation of autophagy of mitochondrion; IC:ParkinsonsUK-UCL.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:ParkinsonsUK-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; TAS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0045859; P:regulation of protein kinase activity; TAS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 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; Acetylation; Alternative splicing; ATP-binding;
KW Calmodulin-binding; Cell projection; Cytoplasm; Kinase; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..588
FT /note="Calcium/calmodulin-dependent protein kinase kinase
FT 2"
FT /id="PRO_0000086144"
FT DOMAIN 165..446
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..33
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 78..100
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 128..149
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 204..226
FT /note="RP domain"
FT REGION 205..225
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 472..477
FT /note="Autoinhibitory domain"
FT /evidence="ECO:0000250"
FT REGION 475..500
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250"
FT REGION 497..588
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 82..100
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 128..142
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 523..540
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 312
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 171..179
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 194
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 100
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8C078"
FT MOD_RES 114
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 129
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 133
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8C078"
FT MOD_RES 137
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8C078"
FT MOD_RES 495
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 511
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 572
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8C078"
FT VAR_SEQ 442..484
FT /note="Missing (in isoform 4, isoform 5 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:11395482,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_012142"
FT VAR_SEQ 520..532
FT /note="KPTRECESLSELK -> QGSEDNLQGTDPP (in isoform 3 and
FT isoform 5)"
FT /evidence="ECO:0000303|PubMed:11395482,
FT ECO:0000303|PubMed:12935886, ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_012143"
FT VAR_SEQ 533..554
FT /note="EARQRRQPPGHRPAPRGGGGSA -> GTKKKKGLDSMTSTVAAGWLDRRV
FT (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:17974005,
FT ECO:0000303|PubMed:9872452"
FT /id="VSP_012148"
FT VAR_SEQ 533..541
FT /note="EARQRRQPP -> PVGEEEVLL (in isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:11395482,
FT ECO:0000303|PubMed:12935886, ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_012144"
FT VAR_SEQ 533
FT /note="E -> T (in isoform 2 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:11395482,
FT ECO:0000303|PubMed:9662074, ECO:0000303|Ref.11"
FT /id="VSP_012146"
FT VAR_SEQ 534..554
FT /note="Missing (in isoform 2 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:11395482,
FT ECO:0000303|PubMed:9662074, ECO:0000303|Ref.11"
FT /id="VSP_012147"
FT VAR_SEQ 542..554
FT /note="Missing (in isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:11395482,
FT ECO:0000303|PubMed:12935886, ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_012145"
FT VAR_SEQ 555..588
FT /note="Missing (in isoform 2, isoform 3, isoform 5, isoform
FT 6 and isoform 7)"
FT /evidence="ECO:0000303|PubMed:11395482,
FT ECO:0000303|PubMed:12935886, ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:17974005,
FT ECO:0000303|PubMed:9662074, ECO:0000303|PubMed:9872452,
FT ECO:0000303|Ref.11"
FT /id="VSP_012149"
FT VARIANT 10
FT /note="S -> N (in dbSNP:rs28360477)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_032788"
FT VARIANT 85
FT /note="T -> S (in dbSNP:rs3817190)"
FT /evidence="ECO:0000269|PubMed:11395482,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:9872452"
FT /id="VAR_020532"
FT VARIANT 123
FT /note="C -> Y (in dbSNP:rs35403710)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040610"
FT VARIANT 127
FT /note="P -> L (in a lung neuroendocrine carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040611"
FT VARIANT 182
FT /note="A -> T (in a colorectal adenocarcinoma sample;
FT somatic mutation; dbSNP:rs1207121718)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040612"
FT VARIANT 363
FT /note="R -> C (in dbSNP:rs1132780)"
FT /id="VAR_020533"
FT VARIANT 492
FT /note="R -> H (in dbSNP:rs34129994)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040613"
FT CONFLICT 206
FT /note="G -> A (in Ref. 2; AAD31507)"
FT /evidence="ECO:0000305"
FT CONFLICT 331
FT /note="F -> I (in Ref. 6; BAF84761)"
FT /evidence="ECO:0000305"
FT CONFLICT 347
FT /note="T -> Y (in Ref. 2; AAD31507)"
FT /evidence="ECO:0000305"
FT CONFLICT 371
FT /note="L -> K (in Ref. 2; AAD31507)"
FT /evidence="ECO:0000305"
FT CONFLICT 554
FT /note="A -> H (in Ref. 1; AAK91829)"
FT /evidence="ECO:0000305"
FT CONFLICT 557
FT /note="R -> N (in Ref. 1; AAK91829)"
FT /evidence="ECO:0000305"
FT STRAND 165..172
FT /evidence="ECO:0007829|PDB:5UYJ"
FT STRAND 175..184
FT /evidence="ECO:0007829|PDB:5UYJ"
FT TURN 185..188
FT /evidence="ECO:0007829|PDB:5UYJ"
FT STRAND 189..197
FT /evidence="ECO:0007829|PDB:5UYJ"
FT HELIX 198..204
FT /evidence="ECO:0007829|PDB:5UYJ"
FT HELIX 231..242
FT /evidence="ECO:0007829|PDB:5UYJ"
FT STRAND 251..256
FT /evidence="ECO:0007829|PDB:5UYJ"
FT STRAND 260..268
FT /evidence="ECO:0007829|PDB:5UYJ"
FT STRAND 273..275
FT /evidence="ECO:0007829|PDB:5UYJ"
FT HELIX 286..305
FT /evidence="ECO:0007829|PDB:5UYJ"
FT HELIX 315..317
FT /evidence="ECO:0007829|PDB:5UYJ"
FT STRAND 318..320
FT /evidence="ECO:0007829|PDB:5UYJ"
FT STRAND 326..328
FT /evidence="ECO:0007829|PDB:5UYJ"
FT STRAND 338..341
FT /evidence="ECO:0007829|PDB:5UY6"
FT STRAND 343..346
FT /evidence="ECO:0007829|PDB:5UYJ"
FT HELIX 351..353
FT /evidence="ECO:0007829|PDB:5UYJ"
FT HELIX 356..358
FT /evidence="ECO:0007829|PDB:5UYJ"
FT STRAND 364..367
FT /evidence="ECO:0007829|PDB:6CMJ"
FT HELIX 368..385
FT /evidence="ECO:0007829|PDB:5UYJ"
FT HELIX 395..404
FT /evidence="ECO:0007829|PDB:5UYJ"
FT STRAND 411..413
FT /evidence="ECO:0007829|PDB:5UYJ"
FT HELIX 417..426
FT /evidence="ECO:0007829|PDB:5UYJ"
FT TURN 431..433
FT /evidence="ECO:0007829|PDB:5UYJ"
FT HELIX 437..440
FT /evidence="ECO:0007829|PDB:5UYJ"
FT HELIX 444..447
FT /evidence="ECO:0007829|PDB:5UYJ"
FT TURN 448..451
FT /evidence="ECO:0007829|PDB:6CMJ"
FT HELIX 457..461
FT /evidence="ECO:0007829|PDB:6CMJ"
FT MOD_RES Q96RR4-3:522
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES Q96RR4-5:479
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
SQ SEQUENCE 588 AA; 64746 MW; 04E3583561341167 CRC64;
MSSCVSSQPS SNRAAPQDEL GGRGSSSSES QKPCEALRGL SSLSIHLGME SFIVVTECEP
GCAVDLGLAR DRPLEADGQE VPLDTSGSQA RPHLSGRKLS LQERSQGGLA AGGSLDMNGR
CICPSLPYSP VSSPQSSPRL PRRPTVESHH VSITGMQDCV QLNQYTLKDE IGKGSYGVVK
LAYNENDNTY YAMKVLSKKK LIRQAGFPRR PPPRGTRPAP GGCIQPRGPI EQVYQEIAIL
KKLDHPNVVK LVEVLDDPNE DHLYMVFELV NQGPVMEVPT LKPLSEDQAR FYFQDLIKGI
EYLHYQKIIH RDIKPSNLLV GEDGHIKIAD FGVSNEFKGS DALLSNTVGT PAFMAPESLS
ETRKIFSGKA LDVWAMGVTL YCFVFGQCPF MDERIMCLHS KIKSQALEFP DQPDIAEDLK
DLITRMLDKN PESRIVVPEI KLHPWVTRHG AEPLPSEDEN CTLVEVTEEE VENSVKHIPS
LATVILVKTM IRKRSFGNPF EGSRREERSL SAPGNLLTKK PTRECESLSE LKEARQRRQP
PGHRPAPRGG GGSALVRGSP CVESCWAPAP GSPARMHPLR PEEAMEPE
