ID CDK16_HUMAN Reviewed; 496 AA. AC Q00536; A8K280; B7Z7C8; J3KN74; J3KQP7; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1993, sequence version 1. DT 27-MAR-2024, entry version 217. DE RecName: Full=Cyclin-dependent kinase 16; DE EC=2.7.11.22 {ECO:0000269|PubMed:22184064, ECO:0000269|PubMed:22796189, ECO:0000269|PubMed:22798068}; DE AltName: Full=Cell division protein kinase 16; DE AltName: Full=PCTAIRE-motif protein kinase 1; DE AltName: Full=Serine/threonine-protein kinase PCTAIRE-1; GN Name=CDK16; Synonyms=PCTAIRE1, PCTK1; 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=Fetal brain; RX PubMed=1639063; DOI=10.1002/j.1460-2075.1992.tb05360.x; RA Meyerson M., Enders G.H., Wu C.-L., Su L.-K., Gorka C., Nelson C., RA Harlow E., Tsai L.-H.; RT "A family of human cdc2-related protein kinases."; RL EMBO J. 11:2909-2917(1992). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Testis, and Thalamus; 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 [4] 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 [5] 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Brain, 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 [7] RP IDENTIFICATION BY 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 [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-78; SER-82; SER-95; SER-119 RP AND SER-138, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-138; SER-153 AND SER-155, 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 [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42; SER-78; SER-82; SER-95; RP SER-119 AND SER-138, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-153, 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 [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-119 AND SER-153, 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 [14] RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH CCNY. RX PubMed=22796189; DOI=10.1016/j.cellsig.2012.06.018; RA Shehata S.N., Hunter R.W., Ohta E., Peggie M.W., Lou H.J., Sicheri F., RA Zeqiraj E., Turk B.E., Sakamoto K.; RT "Analysis of substrate specificity and cyclin Y binding of PCTAIRE-1 RT kinase."; RL Cell. Signal. 24:2085-2094(2012). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH BRSK2, SUBCELLULAR LOCATION, RP MUTAGENESIS OF SER-12; SER-153 AND LYS-194, PHOSPHORYLATION AT SER-12, AND RP TISSUE SPECIFICITY. RX PubMed=22798068; DOI=10.1074/jbc.m112.375618; RA Chen X.Y., Gu X.T., Saiyin H., Wan B., Zhang Y.J., Li J., Wang Y.L., RA Gao R., Wang Y.F., Dong W.P., Najjar S.M., Zhang C.Y., Ding H.F., Liu J.O., RA Yu L.; RT "Brain-selective kinase 2 (BRSK2) phosphorylation on PCTAIRE1 negatively RT regulates glucose-stimulated insulin secretion in pancreatic beta-cells."; RL J. Biol. Chem. 287:30368-30375(2012). RN [16] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH CCNY RP AND, AND MUTAGENESIS OF SER-119; SER-153 AND LYS-194. RX PubMed=22184064; DOI=10.1128/mcb.06261-11; RA Mikolcevic P., Sigl R., Rauch V., Hess M.W., Pfaller K., Barisic M., RA Pelliniemi L.J., Boesl M., Geley S.; RT "Cyclin-dependent kinase 16/PCTAIRE kinase 1 is activated by cyclin Y and RT is essential for spermatogenesis."; RL Mol. Cell. Biol. 32:868-879(2012). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12; SER-65; SER-95; SER-138; RP SER-153 AND SER-155, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 [18] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 163-478. RG Structural genomics consortium (SGC); RT "Crystal structure of the PCTAIRE1 kinase in complex with indirubin e804."; RL Submitted (JUN-2010) to the PDB data bank. CC -!- FUNCTION: Protein kinase that plays a role in vesicle-mediated CC transport processes and exocytosis. Regulates GH1 release by brain CC neurons. Phosphorylates NSF, and thereby regulates NSF oligomerization. CC Required for normal spermatogenesis. Regulates neuron differentiation CC and dendrite development (By similarity). Plays a role in the CC regulation of insulin secretion in response to changes in blood glucose CC levels. Can phosphorylate CCNY at 'Ser-336' (in vitro). {ECO:0000250, CC ECO:0000269|PubMed:22184064, ECO:0000269|PubMed:22796189, CC ECO:0000269|PubMed:22798068}. 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=2.7.11.22; CC Evidence={ECO:0000269|PubMed:22184064, ECO:0000269|PubMed:22796189, CC ECO:0000269|PubMed:22798068}; 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=2.7.11.22; Evidence={ECO:0000269|PubMed:22184064, CC ECO:0000269|PubMed:22796189, ECO:0000269|PubMed:22798068}; CC -!- SUBUNIT: Found in a complex containing CABLES1, CDK17 and TDRD7. CC Interacts with BRSK2. Identified in a complex with NSF, syntaxin-1, CC synaptotagmin, SYN1, SYP and CDK5R1 (By similarity). Interacts with CC YWHAH, YWHAQ and YWHAZ. Interacts with CCNY; this interaction increases CC the CDK16 kinase activity (By similarity). Interacts with CCNYL1; this CC interaction mutually increases the stability of CDK16 and CCNYL1 and CC increases the kinase activity of CDK16 (By similarity). Interacts with CC NSF (By similarity). {ECO:0000250|UniProtKB:Q04735, CC ECO:0000269|PubMed:22184064, ECO:0000269|PubMed:22796189, CC ECO:0000269|PubMed:22798068}. CC -!- INTERACTION: CC Q00536; Q92624: APPBP2; NbExp=3; IntAct=EBI-726261, EBI-743771; CC Q00536; Q8ND76-1: CCNY; NbExp=7; IntAct=EBI-726261, EBI-11615526; CC Q00536; Q8N7R7: CCNYL1; NbExp=4; IntAct=EBI-726261, EBI-10103094; CC Q00536; Q15436: SEC23A; NbExp=3; IntAct=EBI-726261, EBI-81088; CC Q00536; P62258: YWHAE; NbExp=4; IntAct=EBI-726261, EBI-356498; CC Q00536; O43829: ZBTB14; NbExp=3; IntAct=EBI-726261, EBI-10176632; CC Q00536-3; P30281: CCND3; NbExp=3; IntAct=EBI-12401765, EBI-375013; CC Q00536-3; O43829: ZBTB14; NbExp=3; IntAct=EBI-12401765, EBI-10176632; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22798068}. CC Cytoplasmic vesicle, secretory vesicle {ECO:0000250|UniProtKB:Q63686}. CC Cell membrane {ECO:0000269|PubMed:22184064}; Peripheral membrane CC protein {ECO:0000269|PubMed:22184064}; Cytoplasmic side CC {ECO:0000269|PubMed:22184064}. Synapse, synaptosome CC {ECO:0000250|UniProtKB:Q63686}. Note=Colocalizes with insulin in CC pancreas islets. Recruited to the cell membrane by CCNY. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q00536-1; Sequence=Displayed; CC Name=2; CC IsoId=Q00536-2; Sequence=VSP_046134; CC Name=3; CC IsoId=Q00536-3; Sequence=VSP_046342; CC -!- TISSUE SPECIFICITY: Detected in pancreas islets (at protein level). CC Detected in brain and pancreas. {ECO:0000269|PubMed:22798068}. CC -!- PTM: Phosphorylation of CDK16 is essential for the binding of CCNY, but CC also essential for the regulation of CDK16 kinase activity CC (PubMed:22798068). Phosphorylation of CDK16 is essential for the CC binding of CCNYl1, but also essential for the regulation of CDK16 CC kinase activity (By similarity). Ser-146 and Ser-153 are the most CC critical sites for the binding of CCNYL1 and for modulating CDK16 CC kinase activity (By similarity). Phosphorylation at Ser-153 inhibits CC kinase activity (PubMed:22798068). {ECO:0000250|UniProtKB:Q04735, CC ECO:0000269|PubMed:22798068}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr CC protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH01048.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAH15607.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X66363; CAA47006.1; -; mRNA. DR EMBL; BT006827; AAP35473.1; -; mRNA. DR EMBL; AK290145; BAF82834.1; -; mRNA. DR EMBL; AK301832; BAH13564.1; -; mRNA. DR EMBL; AL096791; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL513366; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471164; EAW59295.1; -; Genomic_DNA. DR EMBL; CH471164; EAW59297.1; -; Genomic_DNA. DR EMBL; BC001048; AAH01048.1; ALT_INIT; mRNA. DR EMBL; BC015607; AAH15607.1; ALT_INIT; mRNA. DR CCDS; CCDS14276.1; -. [Q00536-1] DR CCDS; CCDS48101.1; -. [Q00536-3] DR CCDS; CCDS55408.1; -. [Q00536-2] DR PIR; S23385; S23385. DR RefSeq; NP_001163931.1; NM_001170460.1. [Q00536-2] DR RefSeq; NP_006192.1; NM_006201.4. [Q00536-1] DR RefSeq; NP_148978.2; NM_033018.3. [Q00536-3] DR RefSeq; XP_016885059.1; XM_017029570.1. DR RefSeq; XP_016885060.1; XM_017029571.1. DR RefSeq; XP_016885061.1; XM_017029572.1. DR RefSeq; XP_016885062.1; XM_017029573.1. DR PDB; 3MTL; X-ray; 2.40 A; A=163-478. DR PDB; 5G6V; X-ray; 2.20 A; A/B=163-478. DR PDBsum; 3MTL; -. DR PDBsum; 5G6V; -. DR AlphaFoldDB; Q00536; -. DR SMR; Q00536; -. DR BioGRID; 111154; 128. DR ComplexPortal; CPX-379; Cyclin Y-CDK16 complex. DR IntAct; Q00536; 50. DR MINT; Q00536; -. DR STRING; 9606.ENSP00000276052; -. DR BindingDB; Q00536; -. DR ChEMBL; CHEMBL4597; -. DR DrugBank; DB07766; (2Z,3E)-2,3'-biindole-2',3(1H,1'H)-dione 3-{O-[(3R)-3,4-dihydroxybutyl]oxime}. DR DrugBank; DB12010; Fostamatinib. DR DrugCentral; Q00536; -. DR GlyGen; Q00536; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q00536; -. DR PhosphoSitePlus; Q00536; -. DR SwissPalm; Q00536; -. DR BioMuta; CDK16; -. DR DMDM; 266425; -. DR CPTAC; non-CPTAC-2936; -. DR EPD; Q00536; -. DR jPOST; Q00536; -. DR MassIVE; Q00536; -. DR MaxQB; Q00536; -. DR PaxDb; 9606-ENSP00000276052; -. DR PeptideAtlas; Q00536; -. DR ProteomicsDB; 57854; -. [Q00536-1] DR Pumba; Q00536; -. DR Antibodypedia; 374; 269 antibodies from 31 providers. DR DNASU; 5127; -. DR Ensembl; ENST00000276052.10; ENSP00000276052.6; ENSG00000102225.17. [Q00536-2] DR Ensembl; ENST00000357227.9; ENSP00000349762.4; ENSG00000102225.17. [Q00536-1] DR Ensembl; ENST00000457458.6; ENSP00000405798.2; ENSG00000102225.17. [Q00536-3] DR Ensembl; ENST00000518022.5; ENSP00000429751.1; ENSG00000102225.17. [Q00536-1] DR GeneID; 5127; -. DR KEGG; hsa:5127; -. DR MANE-Select; ENST00000357227.9; ENSP00000349762.4; NM_006201.5; NP_006192.1. DR UCSC; uc004dho.4; human. [Q00536-1] DR AGR; HGNC:8749; -. DR CTD; 5127; -. DR DisGeNET; 5127; -. DR GeneCards; CDK16; -. DR HGNC; HGNC:8749; CDK16. DR HPA; ENSG00000102225; Low tissue specificity. DR MIM; 311550; gene. DR neXtProt; NX_Q00536; -. DR OpenTargets; ENSG00000102225; -. DR PharmGKB; PA33095; -. DR VEuPathDB; HostDB:ENSG00000102225; -. DR eggNOG; KOG0594; Eukaryota. DR GeneTree; ENSGT00940000156963; -. DR InParanoid; Q00536; -. DR OrthoDB; 244018at2759; -. DR PhylomeDB; Q00536; -. DR TreeFam; TF106508; -. DR BRENDA; 2.7.11.22; 2681. DR PathwayCommons; Q00536; -. DR SignaLink; Q00536; -. DR SIGNOR; Q00536; -. DR BioGRID-ORCS; 5127; 14 hits in 819 CRISPR screens. DR ChiTaRS; CDK16; human. DR GeneWiki; PCTK1; -. DR GenomeRNAi; 5127; -. DR Pharos; Q00536; Tchem. DR PRO; PR:Q00536; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; Q00536; Protein. DR Bgee; ENSG00000102225; Expressed in right hemisphere of cerebellum and 195 other cell types or tissues. DR ExpressionAtlas; Q00536; baseline and differential. DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IPI:ComplexPortal. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA. DR GO; GO:0043005; C:neuron projection; IEA:UniProtKB-KW. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0008021; C:synaptic vesicle; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IBA:GO_Central. 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:0006887; P:exocytosis; ISS:UniProtKB. DR GO; GO:0030252; P:growth hormone secretion; ISS:UniProtKB. DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB. DR GO; GO:0010508; P:positive regulation of autophagy; IDA:ComplexPortal. DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc. DR GO; GO:0061178; P:regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:UniProtKB. DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB. DR CDD; cd07873; STKc_PCTAIRE1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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 PANTHER; PTHR24056; CELL DIVISION PROTEIN KINASE; 1. DR PANTHER; PTHR24056:SF174; CYCLIN-DEPENDENT KINASE 16; 1. DR Pfam; PF12330; Haspin_kinase; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; Q00536; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane; Cytoplasm; KW Cytoplasmic vesicle; Differentiation; Kinase; Membrane; Nucleotide-binding; KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; KW Spermatogenesis; Synapse; Synaptosome; Transferase. FT CHAIN 1..496 FT /note="Cyclin-dependent kinase 16" FT /id="PRO_0000086484" FT DOMAIN 165..446 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 1..97 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 81..96 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 286 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:0000305" FT MOD_RES 12 FT /note="Phosphoserine; by BRSK2" FT /evidence="ECO:0000269|PubMed:22798068, FT ECO:0007744|PubMed:23186163" FT MOD_RES 36 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q04735" FT MOD_RES 42 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES 64 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q04735" FT MOD_RES 65 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 78 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19369195" FT MOD_RES 82 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19369195" FT MOD_RES 89 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q04735" FT MOD_RES 95 FT /note="Phosphoserine; by CDK5" FT /evidence="ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163" FT MOD_RES 110 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q04735" FT MOD_RES 119 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:21406692" FT MOD_RES 138 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:23186163" FT MOD_RES 146 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q04735" FT MOD_RES 153 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 155 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 175 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q04735" FT MOD_RES 380 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q04735" FT MOD_RES 391 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q04735" FT MOD_RES 478 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q04735" FT MOD_RES 480 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q04735" FT VAR_SEQ 1 FT /note="M -> MPLYGRARDHVTHPSILGTRPGRPMAGPITAAVPEKICNGAFCSCSG FT AFPLDPNNPSLGPLPSISHLNLRTQIAM (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_046134" FT VAR_SEQ 1 FT /note="M -> MQSEIAM (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_046342" FT MUTAGEN 12 FT /note="S->A: Abolishes phosphorylation by BRSK2. Abolishes FT effect on insulin secretion." FT /evidence="ECO:0000269|PubMed:22798068" FT MUTAGEN 119 FT /note="S->A: Strongly reduces interaction with CCNY." FT /evidence="ECO:0000269|PubMed:22184064" FT MUTAGEN 153 FT /note="S->A: Constitutively activated, due to loss of an FT inhibitory phosphorylation site. Increases interaction with FT CCNY." FT /evidence="ECO:0000269|PubMed:22184064, FT ECO:0000269|PubMed:22798068" FT MUTAGEN 153 FT /note="S->D: Abolishes interaction with CCNY." FT /evidence="ECO:0000269|PubMed:22184064, FT ECO:0000269|PubMed:22798068" FT MUTAGEN 194 FT /note="K->A: Loss of kinase activity. Abolishes effect on FT insulin secretion." FT /evidence="ECO:0000269|PubMed:22184064, FT ECO:0000269|PubMed:22798068" FT MUTAGEN 194 FT /note="K->R: Loss of kinase activity." FT /evidence="ECO:0000269|PubMed:22184064, FT ECO:0000269|PubMed:22798068" FT CONFLICT 25 FT /note="N -> D (in Ref. 3; BAH13564)" FT /evidence="ECO:0000305" FT STRAND 165..173 FT /evidence="ECO:0007829|PDB:5G6V" FT STRAND 175..184 FT /evidence="ECO:0007829|PDB:5G6V" FT TURN 185..187 FT /evidence="ECO:0007829|PDB:5G6V" FT STRAND 190..197 FT /evidence="ECO:0007829|PDB:5G6V" FT HELIX 206..217 FT /evidence="ECO:0007829|PDB:5G6V" FT STRAND 226..231 FT /evidence="ECO:0007829|PDB:5G6V" FT STRAND 233..241 FT /evidence="ECO:0007829|PDB:5G6V" FT STRAND 244..246 FT /evidence="ECO:0007829|PDB:5G6V" FT HELIX 247..253 FT /evidence="ECO:0007829|PDB:5G6V" FT TURN 254..256 FT /evidence="ECO:0007829|PDB:5G6V" FT HELIX 260..279 FT /evidence="ECO:0007829|PDB:5G6V" FT STRAND 282..286 FT /evidence="ECO:0007829|PDB:3MTL" FT HELIX 289..291 FT /evidence="ECO:0007829|PDB:5G6V" FT STRAND 292..294 FT /evidence="ECO:0007829|PDB:5G6V" FT STRAND 300..302 FT /evidence="ECO:0007829|PDB:5G6V" FT STRAND 304..309 FT /evidence="ECO:0007829|PDB:3MTL" FT TURN 324..327 FT /evidence="ECO:0007829|PDB:5G6V" FT TURN 330..335 FT /evidence="ECO:0007829|PDB:5G6V" FT HELIX 342..357 FT /evidence="ECO:0007829|PDB:5G6V" FT HELIX 367..378 FT /evidence="ECO:0007829|PDB:5G6V" FT TURN 383..385 FT /evidence="ECO:0007829|PDB:5G6V" FT HELIX 389..391 FT /evidence="ECO:0007829|PDB:5G6V" FT HELIX 393..397 FT /evidence="ECO:0007829|PDB:5G6V" FT HELIX 408..411 FT /evidence="ECO:0007829|PDB:5G6V" FT HELIX 417..426 FT /evidence="ECO:0007829|PDB:5G6V" FT HELIX 431..433 FT /evidence="ECO:0007829|PDB:5G6V" FT HELIX 437..441 FT /evidence="ECO:0007829|PDB:5G6V" FT HELIX 444..449 FT /evidence="ECO:0007829|PDB:5G6V" FT HELIX 452..455 FT /evidence="ECO:0007829|PDB:5G6V" FT HELIX 462..465 FT /evidence="ECO:0007829|PDB:5G6V" SQ SEQUENCE 496 AA; 55716 MW; 9A5DDD34A5E5CBBB CRC64; MDRMKKIKRQ LSMTLRGGRG IDKTNGAPEQ IGLDESGGGG GSDPGEAPTR AAPGELRSAR GPLSSAPEIV HEDLKMGSDG ESDQASATSS DEVQSPVRVR MRNHPPRKIS TEDINKRLSL PADIRLPEGY LEKLTLNSPI FDKPLSRRLR RVSLSEIGFG KLETYIKLDK LGEGTYATVY KGKSKLTDNL VALKEIRLEH EEGAPCTAIR EVSLLKDLKH ANIVTLHDII HTEKSLTLVF EYLDKDLKQY LDDCGNIINM HNVKLFLFQL LRGLAYCHRQ KVLHRDLKPQ NLLINERGEL KLADFGLARA KSIPTKTYSN EVVTLWYRPP DILLGSTDYS TQIDMWGVGC IFYEMATGRP LFPGSTVEEQ LHFIFRILGT PTEETWPGIL SNEEFKTYNY PKYRAEALLS HAPRLDSDGA DLLTKLLQFE GRNRISAEDA MKHPFFLSLG ERIHKLPDTT SIFALKEIQL QKEASLRSSS MPDSGRPAFR VVDTEF //