ID CK5P2_HUMAN Reviewed; 1893 AA. AC Q96SN8; Q5JV18; Q7Z3L4; Q7Z3U1; Q7Z7I6; Q9BSW0; Q9H6J6; Q9HCD9; Q9NV90; AC Q9UIW9; DT 16-JUN-2003, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 5. DT 27-MAR-2024, entry version 198. DE RecName: Full=CDK5 regulatory subunit-associated protein 2; DE AltName: Full=CDK5 activator-binding protein C48; DE AltName: Full=Centrosome-associated protein 215; GN Name=CDK5RAP2; Synonyms=CEP215, KIAA1633; 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 [LARGE SCALE MRNA] (ISOFORM 4), AND VARIANT GLN-289. RC TISSUE=Brain; RX PubMed=10997877; DOI=10.1093/dnares/7.4.271; RA Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XVIII. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 7:273-281(2000). RN [2] RP SEQUENCE REVISION. RA Ohara O., Nagase T., Kikuno R.; RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Guo J.H., Zan Q., Yu L.; RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 575-1893 (ISOFORM 2), AND VARIANTS GLN-289 AND RP LEU-1540. RC TISSUE=Amygdala, Retina, and Testis; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 950-1893 (ISOFORM 3), NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 1576-1654 (ISOFORM 4), AND VARIANT LEU-1540. RC TISSUE=Kidney, 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1401-1893. RC TISSUE=Lung; 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 TISSUE SPECIFICITY. RX PubMed=10721722; DOI=10.1016/s0378-1119(99)00499-0; RA Ching Y.-P., Qi Z., Wang J.H.; RT "Cloning of three novel neuronal Cdk5 activator binding proteins."; RL Gene 242:285-294(2000). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION [LARGE SCALE RP ANALYSIS]. RC TISSUE=Lymphoblast; RX PubMed=14654843; DOI=10.1038/nature02166; RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.; RT "Proteomic characterization of the human centrosome by protein correlation RT profiling."; RL Nature 426:570-574(2003). RN [10] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=18042621; DOI=10.1242/jcs.020248; RA Graser S., Stierhof Y.D., Nigg E.A.; RT "Cep68 and Cep215 (Cdk5rap2) are required for centrosome cohesion."; RL J. Cell Sci. 120:4321-4331(2007). RN [11] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH TUBG1 AND TUBGCP3. RX PubMed=17959831; DOI=10.1091/mbc.e07-04-0371; RA Fong K.W., Choi Y.K., Rattner J.B., Qi R.Z.; RT "CDK5RAP2 is a pericentriolar protein that functions in centrosomal RT attachment of the gamma-tubulin ring complex."; RL Mol. Biol. Cell 19:115-125(2008). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1238 AND SER-1893, 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 [13] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CDC20. RX PubMed=19282672; DOI=10.4161/cc.8.8.8205; RA Zhang X., Liu D., Lv S., Wang H., Zhong X., Liu B., Wang B., Liao J., RA Li J., Pfeifer G.P., Xu X.; RT "CDK5RAP2 is required for spindle checkpoint function."; RL Cell Cycle 8:1206-1216(2009). RN [14] RP FUNCTION, INTERACTION WITH MAPRE1, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP 938-LEU-PRO-939. RX PubMed=19553473; DOI=10.1091/mbc.e09-01-0009; RA Fong K.W., Hau S.Y., Kho Y.S., Jia Y., He L., Qi R.Z.; RT "Interaction of CDK5RAP2 with EB1 to track growing microtubule tips and to RT regulate microtubule dynamics."; RL Mol. Biol. Cell 20:3660-3670(2009). RN [15] RP SUBCELLULAR LOCATION. RX PubMed=19543530; DOI=10.1371/journal.pone.0005976; RA Haren L., Stearns T., Lueders J.; RT "Plk1-dependent recruitment of gamma-tubulin complexes to mitotic RT centrosomes involves multiple PCM components."; RL PLoS ONE 4:E5976-E5976(2009). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1238, AND IDENTIFICATION BY RP 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 [17] RP SUBCELLULAR LOCATION, INTERACTION WITH AKAP9; CALM1 AND PCNT, AND RP MUTAGENESIS OF LYS-1865 AND LYS-1869. RX PubMed=20466722; DOI=10.1074/jbc.m110.105965; RA Wang Z., Wu T., Shi L., Zhang L., Zheng W., Qu J.Y., Niu R., Qi R.Z.; RT "Conserved motif of CDK5RAP2 mediates its localization to centrosomes and RT the Golgi complex."; RL J. Biol. Chem. 285:22658-22665(2010). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-547 AND THR-1001, AND RP IDENTIFICATION BY 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 [19] 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 [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-547; SER-1238 AND SER-1490, RP 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 [21] RP SUBCELLULAR LOCATION. RX PubMed=25657325; DOI=10.1091/mbc.e14-09-1366; RA Ohta S., Wood L., Toramoto I., Yagyu K., Fukagawa T., Earnshaw W.C.; RT "CENP-32 is required to maintain centrosomal dominance in bipolar spindle RT assembly."; RL Mol. Biol. Cell 26:1225-1237(2015). RN [22] RP INTERACTION WITH CEP68, AND SUBCELLULAR LOCATION. RX PubMed=25503564; DOI=10.1038/ncb3076; RA Pagan J.K., Marzio A., Jones M.J., Saraf A., Jallepalli P.V., Florens L., RA Washburn M.P., Pagano M.; RT "Degradation of Cep68 and PCNT cleavage mediate Cep215 removal from the PCM RT to allow centriole separation, disengagement and licensing."; RL Nat. Cell Biol. 17:31-43(2015). RN [23] RP SUBCELLULAR LOCATION. RX PubMed=26482847; DOI=10.1016/j.bbrc.2015.10.069; RA Mori Y., Taniyama Y., Tanaka S., Fukuchi H., Terada Y.; RT "Microtubule-bundling activity of the centrosomal protein, Cep169, and its RT binding to microtubules."; RL Biochem. Biophys. Res. Commun. 467:754-759(2015). RN [24] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH NCKAP5L. RX PubMed=26485573; DOI=10.1371/journal.pone.0140968; RA Mori Y., Inoue Y., Tanaka S., Doda S., Yamanaka S., Fukuchi H., Terada Y.; RT "Cep169, a novel microtubule plus-end-tracking centrosomal protein, binds RT to CDK5RAP2 and regulates microtubule stability."; RL PLoS ONE 10:E0140968-E0140968(2015). RN [25] RP FUNCTION, INTERACTION WITH AKAP9; LGALS3BP; MAPRE1 AND PDE4DIP, AND RP SUBCELLULAR LOCATION. RX PubMed=29162697; DOI=10.1073/pnas.1705682114; RA Bouguenina H., Salaun D., Mangon A., Muller L., Baudelet E., Camoin L., RA Tachibana T., Cianferani S., Audebert S., Verdier-Pinard P., Badache A.; RT "EB1-binding-myomegalin protein complex promotes centrosomal microtubules RT functions."; RL Proc. Natl. Acad. Sci. U.S.A. 114:E10687-E10696(2017). RN [26] RP SUBCELLULAR LOCATION. RX PubMed=31974111; DOI=10.1242/jcs.239616; RA Hossain D., Shih S.Y., Xiao X., White J., Tsang W.Y.; RT "Cep44 functions in centrosome cohesion by stabilizing rootletin."; RL J. Cell Sci. 133:0-0(2020). RN [27] RP INVOLVEMENT IN MCPH3. RX PubMed=15793586; DOI=10.1038/ng1539; RA Bond J., Roberts E., Springell K., Lizarraga S.B., Scott S., Higgins J., RA Hampshire D.J., Morrison E.E., Leal G.F., Silva E.O., Costa S.M.R., RA Baralle D., Raponi M., Karbani G., Rashid Y., Jafri H., Bennett C., RA Corry P., Walsh C.A., Woods C.G.; RT "A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain RT size."; RL Nat. Genet. 37:353-355(2005). RN [28] RP ERRATUM OF PUBMED:15793586. RA Bond J., Roberts E., Springell K., Lizarraga S.B., Scott S., Higgins J., RA Hampshire D.J., Morrison E.E., Leal G.F., Silva E.O., Costa S.M.R., RA Baralle D., Raponi M., Karbani G., Rashid Y., Jafri H., Bennett C., RA Corry P., Walsh C.A., Woods C.G.; RL Nat. Genet. 37:555-555(2005). CC -!- FUNCTION: Potential regulator of CDK5 activity via its interaction with CC CDK5R1. Negative regulator of centriole disengagement (licensing) which CC maintains centriole engagement and cohesion. Involved in regulation of CC mitotic spindle orientation (By similarity). Plays a role in the CC spindle checkpoint activation by acting as a transcriptional regulator CC of both BUBR1 and MAD2 promoter. Together with EB1/MAPRE1, may promote CC microtubule polymerization, bundle formation, growth and dynamics at CC the plus ends. Regulates centrosomal maturation by recruitment of the CC gamma-tubulin ring complex (gamma-TuRC) onto centrosomes CC (PubMed:26485573). In complex with PDE4DIP isoform 13/MMG8/SMYLE, CC MAPRE1 and AKAP9, contributes to microtubules nucleation and extension CC from the centrosome to the cell periphery (PubMed:29162697). Required CC for the recruitment of AKAP9 to centrosomes (PubMed:29162697). Plays a CC role in neurogenesis (By similarity). {ECO:0000250|UniProtKB:Q8K389, CC ECO:0000269|PubMed:17959831, ECO:0000269|PubMed:18042621, CC ECO:0000269|PubMed:19282672, ECO:0000269|PubMed:19553473, CC ECO:0000269|PubMed:26485573, ECO:0000269|PubMed:29162697}. CC -!- SUBUNIT: Interacts with CDK5R1 (p35 form) (By similarity). CDK5RAP1, CC CDK5RAP2 and CDK5RAP3 show competitive binding to CDK5R1. May form a CC complex with CDK5R1 and CDK5 (By similarity). Interacts with CC pericentrin/PCNT; the interaction is leading to centrosomal and Golgi CC localization of CDK5RAP2 and PCNT (PubMed:20466722). Interacts with CC AKAP9; the interaction targets CDK5RAP2 and AKAP9 to Golgi apparatus CC (PubMed:20466722). Interacts with MAPRE1; the interaction is direct and CC targets CDK5RAP2 and EB1/MAPRE1 to microtubule plus ends CC (PubMed:19553473). Interacts with TUBG1; the interaction is leading to CC the centrosomal localization of CDK5RAP2 and TUBG1 (PubMed:17959831). CC Interacts with TUBGCP3 (PubMed:17959831). Interacts with CALM1 CC (PubMed:20466722). Interacts with CDC20 (PubMed:19282672). Interacts CC with CEP68; degradation of CEP68 in early mitosis leads to removal of CC CDK5RAP2 from the centrosome which promotes centriole disengagement and CC subsequent centriole separation (PubMed:25503564). Interacts with CC NCKAP5L (PubMed:26485573). Forms a pericentrosomal complex with AKAP9, CC MAPRE1 and PDE4DIP isoform 13/MMG8/SMYLE; within this complex, MAPRE1 CC binding to CDK5RAP2 may be mediated by PDE4DIP (PubMed:29162697). CC Interacts with LGALS3BP; this interaction may connect the CC pericentrosomal complex to the gamma-tubulin ring complex (gamma-TuRC) CC to promote microtubule assembly and acetylation (PubMed:29162697). CC {ECO:0000250|UniProtKB:Q9JLH5, ECO:0000269|PubMed:17959831, CC ECO:0000269|PubMed:19282672, ECO:0000269|PubMed:19553473, CC ECO:0000269|PubMed:20466722, ECO:0000269|PubMed:25503564, CC ECO:0000269|PubMed:26485573, ECO:0000269|PubMed:29162697}. CC -!- INTERACTION: CC Q96SN8; Q76N32: CEP68; NbExp=8; IntAct=EBI-308374, EBI-9051024; CC Q96SN8; Q9P209: CEP72; NbExp=3; IntAct=EBI-308374, EBI-739498; CC Q96SN8; Q38SD2-1: LRRK1; NbExp=2; IntAct=EBI-308374, EBI-16165296; CC Q96SN8; Q04206: RELA; NbExp=3; IntAct=EBI-308374, EBI-73886; CC Q96SN8; Q96R06: SPAG5; NbExp=3; IntAct=EBI-308374, EBI-413317; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing CC center, centrosome {ECO:0000269|PubMed:14654843, CC ECO:0000269|PubMed:19553473, ECO:0000269|PubMed:25503564, CC ECO:0000269|PubMed:25657325, ECO:0000269|PubMed:26482847, CC ECO:0000269|PubMed:26485573, ECO:0000269|PubMed:29162697, CC ECO:0000269|PubMed:31974111}. Golgi apparatus CC {ECO:0000269|PubMed:20466722}. Cytoplasm {ECO:0000269|PubMed:19553473}. CC Cytoplasm, cytoskeleton {ECO:0000269|PubMed:19553473, CC ECO:0000269|PubMed:26485573}. Note=Found in the pericentriolar region CC adhering to the surface of the centrosome and in the region of the CC centrosomal appendages. Localizes to microtubule plus ends in the CC presence of EB1/MAPRE1. Localization to centrosomes versus Golgi CC apparatus may be cell type-dependent. For instance, in SK-BR-3 and CC HEK293F cells, localizes to centrosomes but not to the Golgi apparatus CC (PubMed:29162697). {ECO:0000269|PubMed:19553473, CC ECO:0000269|PubMed:26485573, ECO:0000269|PubMed:29162697}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q96SN8-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96SN8-2; Sequence=VSP_007563; CC Name=3; CC IsoId=Q96SN8-3; Sequence=VSP_007564; CC Name=4; CC IsoId=Q96SN8-4; Sequence=VSP_007565; CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in heart, brain, CC placenta, lung, liver, skeletal muscle, kidney and pancreas. CC {ECO:0000269|PubMed:10721722}. CC -!- PTM: Phosphorylated in vitro by CDK5. {ECO:0000250|UniProtKB:Q9JLH5}. CC -!- DISEASE: Microcephaly 3, primary, autosomal recessive (MCPH3) CC [MIM:604804]: A disease defined as a head circumference more than 3 CC standard deviations below the age-related mean. Brain weight is CC markedly reduced and the cerebral cortex is disproportionately small. CC Despite this marked reduction in size, the gyral pattern is relatively CC well preserved, with no major abnormality in cortical architecture. CC Affected individuals are mentally retarded. Primary microcephaly is CC further defined by the absence of other syndromic features or CC significant neurological deficits due to degenerative brain disorder. CC {ECO:0000269|PubMed:15793586}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SEQUENCE CAUTION: CC Sequence=AAH04526.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAA91865.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAB13459.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAB15263.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAB55253.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAD97663.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; CC Sequence=CAD97828.1; Type=Frameshift; 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; AB046853; BAB13459.2; ALT_INIT; mRNA. DR EMBL; AF448860; AAP41926.1; -; mRNA. DR EMBL; AL133161; CAB61487.1; -; mRNA. DR EMBL; BX537421; CAD97663.1; ALT_SEQ; mRNA. DR EMBL; BX537759; CAD97828.1; ALT_FRAME; mRNA. DR EMBL; AL138836; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL353736; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL391870; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL590642; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AK001729; BAA91865.1; ALT_INIT; mRNA. DR EMBL; AK025867; BAB15263.1; ALT_INIT; mRNA. DR EMBL; AK027636; BAB55253.1; ALT_INIT; mRNA. DR EMBL; BC004526; AAH04526.2; ALT_INIT; mRNA. DR CCDS; CCDS43871.1; -. [Q96SN8-4] DR CCDS; CCDS6823.1; -. [Q96SN8-1] DR CCDS; CCDS94470.1; -. [Q96SN8-2] DR PIR; T42658; T42658. DR RefSeq; NP_001011649.1; NM_001011649.2. [Q96SN8-4] DR RefSeq; NP_001258968.1; NM_001272039.1. DR RefSeq; NP_060719.4; NM_018249.5. [Q96SN8-1] DR RefSeq; XP_006717245.1; XM_006717182.1. DR PDB; 6X0V; EM; 4.50 A; G/H=1-1893. DR PDBsum; 6X0V; -. DR AlphaFoldDB; Q96SN8; -. DR EMDB; EMD-21985; -. DR SMR; Q96SN8; -. DR BioGRID; 120873; 195. DR DIP; DIP-31632N; -. DR IntAct; Q96SN8; 194. DR MINT; Q96SN8; -. DR STRING; 9606.ENSP00000343818; -. DR GlyGen; Q96SN8; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q96SN8; -. DR MetOSite; Q96SN8; -. DR PhosphoSitePlus; Q96SN8; -. DR SwissPalm; Q96SN8; -. DR BioMuta; CDK5RAP2; -. DR DMDM; 296439505; -. DR EPD; Q96SN8; -. DR jPOST; Q96SN8; -. DR MassIVE; Q96SN8; -. DR MaxQB; Q96SN8; -. DR PaxDb; 9606-ENSP00000343818; -. DR PeptideAtlas; Q96SN8; -. DR ProteomicsDB; 78131; -. [Q96SN8-1] DR ProteomicsDB; 78132; -. [Q96SN8-2] DR ProteomicsDB; 78133; -. [Q96SN8-3] DR ProteomicsDB; 78134; -. [Q96SN8-4] DR Pumba; Q96SN8; -. DR Antibodypedia; 30055; 170 antibodies from 24 providers. DR DNASU; 55755; -. DR Ensembl; ENST00000349780.9; ENSP00000343818.4; ENSG00000136861.19. [Q96SN8-1] DR Ensembl; ENST00000360190.8; ENSP00000353317.4; ENSG00000136861.19. [Q96SN8-4] DR Ensembl; ENST00000416449.6; ENSP00000400395.2; ENSG00000136861.19. [Q96SN8-2] DR GeneID; 55755; -. DR KEGG; hsa:55755; -. DR MANE-Select; ENST00000349780.9; ENSP00000343818.4; NM_018249.6; NP_060719.4. DR UCSC; uc004bkf.5; human. [Q96SN8-1] DR AGR; HGNC:18672; -. DR CTD; 55755; -. DR DisGeNET; 55755; -. DR GeneCards; CDK5RAP2; -. DR HGNC; HGNC:18672; CDK5RAP2. DR HPA; ENSG00000136861; Low tissue specificity. DR MalaCards; CDK5RAP2; -. DR MIM; 604804; phenotype. DR MIM; 608201; gene. DR neXtProt; NX_Q96SN8; -. DR OpenTargets; ENSG00000136861; -. DR Orphanet; 2512; Autosomal recessive primary microcephaly. DR PharmGKB; PA38632; -. DR VEuPathDB; HostDB:ENSG00000136861; -. DR eggNOG; ENOG502QTI7; Eukaryota. DR GeneTree; ENSGT00950000183190; -. DR InParanoid; Q96SN8; -. DR OMA; EIMEDCA; -. DR OrthoDB; 2912560at2759; -. DR PhylomeDB; Q96SN8; -. DR TreeFam; TF329233; -. DR PathwayCommons; Q96SN8; -. DR Reactome; R-HSA-2565942; Regulation of PLK1 Activity at G2/M Transition. DR Reactome; R-HSA-380259; Loss of Nlp from mitotic centrosomes. DR Reactome; R-HSA-380270; Recruitment of mitotic centrosome proteins and complexes. DR Reactome; R-HSA-380284; Loss of proteins required for interphase microtubule organization from the centrosome. DR Reactome; R-HSA-380320; Recruitment of NuMA to mitotic centrosomes. DR Reactome; R-HSA-5620912; Anchoring of the basal body to the plasma membrane. DR Reactome; R-HSA-8854518; AURKA Activation by TPX2. DR SignaLink; Q96SN8; -. DR SIGNOR; Q96SN8; -. DR BioGRID-ORCS; 55755; 36 hits in 1169 CRISPR screens. DR ChiTaRS; CDK5RAP2; human. DR GeneWiki; CDK5RAP2; -. DR GenomeRNAi; 55755; -. DR Pharos; Q96SN8; Tbio. DR PRO; PR:Q96SN8; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; Q96SN8; Protein. DR Bgee; ENSG00000136861; Expressed in sural nerve and 193 other cell types or tissues. DR ExpressionAtlas; Q96SN8; baseline and differential. DR GO; GO:0030054; C:cell junction; IDA:HPA. DR GO; GO:0005813; C:centrosome; IDA:HPA. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005856; C:cytoskeleton; NAS:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0005874; C:microtubule; IDA:UniProtKB. DR GO; GO:0035371; C:microtubule plus-end; IDA:UniProtKB. DR GO; GO:0097431; C:mitotic spindle pole; IBA:GO_Central. DR GO; GO:0000242; C:pericentriolar material; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0000922; C:spindle pole; IDA:UniProtKB. DR GO; GO:0005516; F:calmodulin binding; IDA:UniProtKB. DR GO; GO:0043015; F:gamma-tubulin binding; IDA:UniProtKB. DR GO; GO:0008017; F:microtubule binding; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl. DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB. DR GO; GO:0015631; F:tubulin binding; IPI:UniProtKB. DR GO; GO:0007420; P:brain development; ISS:UniProtKB. DR GO; GO:0007099; P:centriole replication; IMP:UniProtKB. DR GO; GO:0007098; P:centrosome cycle; IMP:UniProtKB. DR GO; GO:0007059; P:chromosome segregation; IMP:UniProtKB. DR GO; GO:0000132; P:establishment of mitotic spindle orientation; ISS:UniProtKB. DR GO; GO:0001578; P:microtubule bundle formation; IDA:UniProtKB. DR GO; GO:0000226; P:microtubule cytoskeleton organization; IDA:UniProtKB. DR GO; GO:0031023; P:microtubule organizing center organization; IMP:UniProtKB. DR GO; GO:0046600; P:negative regulation of centriole replication; ISS:UniProtKB. DR GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl. DR GO; GO:0022008; P:neurogenesis; ISS:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0031116; P:positive regulation of microtubule polymerization; IMP:UniProtKB. DR GO; GO:0090266; P:regulation of mitotic cell cycle spindle assembly checkpoint; IDA:UniProtKB. DR GO; GO:0045664; P:regulation of neuron differentiation; NAS:UniProtKB. DR InterPro; IPR042791; CDK5RAP2. DR InterPro; IPR012943; Cnn_1N. DR PANTHER; PTHR46930; CDK5 REGULATORY SUBUNIT-ASSOCIATED PROTEIN 2; 1. DR PANTHER; PTHR46930:SF1; CDK5 REGULATORY SUBUNIT-ASSOCIATED PROTEIN 2; 1. DR Pfam; PF07989; Cnn_1N; 1. DR Genevisible; Q96SN8; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Calmodulin-binding; Cytoplasm; KW Cytoskeleton; Golgi apparatus; Intellectual disability; Microtubule; KW Phosphoprotein; Primary microcephaly; Reference proteome. FT CHAIN 1..1893 FT /note="CDK5 regulatory subunit-associated protein 2" FT /id="PRO_0000089835" FT REGION 58..196 FT /note="Interaction with NCKAP5L" FT /evidence="ECO:0000269|PubMed:26485573" FT REGION 926..1208 FT /note="Interaction with MAPRE1" FT /evidence="ECO:0000269|PubMed:19553473" FT REGION 1015..1071 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1084..1105 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1347..1381 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1500..1521 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1646..1706 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1726..1893 FT /note="Interaction with PCNT and AKAP9" FT /evidence="ECO:0000269|PubMed:20466722" FT REGION 1726..1768 FT /note="Interaction with CDK5R1" FT /evidence="ECO:0000250" FT REGION 1754..1774 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1861..1870 FT /note="Required for centrosomal attachment, Golgi FT localization and CALM1 interaction" FT COMPBIAS 1030..1047 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1366..1380 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1650..1664 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1666..1706 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1754..1768 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 547 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1001 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 1238 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163" FT MOD_RES 1490 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1663 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9JLH5" FT MOD_RES 1666 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9JLH5" FT MOD_RES 1893 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT VAR_SEQ 702..733 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_007563" FT VAR_SEQ 1009..1049 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_007564" FT VAR_SEQ 1576..1654 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:10997877, FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:17974005" FT /id="VSP_007565" FT VARIANT 183 FT /note="A -> P (in dbSNP:rs13287734)" FT /id="VAR_056831" FT VARIANT 289 FT /note="E -> Q (in dbSNP:rs4836822)" FT /evidence="ECO:0000269|PubMed:10997877, FT ECO:0000269|PubMed:17974005" FT /id="VAR_017443" FT VARIANT 1045 FT /note="R -> T (in dbSNP:rs3780679)" FT /id="VAR_032426" FT VARIANT 1330 FT /note="N -> I (in dbSNP:rs7875294)" FT /id="VAR_059616" FT VARIANT 1540 FT /note="V -> L (in dbSNP:rs4837768)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:17974005" FT /id="VAR_017444" FT VARIANT 1607 FT /note="R -> S (in dbSNP:rs16909747)" FT /id="VAR_056832" FT MUTAGEN 938..939 FT /note="LP->AA: Loss of interaction with MAPRE1." FT /evidence="ECO:0000269|PubMed:19553473" FT MUTAGEN 1865 FT /note="K->A: No effect on centrosomal attachment, Golgi FT localization and loss of interaction with CALM1; when FT associated with A-1869." FT /evidence="ECO:0000269|PubMed:20466722" FT MUTAGEN 1869 FT /note="K->A: No effect on centrosomal attachment, Golgi FT localization and loss of interaction to CALM1; when FT associated with A-1865." FT /evidence="ECO:0000269|PubMed:20466722" FT CONFLICT 27 FT /note="P -> S (in Ref. 4; CAD97663)" FT /evidence="ECO:0000305" FT CONFLICT 43 FT /note="L -> V (in Ref. 3; AAP41926)" FT /evidence="ECO:0000305" FT CONFLICT 292 FT /note="I -> F (in Ref. 4; CAD97828)" FT /evidence="ECO:0000305" FT CONFLICT 414 FT /note="E -> K (in Ref. 4; CAD97828)" FT /evidence="ECO:0000305" FT CONFLICT 1254 FT /note="S -> F (in Ref. 4; CAD97663)" FT /evidence="ECO:0000305" FT CONFLICT 1458 FT /note="Q -> R (in Ref. 6; BAA91865)" FT /evidence="ECO:0000305" FT CONFLICT 1483 FT /note="S -> P (in Ref. 4; CAD97663)" FT /evidence="ECO:0000305" FT CONFLICT 1550 FT /note="N -> D (in Ref. 6; BAB55253)" FT /evidence="ECO:0000305" FT CONFLICT 1838 FT /note="K -> R (in Ref. 6; BAA91865)" FT /evidence="ECO:0000305" SQ SEQUENCE 1893 AA; 215038 MW; 833B9F9EF3CE8D07 CRC64; MMDLVLEEDV TVPGTLSGCS GLVPSVPDDL DGINPNAGLG NGLLPNVSEE TVSPTRARNM KDFENQITEL KKENFNLKLR IYFLEERMQQ EFHGPTEHIY KTNIELKVEV ESLKRELQER EQLLIKASKA VESLAEAGGS EIQRVKEDAR KKVQQVEDLL TKRILLLEKD VTAAQAELEK AFAGTETEKA LRLRLESKLS EMKKMHEGDL AMALVLDEKD RLIEELKLSL KSKEALIQCL KEEKSQMACP DENVSSGELR GLCAAPREEK ERETEAAQME HQKERNSFEE RIQALEEDLR EKEREIATEK KNSLKRDKAI QGLTMALKSK EKKVEELNSE IEKLSAAFAK AREALQKAQT QEFQGSEDYE TALSGKEALS AALRSQNLTK STENHRLRRS IKKITQELSD LQQERERLEK DLEEAHREKS KGDCTIRDLR NEVEKLRNEV NEREKAMENR YKSLLSESNK KLHNQEQVIK HLTESTNQKD VLLQKFNEKD LEVIQQNCYL MAAEDLELRS EGLITEKCSS QQPPGSKTIF SKEKKQSSDY EELIQVLKKE QDIYTHLVKS LQESDSINNL QAELNKIFAL RKQLEQDVLS YQNLRKTLEE QISEIRRREE ESFSLYSDQT SYLSICLEEN NRFQVEHFSQ EELKKKVSDL IQLVKELYTD NQHLKKTIFD LSCMGFQGNG FPDRLASTEQ TELLASKEDE DTIKIGEDDE INFLSDQHLQ QSNEIMKDLS KGGCKNGYLR HTESKISDCD GAHAPGCLEE GAFINLLAPL FNEKATLLLE SRPDLLKVVR ELLLGQLFLT EQEVSGEHLD GKTEKTPKQK GELVHFVQTN SFSKPHDELK LSCEAQLVKA GEVPKVGLKD ASVQTVATEG DLLRFKHEAT REAWEEKPIN TALSAEHRPE NLHGVPGWQA ALLSLPGITN REAKKSRLPI LIKPSRSLGN MYRLPATQEV VTQLQSQILE LQGELKEFKT CNKQLHQKLI LAEAVMEGRP TPDKTLLNAQ PPVGAAYQDS PGEQKGIKTT SSVWRDKEMD SDQQRSYEID SEICPPDDLA SLPSCKENPE DVLSPTSVAT YLSSKSQPSA KVSVMGTDQS ESINTSNETE YLKQKIHDLE TELEGYQNFI FQLQKHSQCS EAIITVLCGT EGAQDGLSKP KNGSDGEEMT FSSLHQVRYV KHVKILGPLA PEMIDSRVLE NLKQQLEEQE YKLQKEQNLN MQLFSEIHNL QNKFRDLSPP RYDSLVQSQA RELSLQRQQI KDGHGICVIS RQHMNTMIKA FEELLQASDV DYCVAEGFQE QLNQCAELLE KLEKLFLNGK SVGVEMNTQN ELMERIEEDN LTYQHLLPES PEPSASHALS DYETSEKSFF SRDQKQDNET EKTSVMVNSF SQDLLMEHIQ EIRTLRKRLE ESIKTNEKLR KQLERQGSEF VQGSTSIFAS GSELHSSLTS EIHFLRKQNQ ALNAMLIKGS RDKQKENDKL RESLSRKTVS LEHLQREYAS VKEENERLQK EGSEKERHNQ QLIQEVRCSG QELSRVQEEV KLRQQLLSQN DKLLQSLRVE LKAYEKLDEE HRRLREASGE GWKGQDPFRD LHSLLMEIQA LRLQLERSIE TSSTLQSRLK EQLARGAEKA QEGALTLAVQ AVSIPEVPLQ PDKHDGDKYP MESDNSFDLF DSSQAVTPKS VSETPPLSGN DTDSLSCDSG SSATSTPCVS RLVTGHHLWA SKNGRHVLGL IEDYEALLKQ ISQGQRLLAE MDIQTQEAPS STSQELGTKG PHPAPLSKFV SSVSTAKLTL EEAYRRLKLL WRVSLPEDGQ CPLHCEQIGE MKAEVTKLHK KLFEQEKKLQ NTMKLLQLSK RQEKVIFDQL VVTHKILRKA RGNLELRPGG AHPGTCSPSR PGS //