CK5P2_HUMAN
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 03-AUG-2022, entry version 189.
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=5; 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; 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};
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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 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. [Q96SN8-2]
DR PDB; 6X0V; EM; 4.50 A; G/H=1-1893.
DR PDBsum; 6X0V; -.
DR AlphaFoldDB; Q96SN8; -.
DR SMR; Q96SN8; -.
DR BioGRID; 120873; 188.
DR DIP; DIP-31632N; -.
DR IntAct; Q96SN8; 76.
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 BioMuta; CDK5RAP2; -.
DR DMDM; 296439505; -.
DR EPD; Q96SN8; -.
DR jPOST; Q96SN8; -.
DR MassIVE; Q96SN8; -.
DR MaxQB; Q96SN8; -.
DR PaxDb; Q96SN8; -.
DR PeptideAtlas; Q96SN8; -.
DR PRIDE; Q96SN8; -.
DR ProteomicsDB; 78131; -. [Q96SN8-1]
DR ProteomicsDB; 78132; -. [Q96SN8-2]
DR ProteomicsDB; 78133; -. [Q96SN8-3]
DR ProteomicsDB; 78134; -. [Q96SN8-4]
DR Antibodypedia; 30055; 143 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 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; RICLAEQ; -.
DR OrthoDB; 1249457at2759; -.
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; 35 hits in 1089 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 191 other tissues.
DR ExpressionAtlas; Q96SN8; baseline and differential.
DR Genevisible; Q96SN8; HS.
DR GO; GO:0030054; C:cell junction; IDA:HPA.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
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:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; IEA:Ensembl.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0022008; P:neurogenesis; ISS:UniProtKB.
DR GO; GO:0031116; P:positive regulation of microtubule polymerization; IMP:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA: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; IPR012943; Cnn_1N.
DR Pfam; PF07989; Cnn_1N; 1.
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
