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Protein

CDK5 regulatory subunit-associated protein 2

Gene

CDK5RAP2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Potential regulator of CDK5 activity via its interaction with CDK5R1. Negative regulator of centriole disengagement (licensing) which maintains centriole engagement and cohesion. Involved in regulation of mitotic spindle orientation (By similarity). Plays a role in the spindle checkpoint activation by acting as a transcriptional regulator of both BUBR1 and MAD2 promoter. Together with EB1/MAPRE1, may promote microtubule polymerization, bundle formation, growth and dynamics at the plus ends. Regulates centrosomal maturation by recruitment of the gamma-tubulin ring complex (gamma-TuRC) onto centrosomes (PubMed:26485573). In complex with PDE4DIP isoform 13/MMG8/SMYLE, MAPRE1 and AKAP9, contributes to microtubules nucleation and extension from the centrosome to the cell periphery (PubMed:29162697). Required for the recruitment of AKAP9 to centrosomes (PubMed:29162697). Plays a role in neurogenesis (By similarity).By similarity6 Publications

GO - Molecular functioni

  • calmodulin binding Source: UniProtKB
  • gamma-tubulin binding Source: UniProtKB
  • microtubule binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • transcription regulatory region DNA binding Source: UniProtKB
  • tubulin binding Source: UniProtKB

GO - Biological processi

  • brain development Source: UniProtKB
  • centriole replication Source: UniProtKB
  • centrosome cycle Source: UniProtKB
  • chromosome segregation Source: UniProtKB
  • ciliary basal body-plasma membrane docking Source: Reactome
  • establishment of mitotic spindle orientation Source: UniProtKB
  • G2/M transition of mitotic cell cycle Source: Reactome
  • microtubule bundle formation Source: UniProtKB
  • microtubule cytoskeleton organization Source: UniProtKB
  • microtubule organizing center organization Source: UniProtKB
  • negative regulation of centriole replication Source: UniProtKB
  • negative regulation of neuron differentiation Source: Ensembl
  • neurogenesis Source: UniProtKB
  • positive regulation of microtubule polymerization Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • regulation of G2/M transition of mitotic cell cycle Source: Reactome
  • regulation of mitotic cell cycle spindle assembly checkpoint Source: UniProtKB
  • regulation of neuron differentiation Source: UniProtKB

Keywordsi

Molecular functionCalmodulin-binding

Enzyme and pathway databases

ReactomeiR-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition
R-HSA-380259 Loss of Nlp from mitotic centrosomes
R-HSA-380270 Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284 Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320 Recruitment of NuMA to mitotic centrosomes
R-HSA-5620912 Anchoring of the basal body to the plasma membrane
R-HSA-8854518 AURKA Activation by TPX2

Names & Taxonomyi

Protein namesi
Recommended name:
CDK5 regulatory subunit-associated protein 2
Alternative name(s):
CDK5 activator-binding protein C48
Centrosome-associated protein 215
Gene namesi
Name:CDK5RAP2
Synonyms:CEP215, KIAA1633
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000136861.17
HGNCiHGNC:18672 CDK5RAP2
MIMi608201 gene
neXtProtiNX_Q96SN8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Golgi apparatus, Microtubule

Pathology & Biotechi

Involvement in diseasei

Microcephaly 3, primary, autosomal recessive (MCPH3)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. Despite this marked reduction in size, the gyral pattern is relatively well preserved, with no major abnormality in cortical architecture. Affected individuals are mentally retarded. Primary microcephaly is further defined by the absence of other syndromic features or significant neurological deficits due to degenerative brain disorder.
See also OMIM:604804

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi938 – 939LP → AA: Loss of interaction with MAPRE1. 1 Publication2
Mutagenesisi1865K → A: No effect on centrosomal attachment, Golgi localization and loss of interaction with CALM1; when associated with A-1869. 1 Publication1
Mutagenesisi1869K → A: No effect on centrosomal attachment, Golgi localization and loss of interaction to CALM1; when associated with A-1865. 1 Publication1

Keywords - Diseasei

Mental retardation, Primary microcephaly

Organism-specific databases

DisGeNETi55755
GeneReviewsiCDK5RAP2
MalaCardsiCDK5RAP2
MIMi604804 phenotype
OpenTargetsiENSG00000136861
Orphaneti2512 Autosomal recessive primary microcephaly
PharmGKBiPA38632

Polymorphism and mutation databases

DMDMi296439505

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000898351 – 1893CDK5 regulatory subunit-associated protein 2Add BLAST1893

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei547PhosphoserineCombined sources1
Modified residuei1001PhosphothreonineCombined sources1
Modified residuei1238PhosphoserineCombined sources1
Modified residuei1490PhosphoserineCombined sources1
Modified residuei1663PhosphoserineBy similarity1
Modified residuei1666PhosphoserineBy similarity1
Modified residuei1893PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated in vitro by CDK5.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ96SN8
MaxQBiQ96SN8
PaxDbiQ96SN8
PeptideAtlasiQ96SN8
PRIDEiQ96SN8
ProteomicsDBi78131
78132 [Q96SN8-2]
78133 [Q96SN8-3]
78134 [Q96SN8-4]

PTM databases

iPTMnetiQ96SN8
PhosphoSitePlusiQ96SN8

Expressioni

Tissue specificityi

Widely expressed. Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.1 Publication

Gene expression databases

BgeeiENSG00000136861
ExpressionAtlasiQ96SN8 baseline and differential
GenevisibleiQ96SN8 HS

Organism-specific databases

HPAiHPA035820
HPA046529

Interactioni

Subunit structurei

Interacts with CDK5R1 (p35 form) (By similarity). CDK5RAP1, CDK5RAP2 and CDK5RAP3 show competitive binding to CDK5R1. May form a complex with CDK5R1 and CDK5 (By similarity). Interacts with pericentrin/PCNT; the interaction is leading to centrosomal and Golgi localization of CDK5RAP2 and PCNT (PubMed:20466722). Interacts with AKAP9; the interaction targets CDK5RAP2 and AKAP9 to Golgi apparatus (PubMed:20466722). Interacts with MAPRE1; the interaction is direct and targets CDK5RAP2 and EB1/MAPRE1 to microtubule plus ends (PubMed:19553473). Interacts with TUBG1; the interaction is leading to the centrosomal localization of CDK5RAP2 and TUBG1 (PubMed:17959831). Interacts with TUBGCP3 (PubMed:17959831). Interacts with CALM1 (PubMed:20466722). Interacts with CDC20 (PubMed:19282672). Interacts with CEP68; degradation of CEP68 in early mitosis leads to removal of CDK5RAP2 from the centrosome which promotes centriole disengagement and subsequent centriole separation (PubMed:25503564). Interacts with NCKAP5L (PubMed:26485573). Forms a pericentrosomal complex with AKAP9, MAPRE1 and PDE4DIP isoform 13/MMG8/SMYLE; within this complex, MAPRE1 binding to CDK5RAP2 may be mediated by PDE4DIP (PubMed:29162697). Interacts with LGALS3BP; this interaction may connect the pericentrosomal complex to the gamma-tubulin ring complex (gamma-TuRC) to promote microtubule assembly and acetylation (PubMed:29162697).By similarity7 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • calmodulin binding Source: UniProtKB
  • gamma-tubulin binding Source: UniProtKB
  • microtubule binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • tubulin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi120873, 80 interactors
DIPiDIP-31632N
IntActiQ96SN8, 52 interactors
STRINGi9606.ENSP00000343818

Structurei

3D structure databases

ProteinModelPortaliQ96SN8
SMRiQ96SN8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni58 – 196Interaction with NCKAP5L1 PublicationAdd BLAST139
Regioni926 – 1208Interaction with MAPRE11 PublicationAdd BLAST283
Regioni1726 – 1893Interaction with PCNT and AKAP91 PublicationAdd BLAST168
Regioni1726 – 1768Interaction with CDK5R1By similarityAdd BLAST43
Regioni1861 – 1870Required for centrosomal attachment, Golgi localization and CALM1 interaction10

Phylogenomic databases

eggNOGiENOG410J2NR Eukaryota
ENOG411281S LUCA
GeneTreeiENSGT00530000063845
HOVERGENiHBG050976
InParanoidiQ96SN8
KOiK16542
OMAiSEICPPD
OrthoDBiEOG091G008W
PhylomeDBiQ96SN8
TreeFamiTF329233

Family and domain databases

InterProiView protein in InterPro
IPR012943 Cnn_1N
PfamiView protein in Pfam
PF07989 Cnn_1N, 1 hit

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96SN8-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MMDLVLEEDV TVPGTLSGCS GLVPSVPDDL DGINPNAGLG NGLLPNVSEE
60 70 80 90 100
TVSPTRARNM KDFENQITEL KKENFNLKLR IYFLEERMQQ EFHGPTEHIY
110 120 130 140 150
KTNIELKVEV ESLKRELQER EQLLIKASKA VESLAEAGGS EIQRVKEDAR
160 170 180 190 200
KKVQQVEDLL TKRILLLEKD VTAAQAELEK AFAGTETEKA LRLRLESKLS
210 220 230 240 250
EMKKMHEGDL AMALVLDEKD RLIEELKLSL KSKEALIQCL KEEKSQMACP
260 270 280 290 300
DENVSSGELR GLCAAPREEK ERETEAAQME HQKERNSFEE RIQALEEDLR
310 320 330 340 350
EKEREIATEK KNSLKRDKAI QGLTMALKSK EKKVEELNSE IEKLSAAFAK
360 370 380 390 400
AREALQKAQT QEFQGSEDYE TALSGKEALS AALRSQNLTK STENHRLRRS
410 420 430 440 450
IKKITQELSD LQQERERLEK DLEEAHREKS KGDCTIRDLR NEVEKLRNEV
460 470 480 490 500
NEREKAMENR YKSLLSESNK KLHNQEQVIK HLTESTNQKD VLLQKFNEKD
510 520 530 540 550
LEVIQQNCYL MAAEDLELRS EGLITEKCSS QQPPGSKTIF SKEKKQSSDY
560 570 580 590 600
EELIQVLKKE QDIYTHLVKS LQESDSINNL QAELNKIFAL RKQLEQDVLS
610 620 630 640 650
YQNLRKTLEE QISEIRRREE ESFSLYSDQT SYLSICLEEN NRFQVEHFSQ
660 670 680 690 700
EELKKKVSDL IQLVKELYTD NQHLKKTIFD LSCMGFQGNG FPDRLASTEQ
710 720 730 740 750
TELLASKEDE DTIKIGEDDE INFLSDQHLQ QSNEIMKDLS KGGCKNGYLR
760 770 780 790 800
HTESKISDCD GAHAPGCLEE GAFINLLAPL FNEKATLLLE SRPDLLKVVR
810 820 830 840 850
ELLLGQLFLT EQEVSGEHLD GKTEKTPKQK GELVHFVQTN SFSKPHDELK
860 870 880 890 900
LSCEAQLVKA GEVPKVGLKD ASVQTVATEG DLLRFKHEAT REAWEEKPIN
910 920 930 940 950
TALSAEHRPE NLHGVPGWQA ALLSLPGITN REAKKSRLPI LIKPSRSLGN
960 970 980 990 1000
MYRLPATQEV VTQLQSQILE LQGELKEFKT CNKQLHQKLI LAEAVMEGRP
1010 1020 1030 1040 1050
TPDKTLLNAQ PPVGAAYQDS PGEQKGIKTT SSVWRDKEMD SDQQRSYEID
1060 1070 1080 1090 1100
SEICPPDDLA SLPSCKENPE DVLSPTSVAT YLSSKSQPSA KVSVMGTDQS
1110 1120 1130 1140 1150
ESINTSNETE YLKQKIHDLE TELEGYQNFI FQLQKHSQCS EAIITVLCGT
1160 1170 1180 1190 1200
EGAQDGLSKP KNGSDGEEMT FSSLHQVRYV KHVKILGPLA PEMIDSRVLE
1210 1220 1230 1240 1250
NLKQQLEEQE YKLQKEQNLN MQLFSEIHNL QNKFRDLSPP RYDSLVQSQA
1260 1270 1280 1290 1300
RELSLQRQQI KDGHGICVIS RQHMNTMIKA FEELLQASDV DYCVAEGFQE
1310 1320 1330 1340 1350
QLNQCAELLE KLEKLFLNGK SVGVEMNTQN ELMERIEEDN LTYQHLLPES
1360 1370 1380 1390 1400
PEPSASHALS DYETSEKSFF SRDQKQDNET EKTSVMVNSF SQDLLMEHIQ
1410 1420 1430 1440 1450
EIRTLRKRLE ESIKTNEKLR KQLERQGSEF VQGSTSIFAS GSELHSSLTS
1460 1470 1480 1490 1500
EIHFLRKQNQ ALNAMLIKGS RDKQKENDKL RESLSRKTVS LEHLQREYAS
1510 1520 1530 1540 1550
VKEENERLQK EGSEKERHNQ QLIQEVRCSG QELSRVQEEV KLRQQLLSQN
1560 1570 1580 1590 1600
DKLLQSLRVE LKAYEKLDEE HRRLREASGE GWKGQDPFRD LHSLLMEIQA
1610 1620 1630 1640 1650
LRLQLERSIE TSSTLQSRLK EQLARGAEKA QEGALTLAVQ AVSIPEVPLQ
1660 1670 1680 1690 1700
PDKHDGDKYP MESDNSFDLF DSSQAVTPKS VSETPPLSGN DTDSLSCDSG
1710 1720 1730 1740 1750
SSATSTPCVS RLVTGHHLWA SKNGRHVLGL IEDYEALLKQ ISQGQRLLAE
1760 1770 1780 1790 1800
MDIQTQEAPS STSQELGTKG PHPAPLSKFV SSVSTAKLTL EEAYRRLKLL
1810 1820 1830 1840 1850
WRVSLPEDGQ CPLHCEQIGE MKAEVTKLHK KLFEQEKKLQ NTMKLLQLSK
1860 1870 1880 1890
RQEKVIFDQL VVTHKILRKA RGNLELRPGG AHPGTCSPSR PGS
Note: No experimental confirmation available.
Length:1,893
Mass (Da):215,038
Last modified:May 18, 2010 - v5
Checksum:i833B9F9EF3CE8D07
GO
Isoform 2 (identifier: Q96SN8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     702-733: Missing.

Note: No experimental confirmation available.
Show »
Length:1,861
Mass (Da):211,381
Checksum:iC56C74BE444511C8
GO
Isoform 3 (identifier: Q96SN8-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1009-1049: Missing.

Note: No experimental confirmation available.
Show »
Length:1,852
Mass (Da):210,471
Checksum:iD34C2C2D6EABDE08
GO
Isoform 4 (identifier: Q96SN8-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1576-1654: Missing.

Show »
Length:1,814
Mass (Da):206,323
Checksum:iC28575B525292309
GO

Sequence cautioni

The sequence AAH04526 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAA91865 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAB13459 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAB15263 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAB55253 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAD97663 differs from that shown. Reason: Erroneous termination at position 1205. Translated as Gln.Curated
The sequence CAD97828 differs from that shown. Reason: Frameshift at position 1831.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti27P → S in CAD97663 (PubMed:17974005).Curated1
Sequence conflicti43L → V in AAP41926 (Ref. 3) Curated1
Sequence conflicti292I → F in CAD97828 (PubMed:17974005).Curated1
Sequence conflicti414E → K in CAD97828 (PubMed:17974005).Curated1
Sequence conflicti1254S → F in CAD97663 (PubMed:17974005).Curated1
Sequence conflicti1458Q → R in BAA91865 (PubMed:14702039).Curated1
Sequence conflicti1483S → P in CAD97663 (PubMed:17974005).Curated1
Sequence conflicti1550N → D in BAB55253 (PubMed:14702039).Curated1
Sequence conflicti1838K → R in BAA91865 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_056831183A → P. Corresponds to variant dbSNP:rs13287734EnsemblClinVar.1
Natural variantiVAR_017443289E → Q2 PublicationsCorresponds to variant dbSNP:rs4836822EnsemblClinVar.1
Natural variantiVAR_0324261045R → T. Corresponds to variant dbSNP:rs3780679EnsemblClinVar.1
Natural variantiVAR_0596161330N → I. Corresponds to variant dbSNP:rs7875294EnsemblClinVar.1
Natural variantiVAR_0174441540V → L2 PublicationsCorresponds to variant dbSNP:rs4837768EnsemblClinVar.1
Natural variantiVAR_0568321607R → S. Corresponds to variant dbSNP:rs16909747EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_007563702 – 733Missing in isoform 2. 1 PublicationAdd BLAST32
Alternative sequenceiVSP_0075641009 – 1049Missing in isoform 3. 1 PublicationAdd BLAST41
Alternative sequenceiVSP_0075651576 – 1654Missing in isoform 4. 3 PublicationsAdd BLAST79

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB046853 mRNA Translation: BAB13459.2 Different initiation.
AF448860 mRNA Translation: AAP41926.1
AL133161 mRNA Translation: CAB61487.1
BX537421 mRNA Translation: CAD97663.1 Sequence problems.
BX537759 mRNA Translation: CAD97828.1 Frameshift.
AL138836 Genomic DNA No translation available.
AL353736 Genomic DNA No translation available.
AL391870 Genomic DNA No translation available.
AL590642 Genomic DNA No translation available.
AK001729 mRNA Translation: BAA91865.1 Different initiation.
AK025867 mRNA Translation: BAB15263.1 Different initiation.
AK027636 mRNA Translation: BAB55253.1 Different initiation.
BC004526 mRNA Translation: AAH04526.2 Different initiation.
CCDSiCCDS43871.1 [Q96SN8-4]
CCDS6823.1 [Q96SN8-1]
PIRiT42658
RefSeqiNP_001011649.1, NM_001011649.2 [Q96SN8-4]
NP_001258968.1, NM_001272039.1
NP_060719.4, NM_018249.5 [Q96SN8-1]
XP_006717245.1, XM_006717182.1 [Q96SN8-2]
UniGeneiHs.269560

Genome annotation databases

EnsembliENST00000349780; ENSP00000343818; ENSG00000136861 [Q96SN8-1]
ENST00000360190; ENSP00000353317; ENSG00000136861 [Q96SN8-4]
GeneIDi55755
KEGGihsa:55755
UCSCiuc004bkf.5 human [Q96SN8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCK5P2_HUMAN
AccessioniPrimary (citable) accession number: Q96SN8
Secondary accession number(s): Q5JV18
, Q7Z3L4, Q7Z3U1, Q7Z7I6, Q9BSW0, Q9H6J6, Q9HCD9, Q9NV90, Q9UIW9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 16, 2003
Last sequence update: May 18, 2010
Last modified: June 20, 2018
This is version 162 of the entry and version 5 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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