CK5P3_MOUSE
ID CK5P3_MOUSE Reviewed; 503 AA.
AC Q99LM2; Q3UE41;
DT 16-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=CDK5 regulatory subunit-associated protein 3 {ECO:0000305};
GN Name=Cdk5rap3 {ECO:0000303|PubMed:30635284, ECO:0000312|MGI:MGI:1933126};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, Forelimb, and Pancreas;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary tumor;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP INTERACTION WITH UFL1, UFMYLATION, AND TISSUE SPECIFICITY.
RX PubMed=21494687; DOI=10.1371/journal.pone.0018517;
RA Lemaire K., Moura R.F., Granvik M., Igoillo-Esteve M., Hohmeier H.E.,
RA Hendrickx N., Newgard C.B., Waelkens E., Cnop M., Schuit F.;
RT "Ubiquitin fold modifier 1 (UFM1) and its target UFBP1 protect pancreatic
RT beta cells from ER stress-induced apoptosis.";
RL PLoS ONE 6:E18517-E18517(2011).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE,
RP AND INTERACTION WITH UFL1.
RX PubMed=30635284; DOI=10.1242/dev.169235;
RA Yang R., Wang H., Kang B., Chen B., Shi Y., Yang S., Sun L., Liu Y.,
RA Xiao W., Zhang T., Yang J., Zhang Y., Zhu M., Xu P., Chang Y., Jia Y.,
RA Huang Y.;
RT "CDK5RAP3, a UFL1 substrate adaptor, is crucial for liver development.";
RL Development 146:0-0(2019).
CC -!- FUNCTION: Substrate adapter for ufmylation, the covalent attachment of
CC the ubiquitin-like modifier UFM1 to substrate proteins, in response to
CC endoplasmic reticulum stress (PubMed:30635284). Negatively regulates
CC NF-kappa-B-mediated gene transcription through the control of RELA
CC phosphorylation (By similarity). Probable tumor suppressor initially
CC identified as a CDK5R1 interactor controlling cell proliferation (By
CC similarity). Also regulates mitotic G2/M transition checkpoint and
CC mitotic G2 DNA damage checkpoint (By similarity). Through its
CC interaction with CDKN2A/ARF and MDM2 may induce MDM2-dependent p53/TP53
CC ubiquitination, stabilization and activation in the nucleus, thereby
CC promoting G1 cell cycle arrest and inhibition of cell proliferation (By
CC similarity). May also play a role in the rupture of the nuclear
CC envelope during apoptosis (By similarity). May regulate MAPK14 activity
CC by regulating its dephosphorylation by PPM1D/WIP1 (By similarity).
CC Required for liver development (PubMed:30635284).
CC {ECO:0000250|UniProtKB:Q96JB5, ECO:0000269|PubMed:30635284}.
CC -!- SUBUNIT: Interacts with CDK5R1; competes with CDK5RAP1 and CDK5RAP2 (By
CC similarity). Interacts with RELA (By similarity). Interacts with CHEK1;
CC may negatively regulate CHEK1 and thereby stimulate entry into mitosis
CC (By similarity). Interacts with CDKN2A/ARF and MDM2; forms a ternary
CC complex involved in regulation of p53/TP53 (By similarity). Interacts
CC with UFL1; the interaction is direct (PubMed:21494687,
CC PubMed:30635284). Interaction with UFL1 anchors CDK5RAP3 in the
CC cytoplasm, preventing its translocation to the nucleus which allows
CC expression of the CCND1 cyclin and progression of cells through the
CC G1/S transition (By similarity). Interacts with DDRGK1 (By similarity).
CC Interacts with MAPK14 (By similarity). Interacts with CCNB1 (By
CC similarity). Interacts with TUBG1; may regulate CDK5RAP3 in mitotic
CC G2/M transition checkpoint (By similarity).
CC {ECO:0000250|UniProtKB:Q96JB5, ECO:0000250|UniProtKB:Q9JLH7,
CC ECO:0000269|PubMed:21494687, ECO:0000269|PubMed:30635284}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q96JB5}. Cytoplasm
CC {ECO:0000269|PubMed:30635284}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250|UniProtKB:Q96JB5}.
CC Note=Colocalizes and associates with microtubules.
CC {ECO:0000250|UniProtKB:Q96JB5}.
CC -!- TISSUE SPECIFICITY: Widely expressed with higher expression in
CC secretory tissues. {ECO:0000269|PubMed:21494687}.
CC -!- DEVELOPMENTAL STAGE: Predominantly expressed in hepatocytes during
CC liver development. {ECO:0000269|PubMed:30635284}.
CC -!- PTM: May be phosphorylated by CDK5. {ECO:0000250|UniProtKB:Q9JLH7}.
CC -!- PTM: May be ufmylated. {ECO:0000305|PubMed:21494687}.
CC -!- PTM: Ubiquitinated. Probably triggers proteasomal degradation and is
CC negatively regulated by UFL1. {ECO:0000250|UniProtKB:Q96JB5}.
CC -!- PTM: Cleaved by caspases early during apoptosis, the resulting peptides
CC may play a role in rupture of the nuclear envelope.
CC {ECO:0000250|UniProtKB:Q96JB5}.
CC -!- DISRUPTION PHENOTYPE: Prenatal lethality, probably caused by severe
CC liver hypoplasia (PubMed:30635284). 16.5 dpc mutant embryos also show
CC defects in definitive erythropoiesis (PubMed:30635284). Conditional
CC knockout mice lacking Cdk5rap3 in hepatocytes causes lethality after
CC weaning -specific Cdk5rap3 display liver hypoplasia and die after
CC weaning (PubMed:30635284). {ECO:0000269|PubMed:30635284}.
CC -!- SIMILARITY: Belongs to the CDK5RAP3 family. {ECO:0000305}.
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DR EMBL; AK075771; BAC35945.1; -; mRNA.
DR EMBL; AK075791; BAC35961.1; -; mRNA.
DR EMBL; AK077853; BAC37034.1; -; mRNA.
DR EMBL; AK149765; BAE29070.1; -; mRNA.
DR EMBL; BC002318; AAH02318.1; -; mRNA.
DR CCDS; CCDS25306.1; -.
DR RefSeq; NP_084524.1; NM_030248.2.
DR AlphaFoldDB; Q99LM2; -.
DR SMR; Q99LM2; -.
DR BioGRID; 219769; 1.
DR IntAct; Q99LM2; 1.
DR MINT; Q99LM2; -.
DR STRING; 10090.ENSMUSP00000099441; -.
DR iPTMnet; Q99LM2; -.
DR PhosphoSitePlus; Q99LM2; -.
DR EPD; Q99LM2; -.
DR jPOST; Q99LM2; -.
DR MaxQB; Q99LM2; -.
DR PaxDb; Q99LM2; -.
DR PRIDE; Q99LM2; -.
DR ProteomicsDB; 283508; -.
DR Antibodypedia; 8591; 237 antibodies from 31 providers.
DR Ensembl; ENSMUST00000103152; ENSMUSP00000099441; ENSMUSG00000018669.
DR GeneID; 80280; -.
DR KEGG; mmu:80280; -.
DR UCSC; uc007lcv.1; mouse.
DR CTD; 80279; -.
DR MGI; MGI:1933126; Cdk5rap3.
DR VEuPathDB; HostDB:ENSMUSG00000018669; -.
DR eggNOG; KOG2607; Eukaryota.
DR GeneTree; ENSGT00390000000713; -.
DR HOGENOM; CLU_025645_1_0_1; -.
DR InParanoid; Q99LM2; -.
DR OMA; PGVRKQM; -.
DR OrthoDB; 619606at2759; -.
DR PhylomeDB; Q99LM2; -.
DR BioGRID-ORCS; 80280; 14 hits in 74 CRISPR screens.
DR ChiTaRS; Cdk5rap3; mouse.
DR PRO; PR:Q99LM2; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q99LM2; protein.
DR Bgee; ENSMUSG00000018669; Expressed in lacrimal gland and 256 other tissues.
DR ExpressionAtlas; Q99LM2; baseline and differential.
DR Genevisible; Q99LM2; MM.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IMP:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005874; C:microtubule; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0030332; F:cyclin binding; ISO:MGI.
DR GO; GO:0097371; F:MDM2/MDM4 family protein binding; ISO:MGI.
DR GO; GO:0051019; F:mitogen-activated protein kinase binding; ISO:MGI.
DR GO; GO:0051059; F:NF-kappaB binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0044389; F:ubiquitin-like protein ligase binding; IPI:UniProtKB.
DR GO; GO:0030262; P:apoptotic nuclear changes; ISS:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; ISS:UniProtKB.
DR GO; GO:0060318; P:definitive erythrocyte differentiation; IMP:UniProtKB.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; ISS:UniProtKB.
DR GO; GO:0001889; P:liver development; IMP:UniProtKB.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; ISS:UniProtKB.
DR GO; GO:0044818; P:mitotic G2/M transition checkpoint; ISS:UniProtKB.
DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; ISS:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; ISS:UniProtKB.
DR GO; GO:0044387; P:negative regulation of protein kinase activity by regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0071901; P:negative regulation of protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; ISS:UniProtKB.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISS:UniProtKB.
DR GO; GO:1901798; P:positive regulation of signal transduction by p53 class mediator; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0071569; P:protein ufmylation; IMP:UniProtKB.
DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0010921; P:regulation of phosphatase activity; ISS:UniProtKB.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IMP:UniProtKB.
DR InterPro; IPR008491; CDK5RAP3.
DR PANTHER; PTHR14894; PTHR14894; 1.
DR Pfam; PF05600; DUF773; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Cytoskeleton; Isopeptide bond; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..503
FT /note="CDK5 regulatory subunit-associated protein 3"
FT /id="PRO_0000220517"
FT REGION 268..503
FT /note="Required for interaction with UFL1 and mediates
FT interaction with CHEK1"
FT /evidence="ECO:0000250|UniProtKB:Q96JB5"
FT CROSSLNK 447
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q96JB5"
SQ SEQUENCE 503 AA; 56991 MW; 61428829BAB406E3 CRC64;
MQDHQHVPID IQTSKLLDWL VDRRHCNLKW QSLVLTIREK INTAIQDMPE SQEIAQLLSG
SYIHYFHCLR IVDLLKGTEA STKNIFGRYS SQRMKDWQEI VSLYEKDNTY LVELCSLLVR
NVSYEIPSLK KQIAKCQQLQ QEYSRKEEEG QAGAAEMREQ FYHSCKQYGI TGDNVRRELL
ALVKDLPSQL AEIGAGAQSL GEAIDLYQAC VEFVCDSPTE QVLPMLRYVQ KKGNSTVYEW
RTGTEPSVVE RPQLEEPPEQ VQEDEIDWGD FGVEAVSDSG IVAETPGIDW GISLESEAKD
AGADKIDWGD DAAAASEITV LETGTEAPEG VARGSDALTL LEYPETRNQF IDELMELEIF
LSQRAVEMSE EADILSVSQF QLAPAILQGQ TKEKMLSLVS TLQQLIGRLT SLRMQHLFMI
LASPRYVDRV TEFLQQKLKQ SQLLALKKEL MVEKQQEALQ EQAALEPKLD LLLEKTRELQ
KLIEADISKR YSGRPVNLMG TSL
