ID   CABL1_MOUSE             Reviewed;         568 AA.
AC   Q9ESJ1; E9QNI6; Q9EPR8;
DT   01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 2.
DT   24-JAN-2024, entry version 161.
DE   RecName: Full=CDK5 and ABL1 enzyme substrate 1;
DE   AltName: Full=Interactor with CDK3 1;
DE            Short=Ik3-1;
GN   Name=Cables1; Synonyms=Cables;
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 [MRNA], TISSUE SPECIFICITY, SUBCELLULAR LOCATION,
RP   DEVELOPMENTAL STAGE, PHOSPHORYLATION BY CDK5 AND ABL1, IDENTIFICATION IN A
RP   TRIMOLECULAR COMPLEX WITH CDK5 AND ABL1, AND INTERACTION WITH CDK5 AND
RP   ABL1.
RC   TISSUE=Brain;
RX   PubMed=10896159; DOI=10.1016/s0896-6273(00)81200-3;
RA   Zukerberg L.R., Patrick G.N., Nikolic M., Humbert S., Wu C.-L.,
RA   Lanier L.M., Gertler F.B., Vidal M., Van Etten R.A., Tsai L.-H.;
RT   "Cables links Cdk5 and c-Abl and facilitates Cdk5 tyrosine phosphorylation,
RT   kinase upregulation, and neurite outgrowth.";
RL   Neuron 26:633-646(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROBABLE FUNCTION IN G1-S CELL CYCLE
RP   TRANSITION, TISSUE SPECIFICITY, AND INTERACTION WITH CDK3.
RC   STRAIN=BALB/cJ; TISSUE=Brain;
RX   PubMed=10873625; DOI=10.1006/bbrc.2000.2965;
RA   Matsuoka M., Matsuura Y., Semba K., Nishimoto I.;
RT   "Molecular cloning of a cyclin-like protein associated with cyclin-
RT   dependent kinase 3 (cdk 3) in vivo.";
RL   Biochem. Biophys. Res. Commun. 273:442-447(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [4]
RP   PHOSPHORYLATION BY CCNA1/CDK2; CCNE1/CDK2; CCNA1/CDK3 AND CCNE1/CDK3,
RP   PHOSPHORYLATION AT SER-274, AND MUTAGENESIS OF SER-274.
RX   PubMed=11733001; DOI=10.1046/j.0014-2956.2001.02555.x;
RA   Yamochi T., Semba K., Tsuji K., Mizumoto K., Sato H., Matsuura Y.,
RA   Nishimoto I., Matsuoka M.;
RT   "ik3-1/Cables is a substrate for cyclin-dependent kinase 3 (cdk 3).";
RL   Eur. J. Biochem. 268:6076-6082(2001).
RN   [5]
RP   SUBCELLULAR LOCATION, INTERACTION WITH TDRD7, AND IDENTIFICATION IN A
RP   COMPLEX WITH TDRD7 AND CDK17.
RX   PubMed=11527406; DOI=10.1006/bbrc.2001.5493;
RA   Yamochi T., Nishimoto I., Okuda T., Matsuoka M.;
RT   "ik3-1/Cables is associated with Trap and Pctaire2.";
RL   Biochem. Biophys. Res. Commun. 286:1045-1050(2001).
RN   [6]
RP   SUBCELLULAR LOCATION, IDENTIFICATION IN A COMPLEX WITH CDK2; CCNA1 AND
RP   CCNE1, AND INTERACTION WITH CDK2.
RX   PubMed=11585773;
RA   Wu C.-L., Kirley S.D., Xiao H., Chuang Y., Chung D.C., Zukerberg L.R.;
RT   "Cables enhances cdk2 tyrosine 15 phosphorylation by Wee1, inhibits cell
RT   growth, and is lost in many human colon and squamous cancers.";
RL   Cancer Res. 61:7325-7332(2001).
RN   [7]
RP   FUNCTION IN CELL DEATH, SUBCELLULAR LOCATION, AND IDENTIFICATION IN A
RP   COMPLEX WITH TP53 AND TP73.
RX   PubMed=11706030; DOI=10.1074/jbc.m108535200;
RA   Tsuji K., Mizumoto K., Yamochi T., Nishimoto I., Matsuoka M.;
RT   "Differential effect of ik3-1/cables on p53- and p73-induced cell death.";
RL   J. Biol. Chem. 277:2951-2957(2002).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-350, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, and Kidney;
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).
CC   -!- FUNCTION: Cyclin-dependent kinase binding protein. Enhances cyclin-
CC       dependent kinase tyrosine phosphorylation by nonreceptor tyrosine
CC       kinases, such as that of CDK5 by activated ABL1, which leads to
CC       increased CDK5 activity and is critical for neuronal development, and
CC       that of CDK2 by WEE1, which leads to decreased CDK2 activity and growth
CC       inhibition. Positively affects neuronal outgrowth. Plays a role as a
CC       regulator for p53/p73-induced cell death (By similarity). {ECO:0000250,
CC       ECO:0000269|PubMed:11706030}.
CC   -!- SUBUNIT: Found in a complex with p53/TP53 (By similarity). Found in a
CC       number of complexes with CDK2, CDK3, CDK5, ABL1, TDRD7, CDK17, CCNA1,
CC       CCNE1 and TP73. Interacts with CDK2, CDK3, CDK5, ABL1 and TDRD7.
CC       {ECO:0000250, ECO:0000269|PubMed:10873625, ECO:0000269|PubMed:10896159,
CC       ECO:0000269|PubMed:11527406, ECO:0000269|PubMed:11585773,
CC       ECO:0000269|PubMed:11706030}.
CC   -!- INTERACTION:
CC       Q9ESJ1; O88898: Tp63; NbExp=2; IntAct=EBI-604411, EBI-2338025;
CC       Q9ESJ1; P04637: TP53; Xeno; NbExp=3; IntAct=EBI-604411, EBI-366083;
CC       Q9ESJ1; O15350: TP73; Xeno; NbExp=3; IntAct=EBI-604411, EBI-389606;
CC   -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Cell projection, growth cone.
CC       Note=Located in the cell body and proximal region of the developing
CC       axonal shaft of immature neurons. Located in axonal growth cone, but
CC       not in the distal part of the axon shaft or in dendritic growth cone of
CC       mature neurons.
CC   -!- TISSUE SPECIFICITY: Ubiquitous. Expressed in postnatal day 1 (P1), in
CC       postmitotic neurons of the subplate, cortex (V/VI) and marginal zone;
CC       in postnatal day 7 (P7), in all layers of the cerebral cortex and in
CC       the CA1 and CA2 regions of the hippocampus (at protein level). Highly
CC       expressed in brain, kidney, liver and lung.
CC       {ECO:0000269|PubMed:10873625, ECO:0000269|PubMed:10896159}.
CC   -!- DEVELOPMENTAL STAGE: Expressed in embryo at 15 dpc and strongly
CC       expressed in postmitotic neurons of the subplate, cortical plate,
CC       subventrical and marginal zones at 18 dpc (at protein level). Expressed
CC       in embryo at 7 dpc onwards. {ECO:0000269|PubMed:10896159}.
CC   -!- PTM: Phosphorylated on Ser-274 by CCNE1/CDK3. Phosphorylated on
CC       serine/threonine residues by CDK5 and on tyrosine residues by ABL1.
CC       Also phosphorylated in vitro by CCNA1/CDK2, CCNE1/CDK2, CCNA1/CDK3 and
CC       CCNE1/CDK3. {ECO:0000269|PubMed:10896159, ECO:0000269|PubMed:11733001}.
CC   -!- SIMILARITY: Belongs to the cyclin family. {ECO:0000305}.
CC   -!- CAUTION: PubMed:10896159 demonstrated that CABLES1 is not associated
CC       with CDK3. {ECO:0000305}.
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DR   EMBL; AF133208; AAG33933.1; -; mRNA.
DR   EMBL; AF328140; AAG42916.1; -; mRNA.
DR   EMBL; AC100751; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC132941; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS29061.1; -.
DR   PIR; JC7317; JC7317.
DR   RefSeq; NP_071304.2; NM_022021.2.
DR   AlphaFoldDB; Q9ESJ1; -.
DR   BioGRID; 211007; 2.
DR   CORUM; Q9ESJ1; -.
DR   ELM; Q9ESJ1; -.
DR   IntAct; Q9ESJ1; 3.
DR   MINT; Q9ESJ1; -.
DR   STRING; 10090.ENSMUSP00000129463; -.
DR   iPTMnet; Q9ESJ1; -.
DR   PhosphoSitePlus; Q9ESJ1; -.
DR   jPOST; Q9ESJ1; -.
DR   MaxQB; Q9ESJ1; -.
DR   PaxDb; 10090-ENSMUSP00000129463; -.
DR   ProteomicsDB; 273872; -.
DR   Antibodypedia; 22022; 206 antibodies from 26 providers.
DR   Ensembl; ENSMUST00000046948.10; ENSMUSP00000040639.8; ENSMUSG00000040957.16.
DR   GeneID; 63955; -.
DR   KEGG; mmu:63955; -.
DR   UCSC; uc012azi.1; mouse.
DR   AGR; MGI:1927065; -.
DR   CTD; 91768; -.
DR   MGI; MGI:1927065; Cables1.
DR   VEuPathDB; HostDB:ENSMUSG00000040957; -.
DR   eggNOG; KOG4164; Eukaryota.
DR   GeneTree; ENSGT00400000022086; -.
DR   InParanoid; Q9ESJ1; -.
DR   OrthoDB; 209340at2759; -.
DR   Reactome; R-MMU-69202; Cyclin E associated events during G1/S transition.
DR   Reactome; R-MMU-69656; Cyclin A:Cdk2-associated events at S phase entry.
DR   BioGRID-ORCS; 63955; 3 hits in 77 CRISPR screens.
DR   ChiTaRS; Cables1; mouse.
DR   PRO; PR:Q9ESJ1; -.
DR   Proteomes; UP000000589; Chromosome 18.
DR   RNAct; Q9ESJ1; Protein.
DR   Bgee; ENSMUSG00000040957; Expressed in habenula and 233 other cell types or tissues.
DR   ExpressionAtlas; Q9ESJ1; baseline and differential.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0030426; C:growth cone; IEA:UniProtKB-SubCell.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR   GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR   GO; GO:0000082; P:G1/S transition of mitotic cell cycle; TAS:MGI.
DR   GO; GO:0007399; P:nervous system development; IMP:MGI.
DR   GO; GO:0051726; P:regulation of cell cycle; TAS:MGI.
DR   CDD; cd20602; CYCLIN_CABLES1; 1.
DR   Gene3D; 1.10.472.10; Cyclin-like; 1.
DR   InterPro; IPR012388; CABLES1/2.
DR   InterPro; IPR036915; Cyclin-like_sf.
DR   InterPro; IPR006671; Cyclin_N.
DR   PANTHER; PTHR22896; CDK5 AND ABL1 ENZYME SUBSTRATE 1; 1.
DR   PANTHER; PTHR22896:SF1; CDK5 AND ABL1 ENZYME SUBSTRATE 1; 1.
DR   Pfam; PF00134; Cyclin_N; 1.
DR   PIRSF; PIRSF025798; Cables; 1.
DR   SUPFAM; SSF47954; Cyclin-like; 1.
DR   Genevisible; Q9ESJ1; MM.
PE   1: Evidence at protein level;
KW   Cell cycle; Cell division; Cell projection; Cyclin; Cytoplasm; Nucleus;
KW   Phosphoprotein; Reference proteome.
FT   CHAIN           1..568
FT                   /note="CDK5 and ABL1 enzyme substrate 1"
FT                   /id="PRO_0000080511"
FT   REGION          1..98
FT                   /note="Interaction with TDRD7"
FT                   /evidence="ECO:0000269|PubMed:11527406"
FT   REGION          1..94
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          130..169
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          140..427
FT                   /note="Interaction with CDK3"
FT                   /evidence="ECO:0000269|PubMed:10873625"
FT   COMPBIAS        8..30
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        31..47
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         248
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8TDN4"
FT   MOD_RES         274
FT                   /note="Phosphoserine; by CDK2 and CDK3"
FT                   /evidence="ECO:0000269|PubMed:11733001"
FT   MOD_RES         350
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MUTAGEN         274
FT                   /note="S->A: Less efficiently phosphorylated in vitro."
FT                   /evidence="ECO:0000269|PubMed:11733001"
FT   MUTAGEN         274
FT                   /note="S->T: Efficiently phosphorylated in vitro."
FT                   /evidence="ECO:0000269|PubMed:11733001"
FT   CONFLICT        84..85
FT                   /note="EE -> DQ (in Ref. 1; AAG33933)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        242
FT                   /note="S -> A (in Ref. 1; AAG33933)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        384
FT                   /note="S -> C (in Ref. 1; AAG33933)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        390
FT                   /note="M -> V (in Ref. 1; AAG33933 and 2; AAG42916)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   568 AA;  61429 MW;  A5B8131FCDAD1B7D CRC64;
     MAAATATAGT AACSSSSSSR GGSTDAAATS GVQPPPPPPA TAPPEPLRKP RMDPRRRQAA
     LSFLTNISLD GRPPLQDHEW GGGEEGGGTK PGARARLSLL AAGCNAFSAP GTAAAPWTAG
     SGSSPCPLPP SLVPRVLGEP SQPPRSAPAV TGAQLQLPDG PGGAGQEELE EDDAFTNVQV
     PSASFLGSGT PGSTSGSRGR LNSFTQGILP IAFSRQNSQN YCALEQSGQG GSTSALEQLQ
     RSRRRLISQR SSLETLEDIE ENAPLRRCRT LSGSPRPKNF KKIHFIKNMR QHDTKNGRDL
     KLDGGRQSAG AMSLKEIIGL EGVELGADGK TVSYTQFLLP TNAFGNRRNT IDSTASFSQF
     RSLSHRSLSM GRAGSTQGSL DAGSDLGDFM DYDPNLLDDP QWPCGKHKRV LTFPSYMTTV
     IDYVKPSDLK KDMNETFKEK FPHIKLTLSK IRSLKREMRK LAQEDCGFEE PTVAMAFVYF
     EKLALRGKLN KQNRKLCAGA CVLLAAKVGS DLRKHEVKHL IDKLEEKFRL NRRELIAFEF
     PVLVALEFAL HLPEHEVMPH YRRLIQSS
//