CABL1_HUMAN
ID CABL1_HUMAN Reviewed; 633 AA.
AC Q8TDN4; B4DK60; Q8N3Y8; Q8NA22; Q9BTG1;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 2.
DT 03-AUG-2022, entry version 172.
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 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] (ISOFORMS 3 AND 4).
RC TISSUE=Testis, and Thalamus;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain, and 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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 201-633 (ISOFORM 1), TISSUE SPECIFICITY,
RP SUBCELLULAR LOCATION, AND INVOLVEMENT IN CANCER.
RC TISSUE=Brain;
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 [5]
RP SUBCELLULAR LOCATION, AND IDENTIFICATION IN A COMPLEX WITH TP53.
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 [6]
RP DEVELOPMENTAL STAGE, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=14729625; DOI=10.1158/0008-5472.can-03-2833;
RA Zukerberg L.R., DeBernardo R.L., Kirley S.D., D'Apuzzo M., Lynch M.P.,
RA Littell R.D., Duska L.R., Boring L., Rueda B.R.;
RT "Loss of cables, a cyclin-dependent kinase regulatory protein, is
RT associated with the development of endometrial hyperplasia and endometrial
RT cancer.";
RL Cancer Res. 64:202-208(2004).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-415, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-168; SER-287 AND THR-415, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [9]
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 [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-168; SER-287 AND THR-415, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-168, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
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).
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).
CC {ECO:0000250}.
CC -!- SUBUNIT: Found in a complex with p53/TP53. Found in a number of
CC complexes with CDK2, CDK3, CDK5, ABL1, TDRD7, CDK17, CCNA1, CCNE1 and
CC TP73. Interacts with CDK2, CDK3, CDK5, ABL1 and TDRD7 (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC Q8TDN4; Q00535: CDK5; NbExp=7; IntAct=EBI-604615, EBI-1041567;
CC Q8TDN4; Q9H3D4-1: TP63; NbExp=7; IntAct=EBI-604615, EBI-2400586;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}.
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 (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q8TDN4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TDN4-2; Sequence=VSP_012696, VSP_012697;
CC Name=3;
CC IsoId=Q8TDN4-3; Sequence=VSP_012695;
CC Name=4;
CC IsoId=Q8TDN4-4; Sequence=VSP_045014;
CC -!- TISSUE SPECIFICITY: Expressed in breast, pancreas, colon, head and neck
CC (at protein level). Strongly decreased in more than half of cases of
CC atypical endometrial hyperplasia and in more than 90% of endometrial
CC cancers. {ECO:0000269|PubMed:11585773, ECO:0000269|PubMed:14729625}.
CC -!- DEVELOPMENTAL STAGE: Expression in the endometrial epithelium
CC fluctuates during the menstrual cycle, being greater during the
CC secretory phase when compared with the proliferative phase.
CC {ECO:0000269|PubMed:14729625}.
CC -!- INDUCTION: Up-regulated by progesterone and down-regulated by estrogen
CC in benign endometrium. {ECO:0000269|PubMed:14729625}.
CC -!- PTM: Phosphorylated on Ser-313 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 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the cyclin family. {ECO:0000305}.
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DR EMBL; AK093243; BAC04107.1; -; mRNA.
DR EMBL; AK296407; BAG59072.1; -; mRNA.
DR EMBL; AC105247; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC011731; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC004124; AAH04124.2; -; mRNA.
DR EMBL; BC037218; AAH37218.1; -; mRNA.
DR EMBL; AF348525; AAL83906.1; -; mRNA.
DR CCDS; CCDS42417.1; -. [Q8TDN4-1]
DR CCDS; CCDS42418.1; -. [Q8TDN4-2]
DR CCDS; CCDS58615.1; -. [Q8TDN4-4]
DR RefSeq; NP_001094089.1; NM_001100619.2. [Q8TDN4-1]
DR RefSeq; NP_001243367.1; NM_001256438.1. [Q8TDN4-4]
DR RefSeq; NP_612384.1; NM_138375.2. [Q8TDN4-2]
DR AlphaFoldDB; Q8TDN4; -.
DR BioGRID; 124877; 38.
DR IntAct; Q8TDN4; 8.
DR MINT; Q8TDN4; -.
DR STRING; 9606.ENSP00000256925; -.
DR iPTMnet; Q8TDN4; -.
DR PhosphoSitePlus; Q8TDN4; -.
DR BioMuta; CABLES1; -.
DR DMDM; 73921298; -.
DR CPTAC; CPTAC-1741; -.
DR CPTAC; CPTAC-1742; -.
DR EPD; Q8TDN4; -.
DR jPOST; Q8TDN4; -.
DR MassIVE; Q8TDN4; -.
DR MaxQB; Q8TDN4; -.
DR PaxDb; Q8TDN4; -.
DR PeptideAtlas; Q8TDN4; -.
DR PRIDE; Q8TDN4; -.
DR ProteomicsDB; 4430; -.
DR ProteomicsDB; 74310; -. [Q8TDN4-1]
DR ProteomicsDB; 74311; -. [Q8TDN4-2]
DR ProteomicsDB; 74312; -. [Q8TDN4-3]
DR Antibodypedia; 22022; 180 antibodies from 26 providers.
DR DNASU; 91768; -.
DR Ensembl; ENST00000256925.12; ENSP00000256925.7; ENSG00000134508.13. [Q8TDN4-1]
DR Ensembl; ENST00000400473.6; ENSP00000383321.2; ENSG00000134508.13. [Q8TDN4-4]
DR Ensembl; ENST00000420687.2; ENSP00000413851.2; ENSG00000134508.13. [Q8TDN4-2]
DR GeneID; 91768; -.
DR KEGG; hsa:91768; -.
DR MANE-Select; ENST00000256925.12; ENSP00000256925.7; NM_001100619.3; NP_001094089.1.
DR UCSC; uc002kuc.3; human. [Q8TDN4-1]
DR CTD; 91768; -.
DR DisGeNET; 91768; -.
DR GeneCards; CABLES1; -.
DR HGNC; HGNC:25097; CABLES1.
DR HPA; ENSG00000134508; Tissue enhanced (brain).
DR MIM; 609194; gene.
DR neXtProt; NX_Q8TDN4; -.
DR OpenTargets; ENSG00000134508; -.
DR PharmGKB; PA134880184; -.
DR VEuPathDB; HostDB:ENSG00000134508; -.
DR eggNOG; KOG4164; Eukaryota.
DR GeneTree; ENSGT00400000022086; -.
DR HOGENOM; CLU_021942_0_0_1; -.
DR InParanoid; Q8TDN4; -.
DR OMA; PIANSAM; -.
DR PhylomeDB; Q8TDN4; -.
DR TreeFam; TF323936; -.
DR PathwayCommons; Q8TDN4; -.
DR Reactome; R-HSA-69202; Cyclin E associated events during G1/S transition.
DR Reactome; R-HSA-69656; Cyclin A:Cdk2-associated events at S phase entry.
DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production.
DR SignaLink; Q8TDN4; -.
DR SIGNOR; Q8TDN4; -.
DR BioGRID-ORCS; 91768; 21 hits in 1088 CRISPR screens.
DR ChiTaRS; CABLES1; human.
DR GeneWiki; CABLES1; -.
DR GenomeRNAi; 91768; -.
DR Pharos; Q8TDN4; Tbio.
DR PRO; PR:Q8TDN4; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q8TDN4; protein.
DR Bgee; ENSG00000134508; Expressed in putamen and 157 other tissues.
DR ExpressionAtlas; Q8TDN4; baseline and differential.
DR Genevisible; Q8TDN4; HS.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007399; P:nervous system development; IBA:GO_Central.
DR GO; GO:0051726; P:regulation of cell cycle; IEA:InterPro.
DR CDD; cd00043; CYCLIN; 1.
DR InterPro; IPR012388; CABLES1/2.
DR InterPro; IPR013763; Cyclin-like.
DR InterPro; IPR036915; Cyclin-like_sf.
DR InterPro; IPR006671; Cyclin_N.
DR PANTHER; PTHR22896; PTHR22896; 1.
DR Pfam; PF00134; Cyclin_N; 1.
DR PIRSF; PIRSF025798; Cables; 1.
DR SUPFAM; SSF47954; SSF47954; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell cycle; Cell division; Cyclin; Cytoplasm;
KW Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..633
FT /note="CDK5 and ABL1 enzyme substrate 1"
FT /id="PRO_0000080510"
FT REGION 1..109
FT /note="Interaction with TDRD7"
FT /evidence="ECO:0000250"
FT REGION 1..99
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 179..492
FT /note="Interaction with CDK3"
FT /evidence="ECO:0000250"
FT COMPBIAS 10..29
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 30..52
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 168
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163"
FT MOD_RES 287
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 313
FT /note="Phosphoserine; by CDK2 and CDK3"
FT /evidence="ECO:0000250|UniProtKB:Q9ESJ1"
FT MOD_RES 415
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195"
FT VAR_SEQ 1..497
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_012695"
FT VAR_SEQ 1..327
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045014"
FT VAR_SEQ 1..265
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_012696"
FT VAR_SEQ 266..282
FT /note="PGQGGSTSAFEQLQRSR -> MLSKRGCHARIYADFPI (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_012697"
FT CONFLICT 412
FT /note="R -> W (in Ref. 4; AAL83906)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 633 AA; 67599 MW; D3569C6BFF635A82 CRC64;
MAAAAAAATT AACSSGSAGT DAAGASGLQQ PPPQPQPQPA AAAPAQPPPE PPRKPRMDPR
RRQAALSFLT NISLDGRLPP QDAEWGGGEE GGAAKPGAGG ACGARTRFSL LAAAERGGCI
ALAAPGTPAA GLAAGSGPCL PQPSSLPPLI PGGHATVSGP GVARGFASPL GAGRASGEQW
QPPRPAPLAA CAQLQLLDGS GAAGQEELEE DDAFISVQVP AAAFLGSGTP GSGSGSRGRL
NSFTQGILPI AFSRPTSQNY CSLEQPGQGG STSAFEQLQR SRRRLISQRS SLETLEDIEE
NAPLRRCRTL SGSPRPKNFK KIHFIKNMRQ HDTRNGRIVL ISGRRSFCSI FSVLPYRDST
QVGDLKLDGG RQSTGAVSLK EIIGLEGVEL GADGKTVSYT QFLLPTNAFG ARRNTIDSTS
SFSQFRNLSH RSLSIGRASG TQGSLDTGSD LGDFMDYDPN LLDDPQWPCG KHKRVLIFPS
YMTTVIDYVK PSDLKKDMNE TFKEKFPHIK LTLSKIRSLK REMRKLAQED CGLEEPTVAM
AFVYFEKLAL KGKLNKQNRK LCAGACVLLA AKIGSDLKKH EVKHLIDKLE EKFRLNRREL
IAFEFPVLVA LEFALHLPEH EVMPHYRRLV QSS
