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Q8TDN4 (CABL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
CDK5 and ABL1 enzyme substrate 1
Alternative name(s):
Interactor with CDK3 1
Short name=Ik3-1
Gene names
Name:CABLES1
Synonyms:CABLES
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length633 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Cyclin-dependent kinase binding protein. Enhances cyclin-dependent kinase tyrosine phosphorylation by nonreceptor tyrosine kinases, such as that of CDK5 by activated ABL1, which leads to increased CDK5 activity and is critical for neuronal development, and that of CDK2 by WEE1, which leads to decreased CDK2 activity and growth inhibition. Positively affects neuronal outgrowth. Plays a role as a regulator for p53/p73-induced cell death By similarity.

Subunit structure

Found in a complex with p53/TP53. Found in a number of complexes with CDK2, CDK3, CDK5, ABL1, TDRD7, CDK17, CCNA1, CCNE1 and TP73. Interacts with CDK2, CDK3, CDK5, ABL1 and TDRD7 By similarity. Ref.5

Subcellular location

Nucleus By similarity. Cytoplasm By similarity. Note: Located in the cell body and proximal region of the developing axonal shaft of immature neurons. Located in axonal growth cone, but not in the distal part of the axon shaft or in dendritic growth cone of mature neurons By similarity. Ref.4 Ref.5

Tissue specificity

Expressed in breast, pancreas, colon, head and neck (at protein level). Strongly decreased in more than half of cases of atypical endometrial hyperplasia and in more than 90% of endometrial cancers. Ref.4 Ref.6

Developmental stage

Expression in the endometrial epithelium fluctuates during the menstrual cycle, being greater during the secretory phase when compared with the proliferative phase. Ref.6

Induction

Up-regulated by progesterone and down-regulated by estrogen in benign endometrium. Ref.6

Post-translational modification

Phosphorylated on Ser-313 by CCNE1/CDK3. Phosphorylated on serine/threonine residues by CDK5 and on tyrosine residues by ABL1. Also phosphorylated in vitro by CCNA1/CDK2, CCNE1/CDK2, CCNA1/CDK3 and CCNE1/CDK3 By similarity.

Sequence similarities

Belongs to the cyclin family.

Binary interactions

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8TDN4-1)

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.
Note: No experimental confirmation available.
Isoform 2 (identifier: Q8TDN4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-265: Missing.
     266-282: PGQGGSTSAFEQLQRSR → MLSKRGCHARIYADFPI
Isoform 3 (identifier: Q8TDN4-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-497: Missing.
Isoform 4 (identifier: Q8TDN4-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-327: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 633633CDK5 and ABL1 enzyme substrate 1
PRO_0000080510

Regions

Region1 – 109109Interacts with TDRD7 By similarity
Region179 – 492314Interacts with CDK3 By similarity
Compositional bias2 – 134133Ala-rich

Amino acid modifications

Modified residue1681Phosphoserine Ref.8 Ref.11
Modified residue2871Phosphoserine Ref.8 Ref.11
Modified residue3131Phosphoserine; by CDK2 and CDK3 By similarity
Modified residue4151Phosphothreonine Ref.7 Ref.8 Ref.11

Natural variations

Alternative sequence1 – 497497Missing in isoform 3.
VSP_012695
Alternative sequence1 – 327327Missing in isoform 4.
VSP_045014
Alternative sequence1 – 265265Missing in isoform 2.
VSP_012696
Alternative sequence266 – 28217PGQGG…LQRSR → MLSKRGCHARIYADFPI in isoform 2.
VSP_012697

Experimental info

Sequence conflict4121R → W in AAL83906. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 1, 2005. Version 2.
Checksum: D3569C6BFF635A82

FASTA63367,599
        10         20         30         40         50         60 
MAAAAAAATT AACSSGSAGT DAAGASGLQQ PPPQPQPQPA AAAPAQPPPE PPRKPRMDPR 

        70         80         90        100        110        120 
RRQAALSFLT NISLDGRLPP QDAEWGGGEE GGAAKPGAGG ACGARTRFSL LAAAERGGCI 

       130        140        150        160        170        180 
ALAAPGTPAA GLAAGSGPCL PQPSSLPPLI PGGHATVSGP GVARGFASPL GAGRASGEQW 

       190        200        210        220        230        240 
QPPRPAPLAA CAQLQLLDGS GAAGQEELEE DDAFISVQVP AAAFLGSGTP GSGSGSRGRL 

       250        260        270        280        290        300 
NSFTQGILPI AFSRPTSQNY CSLEQPGQGG STSAFEQLQR SRRRLISQRS SLETLEDIEE 

       310        320        330        340        350        360 
NAPLRRCRTL SGSPRPKNFK KIHFIKNMRQ HDTRNGRIVL ISGRRSFCSI FSVLPYRDST 

       370        380        390        400        410        420 
QVGDLKLDGG RQSTGAVSLK EIIGLEGVEL GADGKTVSYT QFLLPTNAFG ARRNTIDSTS 

       430        440        450        460        470        480 
SFSQFRNLSH RSLSIGRASG TQGSLDTGSD LGDFMDYDPN LLDDPQWPCG KHKRVLIFPS 

       490        500        510        520        530        540 
YMTTVIDYVK PSDLKKDMNE TFKEKFPHIK LTLSKIRSLK REMRKLAQED CGLEEPTVAM 

       550        560        570        580        590        600 
AFVYFEKLAL KGKLNKQNRK LCAGACVLLA AKIGSDLKKH EVKHLIDKLE EKFRLNRREL 

       610        620        630 
IAFEFPVLVA LEFALHLPEH EVMPHYRRLV QSS 

« Hide

Isoform 2 [UniParc].

Checksum: 4F6D839AD0468961
Show »

FASTA36841,871
Isoform 3 [UniParc].

Checksum: ABF7C651A93CAED8
Show »

FASTA13615,856
Isoform 4 [UniParc].

Checksum: 9586F33703C72027
Show »

FASTA30634,593

References

« Hide 'large scale' references
[1]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4).
Tissue: Testis and Thalamus.
[2]"DNA sequence and analysis of human chromosome 18."
Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J. expand/collapse author list , Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.
Nature 437:551-555(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Brain and Lung.
[4]"Cables enhances cdk2 tyrosine 15 phosphorylation by Wee1, inhibits cell growth, and is lost in many human colon and squamous cancers."
Wu C.-L., Kirley S.D., Xiao H., Chuang Y., Chung D.C., Zukerberg L.R.
Cancer Res. 61:7325-7332(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 201-633 (ISOFORM 1), TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INVOLVEMENT IN CANCER.
Tissue: Brain.
[5]"Differential effect of ik3-1/cables on p53- and p73-induced cell death."
Tsuji K., Mizumoto K., Yamochi T., Nishimoto I., Matsuoka M.
J. Biol. Chem. 277:2951-2957(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, IDENTIFICATION IN A COMPLEX WITH TP53.
[6]"Loss of cables, a cyclin-dependent kinase regulatory protein, is associated with the development of endometrial hyperplasia and endometrial cancer."
Zukerberg L.R., DeBernardo R.L., Kirley S.D., D'Apuzzo M., Lynch M.P., Littell R.D., Duska L.R., Boring L., Rueda B.R.
Cancer Res. 64:202-208(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: DEVELOPMENTAL STAGE, TISSUE SPECIFICITY, INDUCTION.
[7]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-415, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-168; SER-287 AND THR-415, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-168; SER-287 AND THR-415, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK093243 mRNA. Translation: BAC04107.1.
AK296407 mRNA. Translation: BAG59072.1.
AC105247 Genomic DNA. No translation available.
AC011731 Genomic DNA. No translation available.
BC004124 mRNA. Translation: AAH04124.2.
BC037218 mRNA. Translation: AAH37218.1.
AF348525 mRNA. Translation: AAL83906.1.
CCDSCCDS42417.1. [Q8TDN4-1]
CCDS42418.1. [Q8TDN4-2]
CCDS58615.1. [Q8TDN4-4]
RefSeqNP_001094089.1. NM_001100619.2. [Q8TDN4-1]
NP_001243367.1. NM_001256438.1. [Q8TDN4-4]
NP_612384.1. NM_138375.2. [Q8TDN4-2]
UniGeneHs.11108.

3D structure databases

ProteinModelPortalQ8TDN4.
SMRQ8TDN4. Positions 501-629.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid124877. 3 interactions.
IntActQ8TDN4. 4 interactions.
MINTMINT-6615967.
STRING9606.ENSP00000256925.

PTM databases

PhosphoSiteQ8TDN4.

Polymorphism databases

DMDM73921298.

Proteomic databases

MaxQBQ8TDN4.
PaxDbQ8TDN4.
PRIDEQ8TDN4.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000256925; ENSP00000256925; ENSG00000134508. [Q8TDN4-1]
ENST00000400473; ENSP00000383321; ENSG00000134508. [Q8TDN4-4]
ENST00000420687; ENSP00000413851; ENSG00000134508. [Q8TDN4-2]
GeneID91768.
KEGGhsa:91768.
UCSCuc002kub.2. human. [Q8TDN4-3]
uc002kuc.2. human. [Q8TDN4-1]
uc002kud.2. human. [Q8TDN4-2]
uc031rhr.1. human.

Organism-specific databases

CTD91768.
GeneCardsGC18P020714.
HGNCHGNC:25097. CABLES1.
MIM609194. gene.
neXtProtNX_Q8TDN4.
PharmGKBPA134880184.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG256533.
HOGENOMHOG000231236.
HOVERGENHBG050759.
InParanoidQ8TDN4.
OMAQNYCSLE.
OrthoDBEOG7P5T0S.
PhylomeDBQ8TDN4.
TreeFamTF323936.

Enzyme and pathway databases

ReactomeREACT_604. Hemostasis.
SignaLinkQ8TDN4.

Gene expression databases

ArrayExpressQ8TDN4.
BgeeQ8TDN4.
CleanExHS_CABLES1.
GenevestigatorQ8TDN4.

Family and domain databases

Gene3D1.10.472.10. 1 hit.
InterProIPR012388. Cdk5/c-Abl_linker_Cables.
IPR013763. Cyclin-like.
IPR006671. Cyclin_N.
[Graphical view]
PfamPF00134. Cyclin_N. 1 hit.
[Graphical view]
PIRSFPIRSF025798. Cables. 1 hit.
SMARTSM00385. CYCLIN. 1 hit.
[Graphical view]
SUPFAMSSF47954. SSF47954. 1 hit.
ProtoNetSearch...

Other

ChiTaRSCABLES1. human.
GeneWikiCABLES1.
GenomeRNAi91768.
NextBio77447.
PROQ8TDN4.
SOURCESearch...

Entry information

Entry nameCABL1_HUMAN
AccessionPrimary (citable) accession number: Q8TDN4
Secondary accession number(s): B4DK60 expand/collapse secondary AC list , Q8N3Y8, Q8NA22, Q9BTG1
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 2005
Last sequence update: February 1, 2005
Last modified: July 9, 2014
This is version 119 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM