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Q8TDN4

- CABL1_HUMAN

UniProt

Q8TDN4 - CABL1_HUMAN

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Protein

CDK5 and ABL1 enzyme substrate 1

Gene

CABLES1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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).By similarity

GO - Molecular functioni

  1. cyclin-dependent protein serine/threonine kinase regulator activity Source: InterPro

GO - Biological processi

  1. blood coagulation Source: Reactome
  2. cell cycle Source: UniProtKB-KW
  3. cell division Source: UniProtKB-KW
  4. nervous system development Source: Ensembl
  5. regulation of cell cycle Source: InterPro
  6. regulation of cell division Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Cyclin

Keywords - Biological processi

Cell cycle, Cell division

Enzyme and pathway databases

ReactomeiREACT_24970. Factors involved in megakaryocyte development and platelet production.
SignaLinkiQ8TDN4.

Names & Taxonomyi

Protein namesi
Recommended name:
CDK5 and ABL1 enzyme substrate 1
Alternative name(s):
Interactor with CDK3 1
Short name:
Ik3-1
Gene namesi
Name:CABLES1
Synonyms:CABLES
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 18

Organism-specific databases

HGNCiHGNC:25097. CABLES1.

Subcellular locationi

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).By similarity

GO - Cellular componenti

  1. cytosol Source: MGI
  2. nucleus Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134880184.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 633633CDK5 and ABL1 enzyme substrate 1PRO_0000080510Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei168 – 1681Phosphoserine2 Publications
Modified residuei287 – 2871Phosphoserine2 Publications
Modified residuei313 – 3131Phosphoserine; by CDK2 and CDK3By similarity
Modified residuei415 – 4151Phosphothreonine3 Publications

Post-translational modificationi

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).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ8TDN4.
PaxDbiQ8TDN4.
PRIDEiQ8TDN4.

PTM databases

PhosphoSiteiQ8TDN4.

Expressioni

Tissue specificityi

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.2 Publications

Developmental stagei

Expression in the endometrial epithelium fluctuates during the menstrual cycle, being greater during the secretory phase when compared with the proliferative phase.1 Publication

Inductioni

Up-regulated by progesterone and down-regulated by estrogen in benign endometrium.1 Publication

Gene expression databases

BgeeiQ8TDN4.
CleanExiHS_CABLES1.
ExpressionAtlasiQ8TDN4. baseline and differential.
GenevestigatoriQ8TDN4.

Interactioni

Subunit structurei

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).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
CDK5Q005354EBI-604615,EBI-1041567
TP63Q9H3D4-17EBI-604615,EBI-2400586

Protein-protein interaction databases

BioGridi124877. 5 interactions.
IntActiQ8TDN4. 4 interactions.
MINTiMINT-6615967.
STRINGi9606.ENSP00000256925.

Structurei

3D structure databases

ProteinModelPortaliQ8TDN4.
SMRiQ8TDN4. Positions 501-629.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 109109Interacts with TDRD7By similarityAdd
BLAST
Regioni179 – 492314Interacts with CDK3By similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi2 – 134133Ala-richAdd
BLAST

Sequence similaritiesi

Belongs to the cyclin family.Curated

Phylogenomic databases

eggNOGiNOG256533.
GeneTreeiENSGT00400000022086.
HOGENOMiHOG000231236.
HOVERGENiHBG050759.
InParanoidiQ8TDN4.
OMAiQNYCSLE.
OrthoDBiEOG7P5T0S.
PhylomeDBiQ8TDN4.
TreeFamiTF323936.

Family and domain databases

Gene3Di1.10.472.10. 1 hit.
InterProiIPR012388. Cdk5/c-Abl_linker_Cables.
IPR013763. Cyclin-like.
IPR006671. Cyclin_N.
[Graphical view]
PfamiPF00134. Cyclin_N. 1 hit.
[Graphical view]
PIRSFiPIRSF025798. Cables. 1 hit.
SMARTiSM00385. CYCLIN. 1 hit.
[Graphical view]
SUPFAMiSSF47954. SSF47954. 1 hit.

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q8TDN4-1) [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
MAAAAAAATT AACSSGSAGT DAAGASGLQQ PPPQPQPQPA AAAPAQPPPE
60 70 80 90 100
PPRKPRMDPR RRQAALSFLT NISLDGRLPP QDAEWGGGEE GGAAKPGAGG
110 120 130 140 150
ACGARTRFSL LAAAERGGCI ALAAPGTPAA GLAAGSGPCL PQPSSLPPLI
160 170 180 190 200
PGGHATVSGP GVARGFASPL GAGRASGEQW QPPRPAPLAA CAQLQLLDGS
210 220 230 240 250
GAAGQEELEE DDAFISVQVP AAAFLGSGTP GSGSGSRGRL NSFTQGILPI
260 270 280 290 300
AFSRPTSQNY CSLEQPGQGG STSAFEQLQR SRRRLISQRS SLETLEDIEE
310 320 330 340 350
NAPLRRCRTL SGSPRPKNFK KIHFIKNMRQ HDTRNGRIVL ISGRRSFCSI
360 370 380 390 400
FSVLPYRDST QVGDLKLDGG RQSTGAVSLK EIIGLEGVEL GADGKTVSYT
410 420 430 440 450
QFLLPTNAFG ARRNTIDSTS SFSQFRNLSH RSLSIGRASG TQGSLDTGSD
460 470 480 490 500
LGDFMDYDPN LLDDPQWPCG KHKRVLIFPS YMTTVIDYVK PSDLKKDMNE
510 520 530 540 550
TFKEKFPHIK LTLSKIRSLK REMRKLAQED CGLEEPTVAM AFVYFEKLAL
560 570 580 590 600
KGKLNKQNRK LCAGACVLLA AKIGSDLKKH EVKHLIDKLE EKFRLNRREL
610 620 630
IAFEFPVLVA LEFALHLPEH EVMPHYRRLV QSS

Note: No experimental confirmation available.

Length:633
Mass (Da):67,599
Last modified:February 1, 2005 - v2
Checksum:iD3569C6BFF635A82
GO
Isoform 2 (identifier: Q8TDN4-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-265: Missing.
     266-282: PGQGGSTSAFEQLQRSR → MLSKRGCHARIYADFPI

Show »
Length:368
Mass (Da):41,871
Checksum:i4F6D839AD0468961
GO
Isoform 3 (identifier: Q8TDN4-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-497: Missing.

Show »
Length:136
Mass (Da):15,856
Checksum:iABF7C651A93CAED8
GO
Isoform 4 (identifier: Q8TDN4-4) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-327: Missing.

Note: No experimental confirmation available.

Show »
Length:306
Mass (Da):34,593
Checksum:i9586F33703C72027
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti412 – 4121R → W in AAL83906. (PubMed:11585773)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 497497Missing in isoform 3. 1 PublicationVSP_012695Add
BLAST
Alternative sequencei1 – 327327Missing in isoform 4. 1 PublicationVSP_045014Add
BLAST
Alternative sequencei1 – 265265Missing in isoform 2. 1 PublicationVSP_012696Add
BLAST
Alternative sequencei266 – 28217PGQGG…LQRSR → MLSKRGCHARIYADFPI in isoform 2. 1 PublicationVSP_012697Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS42417.1. [Q8TDN4-1]
CCDS42418.1. [Q8TDN4-2]
CCDS58615.1. [Q8TDN4-4]
RefSeqiNP_001094089.1. NM_001100619.2. [Q8TDN4-1]
NP_001243367.1. NM_001256438.1. [Q8TDN4-4]
NP_612384.1. NM_138375.2. [Q8TDN4-2]
UniGeneiHs.11108.

Genome annotation databases

EnsembliENST00000256925; ENSP00000256925; ENSG00000134508. [Q8TDN4-1]
ENST00000400473; ENSP00000383321; ENSG00000134508. [Q8TDN4-4]
ENST00000420687; ENSP00000413851; ENSG00000134508. [Q8TDN4-2]
GeneIDi91768.
KEGGihsa:91768.
UCSCiuc002kub.2. human. [Q8TDN4-3]
uc002kuc.2. human. [Q8TDN4-1]
uc002kud.2. human. [Q8TDN4-2]
uc031rhr.1. human.

Polymorphism databases

DMDMi73921298.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS42417.1. [Q8TDN4-1 ]
CCDS42418.1. [Q8TDN4-2 ]
CCDS58615.1. [Q8TDN4-4 ]
RefSeqi NP_001094089.1. NM_001100619.2. [Q8TDN4-1 ]
NP_001243367.1. NM_001256438.1. [Q8TDN4-4 ]
NP_612384.1. NM_138375.2. [Q8TDN4-2 ]
UniGenei Hs.11108.

3D structure databases

ProteinModelPortali Q8TDN4.
SMRi Q8TDN4. Positions 501-629.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 124877. 5 interactions.
IntActi Q8TDN4. 4 interactions.
MINTi MINT-6615967.
STRINGi 9606.ENSP00000256925.

PTM databases

PhosphoSitei Q8TDN4.

Polymorphism databases

DMDMi 73921298.

Proteomic databases

MaxQBi Q8TDN4.
PaxDbi Q8TDN4.
PRIDEi Q8TDN4.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000256925 ; ENSP00000256925 ; ENSG00000134508 . [Q8TDN4-1 ]
ENST00000400473 ; ENSP00000383321 ; ENSG00000134508 . [Q8TDN4-4 ]
ENST00000420687 ; ENSP00000413851 ; ENSG00000134508 . [Q8TDN4-2 ]
GeneIDi 91768.
KEGGi hsa:91768.
UCSCi uc002kub.2. human. [Q8TDN4-3 ]
uc002kuc.2. human. [Q8TDN4-1 ]
uc002kud.2. human. [Q8TDN4-2 ]
uc031rhr.1. human.

Organism-specific databases

CTDi 91768.
GeneCardsi GC18P020714.
HGNCi HGNC:25097. CABLES1.
MIMi 609194. gene.
neXtProti NX_Q8TDN4.
PharmGKBi PA134880184.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG256533.
GeneTreei ENSGT00400000022086.
HOGENOMi HOG000231236.
HOVERGENi HBG050759.
InParanoidi Q8TDN4.
OMAi QNYCSLE.
OrthoDBi EOG7P5T0S.
PhylomeDBi Q8TDN4.
TreeFami TF323936.

Enzyme and pathway databases

Reactomei REACT_24970. Factors involved in megakaryocyte development and platelet production.
SignaLinki Q8TDN4.

Miscellaneous databases

ChiTaRSi CABLES1. human.
GeneWikii CABLES1.
GenomeRNAii 91768.
NextBioi 77447.
PROi Q8TDN4.
SOURCEi Search...

Gene expression databases

Bgeei Q8TDN4.
CleanExi HS_CABLES1.
ExpressionAtlasi Q8TDN4. baseline and differential.
Genevestigatori Q8TDN4.

Family and domain databases

Gene3Di 1.10.472.10. 1 hit.
InterProi IPR012388. Cdk5/c-Abl_linker_Cables.
IPR013763. Cyclin-like.
IPR006671. Cyclin_N.
[Graphical view ]
Pfami PF00134. Cyclin_N. 1 hit.
[Graphical view ]
PIRSFi PIRSF025798. Cables. 1 hit.
SMARTi SM00385. CYCLIN. 1 hit.
[Graphical view ]
SUPFAMi SSF47954. SSF47954. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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. 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. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-168; SER-287 AND THR-415, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiCABL1_HUMAN
AccessioniPrimary (citable) accession number: Q8TDN4
Secondary accession number(s): B4DK60
, Q8N3Y8, Q8NA22, Q9BTG1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 2005
Last sequence update: February 1, 2005
Last modified: October 29, 2014
This is version 122 of the entry and version 2 of the sequence. [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

Documents

  1. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3