Reviewed, UniProtKB/Swiss-Prot Q8TDN4 (CABL1_HUMAN)

Names and origin

Protein names

Recommended name:
    CDK5 and ABL1 enzyme substrate 1
Alternative name(s):
    Interactor with CDK3 1
      Short name=Ik3-1

Gene names

Name:	CABLES1
Synonyms:	CABLES

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	633 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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, PCTK2, CCNA1, CCNE1 and TP73. Interacts with CDK2, CDK3, CDK5, ABL1 and TDRD7 By similarity.
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.
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.
Involvement in disease	Defects in CABLES1 are associated with some colon and squamous cancers.
Sequence similarities	Belongs to the cyclin family.

Ontologies

Keywords
Biological process	Cell cycle Cell division
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Molecular function	Cyclin
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW cell division Inferred from electronic annotation. Source: UniProtKB-KW regulation of cell cycle Inferred from electronic annotation. Source: InterPro regulation of cell division Inferred from electronic annotation. Source: InterPro
Cellular component	cytosol Inferred from direct assay. Source: MGI nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	cyclin-dependent protein kinase regulator activity Inferred from electronic annotation. Source: InterPro protein binding Ref.5 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TP53	P04637	1	EBI-604615,EBI-366083

Alternative products

This entry describes 3 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.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 633	633	CDK5 and ABL1 enzyme substrate 1		PRO_0000080510
Regions
	Region	1 – 109	109	Interacts with TDRD7 By similarity
	Region	179 – 492	314	Interacts with CDK3 By similarity
	Compositional bias	2 – 134	133	Ala-rich
Amino acid modifications
	Modified residue	168	1	Phosphoserine Ref.7 Ref.9
	Modified residue	242	1	Phosphoserine Ref.9
	Modified residue	287	1	Phosphoserine Ref.9
	Modified residue	290	1	Phosphoserine Ref.9
	Modified residue	291	1	Phosphoserine Ref.9
	Modified residue	311	1	Phosphoserine Ref.9
	Modified residue	313	1	Phosphoserine; by CDK2 and CDK3 By similarity
	Modified residue	373	1	Phosphoserine Ref.9
	Modified residue	415	1	Phosphothreonine Ref.9 Ref.8
	Modified residue	418	1	Phosphoserine Ref.9
	Modified residue	434	1	Phosphoserine Ref.9
Natural variations
	Alternative sequence	1 – 497	497	Missing in isoform 3.		VSP_012695
	Alternative sequence	1 – 265	265	Missing in isoform 2.		VSP_012696
	Alternative sequence	266 – 282	17	PGQGG…LQRSR → MLSKRGCHARIYADFPI in isoform 2.		VSP_012697
Experimental info
	Sequence conflict	412	1	R → W in AAL83906. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 1, 2005. Version 2. Checksum: D3569C6BFF635A82	FASTA	633	67,599
	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
	Isoform 2. Checksum: 4F6D839AD0468961	FASTA	368	41,871
	10 20 30 40 50 60 MLSKRGCHAR IYADFPIRRL ISQRSSLETL EDIEENAPLR RCRTLSGSPR PKNFKKIHFI 70 80 90 100 110 120 KNMRQHDTRN GRIVLISGRR SFCSIFSVLP YRDSTQVGDL KLDGGRQSTG AVSLKEIIGL 130 140 150 160 170 180 EGVELGADGK TVSYTQFLLP TNAFGARRNT IDSTSSFSQF RNLSHRSLSI GRASGTQGSL 190 200 210 220 230 240 DTGSDLGDFM DYDPNLLDDP QWPCGKHKRV LIFPSYMTTV IDYVKPSDLK KDMNETFKEK 250 260 270 280 290 300 FPHIKLTLSK IRSLKREMRK LAQEDCGLEE PTVAMAFVYF EKLALKGKLN KQNRKLCAGA 310 320 330 340 350 360 CVLLAAKIGS DLKKHEVKHL IDKLEEKFRL NRRELIAFEF PVLVALEFAL HLPEHEVMPH YRRLVQSS
	Isoform 3. Checksum: ABF7C651A93CAED8	FASTA	136	15,856
	10 20 30 40 50 60 MNETFKEKFP HIKLTLSKIR SLKREMRKLA QEDCGLEEPT VAMAFVYFEK LALKGKLNKQ 70 80 90 100 110 120 NRKLCAGACV LLAAKIGSDL KKHEVKHLID KLEEKFRLNR RELIAFEFPV LVALEFALHL 130 PEHEVMPHYR RLVQSS

References

	« Hide 'large scale' referencesShow '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. , 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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Testis.
[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. , 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: 16177791] [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: 15489334] [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: 11585773] [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: 11706030] [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: 14729625] [Abstract] Cited for: DEVELOPMENTAL STAGE, TISSUE SPECIFICITY, INDUCTION.
[7]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-168, MASS SPECTROMETRY. Tissue: Epithelium.
[8]	"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: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-415, MASS SPECTROMETRY.
[9]	"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: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-168; SER-242; SER-287; SER-290; SER-291; SER-311; SER-313; SER-373; THR-415; SER-418 AND SER-434, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AK093243 mRNA. Translation: BAC04107.1. 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.
IPI	IPI00178886. IPI00291427. IPI00549691.
RefSeq	NP_001094089.1. NP_612384.1.
UniGene	Hs.11108
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8TDN4. 2 interactions.
PTM databases
PhosphoSite	Q8TDN4.
Proteomic databases
PRIDE	Q8TDN4.
Genome annotation databases
Ensembl	ENSG00000134508. Homo sapiens. [Contig view]
GeneID	91768.
KEGG	hsa:91768.
Organism-specific databases
GeneCards	GC18P018970.
H-InvDB	HIX0014363.
HGNC	HGNC:25097. CABLES1.
MIM	609194. gene.
PharmGKB	PA134880184.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q8TDN4.
HOVERGEN	Q8TDN4.
OMA	Q8TDN4. MDPRRRQ.
Gene expression databases
ArrayExpress	Q8TDN4.
Bgee	Q8TDN4.
CleanEx	HS_CABLES1.
GermOnline	ENSG00000134508. Homo sapiens.
Family and domain databases
InterPro	IPR012388. Cables. IPR006670. Cyclin. [Graphical view]
PIRSF	PIRSF025798. Cables. 1 hit.
SMART	SM00385. CYCLIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	77447.
SOURCE	Search...

Entry information

Entry name

CABL1_HUMAN

Accession

Primary (citable) accession number: Q8TDN4
Secondary accession number(s): Q8N3Y8, Q8NA22, Q9BTG1

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 2005
Last sequence update:	February 1, 2005
Last modified:	June 16, 2009
This is version 67 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)