dbPTM

ABL1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	ABL1_MOUSE
UniProt AC	P00520
Protein Name	Tyrosine-protein kinase ABL1
Gene Name	Abl1
Organism	Mus musculus (Mouse).
Sequence Length	1123
Subcellular Localization	Cytoplasm, cytoskeleton. Nucleus. Mitochondrion. The myristoylated c-ABL protein is reported to be nuclear. Sequestered into the cytoplasm through interaction with 14-3-3 proteins (By similarity). Localizes to mitochondria in response to oxidative st
Protein Description	Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9. Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. In response to oxidative stress, phosphorylates serine/threonine kinase PRKD2 at 'Tyr-717' (By similarity). ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-191' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. Regulates T-cell differentiation in a TBX21-dependent manner. [PubMed: 21690296 Phosphorylates TBX21 on tyrosine residues leading to an enhancement of its transcriptional activator activity]
Protein Sequence	MLEICLKLVGCKSKKGLSSSSSCYLEEALQRPVASDFEPQGLSEAARWNSKENLLAGPSENDPNLFVALYDFVASGDNTLSITKGEKLRVLGYNHNGEWCEAQTKNGQGWVPSNYITPVNSLEKHSWYHGPVSRNAAEYLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSESRFNTLAELVHHHSTVADGLITTLHYPAPKRNKPTIYGVSPNYDKWEMERTDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYLRECNRQEVSAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETMFQESSISDEVEKELGKRGTRGGAGSMLQAPELPTKTRTCRRAAEQKDAPDTPELLHTKGLGESDALDSEPAVSPLLPRKERGPPDGSLNEDERLLPRDRKTNLFSALIKKKKKMAPTPPKRSSSFREMDGQPDRRGASEDDSRELCNGPPALTSDAAEPTKSPKASNGAGVPNGAFREPGNSGFRSPHMWKKSSTLTGSRLAAAEEESGMSSSKRFLRSCSASCMPHGARDTEWRSVTLPRDLPSAGKQFDSSTFGGHKSEKPALPRKRTSESRSEQVAKSTAMPPPRLVKKNEEAAEEGFKDTESSPGSSPPSLTPKLLRRQVTASPSSGLSHKEEATKGSASGMGTPATAEPAPPSNKVGLSKASSEEMRVRRHKHSSESPGRDKGRLAKLKPAPPPPPACTGKAGKPAQSPSQEAGEAGGPTKTKCTSLAMDAVNTDPTKAGPPGEGLRKPVPPSVPKPQSTAKPPGTPTSPVSTPSTAPAPSPLAGDQQPSSAAFIPLISTRVSLRKTRQPPERIASGTITKGVVLDSTEALCLAISRNSEQMASHSAVLEAGKNLYTFCVSYVDSIQQMRNKFAFREAINKLESNLRELQICPATASSGPAATQDFSKLLSSVKEISDIVRR

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2 (in isoform 4)	Myristoylation	-	10.12	12654251
16 (in isoform 4)	Phosphorylation	-	34.23	26824392
43	Phosphorylation	DFEPQGLSEAARWNS CCCCCCHHHHHHHCC	31.82	26643407
50	Phosphorylation	SEAARWNSKENLLAG HHHHHHCCCCCCCCC	34.09	26824392
70	Phosphorylation	PNLFVALYDFVASGD CCCEEEEEEHHHCCC	9.52	-
93	Phosphorylation	EKLRVLGYNHNGEWC CEEEEEEECCCCCEE	14.75	47733
115	Phosphorylation	QGWVPSNYITPVNSL CCCCCCCCCCCCHHH	15.54	23069
128	Phosphorylation	SLEKHSWYHGPVSRN HHCCCCCCCCCCCCH	10.42	61675
139	Phosphorylation	VSRNAAEYLLSSGIN CCCHHHHHHHHCCCC	14.28	48383
172	Phosphorylation	LRYEGRVYHYRINTA EEECCEEEEEEEEEC	7.56	65559
174	Phosphorylation	YEGRVYHYRINTASD ECCEEEEEEEEECCC	8.76	65711
178	Phosphorylation	VYHYRINTASDGKLY EEEEEEEECCCCCEE	25.76	24453211
180	Phosphorylation	HYRINTASDGKLYVS EEEEEECCCCCEEEC	44.87	29514104
185	Phosphorylation	TASDGKLYVSSESRF ECCCCCEEECCHHHH	11.19	12522270
187	O-linked_Glycosylation	SDGKLYVSSESRFNT CCCCEEECCHHHHHH	18.16	30059200
215	Phosphorylation	GLITTLHYPAPKRNK CCEEECCCCCCCCCC	12.28	-
226	Phosphorylation	KRNKPTIYGVSPNYD CCCCCCEEEECCCCC	17.60	12522270
229	Phosphorylation	KPTIYGVSPNYDKWE CCCEEEECCCCCCCC	11.76	-
232	Phosphorylation	IYGVSPNYDKWEMER EEEECCCCCCCCEEC	23.45	23075
253	Phosphorylation	HKLGGGQYGEVYEGV ECCCCCCCCEEECCH	20.66	23077
257	Phosphorylation	GGQYGEVYEGVWKKY CCCCCEEECCHHHHE	11.58	23023260
264	Phosphorylation	YEGVWKKYSLTVAVK ECCHHHHEEEEEEEE	12.75	12522270
389	Phosphorylation	FGLSRLMTGDTYTAH HCCCHHCCCCCEECC	36.18	22499769
392	Phosphorylation	SRLMTGDTYTAHAGA CHHCCCCCEECCCCC	24.90	22499769
393	Phosphorylation	RLMTGDTYTAHAGAK HHCCCCCEECCCCCC	13.48	25521595
394	Phosphorylation	LMTGDTYTAHAGAKF HCCCCCEECCCCCCC	17.66	12522270
413	Phosphorylation	TAPESLAYNKFSIKS CCCHHHHCCCCCCCC	24.95	47737
446	Phosphorylation	PYPGIDLSQVYELLE CCCCCCHHHHHHHHH	17.53	9109492
469	Phosphorylation	EGCPEKVYELMRACW CCCCHHHHHHHHHHH	17.89	12522270
547	Phosphorylation	EQKDAPDTPELLHTK HHCCCCCCHHHHCCC	20.01	1956339
553	Phosphorylation	DTPELLHTKGLGESD CCHHHHCCCCCCCCC	27.12	28066266
559	Phosphorylation	HTKGLGESDALDSEP CCCCCCCCCCCCCCC	26.78	-
564	Phosphorylation	GESDALDSEPAVSPL CCCCCCCCCCCCCCC	46.45	23984901
569	Phosphorylation	LDSEPAVSPLLPRKE CCCCCCCCCCCCCHH	16.37	27087446
618	Phosphorylation	APTPPKRSSSFREMD CCCCCCCCCCHHHCC	36.14	30635358
619	Phosphorylation	PTPPKRSSSFREMDG CCCCCCCCCHHHCCC	37.21	29899451
620	Phosphorylation	TPPKRSSSFREMDGQ CCCCCCCCHHHCCCC	29.57	8548467
656	Phosphorylation	TSDAAEPTKSPKASN CCCCCCCCCCCCCCC	35.34	30482847
658	Phosphorylation	DAAEPTKSPKASNGA CCCCCCCCCCCCCCC	33.83	27149854
682	Phosphorylation	PGNSGFRSPHMWKKS CCCCCCCCCCCCCCC	19.52	-
689	Phosphorylation	SPHMWKKSSTLTGSR CCCCCCCCCCCCHHH	25.48	29514104
690	Phosphorylation	PHMWKKSSTLTGSRL CCCCCCCCCCCHHHH	35.99	27600695
693	Phosphorylation	WKKSSTLTGSRLAAA CCCCCCCCHHHHHHH	32.95	28576409
710	Acetylation	ESGMSSSKRFLRSCS HHCCCHHHHHHHHCC	49.47	-
715	Phosphorylation	SSKRFLRSCSASCMP HHHHHHHHCCCCCCC	17.99	25521595
717	Phosphorylation	KRFLRSCSASCMPHG HHHHHHCCCCCCCCC	25.18	25266776
719	Phosphorylation	FLRSCSASCMPHGAR HHHHCCCCCCCCCCC	8.48	26643407
734	Phosphorylation	DTEWRSVTLPRDLPS CCCCEEEECCCCCCC	32.09	27149854
750	Phosphorylation	GKQFDSSTFGGHKSE CCCCCCCCCCCCCCC	30.19	29514104
769	Phosphorylation	PRKRTSESRSEQVAK CCCCCCCCHHHHHHH	40.65	-
800	Phosphorylation	AEEGFKDTESSPGSS HHHCCCCCCCCCCCC	38.05	25619855
802	Phosphorylation	EGFKDTESSPGSSPP HCCCCCCCCCCCCCC	43.88	25619855
803	Phosphorylation	GFKDTESSPGSSPPS CCCCCCCCCCCCCCC	27.35	25619855
806	Phosphorylation	DTESSPGSSPPSLTP CCCCCCCCCCCCCCH	42.95	25619855
807	Phosphorylation	TESSPGSSPPSLTPK CCCCCCCCCCCCCHH	46.90	25521595
810	Phosphorylation	SPGSSPPSLTPKLLR CCCCCCCCCCHHHHH	48.54	25619855
812	Phosphorylation	GSSPPSLTPKLLRRQ CCCCCCCCHHHHHHH	23.79	25619855
821	Phosphorylation	KLLRRQVTASPSSGL HHHHHHCCCCCCCCC	17.06	29514104
823	Phosphorylation	LRRQVTASPSSGLSH HHHHCCCCCCCCCCC	18.89	29472430
825	Phosphorylation	RQVTASPSSGLSHKE HHCCCCCCCCCCCHH	34.25	29472430
844	Phosphorylation	GSASGMGTPATAEPA CCCCCCCCCCCCCCC	10.80	-
902	Acetylation	PPPACTGKAGKPAQS CCCCCCCCCCCCCCC	35.49	21781306
909	Phosphorylation	KAGKPAQSPSQEAGE CCCCCCCCCCCCCHH	28.73	25521595
911	Phosphorylation	GKPAQSPSQEAGEAG CCCCCCCCCCCHHCC	45.99	30635358
970	Phosphorylation	KPPGTPTSPVSTPST CCCCCCCCCCCCCCC	25.22	-

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
226	Y	Phosphorylation	Kinase	ABL1	P00520	GPS
393	Y	Phosphorylation	Kinase	ABL1	P00520	PhosphoELM
393	Y	Phosphorylation	Kinase	HCK	P08631	PSP
393	Y	Phosphorylation	Kinase	HCK	P08103	PSP
393	Y	Phosphorylation	Kinase	ABL-FAMILY	-	GPS
393	Y	Phosphorylation	Kinase	SRC-TYPE TYR-KINASES	-	Uniprot
547	T	Phosphorylation	Kinase	CDK1	P11440	PSP
547	T	Phosphorylation	Kinase	CDK-FAMILY	-	GPS
547	T	Phosphorylation	Kinase	CDK_GROUP	-	PhosphoELM
569	S	Phosphorylation	Kinase	CDK1	P11440	PSP
569	S	Phosphorylation	Kinase	CDK-FAMILY	-	GPS
569	S	Phosphorylation	Kinase	CDK_GROUP	-	PhosphoELM
618	S	Phosphorylation	Kinase	PAK2	Q8CIN4	Uniprot
619	S	Phosphorylation	Kinase	PAK2	Q8CIN4	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
2	G	Myristoylation	12654251
Isoform IV is myristoylated on Gly-2.
446	S	Phosphorylation	9109492
DNA damage-induced activation of ABL1 requires the function of ATM and Ser-446 phosphorylation.
547	T	Phosphorylation	2183353
Phosphorylation at Thr-547 and Ser-569 has been attributed to a CDC2-associated kinase and is coupled to cell division.
569	S	Phosphorylation	2183353
Phosphorylation at Thr-547 and Ser-569 has been attributed to a CDC2-associated kinase and is coupled to cell division.
618	S	Phosphorylation	12748290
Phosphorylation at Ser-618 and Ser-619 by PAK2 increases binding to CRK and reduces binding to ABI1 (By similarity).
619	S	Phosphorylation	12748290
Phosphorylation at Ser-618 and Ser-619 by PAK2 increases binding to CRK and reduces binding to ABI1 (By similarity).
710	K	Acetylation	-
Acetylated at Lys-710 by EP300 which promotes the cytoplasmic translocation.
734	T	Phosphorylation	12748290
Phosphorylation on Thr-734 is required for binding 14-3-3 proteins for cytoplasmic translocation (By similarity).

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of ABL1_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
RIN1_MOUSE	Rin1	physical	9144171
PAXI_MOUSE	Pxn	physical	9603926
ABL1_MOUSE	Abl1	physical	11274764
PTN11_MOUSE	Ptpn11	physical	9393882
CBL_MOUSE	Cbl	physical	9393882
CRKL_MOUSE	Crkl	physical	8978305
CBL_MOUSE	Cbl	physical	10391678
CBL_MOUSE	Cbl	physical	8635998
SHIP1_MOUSE	Inpp5d	physical	11031258
DOK1_MOUSE	Dok1	physical	10823839
PPARG_MOUSE	Pparg	physical	25368164

Drug and Disease Associations

Kegg Drug
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of ABL1_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Functional interaction between DNA-PK and c-Abl in response to DNAdamage."; Kharbanda S., Pandey P., Jin S., Inoue S., Bharti A., Yuan Z.-M.,Weichselbaum R., Weaver D., Kufe D.; Nature 386:732-735(1997). Cited for: FUNCTION, ENZYME REGULATION, SUBCELLULAR LOCATION, PHOSPHORYLATION ATSER-446, AND MUTAGENESIS OF SER-446.	9109492 [Abstract]
"Differential phosphorylation of c-Abl in cell cycle determined bycdc2 kinase and phosphatase activity."; Kipreos E.T., Wang J.Y.; Science 248:217-220(1990). Cited for: PHOSPHORYLATION AT THR-547 AND SER-569.	2183353 [Abstract]
"Structural mechanism for STI-571 inhibition of Abelson tyrosinekinase."; Schindler T., Bornmann W., Pellicena P., Miller W.T., Clarkson B.,Kuriyan J.; Science 289:1938-1942(2000). Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 229-515 IN COMPLEX WITHINHIBITOR STI-571, CATALYTIC ACTIVITY, ENZYME REGULATION,PHOSPHORYLATION AT TYR-393, AND ACTIVATION LOOP.	10988075 [Abstract]
"Two distinct phosphorylation pathways have additive effects on Ablfamily kinase activation."; Tanis K.Q., Veach D., Duewel H.S., Bornmann W.G., Koleske A.J.; Mol. Cell. Biol. 23:3884-3896(2003). Cited for: FUNCTION, ENZYME REGULATION, INTERACTION WITH CRK, AUTOPHOSPHORYLATIONAT TYR-226 AND TYR-393, AND MUTAGENESIS OF TYR-226; LYS-271 ANDTYR-393.	12748290 [Abstract]

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