EKS-MUM-00242

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-MUM-00242

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TK/Abl	557.1	1.2E-167	261	512	252

Status

Reviewed

Ensembl Protein

ENSMUSP00000075167

UniProt Accession

P00520; P97896; Q61252; Q61253; Q61254; Q61255; Q61256; Q61257; Q61258; Q61259; Q61260; Q61261; Q6PCM5; Q8C1X4;

Protein Name

Tyrosine-protein kinase ABL1

Protein Synonyms/Alias

Abelson murine leukemia viral oncogene homolog 1; Abelson tyrosine-protein kinase 1; Proto-oncogene c-Abl; p150;

Gene Name

Abl1

Gene Synonyms/Alias

Abl1; Abl;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSMUSG00000026842	ENSMUSP00000028190	ENSMUST00000028190
ENSMUSG00000026842	ENSMUSP00000075167	ENSMUST00000075759
ENSMUSG00000026842	ENSMUSP00000117748	ENSMUST00000124089

Organism

Mus musculus

Functional Description

Non-receptor tyrosine-protein kinase that plays a rolein 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. 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 PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks.

Protein Length

1142

Protein Sequence
(FASTA)

MGQQPGKVLG DQRRPSLPAL HFIKGAGKRD SSRHGGPHCN VFVEHEALQR PVASDFEPQG 60

LSEAARWNSK ENLLAGPSEN DPNLFVALYD FVASGDNTLS ITKGEKLRVL GYNHNGEWCE 120

AQTKNGQGWV PSNYITPVNS LEKHSWYHGP VSRNAAEYLL SSGINGSFLV RESESSPGQR 180

SISLRYEGRV YHYRINTASD GKLYVSSESR FNTLAELVHH HSTVADGLIT TLHYPAPKRN 240

KPTIYGVSPN YDKWEMERTD ITMKHKLGGG QYGEVYEGVW KKYSLTVAVK TLKEDTMEVE 300

EFLKEAAVMK EIKHPNLVQL LGVCTREPPF YIITEFMTYG NLLDYLRECN RQEVSAVVLL 360

YMATQISSAM EYLEKKNFIH RDLAARNCLV GENHLVKVAD FGLSRLMTGD TYTAHAGAKF 420

PIKWTAPESL AYNKFSIKSD VWAFGVLLWE IATYGMSPYP GIDLSQVYEL LEKDYRMERP 480

EGCPEKVYEL MRACWQWNPS DRPSFAEIHQ AFETMFQESS ISDEVEKELG KRGTRGGAGS 540

MLQAPELPTK TRTCRRAAEQ KDAPDTPELL HTKGLGESDA LDSEPAVSPL LPRKERGPPD 600

GSLNEDERLL PRDRKTNLFS ALIKKKKKMA PTPPKRSSSF REMDGQPDRR GASEDDSREL 660

CNGPPALTSD AAEPTKSPKA SNGAGVPNGA FREPGNSGFR SPHMWKKSST LTGSRLAAAE 720

EESGMSSSKR FLRSCSASCM PHGARDTEWR SVTLPRDLPS AGKQFDSSTF GGHKSEKPAL 780

PRKRTSESRS EQVAKSTAMP PPRLVKKNEE AAEEGFKDTE SSPGSSPPSL TPKLLRRQVT 840

ASPSSGLSHK EEATKGSASG MGTPATAEPA PPSNKVGLSK ASSEEMRVRR HKHSSESPGR 900

DKGRLAKLKP APPPPPACTG KAGKPAQSPS QEAGEAGGPT KTKCTSLAMD AVNTDPTKAG 960

PPGEGLRKPV PPSVPKPQST AKPPGTPTSP VSTPSTAPAP SPLAGDQQPS SAAFIPLIST 1020

RVSLRKTRQP PERIASGTIT KGVVLDSTEA LCLAISRNSE QMASHSAVLE AGKNLYTFCV 1080

SYVDSIQQMR NKFAFREAIN KLESNLRELQ ICPATASSGP AATQDFSKLL SSVKEISDIV 1140

RR 1142

Nucleotide Sequence
(FASTA)

ATGGGGCAGC AGCCTGGAAA AGTTCTTGGG GACCAAAGAA GGCCTAGTTT GCCCGCCCTG 60

CATTTTATCA AAGGGGCAGG GAAGAGGGAC TCATCGAGGC ATGGGGGCCC ACACTGCAAT 120

GTCTTTGTGG AACACGAAGC CCTGCAGAGG CCAGTGGCAT CTGACTTTGA GCCCCAGGGT 180

CTCAGCGAAG CAGCTCGATG GAACTCCAAG GAAAACCTTC TTGCTGGGCC CAGTGAAAAT 240

GACCCCAACC TTTTTGTGGC ACTCTATGAT TTTGTGGCCA GTGGAGATAA CACTCTCAGC 300

ATCACTAAAG GTGAAAAGCT CCGGGTCTTG GGTTATAATC ACAATGGGGA ATGGTGTGAA 360

GCCCAAACGA AAAATGGCCA AGGATGGGTC CCAAGCAACT ACATCACCCC CGTCAACAGC 420

CTGGAGAAAC ATTCCTGGTA TCATGGCCCT GTATCTCGGA ATGCTGCTGA GTATCTGCTG 480

AGCAGCGGAA TCAACGGCAG CTTCTTAGTG CGGGAGAGTG AGAGTAGCCC TGGCCAGAGA 540

TCCATCTCGC TGCGGTATGA AGGGAGGGTG TACCACTACA GGATCAACAC TGCCTCTGAT 600

GGCAAGCTGT ACGTGTCCTC CGAGAGCCGC TTCAACACTC TGGCTGAGTT AGTTCACCAT 660

CACTCCACGG TGGCTGATGG CCTCATCACC ACACTCCACT ACCCAGCTCC CAAGCGCAAC 720

AAGCCCACTA TCTACGGTGT GTCCCCCAAC TACGACAAGT GGGAAATGGA GCGCACCGAC 780

ATCACCATGA AGCACAAGTT GGGTGGAGGC CAGTACGGGG AGGTGTACGA GGGCGTTTGG 840

AAGAAGTACA GCCTCACTGT GGCCGTGAAG ACCTTGAAGG AGGACACCAT GGAGGTGGAG 900

GAGTTCCTGA AGGAAGCGGC GGTGATGAAG GAGATCAAAC ACCCTAACCT GGTGCAGCTG 960

CTAGGGGTGT GTACCCGGGA ACCACCATTC TACATAATCA CTGAGTTCAT GACCTATGGG 1020

AACCTGCTGG ACTACCTGAG GGAGTGTAAC CGGCAGGAGG TGAGCGCCGT GGTACTGCTC 1080

TACATGGCCA CACAGATCTC ATCAGCCATG GAGTACTTGG AGAAGAAGAA CTTCATCCAC 1140

AGAGACCTTG CTGCCCGGAA CTGCCTGGTA GGGGAAAACC ACTTGGTGAA GGTGGCTGAT 1200

TTTGGCCTGA GCAGGTTGAT GACAGGGGAC ACCTACACGG CCCATGCTGG AGCCAAATTC 1260

CCCATCAAAT GGACCGCACC TGAGAGCCTG GCCTACAACA AGTTCTCCAT CAAGTCGGAC 1320

GTGTGGGCAT TTGGAGTATT GCTCTGGGAG ATTGCTACCT ATGGCATGTC ACCTTACCCG 1380

GGAATTGACC TGTCTCAGGT TTATGAGCTG CTGGAAAAAG ACTACCGCAT GGAGCGCCCT 1440

GAAGGCTGCC CGGAGAAGGT CTACGAGCTC ATGCGAGCAT GTTGGCAGTG GAACCCCTCT 1500

GACCGGCCCT CCTTTGCTGA AATCCACCAA GCCTTTGAAA CCATGTTCCA GGAATCCAGT 1560

ATCTCAGATG AGGTGGAGAA GGAGCTGGGG AAACGAGGCA CGAGAGGAGG TGCTGGGAGT 1620

ATGCTGCAGG CCCCAGAGCT GCCCACCAAG ACCAGAACCT GCAGGAGAGC AGCTGAGCAG 1680

AAAGATGCGC CTGACACCCC TGAGCTGCTC CACACGAAGG GCCTGGGAGA AAGCGATGCA 1740

CTGGACAGTG AGCCTGCTGT ATCGCCACTG CTTCCTCGGA AAGAGCGCGG GCCCCCAGAC 1800

GGCAGCCTAA ATGAAGATGA GCGCCTTCTC CCCAGAGACA GAAAGACCAA CCTGTTCAGC 1860

GCTTTGATCA AGAAGAAGAA GAAAATGGCG CCGACGCCCC CTAAGCGCAG CAGTTCCTTC 1920

CGAGAGATGG ATGGCCAGCC AGACCGCAGA GGGGCTAGTG AGGATGACAG CAGGGAACTC 1980

TGCAATGGAC CACCAGCTCT CACCTCAGAC GCAGCAGAGC CTACCAAGTC CCCAAAGGCC 2040

AGCAATGGGG CTGGCGTCCC TAATGGAGCC TTCCGGGAGC CGGGCAACTC AGGCTTCCGT 2100

TCTCCCCACA TGTGGAAAAA GTCCAGCACA CTGACCGGGA GCCGCCTGGC TGCTGCCGAA 2160

GAGGAGAGCG GCATGAGCTC CAGTAAGCGC TTCCTGCGTT CTTGTTCGGC CTCCTGCATG 2220

CCCCATGGGG CAAGGGACAC AGAGTGGCGG TCGGTCACGC TGCCTCGAGA CCTGCCGTCT 2280

GCTGGCAAGC AGTTTGACTC ATCCACCTTT GGAGGGCACA AAAGCGAAAA GCCAGCTCTG 2340

CCTCGGAAAC GCACCAGTGA GAGCAGGTCT GAGCAGGTGG CCAAAAGCAC GGCGATGCCC 2400

CCTCCCCGGC TGGTGAAGAA GAACGAGGAG GCTGCTGAAG AAGGCTTCAA AGACACAGAA 2460

TCCAGCCCTG GCTCCAGCCC TCCCAGCTTG ACTCCCAAAC TCCTCCGCAG GCAGGTCACT 2520

GCCTCTCCTT CCTCTGGCCT CTCTCACAAG GAAGAGGCCA CCAAGGGCAG TGCCTCAGGC 2580

ATGGGGACTC CGGCCACTGC AGAGCCAGCA CCCCCCAGCA ACAAAGTGGG CCTCAGCAAG 2640

GCCTCCTCTG AGGAGATGCG CGTAAGGAGG CACAAGCACA GCTCGGAGTC CCCAGGGAGA 2700

GACAAGGGGC GACTGGCTAA GCTCAAGCCT GCCCCGCCGC CTCCTCCTGC CTGCACAGGA 2760

AAAGCAGGCA AGCCCGCACA GAGCCCCAGC CAAGAGGCCG GGGAGGCAGG GGGGCCCACA 2820

AAGACAAAAT GCACGAGTCT GGCTATGGAT GCTGTGAACA CTGACCCCAC CAAGGCCGGC 2880

CCACCTGGAG AAGGACTGAG AAAGCCTGTG CCCCCATCTG TGCCAAAGCC CCAGTCGACG 2940

GCTAAGCCTC CAGGGACTCC CACCAGCCCG GTCTCCACCC CCTCCACAGC ACCAGCTCCT 3000

TCACCCCTGG CTGGGGACCA GCAGCCATCT TCTGCCGCCT TCATCCCCCT CATATCAACC 3060

CGTGTGTCTC TTAGGAAGAC CCGCCAGCCG CCAGAGCGCA TTGCCAGTGG CACCATCACC 3120

AAGGGTGTGG TTCTGGACAG TACTGAGGCC CTGTGCCTTG CCATCTCCCG GAACTCAGAG 3180

CAGATGGCCA GCCACAGTGC TGTACTGGAG GCTGGCAAGA ACCTGTACAC TTTCTGTGTG 3240

AGCTATGTGG ACTCTATCCA GCAGATGAGG AACAAGTTTG CCTTCCGTGA GGCTATCAAC 3300

AAGCTGGAGA GCAACCTCCG AGAGCTGCAG ATCTGCCCTG CCACAGCCTC CAGTGGGCCA 3360

GCTGCCACCC AAGACTTCAG CAAGCTGCTC AGCTCTGTGA AGGAGATCAG CGACATTGTC 3420

CGGAGGTAG 3429

Domain Profile

S: 1     iimkhklgggqygevyegvwkkysltvavktlkedtmeveeflkeaavmkelkhpnlvql  60

         i+mkhklgggqygevyegvwkkysltvavktlkedtmeveeflkeaavmke+khpnlvql

Q: 261   ITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQL  320

         89**********************************************************

S: 61    lgvctreppfyiitefmsygnlldylreadreeveavvllymatqissameylekknfih  120

         lgvctreppfyiitefm+ygnlldylre++r+ev+avvllymatqissameylekknfih

Q: 321   LGVCTREPPFYIITEFMTYGNLLDYLRECNRQEVSAVVLLYMATQISSAMEYLEKKNFIH  380

         ************************************************************

S: 121   rdlaarnclvgenklvkvadfglsrlmkedtytahagakfpikwtapeslaynkfsiksd  180

         rdlaarnclvgen+lvkvadfglsrlm++dtytahagakfpikwtapeslaynkfsiksd

Q: 381   RDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSD  440

         ************************************************************

S: 181   vwafgvllweiatygmspypgidlsqvyellekgyrmerpegcppkvyelmracwkwsps  240

         vwafgvllweiatygmspypgidlsqvyellek+yrmerpegcp+kvyelmracw+w+ps

Q: 441   VWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNPS  500

         ************************************************************

S: 241   drpsfaeihqal  252

         drpsfaeihqa+

Q: 501   DRPSFAEIHQAF  512

         *********986

Domain Sequence
(FASTA)

ITMKHKLGGG QYGEVYEGVW KKYSLTVAVK TLKEDTMEVE EFLKEAAVMK EIKHPNLVQL 60

LGVCTREPPF YIITEFMTYG NLLDYLRECN RQEVSAVVLL YMATQISSAM EYLEKKNFIH 120

RDLAARNCLV GENHLVKVAD FGLSRLMTGD TYTAHAGAKF PIKWTAPESL AYNKFSIKSD 180

VWAFGVLLWE IATYGMSPYP GIDLSQVYEL LEKDYRMERP EGCPEKVYEL MRACWQWNPS 240

DRPSFAEIHQ AF 252

Keyword

3D-structure; Acetylation; Alternative splicing; Apoptosis; ATP-binding; Autophagy; Cell adhesion; Chromosomal rearrangement; Complete proteome; Cytoplasm; Cytoskeleton; DNA damage; DNA repair; DNA-binding; Endocytosis; Kinase; Lipoprotein; Magnesium; Manganese; Metal-binding; Mitochondrion; Myristate; Nucleotide-binding; Nucleus; Phosphoprotein; Proto-oncogene; Reference proteome; SH2 domain; SH3 domain; Transferase; Tyrosine-protein kinase; Ubl conjugation.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Caenorhabditis elegans"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Ciona intestinalis"; ?>Ciona savignyi"; ?>Danio rerio"; ?>Dasypus novemcinctus"; ?>Drosophila melanogaster"; ?>Equus caballus"; ?>Felis catus"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Homo sapiens"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Microcebus murinus"; ?>Monodelphis domestica"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Oreochromis niloticus"; ?>Ornithorhynchus anatinus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Petromyzon marinus"; ?>Pongo abelii"; ?>Pteropus vampyrus"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tarsius syrichta"; ?>Tetraodon nigroviridis"; ?>Tursiops truncatus"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0031252	; C:cell leading edge
GO:0005856	; C:cytoskeleton
GO:0005829	; C:cytosol
GO:0005739	; C:mitochondrion
GO:0005730	; C:nucleolus
GO:0005634	; C:nucleus
GO:0048471	; C:perinuclear region of cytoplasm
GO:0005524	; F:ATP binding
GO:0003677	; F:DNA binding
GO:0000287	; F:magnesium ion binding
GO:0030145	; F:manganese ion binding
GO:0004715	; F:non-membrane spanning protein tyrosine kinase activity
GO:0004713	; F:protein tyrosine kinase activity
GO:0030036	; P:actin cytoskeleton organization
GO:0006915	; P:apoptotic process
GO:0006914	; P:autophagy
GO:0007155	; P:cell adhesion
GO:0006975	; P:DNA damage induced protein phosphorylation
GO:0006281	; P:DNA repair
GO:0006897	; P:endocytosis
GO:0071901	; P:negative regulation of protein serine/threonine kinase activity
GO:0018108	; P:peptidyl-tyrosine phosphorylation
GO:0048008	; P:platelet-derived growth factor receptor signaling pathway
GO:0043065	; P:positive regulation of apoptotic process
GO:0051353	; P:positive regulation of oxidoreductase activity
GO:0051726	; P:regulation of cell cycle
GO:2001020	; P:regulation of response to DNA damage stimulus
GO:0042770	; P:signal transduction in response to DNA damage

KEGG

mmu:11350

;

InterPros

IPR015015	; F-actin_binding.
IPR011009	; Kinase-like_dom.
IPR000719	; Prot_kinase_cat_dom.
IPR017441	; Protein_kinase_ATP_BS.
IPR001245	; Ser-Thr/Tyr_kinase_cat_dom.
IPR000980	; SH2.
IPR001452	; SH3_domain.
IPR008266	; Tyr_kinase_AS.
IPR020635	; Tyr_kinase_cat_dom.

Pfam

PF08919	; F_actin_bind; 1.
PF07714	; Pkinase_Tyr; 1.
PF00017	; SH2; 1.
PF00018	; SH3_1; 1.

SMARTs

SM00808	; FABD; 1.
SM00252	; SH2; 1.
SM00326	; SH3; 1.
SM00219	; TyrKc; 1.

Prosites

PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00109	; PROTEIN_KINASE_TYR; 1.
PS50001	; SH2; 1.
PS50002	; SH3; 1.

Prints

PR00401	; SH2DOMAIN.
PR00109	; TYRKINASE.

Created Date

20-Feb-2013