EKS-HOS-00245

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-HOS-00245

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TK/Abl	557.5	1.9E-167	242	493	252

Status

Reviewed

Ensembl Protein

ENSP00000323315

UniProt Accession

P00519; A3KFJ3; Q13869; Q13870; Q16133; Q17R61; Q45F09;

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, JTK7;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSG00000097007	ENSP00000376971	ENST00000393293
ENSG00000097007	ENSP00000361423	ENST00000372348
ENSG00000097007	ENSP00000323315	ENST00000318560

Organism

Homo sapiens

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. ABL1 acts also as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine- phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1.

Protein Length

1130

Protein Sequence
(FASTA)

MLEICLKLVG CKSKKGLSSS SSCYLEEALQ RPVASDFEPQ GLSEAARWNS KENLLAGPSE 60

NDPNLFVALY DFVASGDNTL SITKGEKLRV LGYNHNGEWC EAQTKNGQGW VPSNYITPVN 120

SLEKHSWYHG PVSRNAAEYL LSSGINGSFL VRESESSPGQ RSISLRYEGR VYHYRINTAS 180

DGKLYVSSES RFNTLAELVH HHSTVADGLI TTLHYPAPKR NKPTVYGVSP NYDKWEMERT 240

DITMKHKLGG GQYGEVYEGV WKKYSLTVAV KTLKEDTMEV EEFLKEAAVM KEIKHPNLVQ 300

LLGVCTREPP FYIITEFMTY GNLLDYLREC NRQEVNAVVL LYMATQISSA MEYLEKKNFI 360

HRDLAARNCL VGENHLVKVA DFGLSRLMTG DTYTAHAGAK FPIKWTAPES LAYNKFSIKS 420

DVWAFGVLLW EIATYGMSPY PGIDLSQVYE LLEKDYRMER PEGCPEKVYE LMRACWQWNP 480

SDRPSFAEIH QAFETMFQES SISDEVEKEL GKQGVRGAVS TLLQAPELPT KTRTSRRAAE 540

HRDTTDVPEM PHSKGQGESD PLDHEPAVSP LLPRKERGPP EGGLNEDERL LPKDKKTNLF 600

SALIKKKKKT APTPPKRSSS FREMDGQPER RGAGEEEGRD ISNGALAFTP LDTADPAKSP 660

KPSNGAGVPN GALRESGGSG FRSPHLWKKS STLTSSRLAT GEEEGGGSSS KRFLRSCSAS 720

CVPHGAKDTE WRSVTLPRDL QSTGRQFDSS TFGGHKSEKP ALPRKRAGEN RSDQVTRGTV 780

TPPPRLVKKN EEAADEVFKD IMESSPGSSP PNLTPKPLRR QVTVAPASGL PHKEEAGKGS 840

ALGTPAAAEP VTPTSKAGSG APGGTSKGPA EESRVRRHKH SSESPGRDKG KLSRLKPAPP 900

PPPAASAGKA GGKPSQSPSQ EAAGEAVLGA KTKATSLVDA VNSDAAKPSQ PGEGLKKPVL 960

PATPKPQSAK PSGTPISPAP VPSTLPSASS ALAGDQPSST AFIPLISTRV SLRKTRQPPE 1020

RIASGAITKG VVLDSTEALC LAISRNSEQM ASHSAVLEAG KNLYTFCVSY VDSIQQMRNK 1080

FAFREAINKL ENNLRELQIC PATAGSGPAA TQDFSKLLSS VKEISDIVQR 1130

Nucleotide Sequence
(FASTA)

ATGTTGGAGA TCTGCCTGAA GCTGGTGGGC TGCAAATCCA AGAAGGGGCT GTCCTCGTCC 60

TCCAGCTGTT ATCTGGAAGA AGCCCTTCAG CGGCCAGTAG CATCTGACTT TGAGCCTCAG 120

GGTCTGAGTG AAGCCGCTCG TTGGAACTCC AAGGAAAACC TTCTCGCTGG ACCCAGTGAA 180

AATGACCCCA ACCTTTTCGT TGCACTGTAT GATTTTGTGG CCAGTGGAGA TAACACTCTA 240

AGCATAACTA AAGGTGAAAA GCTCCGGGTC TTAGGCTATA ATCACAATGG GGAATGGTGT 300

GAAGCCCAAA CCAAAAATGG CCAAGGCTGG GTCCCAAGCA ACTACATCAC GCCAGTCAAC 360

AGTCTGGAGA AACACTCCTG GTACCATGGG CCTGTGTCCC GCAATGCCGC TGAGTATCTG 420

CTGAGCAGCG GGATCAATGG CAGCTTCTTG GTGCGTGAGA GTGAGAGCAG TCCTGGCCAG 480

AGGTCCATCT CGCTGAGATA CGAAGGGAGG GTGTACCATT ACAGGATCAA CACTGCTTCT 540

GATGGCAAGC TCTACGTCTC CTCCGAGAGC CGCTTCAACA CCCTGGCCGA GTTGGTTCAT 600

CATCATTCAA CGGTGGCCGA CGGGCTCATC ACCACGCTCC ATTATCCAGC CCCAAAGCGC 660

AACAAGCCCA CTGTCTATGG TGTGTCCCCC AACTACGACA AGTGGGAGAT GGAACGCACG 720

GACATCACCA TGAAGCACAA GCTGGGCGGG GGCCAGTACG GGGAGGTGTA CGAGGGCGTG 780

TGGAAGAAAT ACAGCCTGAC GGTGGCCGTG AAGACCTTGA AGGAGGACAC CATGGAGGTG 840

GAAGAGTTCT TGAAAGAAGC TGCAGTCATG AAAGAGATCA AACACCCTAA CCTGGTGCAG 900

CTCCTTGGGG TCTGCACCCG GGAGCCCCCG TTCTATATCA TCACTGAGTT CATGACCTAC 960

GGGAACCTCC TGGACTACCT GAGGGAGTGC AACCGGCAGG AGGTGAACGC CGTGGTGCTG 1020

CTGTACATGG CCACTCAGAT CTCGTCAGCC ATGGAGTACC TGGAGAAGAA AAACTTCATC 1080

CACAGAGATC TTGCTGCCCG AAACTGCCTG GTAGGGGAGA ACCACTTGGT GAAGGTAGCT 1140

GATTTTGGCC TGAGCAGGTT GATGACAGGG GACACCTACA CAGCCCATGC TGGAGCCAAG 1200

TTCCCCATCA AATGGACTGC ACCCGAGAGC CTGGCCTACA ACAAGTTCTC CATCAAGTCC 1260

GACGTCTGGG CATTTGGAGT ATTGCTTTGG GAAATTGCTA CCTATGGCAT GTCCCCTTAC 1320

CCGGGAATTG ACCTGTCCCA GGTGTATGAG CTGCTAGAGA AGGACTACCG CATGGAGCGC 1380

CCAGAAGGCT GCCCAGAGAA GGTCTATGAA CTCATGCGAG CATGTTGGCA GTGGAATCCC 1440

TCTGACCGGC CCTCCTTTGC TGAAATCCAC CAAGCCTTTG AAACAATGTT CCAGGAATCC 1500

AGTATCTCAG ACGAAGTGGA AAAGGAGCTG GGGAAACAAG GCGTCCGTGG GGCTGTGAGT 1560

ACCTTGCTGC AGGCCCCAGA GCTGCCCACC AAGACGAGGA CCTCCAGGAG AGCTGCAGAG 1620

CACAGAGACA CCACTGACGT GCCTGAGATG CCTCACTCCA AGGGCCAGGG AGAGAGCGAT 1680

CCTCTGGACC ATGAGCCTGC CGTGTCTCCA TTGCTCCCTC GAAAAGAGCG AGGTCCCCCG 1740

GAGGGCGGCC TGAATGAAGA TGAGCGCCTT CTCCCCAAAG ACAAAAAGAC CAACTTGTTC 1800

AGCGCCTTGA TCAAGAAGAA GAAGAAGACA GCCCCAACCC CTCCCAAACG CAGCAGCTCC 1860

TTCCGGGAGA TGGACGGCCA GCCGGAGCGC AGAGGGGCCG GCGAGGAAGA GGGCCGAGAC 1920

ATCAGCAACG GGGCACTGGC TTTCACCCCC TTGGACACAG CTGACCCAGC CAAGTCCCCA 1980

AAGCCCAGCA ATGGGGCTGG GGTCCCCAAT GGAGCCCTCC GGGAGTCCGG GGGCTCAGGC 2040

TTCCGGTCTC CCCACCTGTG GAAGAAGTCC AGCACGCTGA CCAGCAGCCG CCTAGCCACC 2100

GGCGAGGAGG AGGGCGGTGG CAGCTCCAGC AAGCGCTTCC TGCGCTCTTG CTCCGCCTCC 2160

TGCGTTCCCC ATGGGGCCAA GGACACGGAG TGGAGGTCAG TCACGCTGCC TCGGGACTTG 2220

CAGTCCACGG GAAGACAGTT TGACTCGTCC ACATTTGGAG GGCACAAAAG TGAGAAGCCG 2280

GCTCTGCCTC GGAAGAGGGC AGGGGAGAAC AGGTCTGACC AGGTGACCCG AGGCACAGTA 2340

ACGCCTCCCC CCAGGCTGGT GAAAAAGAAT GAGGAAGCTG CTGATGAGGT CTTCAAAGAC 2400

ATCATGGAGT CCAGCCCGGG CTCCAGCCCG CCCAACCTGA CTCCAAAACC CCTCCGGCGG 2460

CAGGTCACCG TGGCCCCTGC CTCGGGCCTC CCCCACAAGG AAGAAGCTGG AAAGGGCAGT 2520

GCCTTAGGGA CCCCTGCTGC AGCTGAGCCA GTGACCCCCA CCAGCAAAGC AGGCTCAGGT 2580

GCACCAGGGG GCACCAGCAA GGGCCCCGCC GAGGAGTCCA GAGTGAGGAG GCACAAGCAC 2640

TCCTCTGAGT CGCCAGGGAG GGACAAGGGG AAATTGTCCA GGCTCAAACC TGCCCCGCCG 2700

CCCCCACCAG CAGCCTCTGC AGGGAAGGCT GGAGGAAAGC CCTCGCAGAG CCCGAGCCAG 2760

GAGGCGGCCG GGGAGGCAGT CCTGGGCGCA AAGACAAAAG CCACGAGTCT GGTTGATGCT 2820

GTGAACAGTG ACGCTGCCAA GCCCAGCCAG CCGGGAGAGG GCCTCAAAAA GCCCGTGCTC 2880

CCGGCCACTC CAAAGCCACA GTCCGCCAAG CCGTCGGGGA CCCCCATCAG CCCAGCCCCC 2940

GTTCCCTCCA CGTTGCCATC AGCATCCTCG GCCCTGGCAG GGGACCAGCC GTCTTCCACC 3000

GCCTTCATCC CTCTCATATC AACCCGAGTG TCTCTTCGGA AAACCCGCCA GCCTCCAGAG 3060

CGGATCGCCA GCGGCGCCAT CACCAAGGGC GTGGTCCTGG ACAGCACCGA GGCGCTGTGC 3120

CTCGCCATCT CTAGGAACTC CGAGCAGATG GCCAGCCACA GCGCAGTGCT GGAGGCCGGC 3180

AAAAACCTCT ACACGTTCTG CGTGAGCTAT GTGGATTCCA TCCAGCAAAT GAGGAACAAG 3240

TTTGCCTTCC GAGAGGCCAT CAACAAACTG GAGAATAATC TCCGGGAGCT TCAGATCTGC 3300

CCGGCGACAG CAGGCAGTGG TCCAGCGGCC ACTCAGGACT TCAGCAAGCT CCTCAGTTCG 3360

GTGAAGGAAA TCAGTGACAT AGTGCAGAGG TAG 3393

Domain Profile

S: 1     iimkhklgggqygevyegvwkkysltvavktlkedtmeveeflkeaavmkelkhpnlvql  60

         i+mkhklgggqygevyegvwkkysltvavktlkedtmeveeflkeaavmke+khpnlvql

Q: 242   ITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQL  301

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

S: 61    lgvctreppfyiitefmsygnlldylreadreeveavvllymatqissameylekknfih  120

         lgvctreppfyiitefm+ygnlldylre++r+ev+avvllymatqissameylekknfih

Q: 302   LGVCTREPPFYIITEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIH  361

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

S: 121   rdlaarnclvgenklvkvadfglsrlmkedtytahagakfpikwtapeslaynkfsiksd  180

         rdlaarnclvgen+lvkvadfglsrlm++dtytahagakfpikwtapeslaynkfsiksd

Q: 362   RDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSD  421

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

S: 181   vwafgvllweiatygmspypgidlsqvyellekgyrmerpegcppkvyelmracwkwsps  240

         vwafgvllweiatygmspypgidlsqvyellek+yrmerpegcp+kvyelmracw+w+ps

Q: 422   VWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNPS  481

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

S: 241   drpsfaeihqal  252

         drpsfaeihqa+

Q: 482   DRPSFAEIHQAF  493

         *********986

Domain Sequence
(FASTA)

ITMKHKLGGG QYGEVYEGVW KKYSLTVAVK TLKEDTMEVE EFLKEAAVMK EIKHPNLVQL 60

LGVCTREPPF YIITEFMTYG NLLDYLRECN RQEVNAVVLL 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; Membrane; Metal-binding; Mitochondrion; Myristate; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; 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"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Microcebus murinus"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>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:0015629	; C:actin cytoskeleton
GO:0005829	; C:cytosol
GO:0005739	; C:mitochondrion
GO:0031965	; C:nuclear membrane
GO:0005730	; C:nucleolus
GO:0048471	; C:perinuclear region of cytoplasm
GO:0003785	; F:actin monomer binding
GO:0005524	; F:ATP binding
GO:0003677	; F:DNA binding
GO:0000287	; F:magnesium ion binding
GO:0030145	; F:manganese ion binding
GO:0004515	; F:nicotinate-nucleotide adenylyltransferase activity
GO:0004715	; F:non-membrane spanning protein tyrosine kinase activity
GO:0030036	; P:actin cytoskeleton organization
GO:0006914	; P:autophagy
GO:0007411	; P:axon guidance
GO:0007596	; P:blood coagulation
GO:0007155	; P:cell adhesion
GO:0006975	; P:DNA damage induced protein phosphorylation
GO:0006897	; P:endocytosis
GO:0008630	; P:intrinsic apoptotic signaling pathway in response to DNA damage response
GO:0006298	; P:mismatch repair
GO:0042692	; P:muscle cell differentiation
GO:0071901	; P:negative regulation of protein serine/threonine kinase activity
GO:0018108	; P:peptidyl-tyrosine phosphorylation
GO:0043065	; P:positive regulation of apoptotic process
GO:0051149	; P:positive regulation of muscle cell differentiation
GO:0051353	; P:positive regulation of oxidoreductase activity
GO:2000249	; P:regulation of actin cytoskeleton reorganization
GO:0010506	; P:regulation of autophagy
GO:0030155	; P:regulation of cell adhesion
GO:0051726	; P:regulation of cell cycle
GO:2000145	; P:regulation of cell motility
GO:0030100	; P:regulation of endocytosis
GO:2001020	; P:regulation of response to DNA damage stimulus
GO:0000115	; P:regulation of transcription involved in S phase of mitotic cell cycle
GO:0042770	; P:signal transduction in response to DNA damage

KEGG

hsa:25

;

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