Abelssonin proteiini tyrosiinikinaasit

ABL1 ABL proto-oncogene 1, non-receptor tyrosine kinase [ Homo sapiens (human) ]

Gene ID: 25, updated on 16-Feb-2020

Official Symbol

ABL1

Official Full Name

ABL proto-oncogene 1, non-receptor tyrosine kinase

Also known as

ABL; JTK7; p150; c-ABL; v-abl; CHDSKM; c-ABL1; BCR-ABL; bcr/abl

Summary

This gene is a protooncogene that encodes a protein tyrosine kinase involved in a variety of cellular processes, including cell division, adhesion, differentiation, and response to stress. The activity of the protein is negatively regulated by its SH3 domain, whereby deletion of the region encoding this domain results in an oncogene. The ubiquitously expressed protein has DNA-binding activity that is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function. This gene has been found fused to a variety of translocation partner genes in various leukemias, most notably the t(9;22) translocation that results in a fusion with the 5' end of the breakpoint cluster region gene (BCR; MIM:151410). Alternative splicing of this gene results in two transcript variants, which contain alternative first exons that are spliced to the remaining common exons. [provided by RefSeq, Aug 2014]

Expression

Ubiquitous expression in endometrium (RPKM 24.7), gall bladder (RPKM 20.6) and 25 other tissues See more

Preferred Names

tyrosine-protein kinase ABL1

Names

ABL protooncogene 1 nonreceptor tyrosine kinase

Abelson tyrosine-protein kinase 1

bcr/c-abl oncogene protein

c-abl oncogene 1, receptor tyrosine kinase

proto-oncogene c-Abl

proto-oncogene tyrosine-protein kinase ABL1

truncated ABL protooncogene 1 nonreceptor tyrosine kinase

tyrosine-protein kinase

v-abl Abelson murine leukemia viral oncogene homolog 1

Conserved Domains (5) summary

smart00808
Location:1006 → 1130

FABD; F-actin binding domain (FABD)

cd09935
Location:123 → 216

SH2_ABL; Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins

cd11850
Location:65 → 118

SH3_Abl; Src homology 3 domain of the Protein Tyrosine Kinase, Abelson kinase

cd05052
Location:235 → 497

PTKc_Abl; Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase

pfam07714
Location:242 → 493

Pkinase_Tyr; Protein tyrosine kinase

ORIGIN      
        1 mleiclklvg ckskkglsss sscyl/ee/alq rpvasdfepq glseaarwns kenllagpse
       61 ndpnlfvaly dfvasgdntl sitkgeklrv lgynhngewc eaqtkngqgw vpsnyitpvn
      121 slekhswyhg pvsrnaaeyl lssgingsfl vresesspgq rsislryegr vyhyrintas
      181 dgklyvsses rfntlaelvh hhstvadgli ttlhypapkr nkptvygvsp nydkwemert
      241 ditmkhklgg gqygevyegv wkkysltvav ktlkedtmev eeflkeaavm keikhpnlvq
      301 llgvctrepp fyiitefmty gnlldylrec nrqevnavvl lymatqissa meylekknfi
      361 hrdlaarncl vgenhlvkva dfglsrlmtg dtytahagak fpikwtapes laynkfsiks
      421 dvwafgvllw eiatygmspy pgidlsqvye llekdyrmer pegcpekvye lmracwqwnp
      481 sdrpsfaeih qafetmfqes sisdevekel gkqgvrgavs tllqapelpt ktrtsrraae
      541 hrdttdvpem phskgqgesd pldhepavsp llprkergpp egglnederl lpkdkktnlf
      601 salikkkkkt aptppkrsss fremdgqper rgageeegrd isngalaftp ldtadpaksp
      661 kpsngagvpn galresggsg frsphlwkks stltssrlat geeegggsss krflrscsas
      721 cvphgakdte wrsvtlprdl qstgrqfdss tfgghksekp alprkragen rsdqvtrgtv
      781 tppprlvkkn eeaadevfkd imesspgssp pnltpkplrr qvtvapasgl phkeeagkgs
      841 algtpaaaep vtptskagsg apggtskgpa eesrvrrhkh ssespgrdkg klsrlkpapp
      901 pppaasagka ggkpsqspsq eaageavlga ktkatslvda vnsdaakpsq pgeglkkpvl
      961 patpkpqsak psgtpispap vpstlpsass alagdqpsst afiplistrv slrktrqppe
     1021 riasgaitkg vvldstealc laisrnseqm ashsavleag knlytfcvsy vdsiqqmrnk
     1081 fafreainkl ennlrelqic patagsgpaa tqdfskllss vkeisdivqr
//

 

Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins

ABL-family proteins are highly conserved tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. Several types of posttranslational modifications control ABL catalytic activity, subcellular localization, and stability, with consequences for both cytoplasmic and nuclear ABL functions. Binding partners provide additional regulation of ABL catalytic activity, substrate specificity, and downstream signaling. By combining this cassette with actin-binding and -bundling domain, ABL proteins are capable of connecting phosphoregulation with actin-filament reorganization. Vertebrate paralogs, ABL1 and ABL2, have evolved to perform specialized functions. ABL1 includes nuclear localization signals and a DNA binding domain which is used to mediate DNA damage-repair functions, while ABL2 has additional binding capacity for actin and for microtubules to enhance its cytoskeletal remodeling functions. SH2 is involved in several autoinhibitory mechanism that constrain the enzymatic activity of the ABL-family kinases. In one mechanism SH2 and SH3 cradle the kinase domain while a cap sequence stabilizes the inactive conformation resulting in a locked inactive state. Another involves phosphatidylinositol 4,5-bisphosphate (PIP2) which binds the SH2 domain through residues normally required for phosphotyrosine binding in the linker segment between the SH2 and kinase domains. The SH2 domain contributes to ABL catalytic activity and target site specificity. It is thought that the ABL catalytic site and SH2 pocket have coevolved to recognize the same sequences. Recent work now supports a hierarchical processivity model in which the substrate target site most compatible with ABL kinase domain preferences is phosphorylated with greatest efficiency. If this site is compatible with the ABL SH2 domain specificity, it will then reposition and dock in the SH2 pocket. This mechanism also explains how ABL kinases phosphorylates poor targets on the same substrate if they are properly positioned and how relatively poor substrate proteins might be recruited to ABL through a complex with strong substrates that can also dock with the SH2 pocket. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing 

 

 

 

Fuusioproteiini  t(9, 22)