Reviewed, UniProtKB/Swiss-Prot P42684 (ABL2_HUMAN)

Names and origin

Protein names

Recommended name:
    Tyrosine-protein kinase ABL2
    EC=2.7.10.2
Alternative name(s):
    Abelson murine leukemia viral oncogene homolog 2
    Abelson-related gene protein
    Tyrosine kinase ARG

Gene names

Name:	ABL2
Synonyms:	ABLL, ARG

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	1182 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Regulates cytoskeleton remodeling during cell differentiation, cell division and cell adhesion. Localizes to dynamic actin structures, and phosphorylates CRK and CRKL, DOK1, and other proteins controlling cytoskeleton dynamics.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Cofactor	Magnesium or manganese.
Enzyme regulation	Stabilized in the inactive form by an association between the SH3 domain and the SH2-TK linker region, interactions of the amino-terminal cap, and contributions from an amino-terminal myristoyl group and phospholipids. Activated by autophosphorylation as well as by SRC-family kinase-mediated phosphorylation. Activated by RIN1 binding to the SH2 and SH3 domains. Inhibited by imatinib mesylate (Gleevec) which is used for the treatment of chronic myeloid leukemia (CML).
Subcellular location	Cytoplasm › cytoskeleton.
Tissue specificity	Widely expressed.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. ABL subfamily. Contains 1 protein kinase domain. Contains 1 SH2 domain. Contains 1 SH3 domain.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cytoplasm Cytoskeleton
Coding sequence diversity	Alternative splicing Polymorphism
Domain	SH2 domain SH3 domain
Ligand	ATP-binding Magnesium Manganese Metal-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Lipoprotein Myristate Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW peptidyl-tyrosine phosphorylation Ref.7 Inferred from direct assay. Source: UniProtKB positive regulation of oxidoreductase activity Inferred from direct assay. Source: UniProtKB signal transduction Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cytoskeleton Inferred from electronic annotation. Source: UniProtKB-KW phosphoinositide 3-kinase complex Inferred from electronic annotation. Source: InterPro
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro magnesium ion binding Ref.7 Inferred from direct assay. Source: UniProtKB manganese ion binding Ref.7 Inferred from direct assay. Source: UniProtKB non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC phosphoinositide 3-kinase regulator activity Inferred from electronic annotation. Source: InterPro protein binding Ref.7 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CRK	P46108	2	EBI-1102694,EBI-886
CRK	Q04929	1	EBI-1102694,EBI-1102801	From a different organism.
FYN	P06241	1	EBI-1102694,EBI-515315
GRB2	P62993	1	EBI-1102694,EBI-401755
NCK1	P16333	1	EBI-1102694,EBI-389883
PIK3R1	P27986	1	EBI-1102694,EBI-79464
PLCG1	P19174	2	EBI-1102694,EBI-79387
RIN1	Q13671	2	EBI-1102694,EBI-366017
SRC	P12931	1	EBI-1102694,EBI-621482

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform IB (identifier: P42684-1)

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.

Isoform IA (identifier: P42684-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-73: MGQQVGRVGE...EGDKTGGSSP → MVLGTVLLPP...ASESALPDLT

Notes: Variant in position: 12:S->T (somatic mutation in a breast cancer sample). Variant in position: 42:R->H (somatic mutation in a breast cancer sample). Variant in position: 748:T->S (somatic mutation in a breast cancer sample). Variant in position: 894:K->R (somatic mutation in a breast cancer sample). Variant in position: 960:P->R (somatic mutation in a breast cancer sample). Variant in position: 63:E->Q (somatic mutation in a breast cancer sample). Variant in position: 483:R->I (somatic mutation in a lung squamous cell carcinoma).

Isoform IC (identifier: P42684-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-52: MGQQVGRVGE...ETGFNIFTQH → MVLGTVLLPP...ASESALPDLT

Isoform 4 (identifier: P42684-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-73: MGQQVGRVGE...EGDKTGGSSP → MVLGTVLLPP...ASESALPDLT
     688-790: Missing.

Notes: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 1182

1181

Tyrosine-protein kinase ABL2

PRO_0000088052

Regions

Domain

107 – 167

61

SH3

Domain

173 – 263

91

SH2

Domain

288 – 539

252

Protein kinase

Nucleotide binding

294 – 302

9

ATP By similarity

Region

2 – 106

105

CAP

Motif

658 – 660

3

Nuclear localization signal Potential

Compositional bias

561 – 564

4

Poly-Ser

Compositional bias

732 – 739

8

Poly-Gly

Compositional bias

843 – 1055

213

Pro-rich

Compositional bias

984 – 988

5

Poly-Pro

Sites

Active site

409

1

Proton acceptor By similarity

Binding site

317

1

ATP By similarity

Amino acid modifications

Modified residue

71

1

Phosphoserine

Modified residue

203

1

Phosphoserine

Modified residue

231

1

Phosphotyrosine By similarity

Modified residue

272

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

299

1

Phosphotyrosine By similarity

Modified residue

303

1

Phosphotyrosine By similarity

Modified residue

310

1

Phosphotyrosine

Modified residue

439

1

Phosphotyrosine; by autocatalysis

Modified residue

440

1

Phosphothreonine

Modified residue

492

1

Phosphoserine By similarity

Modified residue

515

1

Phosphotyrosine

Modified residue

620

1

Phosphoserine

Modified residue

631

1

Phosphoserine

Modified residue

633

1

Phosphoserine

Modified residue

655

1

Phosphoserine

Modified residue

783

1

Phosphoserine

Modified residue

817

1

Phosphoserine

Modified residue

820

1

Phosphoserine

Modified residue

915

1

Phosphoserine

Modified residue

936

1

Phosphoserine

Lipidation

2

1

N-myristoyl glycine By similarity

Natural variations

Alternative sequence

1 – 73

73

MGQQV…GGSSP → MVLGTVLLPPNSYGRDQDTS LCCLCTEASESALPDLT in isoform 4.

VSP_021307

Alternative sequence

1 – 73

73

MGQQV…GGSSP → MVLGTVLLPPNTYGRDQDTS LCCLCTEASESALPDLT in isoform IA.

VSP_004961

Alternative sequence

1 – 52

52

MGQQV…IFTQH → MVLGTVLLPPNSYGRDQDTS LCCLCTEASESALPDLT in isoform IC.

VSP_017112

Alternative sequence

688 – 790

103

Missing in isoform 4.

VSP_021308

Natural variant

930

1

K → R: dbSNP rs17277288.

VAR_029232

Natural variant

946

1

V → M: dbSNP rs28913889.

VAR_029233

Natural variant

996

1

P → R: dbSNP rs28913890.

VAR_029234

Natural variant

1085

1

S → N: dbSNP rs28913891.

VAR_029235

Natural variant

1101

1

T → A: dbSNP rs28913892.

VAR_029236

Experimental info

Sequence conflict

343 – 344

2

NL → TI Ref.5

Sequence conflict

981

1

K → R in CAD98092. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

1182

Helix Strand Turn

Details...

Beta strand

171 – 177

7

Helix

180 – 188

9

Beta strand

194 – 203

10

Beta strand

206 – 212

7

Beta strand

217 – 220

4

Beta strand

226 – 228

3

Helix

241 – 250

10

Beta strand

255 – 257

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform IB [UniParc]. Last modified November 1, 1995. Version 1. Checksum: ED93869BC2B14FAA	FASTA	1,182	128,343
	10 20 30 40 50 60 MGQQVGRVGE APGLQQPQPR GIRGSSAARP SGRRRDPAGR TTETGFNIFT QHDHFASCVE 70 80 90 100 110 120 DGFEGDKTGG SSPEALHRPY GCDVEPQALN EAIRWSSKEN LLGATESDPN LFVALYDFVA 130 140 150 160 170 180 SGDNTLSITK GEKLRVLGYN QNGEWSEVRS KNGQGWVPSN YITPVNSLEK HSWYHGPVSR 190 200 210 220 230 240 SAAEYLLSSL INGSFLVRES ESSPGQLSIS LRYEGRVYHY RINTTADGKV YVTAESRFST 250 260 270 280 290 300 LAELVHHHST VADGLVTTLH YPAPKCNKPT VYGVSPIHDK WEMERTDITM KHKLGGGQYG 310 320 330 340 350 360 EVYVGVWKKY SLTVAVKTLK EDTMEVEEFL KEAAVMKEIK HPNLVQLLGV CTLEPPFYIV 370 380 390 400 410 420 TEYMPYGNLL DYLRECNREE VTAVVLLYMA TQISSAMEYL EKKNFIHRDL AARNCLVGEN 430 440 450 460 470 480 HVVKVADFGL SRLMTGDTYT AHAGAKFPIK WTAPESLAYN TFSIKSDVWA FGVLLWEIAT 490 500 510 520 530 540 YGMSPYPGID LSQVYDLLEK GYRMEQPEGC PPKVYELMRA CWKWSPADRP SFAETHQAFE 550 560 570 580 590 600 TMFHDSSISE EVAEELGRAA SSSSVVPYLP RLPILPSKTR TLKKQVENKE NIEGAQDATE 610 620 630 640 650 660 NSASSLAPGF IRGAQASSGS PALPRKQRDK SPSSLLEDAK ETCFTRDRKG GFFSSFMKKR 670 680 690 700 710 720 NAPTPPKRSS SFREMENQPH KKYELTGNFS SVASLQHADG FSFTPAQQEA NLVPPKCYGG 730 740 750 760 770 780 SFAQRNLCND DGGGGGGSGT AGGGWSGITG FFTPRLIKKT LGLRAGKPTA SDDTSKPFPR 790 800 810 820 830 840 SNSTSSMSSG LPEQDRMAMT LPRNCQRSKL QLERTVSTSS QPEENVDRAN DMLPKKSEES 850 860 870 880 890 900 AAPSRERPKA KLLPRGATAL PLRTPSGDLA ITEKDPPGVG VAGVAAAPKG KEKNGGARLG 910 920 930 940 950 960 MAGVPEDGEQ PGWPSPAKAA PVLPTTHNHK VPVLISPTLK HTPADVQLIG TDSQGNKFKL 970 980 990 1000 1010 1020 LSEHQVTSSG DKDRPRRVKP KCAPPPPPVM RLLQHPSICS DPTEEPTALT AGQSTSETQE 1030 1040 1050 1060 1070 1080 GGKKAALGAV PISGKAGRPV MPPPQVPLPT SSISPAKMAN GTAGTKVALR KTKQAAEKIS 1090 1100 1110 1120 1130 1140 ADKISKEALL ECADLLSSAL TEPVPNSQLV DTGHQLLDYC SGYVDCIPQT RNKFAFREAV 1150 1160 1170 1180 SKLELSLQEL QVSSAAAGVP GTNPVLNNLL SCVQEISDVV QR
	Isoform IA [UniParc]. Checksum: 472FE7CB2CB9BE15		1,146	124,574
	10 20 30 40 50 60 MVLGTVLLPP NTYGRDQDTS LCCLCTEASE SALPDLTEAL HRPYGCDVEP QALNEAIRWS 70 80 90 100 110 120 SKENLLGATE SDPNLFVALY DFVASGDNTL SITKGEKLRV LGYNQNGEWS EVRSKNGQGW 130 140 150 160 170 180 VPSNYITPVN SLEKHSWYHG PVSRSAAEYL LSSLINGSFL VRESESSPGQ LSISLRYEGR 190 200 210 220 230 240 VYHYRINTTA DGKVYVTAES RFSTLAELVH HHSTVADGLV TTLHYPAPKC NKPTVYGVSP 250 260 270 280 290 300 IHDKWEMERT DITMKHKLGG GQYGEVYVGV WKKYSLTVAV KTLKEDTMEV EEFLKEAAVM 310 320 330 340 350 360 KEIKHPNLVQ LLGVCTLEPP FYIVTEYMPY GNLLDYLREC NREEVTAVVL LYMATQISSA 370 380 390 400 410 420 MEYLEKKNFI HRDLAARNCL VGENHVVKVA DFGLSRLMTG DTYTAHAGAK FPIKWTAPES 430 440 450 460 470 480 LAYNTFSIKS DVWAFGVLLW EIATYGMSPY PGIDLSQVYD LLEKGYRMEQ PEGCPPKVYE 490 500 510 520 530 540 LMRACWKWSP ADRPSFAETH QAFETMFHDS SISEEVAEEL GRAASSSSVV PYLPRLPILP 550 560 570 580 590 600 SKTRTLKKQV ENKENIEGAQ DATENSASSL APGFIRGAQA SSGSPALPRK QRDKSPSSLL 610 620 630 640 650 660 EDAKETCFTR DRKGGFFSSF MKKRNAPTPP KRSSSFREME NQPHKKYELT GNFSSVASLQ 670 680 690 700 710 720 HADGFSFTPA QQEANLVPPK CYGGSFAQRN LCNDDGGGGG GSGTAGGGWS GITGFFTPRL 730 740 750 760 770 780 IKKTLGLRAG KPTASDDTSK PFPRSNSTSS MSSGLPEQDR MAMTLPRNCQ RSKLQLERTV 790 800 810 820 830 840 STSSQPEENV DRANDMLPKK SEESAAPSRE RPKAKLLPRG ATALPLRTPS GDLAITEKDP 850 860 870 880 890 900 PGVGVAGVAA APKGKEKNGG ARLGMAGVPE DGEQPGWPSP AKAAPVLPTT HNHKVPVLIS 910 920 930 940 950 960 PTLKHTPADV QLIGTDSQGN KFKLLSEHQV TSSGDKDRPR RVKPKCAPPP PPVMRLLQHP 970 980 990 1000 1010 1020 SICSDPTEEP TALTAGQSTS ETQEGGKKAA LGAVPISGKA GRPVMPPPQV PLPTSSISPA 1030 1040 1050 1060 1070 1080 KMANGTAGTK VALRKTKQAA EKISADKISK EALLECADLL SSALTEPVPN SQLVDTGHQL 1090 1100 1110 1120 1130 1140 LDYCSGYVDC IPQTRNKFAF REAVSKLELS LQELQVSSAA AGVPGTNPVL NNLLSCVQEI SDVVQR
	Isoform IC [UniParc]. Checksum: 0E3923FE9EEEAFEC		1,167	126,684
	10 20 30 40 50 60 MVLGTVLLPP NSYGRDQDTS LCCLCTEASE SALPDLTDHF ASCVEDGFEG DKTGGSSPEA 70 80 90 100 110 120 LHRPYGCDVE PQALNEAIRW SSKENLLGAT ESDPNLFVAL YDFVASGDNT LSITKGEKLR 130 140 150 160 170 180 VLGYNQNGEW SEVRSKNGQG WVPSNYITPV NSLEKHSWYH GPVSRSAAEY LLSSLINGSF 190 200 210 220 230 240 LVRESESSPG QLSISLRYEG RVYHYRINTT ADGKVYVTAE SRFSTLAELV HHHSTVADGL 250 260 270 280 290 300 VTTLHYPAPK CNKPTVYGVS PIHDKWEMER TDITMKHKLG GGQYGEVYVG VWKKYSLTVA 310 320 330 340 350 360 VKTLKEDTME VEEFLKEAAV MKEIKHPNLV QLLGVCTLEP PFYIVTEYMP YGNLLDYLRE 370 380 390 400 410 420 CNREEVTAVV LLYMATQISS AMEYLEKKNF IHRDLAARNC LVGENHVVKV ADFGLSRLMT 430 440 450 460 470 480 GDTYTAHAGA KFPIKWTAPE SLAYNTFSIK SDVWAFGVLL WEIATYGMSP YPGIDLSQVY 490 500 510 520 530 540 DLLEKGYRME QPEGCPPKVY ELMRACWKWS PADRPSFAET HQAFETMFHD SSISEEVAEE 550 560 570 580 590 600 LGRAASSSSV VPYLPRLPIL PSKTRTLKKQ VENKENIEGA QDATENSASS LAPGFIRGAQ 610 620 630 640 650 660 ASSGSPALPR KQRDKSPSSL LEDAKETCFT RDRKGGFFSS FMKKRNAPTP PKRSSSFREM 670 680 690 700 710 720 ENQPHKKYEL TGNFSSVASL QHADGFSFTP AQQEANLVPP KCYGGSFAQR NLCNDDGGGG 730 740 750 760 770 780 GGSGTAGGGW SGITGFFTPR LIKKTLGLRA GKPTASDDTS KPFPRSNSTS SMSSGLPEQD 790 800 810 820 830 840 RMAMTLPRNC QRSKLQLERT VSTSSQPEEN VDRANDMLPK KSEESAAPSR ERPKAKLLPR 850 860 870 880 890 900 GATALPLRTP SGDLAITEKD PPGVGVAGVA AAPKGKEKNG GARLGMAGVP EDGEQPGWPS 910 920 930 940 950 960 PAKAAPVLPT THNHKVPVLI SPTLKHTPAD VQLIGTDSQG NKFKLLSEHQ VTSSGDKDRP 970 980 990 1000 1010 1020 RRVKPKCAPP PPPVMRLLQH PSICSDPTEE PTALTAGQST SETQEGGKKA ALGAVPISGK 1030 1040 1050 1060 1070 1080 AGRPVMPPPQ VPLPTSSISP AKMANGTAGT KVALRKTKQA AEKISADKIS KEALLECADL 1090 1100 1110 1120 1130 1140 LSSALTEPVP NSQLVDTGHQ LLDYCSGYVD CIPQTRNKFA FREAVSKLEL SLQELQVSSA 1150 1160 AAGVPGTNPV LNNLLSCVQE ISDVVQR
	Isoform 4 [UniParc]. Checksum: 973C4751FD7E13F9		1,043	114,159
	10 20 30 40 50 60 MVLGTVLLPP NSYGRDQDTS LCCLCTEASE SALPDLTEAL HRPYGCDVEP QALNEAIRWS 70 80 90 100 110 120 SKENLLGATE SDPNLFVALY DFVASGDNTL SITKGEKLRV LGYNQNGEWS EVRSKNGQGW 130 140 150 160 170 180 VPSNYITPVN SLEKHSWYHG PVSRSAAEYL LSSLINGSFL VRESESSPGQ LSISLRYEGR 190 200 210 220 230 240 VYHYRINTTA DGKVYVTAES RFSTLAELVH HHSTVADGLV TTLHYPAPKC NKPTVYGVSP 250 260 270 280 290 300 IHDKWEMERT DITMKHKLGG GQYGEVYVGV WKKYSLTVAV KTLKEDTMEV EEFLKEAAVM 310 320 330 340 350 360 KEIKHPNLVQ LLGVCTLEPP FYIVTEYMPY GNLLDYLREC NREEVTAVVL LYMATQISSA 370 380 390 400 410 420 MEYLEKKNFI HRDLAARNCL VGENHVVKVA DFGLSRLMTG DTYTAHAGAK FPIKWTAPES 430 440 450 460 470 480 LAYNTFSIKS DVWAFGVLLW EIATYGMSPY PGIDLSQVYD LLEKGYRMEQ PEGCPPKVYE 490 500 510 520 530 540 LMRACWKWSP ADRPSFAETH QAFETMFHDS SISEEVAEEL GRAASSSSVV PYLPRLPILP 550 560 570 580 590 600 SKTRTLKKQV ENKENIEGAQ DATENSASSL APGFIRGAQA SSGSPALPRK QRDKSPSSLL 610 620 630 640 650 660 EDAKETCFTR DRKGGFFSSF MKKRNAPTPP KRSSSFREME NQPHKKYELT GLPEQDRMAM 670 680 690 700 710 720 TLPRNCQRSK LQLERTVSTS SQPEENVDRA NDMLPKKSEE SAAPSRERPK AKLLPRGATA 730 740 750 760 770 780 LPLRTPSGDL AITEKDPPGV GVAGVAAAPK GKEKNGGARL GMAGVPEDGE QPGWPSPAKA 790 800 810 820 830 840 APVLPTTHNH KVPVLISPTL KHTPADVQLI GTDSQGNKFK LLSEHQVTSS GDKDRPRRVK 850 860 870 880 890 900 PKCAPPPPPV MRLLQHPSIC SDPTEEPTAL TAGQSTSETQ EGGKKAALGA VPISGKAGRP 910 920 930 940 950 960 VMPPPQVPLP TSSISPAKMA NGTAGTKVAL RKTKQAAEKI SADKISKEAL LECADLLSSA 970 980 990 1000 1010 1020 LTEPVPNSQL VDTGHQLLDY CSGYVDCIPQ TRNKFAFREA VSKLELSLQE LQVSSAAAGV 1030 1040 PGTNPVLNNL LSCVQEISDV VQR

References

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[1]	"The complete coding sequence of arg defines the Abelson subfamily of cytoplasmic tyrosine kinases." Kruh G.D., Perego R., Miki T., Aaronson S.A. Proc. Natl. Acad. Sci. U.S.A. 87:5802-5806(1990) [PubMed: 2198571] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS IA AND IB).
[2]	The German cDNA consortium Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). Tissue: Uterine endothelium.
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y.,