iUUCD 2.0 - integrated annotations for ubiquitin and ubiquitin-like conjugation database

Protein
Gene
Annotation
Classification
Domain Profile
Function
Protein Sequence
Nucleotide Sequence
Keyword
GO
Orthology
TOP

Tag

Content

iUUCD ID

IUUC-Hsa-045754

Ensembl Protein ID

UniProt Accession

P00519; A3KFJ3; Q13869; Q13870; Q16133; Q17R61; Q45F09; ABL1_HUMAN

Genbank Protein ID

AAA51561.1; CAA34438.1; AAB60394.1; AAB60393.1; AAB60393.1; AAZ38718.1; CAM45752.1; CAM45752.1; CAM45754.1; CAM45756.1; CAM45756.1; EAW87948.1; AAI17452.1; AAD14034.1

Protein Name

Tyrosine-protein kinase ABL1; Abelson murine leukemia viral oncogene homolog 1; Abelson tyrosine-protein kinase 1; Proto-oncogene c-Abl; p150

Genbank Nucleotide ID

M14752; X16416; U07563; U07563; U07561; DQ145721; AL359092; AL161733; AL161733; AL161733; AL359092; CH471090; BC117451; S69223

Gene Name

ABL1; ABL; JTK7

Ensembl Information

Ensembl Gene ID	Ensembl Transcript ID	Ensembl Protein ID

Status

Unreviewed

Classification

Family	E-Value	Score	Start	End
UBD/SH3	8.80e-14	52.9	82	139

Active Site

Position(s)	Description	Evidence
N/A	N/A	N/A

Domain Profile

UBD/SH3

   S: 3    kekvqvlydyeaqnddeLtlkkGdvvlviekeeqdegWlkgvkelegkrGlfPenFvekle 63
            +++ +lyd+ a+ d++L+++kG++++v+  ++++++W+++  ++++ +G +P+n+++ ++
   Q: 82   PNLFVALYDFVASGDNTLSITKGEKLRVL-GYNHNGEWCEA--QTKNGQGWVPSNYITPVN 139
           68899************************.***********..79999**********997 PP

Organism

Homo sapiens

Functional Description
(View)

Functional 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. 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-153' 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. 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 Sequence
(Fasta)

MGQQPGKVLG DQRRPSLPAL HFIKGAGKKE SSRHGGPHCN VFVEHEALQR PVASDFEPQG 60
LSEAARWNSK ENLLAGPSEN DPNLFVALYD FVASGDNTLS ITKGEKLRVL GYNHNGEWCE 120

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Nucleotide Sequence
(Fasta)

TGTGAGAATT GAAATGACTA GCATTATTGA CCCTTTTCAG CATCCCCTGT GAATATTTCT 60
GTTTAGGTTT TTCTTCTTGA AAAGAAATTG TTATTCAGCC CGTTTAAAAC AAATCAAGAA 120

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Sequence Source

Ensembl

Keyword

KW-0002--3D-structure
KW-0007--Acetylation
KW-0025--Alternative splicing
KW-0053--Apoptosis
KW-0067--ATP-binding
KW-0072--Autophagy
KW-0130--Cell adhesion
KW-0160--Chromosomal rearrangement
KW-0181--Complete proteome
KW-0963--Cytoplasm
KW-0206--Cytoskeleton
KW-0227--DNA damage
KW-0234--DNA repair
KW-0238--DNA-binding
KW-0254--Endocytosis
KW-0418--Kinase
KW-0449--Lipoprotein
KW-0460--Magnesium
KW-0464--Manganese
KW-0472--Membrane
KW-0479--Metal-binding
KW-0496--Mitochondrion
KW-0519--Myristate
KW-0547--Nucleotide-binding
KW-0539--Nucleus
KW-0597--Phosphoprotein
KW-0621--Polymorphism
KW-0656--Proto-oncogene
KW-1185--Reference proteome
KW-0727--SH2 domain
KW-0728--SH3 domain
KW-0808--Transferase
KW-0829--Tyrosine-protein kinase
KW-0832--Ubl conjugation

Interpro

IPR033221--ABL1
IPR015015--F-actin_binding
IPR011009--Kinase-like_dom
IPR000719--Prot_kinase_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

PROSITE

PS00107--PROTEIN_KINASE_ATP
PS50011--PROTEIN_KINASE_DOM
PS00109--PROTEIN_KINASE_TYR
PS50001--SH2
PS50002--SH3

Pfam

PF08919--F_actin_bind
PF07714--Pkinase_Tyr
PF00017--SH2
PF00018--SH3_1

PRINTS

PR00401--SH2DOMAIN
PR00109--TYRKINASE

SMART

SM00808--FABD
SM00252--SH2
SM00326--SH3
SM00219--TyrKc

Gene Ontology

GO:0015629--C:actin cytoskeleton
GO:0031252--C:cell leading edge
GO:0005737--C:cytoplasm
GO:0005829--C:cytosol
GO:0031234--C:extrinsic component of cytoplasmic side of plasma membrane
GO:0005739--C:mitochondrion
GO:0016604--C:nuclear body
GO:0031965--C:nuclear membrane
GO:0005730--C:nucleolus
GO:0005654--C:nucleoplasm
GO:0005634--C:nucleus
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:0051019--F:mitogen-activated protein kinase binding
GO:0004515--F:nicotinate-nucleotide adenylyltransferase activity
GO:0004715--F:non-membrane spanning protein tyrosine kinase activity
GO:0070064--F:proline-rich region binding
GO:0008022--F:protein C-terminus binding
GO:0004672--F:protein kinase activity
GO:0005080--F:protein kinase C binding
GO:0004713--F:protein tyrosine kinase activity
GO:0005102--F:receptor binding
GO:0017124--F:SH3 domain binding
GO:0019905--F:syntaxin binding
GO:0030036--P:actin cytoskeleton organization
GO:0090135--P:actin filament branching
GO:0050798--P:activated T cell proliferation
GO:1990051--P:activation of protein kinase C activity
GO:0046632--P:alpha-beta T cell differentiation
GO:0006914--P:autophagy
GO:0002322--P:B cell proliferation involved in immune response
GO:0050853--P:B cell receptor signaling pathway
GO:0001922--P:B-1 B cell homeostasis
GO:0060020--P:Bergmann glial cell differentiation
GO:0072358--P:cardiovascular system development
GO:0007050--P:cell cycle arrest
GO:0006464--P:cellular protein modification process
GO:0006974--P:cellular response to DNA damage stimulus
GO:1903351--P:cellular response to dopamine
GO:0070301--P:cellular response to hydrogen peroxide
GO:0071222--P:cellular response to lipopolysaccharide
GO:0034599--P:cellular response to oxidative stress
GO:0021587--P:cerebellum morphogenesis
GO:0048668--P:collateral sprouting
GO:0006975--P:DNA damage induced protein phosphorylation
GO:0007173--P:epidermal growth factor receptor signaling pathway
GO:0045184--P:establishment of protein localization
GO:0038096--P:Fc-gamma receptor signaling pathway involved in phagocytosis
GO:0045087--P:innate immune response
GO:0008630--P:intrinsic apoptotic signaling pathway in response to DNA damage
GO:0030035--P:microspike assembly
GO:0006298--P:mismatch repair
GO:0051882--P:mitochondrial depolarization
GO:0007067--P:mitotic nuclear division
GO:0030514--P:negative regulation of BMP signaling pathway
GO:0022408--P:negative regulation of cell-cell adhesion
GO:2000773--P:negative regulation of cellular senescence
GO:2000352--P:negative regulation of endothelial cell apoptotic process
GO:0070373--P:negative regulation of ERK1 and ERK2 cascade
GO:0043124--P:negative regulation of I-kappaB kinase/NF-kappaB signaling
GO:0045930--P:negative regulation of mitotic cell cycle
GO:1900275--P:negative regulation of phospholipase C activity
GO:0071901--P:negative regulation of protein serine/threonine kinase activity
GO:0051444--P:negative regulation of ubiquitin-protein transferase activity
GO:0001843--P:neural tube closure
GO:0060563--P:neuroepithelial cell differentiation
GO:0050885--P:neuromuscular process controlling balance
GO:0038083--P:peptidyl-tyrosine autophosphorylation
GO:0018108--P:peptidyl-tyrosine phosphorylation
GO:0035791--P:platelet-derived growth factor receptor-beta signaling pathway
GO:1904531--P:positive regulation of actin filament binding
GO:0043065--P:positive regulation of apoptotic process
GO:0007204--P:positive regulation of cytosolic calcium ion concentration
GO:0070374--P:positive regulation of ERK1 and ERK2 cascade
GO:0043123--P:positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:1902715--P:positive regulation of interferon-gamma secretion
GO:1900042--P:positive regulation of interleukin-2 secretion
GO:1904528--P:positive regulation of microtubule binding
GO:0045931--P:positive regulation of mitotic cell cycle
GO:0051149--P:positive regulation of muscle cell differentiation
GO:1901216--P:positive regulation of neuron death
GO:0033690--P:positive regulation of osteoblast proliferation
GO:0051353--P:positive regulation of oxidoreductase activity
GO:0050731--P:positive regulation of peptidyl-tyrosine phosphorylation
GO:0001934--P:positive regulation of protein phosphorylation
GO:0051281--P:positive regulation of release of sequestered calcium ion into cytosol
GO:2000096--P:positive regulation of Wnt signaling pathway, planar cell polarity pathway
GO:0009791--P:post-embryonic development
GO:0046777--P:protein autophosphorylation
GO:0032956--P:regulation of actin cytoskeleton organization
GO:2000249--P:regulation of actin cytoskeleton reorganization
GO:0010506--P:regulation of autophagy
GO:0030516--P:regulation of axon extension
GO:0030155--P:regulation of cell adhesion
GO:2000145--P:regulation of cell motility
GO:0042127--P:regulation of cell proliferation
GO:0030100--P:regulation of endocytosis
GO:1903053--P:regulation of extracellular matrix organization
GO:0031113--P:regulation of microtubule polymerization
GO:2001020--P:regulation of response to DNA damage stimulus
GO:0006355--P:regulation of transcription, DNA-templated
GO:0006979--P:response to oxidative stress
GO:0042770--P:signal transduction in response to DNA damage
GO:0048536--P:spleen development
GO:0034446--P:substrate adhesion-dependent cell spreading
GO:0048538--P:thymus development
GO:0002333--P:transitional one stage B cell differentiation

KEGG

hsa:25

Created Date

25-Jun-2017

Functional Description

Protein Fasta Sequence

Nucleotide Fasta Sequence