Descriptions

CRK regulates transcription and cytoskeletal reorganization for cell growth and motility by linking tyrosine kinases to small G proteins. The SH2 and nSH3 domains are used to recruit their target proteins. The interaction between SH2 and inter-domain linker between nSH3 and cSH3 detaches the SH2-targeting proteins. In mouse CRK mutant experiments, it was discovered that cSH3 negatively regulates the function of nSH3.

Autoinhibitory domains (AIDs)

Target domain

132-192 (N-terminal SH3 domain)

Relief mechanism

PTM

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for Q63768

Entry ID Method Resolution Chain Position Source
AF-Q63768-F1 Predicted AlphaFoldDB

2 variants for Q63768

Variant ID(s) Position Change Description Diseaes Association Provenance
244 Q>R NRK-23 inactive mutant [UniProt] No
253 K>E NRK-23 inactive mutant [UniProt] No

No associated diseases with Q63768

4 regional properties for Q63768

Type Name Position InterPro Accession
domain SH3 domain 132 - 192 IPR001452-1
domain SH3 domain 235 - 296 IPR001452-2
domain CRK, N-terminal SH3 domain 135 - 189 IPR035457
domain CRK, C-terminal SH3 domain 237 - 293 IPR035458

Functions

Description
EC Number
Subcellular Localization
  • Cytoplasm
  • Cell membrane
  • Translocated to the plasma membrane upon cell adhesion
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

6 GO annotations of cellular component

Name Definition
actin cytoskeleton The part of the cytoskeleton (the internal framework of a cell) composed of actin and associated proteins. Includes actin cytoskeleton-associated complexes.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
membrane A lipid bilayer along with all the proteins and protein complexes embedded in it an attached to it.
membrane raft Any of the small (10-200 nm), heterogeneous, highly dynamic, sterol- and sphingolipid-enriched membrane domains that compartmentalize cellular processes. Small rafts can sometimes be stabilized to form larger platforms through protein-protein and protein-lipid interactions.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
protein-containing complex A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together.

18 GO annotations of molecular function

Name Definition
cytoskeletal protein binding Binding to a protein component of a cytoskeleton (actin, microtubule, or intermediate filament cytoskeleton).
enzyme binding Binding to an enzyme, a protein with catalytic activity.
ephrin receptor binding Binding to an ephrin receptor.
insulin-like growth factor receptor binding Binding to an insulin-like growth factor receptor.
kinase binding Binding to a kinase, any enzyme that catalyzes the transfer of a phosphate group.
phosphotyrosine residue binding Binding to a phosphorylated tyrosine residue within a protein.
protein domain specific binding Binding to a specific domain of a protein.
protein phosphorylated amino acid binding Binding to a phosphorylated amino acid residue within a protein.
protein self-association Binding to a domain within the same polypeptide.
protein tyrosine kinase binding Binding to protein tyrosine kinase.
protein-macromolecule adaptor activity The binding activity of a protein that brings together two or more macromolecules in contact, permitting those molecules to function in a coordinated way. The adaptor can bring together two proteins, or a protein and another macromolecule such as a lipid or a nucleic acid.
receptor tyrosine kinase binding Binding to a receptor that possesses protein tyrosine kinase activity.
scaffold protein binding Binding to a scaffold protein. Scaffold proteins are crucial regulators of many key signaling pathways. Although not strictly defined in function, they are known to interact and/or bind with multiple members of a signaling pathway, tethering them into complexes.
SH2 domain binding Binding to a SH2 domain (Src homology 2) of a protein, a protein domain of about 100 amino-acid residues and belonging to the alpha + beta domain class.
SH3 domain binding Binding to a SH3 domain (Src homology 3) of a protein, small protein modules containing approximately 50 amino acid residues found in a great variety of intracellular or membrane-associated proteins.
signaling adaptor activity The binding activity of a molecule that brings together two or more molecules in a signaling pathway, permitting those molecules to function in a coordinated way. Adaptor molecules themselves do not have catalytic activity.
signaling receptor complex adaptor activity The binding activity of a molecule that provides a physical support for the assembly of a multiprotein receptor signaling complex.
ubiquitin protein ligase binding Binding to a ubiquitin protein ligase enzyme, any of the E3 proteins.

42 GO annotations of biological process

Name Definition
actin cytoskeleton organization A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments and their associated proteins.
activation of GTPase activity Any process that initiates the activity of an inactive GTPase through the replacement of GDP by GTP.
cell chemotaxis The directed movement of a motile cell guided by a specific chemical concentration gradient. Movement may be towards a higher concentration (positive chemotaxis) or towards a lower concentration (negative chemotaxis).
cell migration The controlled self-propelled movement of a cell from one site to a destination guided by molecular cues. Cell migration is a central process in the development and maintenance of multicellular organisms.
cellular response to endothelin Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an endothelin stimulus. Endothelin is any of three secretory vasoconstrictive peptides (endothelin-1, -2, -3).
cellular response to insulin-like growth factor stimulus Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an insulin-like growth factor stimulus.
cellular response to nerve growth factor stimulus A process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a nerve growth factor stimulus.
cellular response to nitric oxide Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a nitric oxide stimulus.
cellular response to transforming growth factor beta stimulus Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a transforming growth factor beta stimulus.
cerebellar neuron development The process whose specific outcome is the progression of a cerebellar neuron over time, from initial commitment of the cell to a specific fate, to the fully functional differentiated cell.
cerebral cortex development The progression of the cerebral cortex over time from its initial formation until its mature state. The cerebral cortex is the outer layered region of the telencephalon.
dendrite development The process whose specific outcome is the progression of the dendrite over time, from its formation to the mature structure.
ephrin receptor signaling pathway The series of molecular signals initiated by ephrin binding to its receptor, and ending with the regulation of a downstream cellular process, e.g. transcription.
establishment of cell polarity The specification and formation of anisotropic intracellular organization or cell growth patterns.
helper T cell diapedesis The passage of a helper T cell between the tight junctions of endothelial cells lining blood vessels, typically the fourth and final step of cellular extravasation.
hippocampus development The progression of the hippocampus over time from its initial formation until its mature state.
lipid metabolic process The chemical reactions and pathways involving lipids, compounds soluble in an organic solvent but not, or sparingly, in an aqueous solvent. Includes fatty acids; neutral fats, other fatty-acid esters, and soaps; long-chain (fatty) alcohols and waxes; sphingoids and other long-chain bases; glycolipids, phospholipids and sphingolipids; and carotenes, polyprenols, sterols, terpenes and other isoprenoids.
negative regulation of cell motility Any process that stops, prevents, or reduces the frequency, rate or extent of cell motility.
negative regulation of natural killer cell mediated cytotoxicity Any process that stops, prevents, or reduces the rate of natural killer mediated cytotoxicity.
negative regulation of wound healing Any process that decreases the rate, frequency, or extent of the series of events that restore integrity to a damaged tissue, following an injury.
neuron migration The characteristic movement of an immature neuron from germinal zones to specific positions where they will reside as they mature.
positive regulation of smooth muscle cell migration Any process that activates, maintains or increases the frequency, rate or extent of smooth muscle cell migration.
positive regulation of substrate adhesion-dependent cell spreading Any process that activates or increases the frequency, rate or extent of substrate adhesion-dependent cell spreading.
reelin-mediated signaling pathway The series of molecular signals initiated by the binding of reelin (a secreted glycoprotein) to a receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
regulation of actin cytoskeleton organization Any process that modulates the frequency, rate or extent of the formation, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments and their associated proteins.
regulation of cell adhesion mediated by integrin Any process that modulates the frequency, rate, or extent of cell adhesion mediated by integrin.
regulation of cell shape Any process that modulates the surface configuration of a cell.
regulation of cellular component movement OBSOLETE. Any process that modulates the frequency, rate or extent of the movement of a cellular component.
regulation of dendrite development Any process that modulates the frequency, rate or extent of dendrite development.
regulation of GTPase activity Any process that modulates the rate of GTP hydrolysis by a GTPase.
regulation of intracellular signal transduction Any process that modulates the frequency, rate or extent of intracellular signal transduction.
regulation of leukocyte migration Any process that modulates the frequency, rate, or extent of leukocyte migration.
regulation of protein binding Any process that modulates the frequency, rate or extent of protein binding.
regulation of Rac protein signal transduction Any process that modulates the frequency, rate or extent of Rac protein signal transduction.
regulation of signal transduction Any process that modulates the frequency, rate or extent of signal transduction.
regulation of T cell migration Any process that modulates the frequency, rate or extent of T cell migration.
response to cholecystokinin Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cholecystokinin stimulus.
response to hepatocyte growth factor Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a hepatocyte growth factor stimulus.
response to hydrogen peroxide Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a hydrogen peroxide (H2O2) stimulus.
response to peptide Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a peptide stimulus.
response to yeast Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a yeast species.
signal transduction The cellular process in which a signal is conveyed to trigger a change in the activity or state of a cell. Signal transduction begins with reception of a signal (e.g. a ligand binding to a receptor or receptor activation by a stimulus such as light), or for signal transduction in the absence of ligand, signal-withdrawal or the activity of a constitutively active receptor. Signal transduction ends with regulation of a downstream cellular process, e.g. regulation of transcription or regulation of a metabolic process. Signal transduction covers signaling from receptors located on the surface of the cell and signaling via molecules located within the cell. For signaling between cells, signal transduction is restricted to events at and within the receiving cell.

8 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q04929 CRK Adapter molecule crk Gallus gallus (Chicken) SS
Q9XYM0 Crk Adapter molecule Crk Drosophila melanogaster (Fruit fly) SS
P46109 CRKL Crk-like protein Homo sapiens (Human) SS
P46108 CRK Adapter molecule crk Homo sapiens (Human) EV
P47941 Crkl Crk-like protein Mus musculus (Mouse) SS
Q64010 Crk Adapter molecule crk Mus musculus (Mouse) EV SS
Q5U2U2 Crkl Crk-like protein Rattus norvegicus (Rat) SS
Q9NHC3 ced-2 Cell death abnormality protein 2 Caenorhabditis elegans SS
10 20 30 40 50 60
MAGNFDSEER SSWYWGRLSR QEAVALLQGQ RHGVFLVRDS STSPGDYVLS VSENSRVSHY
70 80 90 100 110 120
IINSSGPRPP VPPSPAQPPP GVSPSRLRIG DQEFDSLPAL LEFYKIHYLD TTTLIEPVSR
130 140 150 160 170 180
SRQGSGVILR QEEAEYVRAL FDFNGNDEED LPFKKGDILR IRDKPEEQWW NAEDSEGKRG
190 200 210 220 230 240
MIPVPYVEKY RPASASVSAL IGGNQEGSHP QPLGGPEPGP YAQPSVNTPL PNLQNGPIYA
250 260 270 280 290 300
RVIQKRVPNA YDKTALALEV GELVKVTKIN VSGQWEGECN GKRGHFPFTH VRLLDQQNPE
EDFS