Q5U2U2

SS
Gene name
Crkl
Protein name
Crk-like protein
Names
Species
Rattus norvegicus (Rat)
KEGG Pathway
rno:287942
EC number
Protein Class

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. In CRKII, the intramolecular interactions of the SH domains with the inter-domain linker between nSH3 and cSH3 (inter-SH3 region) result in a compact structure.The binding site of SH2 in CRKII is exposed, but nSH3 is masked by SH2. In addition, cSH3 acts as a stabilizer of the assembled structure and thus as a negative regulator of CRKII function. Mutations disrupting the core structure of CRKII disturb the assembly of the SH domains, allowing nSH3 to effectively bind target proteins and transmit signals, thus promoting cell growth and motility.

Autoinhibitory domains (AIDs)

238-293 (cSH3 domain) SS

Target domain

126-180 (N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins)

Relief mechanism

PTM

Assay

224-237 (inter-SH3 region) SS

Target domain

126-180 (N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins)

Relief mechanism

PTM

Assay

11-111 (SH2 region) SS

Target domain

126-180 (N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins)

Relief mechanism

PTM

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for Q5U2U2

Entry ID Method Resolution Chain Position Source
AF-Q5U2U2-F1 Predicted AlphaFoldDB

No variants for Q5U2U2

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q5U2U2

2 associated diseases with Q5U2U2

[MIM: 176807]: Prostate cancer (PC)

A malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. {ECO:0000269|PubMed:15300251, ECO:0000269|PubMed:16155194}. Note=The gene represented in this entry may be involved in disease pathogenesis. EPHB2 mutations have been found in a prostate cancer cell line derived from a brain metastasis.

[MIM: 618462]: Bleeding disorder, platelet-type, 22 (BDPLT22)

An autosomal recessive disorder characterized by increased bleeding tendency due to platelet dysfunction. Clinical features include epistaxis, hematomas, bleeding after minor injuries, and menorrhagia. {ECO:0000269|PubMed:30213874}. Note=The disease may be caused by variants affecting the gene represented in this entry.

Without disease ID
  • A malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. {ECO:0000269|PubMed:15300251, ECO:0000269|PubMed:16155194}. Note=The gene represented in this entry may be involved in disease pathogenesis. EPHB2 mutations have been found in a prostate cancer cell line derived from a brain metastasis.
  • An autosomal recessive disorder characterized by increased bleeding tendency due to platelet dysfunction. Clinical features include epistaxis, hematomas, bleeding after minor injuries, and menorrhagia. {ECO:0000269|PubMed:30213874}. Note=The disease may be caused by variants affecting the gene represented in this entry.

14 regional properties for Q5U2U2

Type Name Position InterPro Accession
domain Protein kinase domain 621 - 884 IPR000719
domain Ephrin receptor ligand binding domain 20 - 202 IPR001090
domain Serine-threonine/tyrosine-protein kinase, catalytic domain 622 - 880 IPR001245
conserved_site Tyrosine-protein kinase, receptor class V, conserved site 178 - 198 IPR001426-1
conserved_site Tyrosine-protein kinase, receptor class V, conserved site 241 - 261 IPR001426-2
domain Sterile alpha motif domain 910 - 977 IPR001660
domain Fibronectin type III 324 - 434 IPR003961-1
domain Fibronectin type III 435 - 530 IPR003961-2
active_site Tyrosine-protein kinase, active site 742 - 754 IPR008266
domain Tyrosine-protein kinase ephrin type A/B receptor-like 268 - 302 IPR011641
binding_site Protein kinase, ATP binding site 627 - 653 IPR017441
domain Tyrosine-protein kinase, catalytic domain 621 - 880 IPR020635
domain Ephrin receptor, transmembrane domain 544 - 617 IPR027936
domain Ephrin type-B receptor 2, ligand binding domain 19 - 196 IPR034238

Functions

Description
EC Number
Subcellular Localization
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

6 GO annotations of cellular component

Name Definition
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
extrinsic component of postsynaptic membrane The component of the postsynaptic membrane consisting of gene products and protein complexes that are loosely bound to one of its surfaces, but not integrated into the hydrophobic region.
neuromuscular junction The junction between the axon of a motor neuron and a muscle fiber. In response to the arrival of action potentials, the presynaptic button releases molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane of the muscle fiber, leading to a change in post-synaptic potential.
nucleoplasm That part of the nuclear content other than the chromosomes or the nucleolus.
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.
synapse The junction between an axon of one neuron and a dendrite of another neuron, a muscle fiber or a glial cell. As the axon approaches the synapse it enlarges into a specialized structure, the presynaptic terminal bouton, which contains mitochondria and synaptic vesicles. At the tip of the terminal bouton is the presynaptic membrane; facing it, and separated from it by a minute cleft (the synaptic cleft) is a specialized area of membrane on the receiving cell, known as the postsynaptic membrane. In response to the arrival of nerve impulses, the presynaptic terminal bouton secretes molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane.

5 GO annotations of molecular function

Name Definition
identical protein binding Binding to an identical protein or proteins.
phosphotyrosine residue binding Binding to a phosphorylated tyrosine residue within a protein.
receptor tyrosine kinase binding Binding to a receptor that possesses protein tyrosine kinase activity.
RNA polymerase II-specific DNA-binding transcription factor binding Binding to a sequence-specific DNA binding RNA polymerase II transcription factor, any of the factors that interact selectively and non-covalently with a specific DNA sequence in order to modulate transcription.
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.

54 GO annotations of biological process

Name Definition
acetylcholine receptor signaling pathway The series of molecular signals generated as a consequence of an acetylcholine receptor binding to one of its physiological ligands.
animal organ morphogenesis Morphogenesis of an animal organ. An organ is defined as a tissue or set of tissues that work together to perform a specific function or functions. Morphogenesis is the process in which anatomical structures are generated and organized. Organs are commonly observed as visibly distinct structures, but may also exist as loosely associated clusters of cells that work together to perform a specific function or functions.
anterior/posterior pattern specification The regionalization process in which specific areas of cell differentiation are determined along the anterior-posterior axis. The anterior-posterior axis is defined by a line that runs from the head or mouth of an organism to the tail or opposite end of the organism.
B cell apoptotic process Any apoptotic process in a B cell, a lymphocyte of B lineage with the phenotype CD19-positive and capable of B cell mediated immunity.
blood vessel development The process whose specific outcome is the progression of a blood vessel over time, from its formation to the mature structure. The blood vessel is the vasculature carrying blood.
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.
cellular response to interleukin-7 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 interleukin-7 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.
cellular response to xenobiotic 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 stimulus from a xenobiotic, a compound foreign to the organism exposed to it. It may be synthesized by another organism (like ampicilin) or it can be a synthetic chemical.
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.
cranial skeletal system development The process whose specific outcome is the progression of a cranial skeletal system over time, from its formation to the mature structure. The cranial skeletal system is the skeletal subdivision of the head, and includes the skull (cranium plus mandible), pharyngeal and/or hyoid apparatus.
dendrite development The process whose specific outcome is the progression of the dendrite over time, from its formation to the mature structure.
endothelin receptor signaling pathway A G protein-coupled receptor signaling pathway initiated by endothelin binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
enzyme-linked receptor protein signaling pathway The series of molecular signals initiated by an extracellular ligand binding to a receptor on the surface of the target cell, where the receptor possesses catalytic activity or is closely associated with an enzyme such as a protein kinase, 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.
fibroblast growth factor receptor signaling pathway The series of molecular signals generated as a consequence of a fibroblast growth factor receptor binding to one of its physiological ligands.
heart development The process whose specific outcome is the progression of the heart over time, from its formation to the mature structure. The heart is a hollow, muscular organ, which, by contracting rhythmically, keeps up the circulation of the blood.
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.
male gonad development The process whose specific outcome is the progression of the male gonad over time, from its formation to the mature structure.
negative regulation of gene expression Any process that decreases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
negative regulation of protein phosphorylation Any process that stops, prevents or reduces the rate of addition of phosphate groups to amino acids within a protein.
neuron migration The characteristic movement of an immature neuron from germinal zones to specific positions where they will reside as they mature.
outflow tract morphogenesis The process in which the anatomical structures of the outflow tract are generated and organized. The outflow tract is the portion of the heart through which blood flows into the arteries.
parathyroid gland development The process whose specific outcome is the progression of the parathyroid gland over time, from its formation to the mature structure. The parathyroid gland is an organ specialised for secretion of parathyroid hormone.
pattern specification process Any developmental process that results in the creation of defined areas or spaces within an organism to which cells respond and eventually are instructed to differentiate.
positive regulation of cell population proliferation Any process that activates or increases the rate or extent of cell proliferation.
positive regulation of ERK1 and ERK2 cascade Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade.
positive regulation of glial cell migration Any process that activates or increases the frequency, rate or extent of glial cell migration.
positive regulation of MAPK cascade Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the MAPK cascade.
positive regulation of protein phosphorylation Any process that activates or increases the frequency, rate or extent of addition of phosphate groups to amino acids within a protein.
positive regulation of Rac protein signal transduction Any process that activates or increases the frequency, rate or extent of Rac protein signal transduction.
positive regulation of skeletal muscle acetylcholine-gated channel clustering Any process that activates or increases the frequency, rate or extent of skeletal muscle acetylcholine-gated channel clustering.
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.
postsynaptic specialization assembly The aggregation, arrangement and bonding together of a set of components to form a postsynaptic specialization, a region that lies adjacent to the cytoplasmic face of the postsynaptic membrane.
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 cell adhesion mediated by integrin Any process that modulates the frequency, rate, or extent of cell adhesion mediated by integrin.
regulation of cell growth Any process that modulates the frequency, rate, extent or direction of cell growth.
regulation of dendrite development Any process that modulates the frequency, rate or extent of dendrite development.
regulation of gene expression Any process that modulates the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
regulation of leukocyte migration Any process that modulates the frequency, rate, or extent of leukocyte migration.
regulation of skeletal muscle acetylcholine-gated channel clustering Any process that modulates the frequency, rate or extent of skeletal muscle acetylcholine-gated channel clustering.
regulation of T cell migration Any process that modulates the frequency, rate or extent of T cell migration.
response to fibroblast 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 fibroblast growth factor stimulus.
retinoic acid receptor signaling pathway The series of molecular signals generated as a consequence of a retinoic acid receptor binding to one of its physiological ligands.
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.
single fertilization The union of male and female gametes to form a zygote.
spermatogenesis The developmental process by which male germ line stem cells self renew or give rise to successive cell types resulting in the development of a spermatozoa.
T cell receptor signaling pathway The series of molecular signals initiated by the cross-linking of an antigen receptor on a T cell.
thymus development The process whose specific outcome is the progression of the thymus over time, from its formation to the mature structure. The thymus is a symmetric bi-lobed organ involved primarily in the differentiation of immature to mature T cells, with unique vascular, nervous, epithelial, and lymphoid cell components.
urogenital system development The process whose specific outcome is the progression of the urogenital system over time, from its formation to the mature structure.

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
P46108 CRK Adapter molecule crk Homo sapiens (Human) EV
P46109 CRKL Crk-like protein Homo sapiens (Human) SS
Q64010 Crk Adapter molecule crk Mus musculus (Mouse) EV SS
P47941 Crkl Crk-like protein Mus musculus (Mouse) SS
Q63768 Crk Adapter molecule crk Rattus norvegicus (Rat) SS
Q9NHC3 ced-2 Cell death abnormality protein 2 Caenorhabditis elegans SS
10 20 30 40 50 60
MSSARFDSSD RSAWYMGPVS RQEAQTRLQG QRHGMFLVRD SSTCPGDYVL SVSENSRVSH
70 80 90 100 110 120
YIINSLPNRR FKIGDQEFDH LPALLEFYKI HYLDTTTLIE PAPRYPNPPM GSVSAPNLST
130 140 150 160 170 180
AEENLEYVRT LYDFPGNDAE DLPFKKGELL VIIEKPEEQW WSARNKDGRV GMIPVPYVEK
190 200 210 220 230 240
LVRSSPHGKH GNRNSNSYGI PEPAHAYAQP QTTTPLPTVA STPGAAINPL PSTQNGPVFA
250 260 270 280 290 300
KAIQKRVPCA YDKTALALEV GDIVKVTRMN INGQWEGEVN GRKGLFPFTH VKIFDPQNPD
DNE