# TRIP Database

Mammalian TRansient receptor potential channel-Interacting Protein

TRP channels

- TRPC
  - TRPC1
  - TRPC2
  - TRPC3
  - TRPC4
  - TRPC5
  - TRPC6
  - TRPC7
- TRPV
  - TRPV1
  - TRPV2
  - TRPV3
  - TRPV4
  - TRPV5
  - TRPV6
- TRPM
  - TRPM1
  - TRPM2
  - TRPM3
  - TRPM4
  - TRPM5
  - TRPM6
  - TRPM7
  - TRPM8
- TRPML
  - TRPML1
  - TRPML2
  - TRPML3
- TRPP
  - TRPP1
  - TRPP2
  - TRPP3
- TRPA
  - TRPA1

» Citation

# SRC / TRP channels

- Basic Information
- External Database
- PPI pairs (9)
- Biological Process (35)
- Disease (1)

Name: Proto-oncogene tyrosine-protein kinase Src (SRC)
Official Symbol: SRC provided by HGNC
Function:
Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates such as AFAP1. Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 and to localize to actin filaments. Cytoskeletal reorganization is also controlled through the phosphorylation of cortactin (CTTN). When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN). In addition to phosphorylating focal adhesion proteins, SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). Another type of cell-cell junction, the gap junction, is also a target for SRC, which phosphorylates connexin-43 (GJA1). SRC is implicated in regulation of pre-mRNA-processing and phosphorylates RNA-binding proteins such as KHDRBS1. Also plays a role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors. Involved in the RAS pathway through phosphorylation of RASA1 and RASGRF1. Plays a role in EGF-mediated calcium-activated chloride channel activation. Required for epidermal growth factor receptor (EGFR) internalization through phosphorylation of clathrin heavy chain (CLTC and CLTCL1) at 'Tyr-1477'. Involved in beta-arrestin (ARRB1 and ARRB2) desensitization through phosphorylation and activation of ADRBK1, leading to beta-arrestin phosphorylation and internalization. Has a critical role in the stimulation of the CDK20/MAPK3 mitogen-activated protein kinase cascade by epidermal growth factor. Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus. Plays an important role in osteoclastic bone resorption in conjunction with PTK2B/PYK2. Both the formation of a SRC-PTK2B/PYK2 complex and SRC kinase activity are necessary for this function. Recruited to activated integrins by PTK2B/PYK2, thereby phosphorylating CBL, which in turn induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function. Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase. Phosphorylates DDR2 on tyrosine residues, thereby promoting its subsequent autophosphorylation. Phosphorylates RUNX3 and COX2 on tyrosine residues, TNK2 on 'Tyr-284' and CBL on 'Tyr-731'. Enhances DDX58/RIG-I-elicited antiviral signaling. Phosphorylates PDPK1 at 'Tyr-9', 'Tyr-373' and 'Tyr-376'. Phosphorylates BCAR1 at 'Tyr-128'.
Source: Reorganizing the protein space at the Universal Protein Resource (UniProt) Nucleic Acids Res. 40: D71-D75 (2012).

Species | External DB
Name | Description
--- | ---
Entrez Gene | A database that contains genome-centered information
UniprotKB | The central hub for collection of functional information on proteins
DIP | A database that documents experimentally determined PPIs
IntAct | An open source database and software suite for modeling, storing and analyzing molecular interaction data
MINT | A database that collects experimentally verified PPIs in a binary or complex representation
BioGRID | A database of known and predicted PPIs
STRING | An online interaction repository with data
IUPHAR-DB | Integrated pharmacological and pathophysiological information on GPCR and voltage-gated & ligand-gated ion channels
KEGG | A database resource consisting of 16 main databases, categorized into systems information, genomic information, and chemical information
OMIM | A database of human genes and genetic disorders
Entrez Gene | UniprotKB | DIP | IntAct | MINT | BioGRID | STRING | IUPHAR-DB | KEGG | OMIM
Human | 6714 | P12931 | DIP-1059N | P12931 | MINT-93621 | 112592 | P12931 |  | hsa:6714 | 190090
Mouse | 20779 | P05480 | DIP-31071N | P05480 | MINT-85032 | 203491 | P05480 |  | mmu:20779 |
Rat | 83805 | Q9WUD9 | DIP-42731N |  | MINT-1488989 | 249840 | Q9WUD9 |  | rno:83805 |

PPI pairs:

TRPC1 | TRPC2 | TRPC3 | TRPC4 | TRPC5 | TRPC6 | TRPV1 | TRPV4
TRPV6

Biological Process:

- GO:0007411 : axon guidance
- GO:0045453 : bone resorption
- GO:0060444 : branching involved in mammary gland duct morphogenesis
- GO:0007155 : cell adhesion
- GO:0007049 : cell cycle
- GO:0016044 : cellular membrane organization
- GO:0071393 : cellular response to progesterone stimulus
- GO:0007173 : epidermal growth factor receptor signaling pathway
- GO:0008543 : fibroblast growth factor receptor signaling pathway
- GO:0030900 : forebrain development
- GO:0007243 : intracellular protein kinase cascade
- GO:0050900 : leukocyte migration
- GO:2000811 : negative regulation of anoikis
- GO:0043154 : negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
- GO:2001237 : negative regulation of extrinsic apoptotic signaling pathway
- GO:0051895 : negative regulation of focal adhesion assembly
- GO:2001243 : negative regulation of intrinsic apoptotic signaling pathway
- GO:0032463 : negative regulation of protein homooligomerization
- GO:0048011 : nerve growth factor receptor signaling pathway
- GO:0048477 : oogenesis
- GO:0018108 : peptidyl-tyrosine phosphorylation
- GO:0030168 : platelet activation
- GO:0090263 : positive regulation of canonical Wnt receptor signaling pathway
- GO:0033625 : positive regulation of integrin activation
- GO:0051897 : positive regulation of protein kinase B signaling cascade
- GO:0050847 : progesterone receptor signaling pathway
- GO:0007265 : Ras protein signal transduction
- GO:0045124 : regulation of bone resorption
- GO:0033146 : regulation of intracellular estrogen receptor signaling pathway
- GO:0043114 : regulation of vascular permeability
- GO:0070555 : response to interleukin-1
- GO:0007172 : signal complex assembly
- GO:0031295 : T cell costimulation
- GO:0060065 : uterus development
- GO:0019048 : virus-host interaction

Source: The Gene Ontology Consortium. Gene ontology: tool for the unification of biology. Nat. Genet.. May 2000;25(1):25-9.
World Wide Web URL: http://www.geneontology.org/
Disease:

- OMIM:190090 : Colon cancer, advanced (OMIM: )

Source: Online Mendelian Inheritance in Man, OMIM®. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD), May, 2012.
World Wide Web URL: http://omim.org/

Screening Validation: In vitro validation Validation: In vivo validation Characterization Functional consequence | top

Screening
| Experimental screening | Non-experimental screening | Reference
--- | --- | --- | ---
TRP channel construct | Interactor source
TRP channel |  | Interactor | Method | Species | Region | Species | Organ/tissue | Sample type
TRPC1 |  | SRC | Inference |  |  |  |  |  | Prediction | 16407161
TRPC2 |  | SRC | Inference |  |  |  |  |  | Prediction | 16407161
TRPC3 |  | SRC | Inference |  |  |  |  |  | Prediction | 16407161
TRPC4 |  | SRC | Inference |  |  |  |  |  | Prediction | 16144838
TRPC5 |  | SRC | Inference |  |  |  |  |  | Prediction | 16407161
TRPC6 |  | SRC | Inference |  |  |  |  |  | Prediction | 16407161
TRPC6 |  | Src | Speculation |  |  |  |  |  | Prediction | 14761972
TRPV1 |  | SRC | Inference |  |  |  |  |  | Prediction | 15084474
TRPV4 |  | SRC | Inference |  |  |  |  |  | Prediction | 12538589
TRPV6 |  | SRC | Inference |  |  |  |  |  | Prediction | 17197020

(: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

Screening Validation: In vitro validation Validation: In vivo validation Characterization Functional consequence | top

Validation: In vitro validation
| Assay with recombinant proteins | Reference
--- | --- | ---
TRP channel construct | Interactor construct
TRP channel |  | Interactor | Method | Species | Region | Expression system | Species | Region | Expression system
TRPC1 |  | SRC | Fusion protein-pull down assay | Mouse | 1-341 | In vitro translation | Chicken | Full-length | E. coli | 16407161
TRPC2 |  | SRC | Fusion protein-pull down assay | Mouse | 1-616 | In vitro translation | Chicken | Full-length | E. coli | 16407161
TRPC3 |  | SRC | Fusion protein-pull down assay | Mouse | 1-340 | In vitro translation | Chicken | Full-length | E. coli | 16407161
TRPC4 |  | SRC | Fusion protein-pull down assay | Mouse | 626-974 | In vitro translation | Chicken | Full-length | E. coli | 16407161
TRPC5 |  | SRC | Fusion protein-pull down assay | Mouse | 630-975 | In vitro translation | Chicken | Full-length | E. coli | 16407161
TRPC5 |  | SRC | Fusion protein-pull down assay | Mouse | 1-321 | In vitro translation | Chicken | Full-length | E. coli | 16407161
TRPC6 |  | SRC | Fusion protein-pull down assay | Mouse | 1-396 | In vitro translation | Chicken | Full-length | E. coli | 16407161

(: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

Screening Validation: In vitro validation Validation: In vivo validation Characterization Functional consequence | top

Validation: In vivo validation
| Assay with endogenous proteins | Assay with overexpressed proteins | Reference
--- | --- | --- | ---
Cell or tissue | Cell or tissue | TRP channel construct | Interactor construct
TRP channel |  | Interactor | Method | Species | Region | Species | Region
TRPC3 |  | SRC | Co-immunoprecipitation |  | COS-7 | Mouse | Full-length | Chicken | Full-length | 16407161
TRPC4 |  | SRC | Co-immunoprecipitation |  | COS-7 | Human | Full-length | Not specifed | Full-length | 16144838
TRPC6 |  | Src | Co-immunoprecipitation | Rat brain microsome |  |  |  |  |  | 14761972
TRPV1 |  | SRC | Co-immunoprecipitation | Rat dorsal root ganglion neuron |  |  |  |  |  | 15084474
TRPV1 |  | SRC | Co-immunoprecipitation | HEK293 |  |  |  |  |  | 16319926
TRPV4 |  | SRC | Co-immunoprecipitation |  | HEK293 | Mouse | Full-length | Not used |  | 12538589
TRPV6 |  | SRC | Co-immunoprecipitation |  | HEK293 | Rat | Full-length | Human | Full-length | 17197020

(: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

Screening Validation: In vitro validation Validation: In vivo validation Characterization Functional consequence | top

Characterization
| Binding region mapping | Stoichiometry | Affinity (Kd) | Reference
--- | --- | --- | --- | ---
TRP channel | Interactor
TRP channel |  | Interactor | Method | Species | Region | Species | Region
TRPC3 |  | SRC | Co-immunoprecipitation | Mouse | 1-370 | Chicken | SH2 domain |  |  | 16407161
TRPV1 |  | SRC | Fusion protein-pull down assay | Human | 1-433 | Rat | 83-144 |  |  | 16319926
TRPV1 |  | SRC | Fusion protein-pull down assay | Human | 681-839 | Rat | 83-144 |  |  | 16319926

(: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

Screening Validation: In vitro validation Validation: In vivo validation Characterization Functional consequence | top

Functional consequence
TRP channel |  | Interactor | Method | Post-translational modification | Subcellular trafficking | Activity | Reference
--- | --- | --- | --- | --- | --- | --- | ---
TRPC3 |  | SRC | Calcium measurement |  |  | Activation | 16407161
TRPC3 |  | SRC | In vivo PTM assay | Phosphorylation (Tyr-226) |  |  | 16407161
TRPV1 |  | SRC | Calcium measurement |  |  | Activation | 16319926
TRPV1 |  | SRC | In vitro PTM assay | Phosphorylayion (Tyr-200) |  |  | 16319926
TRPV1 |  | SRC | In vivo PTM assay | Phosphorylation |  |  | 15084474
TRPV1 |  | SRC | In vivo PTM assay | Phosphorylayion (Tyr-200) |  |  | 16319926
TRPV1 |  | SRC | Patch clamp |  |  | Activation | 15084474
TRPV1 |  | SRC | Patch clamp |  |  | Activation | 16319926
TRPV4 |  | SRC | Calcium measurement |  |  | Activation | 12538589
TRPV4 |  | SRC | Calcium measurement |  |  | Activation | 19033444
TRPV4 |  | SRC | In vitro PTM assay | Phosphorylation (Tyr-273) |  |  | 12538589
TRPV4 |  | SRC | In vivo PTM assay | Phosphorylation (Tyr-110) |  |  | 19033444
TRPV4 |  | SRC | In vivo PTM assay | Phosphorylation (Tyr-805) |  |  | 19033444
TRPV6 |  | SRC | In vitro PTM assay | Phosphorylation |  |  | 17197020
TRPV6 |  | SRC | In vivo PTM assay | Phosphorylation (Tyr-162) |  |  | 17197020
TRPV6 |  | SRC | In vivo PTM assay | Phosphorylation (Tyr-161) |  |  | 17197020

(: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Name Email Title* Comment* TRP
/ Interactor
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