Tbio TIAM1 T-lymphoma invasion and metastasis-inducing protein 1

Protein Summary

Description

Modulates the activity of RHO-like proteins and connects extracellular signals to cytoskeletal activities. Acts as a GDP-dissociation stimulator protein that stimulates the GDP-GTP exchange activity of RHO-like GTPases and activates them. Activates RAC1, CDC42, and to a lesser extent RHOA. Required for normal cell adhesion and cell migration. This gene encodes a RAC1-specific guanine nucleotide exchange factor (GEF). GEFs mediate the exchange of guanosine diphosphate (GDP) for guanosine triphosphate (GTP). The binding of GTP induces a conformational change in RAC1 that allows downstream effectors to bind and transduce a signal. This gene thus regulates RAC1 signaling pathways that affect cell shape, migration, adhesion, growth, survival, and polarity, as well as influencing actin cytoskeletal formation, endocytosis, and membrane trafficking. This gene thus plays an important role in cell invasion, metastasis, and carcinogenesis. In addition to RAC1, the encoded protein activates additional Rho-like GTPases such as CDC42, RAC2, RAC3 and RHOA. This gene encodes multiple protein isoforms that experience a diverse array of intramolecular, protein-protein, and phosphorylation interactions as well as phosphoinositide binding. Both the longer and shorter isoforms have C-terminal Dbl homology (DH) and pleckstrin homology (PH) domains while only the longer isoforms of this gene have the N-terminal myristoylation site and the downstream N-terminal PH domain, ras-binding domain (RBD), and PSD-95/DlgA/ZO-1 (PDZ) domain. [provided by RefSeq, Jul 2017]

Uniprot Accession IDs

• Q13009
• B7ZLR6
• F5GZ53
• Q17RT7
• TIAM-1

Gene Name

• TIAM1

Ensembl ID

• ENST00000286827
• ENSP00000286827
• ENSG00000156299
• ENST00000541036
• ENSP00000441570

Symbol

• TIAM-1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
trait	0.86
protein domain	0.85
hub protein	0.79
microRNA	0.78
PubMedID	0.74

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 255.06   (req: < 5)

Gene RIFs: 107   (req: <= 3)

Antibodies: 192   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 255.06   (req: >= 5)

Gene RIFs: 107   (req: > 3)

Antibodies: 192   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 37

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

GWAS Traits (1)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
amyotrophic lateral sclerosis	EFO_0000253	1	1	0	2	46.6

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
amyotrophic lateral sclerosis	EFO_0000253	0	2	46.6

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Orthologs (9)

1 – 5 of 9

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	T cell lymphoma invasion and metastasis 1	VGNC:1118	473949
Macaque	T-cell lymphoma invasion and metastasis 1		702288
Mouse	T cell lymphoma invasion and metastasis 1	MGI:103306	21844
Rat	T-cell lymphoma invasion and metastasis 1	RGD:1307455	304109
Dog	T-cell lymphoma invasion and metastasis 1		487731

Species	Name	OMA	EggNOG	Inparanoid
Chimp	T cell lymphoma invasion and metastasis 1
Macaque	T-cell lymphoma invasion and metastasis 1
Mouse	T cell lymphoma invasion and metastasis 1
Rat	T-cell lymphoma invasion and metastasis 1
Dog	T-cell lymphoma invasion and metastasis 1

Protein Structure (10 Structures, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-Q13009-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 5 of 10

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (48)

Reactome (19)

KEGG (7)

PathwayCommons (10)

WikiPathways (12)

Activated NTRK2 signals through CDK5 (R-HSA-9032845)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Activated NTRK2 signals through CDK5	6 targets	R-HSA-9032845
Reactome	Axon guidance	533 targets	R-HSA-422475
Reactome	Cell death signalling via NRAGE, NRIF and NADE	76 targets	R-HSA-204998
Reactome	Death Receptor Signalling	141 targets	R-HSA-73887
Reactome	Developmental Biology	1055 targets	R-HSA-1266738

Name	Explore in Pharos	Explore in Source
Activated NTRK2 signals through CDK5	6 targets	R-HSA-9032845
Axon guidance	533 targets	R-HSA-422475
Cell death signalling via NRAGE, NRIF and NADE	76 targets	R-HSA-204998
Death Receptor Signalling	141 targets	R-HSA-73887
Developmental Biology	1055 targets	R-HSA-1266738

Gene Ontology Terms (51)

Functions (7)

Components (14)

Processes (30)

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1 – 7 of 7

GO Term	Evidence	Assigned by
guanyl-nucleotide exchange factor activity	Inferred from Experiment (EXP)	Reactome
Rac guanyl-nucleotide exchange factor activity	Inferred from Direct Assay (IDA)	ParkinsonsUK-UCL
kinase binding	Inferred from Physical Interaction (IPI)	ParkinsonsUK-UCL
Rho guanyl-nucleotide exchange factor activity	Traceable Author Statement (TAS)	Reactome
lipid binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
microtubule binding	Inferred from Electronic Annotation (IEA)	Ensembl
receptor tyrosine kinase binding	Inferred from Electronic Annotation (IEA)	Ensembl

Protein-Protein Interactions (168)

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1 – 10 of 168

• See Interactions on String-DB

ABTB2

Tdark

Novelty: 0.45729157

p_int: 0.979304102

p_ni: 0.001386283

p_wrong: 0.019309614

Data Source: BioPlex

EPHB2

Tchem

Family: Kinase

Novelty: 0.00211785

Score: 0.991

Data Source: STRINGDB

CDC42

Tchem

Family: Enzyme

Novelty: 0.00032619

Score: 0.987

Data Source: STRINGDB

RAC1

Tbio

Family: Enzyme

Novelty: 0.00365325

Score: 0.985

Data Source: Reactome,STRINGDB

RHOA

Tbio

Family: Enzyme

Novelty: 0.00022204

Score: 0.98

Data Source: STRINGDB

NME1

Tbio

Family: Kinase

Novelty: 0.00103216

Score: 0.977

Data Source: STRINGDB

RAC2

Tbio

Family: Enzyme

Novelty: 0.00116234

Score: 0.973

Data Source: STRINGDB

NTRK2

Tclin

Family: Kinase

Novelty: 0.00054534

Score: 0.973

Data Source: Reactome,STRINGDB

RHOC

Tbio

Family: Enzyme

Novelty: 0.00262213

Score: 0.972

Data Source: STRINGDB

HRAS

Tchem

Family: Enzyme

Novelty: 0.00008069

Score: 0.97

Data Source: STRINGDB

Publication Statistics

PubMed Score  255.06

PubMed score by year

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PubTator Score  166.8

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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UniProt Keyword Find Similar Targets

3D-structure
Alternative splicing
Cell junction
Cell membrane
Complete proteome
Guanine-nucleotide releasing factor
Lipid-binding
Lipoprotein
Membrane
Myristate

GWAS Trait Find Similar Targets

amyotrophic lateral sclerosis

MGI Phenotype Find Similar Targets

behavior/neurological phenotype
cellular phenotype
homeostasis/metabolism phenotype
neoplasm
nervous system phenotype