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    TIAM2 TIAM Rac1 associated GEF 2 [ Homo sapiens (human) ]

    Gene ID: 26230, updated on 2-Nov-2024

    Summary

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    Official Symbol
    TIAM2provided by HGNC
    Official Full Name
    TIAM Rac1 associated GEF 2provided by HGNC
    Primary source
    HGNC:HGNC:11806
    See related
    Ensembl:ENSG00000146426 MIM:604709; AllianceGenome:HGNC:11806
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    STEF; TIAM-2
    Summary
    This gene encodes a guanine nucleotide exchange factor. A highly similar mouse protein specifically activates ras-related C3 botulinum substrate 1, converting this Rho-like guanosine triphosphatase (GTPase) from a guanosine diphosphate-bound inactive state to a guanosine triphosphate-bound active state. The encoded protein may play a role in neural cell development. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in testis (RPKM 5.7), brain (RPKM 4.1) and 18 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See TIAM2 in Genome Data Viewer
    Location:
    6q25.2-q25.3
    Exon count:
    30
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (154995315..155257723)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (156197278..156459744)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (155316449..155578857)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene SR-related CTD associated factor 8 Neighboring gene RNA, U6 small nuclear 824, pseudogene Neighboring gene MPRA-validated peak6235 silencer Neighboring gene Sharpr-MPRA regulatory region 2718 Neighboring gene microRNA 1273c Neighboring gene ReSE screen-validated silencer GRCh37_chr6:155259719-155259894 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:155272494-155272994 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:155287362-155288008 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25298 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25299 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:155316951-155317556 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:155316343-155316950 Neighboring gene lysophosphatidylcholine acyltransferase 3 pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:155340532-155341032 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:155434365-155434864 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:155440095-155440876 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:155440877-155441659 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr6:155448114-155449313 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:155450845-155451460 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_91096 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25302 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25300 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25301 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25303 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17702 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:155499148-155499350 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25304 Neighboring gene OCT4-H3K27ac hESC enhancer GRCh37_chr6:155506493-155507300 Neighboring gene OCT4-H3K27ac hESC enhancer GRCh37_chr6:155507301-155508106 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:155508589-155509092 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:155517063-155517562 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:155539515-155540016 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:155540017-155540516 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:155541579-155542078 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr6:155544888-155546087 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:155568469-155569164 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:155574917-155575491 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:155575492-155576065 Neighboring gene transcription factor B1, mitochondrial Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25305 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:155635711-155636701 Neighboring gene claudin 20 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25308 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25309 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:155748671-155749628 Neighboring gene NADPH oxidase 3

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Cloning and characterization of T-cell lymphoma invasion and metastasis 2 (TIAM2), a novel guanine nucleotide exchange factor related to TIAM1. Chiu CY, et al. Genomics, 1999 Oct 1. PMID 10512681
    2. Expression of T-cell lymphoma invasion and metastasis 2 (TIAM2) promotes proliferation and invasion of liver cancer. Chen JS, et al. Int J Cancer, 2012 Mar 15. PMID 21469146
    3. Elevated TIAM2 expression promotes tumor progression and is associated with unfavorable prognosis in pancreatic cancer. Jiang B, et al. Scand J Gastroenterol, 2021 Jan. PMID 33284659
    4. TIAM2 enhances non-small cell lung cancer cell invasion and motility. Zhao ZY, et al. Asian Pac J Cancer Prev, 2013. PMID 24377522
    5. Expression of stef, an activator of Rac1, correlates with the stages of neuronal morphological development in the mouse brain. Yoshizawa M, et al. Mech Dev, 2002 Apr. PMID 11900975

    See all (31) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Novel genetic markers for chronic kidney disease in a geographically isolated population of Indigenous Australians: Individual and multiple phenotype genome-wide association study.
      Title: Novel genetic markers for chronic kidney disease in a geographically isolated population of Indigenous Australians: Individual and multiple phenotype genome-wide association study.
    2. TIAM2S-positive microglia enhance inflammation and neurotoxicity through soluble ICAM-1-mediated immune priming.
      Title: TIAM2S-positive microglia enhance inflammation and neurotoxicity through soluble ICAM-1-mediated immune priming.
    3. FARP1, ARHGEF39, and TIAM2 are essential receptor tyrosine kinase effectors for Rac1-dependent cell motility in human lung adenocarcinoma.
      Title: FARP1, ARHGEF39, and TIAM2 are essential receptor tyrosine kinase effectors for Rac1-dependent cell motility in human lung adenocarcinoma.
    4. Elevated TIAM2 expression promotes tumor progression and is associated with unfavorable prognosis in pancreatic cancer.
      Title: Elevated TIAM2 expression promotes tumor progression and is associated with unfavorable prognosis in pancreatic cancer.
    5. The authors show that the Rac1 selective guanine nucleotide exchange factor Sif and TIAM1-like Exchange Factor STEF, also known as TIAM2, localises to the nuclear envelope, co-localises with key perinuclear proteins and regulates the activity of perinuclear Rac1.
      Title: STEF/TIAM2-mediated Rac1 activity at the nuclear envelope regulates the perinuclear actin cap.
    6. Tiam2/Rac are key components of EphB2 trans-endocytosis and are important for cell repulsion.
      Title: Tiam-Rac signaling mediates trans-endocytosis of ephrin receptor EphB2 and is important for cell repulsion.
    7. Results provide evidence that Sp1 positively controls TIAM2S transcription and that Sp1-mediated transcriptional activation is essential for TIAM2S ectopic expression in liver cancer cells.
      Title: Sp1-mediated ectopic expression of T-cell lymphoma invasion and metastasis 2 in hepatocellular carcinoma.
    8. Knockdown of TIAM2 could up-regulate the expression of E-cadherin.
      Title: TIAM2 enhances non-small cell lung cancer cell invasion and motility.
    9. TIAM2 expression was undetectable in normal human liver but was induced in all HCC cell lines and in 86% (78/91) of HCC biopsies.
      Title: Expression of T-cell lymphoma invasion and metastasis 2 (TIAM2) promotes proliferation and invasion of liver cancer.
    10. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    Submit: New GeneRIF Correction See all GeneRIFs (12)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of T-cell lymphoma invasion and metastasis 2 (TIAM2) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Potential readthrough

    Included gene: SCAF8

    Homology

    Clone Names

    • FLJ41865

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables GTPase activator activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables guanyl-nucleotide exchange factor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables guanyl-nucleotide exchange factor activity TAS
    Traceable Author Statement
    more info
    		  
    Process Evidence Code Pubs
    involved_in activation of GTPase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of axonogenesis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of small GTPase mediated signal transduction TAS
    Traceable Author Statement
    more info
    		  
    involved_in small GTPase-mediated signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in filopodium IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in growth cone IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in lamellipodium IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in perikaryon IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in synapse IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    rho guanine nucleotide exchange factor TIAM2
    Names
    SIF and TIAM1-like exchange factor
    T cell lymphoma invasion and metastasis 2
    T-lymphoma invasion and metastasis-inducing protein 2

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001010927.3 → NP_001010927.2  rho guanine nucleotide exchange factor TIAM2 isoform b

      Status: REVIEWED

      Source sequence(s)
      AL139101, AL355343, AL596202
      Consensus CDS
      CCDS34559.1
      UniProtKB/TrEMBL
      B7Z624
      Related
      ENSP00000275246.7, ENST00000275246.11
      Conserved Domains (2) summary
      smart00325
      Location:28 → 217
      RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases
      cd01255
      Location:219 → 391
      PH2_Tiam1_2; T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, C-terminal domain

    2. NM_001384546.1 → NP_001371475.1  rho guanine nucleotide exchange factor TIAM2 isoform a

      Status: REVIEWED

      Source sequence(s)
      AL136228, AL139101, AL355343, AL596202
      Consensus CDS
      CCDS34558.1
      UniProtKB/Swiss-Prot
      B2RP56, C9JZV2, Q6NXN9, Q6ZUP9, Q8IVF5, Q9UFG6, Q9UKV9, Q9UKW0
      UniProtKB/TrEMBL
      Q59EY7
      Related
      ENSP00000437188.2, ENST00000461783.7
      Conserved Domains (6) summary
      smart00325
      Location:1103 → 1292
      RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases
      cd00992
      Location:888 → 973
      PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...
      cd01230
      Location:505 → 631
      PH1_Tiam1_2; T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, N-terminal domain
      cd01255
      Location:1294 → 1466
      PH2_Tiam1_2; T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, C-terminal domain
      pfam18385
      Location:645 → 742
      Tiam_CC_Ex; T-lymphoma invasion and metastasis CC-Ex domain
      cl28922
      Location:811 → 881
      Ubiquitin_like_fold; Beta-grasp ubiquitin-like fold

    3. NM_001384547.1 → NP_001371476.1  rho guanine nucleotide exchange factor TIAM2 isoform a

      Status: REVIEWED

      Source sequence(s)
      AL139101, AL355343, AL596202
      Consensus CDS
      CCDS34558.1
      UniProtKB/Swiss-Prot
      B2RP56, C9JZV2, Q6NXN9, Q6ZUP9, Q8IVF5, Q9UFG6, Q9UKV9, Q9UKW0
      UniProtKB/TrEMBL
      Q59EY7
      Related
      ENSP00000353528.4, ENST00000360366.8
      Conserved Domains (6) summary
      smart00325
      Location:1103 → 1292
      RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases
      cd00992
      Location:888 → 973
      PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...
      cd01230
      Location:505 → 631
      PH1_Tiam1_2; T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, N-terminal domain
      cd01255
      Location:1294 → 1466
      PH2_Tiam1_2; T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, C-terminal domain
      pfam18385
      Location:645 → 742
      Tiam_CC_Ex; T-lymphoma invasion and metastasis CC-Ex domain
      cl28922
      Location:811 → 881
      Ubiquitin_like_fold; Beta-grasp ubiquitin-like fold

    4. NM_012454.4 → NP_036586.3  rho guanine nucleotide exchange factor TIAM2 isoform a

      Status: REVIEWED

      Source sequence(s)
      AL136228, AL139101, AL355343, AL596202
      Consensus CDS
      CCDS34558.1
      UniProtKB/Swiss-Prot
      B2RP56, C9JZV2, Q6NXN9, Q6ZUP9, Q8IVF5, Q9UFG6, Q9UKV9, Q9UKW0
      UniProtKB/TrEMBL
      Q59EY7
      Related
      ENSP00000507157.1, ENST00000682666.1
      Conserved Domains (6) summary
      smart00325
      Location:1103 → 1292
      RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases
      cd00992
      Location:888 → 973
      PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...
      cd01230
      Location:505 → 631
      PH1_Tiam1_2; T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, N-terminal domain
      cd01255
      Location:1294 → 1466
      PH2_Tiam1_2; T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, C-terminal domain
      pfam18385
      Location:645 → 742
      Tiam_CC_Ex; T-lymphoma invasion and metastasis CC-Ex domain
      cl28922
      Location:811 → 881
      Ubiquitin_like_fold; Beta-grasp ubiquitin-like fold

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      154995315..155257723
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      156197278..156459744
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8IVF5.4 GenPept UniProtKB/Swiss-Prot:Q8IVF5

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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