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    Tcf4 transcription factor 4 [ Rattus norvegicus (Norway rat) ]

    Gene ID: 84382, updated on 13-Apr-2024

    Summary

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    Official Symbol
    Tcf4provided by RGD
    Official Full Name
    transcription factor 4provided by RGD
    Primary source
    RGD:69271
    See related
    Ensembl:ENSRNOG00000012405 AllianceGenome:RGD:69271
    Gene type
    protein coding
    RefSeq status
    PROVISIONAL
    Organism
    Rattus norvegicus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
    Summary
    Enables bHLH transcription factor binding activity and double-stranded DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Predicted to be located in chromatin and nucleus. Predicted to be part of beta-catenin-TCF7L2 complex. Human ortholog(s) of this gene implicated in Fuchs' endothelial dystrophy and Pitt-Hopkins syndrome. Orthologous to human TCF4 (transcription factor 4). [provided by Alliance of Genome Resources, Apr 2022]
    Expression
    Biased expression in Heart (RPKM 220.1), Brain (RPKM 214.5) and 9 other tissues See more
    Orthologs
    human mouse all
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    Genomic context

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    Location:
    18q12.1
    Exon count:
    29
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCr8 (GCF_036323735.1) 18 NC_086036.1 (65216840..65563186)
    RS_2023_06 previous assembly mRatBN7.2 (GCF_015227675.2) 18 NC_051353.1 (62941739..63288126)
    106 previous assembly Rnor_6.0 (GCF_000001895.5) 18 NC_005117.4 (65285320..65507983)

    Chromosome 18 - NC_086036.1Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC108348808 Neighboring gene uncharacterized LOC108348809 Neighboring gene uncharacterized LOC134482985 Neighboring gene coiled-coil domain containing 68

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
    • Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
    • BioProject: PRJNA238328
    • Publication: PMID 24510058
    • Analysis date: Mon Jun 6 17:44:12 2016

    Bibliography

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    Related articles in PubMed

    1. Upregulation of transcription factor 4 downregulates Na(V)1.8 expression in DRG neurons and prevents the development of rat inflammatory and neuropathic hypersensitivity. Li N, et al. Exp Neurol, 2020 May. PMID 32045596
    2. The Intellectual Disability and Schizophrenia Associated Transcription Factor TCF4 Is Regulated by Neuronal Activity and Protein Kinase A. Sepp M, et al. J Neurosci, 2017 Oct 25. PMID 28951451, Free PMC Article
    3. T-cell factor (TCF/LEF1) binding elements (TBEs) of FasL (Fas ligand or CD95 ligand) bind and cluster Fas (CD95) and form complexes with the TCF-4 and b-catenin transcription factors in vitro and in vivo which result in triggering cell death and/or cell activation. Liu X, et al. Cell Mol Neurobiol, 2016 Aug. PMID 27090258
    4. TCF4 Mediates the Maintenance of Neuropathic Pain Through Wnt/β-Catenin Signaling Following Peripheral Nerve Injury in Rats. Xu Z, et al. J Mol Neurosci, 2015 Jun. PMID 25963533
    5. Role of the basic helix-loop-helix protein ITF2 in the hormonal regulation of Sertoli cell differentiation. Muir T, et al. Mol Reprod Dev, 2006 Apr. PMID 16425294

    See all (32) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Functional consequences of TCF4 missense substitutions associated with Pitt-Hopkins syndrome, mild intellectual disability, and schizophrenia.
      Title: Functional consequences of TCF4 missense substitutions associated with Pitt-Hopkins syndrome, mild intellectual disability, and schizophrenia.
    2. Upregulation of transcription factor 4 downregulates NaV1.8 expression in DRG neurons and prevents the development of rat inflammatory and neuropathic hypersensitivity.
      Title: Upregulation of transcription factor 4 downregulates Na(V)1.8 expression in DRG neurons and prevents the development of rat inflammatory and neuropathic hypersensitivity.
    3. TCF4-controlled transcription in primary cortical neurons is induced by neuronal activity and protein kinase A.
      Title: The Intellectual Disability and Schizophrenia Associated Transcription Factor TCF4 Is Regulated by Neuronal Activity and Protein Kinase A.
    4. TCF4 might promote neuronal apoptosis and microglial proliferation after traumatic brain injury
      Title: T-cell factor (TCF/LEF1) binding elements (TBEs) of FasL (Fas ligand or CD95 ligand) bind and cluster Fas (CD95) and form complexes with the TCF-4 and b-catenin transcription factors in vitro and in vivo which result in triggering cell death and/or cell activation.
    5. expression of Prx1 and Tcf4 is decreased in the developing diaphragm in the nitrofen-induced congenital diaphragmatic hernia in Sprague- Dawley rats animal model.
      Title: Expression of Prx1 and Tcf4 is decreased in the diaphragmatic muscle connective tissue of nitrofen-induced congenital diaphragmatic hernia.
    6. TCF4 is a regulator of neuronal intrinsic excitability in part by repression of Kcnq1 and Scn10a.
      Title: Psychiatric Risk Gene Transcription Factor 4 Regulates Intrinsic Excitability of Prefrontal Neurons via Repression of SCN10a and KCNQ1.
    7. Chronic constriction injury induced persistent TCF4 upregulation in the dorsal root ganglion and spinal cord.
      Title: TCF4 Mediates the Maintenance of Neuropathic Pain Through Wnt/β-Catenin Signaling Following Peripheral Nerve Injury in Rats.
    8. ITF2/Tcf4 enhances follicle-stimulating hormone activity by suppressing the actions of the inhibitors of differentiation (ID)transcription factor proteins and increasing the actions of stimulatory basic helix-loop-helix proteins in Sertoli cells.
      Title: Role of the basic helix-loop-helix protein ITF2 in the hormonal regulation of Sertoli cell differentiation.
    Submit: New GeneRIF Correction

    Pathways from PubChem

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    General gene information

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    Markers

    Homology

    Gene Ontology Provided by RGD

    Function Evidence Code Pubs
    enables DNA binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables DNA-binding transcription activator activity, RNA polymerase II-specific ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables DNA-binding transcription factor activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables DNA-binding transcription factor activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables DNA-binding transcription factor activity, RNA polymerase II-specific IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables DNA-binding transcription factor activity, RNA polymerase II-specific ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables E-box binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables E-box binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables RNA polymerase II cis-regulatory region sequence-specific DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables RNA polymerase II cis-regulatory region sequence-specific DNA binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables RNA polymerase II transcription regulatory region sequence-specific DNA binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables TFIIB-class transcription factor binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables bHLH transcription factor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables beta-catenin binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables chromatin binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables double-stranded DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables identical protein binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables protein dimerization activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein heterodimerization activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables protein heterodimerization activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables sequence-specific double-stranded DNA binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables transcription corepressor activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    Process Evidence Code Pubs
    acts_upstream_of_or_within endothelial cell activation ISO
    Inferred from Sequence Orthology
    more info
    		  
    acts_upstream_of_or_within negative regulation of angiogenesis ISO
    Inferred from Sequence Orthology
    more info
    		  
    acts_upstream_of_or_within negative regulation of gene expression ISO
    Inferred from Sequence Orthology
    more info
    		  
    acts_upstream_of_or_within negative regulation of transcription by RNA polymerase II ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in positive regulation of DNA-templated transcription ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in positive regulation of neuron differentiation ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in positive regulation of neuron differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of transcription by RNA polymerase II ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in protein-DNA complex assembly ISO
    Inferred from Sequence Orthology
    more info
    		  
    acts_upstream_of_or_within regulation of DNA-templated transcription ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in regulation of transcription by RNA polymerase II IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    acts_upstream_of_or_within regulation of vascular endothelial growth factor signaling pathway ISO
    Inferred from Sequence Orthology
    more info
    		  
    Component Evidence Code Pubs
    part_of beta-catenin-TCF complex ISO
    Inferred from Sequence Orthology
    more info
    		  
    part_of beta-catenin-TCF7L2 complex ISO
    Inferred from Sequence Orthology
    more info
    		  
    part_of chromatin IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of chromatin ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in nucleus IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in nucleus ISO
    Inferred from Sequence Orthology
    more info
    		  
    part_of transcription regulator complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of transcription regulator complex ISO
    Inferred from Sequence Orthology
    more info
    		  

    General protein information

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    Preferred Names
    transcription factor 4
    Names
    ITF-2
    R8f DNA-binding protein
    RITF-2
    SEF-2
    SL3-3 enhancer factor 2
    TCF-4
    immunoglobulin transcription factor 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_053369.2 → NP_445821.2  transcription factor 4

      Status: PROVISIONAL

      Source sequence(s)
      JAXUCZ010000018
      UniProtKB/TrEMBL
      A0A0G2JWU7
      Related
      ENSRNOP00000070021.2, ENSRNOT00000081797.2
      Conserved Domains (2) summary
      COG5422
      Location:81 → 295
      ROM1; RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms]
      cd18945
      Location:555 → 639
      bHLH_E-protein_TCF4_E2-2; basic helix-loop-helix (bHLH) domain found in transcription factor 4 (TCF-4) and similar proteins

    RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

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

    Reference GRCr8

    Genomic

    1. NC_086036.1 Reference GRCr8

      Range
      65216840..65563186
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_063277625.1 → XP_063133695.1  transcription factor 4 isoform X13

    2. XM_063277624.1 → XP_063133694.1  transcription factor 4 isoform X12

    3. XM_039097159.2 → XP_038953087.1  transcription factor 4 isoform X1

      UniProtKB/TrEMBL
      A0A0G2JWU7, A6IXY6, F1LQ90
      Conserved Domains (2) summary
      COG5422
      Location:135 → 296
      ROM1; RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms]
      cd18945
      Location:560 → 644
      bHLH_E-protein_TCF4_E2-2; basic helix-loop-helix (bHLH) domain found in transcription factor 4 (TCF-4) and similar proteins

    4. XM_039097169.2 → XP_038953097.1  transcription factor 4 isoform X10

      UniProtKB/Swiss-Prot
      Q62655, Q99N33
      UniProtKB/TrEMBL
      A6IXY7
      Conserved Domains (2) summary
      COG5422
      Location:111 → 272
      ROM1; RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms]
      cd18945
      Location:536 → 620
      bHLH_E-protein_TCF4_E2-2; basic helix-loop-helix (bHLH) domain found in transcription factor 4 (TCF-4) and similar proteins

    5. XM_063277623.1 → XP_063133693.1  transcription factor 4 isoform X11

    6. XM_063277626.1 → XP_063133696.1  transcription factor 4 isoform X14

    7. XM_039097157.2 → XP_038953085.1  transcription factor 4 isoform X1

      UniProtKB/TrEMBL
      A0A0G2JWU7, A6IXY6, F1LQ90
      Conserved Domains (2) summary
      COG5422
      Location:135 → 296
      ROM1; RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms]
      cd18945
      Location:560 → 644
      bHLH_E-protein_TCF4_E2-2; basic helix-loop-helix (bHLH) domain found in transcription factor 4 (TCF-4) and similar proteins

    8. XM_063277622.1 → XP_063133692.1  transcription factor 4 isoform X10

      UniProtKB/TrEMBL
      A6IXY7

    9. XM_063277621.1 → XP_063133691.1  transcription factor 4 isoform X9

    10. XM_063277618.1 → XP_063133688.1  transcription factor 4 isoform X6

    11. XM_063277617.1 → XP_063133687.1  transcription factor 4 isoform X5

    12. XM_063277615.1 → XP_063133685.1  transcription factor 4 isoform X3

    13. XM_063277616.1 → XP_063133686.1  transcription factor 4 isoform X4

    14. XM_063277620.1 → XP_063133690.1  transcription factor 4 isoform X8

    15. XM_039097158.2 → XP_038953086.1  transcription factor 4 isoform X1

      UniProtKB/TrEMBL
      A0A0G2JWU7, A6IXY6, F1LQ90
      Conserved Domains (2) summary
      COG5422
      Location:135 → 296
      ROM1; RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms]
      cd18945
      Location:560 → 644
      bHLH_E-protein_TCF4_E2-2; basic helix-loop-helix (bHLH) domain found in transcription factor 4 (TCF-4) and similar proteins

    16. XM_063277619.1 → XP_063133689.1  transcription factor 4 isoform X7

    17. XM_063277614.1 → XP_063133684.1  transcription factor 4 isoform X2

    18. XM_039097170.2 → XP_038953098.1  transcription factor 4 isoform X10

      UniProtKB/Swiss-Prot
      Q62655, Q99N33
      UniProtKB/TrEMBL
      A6IXY7
      Conserved Domains (2) summary
      COG5422
      Location:111 → 272
      ROM1; RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms]
      cd18945
      Location:536 → 620
      bHLH_E-protein_TCF4_E2-2; basic helix-loop-helix (bHLH) domain found in transcription factor 4 (TCF-4) and similar proteins

    19. XM_039097160.2 → XP_038953088.1  transcription factor 4 isoform X1

      UniProtKB/TrEMBL
      A0A0G2JWU7, A6IXY6, F1LQ90
      Related
      ENSRNOP00000020431.8
      Conserved Domains (2) summary
      COG5422
      Location:135 → 296
      ROM1; RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms]
      cd18945
      Location:560 → 644
      bHLH_E-protein_TCF4_E2-2; basic helix-loop-helix (bHLH) domain found in transcription factor 4 (TCF-4) and similar proteins

    20. XM_039097177.2 → XP_038953105.2  transcription factor 4 isoform X19

      UniProtKB/TrEMBL
      A6IXY8

    21. XM_039097173.2 → XP_038953101.1  transcription factor 4 isoform X15

      UniProtKB/Swiss-Prot
      Q62655, Q99N33
      Conserved Domains (2) summary
      COG5422
      Location:65 → 226
      ROM1; RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms]
      cd18945
      Location:490 → 574
      bHLH_E-protein_TCF4_E2-2; basic helix-loop-helix (bHLH) domain found in transcription factor 4 (TCF-4) and similar proteins

    22. XM_063277627.1 → XP_063133697.1  transcription factor 4 isoform X17

    23. XM_039097174.2 → XP_038953102.1  transcription factor 4 isoform X16

      UniProtKB/Swiss-Prot
      Q62655, Q99N33
      Conserved Domains (2) summary
      COG5422
      Location:64 → 225
      ROM1; RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms]
      cd18945
      Location:489 → 573
      bHLH_E-protein_TCF4_E2-2; basic helix-loop-helix (bHLH) domain found in transcription factor 4 (TCF-4) and similar proteins

    24. XM_039097176.2 → XP_038953104.1  transcription factor 4 isoform X18

      UniProtKB/Swiss-Prot
      Q62655, Q99N33
      Conserved Domains (2) summary
      COG5422
      Location:64 → 225
      ROM1; RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms]
      cd18945
      Location:485 → 569
      bHLH_E-protein_TCF4_E2-2; basic helix-loop-helix (bHLH) domain found in transcription factor 4 (TCF-4) and similar proteins

    25. XM_063277628.1 → XP_063133698.1  transcription factor 4 isoform X20

    26. XM_039097184.2 → XP_038953112.1  transcription factor 4 isoform X19

      UniProtKB/TrEMBL
      A0A0G2JXN5, A6IXY8
      Conserved Domains (2) summary
      COG5422
      Location:6 → 167
      ROM1; RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms]
      cd18945
      Location:431 → 515
      bHLH_E-protein_TCF4_E2-2; basic helix-loop-helix (bHLH) domain found in transcription factor 4 (TCF-4) and similar proteins

    27. XM_039097185.2 → XP_038953113.1  transcription factor 4 isoform X19

      UniProtKB/TrEMBL
      A0A0G2JXN5, A6IXY8
      Related
      ENSRNOP00000070343.2
      Conserved Domains (2) summary
      COG5422
      Location:6 → 167
      ROM1; RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms]
      cd18945
      Location:431 → 515
      bHLH_E-protein_TCF4_E2-2; basic helix-loop-helix (bHLH) domain found in transcription factor 4 (TCF-4) and similar proteins

    28. XM_063277629.1 → XP_063133699.1  transcription factor 4 isoform X20

    29. XM_039097186.2 → XP_038953114.1  transcription factor 4 isoform X21

      UniProtKB/TrEMBL
      A0A8I6A561, A0A8I6GLJ0, A6IXY9
      Related
      ENSRNOP00000096285.1
      Conserved Domains (1) summary
      cd18945
      Location:401 → 485
      bHLH_E-protein_TCF4_E2-2; basic helix-loop-helix (bHLH) domain found in transcription factor 4 (TCF-4) and similar proteins

    30. XM_039097189.2 → XP_038953117.1  transcription factor 4 isoform X24

      UniProtKB/TrEMBL
      A0A8I6A561
      Related
      ENSRNOP00000087117.1
      Conserved Domains (1) summary
      cd18945
      Location:397 → 481
      bHLH_E-protein_TCF4_E2-2; basic helix-loop-helix (bHLH) domain found in transcription factor 4 (TCF-4) and similar proteins

    31. XM_039097187.2 → XP_038953115.1  transcription factor 4 isoform X23

      UniProtKB/TrEMBL
      A0A8I6A561
      Conserved Domains (1) summary
      cd18945
      Location:400 → 484
      bHLH_E-protein_TCF4_E2-2; basic helix-loop-helix (bHLH) domain found in transcription factor 4 (TCF-4) and similar proteins

    32. XM_063277630.1 → XP_063133700.1  transcription factor 4 isoform X25

    33. XM_039097188.2 → XP_038953116.1  transcription factor 4 isoform X22

      UniProtKB/TrEMBL
      A0A8I6A561
      Conserved Domains (1) summary
      cd18945
      Location:400 → 484
      bHLH_E-protein_TCF4_E2-2; basic helix-loop-helix (bHLH) domain found in transcription factor 4 (TCF-4) and similar proteins

    34. XM_039097190.2 → XP_038953118.1  transcription factor 4 isoform X26

      UniProtKB/TrEMBL
      A0A8I6A561
      Conserved Domains (1) summary
      cd18945
      Location:396 → 480
      bHLH_E-protein_TCF4_E2-2; basic helix-loop-helix (bHLH) domain found in transcription factor 4 (TCF-4) and similar proteins

    35. XM_063277631.1 → XP_063133701.1  transcription factor 4 isoform X27

    36. XM_039097191.2 → XP_038953119.1  transcription factor 4 isoform X28

      UniProtKB/TrEMBL
      A0A8I6A561
      Conserved Domains (1) summary
      cd18945
      Location:345 → 429
      bHLH_E-protein_TCF4_E2-2; basic helix-loop-helix (bHLH) domain found in transcription factor 4 (TCF-4) and similar proteins
    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q62655.2 GenPept UniProtKB/Swiss-Prot:Q62655

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