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RAPGEF1 Rap guanine nucleotide exchange factor 1 [ Homo sapiens (human) ]

Gene ID: 2889, updated on 2-Aug-2021

Summary

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Official Symbol
RAPGEF1provided by HGNC
Official Full Name
Rap guanine nucleotide exchange factor 1provided by HGNC
Primary source
HGNC:HGNC:4568
See related
Ensembl:ENSG00000107263 MIM:600303
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
C3G; GRF2
Summary
This gene encodes a human guanine nucleotide exchange factor. It transduces signals from CRK by binding the SH3 domain of CRK, and activating several members of the Ras family of GTPases. This signaling cascade that may be involved in apoptosis, integrin-mediated signal transduction, and cell transformation. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some variants has not been determined. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in placenta (RPKM 13.7), lymph node (RPKM 12.3) and 25 other tissues See more
Orthologs
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Genomic context

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See RAPGEF1 in Genome Data Viewer
Location:
9q34.13
Exon count:
37
Annotation release Status Assembly Chr Location
109.20210514 current GRCh38.p13 (GCF_000001405.39) 9 NC_000009.12 (131576770..131740076, complement)
105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (134452162..134615463, complement)

Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene protein O-mannosyltransferase 1 Neighboring gene uridine-cytidine kinase 1 Neighboring gene proline rich transmembrane protein 1B Neighboring gene Sharpr-MPRA regulatory region 10461 Neighboring gene Sharpr-MPRA regulatory region 12258 Neighboring gene Sharpr-MPRA regulatory region 10210 Neighboring gene RNA, 7SL, cytoplasmic 328, pseudogene Neighboring gene eukaryotic translation initiation factor 4A1 pseudogene 3 Neighboring gene mediator complex subunit 27

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
  • 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. C3G, through its GEF activity, induces megakaryocytic differentiation and proplatelet formation. Ortiz-Rivero S, et al. Cell Commun Signal, 2018 Dec 19. PMID 30567575, Free PMC Article
  2. C3G knock-down enhances migration and invasion by increasing Rap1-mediated p38α activation, while it impairs tumor growth through p38α-independent mechanisms. Priego N, et al. Oncotarget, 2016 Jul 19. PMID 27286263, Free PMC Article
  3. Frequent somatic demethylation of RAPGEF1/C3G intronic sequences in gastrointestinal and gynecological cancer. Samuelsson J, et al. Int J Oncol, 2011 Jun. PMID 21399874
  4. Cytoskeletal remodeling by C3G to induce neurite-like extensions and inhibit motility in highly invasive breast carcinoma cells. Dayma K, et al. Biochim Biophys Acta, 2011 Mar. PMID 21223981
  5. RAPGEF1 gene variants associated with type 2 diabetes in the Korean population. Hong KW, et al. Diabetes Res Clin Pract, 2009 May. PMID 19297053

See all (94) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. C3G localizes to the mother centriole in a cenexin-dependent manner and regulates centrosome duplication and primary cilium length.
    Title: C3G localizes to the mother centriole in a cenexin-dependent manner and regulates centrosome duplication and primary cilium length.
  2. C3G plays a significant role in different steps of megakaryopoiesis
    Title: C3G, through its GEF activity, induces megakaryocytic differentiation and proplatelet formation.
  3. our studies uncover novel mechanisms by which C3G controls key aspects of tumorigenesis.
    Title: C3G knock-down enhances migration and invasion by increasing Rap1-mediated p38α activation, while it impairs tumor growth through p38α-independent mechanisms.
  4. C3G/RAP1 activity is involved in the metastatic spread of epithelial ovarian cancer.
    Title: The C3G/Rap1 pathway promotes secretion of MMP-2 and MMP-9 and is involved in serous ovarian cancer metastasis.
  5. C3G plays an important role in platelet clotting through a mechanism involving its GEF activity and suggest that it might be also involved in neutrophil development.
    Title: C3G transgenic mouse models with specific expression in platelets reveal a new role for C3G in platelet clotting through its GEF activity.
  6. The possibility of cellular phospho-C3G (pC3G) being a substrate of the intracellular T-cell protein tyrosine phosphatase TC-PTP (PTPN2) using the human neuroblastoma cell line, was studied.
    Title: TC-PTP dephosphorylates the guanine nucleotide exchange factor C3G (RapGEF1) and negatively regulates differentiation of human neuroblastoma cells.
  7. Lyn controls spatial activation of Rap1 by recruiting the CrkL-C3G protein complex to the leading edge
    Title: The non-receptor tyrosine kinase Lyn controls neutrophil adhesion by recruiting the CrkL-C3G complex and activating Rap1 at the leading edge.
  8. found somatic demethylation of a relaxed-criterion CpG island (CGI-B) located in the first intron of RAPGEF1 in 40% of colon cancers and 8% of gastric cancers relative to their matching normal tissues that were always methylated
    Title: Frequent somatic demethylation of RAPGEF1/C3G intronic sequences in gastrointestinal and gynecological cancer.
  9. Data demonstrated that the polymorphism in TP53 (rs1042522) was associated with type 2 diabetes, and that potential interaction of TP53 (rs1042522) and RAPGEF1 (rs11243444), or NRF1 (rs1882095) increased the risk of type 2 diabetes.
    Title: Association between polymorphisms in RAPGEF1, TP53, NRF1 and type 2 diabetes in Chinese Han population.
  10. significant positive correlation between layers II and IV of the dorso-lateral prefrontal cortex in the percentage of MR-GEF expressing neurons in individuals with bipolar disorder
    Title: Expression of the Rap1 guanine nucleotide exchange factor, MR-GEF, is altered in individuals with bipolar disorder.
Submit: New GeneRIF Correction See all GeneRIFs (27)

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 Rap guanine nucleotide exchange factor 1 (RAPGEF1) 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

Homology

Clone Names

  • DKFZp781P1719

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables SH3 domain binding IEA
Inferred from Electronic Annotation
more info
  
enables guanyl-nucleotide exchange factor activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables guanyl-nucleotide exchange factor activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables guanyl-nucleotide exchange factor activity TAS
Traceable Author Statement
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in Rap protein signal transduction IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cellular response to cAMP IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cellular response to nerve growth factor stimulus IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in establishment of endothelial barrier IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in nerve growth factor signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in nervous system development IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of GTPase activity IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of GTPase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of neuron projection development IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of cell junction assembly IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in signal transduction NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in transmembrane receptor protein tyrosine kinase signaling pathway TAS
Traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in early endosome IDA
Inferred from Direct Assay
more info
 PubMed 
located_in intracellular membrane-bounded organelle IDA
Inferred from Direct Assay
more info
  

General protein information

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Preferred Names
rap guanine nucleotide exchange factor 1
Names
CRK SH3-binding GNRP
Rap guanine nucleotide exchange factor (GEF) 1
guanine nucleotide-releasing factor 2 (specific for crk proto-oncogene)

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.

Genomic

  1. NG_050622.1 RefSeqGene

    Range
    5001..168175
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001304275.2 → NP_001291204.1  rap guanine nucleotide exchange factor 1 isoform c

    See identical proteins and their annotated locations for NP_001291204.1

    Status: REVIEWED

    Source sequence(s)
    AL160271, AL160276
    Consensus CDS
    CCDS78450.1
    UniProtKB/Swiss-Prot
    Q13905
    Related
    ENSP00000361269.1, ENST00000372195.5
    Conserved Domains (2) summary
    smart00147
    Location:853 → 1082
    RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
    smart00229
    Location:705 → 846
    RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif

  2. NM_001377935.1 → NP_001364864.1  rap guanine nucleotide exchange factor 1 isoform d

    Status: REVIEWED

    Source sequence(s)
    AL160271, AL160276
    Related
    ENSP00000508246.1, ENST00000683357.1
    Conserved Domains (3) summary
    smart00147
    Location:1022 → 1251
    RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
    smart00229
    Location:874 → 1015
    RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif
    PHA03247
    Location:227 → 824
    PHA03247; large tegument protein UL36; Provisional

  3. NM_001377936.1 → NP_001364865.1  rap guanine nucleotide exchange factor 1 isoform e

    Status: REVIEWED

    Source sequence(s)
    AL160276
    Conserved Domains (3) summary
    smart00147
    Location:835 → 1064
    RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
    smart00229
    Location:687 → 828
    RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif
    PHA03247
    Location:179 → 437
    PHA03247; large tegument protein UL36; Provisional

  4. NM_001377937.1 → NP_001364866.1  rap guanine nucleotide exchange factor 1 isoform f

    Status: REVIEWED

    Source sequence(s)
    AL160271, AL160276
    Conserved Domains (3) summary
    smart00147
    Location:815 → 1044
    RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
    smart00229
    Location:667 → 808
    RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif
    PHA03247
    Location:190 → 448
    PHA03247; large tegument protein UL36; Provisional

  5. NM_001377938.1 → NP_001364867.1  rap guanine nucleotide exchange factor 1 isoform g

    Status: REVIEWED

    Source sequence(s)
    AL160271, AL160276
    Conserved Domains (4) summary
    smart00147
    Location:985 → 1214
    RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
    smart00229
    Location:837 → 978
    RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif
    PHA03247
    Location:190 → 448
    PHA03247; large tegument protein UL36; Provisional
    PHA03307
    Location:675 → 846
    PHA03307; transcriptional regulator ICP4; Provisional

  6. NM_005312.4 → NP_005303.2  rap guanine nucleotide exchange factor 1 isoform a

    See identical proteins and their annotated locations for NP_005303.2

    Status: REVIEWED

    Source sequence(s)
    AL160271, AL160276
    Consensus CDS
    CCDS48047.1
    UniProtKB/Swiss-Prot
    Q13905
    Related
    ENSP00000361263.2, ENST00000372189.7
    Conserved Domains (2) summary
    smart00147
    Location:836 → 1065
    RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
    smart00229
    Location:688 → 829
    RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif

  7. NM_198679.2 → NP_941372.1  rap guanine nucleotide exchange factor 1 isoform b

    See identical proteins and their annotated locations for NP_941372.1

    Status: REVIEWED

    Source sequence(s)
    AL160271, AL160276
    Consensus CDS
    CCDS48048.1
    UniProtKB/Swiss-Prot
    Q13905
    Related
    ENSP00000361264.3, ENST00000372190.7
    Conserved Domains (2) summary
    smart00147
    Location:854 → 1083
    RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
    smart00229
    Location:706 → 847
    RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000009.12 Reference GRCh38.p13 Primary Assembly

    Range
    131576770..131740076 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005272186.4 → XP_005272243.1  rap guanine nucleotide exchange factor 1 isoform X6

    See identical proteins and their annotated locations for XP_005272243.1

    Conserved Domains (2) summary
    smart00147
    Location:1023 → 1252
    RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
    smart00229
    Location:875 → 1016
    RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif

  2. XM_011518572.2 → XP_011516874.1  rap guanine nucleotide exchange factor 1 isoform X4

    Conserved Domains (2) summary
    smart00147
    Location:1031 → 1260
    RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
    smart00229
    Location:883 → 1024
    RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif

  3. XM_017014633.1 → XP_016870122.1  rap guanine nucleotide exchange factor 1 isoform X8

  4. XM_011518573.3 → XP_011516875.1  rap guanine nucleotide exchange factor 1 isoform X7

    Conserved Domains (2) summary
    smart00147
    Location:1014 → 1243
    RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
    smart00229
    Location:866 → 1007
    RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif

  5. XM_011518571.2 → XP_011516873.1  rap guanine nucleotide exchange factor 1 isoform X3

    Conserved Domains (2) summary
    smart00147
    Location:1032 → 1261
    RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
    smart00229
    Location:884 → 1025
    RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif

  6. XM_011518569.3 → XP_011516871.1  rap guanine nucleotide exchange factor 1 isoform X1

    Conserved Domains (2) summary
    smart00147
    Location:1037 → 1266
    RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
    smart00229
    Location:889 → 1030
    RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif

  7. XM_024447521.1 → XP_024303289.1  rap guanine nucleotide exchange factor 1 isoform X23

    Conserved Domains (3) summary
    smart00147
    Location:852 → 1081
    RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
    smart00229
    Location:704 → 845
    RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif
    cl26464
    Location:196 → 454
    Atrophin-1; Atrophin-1 family

  8. XM_006717072.3 → XP_006717135.1  rap guanine nucleotide exchange factor 1 isoform X13

    Conserved Domains (2) summary
    smart00147
    Location:991 → 1220
    RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
    smart00229
    Location:843 → 984
    RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif

  9. XM_006717074.3 → XP_006717137.1  rap guanine nucleotide exchange factor 1 isoform X22

    Conserved Domains (2) summary
    smart00147
    Location:859 → 1088
    RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
    smart00229
    Location:711 → 852
    RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif

  10. XM_006717067.3 → XP_006717130.1  rap guanine nucleotide exchange factor 1 isoform X5

    Conserved Domains (2) summary
    smart00147
    Location:1029 → 1258
    RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
    smart00229
    Location:881 → 1022
    RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif

  11. XM_011518579.3 → XP_011516881.1  rap guanine nucleotide exchange factor 1 isoform X21

    Conserved Domains (2) summary
    smart00147
    Location:867 → 1096
    RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
    smart00229
    Location:719 → 860
    RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif

  12. XM_011518578.3 → XP_011516880.1  rap guanine nucleotide exchange factor 1 isoform X20

    Conserved Domains (2) summary
    smart00147
    Location:898 → 1127
    RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
    smart00229
    Location:750 → 891
    RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif

  13. XM_017014638.2 → XP_016870127.1  rap guanine nucleotide exchange factor 1 isoform X16

  14. XM_017014637.2 → XP_016870126.1  rap guanine nucleotide exchange factor 1 isoform X15

  15. XM_011518577.3 → XP_011516879.1  rap guanine nucleotide exchange factor 1 isoform X19

    Conserved Domains (2) summary
    smart00147
    Location:919 → 1148
    RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
    smart00229
    Location:771 → 912
    RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif

  16. XM_011518575.3 → XP_011516877.1  rap guanine nucleotide exchange factor 1 isoform X10

    Conserved Domains (2) summary
    smart00147
    Location:1005 → 1234
    RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
    smart00229
    Location:857 → 998
    RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif

  17. XM_011518570.3 → XP_011516872.1  rap guanine nucleotide exchange factor 1 isoform X2

    Conserved Domains (2) summary
    smart00147
    Location:1036 → 1265
    RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
    smart00229
    Location:888 → 1029
    RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif

  18. XM_011518576.3 → XP_011516878.1  rap guanine nucleotide exchange factor 1 isoform X18

    Conserved Domains (2) summary
    smart00147
    Location:920 → 1149
    RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
    smart00229
    Location:772 → 913
    RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif

  19. XM_017014639.2 → XP_016870128.1  rap guanine nucleotide exchange factor 1 isoform X17

  20. XM_011518574.3 → XP_011516876.1  rap guanine nucleotide exchange factor 1 isoform X9

    Conserved Domains (2) summary
    smart00147
    Location:1006 → 1235
    RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
    smart00229
    Location:858 → 999
    RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif

  21. XM_017014635.2 → XP_016870124.1  rap guanine nucleotide exchange factor 1 isoform X11

  22. XM_017014636.2 → XP_016870125.1  rap guanine nucleotide exchange factor 1 isoform X12

  23. XM_017014634.1 → XP_016870123.1  rap guanine nucleotide exchange factor 1 isoform X11

  24. XM_017014640.2 → XP_016870129.1  rap guanine nucleotide exchange factor 1 isoform X24

  25. XM_017014641.2 → XP_016870130.1  rap guanine nucleotide exchange factor 1 isoform X25

  26. XM_011518580.3 → XP_011516882.1  rap guanine nucleotide exchange factor 1 isoform X26

    Conserved Domains (1) summary
    PHA03247
    Location:242 → 500
    PHA03247; large tegument protein UL36; Provisional

  27. XM_011518581.3 → XP_011516883.1  rap guanine nucleotide exchange factor 1 isoform X27

    Conserved Domains (1) summary
    PHA03247
    Location:242 → 500
    PHA03247; large tegument protein UL36; Provisional

  28. XM_011518582.3 → XP_011516884.1  rap guanine nucleotide exchange factor 1 isoform X28

    Conserved Domains (1) summary
    PHA03247
    Location:242 → 500
    PHA03247; large tegument protein UL36; Provisional

RNA

  1. XR_001746282.2 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q13905.3 GenPept UniProtKB/Swiss-Prot:Q13905

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