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ARHGEF3 Rho guanine nucleotide exchange factor 3 [ Homo sapiens (human) ]

Gene ID: 50650, updated on 2-Nov-2024

Summary

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Official Symbol
ARHGEF3provided by HGNC
Official Full Name
Rho guanine nucleotide exchange factor 3provided by HGNC
Primary source
HGNC:HGNC:683
See related
Ensembl:ENSG00000163947 MIM:612115; AllianceGenome:HGNC:683
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
GEF3; STA3; XPLN
Summary
Rho-like GTPases are involved in a variety of cellular processes, and they are activated by binding GTP and inactivated by conversion of GTP to GDP by their intrinsic GTPase activity. Guanine nucleotide exchange factors (GEFs) accelerate the GTPase activity of Rho GTPases by catalyzing their release of bound GDP. This gene encodes a guanine nucleotide exchange factor, which specifically activates two members of the Rho GTPase family: RHOA and RHOB, both of which have a role in bone cell biology. It has been identified that genetic variation in this gene plays a role in the determination of bone mineral density (BMD), indicating the implication of this gene in postmenopausal osteoporosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in endometrium (RPKM 17.9), adrenal (RPKM 16.7) and 24 other tissues See more
Orthologs
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Genomic context

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See ARHGEF3 in Genome Data Viewer
Location:
3p14.3
Exon count:
22
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (56727420..57079268, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (56767765..57119568, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (56761448..57113296, complement)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene ELKS/RAB6-interacting/CAST family member 2 Neighboring gene NANOG hESC enhancer GRCh37_chr3:56469501-56470002 Neighboring gene uncharacterized LOC105377099 Neighboring gene Sharpr-MPRA regulatory region 10072 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:56590646-56591318 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:56591319-56591990 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:56716124-56717068 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14471 Neighboring gene coiled-coil domain containing 66 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr3:56796980-56797857 Neighboring gene transcription activation suppressor Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19982 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19983 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14472 Neighboring gene Sharpr-MPRA regulatory region 9253 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr3:56886037-56887236 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14473 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14474 Neighboring gene Sharpr-MPRA regulatory region 9226 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:56949810-56950362 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:56950363-56950913 Neighboring gene ARHGEF3 antisense RNA 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:57040522-57041053 Neighboring gene Sharpr-MPRA regulatory region 6639 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:57049075-57049840 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:57086410-57086910 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:57086911-57087411 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:57097817-57098598 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19985 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14476 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14477 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr3:57131244-57132443 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:57144939-57145652 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancers GRCh37_chr3:57162623-57163448 and GRCh37_chr3:57163449-57164275 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:57164276-57165101 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:57165102-57165928 Neighboring gene uncharacterized LOC105377101 Neighboring gene spermatogenesis associated 12 Neighboring gene interleukin 17 receptor D Neighboring gene ribosomal protein L19 pseudogene 2

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. Identification of a role for the ARHGEF3 gene in postmenopausal osteoporosis. Mullin BH, et al. Am J Hum Genet, 2008 Jun. PMID 18499081, Free PMC Article
  2. ARHGEF3 Associated with Invasion, Metastasis, and Proliferation in Human Osteosarcoma. Gong J, et al. Biomed Res Int, 2021. PMID 34350290, Free PMC Article
  3. Redefining the specificity of phosphoinositide-binding by human PH domain-containing proteins. Singh N, et al. Nat Commun, 2021 Jul 15. PMID 34267198, Free PMC Article
  4. Further genetic evidence suggesting a role for the RhoGTPase-RhoGEF pathway in osteoporosis. Mullin BH, et al. Bone, 2009 Aug. PMID 19427924
  5. ARHGEF3 controls HDACi-induced differentiation via RhoA-dependent pathways in acute myeloid leukemias. D'Amato L, et al. Epigenetics, 2015. PMID 25494542, Free PMC Article

See all (49) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. ARHGEF3 regulates the stability of ACLY to promote the proliferation of lung cancer.
    Title: ARHGEF3 regulates the stability of ACLY to promote the proliferation of lung cancer.
  2. ARHGEF3 Associated with Invasion, Metastasis, and Proliferation in Human Osteosarcoma.
    Title: ARHGEF3 Associated with Invasion, Metastasis, and Proliferation in Human Osteosarcoma.
  3. Redefining the specificity of phosphoinositide-binding by human PH domain-containing proteins.
    Title: Redefining the specificity of phosphoinositide-binding by human PH domain-containing proteins.
  4. Genetic variants in RET, ARHGEF3 and CTNNAL1, and relevant interaction networks, contribute to the risk of Hirschsprung disease.
    Title: Genetic variants in RET, ARHGEF3 and CTNNAL1, and relevant interaction networks, contribute to the risk of Hirschsprung disease.
  5. The predicted expression of the ARHGEF3 gene in fibroblasts (effect, -0.48; P = 9.8 x 10-04) was associated with Major Depression.
    Title: DNA Methylation Signatures of Depressive Symptoms in Middle-aged and Elderly Persons: Meta-analysis of Multiethnic Epigenome-wide Studies.
  6. This is the first study describing the involvement of XPLN in the regulation of the mTORC2-SPARC axis, and these findings may help uncover regulatory mechanisms mediated by XPLN in idiopathic pulmonary fibrosis
    Title: XPLN is modulated by HDAC inhibitors and negatively regulates SPARC expression by targeting mTORC2 in human lung fibroblasts.
  7. Our findings suggest that increased expression of ARHGEF3 plays a critical oncogenic role in nasopharyngeal carcinoma pathogenesis
    Title: The putative tumor activator ARHGEF3 promotes nasopharyngeal carcinoma cell pathogenesis by inhibiting cellular apoptosis.
  8. Data suggest that modulation of ARHGEF3 gene expression in humans with a promoter-localized SNP plays a role in human megakaryocytes and human platelet function-a finding resulting from the biological follow-up of human genetic studies. Arhgef3 KO mice partially recapitulate the human phenotype.
    Title: SNP in human ARHGEF3 promoter is associated with DNase hypersensitivity, transcript level and platelet function, and Arhgef3 KO mice have increased mean platelet volume.
  9. ARHGEF3 has a crucial role in myeloid differentiation.
    Title: ARHGEF3 controls HDACi-induced differentiation via RhoA-dependent pathways in acute myeloid leukemias.
  10. ARHGEF3 and RHOA are potential regulators of a number of genes in bone cells, with influences on ACTA2 evident in both osteoblast-like and osteoclast-like cells.
    Title: Influence of ARHGEF3 and RHOA knockdown on ACTA2 and other genes in osteoblasts and osteoclasts.
Submit: New GeneRIF Correction See all GeneRIFs (17)

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

EBI GWAS Catalog

Description
A genome- and phenome-wide association study to identify genetic variants influencing platelet count and volume and their pleiotropic effects.
EBI GWAS Catalog
A genome-wide association study identifies three loci associated with mean platelet volume.
EBI GWAS Catalog
A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium.
EBI GWAS Catalog
Genome-wide association study of rheumatoid arthritis in Koreans: population-specific loci as well as overlap with European susceptibility loci.
EBI GWAS Catalog
GWAS of blood cell traits identifies novel associated loci and epistatic interactions in Caucasian and African-American children.
EBI GWAS Catalog
New gene functions in megakaryopoiesis and platelet formation.
EBI GWAS Catalog
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

  • FLJ98126, MGC118905, DKFZp434F2429

Gene Ontology Provided by GOA

Function Evidence Code Pubs
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 Rho protein signal transduction TAS
Traceable Author Statement
more info
 PubMed 
involved_in positive regulation of Rho protein signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of small GTPase mediated signal transduction TAS
Traceable Author Statement
more info
  
Component Evidence Code Pubs
located_in cytosol TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
rho guanine nucleotide exchange factor 3
Names
59.8 kDA protein
Rho guanine nucleotide exchange factor (GEF) 3
RhoGEF protein
exchange factor found in platelets and leukemic and neuronal tissues, XPLN

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_001128615.2 → NP_001122087.1  rho guanine nucleotide exchange factor 3 isoform 1

    See identical proteins and their annotated locations for NP_001122087.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1).
    Source sequence(s)
    AF433662, AL136832, DC334772
    Consensus CDS
    CCDS46854.1
    UniProtKB/TrEMBL
    B7Z6B2
    Related
    ENSP00000341071.4, ENST00000338458.8
    Conserved Domains (2) summary
    cd10572
    Location:348 → 480
    PH_RhoGEF3_XPLN; Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain
    pfam00621
    Location:158 → 334
    RhoGEF; RhoGEF domain

  2. NM_001128616.2 → NP_001122088.1  rho guanine nucleotide exchange factor 3 isoform 2

    See identical proteins and their annotated locations for NP_001122088.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks several 5' exons but has an alternate 5' exon, as compared to variant 1. The resulting isoform (2) has a distinct and shorter N-terminus, as compared to isoform 1. Isoforms 2 and 4 are the same length but have different N-termini.
    Source sequence(s)
    AB209661, AL136832, DC334437
    Consensus CDS
    CCDS46855.1
    UniProtKB/TrEMBL
    B7Z1T0
    Related
    ENSP00000410922.2, ENST00000413728.6
    Conserved Domains (2) summary
    cd10572
    Location:322 → 454
    PH_RhoGEF3_XPLN; Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain
    pfam00621
    Location:132 → 308
    RhoGEF; RhoGEF domain

  3. NM_001289698.2 → NP_001276627.1  rho guanine nucleotide exchange factor 3 isoform 4

    See identical proteins and their annotated locations for NP_001276627.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks several 5' exons but has an alternate 5' exon, as compared to variant 1. The resulting isoform (4) has a distinct and shorter N-terminus, as compared to isoform 1. Isoforms 2 and 4 are the same length but have different N-termini.
    Source sequence(s)
    AF433662, AK300045, AL136832
    Consensus CDS
    CCDS74948.1
    UniProtKB/TrEMBL
    B7Z6B2, E9PG37
    Related
    ENSP00000420420.1, ENST00000496106.5
    Conserved Domains (2) summary
    cd10572
    Location:322 → 454
    PH_RhoGEF3_XPLN; Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain
    pfam00621
    Location:132 → 308
    RhoGEF; RhoGEF domain

  4. NM_001377407.1 → NP_001364336.1  rho guanine nucleotide exchange factor 3 isoform 1

    Status: REVIEWED

    Source sequence(s)
    AC097358, AC099327, AC099559, AC099781
    Consensus CDS
    CCDS46854.1
    UniProtKB/TrEMBL
    B7Z6B2
    Conserved Domains (2) summary
    cd10572
    Location:348 → 480
    PH_RhoGEF3_XPLN; Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain
    pfam00621
    Location:158 → 334
    RhoGEF; RhoGEF domain

  5. NM_001377408.1 → NP_001364337.1  rho guanine nucleotide exchange factor 3 isoform 5

    Status: REVIEWED

    Source sequence(s)
    AC097358, AC099327, AC099559, AC099781
    UniProtKB/TrEMBL
    B7Z6B2
    Conserved Domains (2) summary
    cd10572
    Location:328 → 460
    PH_RhoGEF3_XPLN; Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain
    pfam00621
    Location:138 → 314
    RhoGEF; RhoGEF domain

  6. NM_001377409.1 → NP_001364338.1  rho guanine nucleotide exchange factor 3 isoform 5

    Status: REVIEWED

    Source sequence(s)
    AC097358, AC099327, AC099559, AC099781
    UniProtKB/TrEMBL
    B7Z6B2
    Conserved Domains (2) summary
    cd10572
    Location:328 → 460
    PH_RhoGEF3_XPLN; Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain
    pfam00621
    Location:138 → 314
    RhoGEF; RhoGEF domain

  7. NM_001377410.1 → NP_001364339.1  rho guanine nucleotide exchange factor 3 isoform 5

    Status: REVIEWED

    Source sequence(s)
    AC097358, AC099327, AC099559, AC099781
    UniProtKB/TrEMBL
    B7Z6B2
    Conserved Domains (2) summary
    cd10572
    Location:328 → 460
    PH_RhoGEF3_XPLN; Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain
    pfam00621
    Location:138 → 314
    RhoGEF; RhoGEF domain

  8. NM_001377411.1 → NP_001364340.1  rho guanine nucleotide exchange factor 3 isoform 6

    Status: REVIEWED

    Source sequence(s)
    AC097358, AC099327, AC099559, AC099781
    UniProtKB/TrEMBL
    B7Z6B2
    Conserved Domains (2) summary
    cd10572
    Location:317 → 449
    PH_RhoGEF3_XPLN; Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain
    pfam00621
    Location:127 → 303
    RhoGEF; RhoGEF domain

  9. NM_001377412.1 → NP_001364341.1  rho guanine nucleotide exchange factor 3 isoform 6

    Status: REVIEWED

    Source sequence(s)
    AC097358, AC099327, AC099559, AC099781
    UniProtKB/TrEMBL
    B7Z6B2
    Conserved Domains (2) summary
    cd10572
    Location:317 → 449
    PH_RhoGEF3_XPLN; Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain
    pfam00621
    Location:127 → 303
    RhoGEF; RhoGEF domain

  10. NM_001377413.1 → NP_001364342.1  rho guanine nucleotide exchange factor 3 isoform 7

    Status: REVIEWED

    Source sequence(s)
    AC099781
    Conserved Domains (2) summary
    pfam00621
    Location:132 → 308
    RhoGEF; RhoGEF domain
    cl17171
    Location:322 → 403
    PH-like; Pleckstrin homology-like domain

  11. NM_001377414.1 → NP_001364343.1  rho guanine nucleotide exchange factor 3 isoform 8

    Status: REVIEWED

    Source sequence(s)
    AC099559, AC099781
    Conserved Domains (2) summary
    pfam00621
    Location:126 → 302
    RhoGEF; RhoGEF domain
    cl17171
    Location:316 → 397
    PH-like; Pleckstrin homology-like domain

  12. NM_001377415.1 → NP_001364344.1  rho guanine nucleotide exchange factor 3 isoform 9

    Status: REVIEWED

    Source sequence(s)
    AC099559, AC099781
    Consensus CDS
    CCDS93293.1
    UniProtKB/TrEMBL
    C9J586
    Related
    ENSP00000417986.1, ENST00000495373.5
    Conserved Domains (2) summary
    pfam00621
    Location:126 → 302
    RhoGEF; RhoGEF domain
    cl17171
    Location:316 → 410
    PH-like; Pleckstrin homology-like domain

  13. NM_019555.3 → NP_062455.1  rho guanine nucleotide exchange factor 3 isoform 3

    See identical proteins and their annotated locations for NP_062455.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks several 5' exons but has an alternate 5' exon, as compared to variant 1. The resulting isoform (3) has a distinct and shorter N-terminus, as compared to isoform 1.
    Source sequence(s)
    AL136832, DA401228
    Consensus CDS
    CCDS2878.1
    UniProtKB/Swiss-Prot
    A8K5U7, Q4FZB6, Q4QQI5, Q4QQQ0, Q59F00, Q6NUN3, Q7Z4U2, Q7Z5T2, Q9H7T4, Q9NR81
    UniProtKB/TrEMBL
    B7Z1T0
    Related
    ENSP00000296315.3, ENST00000296315.8
    Conserved Domains (2) summary
    cd10572
    Location:316 → 448
    PH_RhoGEF3_XPLN; Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain
    pfam00621
    Location:126 → 302
    RhoGEF; RhoGEF domain

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_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    56727420..57079268 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017006503.2 → XP_016861992.1  rho guanine nucleotide exchange factor 3 isoform X4

  2. XM_047448224.1 → XP_047304180.1  rho guanine nucleotide exchange factor 3 isoform X1

  3. XM_047448226.1 → XP_047304182.1  rho guanine nucleotide exchange factor 3 isoform X4

  4. XM_047448223.1 → XP_047304179.1  rho guanine nucleotide exchange factor 3 isoform X1

  5. XM_047448222.1 → XP_047304178.1  rho guanine nucleotide exchange factor 3 isoform X1

  6. XM_011533764.2 → XP_011532066.1  rho guanine nucleotide exchange factor 3 isoform X2

    See identical proteins and their annotated locations for XP_011532066.1

    UniProtKB/TrEMBL
    B7Z6B2
    Conserved Domains (2) summary
    cd10572
    Location:334 → 466
    PH_RhoGEF3_XPLN; Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain
    pfam00621
    Location:144 → 320
    RhoGEF; RhoGEF domain

  7. XM_047448225.1 → XP_047304181.1  rho guanine nucleotide exchange factor 3 isoform X3

  8. XM_047448227.1 → XP_047304183.1  rho guanine nucleotide exchange factor 3 isoform X5

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060927.1 Alternate T2T-CHM13v2.0

    Range
    56767765..57119568 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054346678.1 → XP_054202653.1  rho guanine nucleotide exchange factor 3 isoform X4

  2. XM_054346674.1 → XP_054202649.1  rho guanine nucleotide exchange factor 3 isoform X1

    UniProtKB/TrEMBL
    B7Z7T8

  3. XM_054346677.1 → XP_054202652.1  rho guanine nucleotide exchange factor 3 isoform X4

  4. XM_054346673.1 → XP_054202648.1  rho guanine nucleotide exchange factor 3 isoform X1

    UniProtKB/TrEMBL
    B7Z7T8

  5. XM_054346675.1 → XP_054202650.1  rho guanine nucleotide exchange factor 3 isoform X1

    UniProtKB/TrEMBL
    B7Z7T8

  6. XM_054346672.1 → XP_054202647.1  rho guanine nucleotide exchange factor 3 isoform X1

    UniProtKB/TrEMBL
    B7Z7T8

  7. XM_054346676.1 → XP_054202651.1  rho guanine nucleotide exchange factor 3 isoform X2

  8. XM_054346679.1 → XP_054202654.1  rho guanine nucleotide exchange factor 3 isoform X5

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9NR81.1 GenPept UniProtKB/Swiss-Prot:Q9NR81

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