RAPGEF6 Rap guanine nucleotide exchange factor 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: RAPGEF6provided by HGNC
Official Full Name: Rap guanine nucleotide exchange factor 6provided by HGNC
Primary source: HGNC:HGNC:20655
See related: Ensembl:ENSG00000158987 MIM:610499; AllianceGenome:HGNC:20655
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: RAGEF2; PDZGEF2; KIA001LB; PDZ-GEF2; RA-GEF-2
Summary: Enables several functions, including GTP-dependent protein binding activity; guanyl-nucleotide exchange factor activity; and phosphatidic acid binding activity. Involved in microvillus assembly; positive regulation of GTPase activity; and protein localization to plasma membrane. Located in several cellular components, including apical plasma membrane; centrosome; and endocytic vesicle. [provided by Alliance of Genome Resources, Nov 2024]
Expression: Ubiquitous expression in lymph node (RPKM 9.8), appendix (RPKM 6.5) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 5q31.1

Exon count:: 31

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (131423921..131635229, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (131943517..132155185, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (130759614..130970922, complement)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

local accumulation of PDZGEF at the apical membrane during establishment of epithelial polarity is mediated by electrostatic interactions between positively charged side chains in the PDZ domain and negatively charged phosphatidic acid.
Title: The PDZ domain of the guanine nucleotide exchange factor PDZGEF directs binding to phosphatidic acid during brush border formation.
BAG3 overexpression increases cell adhesion in Cos7 cells, but not in PDZGEF2 gene knockdown cells indicating that PDZGEF2 is a critical partner for BAG3 in regulating cell adhesion
Title: BAG3 directly associates with guanine nucleotide exchange factor of Rap1, PDZGEF2, and regulates cell adhesion.
JAM-A dimerization facilitates formation of a complex with Afadin and PDZ-GEF2 that activates Rap1A, which regulates beta1 integrin levels and cell migration.
Title: Junctional adhesion molecule A interacts with Afadin and PDZ-GEF2 to activate Rap1A, regulate beta1 integrin levels, and enhance cell migration.
Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
Title: Interaction between interleukin 3 and dystrobrevin-binding protein 1 in schizophrenia.
PDZ-GEF2 plays a critical role in the maturation of adherens junctions.
Title: The RapGEF PDZ-GEF2 is required for maturation of cell-cell junctions.
When males and females were analysed separately, SNP4 (rs31251) in PDZ-GEF2 is associated with schizophrenia in females in Han Chinese.
Title: Association of haplotypes spanning PDZ-GEF2, LOC728637 and ACSL6 with schizophrenia in Han Chinese.
Observational study of gene-disease association. (HuGE Navigator)
Title: Association of haplotypes spanning PDZ-GEF2, LOC728637 and ACSL6 with schizophrenia in Han Chinese.
haplotypes underlying the SPEC2/PDZ-GEF2/acyl-CoA synthetase long-chain family member 6 region are associated with schizophrenia
Title: Haplotypes spanning SPEC2, PDZ-GEF2 and ACSL6 genes are associated with schizophrenia.
the second PDZ domain from human phosphatase hPTP1E in complex with a C-terminal peptide from the guanine nucleotide exchange factor RA-GEF-2 has been determined
Title: Solution structure of the PDZ2 domain from cytosolic human phosphatase hPTP1E complexed with a peptide reveals contribution of the beta2-beta3 loop to PDZ domain-ligand interactions.

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Phenotypes

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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)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of Rap guanine nucleotide exchange factor (GEF) 6 (RAPGEF6) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH16425 (e-PCR)
- UniSTS:78864

RH68639 (e-PCR)
- UniSTS:75801

SHGC-83444 (e-PCR)
- UniSTS:101937

SHGC-83445 (e-PCR)
- UniSTS:101938

D8S2279 (e-PCR)
- UniSTS:473907

STS-R70741 (e-PCR)
- UniSTS:70979

L18426 (e-PCR)
- UniSTS:34648

SHGC-82940 (e-PCR)
- UniSTS:96106

D1S1423 (e-PCR)
- UniSTS:149619

D5S2110 (e-PCR), detects polymorphism
- UniSTS:37796

D5S2057 (e-PCR)
- UniSTS:74733

A005Y25 (e-PCR)
- UniSTS:76534

D5S1781 (e-PCR)
- UniSTS:153593

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables GTP-dependent protein binding	IDA Inferred from Direct Assay more info	PubMed
enables guanyl-nucleotide exchange factor activity	IBA Inferred from Biological aspect of Ancestor more info
enables guanyl-nucleotide exchange factor activity	IDA Inferred from Direct Assay more info	PubMed
enables phosphatidic acid binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables small GTPase binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in Ras protein signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in Ras protein signal transduction	NAS Non-traceable Author Statement more info	PubMed
NOT involved_in establishment of endothelial intestinal barrier	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in microvillus assembly	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of GTPase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein localization to plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of GTPase activity	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
is_active_in apical plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in centrosome	IDA Inferred from Direct Assay more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
is_active_in endocytic vesicle	IBA Inferred from Biological aspect of Ancestor more info
located_in endocytic vesicle	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: rap guanine nucleotide exchange factor 6

Names: PDZ domain containing guanine nucleotide exchange factor (GEF) 2; PDZ domain-containing guanine nucleotide exchange factor 2; PDZ domain-containing guanine nucleotide exchange factor I; Rap guanine nucleotide exchange factor (GEF) 6

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)

NM_001164386.2 → NP_001157858.1 rap guanine nucleotide exchange factor 6 isoform 1

See identical proteins and their annotated locations for NP_001157858.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AF478567, AL832899, AV726501, BC140820, DA817493

Consensus CDS

CCDS54900.1

UniProtKB/TrEMBL

B2RTU6

Related

ENSP00000296859.6, ENST00000296859.10

Conserved Domains (7) summary

smart00229
Location:412 → 525

RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif

COG0664
Location:274 → 448

Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]

cd00038
Location:280 → 380

CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...

cd00155
Location:857 → 1081

RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. ...

cd00992
Location:529 → 609

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) ...

cl00047
Location:37 → 82

CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...

cl00155
Location:749 → 833

UBQ; Ubiquitin-like proteins
NM_001164387.2 → NP_001157859.1 rap guanine nucleotide exchange factor 6 isoform 3

Status: VALIDATED

Description

Transcript Variant: This variant (3) includes an alternate in-frame exon in the central coding region but lacks another alternate in-frame exon in the 3' coding region, compared to variant 1. The resulting protein (isoform 3) is shorter than isoform 1.

Source sequence(s)

AF394782, AF478567, AL832899, AV726501, BU568060, DA817493

Consensus CDS

CCDS54901.1

UniProtKB/TrEMBL

B2RTU6

Related

ENSP00000426081.2, ENST00000507093.5

Conserved Domains (7) summary

smart00229
Location:412 → 525

RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif

COG0664
Location:274 → 448

Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]

cd00038
Location:280 → 380

CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...

cd00155
Location:862 → 1086

RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. ...

cd00992
Location:529 → 609

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) ...

cl00047
Location:37 → 82

CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...

cl00155
Location:754 → 838

UBQ; Ubiquitin-like proteins
NM_001164388.2 → NP_001157860.1 rap guanine nucleotide exchange factor 6 isoform 4

See identical proteins and their annotated locations for NP_001157860.1

Status: VALIDATED

Description

Transcript Variant: This variant (4) lacks an alternate in-frame exon in the 3' coding region compared to variant 1. The resulting protein (isoform 4) is shorter than isoform 1.

Source sequence(s)

AF478567, AL832899, BC133703, DA817493

Consensus CDS

CCDS54899.1

UniProtKB/TrEMBL

B2RTU6

Related

ENSP00000487439.1, ENST00000627212.2

Conserved Domains (6) summary

smart00229
Location:412 → 525

RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif

cd00038
Location:280 → 380

CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...

cd00155
Location:857 → 1081

RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. ...

cd00992
Location:529 → 609

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) ...

cl00047
Location:37 → 82

CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...

cl00155
Location:749 → 833

UBQ; Ubiquitin-like proteins
NM_001164389.2 → NP_001157861.1 rap guanine nucleotide exchange factor 6 isoform 5

See identical proteins and their annotated locations for NP_001157861.1

Status: VALIDATED

Description

Transcript Variant: This variant (5) differs in the 3' UTR and 3' coding region, compared to variant 1. It encodes isoform 5 which has a shorter and distinct C-terminus compared to isoform 1.

Source sequence(s)

AC008497, AF478469, AF478567, AW204176, BX117281

Consensus CDS

CCDS54898.1

UniProtKB/TrEMBL

B7Z7Y1

Related

ENSP00000311419.6, ENST00000308008.10

Conserved Domains (6) summary

smart00229
Location:412 → 525

RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif

cd00038
Location:280 → 380

CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...

cd00155
Location:857 → 1067

RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. ...

cd00992
Location:529 → 609

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) ...

cl00047
Location:37 → 82

CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...

cl00155
Location:749 → 833

UBQ; Ubiquitin-like proteins
NM_001164390.2 → NP_001157862.1 rap guanine nucleotide exchange factor 6 isoform 6

Status: VALIDATED

Description

Transcript Variant: This variant (6) differs in the 3' UTR and lacks a significant portion of the 3' coding region, compared to variant 1. This results in a protein (isoform 6) that maintains the reading frame but is shorter at the C-terminus, compared to isoform 1.

Source sequence(s)

AC004622, AF478567, BC142964

Consensus CDS

CCDS54897.1

UniProtKB/Swiss-Prot

Q8TEU7

Related

ENSP00000425389.1, ENST00000510071.5

Conserved Domains (6) summary

smart00229
Location:412 → 525

RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif

COG0265
Location:541 → 609

DegQ; Periplasmic serine protease, S1-C subfamily, contain C-terminal PDZ domain [Posttranslational modification, protein turnover, chaperones]

cd00038
Location:280 → 380

CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...

cd00992
Location:529 → 609

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) ...

cl00047
Location:37 → 82

CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...

cl00155
Location:749 → 827

UBQ; Ubiquitin-like proteins
NM_016340.6 → NP_057424.3 rap guanine nucleotide exchange factor 6 isoform 2

See identical proteins and their annotated locations for NP_057424.3

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting protein (isoform 2) is shorter than isoform 1.

Source sequence(s)

AF478567, AL832899, BC144627, DA817493

Consensus CDS

CCDS34225.1

UniProtKB/Swiss-Prot

A3KN82, A5PLL6, B7ZML2, E9PDV7, Q8NI21, Q8TEU6, Q8TEU7, Q96PC1

UniProtKB/TrEMBL

B2RTU6

Related

ENSP00000421684.1, ENST00000509018.6

Conserved Domains (7) summary

smart00229
Location:412 → 525

RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif

COG0664
Location:274 → 448

Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]

cd00038
Location:280 → 380

CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...

cd00155
Location:857 → 1067

RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. ...

cd00992
Location:529 → 609

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) ...

cl00047
Location:37 → 82

CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...

cl00155
Location:749 → 833

UBQ; Ubiquitin-like proteins