CYTH2 cytohesin 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CYTH2provided by HGNC
Official Full Name: cytohesin 2provided by HGNC
Primary source: HGNC:HGNC:9502
See related: Ensembl:ENSG00000105443 MIM:602488; AllianceGenome:HGNC:9502
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: ARNO; CTS18; PSCD2; SEC7L; PSCD2L; CTS18.1; Sec7p-L; Sec7p-like; cytohesin-2
Summary: The protein encoded by this gene is a member of the PSCD family. Members of this family have identical structural organization that consists of an N-terminal coiled-coil motif, a central Sec7 domain, and a C-terminal pleckstrin homology (PH) domain. The coiled-coil motif is involved in homodimerization, the Sec7 domain contains guanine-nucleotide exchange protein (GEP) activity, and the PH domain interacts with phospholipids and is responsible for association of PSCDs with membranes. Members of this family appear to mediate the regulation of protein sorting and membrane trafficking. The encoded protein exhibits GEP activity in vitro with ARF1, ARF3, and ARF6 and is 83% homologous to CYTH1. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]
Expression: Ubiquitous expression in testis (RPKM 10.9), thyroid (RPKM 9.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19q13.33

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (48469369..48482314)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (51463531..51476477)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (48972626..48985571)

Chromosome 19 - NC_000019.10 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?

Molecular Architecture of a Network of Potential Intracellular EGFR Modulators: ARNO, CaM, Phospholipids, and the Juxtamembrane Segment.
Title: Molecular Architecture of a Network of Potential Intracellular EGFR Modulators: ARNO, CaM, Phospholipids, and the Juxtamembrane Segment.
INAVA-CUPID exhibits dual functions, coordinated directly by ARNO, that bridge epithelial barrier function with extracellular signals and inflammation.
Title: INAVA-ARNO complexes bridge mucosal barrier function with inflammatory signaling.
ARNO-ARF1 regulates formation of podosomes by inhibition of RhoA/myosin-II and promotion of actin core assembly.
Title: Podosome assembly is controlled by the GTPase ARF1 and its nucleotide exchange factor ARNO.
Authors' experiments argue against ARNO being a robust modifier of EGFR catalytic activity.
Title: Lack of Evidence that CYTH2/ARNO Functions as a Direct Intracellular EGFR Activator.
Data establish a role for cytohesin-2/ARNO as a regulator of R-Ras and integrin recycling and suggest that ARF-regulated trafficking of R-Ras is required for R-Ras-dependent effects on spreading and adhesion formation.
Title: ARF-GEF cytohesin-2/ARNO regulates R-Ras and α5-integrin recycling through an EHD1-positive compartment.
The authors show that Shigella flexneri IpgD phosphatase activity is required for recruitment of the ARF6 guanine nucleotide exchange factor (GEF) ARF nucleotide binding site opener (ARNO) to bacterial entry sites.
Title: Shigella flexneri regulation of ARF6 activation during bacterial entry via an IpgD-mediated positive feedback loop.
inhibiting cytohesins or ARNO as cytoplasmic activators of EGFR and IGF-I in colorectal cancer resulted in anti-proliferation, reduced invasion, decreased migration, and suppressed growth in vivo and in vitro.
Title: Cytohesins/ARNO: the function in colorectal cancer cells.
Cytohesin-2 constitutively suppresses platelet dense granule secretion and aggregation by keeping ARF6 in a GTP-bound state
Title: Cytohesin-2 phosphorylation by protein kinase C relieves the constitutive suppression of platelet dense granule secretion by ADP-ribosylation factor 6.
Expression of CYTH2 mutant deficient of the EFh2 domain in cells also inhibits Arf6 activation and neurite extension.
Title: Arf6 guanine-nucleotide exchange factor, cytohesin-2, interacts with actinin-1 to regulate neurite extension.
Phosphorylation of Ser392 of ARNO stabilized the C-terminal alpha-helix via formation of salt bridges between phospho-Ser392 and Arg390, Lys395, and Lys396.
Title: Effect of Ser392 phosphorylation on the structure and dynamics of the polybasic domain of ADP ribosylation factor nucleotide site opener protein: a molecular simulation study.

Submit: New GeneRIF Correction See all GeneRIFs (29)

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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S3114 (e-PCR)
- UniSTS:152207

G32287 (e-PCR)
- UniSTS:116884

A005S30 (e-PCR)
- UniSTS:58772

STS-U59752 (e-PCR)
- UniSTS:31666

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables guanyl-nucleotide exchange factor activity	ISS Inferred from Sequence or Structural Similarity more info
enables inositol 1,4,5 trisphosphate binding	ISS Inferred from Sequence or Structural Similarity more info
enables lipid binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in actin cytoskeleton organization	TAS Traceable Author Statement more info	PubMed
involved_in endocytosis	TAS Traceable Author Statement more info	PubMed
involved_in regulation of ARF protein signal transduction	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in Golgi membrane	TAS Traceable Author Statement more info
located_in adherens junction	IEA Inferred from Electronic Annotation more info
located_in bicellular tight junction	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in growth cone	IEA Inferred from Electronic Annotation more info
located_in membrane	TAS Traceable Author Statement more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: cytohesin-2

Names: ARF exchange factor; ARF nucleotide-binding site opener; CTC-273B12.8; PH, SEC7 and coiled-coil domain-containing protein 2; pleckstrin homology, Sec7 and coiled-coil domains 2; pleckstrin homology, Sec7 and coiled/coil domains 2 (cytohesin-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)

NM_004228.7 → NP_004219.3 cytohesin-2 isoform 2

See identical proteins and their annotated locations for NP_004219.3

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks a 3-nucleotide exon in the PH domain region, compared to variant 1. This results in a protein (isoform 2) missing a single glycine residue, compared to isoform 1.

Source sequence(s)

AC008403, BC012771, DC344850, X99753

Consensus CDS

CCDS12722.1

UniProtKB/TrEMBL

A0A994J5E5

Related

ENSP00000408236.2, ENST00000452733.7

Conserved Domains (2) summary

cd01252
Location:258 → 377

PH_GRP1-like; General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain

pfam01369
Location:61 → 243

Sec7; Sec7 domain
NM_017457.6 → NP_059431.1 cytohesin-2 isoform 1

See identical proteins and their annotated locations for NP_059431.1

Status: REVIEWED

Description

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

Source sequence(s)

AC008403, BC012771, BC038713

Consensus CDS

CCDS86786.1

UniProtKB/Swiss-Prot

A8K8P0, Q8IXY9, Q92958, Q99418

UniProtKB/TrEMBL

A0A994J5E5

Related

ENSP00000493357.1, ENST00000641098.1

Conserved Domains (2) summary

cd01252
Location:258 → 378

PH_GRP1-like; General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain

pfam01369
Location:61 → 243

Sec7; Sec7 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

NC_000019.10 Reference GRCh38.p14 Primary Assembly

Range

48469369..48482314

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047439683.1 → XP_047295639.1 cytohesin-2 isoform X2
XM_006723472.3 → XP_006723535.1 cytohesin-2 isoform X1

UniProtKB/TrEMBL

A0A994J5E5

Conserved Domains (2) summary

cd01252
Location:280 → 399

PH_GRP1-like; General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain

pfam01369
Location:83 → 265

Sec7; Sec7 domain
XM_047439682.1 → XP_047295638.1 cytohesin-2 isoform X1