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O08967 (CYH3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cytohesin-3
Alternative name(s):
ARF nucleotide-binding site opener 3
Short name=Protein ARNO3
General receptor of phosphoinositides 1
Short name=Grp1
PH, SEC7 and coiled-coil domain-containing protein 3
Short name=CLM3
SEC7 homolog C
Short name=mSec7-3
Gene names
Name:Cyth3
Synonyms:Grp1, Pscd3
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length399 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Promotes guanine-nucleotide exchange on ARF1. Promotes the activation of ARF factors through replacement of GDP with GTP. Ref.9

Subunit structure

Interacts with GRASP. Ref.5

Subcellular location

Cytoplasmcytosol By similarity. Cell membrane; Peripheral membrane protein. Note: Translocates from the cytosol to membranes enriched in phosphatidylinositol 3,4,5-trisphosphate. Ref.9

Domain

Binds via its PH domain to the inositol head group of phosphatidylinositol 3,4,5-trisphosphate. Ref.6 Ref.7 Ref.8 Ref.9

Autoinhibited by its C-terminal basic region. Ref.6 Ref.7 Ref.8 Ref.9

Sequence similarities

Contains 1 PH domain.

Contains 1 SEC7 domain.

Ontologies

Keywords
   Cellular componentCell membrane
Cytoplasm
Membrane
   DomainCoiled coil
   LigandLipid-binding
   Molecular functionGuanine-nucleotide releasing factor
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processGolgi vesicle transport

Inferred from sequence or structural similarity. Source: UniProtKB

establishment of epithelial cell polarity

Inferred from mutant phenotype PubMed 20080746. Source: MGI

positive regulation of cell adhesion

Inferred from direct assay Ref.3. Source: MGI

regulation of ARF protein signal transduction

Inferred from electronic annotation. Source: InterPro

regulation of GTPase activity

Inferred from Biological aspect of Ancestor. Source: GOC

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 11445584. Source: MGI

cytosol

Inferred from sequence or structural similarity. Source: UniProtKB

extrinsic component of cytoplasmic side of plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from direct assay Ref.3. Source: MGI

ruffle

Inferred from physical interaction PubMed 11445584. Source: MGI

   Molecular_functionARF guanyl-nucleotide exchange factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

guanyl-nucleotide exchange factor activity

Inferred from sequence or structural similarity PubMed 10652516. Source: MGI

phosphatidylinositol-3,4,5-trisphosphate binding

Inferred from direct assay Ref.1. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 399399Cytohesin-3
PRO_0000120201

Regions

Domain77 – 206130SEC7
Domain264 – 380117PH
Region273 – 2808Phosphatidylinositol 3,4,5-trisphosphate binding
Region391 – 3999C-terminal autoinhibitory region
Coiled coil14 – 6148 Potential

Sites

Binding site2841Phosphatidylinositol 3,4,5-trisphosphate
Binding site2951Phosphatidylinositol 3,4,5-trisphosphate
Binding site3051Phosphatidylinositol 3,4,5-trisphosphate
Binding site3541Phosphatidylinositol 3,4,5-trisphosphate

Experimental info

Mutagenesis2731K → A: Abolishes phosphatidylinositol 3,4,5-trisphosphate binding. Ref.8
Mutagenesis2771R → A or G: Reduces phosphatidylinositol 3,4,5-trisphosphate binding. Ref.8
Mutagenesis2801T → A or G: Reduces phosphatidylinositol 3,4,5-trisphosphate binding. Ref.8
Mutagenesis2821K → A: Reduces phosphatidylinositol 3,4,5-trisphosphate binding. Ref.8
Mutagenesis2841R → A: Abolishes phosphatidylinositol 3,4,5-trisphosphate binding. Ref.8
Mutagenesis2951Y → F: Reduces phosphatidylinositol 3,4,5-trisphosphate binding. Ref.8
Mutagenesis3051R → A: Abolishes phosphatidylinositol 3,4,5-trisphosphate binding. Ref.8
Mutagenesis3431K → A: Abolishes phosphatidylinositol 3,4,5-trisphosphate binding. Ref.8
Mutagenesis3541N → A: Slightly reduces phosphatidylinositol 3,4,5-trisphosphate binding. Ref.8
Mutagenesis3551H → A: Abolishes phosphatidylinositol 3,4,5-trisphosphate binding. Ref.8
Mutagenesis3881L → A: Impairs autoinhibition; when associated with A-392. Ref.9
Mutagenesis3921K → A: Impairs autoinhibition; when associated with A-388. Ref.9

Secondary structure

.................................................... 399
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O08967 [UniParc].

Last modified July 1, 1997. Version 1.
Checksum: 00F7FEB9C3849157

FASTA39946,280
        10         20         30         40         50         60 
MDEGGGGEGG SVPEDLSLEE REELLDIRRR KKELIDDIER LKYEIAEVMT EIDNLTSVEE 

        70         80         90        100        110        120 
SKTTQRNKQI AMGRKKFNMD PKKGIQFLIE NDLLQSSPED VAQFLYKGEG LNKTVIGDYL 

       130        140        150        160        170        180 
GERDDFNIKV LQAFVELHEF ADLNLVQALR QFLWSFRLPG EAQKIDRMME AFASRYCLCN 

       190        200        210        220        230        240 
PGVFQSTDTC YVLSFAIIML NTSLHNHNVR DKPTAERFIT MNRGINEGGD LPEELLRNLY 

       250        260        270        280        290        300 
ESIKNEPFKI PEDDGNDLTH TFFNPDREGW LLKLGGRVKT WKRRWFILTD NCLYYFEYTT 

       310        320        330        340        350        360 
DKEPRGIIPL ENLSIREVED PRKPNCFELY NPSHKGQVIK ACKTEADGRV VEGNHVVYRI 

       370        380        390 
SAPSPEEKEE WMKSIKASIS RDPFYDMLAT RKRRIANKK 

« Hide

References

« Hide 'large scale' references
[1]"Signaling by phosphoinositide-3,4,5-trisphosphate through proteins containing pleckstrin and Sec7 homology domains."
Klarlund J.K., Guilherme A., Holik J.J., Virbasius J.V., Chawla A., Czech M.P.
Science 275:1927-1930(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Complex regulation of multiple cytohesin-like genes in murine tissues and cells."
Kim H.-S., Chen Y., Lonai P.
FEBS Lett. 433:312-316(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Anergic T lymphocytes selectively express an integrin regulatory protein of the cytohesin family."
Korthauer U., Nagel W., Davis E.M., Le Beau M.M., Menon R.S., Mitchell E.O., Kozak C.A., Kolanus W., Bluestone J.A.
J. Immunol. 164:308-318(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: NIH Swiss.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: FVB/N.
Tissue: Mammary gland.
[5]"Interaction of GRASP, a protein encoded by a novel retinoic acid-induced gene, with members of the cytohesin family of guanine nucleotide exchange factors."
Nevrivy D.J., Peterson V.J., Avram D., Ishmael J.E., Hansen S.G., Dowell P., Hruby D.E., Dawson M.I., Leid M.
J. Biol. Chem. 275:16827-16836(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GRASP.
[6]"Structural basis for discrimination of 3-phosphoinositides by pleckstrin homology domains."
Ferguson K.M., Kavran J.M., Sankaran V.G., Fournier E., Isakoff S.J., Skolnik E.Y., Lemmon M.A.
Mol. Cell 6:373-384(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 264-391 IN COMPLEX WITH PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE, LIPID-BINDING, DOMAIN.
[7]"Structural basis of 3-phosphoinositide recognition by pleckstrin homology domains."
Lietzke S.E., Bose S., Cronin T., Klarlund J., Chawla A., Czech M.P., Lambright D.G.
Mol. Cell 6:385-394(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 261-387 IN COMPLEX WITH PHOSPHATIDYLINOSITOL 1,3,4,5-TETRAPHOSPHATE, DOMAIN, LIPID-BINDING.
[8]"Structural determinants of phosphoinositide selectivity in splice variants of Grp1 family PH domains."
Cronin T.C., DiNitto J.P., Czech M.P., Lambright D.G.
EMBO J. 23:3711-3720(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 261-387 IN COMPLEX WITH PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE, LIPID-BINDING, DOMAIN, MUTAGENESIS OF LYS-273; ARG-277; THR-280; LYS-282; ARG-284; TYR-295; ARG-305; LYS-343; ASN-354 AND HIS-355.
[9]"Structural basis and mechanism of autoregulation in 3-phosphoinositide-dependent Grp1 family Arf GTPase exchange factors."
DiNitto J.P., Delprato A., Gabe Lee M.T., Cronin T.C., Huang S., Guilherme A., Czech M.P., Lambright D.G.
Mol. Cell 28:569-583(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 63-399 IN COMPLEX WITH PHOSPHATIDYLINOSITOL 1,3,4,5-TETRAPHOSPHATE, FUNCTION, DOMAIN, AUTOINHIBITORY REGION, SUBCELLULAR LOCATION, MUTAGENESIS OF LEU-388 AND LYS-392, LIPID-BINDING.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF001871 Genomic DNA. Translation: AAB60876.1.
AB013470 mRNA. Translation: BAA33433.1.
AF084221 mRNA. Translation: AAF23858.1.
BC035296 mRNA. Translation: AAH35296.2.
RefSeqNP_035312.3. NM_011182.4.
UniGeneMm.281003.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1FGYX-ray1.50A261-387[»]
1FGZX-ray2.05A261-387[»]
1FHWX-ray1.90A/B264-391[»]
1FHXX-ray2.50A/B264-391[»]
1U2BX-ray1.80A261-387[»]
2R09X-ray1.90A/B63-399[»]
2R0DX-ray2.04A/B63-399[»]
ProteinModelPortalO08967.
SMRO08967. Positions 63-396.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202413. 2 interactions.

PTM databases

PhosphoSiteO08967.

Proteomic databases

PaxDbO08967.
PRIDEO08967.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000116456; ENSMUSP00000112157; ENSMUSG00000018001.
GeneID19159.
KEGGmmu:19159.
UCSCuc009ako.2. mouse.

Organism-specific databases

CTD9265.
MGIMGI:1335107. Cyth3.

Phylogenomic databases

eggNOGCOG5307.
HOGENOMHOG000253023.
HOVERGENHBG002647.
InParanoidO08967.
OMAMKSIRAS.
OrthoDBEOG7RBZ9C.
PhylomeDBO08967.
TreeFamTF352091.

Gene expression databases

ArrayExpressO08967.
BgeeO08967.
GenevestigatorO08967.

Family and domain databases

Gene3D1.10.1000.11. 1 hit.
2.30.29.30. 1 hit.
InterProIPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR023394. Sec7_alpha_orthog.
IPR000904. Sec7_dom.
[Graphical view]
PfamPF00169. PH. 1 hit.
PF01369. Sec7. 1 hit.
[Graphical view]
SMARTSM00233. PH. 1 hit.
SM00222. Sec7. 1 hit.
[Graphical view]
SUPFAMSSF48425. SSF48425. 1 hit.
PROSITEPS50003. PH_DOMAIN. 1 hit.
PS50190. SEC7. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCYTH3. mouse.
EvolutionaryTraceO08967.
NextBio295818.
PROO08967.
SOURCESearch...

Entry information

Entry nameCYH3_MOUSE
AccessionPrimary (citable) accession number: O08967
Secondary accession number(s): Q8CI93
Entry history
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: July 1, 1997
Last modified: April 16, 2014
This is version 113 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot