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O43739 (CYH3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·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
Gene names
Name:CYTH3
Synonyms:ARNO3, GRP1, PSCD3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length400 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Promotes guanine-nucleotide exchange on ARF1 and ARF6. Promotes the activation of ARF factors through replacement of GDP with GTP. Ref.2 Ref.8

Subunit structure

Interacts with GRASP By similarity. Interacts with ARF6. Ref.8

Subcellular location

Cytoplasmcytosol. Cell membrane; Peripheral membrane protein. Note: Translocates from the cytosol to membranes enriched in phosphatidylinositol 3,4,5-trisphosphate. Ref.1 Ref.7

Tissue specificity

Almost absent from liver, thymus and peripheral blood lymphocytes.

Domain

Binds via its PH domain to the inositol head group of phosphatidylinositol 3,4,5-trisphosphate. Ref.1 Ref.8

Autoinhibited by its C-terminal basic region. Ref.1 Ref.8

Sequence similarities

Contains 1 PH domain.

Contains 1 SEC7 domain.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O43739-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O43739-2)

The sequence of this isoform differs from the canonical sequence as follows:
     277-277: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 400400Cytohesin-3
PRO_0000120200

Regions

Domain77 – 206130SEC7
Domain264 – 381118PH
Region273 – 2819Phosphatidylinositol 3,4,5-trisphosphate binding
Region392 – 4009C-terminal autoinhibitory region
Coiled coil14 – 6148 Potential

Sites

Binding site2851Phosphatidylinositol 3,4,5-trisphosphate
Binding site2961Phosphatidylinositol 3,4,5-trisphosphate
Binding site3061Phosphatidylinositol 3,4,5-trisphosphate
Binding site3551Phosphatidylinositol 3,4,5-trisphosphate

Natural variations

Alternative sequence2771Missing in isoform 2.
VSP_006039

Experimental info

Mutagenesis398 – 4003NKK → AAA: Abolishes autoinhibition and increases guanine-nucleotide exchange activity. Ref.8

Secondary structure

........................... 400
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 21, 2001. Version 2.
Checksum: 87FB917899EE957D

FASTA40046,349
        10         20         30         40         50         60 
MDEDGGGEGG GVPEDLSLEE REELLDIRRR KKELIDDIER LKYEIAEVMT EIDNLTSVEE 

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

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

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

       250        260        270        280        290        300 
ESIKNEPFKI PEDDGNDLTH TFFNPDREGW LLKLGGGRVK TWKRRWFILT DNCLYYFEYT 

       310        320        330        340        350        360 
TDKEPRGIIP LENLSIREVE DPRKPNCFEL YNPSHKGQVI KACKTEADGR VVEGNHVVYR 

       370        380        390        400 
ISAPSPEEKE EWMKSIKASI SRDPFYDMLA TRKRRIANKK 

« Hide

Isoform 2 [UniParc].

Checksum: DAFCAD4131A9C42D
Show »

FASTA39946,292

References

« Hide 'large scale' references
[1]"Nerve growth factor- and epidermal growth factor-stimulated translocation of the ADP-ribosylation factor-exchange factor GRP1 to the plasma membrane of PC12 cells requires activation of phosphatidylinositol 3-kinase and the GRP1 pleckstrin homology domain."
Venkateswarlu K., Gunn-Moore F., Oatey P.B., Tavare J.M., Cullen P.J.
Biochem. J. 335:139-146(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), LIPID-BINDING, DOMAIN, SUBCELLULAR LOCATION.
[2]"ARNO3, a Sec7-domain guanine nucleotide exchange factor for ADP ribosylation factor 1, is involved in the control of Golgi structure and function."
Franco M., Boretto J., Robineau S., Monier S., Goud B., Chardin P., Chavrier P.
Proc. Natl. Acad. Sci. U.S.A. 95:9926-9931(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION.
Tissue: Placenta.
[3]"Human chromosome 7: DNA sequence and biology."
Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. expand/collapse author list , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] (ISOFORM 2).
Tissue: Brain.
[6]"Similarities in function and gene structure of cytohesin-4 and cytohesin-1, guanine nucleotide-exchange proteins for ADP-ribosylation factors."
Ogasawara M., Kim S.C., Adamik R., Togawa A., Ferrans V.J., Takeda K., Kirby M., Moss J., Vaughan M.
J. Biol. Chem. 275:3221-3230(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING.
[7]"The Arl4 family of small G proteins can recruit the cytohesin Arf6 exchange factors to the plasma membrane."
Hofmann I., Thompson A., Sanderson C.M., Munro S.
Curr. Biol. 17:711-716(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[8]"Structural basis for membrane recruitment and allosteric activation of cytohesin family Arf GTPase exchange factors."
Malaby A.W., van den Berg B., Lambright D.G.
Proc. Natl. Acad. Sci. U.S.A. 110:14213-14218(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 247-400 IN COMPLEX WITH PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE AND ARF6, FUNCTION, DOMAIN, LIPID-BINDING, MUTAGENESIS OF 398-ASN--LYS-400, AUTOINHIBITORY REGION, INTERACTION WITH ARF6.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ005197 mRNA. Translation: CAA06434.1.
AJ223957 mRNA. Translation: CAA11686.1.
CH236963 Genomic DNA. Translation: EAL23717.1.
CH878731 Genomic DNA. Translation: EAW55046.1.
BC028717 mRNA. Translation: AAH28717.1.
CCDSCCDS5346.1. [O43739-2]
RefSeqNP_004218.1. NM_004227.3. [O43739-2]
UniGeneHs.487479.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4KAXX-ray1.85B247-400[»]
ProteinModelPortalO43739.
SMRO43739. Positions 63-397.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114686. 5 interactions.
DIPDIP-60444N.
IntActO43739. 2 interactions.
MINTMINT-1466258.
STRING9606.ENSP00000297044.

PTM databases

PhosphoSiteO43739.

Proteomic databases

MaxQBO43739.
PaxDbO43739.
PRIDEO43739.

Protocols and materials databases

DNASU9265.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000350796; ENSP00000297044; ENSG00000008256. [O43739-2]
GeneID9265.
KEGGhsa:9265.
UCSCuc003spt.3. human. [O43739-2]

Organism-specific databases

CTD9265.
GeneCardsGC07M006168.
HGNCHGNC:9504. CYTH3.
HPAHPA013979.
MIM605081. gene.
neXtProtNX_O43739.
PharmGKBPA164718590.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5307.
HOGENOMHOG000253023.
HOVERGENHBG002647.
InParanoidO43739.
OMANLTCVEE.
OrthoDBEOG7RBZ9C.
PhylomeDBO43739.
TreeFamTF352091.

Gene expression databases

ArrayExpressO43739.
BgeeO43739.
CleanExHS_CYTH3.
GenevestigatorO43739.

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

GeneWikiCYTH3.
GenomeRNAi9265.
NextBio34729.
PROO43739.
SOURCESearch...

Entry information

Entry nameCYH3_HUMAN
AccessionPrimary (citable) accession number: O43739
Secondary accession number(s): A4D2N8
Entry history
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: February 21, 2001
Last modified: July 9, 2014
This is version 130 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM