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Protein

Cytohesin-3

Gene

CYTH3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei285 – 2851Phosphatidylinositol 3,4,5-trisphosphate1 Publication
Binding sitei296 – 2961Phosphatidylinositol 3,4,5-trisphosphate1 Publication
Binding sitei306 – 3061Phosphatidylinositol 3,4,5-trisphosphate1 Publication
Binding sitei355 – 3551Phosphatidylinositol 3,4,5-trisphosphate1 Publication

GO - Molecular functioni

  • ARF guanyl-nucleotide exchange factor activity Source: UniProtKB
  • phosphatidylinositol-3,4,5-trisphosphate binding Source: UniProtKB

GO - Biological processi

  • establishment of epithelial cell polarity Source: Ensembl
  • Golgi vesicle transport Source: UniProtKB
  • positive regulation of cell adhesion Source: Ensembl
  • positive regulation of GTPase activity Source: GOC
  • regulation of cell adhesion Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Keywords - Ligandi

Lipid-binding

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:CYTH3
Synonyms:ARNO3, GRP1, PSCD3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:9504. CYTH3.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • extrinsic component of cytoplasmic side of plasma membrane Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • ruffle Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi398 – 4003NKK → AAA: Abolishes autoinhibition and increases guanine-nucleotide exchange activity. 1 Publication

Organism-specific databases

PharmGKBiPA164718590.

Polymorphism and mutation databases

BioMutaiCYTH3.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 400400Cytohesin-3PRO_0000120200Add
BLAST

Proteomic databases

MaxQBiO43739.
PaxDbiO43739.
PRIDEiO43739.

PTM databases

PhosphoSiteiO43739.

Expressioni

Tissue specificityi

Almost absent from liver, thymus and peripheral blood lymphocytes.

Gene expression databases

BgeeiO43739.
CleanExiHS_CYTH3.
GenevisibleiO43739. HS.

Organism-specific databases

HPAiHPA013979.

Interactioni

Subunit structurei

Interacts with GRASP (By similarity). Interacts with ARF6.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
CCDC120Q96HB5-43EBI-741648,EBI-10185348
CNKSR1Q969H44EBI-741648,EBI-741671
SYCE1Q8N0S23EBI-741648,EBI-6872807

Protein-protein interaction databases

BioGridi114686. 12 interactions.
DIPiDIP-60444N.
IntActiO43739. 4 interactions.
MINTiMINT-1466258.
STRINGi9606.ENSP00000297044.

Structurei

Secondary structure

1
400
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi259 – 2624Combined sources
Beta strandi266 – 2749Combined sources
Beta strandi282 – 2909Combined sources
Beta strandi293 – 2997Combined sources
Beta strandi306 – 3105Combined sources
Beta strandi315 – 3195Combined sources
Beta strandi322 – 33110Combined sources
Beta strandi333 – 3353Combined sources
Beta strandi343 – 3453Combined sources
Beta strandi351 – 3533Combined sources
Beta strandi359 – 3624Combined sources
Helixi366 – 37914Combined sources
Helixi384 – 39613Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4KAXX-ray1.85B247-400[»]
ProteinModelPortaliO43739.
SMRiO43739. Positions 63-397.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini77 – 206130SEC7PROSITE-ProRule annotationAdd
BLAST
Domaini264 – 381118PHPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni273 – 2819Phosphatidylinositol 3,4,5-trisphosphate binding
Regioni392 – 4009C-terminal autoinhibitory region

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili14 – 6148Sequence AnalysisAdd
BLAST

Domaini

Binds via its PH domain to the inositol head group of phosphatidylinositol 3,4,5-trisphosphate.
Autoinhibited by its C-terminal basic region.

Sequence similaritiesi

Contains 1 PH domain.PROSITE-ProRule annotation
Contains 1 SEC7 domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiCOG5307.
GeneTreeiENSGT00760000119036.
HOGENOMiHOG000253023.
HOVERGENiHBG002647.
InParanoidiO43739.
KOiK18441.
OMAiWMKSIRA.
OrthoDBiEOG7RBZ9C.
PhylomeDBiO43739.
TreeFamiTF352091.

Family and domain databases

Gene3Di1.10.1000.11. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR023394. Sec7_alpha_orthog.
IPR000904. Sec7_dom.
[Graphical view]
PfamiPF00169. PH. 1 hit.
PF01369. Sec7. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00222. Sec7. 1 hit.
[Graphical view]
SUPFAMiSSF48425. SSF48425. 1 hit.
PROSITEiPS50003. PH_DOMAIN. 1 hit.
PS50190. SEC7. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O43739-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MDEDGGGEGG GVPEDLSLEE REELLDIRRR KKELIDDIER LKYEIAEVMT
60 70 80 90 100
EIDNLTSVEE SKTTQRNKQI AMGRKKFNMD PKKGIQFLIE NDLLQSSPED
110 120 130 140 150
VAQFLYKGEG LNKTVIGDYL GERDEFNIKV LQAFVELHEF ADLNLVQALR
160 170 180 190 200
QFLWSFRLPG EAQKIDRMME AFASRYCLCN PGVFQSTDTC YVLSFAIIML
210 220 230 240 250
NTSLHNHNVR DKPTAERFIA MNRGINEGGD LPEELLRNLY ESIKNEPFKI
260 270 280 290 300
PEDDGNDLTH TFFNPDREGW LLKLGGGRVK TWKRRWFILT DNCLYYFEYT
310 320 330 340 350
TDKEPRGIIP LENLSIREVE DPRKPNCFEL YNPSHKGQVI KACKTEADGR
360 370 380 390 400
VVEGNHVVYR ISAPSPEEKE EWMKSIKASI SRDPFYDMLA TRKRRIANKK
Length:400
Mass (Da):46,349
Last modified:February 21, 2001 - v2
Checksum:i87FB917899EE957D
GO
Isoform 2 (identifier: O43739-2) [UniParc]FASTAAdd to basket

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

Show »
Length:399
Mass (Da):46,292
Checksum:iDAFCAD4131A9C42D
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei277 – 2771Missing in isoform 2. 3 PublicationsVSP_006039

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS5346.1. [O43739-2]
RefSeqiNP_004218.1. NM_004227.3. [O43739-2]
UniGeneiHs.487479.

Genome annotation databases

EnsembliENST00000350796; ENSP00000297044; ENSG00000008256. [O43739-2]
ENST00000396741; ENSP00000379967; ENSG00000008256. [O43739-1]
GeneIDi9265.
KEGGihsa:9265.
UCSCiuc003spt.3. human. [O43739-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS5346.1. [O43739-2]
RefSeqiNP_004218.1. NM_004227.3. [O43739-2]
UniGeneiHs.487479.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4KAXX-ray1.85B247-400[»]
ProteinModelPortaliO43739.
SMRiO43739. Positions 63-397.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114686. 12 interactions.
DIPiDIP-60444N.
IntActiO43739. 4 interactions.
MINTiMINT-1466258.
STRINGi9606.ENSP00000297044.

Chemistry

BindingDBiO43739.
ChEMBLiCHEMBL3259466.

PTM databases

PhosphoSiteiO43739.

Polymorphism and mutation databases

BioMutaiCYTH3.

Proteomic databases

MaxQBiO43739.
PaxDbiO43739.
PRIDEiO43739.

Protocols and materials databases

DNASUi9265.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000350796; ENSP00000297044; ENSG00000008256. [O43739-2]
ENST00000396741; ENSP00000379967; ENSG00000008256. [O43739-1]
GeneIDi9265.
KEGGihsa:9265.
UCSCiuc003spt.3. human. [O43739-2]

Organism-specific databases

CTDi9265.
GeneCardsiGC07M006168.
HGNCiHGNC:9504. CYTH3.
HPAiHPA013979.
MIMi605081. gene.
neXtProtiNX_O43739.
PharmGKBiPA164718590.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG5307.
GeneTreeiENSGT00760000119036.
HOGENOMiHOG000253023.
HOVERGENiHBG002647.
InParanoidiO43739.
KOiK18441.
OMAiWMKSIRA.
OrthoDBiEOG7RBZ9C.
PhylomeDBiO43739.
TreeFamiTF352091.

Miscellaneous databases

GeneWikiiCYTH3.
GenomeRNAii9265.
NextBioi34729.
PROiO43739.
SOURCEiSearch...

Gene expression databases

BgeeiO43739.
CleanExiHS_CYTH3.
GenevisibleiO43739. HS.

Family and domain databases

Gene3Di1.10.1000.11. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR023394. Sec7_alpha_orthog.
IPR000904. Sec7_dom.
[Graphical view]
PfamiPF00169. PH. 1 hit.
PF01369. Sec7. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00222. Sec7. 1 hit.
[Graphical view]
SUPFAMiSSF48425. SSF48425. 1 hit.
PROSITEiPS50003. PH_DOMAIN. 1 hit.
PS50190. SEC7. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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.

Entry informationi

Entry nameiCYH3_HUMAN
AccessioniPrimary (citable) accession number: O43739
Secondary accession number(s): A4D2N8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: February 21, 2001
Last modified: June 24, 2015
This is version 140 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.