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Protein

Cytohesin-2

Gene

CYTH2

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

Functioni

Acts as a guanine-nucleotide exchange factor (GEF). Promotes guanine-nucleotide exchange on ARF1, ARF3 and ARF6. Promotes the activation of ARF factors through replacement of GDP with GTP. The cell membrane form, in association with ARL4 proteins, recruits ARF6 to the plasma membrane. Involved in neurite growth (By similarity).By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei280Phosphatidylinositol 1,4,5-trisphosphateBy similarity1
Binding sitei291Phosphatidylinositol 1,4,5-trisphosphateBy similarity1
Binding sitei301Phosphatidylinositol 1,4,5-trisphosphateBy similarity1
Binding sitei339Phosphatidylinositol 1,4,5-trisphosphateBy similarity1
Binding sitei350Phosphatidylinositol 1,4,5-trisphosphateBy similarity1
Binding sitei351Phosphatidylinositol 1,4,5-trisphosphateBy similarity1

GO - Molecular functioni

GO - Biological processi

  • actin cytoskeleton organization Source: ProtInc
  • endocytosis Source: ProtInc
  • regulation of ARF protein signal transduction Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Keywords - Ligandi

Lipid-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000105443-MONOMER.
ReactomeiR-HSA-6811438. Intra-Golgi traffic.
SIGNORiQ99418.

Names & Taxonomyi

Protein namesi
Recommended name:
Cytohesin-2
Alternative name(s):
ARF exchange factor
ARF nucleotide-binding site opener
Short name:
Protein ARNO
PH, SEC7 and coiled-coil domain-containing protein 2
Gene namesi
Name:CYTH2
Synonyms:ARNO, PSCD2, PSCD2L
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:9502. CYTH2.

Subcellular locationi

  • Cell membrane 1 Publication; Peripheral membrane protein 1 Publication
  • Cytoplasm 1 Publication
  • Cell projection By similarity
  • Cell projectiongrowth cone By similarity

  • Note: Both isoform 1 and isoform 2 are recruited to the cell membrane through its association with ARL4A, ARL4C and ARL4D. They require also interaction with phosphoinositides for targeting to plasma membrane (PubMed:17398095). In differentiating neuroblastoma cells, colocalizes with CCDC120 in both neurite shaft and growth cone areas.By similarity1 Publication

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • Golgi membrane Source: Reactome
  • growth cone Source: UniProtKB-SubCell
  • membrane Source: ProtInc
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi156E → D: Inhibits GTP GDP exchange activity. Abolishes recruitment of ARF6 to the plasma membrane. 1 Publication1
Mutagenesisi268K → R: Does not reduces ARL4D GTP-dependent interaction but inhibits targeting to the plasma membrane mediated by ARL4C, ARL4C and ARL4D. 1 Publication1
Mutagenesisi280R → D: Does not reduces ARL4D GTP-dependent interaction but inhibits targeting to the plasma membrane mediated by ARL4C, ARL4C and ARL4D. 1 Publication1
Mutagenesisi303I → A: Reduces ARL4D GTP-dependent interaction and targeting to the plasma membrane mediated by ARL4C, ARL4C and ARL4D. 1 Publication1
Mutagenesisi336K → A: Reduces ARL4D GTP-dependent interaction and targeting to the plasma membrane mediated by ARL4C, ARL4C and ARL4D. 1 Publication1

Organism-specific databases

DisGeNETi9266.
OpenTargetsiENSG00000105443.
PharmGKBiPA33849.

Chemistry databases

ChEMBLiCHEMBL5995.

Polymorphism and mutation databases

BioMutaiCYTH2.
DMDMi13124707.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001201971 – 400Cytohesin-2Add BLAST400

Proteomic databases

EPDiQ99418.
MaxQBiQ99418.
PaxDbiQ99418.
PeptideAtlasiQ99418.
PRIDEiQ99418.

PTM databases

iPTMnetiQ99418.
PhosphoSitePlusiQ99418.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSG00000105443.
CleanExiHS_CYTH2.
ExpressionAtlasiQ99418. baseline and differential.
GenevisibleiQ99418. HS.

Organism-specific databases

HPAiCAB014872.

Interactioni

Subunit structurei

Heteromer. Composed of GRASP, CYTH2 and at least one GRM1 (By similarity). Interacts with ARRB1. Interacts with ARL4D; the interaction is direct. Directly interacts with CCDC120 through the coiled coil domain; this interaction stabilizes CCDC120, possibly by preventing its ubiquitination, and is required for neurite growth in neuroblastoma cells.By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ADORA2AP292746EBI-448974,EBI-2902702
ARF1P840774EBI-448974,EBI-447171
ATP6V0A2Q9Y4872EBI-448974,EBI-988630
CCDC120Q96HB55EBI-448974,EBI-744556
CCDC120Q96HB5-43EBI-448974,EBI-10185348
EGFRP005335EBI-448974,EBI-297353

Protein-protein interaction databases

BioGridi114687. 18 interactors.
DIPiDIP-31598N.
IntActiQ99418. 13 interactors.
MINTiMINT-3058896.
STRINGi9606.ENSP00000408236.

Chemistry databases

BindingDBiQ99418.

Structurei

Secondary structure

1400
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi63 – 74Combined sources12
Helixi76 – 85Combined sources10
Helixi93 – 102Combined sources10
Helixi108 – 115Combined sources8
Helixi120 – 131Combined sources12
Helixi140 – 149Combined sources10
Helixi157 – 174Combined sources18
Beta strandi178 – 180Combined sources3
Helixi182 – 200Combined sources19
Helixi210 – 216Combined sources7
Turni217 – 220Combined sources4
Beta strandi221 – 224Combined sources4
Helixi228 – 240Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1PBVX-ray2.00A52-246[»]
1R8MX-ray1.70E50-252[»]
1R8QX-ray1.86E/F50-252[»]
1R8SX-ray1.46E50-252[»]
1S9DX-ray1.80E50-252[»]
4JMIX-ray1.50A56-251[»]
4JMOX-ray1.80A56-251[»]
4JWLX-ray1.95A56-251[»]
4JXHX-ray1.47A56-251[»]
4L5MX-ray1.80A56-251[»]
4Z21X-ray2.05A51-252[»]
ProteinModelPortaliQ99418.
SMRiQ99418.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99418.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini72 – 201SEC7PROSITE-ProRule annotationAdd BLAST130
Domaini259 – 376PHPROSITE-ProRule annotationAdd BLAST118

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni268 – 276Phosphatidylinositol 1,4,5-trisphosphate bindingBy similarity9
Regioni387 – 395C-terminal autoinhibitory regionBy similarity9

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili10 – 63Sequence analysisAdd BLAST54

Domaini

Binds via its PH domain to the inositol head group of phosphatidylinositol 1,4,5-trisphosphate. The PH domain is necessary and sufficient for plasma membrane relocalization.
Autoinhibited by its C-terminal basic region.By similarity
The coiled coil domain is involved in interaction with CCDC120.By similarity

Sequence similaritiesi

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

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG0930. Eukaryota.
COG5307. LUCA.
GeneTreeiENSGT00760000119036.
HOGENOMiHOG000253023.
HOVERGENiHBG002647.
InParanoidiQ99418.
KOiK18441.
PhylomeDBiQ99418.
TreeFamiTF352091.

Family and domain databases

Gene3Di1.10.1000.11. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR011993. PH_dom-like.
IPR001849. PH_domain.
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.
SSF50729. SSF50729. 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: Q99418-1) [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
MEDGVYEPPD LTPEERMELE NIRRRKQELL VEIQRLREEL SEAMSEVEGL
60 70 80 90 100
EANEGSKTLQ RNRKMAMGRK KFNMDPKKGI QFLVENELLQ NTPEEIARFL
110 120 130 140 150
YKGEGLNKTA IGDYLGEREE LNLAVLHAFV DLHEFTDLNL VQALRQFLWS
160 170 180 190 200
FRLPGEAQKI DRMMEAFAQR YCLCNPGVFQ STDTCYVLSF AVIMLNTSLH
210 220 230 240 250
NPNVRDKPGL ERFVAMNRGI NEGGDLPEEL LRNLYDSIRN EPFKIPEDDG
260 270 280 290 300
NDLTHTFFNP DREGWLLKLG GGRVKTWKRR WFILTDNCLY YFEYTTDKEP
310 320 330 340 350
RGIIPLENLS IREVDDPRKP NCFELYIPNN KGQLIKACKT EADGRVVEGN
360 370 380 390 400
HMVYRISAPT QEEKDEWIKS IQAAVSVDPF YEMLAARKKR ISVKKKQEQP
Length:400
Mass (Da):46,546
Last modified:February 21, 2001 - v2
Checksum:i70441A58483BD0E1
GO
Isoform 2 (identifier: Q99418-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     272-272: Missing.

Show »
Length:399
Mass (Da):46,489
Checksum:i436A1C1651C8894C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti306L → Q in AAH38713 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_006036272Missing in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X99753 mRNA. Translation: CAA68084.1.
U70728 mRNA. Translation: AAB09591.1.
AK292405 mRNA. Translation: BAF85094.1.
BC004361 mRNA. Translation: AAH04361.1.
BC038713 mRNA. Translation: AAH38713.1.
CCDSiCCDS12722.1. [Q99418-2]
RefSeqiNP_004219.3. NM_004228.6. [Q99418-2]
NP_059431.1. NM_017457.5. [Q99418-1]
UniGeneiHs.144011.

Genome annotation databases

EnsembliENST00000452733; ENSP00000408236; ENSG00000105443. [Q99418-2]
GeneIDi9266.
KEGGihsa:9266.
UCSCiuc002pjj.5. human. [Q99418-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X99753 mRNA. Translation: CAA68084.1.
U70728 mRNA. Translation: AAB09591.1.
AK292405 mRNA. Translation: BAF85094.1.
BC004361 mRNA. Translation: AAH04361.1.
BC038713 mRNA. Translation: AAH38713.1.
CCDSiCCDS12722.1. [Q99418-2]
RefSeqiNP_004219.3. NM_004228.6. [Q99418-2]
NP_059431.1. NM_017457.5. [Q99418-1]
UniGeneiHs.144011.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1PBVX-ray2.00A52-246[»]
1R8MX-ray1.70E50-252[»]
1R8QX-ray1.86E/F50-252[»]
1R8SX-ray1.46E50-252[»]
1S9DX-ray1.80E50-252[»]
4JMIX-ray1.50A56-251[»]
4JMOX-ray1.80A56-251[»]
4JWLX-ray1.95A56-251[»]
4JXHX-ray1.47A56-251[»]
4L5MX-ray1.80A56-251[»]
4Z21X-ray2.05A51-252[»]
ProteinModelPortaliQ99418.
SMRiQ99418.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114687. 18 interactors.
DIPiDIP-31598N.
IntActiQ99418. 13 interactors.
MINTiMINT-3058896.
STRINGi9606.ENSP00000408236.

Chemistry databases

BindingDBiQ99418.
ChEMBLiCHEMBL5995.

PTM databases

iPTMnetiQ99418.
PhosphoSitePlusiQ99418.

Polymorphism and mutation databases

BioMutaiCYTH2.
DMDMi13124707.

Proteomic databases

EPDiQ99418.
MaxQBiQ99418.
PaxDbiQ99418.
PeptideAtlasiQ99418.
PRIDEiQ99418.

Protocols and materials databases

DNASUi9266.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000452733; ENSP00000408236; ENSG00000105443. [Q99418-2]
GeneIDi9266.
KEGGihsa:9266.
UCSCiuc002pjj.5. human. [Q99418-1]

Organism-specific databases

CTDi9266.
DisGeNETi9266.
GeneCardsiCYTH2.
HGNCiHGNC:9502. CYTH2.
HPAiCAB014872.
MIMi602488. gene.
neXtProtiNX_Q99418.
OpenTargetsiENSG00000105443.
PharmGKBiPA33849.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0930. Eukaryota.
COG5307. LUCA.
GeneTreeiENSGT00760000119036.
HOGENOMiHOG000253023.
HOVERGENiHBG002647.
InParanoidiQ99418.
KOiK18441.
PhylomeDBiQ99418.
TreeFamiTF352091.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000105443-MONOMER.
ReactomeiR-HSA-6811438. Intra-Golgi traffic.
SIGNORiQ99418.

Miscellaneous databases

ChiTaRSiCYTH2. human.
EvolutionaryTraceiQ99418.
GeneWikiiCYTH2.
GenomeRNAii9266.
PROiQ99418.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000105443.
CleanExiHS_CYTH2.
ExpressionAtlasiQ99418. baseline and differential.
GenevisibleiQ99418. HS.

Family and domain databases

Gene3Di1.10.1000.11. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR011993. PH_dom-like.
IPR001849. PH_domain.
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.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50003. PH_DOMAIN. 1 hit.
PS50190. SEC7. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCYH2_HUMAN
AccessioniPrimary (citable) accession number: Q99418
Secondary accession number(s): A8K8P0, Q8IXY9, Q92958
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: February 21, 2001
Last modified: November 30, 2016
This is version 164 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 19
    Human chromosome 19: 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

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 one 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.