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Protein

Cytohesin-2

Gene

CYTH2

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

Functioni

Acts as a guanine-nucleotide exchange factor (GEF). Promotes guanine-nucleotide exchange on ARF1, ARF3 and ARF6. Activates ARF factors through replacement of GDP with GTP (By similarity). The cell membrane form, in association with ARL4 proteins, recruits ARF6 to the plasma membrane (PubMed:17398095). 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

Keywordsi

Molecular functionGuanine-nucleotide releasing factor
LigandLipid-binding

Enzyme and pathway databases

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:CYTH2Imported
Synonyms:ARNO, PSCD2, PSCD2L
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000105443.13
HGNCiHGNC:9502 CYTH2
MIMi602488 gene
neXtProtiNX_Q99418

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasm, Membrane, Tight junction

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
DrugBankiDB01942 Formic Acid

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
ProteomicsDBi78258
78259 [Q99418-2]

PTM databases

iPTMnetiQ99418
PhosphoSitePlusiQ99418

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSG00000105443 Expressed in 224 organ(s), highest expression level in left testis
CleanExiHS_CYTH2
ExpressionAtlasiQ99418 baseline and differential
GenevisibleiQ99418 HS

Organism-specific databases

HPAiCAB014872
HPA060662

Interactioni

Subunit structurei

Heteromer. Composed of GRASP, CYTH2 and at least one GRM1 (By similarity). Interacts with ARRB1 (PubMed:17623778, PubMed:17398095). Interacts with ARL4D; the interaction is direct (PubMed:17398095). 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 (PubMed:25326380). Interacts with ARF1 (PubMed:14654833). Interacts with FRMD4A (By similarity). Interacts (via N-terminal domain) with INAVA (via N-terminal domain) (PubMed:29420262).By similarity5 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114687, 27 interactors
DIPiDIP-31598N
IntActiQ99418, 17 interactors
MINTiQ99418
STRINGi9606.ENSP00000408236

Chemistry databases

BindingDBiQ99418

Structurei

Secondary structure

1400
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG0930 Eukaryota
COG5307 LUCA
GeneTreeiENSGT00760000119036
HOGENOMiHOG000253023
HOVERGENiHBG002647
InParanoidiQ99418
KOiK18441
PhylomeDBiQ99418
TreeFamiTF352091

Family and domain databases

CDDicd00171 Sec7, 1 hit
Gene3Di1.10.1000.11, 1 hit
2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR023394 Sec7_C_sf
IPR000904 Sec7_dom
IPR035999 Sec7_dom_sf
PfamiView protein in Pfam
PF00169 PH, 1 hit
PF01369 Sec7, 1 hit
SMARTiView protein in SMART
SM00233 PH, 1 hit
SM00222 Sec7, 1 hit
SUPFAMiSSF48425 SSF48425, 1 hit
PROSITEiView protein in PROSITE
PS50003 PH_DOMAIN, 1 hit
PS50190 SEC7, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G5E9B7G5E9B7_HUMAN
Pleckstrin homology, Sec7 and coile...
CYTH2 PSCD2, hCG_1998017
292Annotation score:
F8W8E2F8W8E2_HUMAN
Cytohesin-2
CYTH2
254Annotation score:
A0A0D9SFG6A0A0D9SFG6_HUMAN
Cytohesin-2
CYTH2
400Annotation score:
A0A286YF81A0A286YF81_HUMAN
Cytohesin-2
CYTH2
274Annotation score:
M0R2J0M0R2J0_HUMAN
Cytohesin-2
CYTH2
214Annotation score:
Q8WYS2Q8WYS2_HUMAN
Cytohesin-2
CYTH2 pp9943
139Annotation score:

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]
CCDS86786.1 [Q99418-1]
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]
ENST00000641098; ENSP00000493357; ENSG00000105443 [Q99418-1]
GeneIDi9266
KEGGihsa:9266
UCSCiuc002pjj.5 human [Q99418-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

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]
CCDS86786.1 [Q99418-1]
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, 27 interactors
DIPiDIP-31598N
IntActiQ99418, 17 interactors
MINTiQ99418
STRINGi9606.ENSP00000408236

Chemistry databases

BindingDBiQ99418
ChEMBLiCHEMBL5995
DrugBankiDB01942 Formic Acid

PTM databases

iPTMnetiQ99418
PhosphoSitePlusiQ99418

Polymorphism and mutation databases

BioMutaiCYTH2
DMDMi13124707

Proteomic databases

EPDiQ99418
MaxQBiQ99418
PaxDbiQ99418
PeptideAtlasiQ99418
PRIDEiQ99418
ProteomicsDBi78258
78259 [Q99418-2]

Protocols and materials databases

DNASUi9266
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000452733; ENSP00000408236; ENSG00000105443 [Q99418-2]
ENST00000641098; ENSP00000493357; ENSG00000105443 [Q99418-1]
GeneIDi9266
KEGGihsa:9266
UCSCiuc002pjj.5 human [Q99418-1]

Organism-specific databases

CTDi9266
DisGeNETi9266
EuPathDBiHostDB:ENSG00000105443.13
GeneCardsiCYTH2
HGNCiHGNC:9502 CYTH2
HPAiCAB014872
HPA060662
MIMi602488 gene
neXtProtiNX_Q99418
OpenTargetsiENSG00000105443
PharmGKBiPA33849
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0930 Eukaryota
COG5307 LUCA
GeneTreeiENSGT00760000119036
HOGENOMiHOG000253023
HOVERGENiHBG002647
InParanoidiQ99418
KOiK18441
PhylomeDBiQ99418
TreeFamiTF352091

Enzyme and pathway databases

ReactomeiR-HSA-6811438 Intra-Golgi traffic
SIGNORiQ99418

Miscellaneous databases

ChiTaRSiCYTH2 human
EvolutionaryTraceiQ99418
GeneWikiiCYTH2
GenomeRNAii9266
PROiPR:Q99418
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000105443 Expressed in 224 organ(s), highest expression level in left testis
CleanExiHS_CYTH2
ExpressionAtlasiQ99418 baseline and differential
GenevisibleiQ99418 HS

Family and domain databases

CDDicd00171 Sec7, 1 hit
Gene3Di1.10.1000.11, 1 hit
2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR023394 Sec7_C_sf
IPR000904 Sec7_dom
IPR035999 Sec7_dom_sf
PfamiView protein in Pfam
PF00169 PH, 1 hit
PF01369 Sec7, 1 hit
SMARTiView protein in SMART
SM00233 PH, 1 hit
SM00222 Sec7, 1 hit
SUPFAMiSSF48425 SSF48425, 1 hit
PROSITEiView protein in PROSITE
PS50003 PH_DOMAIN, 1 hit
PS50190 SEC7, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCYH2_HUMAN
AccessioniPrimary (citable) accession number: Q99418
Secondary accession number(s): A8K8P0, Q8IXY9, Q92958
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: February 21, 2001
Last modified: November 7, 2018
This is version 178 of the entry and version 2 of the sequence. See 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. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  2. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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