UniProtKB - Q99418 (CYH2_HUMAN)
Cytohesin-2
CYTH2
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 PublicationSites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 280 | Phosphatidylinositol 3,4,5-trisphosphateBy similarity | 1 | |
Binding sitei | 291 | Phosphatidylinositol 3,4,5-trisphosphateBy similarity | 1 | |
Binding sitei | 301 | Phosphatidylinositol 3,4,5-trisphosphateBy similarity | 1 | |
Binding sitei | 339 | Phosphatidylinositol 3,4,5-trisphosphateBy similarity | 1 | |
Binding sitei | 350 | Phosphatidylinositol 3,4,5-trisphosphateBy similarity | 1 | |
Binding sitei | 351 | Phosphatidylinositol 3,4,5-trisphosphateBy similarity | 1 |
GO - Molecular functioni
- guanyl-nucleotide exchange factor activity Source: UniProtKB
- inositol 1,4,5 trisphosphate binding Source: UniProtKB
- lipid binding Source: UniProtKB-KW
GO - Biological processi
- actin cytoskeleton organization Source: ProtInc
- endocytosis Source: ProtInc
- regulation of ARF protein signal transduction Source: InterPro
Keywordsi
Molecular function | Guanine-nucleotide releasing factor |
Ligand | Lipid-binding |
Enzyme and pathway databases
PathwayCommonsi | Q99418 |
Reactomei | R-HSA-6811438, Intra-Golgi traffic |
SignaLinki | Q99418 |
SIGNORi | Q99418 |
Names & Taxonomyi
Protein namesi | Recommended name: Cytohesin-2Alternative 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 | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:9502, CYTH2 |
MIMi | 602488, gene |
neXtProti | NX_Q99418 |
VEuPathDBi | HostDB:ENSG00000105443 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication; Peripheral membrane protein 1 Publication
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Other locations
- Cell projection By similarity
- growth cone By similarity
- tight junction By similarity
- adherens junction 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
Cytosol
- cytosol Source: Reactome
Golgi apparatus
- Golgi membrane Source: Reactome
Plasma Membrane
- plasma membrane Source: UniProtKB
Other locations
- adherens junction Source: UniProtKB-SubCell
- bicellular tight junction Source: UniProtKB-SubCell
- cytoplasm Source: UniProtKB
- growth cone Source: UniProtKB-SubCell
- membrane Source: ProtInc
Keywords - Cellular componenti
Cell junction, Cell membrane, Cell projection, Cytoplasm, Membrane, Tight junctionPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 156 | E → D: Inhibits GTP GDP exchange activity. Abolishes recruitment of ARF6 to the plasma membrane. 1 Publication | 1 | |
Mutagenesisi | 268 | K → R: Does not reduces ARL4D GTP-dependent interaction but inhibits targeting to the plasma membrane mediated by ARL4C, ARL4C and ARL4D. 1 Publication | 1 | |
Mutagenesisi | 280 | R → D: Does not reduces ARL4D GTP-dependent interaction but inhibits targeting to the plasma membrane mediated by ARL4C, ARL4C and ARL4D. 1 Publication | 1 | |
Mutagenesisi | 303 | I → A: Reduces ARL4D GTP-dependent interaction and targeting to the plasma membrane mediated by ARL4C, ARL4C and ARL4D. 1 Publication | 1 | |
Mutagenesisi | 336 | K → A: Reduces ARL4D GTP-dependent interaction and targeting to the plasma membrane mediated by ARL4C, ARL4C and ARL4D. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 9266 |
OpenTargetsi | ENSG00000105443 |
PharmGKBi | PA33849 |
Miscellaneous databases
Pharosi | Q99418, Tbio |
Chemistry databases
ChEMBLi | CHEMBL5995 |
DrugBanki | DB03401, 1D-myo-inositol 1,4,5-trisphosphate DB07348, Brefeldin A DB01942, Formic acid DB01863, Inositol 1,3,4,5-Tetrakisphosphate DB04530, S,S-(2-Hydroxyethyl)Thiocysteine |
Genetic variation databases
BioMutai | CYTH2 |
DMDMi | 13124707 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000120197 | 1 – 400 | Cytohesin-2Add BLAST | 400 |
Proteomic databases
EPDi | Q99418 |
jPOSTi | Q99418 |
MassIVEi | Q99418 |
MaxQBi | Q99418 |
PaxDbi | Q99418 |
PeptideAtlasi | Q99418 |
PRIDEi | Q99418 |
ProteomicsDBi | 78258 [Q99418-1] 78259 [Q99418-2] |
PTM databases
iPTMneti | Q99418 |
PhosphoSitePlusi | Q99418 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000105443, Expressed in cortical plate and 236 other tissues |
ExpressionAtlasi | Q99418, baseline and differential |
Genevisiblei | Q99418, HS |
Organism-specific databases
HPAi | ENSG00000105443, Low tissue specificity |
Interactioni
Subunit structurei
Heteromer. Composed of TAMALIN, 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 PublicationsBinary interactionsi
Q99418
Protein-protein interaction databases
BioGRIDi | 114687, 49 interactors |
DIPi | DIP-31598N |
IntActi | Q99418, 20 interactors |
MINTi | Q99418 |
STRINGi | 9606.ENSP00000408236 |
Chemistry databases
BindingDBi | Q99418 |
Miscellaneous databases
RNActi | Q99418, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q99418 |
BMRBi | Q99418 |
SASBDBi | Q99418 |
SMRi | Q99418 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q99418 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 72 – 201 | SEC7PROSITE-ProRule annotationAdd BLAST | 130 | |
Domaini | 259 – 376 | PHPROSITE-ProRule annotationAdd BLAST | 118 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 268 – 276 | Phosphatidylinositol 3,4,5-trisphosphate bindingBy similarity | 9 | |
Regioni | 387 – 395 | C-terminal autoinhibitory regionBy similarity | 9 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 10 – 63 | Sequence analysisAdd BLAST | 54 |
Domaini
Keywords - Domaini
Coiled coilPhylogenomic databases
eggNOGi | KOG0930, Eukaryota |
GeneTreei | ENSGT00940000160074 |
HOGENOMi | CLU_032820_3_0_1 |
InParanoidi | Q99418 |
OMAi | PDTCYVL |
OrthoDBi | 657055at2759 |
PhylomeDBi | Q99418 |
TreeFami | TF352091 |
Family and domain databases
CDDi | cd00171, Sec7, 1 hit |
Gene3Di | 1.10.1000.11, 1 hit 2.30.29.30, 1 hit |
InterProi | View protein in InterPro IPR011993, PH-like_dom_sf IPR001849, PH_domain IPR023394, Sec7_C_sf IPR000904, Sec7_dom IPR035999, Sec7_dom_sf |
Pfami | View protein in Pfam PF00169, PH, 1 hit PF01369, Sec7, 1 hit |
SMARTi | View protein in SMART SM00233, PH, 1 hit SM00222, Sec7, 1 hit |
SUPFAMi | SSF48425, SSF48425, 1 hit |
PROSITEi | View protein in PROSITE PS50003, PH_DOMAIN, 1 hit PS50190, SEC7, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketF8W8E2 | F8W8E2_HUMAN | Cytohesin-2 | CYTH2 | 254 | Annotation score: | ||
G5E9B7 | G5E9B7_HUMAN | Cytohesin-2 | CYTH2 PSCD2, hCG_1998017 | 292 | Annotation score: | ||
A0A0D9SFG6 | A0A0D9SFG6_HUMAN | Cytohesin-2 | CYTH2 | 400 | Annotation score: | ||
A0A286YF81 | A0A286YF81_HUMAN | Cytohesin-2 | CYTH2 | 274 | Annotation score: | ||
M0R2J0 | M0R2J0_HUMAN | Cytohesin-2 | CYTH2 | 214 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 306 | L → Q in AAH38713 (PubMed:15489334).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_006036 | 272 | Missing in isoform 2. 1 Publication | 1 |
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 |
CCDSi | CCDS12722.1 [Q99418-2] CCDS86786.1 [Q99418-1] |
RefSeqi | NP_004219.3, NM_004228.6 [Q99418-2] NP_059431.1, NM_017457.5 [Q99418-1] |
Genome annotation databases
Ensembli | ENST00000452733.7; ENSP00000408236.2; ENSG00000105443.16 [Q99418-2] ENST00000641098.1; ENSP00000493357.1; ENSG00000105443.16 |
GeneIDi | 9266 |
KEGGi | hsa:9266 |
MANE-Selecti | ENST00000452733.7; ENSP00000408236.2; NM_004228.7; NP_004219.3 [Q99418-2] |
UCSCi | uc002pjj.5, human [Q99418-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar 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 |
CCDSi | CCDS12722.1 [Q99418-2] CCDS86786.1 [Q99418-1] |
RefSeqi | NP_004219.3, NM_004228.6 [Q99418-2] NP_059431.1, NM_017457.5 [Q99418-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1PBV | X-ray | 2.00 | A | 52-246 | [»] | |
1R8M | X-ray | 1.70 | E | 50-252 | [»] | |
1R8Q | X-ray | 1.86 | E/F | 50-252 | [»] | |
1R8S | X-ray | 1.46 | E | 50-252 | [»] | |
1S9D | X-ray | 1.80 | E | 50-252 | [»] | |
4JMI | X-ray | 1.50 | A | 56-251 | [»] | |
4JMO | X-ray | 1.80 | A | 56-251 | [»] | |
4JWL | X-ray | 1.95 | A | 56-251 | [»] | |
4JXH | X-ray | 1.47 | A | 56-251 | [»] | |
4L5M | X-ray | 1.80 | A | 56-251 | [»] | |
4Z21 | X-ray | 2.05 | A | 51-252 | [»] | |
AlphaFoldDBi | Q99418 | |||||
BMRBi | Q99418 | |||||
SASBDBi | Q99418 | |||||
SMRi | Q99418 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 114687, 49 interactors |
DIPi | DIP-31598N |
IntActi | Q99418, 20 interactors |
MINTi | Q99418 |
STRINGi | 9606.ENSP00000408236 |
Chemistry databases
BindingDBi | Q99418 |
ChEMBLi | CHEMBL5995 |
DrugBanki | DB03401, 1D-myo-inositol 1,4,5-trisphosphate DB07348, Brefeldin A DB01942, Formic acid DB01863, Inositol 1,3,4,5-Tetrakisphosphate DB04530, S,S-(2-Hydroxyethyl)Thiocysteine |
PTM databases
iPTMneti | Q99418 |
PhosphoSitePlusi | Q99418 |
Genetic variation databases
BioMutai | CYTH2 |
DMDMi | 13124707 |
Proteomic databases
EPDi | Q99418 |
jPOSTi | Q99418 |
MassIVEi | Q99418 |
MaxQBi | Q99418 |
PaxDbi | Q99418 |
PeptideAtlasi | Q99418 |
PRIDEi | Q99418 |
ProteomicsDBi | 78258 [Q99418-1] 78259 [Q99418-2] |
Protocols and materials databases
Antibodypediai | 4437, 293 antibodies from 33 providers |
DNASUi | 9266 |
Genome annotation databases
Ensembli | ENST00000452733.7; ENSP00000408236.2; ENSG00000105443.16 [Q99418-2] ENST00000641098.1; ENSP00000493357.1; ENSG00000105443.16 |
GeneIDi | 9266 |
KEGGi | hsa:9266 |
MANE-Selecti | ENST00000452733.7; ENSP00000408236.2; NM_004228.7; NP_004219.3 [Q99418-2] |
UCSCi | uc002pjj.5, human [Q99418-1] |
Organism-specific databases
CTDi | 9266 |
DisGeNETi | 9266 |
GeneCardsi | CYTH2 |
HGNCi | HGNC:9502, CYTH2 |
HPAi | ENSG00000105443, Low tissue specificity |
MIMi | 602488, gene |
neXtProti | NX_Q99418 |
OpenTargetsi | ENSG00000105443 |
PharmGKBi | PA33849 |
VEuPathDBi | HostDB:ENSG00000105443 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0930, Eukaryota |
GeneTreei | ENSGT00940000160074 |
HOGENOMi | CLU_032820_3_0_1 |
InParanoidi | Q99418 |
OMAi | PDTCYVL |
OrthoDBi | 657055at2759 |
PhylomeDBi | Q99418 |
TreeFami | TF352091 |
Enzyme and pathway databases
PathwayCommonsi | Q99418 |
Reactomei | R-HSA-6811438, Intra-Golgi traffic |
SignaLinki | Q99418 |
SIGNORi | Q99418 |
Miscellaneous databases
BioGRID-ORCSi | 9266, 12 hits in 1079 CRISPR screens |
ChiTaRSi | CYTH2, human |
EvolutionaryTracei | Q99418 |
GeneWikii | CYTH2 |
GenomeRNAii | 9266 |
Pharosi | Q99418, Tbio |
PROi | PR:Q99418 |
RNActi | Q99418, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000105443, Expressed in cortical plate and 236 other tissues |
ExpressionAtlasi | Q99418, baseline and differential |
Genevisiblei | Q99418, HS |
Family and domain databases
CDDi | cd00171, Sec7, 1 hit |
Gene3Di | 1.10.1000.11, 1 hit 2.30.29.30, 1 hit |
InterProi | View protein in InterPro IPR011993, PH-like_dom_sf IPR001849, PH_domain IPR023394, Sec7_C_sf IPR000904, Sec7_dom IPR035999, Sec7_dom_sf |
Pfami | View protein in Pfam PF00169, PH, 1 hit PF01369, Sec7, 1 hit |
SMARTi | View protein in SMART SM00233, PH, 1 hit SM00222, Sec7, 1 hit |
SUPFAMi | SSF48425, SSF48425, 1 hit |
PROSITEi | View protein in PROSITE PS50003, PH_DOMAIN, 1 hit PS50190, SEC7, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CYH2_HUMAN | |
Accessioni | Q99418Primary (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: | May 25, 2022 | |
This is version 200 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references