P63035

SS
Gene name
Cyth2 (Pscd2, Sec7b)
Protein name
Cytohesin-2
Names
ARF nucleotide-binding site opener , Protein ARNO , PH, SEC7 and coiled-coil domain-containing protein 2 , CLM2 , SEC7 homolog B
Species
Rattus norvegicus (Rat)
KEGG Pathway
rno:116692
EC number
Protein Class

Descriptions

Cytohesin-3 (CYTH3) promotes guanine-nucleotide exchange on Arf1 and Arf6. Cytohesins share a modular architecture consisting of heptad repeats, a Sec7 domain with exchange activity for Arf1 and Arf6, a PH domain that binds phosphatidylinositol (PI) polyphosphates, and a C-terminal helix (CtH) that overlaps with a polybasic region (PBR). Cytohesins are autoinhibited by the Sec7-PH linker (252-264) and CtH/PBR (380-399), which obstruct substrate binding. The autoinhibition can be relieved by Arf6-GTP binding in the presence of the PIP3 head group.

Autoinhibitory domains (AIDs)

247-259 (Sec7-PH linker) SS

Target domain

58-246 (Sec7 domain)

Relief mechanism

Partner binding

Assay

375-394 (C-terminal helix/polybasic region) SS

Target domain

58-246 (Sec7 domain)

Relief mechanism

Partner binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for P63035

Entry ID Method Resolution Chain Position Source
AF-P63035-F1 Predicted AlphaFoldDB

1 variants for P63035

Variant ID(s) Position Change Description Diseaes Association Provenance
rs8150648 370 S>F No EVA

No associated diseases with P63035

2 regional properties for P63035

Type Name Position InterPro Accession
domain Sec7 domain 54 - 243 IPR000904
domain Pleckstrin homology domain 259 - 378 IPR001849

Functions

Description
EC Number
Subcellular Localization
  • Cell membrane ; Peripheral membrane protein
  • Cytoplasm
  • Cell projection
  • Cell projection, growth cone
  • Cell junction, tight junction
  • Cell junction, adherens junction
  • Recruited to the cell membrane through its association with ARL4A, ARL4C and ARL4D
  • Requires also interaction with phosphoinositides for targeting to plasma membrane (By similarity)
  • In differentiating neuroblastoma cells, colocalizes with CCDC120 in both neurite shaft and growth cone areas (By similarity)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

9 GO annotations of cellular component

Name Definition
adherens junction A cell-cell junction composed of the epithelial cadherin-catenin complex. The epithelial cadherins, or E-cadherins, of each interacting cell extend through the plasma membrane into the extracellular space and bind to each other. The E-cadherins bind to catenins on the cytoplasmic side of the membrane, where the E-cadherin-catenin complex binds to cytoskeletal components and regulatory and signaling molecules.
bicellular tight junction An occluding cell-cell junction that is composed of a branching network of sealing strands that completely encircles the apical end of each cell in an epithelial sheet; the outer leaflets of the two interacting plasma membranes are seen to be tightly apposed where sealing strands are present. Each sealing strand is composed of a long row of transmembrane adhesion proteins embedded in each of the two interacting plasma membranes.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
extrinsic component of postsynaptic specialization membrane The component of the postsynaptic specialization membrane consisting of gene products and protein complexes that are loosely bound to one of its surfaces, but not integrated into the hydrophobic region.
glutamatergic synapse A synapse that uses glutamate as a neurotransmitter.
growth cone The migrating motile tip of a growing neuron projection, where actin accumulates, and the actin cytoskeleton is the most dynamic.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
postsynapse The part of a synapse that is part of the post-synaptic cell.
ruffle Projection at the leading edge of a crawling cell; the protrusions are supported by a microfilament meshwork.

3 GO annotations of molecular function

Name Definition
guanyl-nucleotide exchange factor activity Stimulates the exchange of GDP to GTP on a signaling GTPase, changing its conformation to its active form. Guanine nucleotide exchange factors (GEFs) act by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP), which is more abundant in the cell under normal cellular physiological conditions.
inositol 1,4,5 trisphosphate binding Binding to inositol 1,4,5 trisphosphate.
lipid binding Binding to a lipid.

2 GO annotations of biological process

Name Definition
negative regulation of dendrite development Any process that stops, prevents, or reduces the frequency, rate or extent of dendrite development.
regulation of ARF protein signal transduction Any process that modulates the frequency, rate or extent of ARF protein signal transduction.

15 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q2KI41 CYTH2 Cytohesin-2 Bos taurus (Bovine) SS
Q9UIA0 CYTH4 Cytohesin-4 Homo sapiens (Human) SS
O43739 CYTH3 Cytohesin-3 Homo sapiens (Human) EV
Q15438 CYTH1 Cytohesin-1 Homo sapiens (Human) SS
Q99418 CYTH2 Cytohesin-2 Homo sapiens (Human) SS
Q9QX11 Cyth1 Cytohesin-1 Mus musculus (Mouse) SS
Q80YW0 Cyth4 Cytohesin-4 Mus musculus (Mouse) SS
O08967 Cyth3 Cytohesin-3 Mus musculus (Mouse) EV
P63034 Cyth2 Cytohesin-2 Mus musculus (Mouse) SS
Q7TSU1 Arfgef2 Brefeldin A-inhibited guanine nucleotide-exchange protein 2 Rattus norvegicus (Rat) PR
D4A631 Arfgef1 Brefeldin A-inhibited guanine nucleotide-exchange protein 1 Rattus norvegicus (Rat) PR
Q76M68 Iqsec3 IQ motif and SEC7 domain-containing protein 3 Rattus norvegicus (Rat) SS
A0A0G2JUG7 Iqsec1 IQ motif and SEC7 domain-containing protein 1 Rattus norvegicus (Rat) SS
P97694 Cyth1 Cytohesin-1 Rattus norvegicus (Rat) SS
P97696 Cyth3 Cytohesin-3 Rattus norvegicus (Rat) SS
10 20 30 40 50 60
MEDGVYEPPD LTPEERMELE NIRRRKQELL VEIQRLREEL SEAMSEVEGL EANEGSKTLQ
70 80 90 100 110 120
RNRKMAMGRK KFNMDPKKGI QFLVEHELLQ NTPEEIARFL YKGEGLNKTA IGDYLGEREE
130 140 150 160 170 180
LNLSVLHAFV DLHEFTDLNL VQALRQFLWS FRLPGEAQKI DRMMEAFAQR YCLCNPGVFQ
190 200 210 220 230 240
STDTCYVLSF AVIMLNTSLH NPNVRDKPGL ERFVAMNRGI NEGGDLPEDL LRNLYDSIRN
250 260 270 280 290 300
EPFKIPEDDG NDLTHTFFNP DREGWLLKLG GGRVKTWKRR WFILTDNCLY YFEYTTDKEP
310 320 330 340 350 360
RGIIPLENLS IREVDDPRKP NCFELYIPNN KGQLIKACKT EADGRVVEGN HMVYRISAPT
370 380 390
QEEKDEWIKS IQAAVSVDPF YEMLAARKKR ISVKKKQEQP