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Protein

Cytohesin-2

Gene

Cyth2

Organism
Mus musculus (Mouse)
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 (PubMed:25326380).2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei280 – 2801Phosphatidylinositol 1,4,5-trisphosphate1 Publication
Binding sitei291 – 2911Phosphatidylinositol 1,4,5-trisphosphate1 Publication
Binding sitei301 – 3011Phosphatidylinositol 1,4,5-trisphosphate1 Publication
Binding sitei339 – 3391Phosphatidylinositol 1,4,5-trisphosphate1 Publication
Binding sitei350 – 3501Phosphatidylinositol 1,4,5-trisphosphate1 Publication
Binding sitei351 – 3511Phosphatidylinositol 1,4,5-trisphosphate1 Publication

GO - Molecular functioni

  • ARF guanyl-nucleotide exchange factor activity Source: UniProtKB
  • inositol 1,4,5 trisphosphate binding Source: UniProtKB
  • lipid binding Source: UniProtKB-KW

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Keywords - Ligandi

Lipid-binding

Enzyme and pathway databases

ReactomeiR-MMU-6811438. Intra-Golgi traffic.

Names & Taxonomyi

Protein namesi
Recommended name:
Cytohesin-2
Alternative name(s):
ARF nucleotide-binding site opener
Short name:
Protein ARNO
PH, SEC7 and coiled-coil domain-containing protein 2
Short name:
CLM2
SEC7 homolog B
Short name:
mSec7-2
Gene namesi
Name:Cyth2
Synonyms:Pscd2, Sec7b
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1334255. Cyth2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi268 – 2681K → A: Abolishes phosphatidylinositol 1,4,5-trisphosphate binding. 1 Publication
Mutagenesisi274 – 2741V → G: Increased phosphatidylinositol 1,4,5-trisphosphate binding. 1 Publication
Mutagenesisi278 – 2781K → A: Strongly reduces phosphatidylinositol 1,4,5-trisphosphate binding. 1 Publication
Mutagenesisi280 – 2801R → A: Abolishes phosphatidylinositol 1,4,5-trisphosphate binding. 1 Publication
Mutagenesisi291 – 2911Y → F: Abolishes phosphatidylinositol 1,4,5-trisphosphate binding. 1 Publication
Mutagenesisi301 – 3011R → A: Abolishes phosphatidylinositol 1,4,5-trisphosphate binding. 1 Publication
Mutagenesisi339 – 3391K → A: Abolishes phosphatidylinositol 1,4,5-trisphosphate binding. 1 Publication
Mutagenesisi351 – 3511H → A: Abolishes phosphatidylinositol 1,4,5-trisphosphate binding. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 400400Cytohesin-2PRO_0000120198Add
BLAST

Proteomic databases

MaxQBiP63034.
PaxDbiP63034.
PRIDEiP63034.

PTM databases

iPTMnetiP63034.
PhosphoSiteiP63034.

Expressioni

Tissue specificityi

Present in all tissues tested, with highest protein levels in brain and adrenal.

Developmental stagei

Up-regulated in differentiating neuroblastoma cells.1 Publication

Gene expression databases

BgeeiENSMUSG00000003269.
ExpressionAtlasiP63034. baseline and differential.
GenevisibleiP63034. MM.

Interactioni

Subunit structurei

Heteromer. Composed of GRASP, CYTH2 and at least one GRM1. Interacts with ARRB1. Interacts with ARL4D; the interaction is direct (By similarity). 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 a neuroblastoma cell line (PubMed:25326380).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Atp6v0a2P159205EBI-988425,EBI-988456

Protein-protein interaction databases

BioGridi202412. 2 interactions.
IntActiP63034. 1 interaction.
STRINGi10090.ENSMUSP00000103357.

Structurei

Secondary structure

1
400
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi262 – 2698Combined sources
Beta strandi272 – 2743Combined sources
Beta strandi277 – 2859Combined sources
Beta strandi288 – 2947Combined sources
Beta strandi301 – 3055Combined sources
Beta strandi310 – 3145Combined sources
Beta strandi317 – 32610Combined sources
Beta strandi338 – 3403Combined sources
Beta strandi346 – 3483Combined sources
Beta strandi352 – 3576Combined sources
Helixi361 – 37616Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1U27X-ray2.30A260-378[»]
1U29X-ray1.80A260-378[»]
ProteinModelPortaliP63034.
SMRiP63034. Positions 56-400.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP63034.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini72 – 201130SEC7PROSITE-ProRule annotationAdd
BLAST
Domaini259 – 376118PHPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni268 – 2769Phosphatidylinositol 1,4,5-trisphosphate binding
Regioni387 – 3959C-terminal autoinhibitory regionBy similarity

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili10 – 6758Sequence analysisAdd
BLAST

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 (By similarity).By similarity
Autoinhibited by its C-terminal basic region.By similarity
The coiled coil domain is involved in interaction with CCDC120.1 Publication

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.
InParanoidiP63034.
KOiK18441.
OMAiEKDEWIH.

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 (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P63034-1) [UniParc]FASTAAdd to basket
Also known as: CLM2-A

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 QFLVEHELLQ NTPEEIARFL
110 120 130 140 150
YKGEGLNKTA IGDYLGEREE LNLSVLHAFV DLHEFTDLNL VQALRQFLWS
160 170 180 190 200
FRLPGEAQKI DRMMEAFAQR YCLCNPGVFQ STDTCYVLSF AVIMLNTSLH
210 220 230 240 250
NPNVRDKPGL ERFVAMNRGI NEGGDLPEDL LRNLYDSIRN EPFKIPEDDG
260 270 280 290 300
NDLTHTFFNP DREGWLLKLA 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):46,585
Last modified:July 27, 2011 - v2
Checksum:i8F6F4F7C2F931A89
GO
Isoform 2 (identifier: P63034-2) [UniParc] [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     273-273: Missing.

Note: No experimental confirmation available.
Show »
Length:399
Mass (Da):46,429
Checksum:iD9234871F91E91F8
GO
Isoform 3 (identifier: P63034-3) [UniParc] [UniParc]FASTAAdd to basket
Also known as: CLM2-B

The sequence of this isoform differs from the canonical sequence as follows:
     1-16: Missing.

Show »
Length:384
Mass (Da):44,726
Checksum:i7618245206969DB0
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti270 – 2701A → G in BAA33429 (PubMed:9744817).Curated
Sequence conflicti270 – 2701A → G in BAA33430 (PubMed:9744817).Curated
Sequence conflicti270 – 2701A → G in BAA33431 (PubMed:9744817).Curated
Sequence conflicti270 – 2701A → G in BAA33432 (PubMed:9744817).Curated
Sequence conflicti270 – 2701A → G in AAC77924 (Ref. 2) Curated
Sequence conflicti270 – 2701A → G in BAC32376 (Ref. 2) Curated
Sequence conflicti270 – 2701A → G in BAE25558 (PubMed:16141072).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1616Missing in isoform 3. 1 PublicationVSP_006037Add
BLAST
Alternative sequencei273 – 2731Missing in isoform 2. CuratedVSP_006038

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB013466 mRNA. Translation: BAA33429.1.
AB013467 mRNA. Translation: BAA33430.1.
AB013469 Genomic DNA. Translation: BAA33431.1.
AB013469 Genomic DNA. Translation: BAA33432.1.
AF079971 mRNA. Translation: AAC77924.1.
AK045451 mRNA. Translation: BAC32376.1.
AK143829 mRNA. Translation: BAE25558.1.
AC149053 Genomic DNA. No translation available.
CCDSiCCDS52249.1. [P63034-2]
RefSeqiNP_001106171.1. NM_001112701.1.
NP_035311.1. NM_011181.3.
UniGeneiMm.272130.

Genome annotation databases

EnsembliENSMUST00000056820; ENSMUSP00000051423; ENSMUSG00000003269. [P63034-1]
GeneIDi19158.
KEGGimmu:19158.
UCSCiuc009gxf.2. mouse.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB013466 mRNA. Translation: BAA33429.1.
AB013467 mRNA. Translation: BAA33430.1.
AB013469 Genomic DNA. Translation: BAA33431.1.
AB013469 Genomic DNA. Translation: BAA33432.1.
AF079971 mRNA. Translation: AAC77924.1.
AK045451 mRNA. Translation: BAC32376.1.
AK143829 mRNA. Translation: BAE25558.1.
AC149053 Genomic DNA. No translation available.
CCDSiCCDS52249.1. [P63034-2]
RefSeqiNP_001106171.1. NM_001112701.1.
NP_035311.1. NM_011181.3.
UniGeneiMm.272130.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1U27X-ray2.30A260-378[»]
1U29X-ray1.80A260-378[»]
ProteinModelPortaliP63034.
SMRiP63034. Positions 56-400.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202412. 2 interactions.
IntActiP63034. 1 interaction.
STRINGi10090.ENSMUSP00000103357.

PTM databases

iPTMnetiP63034.
PhosphoSiteiP63034.

Proteomic databases

MaxQBiP63034.
PaxDbiP63034.
PRIDEiP63034.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000056820; ENSMUSP00000051423; ENSMUSG00000003269. [P63034-1]
GeneIDi19158.
KEGGimmu:19158.
UCSCiuc009gxf.2. mouse.

Organism-specific databases

CTDi9266.
MGIiMGI:1334255. Cyth2.

Phylogenomic databases

eggNOGiKOG0930. Eukaryota.
COG5307. LUCA.
GeneTreeiENSGT00760000119036.
HOGENOMiHOG000253023.
HOVERGENiHBG002647.
InParanoidiP63034.
KOiK18441.
OMAiEKDEWIH.

Enzyme and pathway databases

ReactomeiR-MMU-6811438. Intra-Golgi traffic.

Miscellaneous databases

EvolutionaryTraceiP63034.
PROiP63034.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000003269.
ExpressionAtlasiP63034. baseline and differential.
GenevisibleiP63034. MM.

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_MOUSE
AccessioniPrimary (citable) accession number: P63034
Secondary accession number(s): E9QJX3
, O89099, P97695, Q3UP39
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 31, 2004
Last sequence update: July 27, 2011
Last modified: September 7, 2016
This is version 103 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.