CYH2_RAT
ID CYH2_RAT Reviewed; 400 AA.
AC P63035; O89099; P97695;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 31-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Cytohesin-2;
DE AltName: Full=ARF nucleotide-binding site opener;
DE Short=Protein ARNO;
DE AltName: Full=PH, SEC7 and coiled-coil domain-containing protein 2;
DE Short=CLM2;
DE AltName: Full=SEC7 homolog B;
GN Name=Cyth2; Synonyms=Pscd2, Sec7b;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=9352219;
RA Telemenakis I., Benseler F., Stenius K., Suedhof T.C., Brose N.;
RT "Rat homologues of yeast sec7p.";
RL Eur. J. Cell Biol. 74:143-149(1997).
RN [2]
RP INTERACTION WITH TAMALIN.
RC TISSUE=Brain;
RX PubMed=11850456; DOI=10.1523/jneurosci.22-04-01280.2002;
RA Kitano J., Kimura K., Yamazaki Y., Soda T., Shigemoto R., Nakajima Y.,
RA Nakanishi S.;
RT "Tamalin, a PDZ domain-containing protein, links a protein complex
RT formation of group 1 metabotropic glutamate receptors and the guanine
RT nucleotide exchange factor cytohesins.";
RL J. Neurosci. 22:1280-1289(2002).
RN [3]
RP DEVELOPMENTAL STAGE.
RX PubMed=11834294; DOI=10.1016/s0169-328x(01)00312-6;
RA Suzuki I., Owada Y., Suzuki R., Yoshimoto T., Kondo H.;
RT "Localization of mRNAs for subfamily of guanine nucleotide-exchange
RT proteins (GEP) for ARFs (ADP-ribosylation factors) in the brain of
RT developing and mature rats under normal and postaxotomy conditions.";
RL Brain Res. Mol. Brain Res. 98:41-50(2002).
CC -!- FUNCTION: Acts as a guanine-nucleotide exchange factor (GEF). Promotes
CC guanine-nucleotide exchange on ARF1, ARF3 and ARF6. Promotes the
CC activation of ARF factors through replacement of GDP with GTP. The cell
CC membrane form, in association with ARL4 proteins, recruits ARF6 to the
CC plasma membrane (By similarity). Involved in neurite growth (By
CC similarity). {ECO:0000250|UniProtKB:P63034,
CC ECO:0000250|UniProtKB:Q99418}.
CC -!- SUBUNIT: Heteromer. Composed of TAMALIN, CYTH2 and at least one GRM1.
CC Interacts with ARRB1. Interacts with ARL4D; the interaction is direct
CC (By similarity). Directly interacts with CCDC120 through the coiled
CC coil domain; this interaction stabilizes CCDC120, possibly by
CC preventing its ubiquitination, and is required for neurite growth in a
CC neuroblastoma cell line. Interacts with FRMD4A (By similarity).
CC Interacts (via N-terminal domain) with INAVA (via N-terminal domain)
CC (By similarity). {ECO:0000250|UniProtKB:P63034,
CC ECO:0000250|UniProtKB:Q99418}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q99418};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:Q99418}. Cytoplasm
CC {ECO:0000250|UniProtKB:P63034}. Cell projection
CC {ECO:0000250|UniProtKB:P63034}. Cell projection, growth cone
CC {ECO:0000250|UniProtKB:P63034}. Cell junction, tight junction
CC {ECO:0000250|UniProtKB:P63034}. Cell junction, adherens junction
CC {ECO:0000250|UniProtKB:P63034}. Note=Recruited to the cell membrane
CC through its association with ARL4A, ARL4C and ARL4D. Requires also
CC interaction with phosphoinositides for targeting to plasma membrane (By
CC similarity). In differentiating neuroblastoma cells, colocalizes with
CC CCDC120 in both neurite shaft and growth cone areas (By similarity).
CC {ECO:0000250, ECO:0000250|UniProtKB:P63034}.
CC -!- TISSUE SPECIFICITY: Present in all tissues tested, with highest protein
CC levels in brain and adrenal. {ECO:0000269|PubMed:9352219}.
CC -!- DEVELOPMENTAL STAGE: On embryonic days 15 (E15) and E18, a weak
CC expression is seen in the mantle and ventricular germinal zones
CC throughout the neuraxis. On postnatal days 0 (P0) and P7, weakly
CC expressed in the gray matter, but not in the white matter, throughout
CC the brain. In the cerebellum, the expression is seen in the external
CC granule cell layer. {ECO:0000269|PubMed:11834294}.
CC -!- DOMAIN: Binds via its PH domain to the inositol head group of
CC phosphatidylinositol 3,4,5-trisphosphate. The PH domain is necessary
CC and sufficient for plasma membrane relocalization (By similarity).
CC {ECO:0000250}.
CC -!- DOMAIN: Autoinhibited by its C-terminal basic region. {ECO:0000250}.
CC -!- DOMAIN: The coiled coil domain is involved in interaction with CCDC120.
CC {ECO:0000250|UniProtKB:P63034}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U83896; AAB41444.1; -; mRNA.
DR RefSeq; NP_446363.1; NM_053911.2.
DR AlphaFoldDB; P63035; -.
DR BMRB; P63035; -.
DR SMR; P63035; -.
DR BioGRID; 250574; 2.
DR CORUM; P63035; -.
DR IntAct; P63035; 2.
DR MINT; P63035; -.
DR STRING; 10116.ENSRNOP00000028588; -.
DR PhosphoSitePlus; P63035; -.
DR jPOST; P63035; -.
DR PaxDb; P63035; -.
DR PRIDE; P63035; -.
DR Ensembl; ENSRNOT00000028588; ENSRNOP00000028588; ENSRNOG00000021051.
DR GeneID; 116692; -.
DR KEGG; rno:116692; -.
DR UCSC; RGD:620398; rat.
DR CTD; 9266; -.
DR RGD; 620398; Cyth2.
DR eggNOG; KOG0930; Eukaryota.
DR GeneTree; ENSGT00940000160074; -.
DR InParanoid; P63035; -.
DR OrthoDB; 657055at2759; -.
DR PhylomeDB; P63035; -.
DR Reactome; R-RNO-6811438; Intra-Golgi traffic.
DR PRO; PR:P63035; -.
DR Proteomes; UP000002494; Chromosome 1.
DR GO; GO:0005912; C:adherens junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005923; C:bicellular tight junction; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0098892; C:extrinsic component of postsynaptic specialization membrane; IDA:SynGO.
DR GO; GO:0030426; C:growth cone; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0001726; C:ruffle; IDA:RGD.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISS:UniProtKB.
DR GO; GO:0070679; F:inositol 1,4,5 trisphosphate binding; ISS:UniProtKB.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:2000171; P:negative regulation of dendrite development; IMP:RGD.
DR GO; GO:0032012; P:regulation of ARF protein signal transduction; IEA:InterPro.
DR CDD; cd00171; Sec7; 1.
DR Gene3D; 1.10.1000.11; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR023394; Sec7_C_sf.
DR InterPro; IPR000904; Sec7_dom.
DR InterPro; IPR035999; Sec7_dom_sf.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF01369; Sec7; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00222; Sec7; 1.
DR SUPFAM; SSF48425; SSF48425; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50190; SEC7; 1.
PE 1: Evidence at protein level;
KW Cell junction; Cell membrane; Cell projection; Coiled coil; Cytoplasm;
KW Guanine-nucleotide releasing factor; Lipid-binding; Membrane;
KW Reference proteome; Tight junction.
FT CHAIN 1..400
FT /note="Cytohesin-2"
FT /id="PRO_0000120199"
FT DOMAIN 72..201
FT /note="SEC7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00189"
FT DOMAIN 259..376
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 387..395
FT /note="C-terminal autoinhibitory region"
FT /evidence="ECO:0000250"
FT COILED 10..67
FT /evidence="ECO:0000255"
FT BINDING 268..276
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3,4,5-trisphosphate)"
FT /ligand_id="ChEBI:CHEBI:57836"
FT /evidence="ECO:0000250"
FT BINDING 280
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3,4,5-trisphosphate)"
FT /ligand_id="ChEBI:CHEBI:57836"
FT /evidence="ECO:0000250"
FT BINDING 291
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3,4,5-trisphosphate)"
FT /ligand_id="ChEBI:CHEBI:57836"
FT /evidence="ECO:0000250"
FT BINDING 301
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3,4,5-trisphosphate)"
FT /ligand_id="ChEBI:CHEBI:57836"
FT /evidence="ECO:0000250"
FT BINDING 339
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3,4,5-trisphosphate)"
FT /ligand_id="ChEBI:CHEBI:57836"
FT /evidence="ECO:0000250"
FT BINDING 350
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3,4,5-trisphosphate)"
FT /ligand_id="ChEBI:CHEBI:57836"
FT /evidence="ECO:0000250"
FT BINDING 351
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3,4,5-trisphosphate)"
FT /ligand_id="ChEBI:CHEBI:57836"
FT /evidence="ECO:0000250"
SQ SEQUENCE 400 AA; 46571 MW; 88F14D422A331A89 CRC64;
MEDGVYEPPD LTPEERMELE NIRRRKQELL VEIQRLREEL SEAMSEVEGL EANEGSKTLQ
RNRKMAMGRK KFNMDPKKGI QFLVEHELLQ NTPEEIARFL YKGEGLNKTA IGDYLGEREE
LNLSVLHAFV DLHEFTDLNL VQALRQFLWS FRLPGEAQKI DRMMEAFAQR YCLCNPGVFQ
STDTCYVLSF AVIMLNTSLH NPNVRDKPGL ERFVAMNRGI NEGGDLPEDL LRNLYDSIRN
EPFKIPEDDG NDLTHTFFNP DREGWLLKLG GGRVKTWKRR WFILTDNCLY YFEYTTDKEP
RGIIPLENLS IREVDDPRKP NCFELYIPNN KGQLIKACKT EADGRVVEGN HMVYRISAPT
QEEKDEWIKS IQAAVSVDPF YEMLAARKKR ISVKKKQEQP
