ID   OPHN1_RAT               Reviewed;         802 AA.
AC   P0CAX5;
DT   07-JUL-2009, integrated into UniProtKB/Swiss-Prot.
DT   07-JUL-2009, sequence version 1.
DT   03-AUG-2022, entry version 91.
DE   RecName: Full=Oligophrenin-1;
GN   Name=Ophn1;
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 [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP   HOMER1.
RX   PubMed=15034583; DOI=10.1038/nn1210;
RA   Govek E.E., Newey S.E., Akerman C.J., Cross J.R., Van der Veken L.,
RA   Van Aelst L.;
RT   "The X-linked mental retardation protein oligophrenin-1 is required for
RT   dendritic spine morphogenesis.";
RL   Nat. Neurosci. 7:364-372(2004).
RN   [3]
RP   TISSUE SPECIFICITY.
RX   PubMed=15026118; DOI=10.1016/j.neuroscience.2004.01.007;
RA   Xiao J., Neylon C.B., Nicholson G.A., Furness J.B.;
RT   "Evidence that a major site of expression of the RHO-GTPASE activating
RT   protein, oligophrenin-1, is peripheral myelin.";
RL   Neuroscience 124:781-787(2004).
RN   [4]
RP   FUNCTION, AND INTERACTION WITH SH3GL2.
RX   PubMed=19481455; DOI=10.1016/j.cub.2009.05.022;
RA   Nakano-Kobayashi A., Kasri N.N., Newey S.E., Van Aelst L.;
RT   "The Rho-linked mental retardation protein OPHN1 controls synaptic vesicle
RT   endocytosis via endophilin A1.";
RL   Curr. Biol. 19:1133-1139(2009).
RN   [5]
RP   FUNCTION, INTERACTION WITH AMPA RECEPTOR COMPLEXES, AND SUBCELLULAR
RP   LOCATION.
RX   PubMed=19487570; DOI=10.1101/gad.1783809;
RA   Nadif Kasri N., Nakano-Kobayashi A., Malinow R., Li B., Van Aelst L.;
RT   "The Rho-linked mental retardation protein oligophrenin-1 controls synapse
RT   maturation and plasticity by stabilizing AMPA receptors.";
RL   Genes Dev. 23:1289-1302(2009).
RN   [6]
RP   INTERACTION WITH NR1D1.
RX   PubMed=21874017; DOI=10.1038/nn.2911;
RA   Valnegri P., Khelfaoui M., Dorseuil O., Bassani S., Lagneaux C.,
RA   Gianfelice A., Benfante R., Chelly J., Billuart P., Sala C., Passafaro M.;
RT   "A circadian clock in hippocampus is regulated by interaction between
RT   oligophrenin-1 and Rev-erbalpha.";
RL   Nat. Neurosci. 14:1293-1301(2011).
CC   -!- FUNCTION: Stimulates GTP hydrolysis of members of the Rho family. Its
CC       action on RHOA activity and signaling is implicated in growth and
CC       stabilization of dendritic spines, and therefore in synaptic function,
CC       in hippocampal neurons. Critical for the stabilization of AMPA
CC       receptors at postsynaptic sites. Critical for the regulation of
CC       synaptic vesicle endocytosis at pre-synaptic terminals. Required for
CC       the localization of NR1D1 to dendrites, can suppress its repressor
CC       activity and protect it from proteasomal degradation.
CC       {ECO:0000269|PubMed:15034583, ECO:0000269|PubMed:19481455,
CC       ECO:0000269|PubMed:19487570}.
CC   -!- SUBUNIT: Interacts with HOMER1. Interacts with AMPA receptor complexes.
CC       Interacts with SH3GL2 (endophilin-A1). Interacts (via C-terminus) with
CC       NR1D1. {ECO:0000269|PubMed:15034583, ECO:0000269|PubMed:19481455,
CC       ECO:0000269|PubMed:19487570, ECO:0000269|PubMed:21874017}.
CC   -!- SUBCELLULAR LOCATION: Postsynapse {ECO:0000269|PubMed:15034583,
CC       ECO:0000269|PubMed:19487570}. Presynapse {ECO:0000269|PubMed:15034583,
CC       ECO:0000305|PubMed:19481455}. Cell projection, axon
CC       {ECO:0000269|PubMed:15034583}. Cell projection, dendritic spine
CC       {ECO:0000269|PubMed:15034583}. Cell projection, dendrite
CC       {ECO:0000250|UniProtKB:Q99J31}. Cytoplasm
CC       {ECO:0000250|UniProtKB:Q99J31}.
CC   -!- TISSUE SPECIFICITY: High expression in brain, particularly in the
CC       cerebellum, hippocampus, thalamus, frontal lobes, sensory cortex. Found
CC       in the myelin sheaths of peripheral nerves, chromaffin cells within the
CC       adrenal medulla, and in extra-adrenal chromaffin cells associated with
CC       celiac ganglia. {ECO:0000269|PubMed:15026118,
CC       ECO:0000269|PubMed:15034583}.
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DR   EMBL; CH473966; EDL95953.1; -; Genomic_DNA.
DR   RefSeq; NP_001101318.1; NM_001107848.1.
DR   RefSeq; XP_006257134.1; XM_006257072.3.
DR   RefSeq; XP_017457518.1; XM_017602029.1.
DR   AlphaFoldDB; P0CAX5; -.
DR   SMR; P0CAX5; -.
DR   STRING; 10116.ENSRNOP00000035867; -.
DR   PhosphoSitePlus; P0CAX5; -.
DR   PaxDb; P0CAX5; -.
DR   PRIDE; P0CAX5; -.
DR   Ensembl; ENSRNOT00000034772; ENSRNOP00000035867; ENSRNOG00000026573.
DR   GeneID; 312108; -.
DR   KEGG; rno:312108; -.
DR   CTD; 4983; -.
DR   RGD; 1563435; Ophn1.
DR   eggNOG; KOG1451; Eukaryota.
DR   GeneTree; ENSGT00940000160157; -.
DR   HOGENOM; CLU_011532_2_1_1; -.
DR   InParanoid; P0CAX5; -.
DR   OMA; MKRMKQP; -.
DR   OrthoDB; 693048at2759; -.
DR   PhylomeDB; P0CAX5; -.
DR   Reactome; R-RNO-8980692; RHOA GTPase cycle.
DR   Reactome; R-RNO-9013026; RHOB GTPase cycle.
DR   Reactome; R-RNO-9013106; RHOC GTPase cycle.
DR   Reactome; R-RNO-9013148; CDC42 GTPase cycle.
DR   Reactome; R-RNO-9013149; RAC1 GTPase cycle.
DR   Reactome; R-RNO-9013404; RAC2 GTPase cycle.
DR   Reactome; R-RNO-9013406; RHOQ GTPase cycle.
DR   Reactome; R-RNO-9013408; RHOG GTPase cycle.
DR   Reactome; R-RNO-9013409; RHOJ GTPase cycle.
DR   Reactome; R-RNO-9013423; RAC3 GTPase cycle.
DR   PRO; PR:P0CAX5; -.
DR   Proteomes; UP000002494; Chromosome X.
DR   Proteomes; UP000234681; Chromosome x.
DR   Bgee; ENSRNOG00000026573; Expressed in heart and 19 other tissues.
DR   ExpressionAtlas; P0CAX5; baseline and differential.
DR   Genevisible; P0CAX5; RN.
DR   GO; GO:0015629; C:actin cytoskeleton; ISO:RGD.
DR   GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR   GO; GO:0030425; C:dendrite; ISO:RGD.
DR   GO; GO:0043197; C:dendritic spine; ISO:RGD.
DR   GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR   GO; GO:0043195; C:terminal bouton; ISO:RGD.
DR   GO; GO:0003779; F:actin binding; ISO:RGD.
DR   GO; GO:0005096; F:GTPase activator activity; ISO:RGD.
DR   GO; GO:0035255; F:ionotropic glutamate receptor binding; IPI:RGD.
DR   GO; GO:0005543; F:phospholipid binding; ISO:RGD.
DR   GO; GO:0030036; P:actin cytoskeleton organization; ISO:RGD.
DR   GO; GO:0034329; P:cell junction assembly; ISS:UniProtKB.
DR   GO; GO:0048667; P:cell morphogenesis involved in neuron differentiation; ISO:RGD.
DR   GO; GO:0021707; P:cerebellar granule cell differentiation; ISO:RGD.
DR   GO; GO:0021895; P:cerebral cortex neuron differentiation; ISO:RGD.
DR   GO; GO:0045198; P:establishment of epithelial cell apical/basal polarity; ISS:UniProtKB.
DR   GO; GO:0098880; P:maintenance of postsynaptic specialization structure; IDA:SynGO.
DR   GO; GO:1901799; P:negative regulation of proteasomal protein catabolic process; ISO:RGD.
DR   GO; GO:0030182; P:neuron differentiation; ISO:RGD.
DR   GO; GO:0031175; P:neuron projection development; ISO:RGD.
DR   GO; GO:0030100; P:regulation of endocytosis; ISO:RGD.
DR   GO; GO:0099149; P:regulation of postsynaptic neurotransmitter receptor internalization; ISO:RGD.
DR   GO; GO:0035023; P:regulation of Rho protein signal transduction; ISO:RGD.
DR   GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; ISO:RGD.
DR   GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR   GO; GO:0048488; P:synaptic vesicle endocytosis; ISO:RGD.
DR   Gene3D; 1.10.555.10; -; 1.
DR   Gene3D; 1.20.1270.60; -; 1.
DR   Gene3D; 2.30.29.30; -; 1.
DR   InterPro; IPR027267; AH/BAR_dom_sf.
DR   InterPro; IPR011993; PH-like_dom_sf.
DR   InterPro; IPR001849; PH_domain.
DR   InterPro; IPR008936; Rho_GTPase_activation_prot.
DR   InterPro; IPR000198; RhoGAP_dom.
DR   Pfam; PF00169; PH; 1.
DR   Pfam; PF00620; RhoGAP; 1.
DR   SMART; SM00233; PH; 1.
DR   SMART; SM00324; RhoGAP; 1.
DR   SUPFAM; SSF103657; SSF103657; 1.
DR   SUPFAM; SSF48350; SSF48350; 1.
DR   PROSITE; PS50003; PH_DOMAIN; 1.
DR   PROSITE; PS50238; RHOGAP; 1.
PE   1: Evidence at protein level;
KW   Cell projection; Cytoplasm; Endocytosis; GTPase activation; Neurogenesis;
KW   Reference proteome; Synapse.
FT   CHAIN           1..802
FT                   /note="Oligophrenin-1"
FT                   /id="PRO_0000379470"
FT   DOMAIN          265..368
FT                   /note="PH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT   DOMAIN          380..564
FT                   /note="Rho-GAP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT   REGION          641..663
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          682..802
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        713..728
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        737..751
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        752..802
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   802 AA;  91839 MW;  3CC11A730587B97A CRC64;
     MGHPPLEFSD CYLDSPDFRE RLKCYEQELE RTNKFIKDVI KDGSALISAM RSYSSAVQKF
     SQTLQSFQFD FIGDTLTDDE INIAESFKEF AELLNEVENE RMMMVQNASD LLIKPLETFR
     KEQIGFTKER KKKFEKDGER FYSLLDRHLH LSSKKKESQL LEADLQVDKE RHNFFESSLD
     YVYQIQEVQE SKKFNIVEPV LAFLHSLFIS NSLTVELTQD FLPYKQQLQL SLQNTRNHFS
     STREEMEELK KRMKEAPQTC KLPGQPTIEG YLYTQEKWAL GISWVKYYCR YEKETRTLTM
     TPTEQKPGAK QGPVDLTLKY CVRRKTESID KRFCFDIEAN ERTGTITLQA PSEANRRLWM
     EAMDGKEPIY HSPITKQEEM ELNEVGFKFV RKCINFIETK GIKTEGLYRT VGSNIQVQKL
     LNAFFDPKCP GDVDFYNSDW DIKTITSSLK FYLRNLSEPV MTYKLHKELV SAAKSDNLDY
     RLGAIHSLVY KLPEKNREML ELLIKHLVNV CEHSKENLMT PSNMGVIFGP TLMRAQEDTV
     AAMMNIKFQN IVVEILIEHF GKIYLGPPED SQVPPVPPPR VTARRHKPIT ISKRLLREKA
     VFYTPSLDDV EDEIHHPTPN GTIASNLDPP KQLQHLKLPM QKSGEMDPGR KSPSRPVSDC
     QTEPCLEADM GKLVYRLQDG GTKAIPKASN GPVPGSGHTK TSSFHIKRPA PRPIVHHKEG
     DTDCFSKVRP PGEKQTIIRP PVRPPDPPCR SSTSQKPESK PETVSSNAEE IPSSVVASRT
     RFFETASRKT GSSQGKLPGD ES