RIPR2_RAT
ID RIPR2_RAT Reviewed; 1310 AA.
AC Q7TP54;
DT 07-JAN-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Rho family-interacting cell polarization regulator 2 {ECO:0000312|RGD:1306939};
GN Name=Ripor2 {ECO:0000312|RGD:1306939}; Synonyms=Fam65b;
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 MRNA].
RA Xu C.S., Li W.Q., Li Y.C., Ma H., Wang L., Wang S.F., Han H.P., Wang G.P.,
RA Chai L.Q., Yuan J.Y., Yang K.J., Yan H.M., Chang C.F., Zhao L.F., Shi J.B.,
RA Rahman S., Wang Q.N., Zhang J.B.;
RT "Liver regeneration after PH.";
RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-682, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [4]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=24958875; DOI=10.1073/pnas.1401950111;
RA Diaz-Horta O., Subasioglu-Uzak A., Grati M., DeSmidt A., Foster J., Cao L.,
RA Bademci G., Tokgoz-Yilmaz S., Duman D., Cengiz F.B., Abad C., Mittal R.,
RA Blanton S., Liu X.Z., Farooq A., Walz K., Lu Z., Tekin M.;
RT "FAM65B is a membrane-associated protein of hair cell stereocilia required
RT for hearing.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:9864-9868(2014).
CC -!- FUNCTION: Acts as an inhibitor of the small GTPase RHOA and plays
CC several roles in the regulation of myoblast and hair cell
CC differentiation, lymphocyte T proliferation and neutrophil
CC polarization. Plays a role in fetal mononuclear myoblast
CC differentiation by promoting filopodia and myotube formation (By
CC similarity). Maintains naive T lymphocytes in a quiescent state and
CC prevents chemokine-induced T lymphocyte responses, such as cell
CC adhesion, polarization and migration (By similarity). Involved also in
CC the regulation of neutrophil polarization, chemotaxis and adhesion.
CC Required for normal development of inner and outer hair cell
CC stereocilia within the cochlea of the inner ear. Plays a role for
CC maintaining the structural organization of the basal domain of
CC stereocilia. Involved in mechanosensory hair cell function. Required
CC for normal hearing (By similarity). {ECO:0000250|UniProtKB:Q80U16,
CC ECO:0000250|UniProtKB:Q9Y4F9}.
CC -!- SUBUNIT: Homooligomer; homooligomerization is regulated by RHOC and
CC leads to the formation of concatemers through the association of N- and
CC C-termini (By similarity). Interacts (phosphorylated form) with 14-3-3
CC proteins; these interactions occur during myogenic cell differentiation
CC and also induces T cell proliferation arrest (By similarity). Interacts
CC (phosphorylated form) with HDAC6; this interaction occurs during early
CC myogenic differentiation, prevents HDAC6 to deacetylate tubulin and
CC also induces T cell proliferation arrest (By similarity). Interacts
CC with DYSF; this interaction occurs during early myogenic
CC differentiation (By similarity). Interacts with MYOF (By similarity).
CC Interacts (via active GTP- or inactive GDP-bound forms) with RHOA; this
CC interaction is direct, blocks the loading of GTP to RHOA and decreases
CC upon chemokine CCL19 stimulation in primary T lymphocytes. Interacts
CC with RHOC (By similarity). Interacts (via phosphorylated form) with
CC YWHAB; this interaction occurs in a chemokine-dependent manner and does
CC not compete for binding of RIPOR2 with RHOA nor blocks inhibition of
CC RIPOR2-mediated RHOA activity (By similarity). Interacts with YWHAE (By
CC similarity). Interacts with YWHAQ (By similarity).
CC {ECO:0000250|UniProtKB:Q80U16, ECO:0000250|UniProtKB:Q9Y4F9}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9Y4F9}.
CC Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:Q9Y4F9}. Cell
CC projection, filopodium {ECO:0000250|UniProtKB:Q9Y4F9}. Apical cell
CC membrane {ECO:0000269|PubMed:24958875}. Cell projection, stereocilium
CC {ECO:0000250|UniProtKB:Q80U16}. Cell projection, stereocilium membrane
CC {ECO:0000269|PubMed:24958875}. Note=Localized in the cytoplasm in cells
CC undergoing mitosis (By similarity). Colocalized with F-actin.
CC Accumulates at the leading edge of polarized neutrophils in a
CC chemokine-dependent manner. Localized with RHOC within the basal domain
CC of hair cell stereocilia, near the taper region. Detected in punctate
CC pattern forming a circumferential ring at the stereocilia base (By
CC similarity). Localized to the apical stereocilia of inner and outer
CC hair cells (PubMed:24958875). {ECO:0000250|UniProtKB:Q80U16,
CC ECO:0000250|UniProtKB:Q9Y4F9, ECO:0000269|PubMed:24958875}.
CC -!- TISSUE SPECIFICITY: Expressed in the cochlea (at protein level).
CC {ECO:0000269|PubMed:24958875}.
CC -!- PTM: Phosphorylated. Chemokine-induced phosphorylation in neutrophils
CC occurs in a PKC- and AKT-dependent manner, resulting in RIPOR2
CC interaction with YWHAB and stabilization. Phosphorylated by PKCA, AKT1
CC and MAPKAPK1A; in vitro. {ECO:0000250|UniProtKB:Q9Y4F9}.
CC -!- SIMILARITY: Belongs to the RIPOR family. {ECO:0000305}.
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; AABR06091621; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AY325194; AAP92595.1; -; mRNA.
DR RefSeq; NP_001014031.2; NM_001014009.2.
DR AlphaFoldDB; Q7TP54; -.
DR SMR; Q7TP54; -.
DR IntAct; Q7TP54; 2.
DR MINT; Q7TP54; -.
DR STRING; 10116.ENSRNOP00000048390; -.
DR iPTMnet; Q7TP54; -.
DR PhosphoSitePlus; Q7TP54; -.
DR jPOST; Q7TP54; -.
DR PaxDb; Q7TP54; -.
DR PRIDE; Q7TP54; -.
DR Ensembl; ENSRNOT00000048298; ENSRNOP00000048390; ENSRNOG00000018804.
DR GeneID; 306934; -.
DR KEGG; rno:306934; -.
DR UCSC; RGD:1306939; rat.
DR CTD; 9750; -.
DR RGD; 1306939; Ripor2.
DR eggNOG; KOG2332; Eukaryota.
DR GeneTree; ENSGT00940000153717; -.
DR HOGENOM; CLU_006211_0_0_1; -.
DR InParanoid; Q7TP54; -.
DR OMA; HENEQSR; -.
DR OrthoDB; 1121546at2759; -.
DR PhylomeDB; Q7TP54; -.
DR TreeFam; TF329332; -.
DR PRO; PR:Q7TP54; -.
DR Proteomes; UP000002494; Chromosome 17.
DR Bgee; ENSRNOG00000018804; Expressed in spleen and 19 other tissues.
DR GO; GO:0016324; C:apical plasma membrane; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; ISS:UniProtKB.
DR GO; GO:0030175; C:filopodium; ISS:UniProtKB.
DR GO; GO:0032420; C:stereocilium; IDA:UniProtKB.
DR GO; GO:0060171; C:stereocilium membrane; IDA:MGI.
DR GO; GO:0071889; F:14-3-3 protein binding; ISS:UniProtKB.
DR GO; GO:0008199; F:ferric iron binding; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0060088; P:auditory receptor cell stereocilium organization; ISO:RGD.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:1990869; P:cellular response to chemokine; ISS:UniProtKB.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; ISO:RGD.
DR GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR GO; GO:0045184; P:establishment of protein localization; ISO:RGD.
DR GO; GO:0007162; P:negative regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:1903904; P:negative regulation of establishment of T cell polarity; ISS:UniProtKB.
DR GO; GO:1905872; P:negative regulation of protein localization to cell leading edge; ISS:UniProtKB.
DR GO; GO:2001107; P:negative regulation of Rho guanyl-nucleotide exchange factor activity; ISS:UniProtKB.
DR GO; GO:0035024; P:negative regulation of Rho protein signal transduction; ISS:UniProtKB.
DR GO; GO:2000405; P:negative regulation of T cell migration; ISS:UniProtKB.
DR GO; GO:0051491; P:positive regulation of filopodium assembly; ISS:UniProtKB.
DR GO; GO:0045663; P:positive regulation of myoblast differentiation; ISS:UniProtKB.
DR GO; GO:1901741; P:positive regulation of myoblast fusion; ISS:UniProtKB.
DR GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; ISS:UniProtKB.
DR GO; GO:2000391; P:positive regulation of neutrophil extravasation; ISS:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; ISO:RGD.
DR GO; GO:2000114; P:regulation of establishment of cell polarity; ISS:UniProtKB.
DR GO; GO:0007605; P:sensory perception of sound; ISS:UniProtKB.
DR GO; GO:0048741; P:skeletal muscle fiber development; IEA:InterPro.
DR Gene3D; 1.20.1260.10; -; 2.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR031780; FAM65_N.
DR InterPro; IPR033035; FAM65B.
DR InterPro; IPR012347; Ferritin-like.
DR InterPro; IPR009040; Ferritin-like_diiron.
DR InterPro; IPR009078; Ferritin-like_SF.
DR InterPro; IPR014034; Ferritin_CS.
DR InterPro; IPR008331; Ferritin_DPS_dom.
DR InterPro; IPR026136; RIPOR3.
DR PANTHER; PTHR15829; PTHR15829; 2.
DR PANTHER; PTHR15829:SF2; PTHR15829:SF2; 2.
DR Pfam; PF00210; Ferritin; 1.
DR Pfam; PF15903; PL48; 2.
DR SUPFAM; SSF47240; SSF47240; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS00204; FERRITIN_2; 1.
DR PROSITE; PS50905; FERRITIN_LIKE; 1.
PE 1: Evidence at protein level;
KW Cell adhesion; Cell membrane; Cell projection; Chemotaxis; Coiled coil;
KW Cytoplasm; Cytoskeleton; Differentiation; Hearing; Membrane; Myogenesis;
KW Phosphoprotein; Reference proteome; Signal transduction inhibitor.
FT CHAIN 1..1310
FT /note="Rho family-interacting cell polarization regulator
FT 2"
FT /id="PRO_0000431658"
FT REGION 196..254
FT /note="Involved in cell filopodia formation"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4F9"
FT REGION 588..639
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 224..253
FT /evidence="ECO:0000255"
FT COMPBIAS 588..608
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 609..632
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 123
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4F9"
FT MOD_RES 178
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4F9"
FT MOD_RES 508
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4F9"
FT MOD_RES 682
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 1310 AA; 144709 MW; A87C9C7C5CC95BA1 CRC64;
MQHCLEQSDI TQYQQYYSSW CDARALGPRL SPVALSLLVG RNEHRLSAEP EVHRSQGRCV
GVEVPREDIN YLSTTCKPEI KSRNLKEDSE DQGRLPTRLP EIMLVGSQSF SPGGPNGIIR
SQSFAGFSGL QERRSRQVLG VSPGITRAPS KDVYCKPGYA CRVEFLLCKA FSKQTCNSFI
ENASALKKPQ AKLKKMHNLG HKNTNTPKEP QPKRVEEVYR ALKNGLDEYL EFHQTELDKL
TAQLKDMKRN SRLGVLYDLD KGVLYDLDKV DELYEAYCIQ RRLQDGASKM KQAFATSPAS
KAARESLSEI NRSYKEYTEN MCTIEAELES LLGEFSIKMK GLAGFARLCP GDQYESMDGP
NPYQRQQGEV YFSLLATRRI GDGSCLSKGA RIFMKYGRQR WKLKGKIEVN GKQSWDGEET
VFLPLIVGFI SIKVTELKGL ATHILVGSVT CETKELFAAR PQVVAVDIND LGTIKLNLEI
TWYPFDVEDT TPSSGPGNKT AALQRRMSMY SQGTPETPTF KDQSFFSNLP DDIFESGNAA
EEKRPLSLSF SDLQDGDCVF TSSSTTSPSS SHSAHPEITI TPAELTHSSL SSQNEGTEDS
SSASSRNSLG EDHEPKSHSK SDTVEPKKPS VDARSGTESL FLENSVAEAL LQESDEASEL
KPVELDTFEG NITKQLVKRL TSAEGPITTN KLFFEGSVGS ESEAGRSFLD GSLEDAFNGL
FLALDPHKEQ YKEFQDLNQE VTHLDDVLKC KPAGSRSRSS SLSLTVESAL ESFDFLNTSD
FDEEEEDGDE VCHVGGGADS VFSDTETEKS GSVHPEARGH LSEALTEDTG VGTSVAGSPL
PLTTGNESLD ITIVKHLQYC TQLVQQIVFS SKTPFVARSL LEKLSRQVLV LQKLAAVSDE
NLGNITSVVE AIPEFHKKPS LLSFWTKCCS PSGVYHSSAA HLIKQLEASF ARNINKDYPG
LAEPVFRTLV SQILDRAEPL LCSGLSSEVI TVFQYYSFLT SHGVSDLETH LGQLARQVAM
VQTLQSLRDE KLLQTMSDLA PSNLPAQQEV LRTLALLLTK DDNEVSEAVT LYLAAASKNE
HFREKALLYY CEALTKTNLQ LQKAACLALK SLEATESIKM LVTLCQSDTE EIRTVASETL
LSLAPYSGSA MTSQIRQNYS TEVEAAVNRL VNLHLRASYT YLSLGFFFDP DDVALEGNER
GGRALFQDVQ KPSQDEWGKT LEAMEAALAL EKNLNQALLD LHALGSARTD PHLCDFLESH
FLDKEVKLIK KMGNHLTNLR RVAGPQPAQT GVAQASLGEY LFERLTLKHD
