RIPR2_DANRE
ID RIPR2_DANRE Reviewed; 1083 AA.
AC Q1LU99; Q1LWU7;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 1.
DT 03-AUG-2022, entry version 98.
DE RecName: Full=Rho family-interacting cell polarization regulator 2 {ECO:0000250|UniProtKB:Q9Y4F9};
GN Name=ripor2 {ECO:0000250|UniProtKB:Q9Y4F9}; Synonyms=fam65b;
GN ORFNames=si:ch211-81e5.1, si:dkey-218n20.1;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=24687993; DOI=10.1096/fj.13-246470;
RA Balasubramanian A., Kawahara G., Gupta V.A., Rozkalne A., Beauvais A.,
RA Kunkel L.M., Gussoni E.;
RT "Fam65b is important for formation of the HDAC6-dysferlin protein complex
RT during myogenic cell differentiation.";
RL FASEB J. 28:2955-2969(2014).
RN [3]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
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 polarization
CC (By similarity). Plays a role in fetal mononuclear myoblast
CC differentiation by promoting filopodia and myotube formation
CC (PubMed:24958875). Maintains naive T lymphocytes in a quiescent state
CC and prevents chemokine-induced T lymphocyte responses, such as cell
CC adhesion, polarization and migration. Involved also in the regulation
CC of neutrophil polarization, chemotaxis and adhesion. Required for
CC normal development of inner and outer hair cell stereocilia within the
CC cochlea of the inner ear. Plays a role for maintaining the structural
CC organization of the basal domain of stereocilia. Involved in
CC mechanosensory hair cell function (By similarity). Required for normal
CC hearing (PubMed:24958875). {ECO:0000250|UniProtKB:Q80U16,
CC ECO:0000250|UniProtKB:Q9Y4F9, ECO:0000269|PubMed:24687993,
CC ECO:0000269|PubMed:24958875}.
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. {ECO:0000250|UniProtKB:Q80U16}.
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:0000250|UniProtKB:Q7TP54}. Cell projection, stereocilium
CC {ECO:0000250|UniProtKB:Q80U16}. Cell projection, stereocilium membrane
CC {ECO:0000250|UniProtKB:Q7TP54}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q1LU99-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q1LU99-2; Sequence=VSP_034976, VSP_034977, VSP_034978;
CC -!- TISSUE SPECIFICITY: Expressed in the eye, nervous system, and skeletal
CC muscles (PubMed:24687993). Expressed in the otic vesicle
CC (PubMed:24958875). {ECO:0000269|PubMed:24687993,
CC ECO:0000269|PubMed:24958875}.
CC -!- DISRUPTION PHENOTYPE: FAM65B morpholino knockdown leads to significant
CC reduction of numbers of saccular hair cells and neuromasts and to
CC hearing loss (PubMed:24958875). FAM65B knockdown also results in
CC abnormal muscle, with low birefringence, tears at the myosepta, and
CC increased embryo lethality (PubMed:24687993).
CC {ECO:0000269|PubMed:24687993, ECO:0000269|PubMed:24958875}.
CC -!- SIMILARITY: Belongs to the RIPOR family. {ECO:0000305}.
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DR EMBL; BX511258; CAK05003.1; -; Genomic_DNA.
DR EMBL; BX957279; CAK05420.1; -; Genomic_DNA.
DR RefSeq; NP_001038491.1; NM_001045026.1. [Q1LU99-1]
DR AlphaFoldDB; Q1LU99; -.
DR STRING; 7955.ENSDARP00000122491; -.
DR PaxDb; Q1LU99; -.
DR Ensembl; ENSDART00000088427; ENSDARP00000082860; ENSDARG00000061752. [Q1LU99-1]
DR GeneID; 563800; -.
DR KEGG; dre:563800; -.
DR CTD; 9750; -.
DR ZFIN; ZDB-GENE-060503-342; ripor2.
DR eggNOG; ENOG502QQ7T; Eukaryota.
DR GeneTree; ENSGT00940000153717; -.
DR InParanoid; Q1LU99; -.
DR OMA; HENEQSR; -.
DR OrthoDB; 1121546at2759; -.
DR PhylomeDB; Q1LU99; -.
DR PRO; PR:Q1LU99; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 19.
DR Bgee; ENSDARG00000061752; Expressed in granulocyte and 19 other tissues.
DR ExpressionAtlas; Q1LU99; baseline.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
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:0060171; C:stereocilium membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0071889; F:14-3-3 protein binding; ISS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:1990869; P:cellular response to chemokine; ISS:UniProtKB.
DR GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
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:2000114; P:regulation of establishment of cell polarity; ISS:UniProtKB.
DR GO; GO:0007605; P:sensory perception of sound; IMP:ZFIN.
DR GO; GO:0048741; P:skeletal muscle fiber development; IMP:ZFIN.
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; IPR026136; RIPOR3.
DR PANTHER; PTHR15829; PTHR15829; 1.
DR PANTHER; PTHR15829:SF2; PTHR15829:SF2; 1.
DR Pfam; PF15903; PL48; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cell adhesion; Cell membrane; Cell projection;
KW Chemotaxis; Coiled coil; Cytoplasm; Cytoskeleton; Differentiation; Hearing;
KW Membrane; Myogenesis; Reference proteome; Signal transduction inhibitor.
FT CHAIN 1..1083
FT /note="Rho family-interacting cell polarization regulator
FT 2"
FT /id="PRO_0000345987"
FT REGION 21..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 71..111
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 471..508
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 206..240
FT /evidence="ECO:0000255"
FT COMPBIAS 471..492
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 396..405
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_034976"
FT VAR_SEQ 442..444
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_034977"
FT VAR_SEQ 1051
FT /note="G -> GKVSSHKDYTYTAGLVS (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_034978"
FT CONFLICT 783
FT /note="L -> S (in Ref. 1; CAK05003)"
FT /evidence="ECO:0000305"
FT CONFLICT 843
FT /note="T -> S (in Ref. 1; CAK05003)"
FT /evidence="ECO:0000305"
FT CONFLICT 932
FT /note="S -> R (in Ref. 1; CAK05003)"
FT /evidence="ECO:0000305"
FT CONFLICT 944..945
FT /note="KK -> QE (in Ref. 1; CAK05003)"
FT /evidence="ECO:0000305"
FT CONFLICT 977
FT /note="T -> S (in Ref. 1; CAK05003)"
FT /evidence="ECO:0000305"
FT CONFLICT 1005
FT /note="E -> Q (in Ref. 1; CAK05003)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1083 AA; 120498 MW; 97250264211BFB49 CRC64;
MAFPDITEDD LNELMREEAE DVFDDDGVSS RFPDIMAAGT HSPGGPNGII RSQSFAGFST
LQERRSRCNS FMGNSAVQKK PISKPRKPHL SGHKSSSSSS SSREPQPKRV EEVYSALKQG
LDEYLEVHQT ELDKLTSLMK DMKRNSRLGV LYDLDKQIKT IERYMRRLEF HISKVDELYE
GFCIQRRLRD GASKMKQAFT ASPSTKGTRE SLAEVNRRYK EYTENMSTFE GELENLLGEF
HIKMKGLAGF ARLCPGDQYE IFMRYGRQRW KLKGKIEGNS KQSWDGEEMI FMPLISDLIN
IKVTELKGLA THVLVGSVIC ETKDLFTAMP QVVAVDVNDL GTIKLNLEVA WFPFDVEDLT
LSSGNVSKAT ALQRRVSVYS QGTPETPTFQ DTSFFKWQPR RWEGQRLSFL HTLRETLIEK
LRRSRSFGDL AALRPRSRSS LEVYSTLPDD VFENGGCGVA ECKRLSFTFS DTSTSSPVPV
QSNPEITVTP PETDPSSEPP PTSEEQLVEE ECVEEDCGSI SVSVSVSDPD LEWDQVETQG
PETGSVALSL CSESQLSAVG PEDVVFLEPN VSDEALELKP VELDGEEGSL TRQLVRRLTS
SDMLPETSAL SWAGENSRTF MESSLEEVIQ SLLLRLESLG QRCGELQDLE QEVMRLEDLL
KCRVHAHRSR SSSLSLTVES ALESFDFLNT SDFDDDDTGD DAGTLSRAVF FDMESERMGS
GQHPEARGHL SEALTEDTGV GNSVAGSPLP LTTGNENLDV AVVIHLQYCN HLIQLLTSGG
SQLQHKTYLH KLATQTLLLE ELSERNFDRP SSCTSVPDVL PGLVERPALM SLWSDCSGGL
FHTTLDRVLK HMHLSFALGL QQVLPHSPDS VIKMVVNEMM DRSELASSST SPAQDVITVF
QFHRYIVEHC ITDMEQHLLD LAKEVMLEEA LSCGDPERSL KELKKVSITC LQPRSQTLLA
VAGLLTTDDP EVMKATTDFL SSAASHQPFR SKAVDCYTQA LSESELHTQR AACAALSCLQ
AVESIDAVIL LCDSVDEELR QIAIETLLTF GEDGRLAYEQ LDTVPREMVR LGTRRGNAVT
TSF
