RIPR2_HUMAN
ID RIPR2_HUMAN Reviewed; 1068 AA.
AC Q9Y4F9; A6NHP2; Q13529; Q5VV37; Q5VV38; Q9BQ28;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 4.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Rho family-interacting cell polarization regulator 2;
GN Name=RIPOR2;
GN Synonyms=C6orf32, DIFF48, FAM65B, KIAA0386,
GN PL48 {ECO:0000303|PubMed:9055809};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, AND INDUCTION.
RC TISSUE=Placenta;
RX PubMed=9055809; DOI=10.1016/s0378-1119(96)00587-2;
RA Dakour J., Li H., Morrish D.W.;
RT "PL48: a novel gene associated with cytotrophoblast and lineage-specific
RT HL-60 cell differentiation.";
RL Gene 185:153-157(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS MET-320
RP AND GLN-868.
RC TISSUE=Brain;
RX PubMed=9205841; DOI=10.1093/dnares/4.2.141;
RA Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. VII. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 4:141-150(1997).
RN [3]
RP SEQUENCE REVISION.
RA Ohara O., Nagase T., Kikuno R., Nomura N.;
RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION (ISOFORM 2), TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=17150207; DOI=10.1016/j.ydbio.2006.11.002;
RA Yoon S., Molloy M.J., Wu M.P., Cowan D.B., Gussoni E.;
RT "C6ORF32 is upregulated during muscle cell differentiation and induces the
RT formation of cellular filopodia.";
RL Dev. Biol. 301:70-81(2007).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=T-cell;
RX PubMed=19367720; DOI=10.1021/pr800500r;
RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.;
RT "Phosphorylation analysis of primary human T lymphocytes using sequential
RT IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [9]
RP FUNCTION, INTERACTION WITH RHOA (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND INDUCTION (ISOFORMS 1 AND 2).
RX PubMed=23241886; DOI=10.4049/jimmunol.1201174;
RA Rougerie P., Largeteau Q., Megrelis L., Carrette F., Lejeune T.,
RA Toffali L., Rossi B., Zeghouf M., Cherfils J., Constantin G., Laudanna C.,
RA Bismuth G., Mangeney M., Delon J.;
RT "Fam65b is a new transcriptional target of FOXO1 that regulates RhoA
RT signaling for T lymphocyte migration.";
RL J. Immunol. 190:748-755(2013).
RN [10]
RP FUNCTION, TISSUE SPECIFICITY, ACETYLATION, SUBCELLULAR LOCATION,
RP INTERACTION WITH 14-3-3 PROTEINS; HDAC6; DYSF AND MYOF, AND INDUCTION.
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 [11]
RP FUNCTION, AND INVOLVEMENT IN DFNB104.
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).
RN [12]
RP FUNCTION (ISOFORM 2), INTERACTION WITH 14-3-3 PROTEINS; RHOA; YWHAB; YWHAE
RP AND YWHAQ (ISOFORM 2), PHOSPHORYLATION AT SER-21; SER-37; SER-341; SER-523
RP AND SER-585 (ISOFORM 2), SUBCELLULAR LOCATION (ISOFORM 2), MUTAGENESIS OF
RP SER-21; SER-37; 151-ARG-LEU-152; 155-GLY-ALA-156; SER-341; SER-523 AND
RP SER-585, AND IDENTIFICATION BY MASS SPECTROMETRY (ISOFORM 2).
RX PubMed=25588844; DOI=10.1242/jcs.161497;
RA Gao K., Tang W., Li Y., Zhang P., Wang D., Yu L., Wang C., Wu D.;
RT "Front-signal-dependent accumulation of the RHOA inhibitor FAM65B at
RT leading edges polarizes neutrophils.";
RL J. Cell Sci. 128:992-1000(2015).
RN [13]
RP FUNCTION (ISOFORM 2), INTERACTION WITH 14-3-3 PROTEINS AND HDAC6 (ISOFORM
RP 2), PHOSPHORYLATION (ISOFORM 2), MUTAGENESIS OF SER-21; SER-37;
RP 151-ARG-LEU-152; SER-341; SER-523 AND SER-585, INDUCTION (ISOFORMS 1 AND
RP 2), AND TISSUE SPECIFICITY.
RX PubMed=27556504; DOI=10.18632/oncotarget.11438;
RA Froehlich J., Versapuech M., Megrelis L., Largeteau Q., Meunier S.,
RA Tanchot C., Bismuth G., Delon J., Mangeney M.;
RT "FAM65B controls the proliferation of transformed and primary T cells.";
RL Oncotarget 7:63215-63225(2016).
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 (PubMed:17150207, PubMed:24687993, PubMed:23241886, PubMed:24958875,
CC PubMed:25588844, PubMed:27556504). Inhibits chemokine-induced T
CC lymphocyte responses, such as cell adhesion, polarization and migration
CC (PubMed:23241886). Involved also in the regulation of neutrophil
CC polarization, chemotaxis and adhesion (By similarity). Required for
CC normal development of inner and outer hair cell stereocilia within the
CC cochlea of the inner ear (By similarity). Plays a role for maintaining
CC the structural organization of the basal domain of stereocilia (By
CC similarity). Involved in mechanosensory hair cell function (By
CC similarity). Required for normal hearing (PubMed:24958875).
CC {ECO:0000250|UniProtKB:Q80U16, ECO:0000269|PubMed:17150207,
CC ECO:0000269|PubMed:23241886, ECO:0000269|PubMed:24687993,
CC ECO:0000269|PubMed:24958875, ECO:0000269|PubMed:27556504}.
CC -!- FUNCTION: [Isoform 2]: Acts as an inhibitor of the small GTPase RHOA
CC (PubMed:25588844). Plays a role in fetal mononuclear myoblast
CC differentiation by promoting filopodia and myotube formation
CC (PubMed:17150207). Maintains naive T lymphocytes in a quiescent state
CC (PubMed:27556504). {ECO:0000269|PubMed:17150207,
CC ECO:0000269|PubMed:25588844, ECO:0000269|PubMed:27556504}.
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 with 14-3-3 proteins; these
CC interactions occur during myogenic cell differentiation
CC (PubMed:24687993). Interacts with HDAC6; this interaction occurs during
CC early myogenic differentiation and prevents HDAC6 to deacetylate
CC tubulin (PubMed:24687993). Interacts with DYSF; this interaction occurs
CC during early myogenic differentiation (PubMed:24687993). Interacts with
CC MYOF (PubMed:24687993). Interacts with RHOC (By similarity). Isoform 1
CC and isoform 2 interact (via active GTP- or inactive GDP-bound forms)
CC with RHOA; these interactions are direct, block the loading of GTP to
CC RHOA and decrease upon chemokine CCL19 stimulation in primary T
CC lymphocytes (PubMed:23241886, PubMed:25588844). Isoform 2 interacts
CC (phosphorylated form) with HDAC6; this interaction induces T cell
CC proliferation arrest (PubMed:27556504). Isoform 2 interacts
CC (phosphorylated form) with 14-3-3 proteins; these interactions induces
CC T cell proliferation arrest (PubMed:27556504). Isoform 2 interacts with
CC 14-3-3 proteins (PubMed:25588844). Isoform 2 interacts (via
CC phosphorylated form) with YWHAB; this interaction occurs in a
CC chemokine-dependent manner and does not compete for binding of RIPOR2
CC with RHOA nor blocks inhibition of RIPOR2-mediated RHOA activity
CC (PubMed:25588844). Isoform 2 interacts with YWHAE (PubMed:25588844).
CC Isoform 2 interacts with YWHAQ (PubMed:25588844).
CC {ECO:0000250|UniProtKB:Q80U16, ECO:0000269|PubMed:23241886,
CC ECO:0000269|PubMed:24687993, ECO:0000269|PubMed:25588844,
CC ECO:0000269|PubMed:27556504}.
CC -!- INTERACTION:
CC Q9Y4F9; P61586: RHOA; NbExp=4; IntAct=EBI-2798942, EBI-446668;
CC Q9Y4F9; P08134: RHOC; NbExp=5; IntAct=EBI-2798942, EBI-747589;
CC Q9Y4F9-2; P61586: RHOA; NbExp=3; IntAct=EBI-14509742, EBI-446668;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17150207,
CC ECO:0000269|PubMed:23241886}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:17150207}. Cell projection, filopodium
CC {ECO:0000269|PubMed:17150207}. Cell projection, stereocilium
CC {ECO:0000250|UniProtKB:Q80U16}. Cell projection, stereocilium membrane
CC {ECO:0000250|UniProtKB:Q7TP54}. Apical cell membrane
CC {ECO:0000250|UniProtKB:Q7TP54}. Note=Localized in the cytoplasm in
CC cells undergoing mitosis (PubMed:17150207). Colocalized with F-actin
CC (PubMed:17150207). Localized with RHOC within the basal domain of hair
CC cell stereocilia, near the taper region (By similarity). Detected in
CC punctate pattern forming a circumferential ring at the stereocilia base
CC (By similarity). Localized to the apical stereocilia of inner and outer
CC hair cells (By similarity). Not detected as a membrane-associated
CC protein in stereocilia (By similarity). {ECO:0000250|UniProtKB:Q7TP54,
CC ECO:0000250|UniProtKB:Q80U16, ECO:0000269|PubMed:17150207}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm
CC {ECO:0000269|PubMed:24687993}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000269|PubMed:25588844}. Note=Accumulates at the leading edge of
CC polarized neutrophils in a chemokine-dependent manner
CC (PubMed:25588844). {ECO:0000269|PubMed:25588844}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y4F9-1; Sequence=Displayed;
CC Name=2; Synonyms=PL48 {ECO:0000303|PubMed:9055809};
CC IsoId=Q9Y4F9-2; Sequence=VSP_025904, VSP_025905, VSP_025906;
CC -!- TISSUE SPECIFICITY: Expressed in primary fetal mononuclear myoblast
CC (PubMed:17150207). Expressed strongly in naive T lymphocytes
CC (PubMed:27556504). Expressed weakly in activated T lymphocytes (at
CC protein level) (PubMed:27556504). Expressed in blood cells and adult
CC tissues of hematopoietic origin, such as the secondary lymphoid organs
CC (PubMed:23241886). Expressed in cytotrophoblast (PubMed:9055809).
CC {ECO:0000269|PubMed:17150207, ECO:0000269|PubMed:23241886,
CC ECO:0000269|PubMed:27556504, ECO:0000269|PubMed:9055809}.
CC -!- INDUCTION: Up-regulated during fetal mononuclear myoblast
CC differentiation (PubMed:17150207, PubMed:24687993). Up-regulated during
CC cytotrophoblast differentiation (PubMed:9055809). Up-regulated during
CC granulocyte differentiation (PubMed:9055809). Isoform 1 and isoform 2
CC are down-regulated in T lymphocytes upon T-cell antigen receptor (TCR)
CC stimulation (PubMed:27556504). Isoform 1 and isoform 2 are up-regulated
CC by FOXO1 (PubMed:23241886). {ECO:0000269|PubMed:17150207,
CC ECO:0000269|PubMed:23241886, ECO:0000269|PubMed:24687993,
CC ECO:0000269|PubMed:27556504, ECO:0000269|PubMed:9055809}.
CC -!- PTM: Phosphorylated. Isoform 2 is phosphorylated in T cells
CC (PubMed:27556504). Chemokine-induced phosphorylation of isoform 2 in
CC neutrophils occurs in a PKC- and AKT-dependent manner, resulting in
CC RIPOR2 interaction with YWHAB and stabilization (PubMed:25588844).
CC Isoform 2 is phosphorylated by PKCA, AKT1 and MAPKAPK1A; in vitro
CC (PubMed:25588844). {ECO:0000269|PubMed:25588844,
CC ECO:0000269|PubMed:27556504}.
CC -!- PTM: Acetylated during myogenic differentiation.
CC {ECO:0000269|PubMed:24687993}.
CC -!- DISEASE: Deafness, autosomal recessive, 104 (DFNB104) [MIM:616515]: A
CC form of non-syndromic sensorineural hearing loss. Sensorineural
CC deafness results from damage to the neural receptors of the inner ear,
CC the nerve pathways to the brain, or the area of the brain that receives
CC sound information. {ECO:0000269|PubMed:24958875}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Cells lacking isoform 2 exhibit a severe reduction of
CC myotube formation. In contrast, isoform 2 overexpression induces
CC formation of filopodia.
CC -!- SIMILARITY: Belongs to the RIPOR family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC51134.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAA20840.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U49187; AAC51134.1; ALT_FRAME; mRNA.
DR EMBL; AB002384; BAA20840.2; ALT_INIT; mRNA.
DR EMBL; AL512428; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL078584; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471087; EAW55470.1; -; Genomic_DNA.
DR EMBL; BC001232; AAH01232.1; -; mRNA.
DR CCDS; CCDS47383.1; -. [Q9Y4F9-1]
DR CCDS; CCDS47384.1; -. [Q9Y4F9-2]
DR RefSeq; NP_001273375.1; NM_001286446.2.
DR RefSeq; NP_001273376.1; NM_001286447.1.
DR RefSeq; NP_055537.2; NM_014722.4. [Q9Y4F9-1]
DR RefSeq; NP_056948.2; NM_015864.3. [Q9Y4F9-2]
DR RefSeq; XP_016867015.1; XM_017011526.1. [Q9Y4F9-2]
DR RefSeq; XP_016867016.1; XM_017011527.1. [Q9Y4F9-2]
DR AlphaFoldDB; Q9Y4F9; -.
DR BioGRID; 115098; 11.
DR IntAct; Q9Y4F9; 10.
DR STRING; 9606.ENSP00000482957; -.
DR GlyGen; Q9Y4F9; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y4F9; -.
DR PhosphoSitePlus; Q9Y4F9; -.
DR BioMuta; RIPOR2; -.
DR DMDM; 296439477; -.
DR EPD; Q9Y4F9; -.
DR jPOST; Q9Y4F9; -.
DR MassIVE; Q9Y4F9; -.
DR MaxQB; Q9Y4F9; -.
DR PaxDb; Q9Y4F9; -.
DR PeptideAtlas; Q9Y4F9; -.
DR PRIDE; Q9Y4F9; -.
DR ProteomicsDB; 86200; -. [Q9Y4F9-1]
DR ProteomicsDB; 86201; -. [Q9Y4F9-2]
DR Antibodypedia; 25358; 175 antibodies from 26 providers.
DR DNASU; 9750; -.
DR Ensembl; ENST00000259698.9; ENSP00000259698.4; ENSG00000111913.20. [Q9Y4F9-1]
DR Ensembl; ENST00000378023.8; ENSP00000367262.4; ENSG00000111913.20. [Q9Y4F9-2]
DR Ensembl; ENST00000613507.4; ENSP00000482957.1; ENSG00000111913.20. [Q9Y4F9-1]
DR Ensembl; ENST00000643623.1; ENSP00000495245.1; ENSG00000111913.20. [Q9Y4F9-2]
DR Ensembl; ENST00000644621.1; ENSP00000495914.1; ENSG00000111913.20. [Q9Y4F9-2]
DR GeneID; 9750; -.
DR KEGG; hsa:9750; -.
DR UCSC; uc003neo.3; human. [Q9Y4F9-1]
DR CTD; 9750; -.
DR DisGeNET; 9750; -.
DR GeneCards; RIPOR2; -.
DR HGNC; HGNC:13872; RIPOR2.
DR HPA; ENSG00000111913; Tissue enhanced (lymphoid).
DR MalaCards; RIPOR2; -.
DR MIM; 611410; gene.
DR MIM; 616515; phenotype.
DR neXtProt; NX_Q9Y4F9; -.
DR OpenTargets; ENSG00000111913; -.
DR Orphanet; 90636; Autosomal recessive non-syndromic sensorineural deafness type DFNB.
DR PharmGKB; PA162387677; -.
DR VEuPathDB; HostDB:ENSG00000111913; -.
DR eggNOG; ENOG502QQ7T; Eukaryota.
DR GeneTree; ENSGT00940000153717; -.
DR HOGENOM; CLU_432085_0_0_1; -.
DR InParanoid; Q9Y4F9; -.
DR OrthoDB; 1121546at2759; -.
DR PhylomeDB; Q9Y4F9; -.
DR TreeFam; TF329332; -.
DR PathwayCommons; Q9Y4F9; -.
DR Reactome; R-HSA-9662360; Sensory processing of sound by inner hair cells of the cochlea.
DR Reactome; R-HSA-9662361; Sensory processing of sound by outer hair cells of the cochlea.
DR SignaLink; Q9Y4F9; -.
DR BioGRID-ORCS; 9750; 6 hits in 1066 CRISPR screens.
DR ChiTaRS; FAM65B; human.
DR GenomeRNAi; 9750; -.
DR Pharos; Q9Y4F9; Tbio.
DR PRO; PR:Q9Y4F9; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9Y4F9; protein.
DR Bgee; ENSG00000111913; Expressed in blood and 165 other tissues.
DR ExpressionAtlas; Q9Y4F9; baseline and differential.
DR Genevisible; Q9Y4F9; HS.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IDA:UniProtKB.
DR GO; GO:0030175; C:filopodium; IDA:UniProtKB.
DR GO; GO:0032420; C:stereocilium; ISS:UniProtKB.
DR GO; GO:0060171; C:stereocilium membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0071889; F:14-3-3 protein binding; IDA:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:1990869; P:cellular response to chemokine; IDA:UniProtKB.
DR GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR GO; GO:0007162; P:negative regulation of cell adhesion; IMP:UniProtKB.
DR GO; GO:1903904; P:negative regulation of establishment of T cell polarity; IMP: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; IMP:UniProtKB.
DR GO; GO:0035024; P:negative regulation of Rho protein signal transduction; IMP:UniProtKB.
DR GO; GO:2000405; P:negative regulation of T cell migration; IMP:UniProtKB.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; IMP:UniProtKB.
DR GO; GO:0051491; P:positive regulation of filopodium assembly; IMP:UniProtKB.
DR GO; GO:0045663; P:positive regulation of myoblast differentiation; IMP:UniProtKB.
DR GO; GO:1901741; P:positive regulation of myoblast fusion; IMP: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:0051726; P:regulation of cell cycle; IMP:UniProtKB.
DR GO; GO:2000114; P:regulation of establishment of cell polarity; ISS:UniProtKB.
DR GO; GO:1901673; P:regulation of mitotic spindle assembly; IMP:UniProtKB.
DR GO; GO:0007605; P:sensory perception of sound; IMP:UniProtKB.
DR GO; GO:0048741; P:skeletal muscle fiber development; IEA:InterPro.
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 1: Evidence at protein level;
KW Alternative splicing; Cell adhesion; Cell membrane; Cell projection;
KW Chemotaxis; Coiled coil; Cytoplasm; Cytoskeleton; Deafness;
KW Developmental protein; Differentiation; Hearing; Membrane; Myogenesis;
KW Non-syndromic deafness; Phosphoprotein; Reference proteome;
KW Signal transduction inhibitor.
FT CHAIN 1..1068
FT /note="Rho family-interacting cell polarization regulator
FT 2"
FT /id="PRO_0000289114"
FT REGION 45..73
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 55..113
FT /note="Involved in cell filopodia formation"
FT /evidence="ECO:0000269|PubMed:17150207"
FT REGION 474..524
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 83..112
FT /evidence="ECO:0000255"
FT COILED 768..793
FT /evidence="ECO:0000255"
FT COMPBIAS 474..493
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 494..514
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 21
FT /note="Phosphoserine; in isoform 2"
FT /evidence="ECO:0000269|PubMed:25588844"
FT MOD_RES 37
FT /note="Phosphoserine; in isoform 2"
FT /evidence="ECO:0000269|PubMed:25588844"
FT MOD_RES 341
FT /note="Phosphoserine; in isoform 2"
FT /evidence="ECO:0000269|PubMed:25588844"
FT MOD_RES 523
FT /note="Phosphoserine; in isoform 2"
FT /evidence="ECO:0000269|PubMed:25588844"
FT MOD_RES 573
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80U16"
FT MOD_RES 585
FT /note="Phosphoserine; in isoform 2"
FT /evidence="ECO:0000269|PubMed:25588844"
FT VAR_SEQ 360..409
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9055809"
FT /id="VSP_025904"
FT VAR_SEQ 641
FT /note="C -> K (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9055809"
FT /id="VSP_025905"
FT VAR_SEQ 642..1068
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9055809"
FT /id="VSP_025906"
FT VARIANT 145
FT /note="A -> G (in dbSNP:rs11967003)"
FT /id="VAR_032572"
FT VARIANT 320
FT /note="V -> M (in dbSNP:rs35331811)"
FT /evidence="ECO:0000269|PubMed:9205841"
FT /id="VAR_032573"
FT VARIANT 424
FT /note="E -> K (in dbSNP:rs34016544)"
FT /id="VAR_032574"
FT VARIANT 452
FT /note="S -> C (in dbSNP:rs34298086)"
FT /id="VAR_032575"
FT VARIANT 495
FT /note="E -> K (in dbSNP:rs35514577)"
FT /id="VAR_032576"
FT VARIANT 520
FT /note="R -> C (in dbSNP:rs35780910)"
FT /id="VAR_032577"
FT VARIANT 868
FT /note="R -> Q (in dbSNP:rs9461073)"
FT /evidence="ECO:0000269|PubMed:9205841"
FT /id="VAR_062193"
FT MUTAGEN 21
FT /note="S->A: Reduces phosphorylation, interaction with
FT HDAC6, YWHAB and 14-3-3 proteins, localization at the front
FT of the neutrophil upon chemokine stimulation and prevents T
FT cell proliferation inhibition; when associated with A-37;
FT A-341; A-523 and A-585 (isoform 2)."
FT /evidence="ECO:0000269|PubMed:25588844,
FT ECO:0000269|PubMed:27556504"
FT MUTAGEN 37
FT /note="S->A: Reduces phosphorylation, interaction with
FT HDAC6, YWHAB and 14-3-3 proteins, localization at the front
FT of the neutrophil upon chemokine stimulation and prevents T
FT cell proliferation inhibition; when associated with A-21;
FT A-341; A-523 and A-585 (isoform 2)."
FT /evidence="ECO:0000269|PubMed:25588844,
FT ECO:0000269|PubMed:27556504"
FT MUTAGEN 151..152
FT /note="RL->AA: Inhibits interaction with RHOA and does not
FT prevent T cell proliferation inhibition; in isoform 2."
FT /evidence="ECO:0000269|PubMed:25588844,
FT ECO:0000269|PubMed:27556504"
FT MUTAGEN 155..156
FT /note="GA->RR: Inhibits interaction with RHOA; in isoform
FT 2."
FT /evidence="ECO:0000269|PubMed:25588844,
FT ECO:0000269|PubMed:27556504"
FT MUTAGEN 341
FT /note="S->A: Reduces phosphorylation, interaction with
FT HDAC6, YWHAB and 14-3-3 proteins, localization at the front
FT of the neutrophil upon chemokine stimulation and prevents T
FT cell proliferation inhibition; when associated with A-21;
FT A-37; A-523 and A-585 (isoform 2)."
FT /evidence="ECO:0000269|PubMed:25588844,
FT ECO:0000269|PubMed:27556504"
FT MUTAGEN 523
FT /note="S->A: Reduces phosphorylation, interaction with
FT HDAC6, YWHAB and 14-3-3 proteins, localization at the front
FT of the neutrophil upon chemokine stimulation and prevents T
FT cell proliferation inhibition; when associated with A-21;
FT A-37; A-341 and A-585 (isoform 2)."
FT /evidence="ECO:0000269|PubMed:25588844,
FT ECO:0000269|PubMed:27556504"
FT MUTAGEN 585
FT /note="S->A: Reduces phosphorylation, interaction with
FT HDAC6, YWHAB and 14-3-3 proteins, localization at the front
FT of the neutrophil upon chemokine stimulation and prevents T
FT cell proliferation inhibition; when associated with A-21;
FT A-37; A-341 and A-523 (isoform 2)."
FT /evidence="ECO:0000269|PubMed:25588844,
FT ECO:0000269|PubMed:27556504"
FT CONFLICT 13
FT /note="P -> A (in Ref. 1; AAC51134)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1068 AA; 118519 MW; CCA7DEB3A66F36AA CRC64;
MLVGSQSFSP GGPNGIIRSQ SFAGFSGLQE RRSRCNSFIE NSSALKKPQA KLKKMHNLGH
KNNNPPKEPQ PKRVEEVYRA LKNGLDEYLE VHQTELDKLT AQLKDMKRNS RLGVLYDLDK
QIKTIERYMR RLEFHISKVD ELYEAYCIQR RLQDGASKMK QAFATSPASK AARESLTEIN
RSFKEYTENM CTIEVELENL LGEFSIKMKG LAGFARLCPG DQYEIFMKYG RQRWKLKGKI
EVNGKQSWDG EETVFLPLIV GFISIKVTEL KGLATHILVG SVTCETKELF AARPQVVAVD
INDLGTIKLN LEITWYPFDV EDMTASSGAG NKAAALQRRM SMYSQGTPET PTFKDHSFFR
WLHPSPDKPR RLSVLSALQD TFFAKLHRSR SFSDLPSLRP SPKAVLELYS NLPDDIFENG
KAAEEKMPLS LSFSDLPNGD CALTSHSTGS PSNSTNPEIT ITPAEFNLSS LASQNEGMDD
TSSASSRNSL GEGQEPKSHL KEEDPEEPRK PASAPSEACR RQSSGAGAEH LFLENDVAEA
LLQESEEASE LKPVELDTSE GNITKQLVKR LTSAEVPMAT DRLLSEGSVG GESEGCRSFL
DGSLEDAFNG LLLALEPHKE QYKEFQDLNQ EVMNLDDILK CKPAVSRSRS SSLSLTVESA
LESFDFLNTS DFDEEEDGDE VCNVGGGADS VFSDTETEKH SYRSVHPEAR GHLSEALTED
TGVGTSVAGS PLPLTTGNES LDITIVRHLQ YCTQLVQQIV FSSKTPFVAR SLLEKLSRQI
QVMEKLAAVS DENIGNISSV VEAIPEFHKK LSLLSFWTKC CSPVGVYHSP ADRVMKQLEA
SFARTVNKEY PGLADPVFRT LVSQILDRAE PLLSSSLSSE VVTVFQYYSY FTSHGVSDLE
SYLSQLARQV SMVQTLQSLR DEKLLQTMSD LAPSNLLAQQ EVLRTLALLL TREDNEVSEA
VTLYLAAASK NQHFREKALL YYCEALTKTN LQLQKAACLA LKILEATESI KMLVTLCQSD
TEEIRNVASE TLLSLGEDGR LAYEQLDKFP RDCVKVGGRH GTEVATAF
