XRP2_HUMAN
ID XRP2_HUMAN Reviewed; 350 AA.
AC O75695; Q86XJ7; Q9NU67;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=Protein XRP2;
GN Name=RP2;
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], AND VARIANTS RP2 SER-6 DEL AND HIS-118.
RC TISSUE=Brain;
RX PubMed=9697692; DOI=10.1038/1214;
RA Schwahn U., Lenzner S., Dong J., Feil S., Hinzmann B., van Duijnhoven G.,
RA Kirschner R., Hemberger M., Bergen A.A.B., Rosenberg T., Pinckers A.J.L.G.,
RA Fundele R., Rosenthal A., Cremers F.P.M., Ropers H.-H., Berger W.;
RT "Positional cloning of the gene for X-linked retinitis pigmentosa 2.";
RL Nat. Genet. 19:327-332(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye, and Uterus;
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [6]
RP MYRISTOYLATION AT GLY-2, CLEAVAGE OF INITIATOR METHIONINE, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=25255805; DOI=10.1038/ncomms5919;
RA Thinon E., Serwa R.A., Broncel M., Brannigan J.A., Brassat U., Wright M.H.,
RA Heal W.P., Wilkinson A.J., Mann D.J., Tate E.W.;
RT "Global profiling of co- and post-translationally N-myristoylated proteomes
RT in human cells.";
RL Nat. Commun. 5:4919-4919(2014).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [8]
RP CHARACTERIZATION OF VARIANTS RP2 SER-6 DEL AND HIS-118, MYRISTOYLATION AT
RP GLY-2, PALMITOYLATION AT CYS-3, MUTAGENESIS OF GLY-2 AND CYS-3, TISSUE
RP SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=10942419; DOI=10.1093/hmg/9.13.1919;
RA Chapple J.P., Hardcastle A.J., Grayson C., Spackman L.A., Willison K.R.,
RA Cheetham M.E.;
RT "Mutations in the N-terminus of the X-linked retinitis pigmentosa protein
RT RP2 interfere with the normal targeting of the protein to the plasma
RT membrane.";
RL Hum. Mol. Genet. 9:1919-1926(2000).
RN [9]
RP FUNCTION, CHARACTERIZATION OF VARIANTS RP2 SER-6 DEL AND HIS-118, AND
RP INTERACTION WITH ARL3.
RX PubMed=11847227; DOI=10.1074/jbc.m200128200;
RA Bartolini F., Bhamidipati A., Thomas S., Schwahn U., Lewis S.A.,
RA Cowan N.J.;
RT "Functional overlap between retinitis pigmentosa 2 protein and the tubulin-
RT specific chaperone cofactor C.";
RL J. Biol. Chem. 277:14629-14634(2002).
RN [10]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12417528; DOI=10.1093/hmg/11.24.3065;
RA Grayson C., Bartolini F., Chapple J.P., Willison K.R., Bhamidipati A.,
RA Lewis S.A., Luthert P.J., Hardcastle A.J., Cowan N.J., Cheetham M.E.;
RT "Localization in the human retina of the X-linked retinitis pigmentosa
RT protein RP2, its homologue cofactor C and the RP2 interacting protein
RT Arl3.";
RL Hum. Mol. Genet. 11:3065-3074(2002).
RN [11]
RP IDENTIFICATION IN A COMPLEX WITH ARL3 AND UNC119.
RX PubMed=18588884; DOI=10.1016/j.febslet.2008.05.053;
RA Veltel S., Kravchenko A., Ismail S., Wittinghofer A.;
RT "Specificity of Arl2/Arl3 signaling is mediated by a ternary Arl3-effector-
RT GAP complex.";
RL FEBS Lett. 582:2501-2507(2008).
RN [12]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=20106869; DOI=10.1093/hmg/ddq012;
RA Evans R.J., Schwarz N., Nagel-Wolfrum K., Wolfrum U., Hardcastle A.J.,
RA Cheetham M.E.;
RT "The retinitis pigmentosa protein RP2 links pericentriolar vesicle
RT transport between the Golgi and the primary cilium.";
RL Hum. Mol. Genet. 19:1358-1367(2010).
RN [13]
RP FUNCTION.
RX PubMed=22085962; DOI=10.1101/gad.173443.111;
RA Wright K.J., Baye L.M., Olivier-Mason A., Mukhopadhyay S., Sang L.,
RA Kwong M., Wang W., Pretorius P.R., Sheffield V.C., Sengupta P.,
RA Slusarski D.C., Jackson P.K.;
RT "An ARL3-UNC119-RP2 GTPase cycle targets myristoylated NPHP3 to the primary
RT cilium.";
RL Genes Dev. 25:2347-2360(2011).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS), INTERACTION WITH ARL3,
RP CHARACTERIZATION OF VARIANTS RP2 HIS-118 AND GLY-138, AND CHARACTERIZATION
RP OF VARIANT TRP-282.
RX PubMed=16472755; DOI=10.1016/j.str.2005.11.008;
RA Kuehnel K., Veltel S., Schlichting I., Wittinghofer A.;
RT "Crystal structure of the human retinitis pigmentosa 2 protein and its
RT interaction with Arl3.";
RL Structure 14:367-378(2006).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 1-350 OF COMPLEX WITH MOUSE ARL3
RP AND GTP, FUNCTION, INTERACTION WITH ARL3, TISSUE SPECIFICITY,
RP CHARACTERIZATION OF VARIANTS LEU-118 AND GLY-138, AND MUTAGENESIS OF
RP SER-28; TRP-29; GLN-31; ARG-32; PHE-101; GLN-115; GLN-116; ARG-118; ARG-120
RP AND PHE-177.
RX PubMed=18376416; DOI=10.1038/nsmb.1396;
RA Veltel S., Gasper R., Eisenacher E., Wittinghofer A.;
RT "The retinitis pigmentosa 2 gene product is a GTPase-activating protein for
RT Arf-like 3.";
RL Nat. Struct. Mol. Biol. 15:373-380(2008).
RN [16]
RP VARIANT RP2 HIS-118.
RX PubMed=10090907; DOI=10.1086/302325;
RA Hardcastle A.J., Thiselton D.L., Van Maldergem L., Saha B.K., Jay M.,
RA Plant C., Taylor R., Bird A.C., Bhattacharya S.;
RT "Mutations in the RP2 gene cause disease in 10% of families with familial
RT X-Linked retinitis pigmentosa assessed in this study.";
RL Am. J. Hum. Genet. 64:1210-1215(1999).
RN [17]
RP VARIANTS RP2 SER-6 DEL AND HIS-118.
RX PubMed=10520237; DOI=10.1076/opge.20.3.161.2278;
RA Rosenberg T., Schwahn U., Feil S., Berger W.;
RT "Genotype-phenotype correlation in X-linked retinitis pigmentosa 2 (RP2).";
RL Ophthalmic Genet. 20:161-172(1999).
RN [18]
RP VARIANTS TRP-282 AND TYR-338.
RX PubMed=10862093;
RX DOI=10.1002/1098-1004(200006)15:6<580::aid-humu15>3.0.co;2-3;
RA Thiselton D.L., Zito I., Plant C., Jay M., Hodgson S.V., Bird A.C.,
RA Bhattacharya S.S., Hardcastle A.J.;
RT "Novel frameshift mutations in the RP2 gene and polymorphic variants.";
RL Hum. Mutat. 15:580-580(2000).
RN [19]
RP VARIANT RP2 ARG-253.
RX PubMed=10634633;
RA Wada Y., Nakazawa M., Abe T., Tamai M.;
RT "A new Leu253Arg mutation in the RP2 gene in a Japanese family with X-
RT linked retinitis pigmentosa.";
RL Invest. Ophthalmol. Vis. Sci. 41:290-293(2000).
RN [20]
RP VARIANTS RP2 TYR-86; LEU-95; HIS-118 AND ILE-137 DEL, AND VARIANT TRP-282.
RX PubMed=10937588;
RA Sharon D., Bruns G.A.P., McGee T.L., Sandberg M.A., Berson E.L.,
RA Dryja T.P.;
RT "X-linked retinitis pigmentosa: mutation spectrum of the RPGR and RP2 genes
RT and correlation with visual function.";
RL Invest. Ophthalmol. Vis. Sci. 41:2712-2721(2000).
RN [21]
RP VARIANTS RP2 LEU-118 AND GLY-138, AND VARIANT TRP-282.
RX PubMed=11462235; DOI=10.1002/humu.1160;
RA Miano M.G., Testa F., Filippini F., Trujillo M., Conte I., Lanzara C.,
RA Millan J.M., De Bernardo C., Grammatico B., Mangino M., Torrente I.,
RA Carrozzo R., Simonelli F., Rinaldi E., Ventruto V., D'Urso M., Ayuso C.,
RA Ciccodicola A.;
RT "Identification of novel RP2 mutations in a subset of X-linked retinitis
RT pigmentosa families and prediction of new domains.";
RL Hum. Mutat. 18:109-119(2001).
RN [22]
RP VARIANTS RP2 TYR-67; HIS-118; ILE-137 DEL AND PRO-188, AND VARIANT TRP-282.
RX PubMed=11992260; DOI=10.1086/340848;
RA Breuer D.K., Yashar B.M., Filippova E., Hiriyanna S., Lyons R.H.,
RA Mears A.J., Asaye B., Acar C., Vervoort R., Wright A.F., Musarella M.A.,
RA Wheeler P., MacDonald I., Iannaccone A., Birch D., Hoffman D.R.,
RA Fishman G.A., Heckenlively J.R., Jacobson S.G., Sieving P.A., Swaroop A.;
RT "A comprehensive mutation analysis of RP2 and RPGR in a North American
RT cohort of families with X-linked retinitis pigmentosa.";
RL Am. J. Hum. Genet. 70:1545-1554(2002).
RN [23]
RP VARIANTS RP2 TYR-86; LEU-95; HIS-118 AND ILE-137 DEL, AND VARIANT TRP-282.
RX PubMed=14564670; DOI=10.1086/379379;
RA Sharon D., Sandberg M.A., Rabe V.W., Stillberger M., Dryja T.P.,
RA Berson E.L.;
RT "RP2 and RPGR mutations and clinical correlations in patients with X-linked
RT retinitis pigmentosa.";
RL Am. J. Hum. Genet. 73:1131-1146(2003).
RN [24]
RP VARIANTS RP2 HIS-118 AND CYS-118.
RX PubMed=12657579; DOI=10.1167/iovs.02-0605;
RA Bader I., Brandau O., Achatz H., Apfelstedt-Sylla E., Hergersberg M.,
RA Lorenz B., Wissinger B., Wittwer B., Rudolph G., Meindl A., Meitinger T.;
RT "X-linked retinitis pigmentosa: RPGR mutations in most families with
RT definite X linkage and clustering of mutations in a short sequence stretch
RT of exon ORF15.";
RL Invest. Ophthalmol. Vis. Sci. 44:1458-1463(2003).
RN [25]
RP VARIANT RP2 TYR-108.
RX PubMed=22334370; DOI=10.1002/humu.22045;
RA Neveling K., Collin R.W., Gilissen C., van Huet R.A., Visser L.,
RA Kwint M.P., Gijsen S.J., Zonneveld M.N., Wieskamp N., de Ligt J.,
RA Siemiatkowska A.M., Hoefsloot L.H., Buckley M.F., Kellner U., Branham K.E.,
RA den Hollander A.I., Hoischen A., Hoyng C., Klevering B.J.,
RA van den Born L.I., Veltman J.A., Cremers F.P., Scheffer H.;
RT "Next-generation genetic testing for retinitis pigmentosa.";
RL Hum. Mutat. 33:963-972(2012).
RN [26]
RP VARIANT TRP-282.
RX PubMed=27535533; DOI=10.1038/nature19057;
RG Exome Aggregation Consortium;
RA Lek M., Karczewski K.J., Minikel E.V., Samocha K.E., Banks E., Fennell T.,
RA O'Donnell-Luria A.H., Ware J.S., Hill A.J., Cummings B.B., Tukiainen T.,
RA Birnbaum D.P., Kosmicki J.A., Duncan L.E., Estrada K., Zhao F., Zou J.,
RA Pierce-Hoffman E., Berghout J., Cooper D.N., Deflaux N., DePristo M.,
RA Do R., Flannick J., Fromer M., Gauthier L., Goldstein J., Gupta N.,
RA Howrigan D., Kiezun A., Kurki M.I., Moonshine A.L., Natarajan P.,
RA Orozco L., Peloso G.M., Poplin R., Rivas M.A., Ruano-Rubio V., Rose S.A.,
RA Ruderfer D.M., Shakir K., Stenson P.D., Stevens C., Thomas B.P., Tiao G.,
RA Tusie-Luna M.T., Weisburd B., Won H.H., Yu D., Altshuler D.M.,
RA Ardissino D., Boehnke M., Danesh J., Donnelly S., Elosua R., Florez J.C.,
RA Gabriel S.B., Getz G., Glatt S.J., Hultman C.M., Kathiresan S., Laakso M.,
RA McCarroll S., McCarthy M.I., McGovern D., McPherson R., Neale B.M.,
RA Palotie A., Purcell S.M., Saleheen D., Scharf J.M., Sklar P.,
RA Sullivan P.F., Tuomilehto J., Tsuang M.T., Watkins H.C., Wilson J.G.,
RA Daly M.J., MacArthur D.G.;
RT "Analysis of protein-coding genetic variation in 60,706 humans.";
RL Nature 536:285-291(2016).
CC -!- FUNCTION: Acts as a GTPase-activating protein (GAP) involved in
CC trafficking between the Golgi and the ciliary membrane. Involved in
CC localization of proteins, such as NPHP3, to the cilium membrane by
CC inducing hydrolysis of GTP ARL3, leading to the release of UNC119 (or
CC UNC119B). Acts as a GTPase-activating protein (GAP) for tubulin in
CC concert with tubulin-specific chaperone C, but does not enhance tubulin
CC heterodimerization. Acts as guanine nucleotide dissociation inhibitor
CC towards ADP-ribosylation factor-like proteins.
CC {ECO:0000269|PubMed:11847227, ECO:0000269|PubMed:18376416,
CC ECO:0000269|PubMed:20106869, ECO:0000269|PubMed:22085962}.
CC -!- SUBUNIT: Found in a complex with ARL3, RP2 and UNC119 (or UNC119B); RP2
CC induces hydrolysis of GTP ARL3 in the complex, leading to the release
CC of UNC119 (or UNC119B). Interacts with ARL3; interaction is direct and
CC stimulated with the activated GTP-bound form of ARL3.
CC {ECO:0000269|PubMed:11847227, ECO:0000269|PubMed:16472755,
CC ECO:0000269|PubMed:18376416, ECO:0000269|PubMed:18588884}.
CC -!- INTERACTION:
CC O75695; Q8IYS1: PM20D2; NbExp=3; IntAct=EBI-7996807, EBI-11339910;
CC O75695; Q9WUL7: Arl3; Xeno; NbExp=5; IntAct=EBI-7996807, EBI-6860857;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10942419,
CC ECO:0000269|PubMed:12417528}; Lipid-anchor
CC {ECO:0000269|PubMed:10942419}; Cytoplasmic side
CC {ECO:0000269|PubMed:10942419}. Cell projection, cilium
CC {ECO:0000269|PubMed:20106869}. Note=Detected predominantly at the
CC plasma membrane of rod and cone photoreceptors. Not detected in the
CC nucleus. {ECO:0000269|PubMed:12417528}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. Expressed in the rod and cone
CC photoreceptors, extending from the tips of the outer segment (OS)
CC through the inner segment (IS) and outer nuclear layer (ONL) and into
CC the synaptic terminals of the outer plexiform layer (ONL). Also
CC detected in the bipolar, horizontal and amacrine cells in the inner
CC nuclear layer (INL), extending to the inner plexiform layer (IPL) and
CC though the ganglion cell layer (GCL) and into the nerve fiber layer
CC (NFL) (at protein level). {ECO:0000269|PubMed:10942419,
CC ECO:0000269|PubMed:12417528, ECO:0000269|PubMed:18376416}.
CC -!- PTM: Myristoylated on Gly-2; which may be required for membrane
CC targeting. {ECO:0000305|PubMed:10942419}.
CC -!- PTM: Palmitoylated on Cys-3; which may be required for plasma membrane
CC targeting (Probable). Mutation of Cys-3 targets the protein to internal
CC membranes. {ECO:0000269|PubMed:10942419, ECO:0000305}.
CC -!- DISEASE: Retinitis pigmentosa 2 (RP2) [MIM:312600]: A retinal dystrophy
CC belonging to the group of pigmentary retinopathies. Retinitis
CC pigmentosa is characterized by retinal pigment deposits visible on
CC fundus examination and primary loss of rod photoreceptor cells followed
CC by secondary loss of cone photoreceptors. Patients typically have night
CC vision blindness and loss of midperipheral visual field. As their
CC condition progresses, they lose their far peripheral visual field and
CC eventually central vision as well. {ECO:0000269|PubMed:10090907,
CC ECO:0000269|PubMed:10520237, ECO:0000269|PubMed:10634633,
CC ECO:0000269|PubMed:10937588, ECO:0000269|PubMed:10942419,
CC ECO:0000269|PubMed:11462235, ECO:0000269|PubMed:11847227,
CC ECO:0000269|PubMed:11992260, ECO:0000269|PubMed:12657579,
CC ECO:0000269|PubMed:14564670, ECO:0000269|PubMed:16472755,
CC ECO:0000269|PubMed:22334370, ECO:0000269|PubMed:9697692}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the TBCC family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Mutations of the RP2 gene; Note=Retina
CC International's Scientific Newsletter;
CC URL="https://www.retina-international.org/files/sci-news/rp2mut.htm";
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DR EMBL; AJ007590; CAA07577.1; -; mRNA.
DR EMBL; AL050307; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL627143; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC043348; AAH43348.1; -; mRNA.
DR EMBL; BC053530; AAH53530.1; -; mRNA.
DR CCDS; CCDS14270.1; -.
DR RefSeq; NP_008846.2; NM_006915.2.
DR PDB; 2BX6; X-ray; 2.10 A; A=1-350.
DR PDB; 3BH6; X-ray; 2.60 A; B=1-350.
DR PDB; 3BH7; X-ray; 1.90 A; B=1-350.
DR PDBsum; 2BX6; -.
DR PDBsum; 3BH6; -.
DR PDBsum; 3BH7; -.
DR AlphaFoldDB; O75695; -.
DR BMRB; O75695; -.
DR SMR; O75695; -.
DR BioGRID; 112029; 117.
DR DIP; DIP-29024N; -.
DR ELM; O75695; -.
DR IntAct; O75695; 40.
DR MINT; O75695; -.
DR STRING; 9606.ENSP00000218340; -.
DR GlyGen; O75695; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O75695; -.
DR PhosphoSitePlus; O75695; -.
DR SwissPalm; O75695; -.
DR BioMuta; RP2; -.
DR EPD; O75695; -.
DR jPOST; O75695; -.
DR MassIVE; O75695; -.
DR MaxQB; O75695; -.
DR PaxDb; O75695; -.
DR PeptideAtlas; O75695; -.
DR PRIDE; O75695; -.
DR ProteomicsDB; 50167; -.
DR Antibodypedia; 373; 161 antibodies from 26 providers.
DR DNASU; 6102; -.
DR Ensembl; ENST00000218340.4; ENSP00000218340.3; ENSG00000102218.6.
DR GeneID; 6102; -.
DR KEGG; hsa:6102; -.
DR MANE-Select; ENST00000218340.4; ENSP00000218340.3; NM_006915.3; NP_008846.2.
DR UCSC; uc004dgw.5; human.
DR CTD; 6102; -.
DR DisGeNET; 6102; -.
DR GeneCards; RP2; -.
DR GeneReviews; RP2; -.
DR HGNC; HGNC:10274; RP2.
DR HPA; ENSG00000102218; Tissue enhanced (bone).
DR MalaCards; RP2; -.
DR MIM; 300757; gene.
DR MIM; 312600; phenotype.
DR neXtProt; NX_O75695; -.
DR OpenTargets; ENSG00000102218; -.
DR Orphanet; 791; Retinitis pigmentosa.
DR PharmGKB; PA34641; -.
DR VEuPathDB; HostDB:ENSG00000102218; -.
DR eggNOG; KOG2512; Eukaryota.
DR GeneTree; ENSGT00940000158262; -.
DR HOGENOM; CLU_056119_0_0_1; -.
DR InParanoid; O75695; -.
DR OMA; DYMLTGL; -.
DR OrthoDB; 1458550at2759; -.
DR PhylomeDB; O75695; -.
DR TreeFam; TF105832; -.
DR PathwayCommons; O75695; -.
DR Reactome; R-HSA-5624138; Trafficking of myristoylated proteins to the cilium.
DR SignaLink; O75695; -.
DR BioGRID-ORCS; 6102; 12 hits in 705 CRISPR screens.
DR ChiTaRS; RP2; human.
DR EvolutionaryTrace; O75695; -.
DR GeneWiki; RP2_(gene); -.
DR GenomeRNAi; 6102; -.
DR Pharos; O75695; Tbio.
DR PRO; PR:O75695; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; O75695; protein.
DR Bgee; ENSG00000102218; Expressed in monocyte and 163 other tissues.
DR ExpressionAtlas; O75695; baseline and differential.
DR Genevisible; O75695; HS.
DR GO; GO:0005814; C:centriole; IEA:Ensembl.
DR GO; GO:0036064; C:ciliary basal body; IDA:UniProtKB.
DR GO; GO:0005929; C:cilium; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IGI:MGI.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:1990075; C:periciliary membrane compartment; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0005096; F:GTPase activator activity; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0051082; F:unfolded protein binding; TAS:ProtInc.
DR GO; GO:0060271; P:cilium assembly; TAS:Reactome.
DR GO; GO:0006892; P:post-Golgi vesicle-mediated transport; IMP:MGI.
DR GO; GO:0006457; P:protein folding; TAS:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0007601; P:visual perception; TAS:ProtInc.
DR Gene3D; 2.160.20.70; -; 1.
DR Gene3D; 3.30.70.141; -; 1.
DR InterPro; IPR017901; C-CAP_CF_C-like.
DR InterPro; IPR016098; CAP/MinC_C.
DR InterPro; IPR036223; CAP_C_sf.
DR InterPro; IPR006599; CARP_motif.
DR InterPro; IPR036850; NDK-like_dom_sf.
DR InterPro; IPR012945; Tubulin-bd_cofactor_C_dom.
DR InterPro; IPR039093; XRP2.
DR PANTHER; PTHR15440; PTHR15440; 1.
DR Pfam; PF07986; TBCC; 1.
DR PIRSF; PIRSF037947; Protein_XRP2; 1.
DR SMART; SM00673; CARP; 2.
DR SUPFAM; SSF54919; SSF54919; 1.
DR SUPFAM; SSF69340; SSF69340; 1.
DR PROSITE; PS51329; C_CAP_COFACTOR_C; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cell projection; Cilium; Disease variant;
KW GTP-binding; GTPase activation; Lipoprotein; Membrane; Myristate;
KW Nucleotide-binding; Palmitate; Protein transport; Reference proteome;
KW Retinitis pigmentosa; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:25255805"
FT CHAIN 2..350
FT /note="Protein XRP2"
FT /id="PRO_0000080047"
FT DOMAIN 24..179
FT /note="C-CAP/cofactor C-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00659"
FT REGION 1..31
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 98..99
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT BINDING 115..118
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000305|PubMed:10942419"
FT LIPID 3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:25255805,
FT ECO:0000305|PubMed:10942419"
FT VARIANT 6
FT /note="Missing (in RP2; loss of membrane association;
FT enhances interaction with ARL3; dbSNP:rs137852284)"
FT /evidence="ECO:0000269|PubMed:10520237,
FT ECO:0000269|PubMed:10942419, ECO:0000269|PubMed:11847227,
FT ECO:0000269|PubMed:9697692"
FT /id="VAR_008497"
FT VARIANT 67
FT /note="C -> Y (in RP2)"
FT /evidence="ECO:0000269|PubMed:11992260"
FT /id="VAR_018069"
FT VARIANT 86
FT /note="C -> Y (in RP2)"
FT /evidence="ECO:0000269|PubMed:10937588,
FT ECO:0000269|PubMed:14564670"
FT /id="VAR_018070"
FT VARIANT 95
FT /note="P -> L (in RP2; uncertain pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:10937588,
FT ECO:0000269|PubMed:14564670"
FT /id="VAR_018071"
FT VARIANT 108
FT /note="C -> G (in RP2)"
FT /id="VAR_008498"
FT VARIANT 108
FT /note="C -> Y (in RP2)"
FT /evidence="ECO:0000269|PubMed:22334370"
FT /id="VAR_068353"
FT VARIANT 118
FT /note="R -> C (in RP2; dbSNP:rs1556318633)"
FT /evidence="ECO:0000269|PubMed:12657579"
FT /id="VAR_026058"
FT VARIANT 118
FT /note="R -> H (in RP2; reduces affinity for ARL3 800-fold;
FT loss of stimulation of tubulin GTPase activity; no effect
FT on subcellular location; dbSNP:rs28933687)"
FT /evidence="ECO:0000269|PubMed:10090907,
FT ECO:0000269|PubMed:10520237, ECO:0000269|PubMed:10937588,
FT ECO:0000269|PubMed:10942419, ECO:0000269|PubMed:11847227,
FT ECO:0000269|PubMed:11992260, ECO:0000269|PubMed:12657579,
FT ECO:0000269|PubMed:14564670, ECO:0000269|PubMed:16472755,
FT ECO:0000269|PubMed:9697692"
FT /id="VAR_008499"
FT VARIANT 118
FT /note="R -> L (in RP2; dbSNP:rs28933687)"
FT /evidence="ECO:0000269|PubMed:11462235,
FT ECO:0000269|PubMed:18376416"
FT /id="VAR_018072"
FT VARIANT 137
FT /note="Missing (in RP2)"
FT /evidence="ECO:0000269|PubMed:10937588,
FT ECO:0000269|PubMed:11992260, ECO:0000269|PubMed:14564670"
FT /id="VAR_018073"
FT VARIANT 138
FT /note="E -> G (in RP2; reduces affinity for ARL3 150-fold
FT and inhibits the GTP-hydrolysis rate of ARL3)"
FT /evidence="ECO:0000269|PubMed:11462235,
FT ECO:0000269|PubMed:16472755, ECO:0000269|PubMed:18376416"
FT /id="VAR_018074"
FT VARIANT 144
FT /note="K -> R (in dbSNP:rs3126141)"
FT /id="VAR_053961"
FT VARIANT 188
FT /note="L -> P (in RP2)"
FT /evidence="ECO:0000269|PubMed:11992260"
FT /id="VAR_018075"
FT VARIANT 253
FT /note="L -> R (in RP2)"
FT /evidence="ECO:0000269|PubMed:10634633"
FT /id="VAR_008500"
FT VARIANT 282
FT /note="R -> W (reduces affinity for ARL3 3-fold;
FT dbSNP:rs1805147)"
FT /evidence="ECO:0000269|PubMed:10862093,
FT ECO:0000269|PubMed:10937588, ECO:0000269|PubMed:11462235,
FT ECO:0000269|PubMed:11992260, ECO:0000269|PubMed:14564670,
FT ECO:0000269|PubMed:16472755, ECO:0000269|PubMed:27535533"
FT /id="VAR_014535"
FT VARIANT 338
FT /note="D -> Y (in dbSNP:rs1805148)"
FT /evidence="ECO:0000269|PubMed:10862093"
FT /id="VAR_014536"
FT MUTAGEN 2
FT /note="G->A: Loss of membrane association."
FT /evidence="ECO:0000269|PubMed:10942419"
FT MUTAGEN 3
FT /note="C->S: Targeting to internal membranes. Loss of
FT targeting to the plasma membrane."
FT /evidence="ECO:0000269|PubMed:10942419"
FT MUTAGEN 28
FT /note="S->A: Reduces affinity for mouse ARL3; when
FT associated with A-29."
FT /evidence="ECO:0000269|PubMed:18376416"
FT MUTAGEN 29
FT /note="W->A: Reduces affinity for mouse ARL3; when
FT associated with A-28."
FT /evidence="ECO:0000269|PubMed:18376416"
FT MUTAGEN 31
FT /note="Q->A: Does not reduce affinity for mouse ARL3; when
FT associated with A-32."
FT /evidence="ECO:0000269|PubMed:18376416"
FT MUTAGEN 32
FT /note="R->A: Does not reduce affinity for mouse ARL3; when
FT associated with A-31."
FT /evidence="ECO:0000269|PubMed:18376416"
FT MUTAGEN 101
FT /note="F->A: Reduces affinity for mouse ARL3."
FT /evidence="ECO:0000269|PubMed:18376416"
FT MUTAGEN 115
FT /note="Q->A: Reduces affinity for mouse ARL3."
FT /evidence="ECO:0000269|PubMed:18376416"
FT MUTAGEN 116
FT /note="Q->A: Reduces affinity and GTP-hydrolysis rate for
FT mouse ARL3."
FT /evidence="ECO:0000269|PubMed:18376416"
FT MUTAGEN 118
FT /note="R->A: Reduces affinity and GTP-hydrolysis rate for
FT mouse ARL3."
FT /evidence="ECO:0000269|PubMed:18376416"
FT MUTAGEN 120
FT /note="R->H: Reduces affinity for mouse ARL3; when
FT associated with S-121."
FT /evidence="ECO:0000269|PubMed:18376416"
FT MUTAGEN 121
FT /note="D->S: Reduces affinity for mouse ARL3; when
FT associated with H-120."
FT MUTAGEN 177
FT /note="F->A: Reduces affinity and GTP-hydrolysis rate for
FT mouse ARL3."
FT /evidence="ECO:0000269|PubMed:18376416"
FT CONFLICT 168
FT /note="N -> D (in Ref. 1; CAA07577)"
FT /evidence="ECO:0000305"
FT STRAND 39..44
FT /evidence="ECO:0007829|PDB:3BH7"
FT STRAND 49..52
FT /evidence="ECO:0007829|PDB:3BH7"
FT STRAND 62..66
FT /evidence="ECO:0007829|PDB:3BH7"
FT STRAND 71..74
FT /evidence="ECO:0007829|PDB:3BH7"
FT STRAND 81..85
FT /evidence="ECO:0007829|PDB:3BH7"
FT STRAND 90..104
FT /evidence="ECO:0007829|PDB:3BH7"
FT STRAND 106..121
FT /evidence="ECO:0007829|PDB:3BH7"
FT STRAND 123..133
FT /evidence="ECO:0007829|PDB:3BH7"
FT STRAND 136..139
FT /evidence="ECO:0007829|PDB:3BH7"
FT STRAND 141..147
FT /evidence="ECO:0007829|PDB:3BH7"
FT HELIX 155..161
FT /evidence="ECO:0007829|PDB:3BH7"
FT STRAND 175..178
FT /evidence="ECO:0007829|PDB:3BH7"
FT STRAND 185..188
FT /evidence="ECO:0007829|PDB:3BH7"
FT HELIX 195..197
FT /evidence="ECO:0007829|PDB:3BH7"
FT HELIX 205..207
FT /evidence="ECO:0007829|PDB:3BH7"
FT TURN 216..218
FT /evidence="ECO:0007829|PDB:3BH7"
FT STRAND 235..240
FT /evidence="ECO:0007829|PDB:3BH7"
FT HELIX 246..259
FT /evidence="ECO:0007829|PDB:3BH7"
FT STRAND 263..270
FT /evidence="ECO:0007829|PDB:3BH7"
FT HELIX 274..281
FT /evidence="ECO:0007829|PDB:3BH7"
FT HELIX 282..287
FT /evidence="ECO:0007829|PDB:3BH7"
FT HELIX 289..294
FT /evidence="ECO:0007829|PDB:3BH7"
FT STRAND 297..304
FT /evidence="ECO:0007829|PDB:3BH7"
FT HELIX 307..318
FT /evidence="ECO:0007829|PDB:3BH7"
FT STRAND 324..326
FT /evidence="ECO:0007829|PDB:3BH7"
FT HELIX 330..348
FT /evidence="ECO:0007829|PDB:3BH7"
SQ SEQUENCE 350 AA; 39641 MW; 3C912B52C53A817E CRC64;
MGCFFSKRRK ADKESRPENE EERPKQYSWD QREKVDPKDY MFSGLKDETV GRLPGTVAGQ
QFLIQDCENC NIYIFDHSAT VTIDDCTNCI IFLGPVKGSV FFRNCRDCKC TLACQQFRVR
DCRKLEVFLC CATQPIIESS SNIKFGCFQW YYPELAFQFK DAGLSIFNNT WSNIHDFTPV
SGELNWSLLP EDAVVQDYVP IPTTEELKAV RVSTEANRSI VPISRGQRQK SSDESCLVVL
FAGDYTIANA RKLIDEMVGK GFFLVQTKEV SMKAEDAQRV FREKAPDFLP LLNKGPVIAL
EFNGDGAVEV CQLIVNEIFN GTKMFVSESK ETASGDVDSF YNFADIQMGI
