RENR_HUMAN
ID RENR_HUMAN Reviewed; 350 AA.
AC O75787; B7Z9I3; Q5QTQ7; Q6T7F5; Q8NBP3; Q8NG15; Q96FV6; Q96LB5; Q9H2P8;
AC Q9UG89;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2005, sequence version 2.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Renin receptor {ECO:0000305};
DE AltName: Full=ATPase H(+)-transporting lysosomal accessory protein 2;
DE AltName: Full=ATPase H(+)-transporting lysosomal-interacting protein 2;
DE AltName: Full=ER-localized type I transmembrane adapter;
DE AltName: Full=Embryonic liver differentiation factor 10;
DE AltName: Full=N14F;
DE AltName: Full=Renin/prorenin receptor;
DE AltName: Full=Vacuolar ATP synthase membrane sector-associated protein M8-9;
DE Short=ATP6M8-9;
DE Short=V-ATPase M8.9 subunit;
DE Contains:
DE RecName: Full=Renin receptor N-terminal fragment {ECO:0000303|PubMed:29127204};
DE Contains:
DE RecName: Full=Renin receptor C-terminal fragment {ECO:0000303|PubMed:29127204};
DE Flags: Precursor;
GN Name=ATP6AP2 {ECO:0000312|HGNC:HGNC:18305};
GN Synonyms=ATP6IP2, CAPER, ELDF10; ORFNames=HT028, MSTP009, PSEC0072;
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 1), INTERACTION WITH REN,
RP PHOSPHORYLATION, TISSUE SPECIFICITY, AND FUNCTION.
RC TISSUE=Mesangial cell;
RX PubMed=12045255; DOI=10.1172/jci14276;
RA Nguyen G., Delarue F., Burckle C., Bouzhir L., Giller T., Sraer J.-D.;
RT "Pivotal role of the renin/prorenin receptor in angiotensin II production
RT and cellular responses to renin.";
RL J. Clin. Invest. 109:1417-1427(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Cervix carcinoma;
RA Wang J., Kirby C., Herbst R.;
RT "Cell cycle-dependent subcellular localization of the protein tyrosine
RT phosphatase PTPCAAX1 and its implication in cell cycle regulation.";
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Aorta;
RA Hui R.T., Liu Y.Q., Liu B., Zhao B., Meng X.M., Sheng H., Xu Y.Y.,
RA Wang X.Y., Ye J., Song L., Gao Y., Wei Y.J., Zhang C.L., Zhang J.,
RA Chai M.Q., Chen J.Z., Sun Y.H., Zhou X.L., Jiang Y.X., Zhao X.W., Liu S.,
RA Cao H.Q., Zhao Y., Liu D.Q., Ding J.F., Liu L.S., Gao R.L., Wu Q.Y.,
RA Qiang B.Q., Yuan J.G., Liew C.C., Zhao M.S.;
RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Hypothalamus;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W.,
RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J.,
RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z.,
RA Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis
RT and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain cortex;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Teratocarcinoma;
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [7]
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Prostate;
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 [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 13-350 (ISOFORM 1).
RC TISSUE=Liver;
RA Zhang S., Yan H., Yang F.;
RT "The cloning of a novel gene related with erythroid differentiation.";
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 21-350 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 188-350 (ISOFORM 1).
RX PubMed=9556572; DOI=10.1074/jbc.273.18.10939;
RA Ludwig J., Kerscher S., Brandt U., Pfeiffer K., Getlawi F., Apps D.K.,
RA Schaegger H.;
RT "Identification and characterization of a novel 9.2-kDa membrane sector-
RT associated protein of vacuolar proton-ATPase from chromaffin granules.";
RL J. Biol. Chem. 273:10939-10947(1998).
RN [12]
RP INVOLVEMENT IN MRXSH, TISSUE SPECIFICITY, AND ALTERNATIVE SPLICING.
RX PubMed=15746149; DOI=10.1093/hmg/ddi094;
RA Ramser J., Abidi F.E., Burckle C.A., Lenski C., Toriello H., Wen G.,
RA Lubs H.A., Engert S., Stevenson R.E., Meindl A., Schwartz C.E., Nguyen G.;
RT "A unique exonic splice enhancer mutation in a family with X-linked mental
RT retardation and epilepsy points to a novel role of the renin receptor.";
RL Hum. Mol. Genet. 14:1019-1027(2005).
RN [13]
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 [14]
RP INVOLVEMENT IN XPDS.
RX PubMed=23595882; DOI=10.1093/hmg/ddt180;
RA Korvatska O., Strand N.S., Berndt J.D., Strovas T., Chen D.H.,
RA Leverenz J.B., Kiianitsa K., Mata I.F., Karakoc E., Greenup J.L.,
RA Bonkowski E., Chuang J., Moon R.T., Eichler E.E., Nickerson D.A.,
RA Zabetian C.P., Kraemer B.C., Bird T.D., Raskind W.H.;
RT "Altered splicing of ATP6AP2 causes X-linked parkinsonism with spasticity
RT (XPDS).";
RL Hum. Mol. Genet. 22:3259-3268(2013).
RN [15]
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 [16]
RP FUNCTION, INTERACTION WITH ATP6AP1 AND VMA21, SUBCELLULAR LOCATION,
RP INVOLVEMENT IN CDG2R, MOTIF, CHARACTERIZATION OF VARIANTS CDG2R HIS-71 AND
RP SER-98, AND MUTAGENESIS OF LYS-346 AND ARG-348.
RX PubMed=29127204; DOI=10.1084/jem.20170453;
RA Rujano M.A., Cannata Serio M., Panasyuk G., Peanne R., Reunert J.,
RA Rymen D., Hauser V., Park J.H., Freisinger P., Souche E., Guida M.C.,
RA Maier E.M., Wada Y., Jaeger S., Krogan N.J., Kretz O., Nobre S., Garcia P.,
RA Quelhas D., Bird T.D., Raskind W.H., Schwake M., Duvet S., Foulquier F.,
RA Matthijs G., Marquardt T., Simons M.;
RT "Mutations in the X-linked ATP6AP2 cause a glycosylation disorder with
RT autophagic defects.";
RL J. Exp. Med. 214:3707-3729(2017).
RN [17]
RP FUNCTION, AND INTERACTION WITH TMEM9 AND ATP6V0D1.
RX PubMed=30374053; DOI=10.1038/s41556-018-0219-8;
RA Jung Y.S., Jun S., Kim M.J., Lee S.H., Suh H.N., Lien E.M., Jung H.Y.,
RA Lee S., Zhang J., Yang J.I., Ji H., Wu J.Y., Wang W., Miller R.K., Chen J.,
RA McCrea P.D., Kopetz S., Park J.I.;
RT "TMEM9 promotes intestinal tumorigenesis through vacuolar-ATPase-activated
RT Wnt/beta-catenin signalling.";
RL Nat. Cell Biol. 20:1421-1433(2018).
RN [18]
RP INVOLVEMENT IN MRXSH.
RX PubMed=30985297; DOI=10.1172/jci79990;
RA Hirose T., Cabrera-Socorro A., Chitayat D., Lemonnier T., Feraud O.,
RA Cifuentes-Diaz C., Gervasi N., Mombereau C., Ghosh T., Stoica L.,
RA Bacha J.D.A., Yamada H., Lauterbach M.A., Guillon M., Kaneko K.,
RA Norris J.W., Siriwardena K., Blaser S., Teillon J., Mendoza-Londono R.,
RA Russeau M., Hadoux J., Ito S., Corvol P., Matheus M.G., Holden K.R.,
RA Takei K., Emiliani V., Bennaceur-Griscelli A., Schwartz C.E., Nguyen G.,
RA Groszer M.;
RT "ATP6AP2 variant impairs CNS development and neuronal survival to cause
RT fulminant neurodegeneration.";
RL J. Clin. Invest. 129:2145-2162(2019).
RN [19]
RP FUNCTION.
RX PubMed=32276428; DOI=10.3390/v12040414;
RA Su W., Huang S., Zhu H., Zhang B., Wu X.;
RT "Interaction between PHB2 and Enterovirus A71 VP1 Induces Autophagy and
RT Affects EV-A71 Infection.";
RL Viruses 12:0-0(2020).
RN [20] {ECO:0007744|PDB:3LBS, ECO:0007744|PDB:3LC8}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 333-350.
RX PubMed=21420935; DOI=10.1016/j.bbrc.2011.03.074;
RA Zhang Y., Gao X., Michael Garavito R.;
RT "Structural analysis of the intracellular domain of (pro)renin receptor
RT fused to maltose-binding protein.";
RL Biochem. Biophys. Res. Commun. 407:674-679(2011).
RN [21] {ECO:0007744|PDB:6WLW, ECO:0007744|PDB:6WM2, ECO:0007744|PDB:6WM3, ECO:0007744|PDB:6WM4}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.00 ANGSTROMS) IN COMPLEX WITH THE
RP V-ATPASE.
RX PubMed=33065002; DOI=10.1016/j.molcel.2020.09.029;
RA Wang L., Wu D., Robinson C.V., Wu H., Fu T.M.;
RT "Structures of a Complete Human V-ATPase Reveal Mechanisms of Its
RT Assembly.";
RL Mol. Cell 80:501-511.e3(2020).
CC -!- FUNCTION: Multifunctional protein which functions as a renin, prorenin
CC cellular receptor and is involved in the assembly of the lysosomal
CC proton-transporting V-type ATPase (V-ATPase) and the acidification of
CC the endo-lysosomal system (PubMed:12045255, PubMed:29127204,
CC PubMed:30374053, PubMed:32276428). May mediate renin-dependent cellular
CC responses by activating ERK1 and ERK2 (PubMed:12045255). By increasing
CC the catalytic efficiency of renin in AGT/angiotensinogen conversion to
CC angiotensin I, may also play a role in the renin-angiotensin system
CC (RAS) (PubMed:12045255). Through its function in V-type ATPase (v-
CC ATPase) assembly and acidification of the lysosome it regulates protein
CC degradation and may control different signaling pathways important for
CC proper brain development, synapse morphology and synaptic transmission
CC (By similarity). {ECO:0000250|UniProtKB:Q9CYN9,
CC ECO:0000269|PubMed:12045255, ECO:0000269|PubMed:29127204,
CC ECO:0000269|PubMed:30374053, ECO:0000269|PubMed:32276428}.
CC -!- SUBUNIT: Interacts with renin (PubMed:12045255). Accessory component of
CC the multisubunit proton-transporting vacuolar (V)-ATPase protein pump
CC (PubMed:33065002). Interacts (via N-terminus) with ATP6AP1 (via N-
CC terminus) (PubMed:29127204, PubMed:33065002). Interacts with ATP6V0D1;
CC ATP6V0D1 is a V-ATPase complex subunit and the interaction promotes V-
CC ATPase complex assembly (PubMed:33065002, PubMed:30374053). Interacts
CC with TMEM9; TMEM9 is a V-ATPase assembly regulator and the interaction
CC induces the interaction with ATP6V0D1 (PubMed:30374053). Interacts with
CC VMA21 (via N-terminus); VMA21 is a V-ATPase accessory component
CC (PubMed:29127204). {ECO:0000269|PubMed:12045255,
CC ECO:0000269|PubMed:29127204, ECO:0000269|PubMed:30374053,
CC ECO:0000269|PubMed:33065002}.
CC -!- INTERACTION:
CC O75787; P21854: CD72; NbExp=3; IntAct=EBI-2512037, EBI-307924;
CC O75787; Q16617: NKG7; NbExp=3; IntAct=EBI-2512037, EBI-3919611;
CC O75787; P42857: NSG1; NbExp=3; IntAct=EBI-2512037, EBI-6380741;
CC O75787; Q01453: PMP22; NbExp=3; IntAct=EBI-2512037, EBI-2845982;
CC O75787; P53801: PTTG1IP; NbExp=3; IntAct=EBI-2512037, EBI-3906138;
CC O75787; Q96IW7: SEC22A; NbExp=3; IntAct=EBI-2512037, EBI-8652744;
CC O75787; Q9NPL8: TIMMDC1; NbExp=3; IntAct=EBI-2512037, EBI-6268651;
CC O75787; Q969S6: TMEM203; NbExp=3; IntAct=EBI-2512037, EBI-12274070;
CC O75787; Q5BJF2: TMEM97; NbExp=3; IntAct=EBI-2512037, EBI-12111910;
CC O75787; O00526: UPK2; NbExp=3; IntAct=EBI-2512037, EBI-10179682;
CC O75787; O95183: VAMP5; NbExp=3; IntAct=EBI-2512037, EBI-10191195;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:29127204}; Single-pass type I membrane protein
CC {ECO:0000305}. Lysosome membrane {ECO:0000269|PubMed:29127204}; Single-
CC pass type I membrane protein {ECO:0000305}. Cytoplasmic vesicle,
CC autophagosome membrane {ECO:0000250|UniProtKB:Q9CYN9}; Single-pass type
CC I membrane protein {ECO:0000305}. Cell projection, dendritic spine
CC membrane {ECO:0000250|UniProtKB:Q9CYN9}; Single-pass type I membrane
CC protein {ECO:0000305}. Cell projection, axon
CC {ECO:0000250|UniProtKB:Q9CYN9}. Endosome membrane
CC {ECO:0000250|UniProtKB:Q9CYN9}; Single-pass type I membrane protein
CC {ECO:0000305}. Cytoplasmic vesicle, clathrin-coated vesicle membrane
CC {ECO:0000250|UniProtKB:Q6AXS4}; Single-pass type I membrane protein
CC {ECO:0000305}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle
CC membrane {ECO:0000250|UniProtKB:Q6AXS4}; Single-pass type I membrane
CC protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O75787-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75787-2; Sequence=VSP_056910;
CC -!- TISSUE SPECIFICITY: Expressed in brain, heart, placenta, liver, kidney
CC and pancreas. Barely detectable in lung and skeletal muscles. In the
CC kidney cortex it is restricted to the mesangium of glomeruli. In the
CC coronary and kidney artery it is expressed in the subendothelium,
CC associated to smooth muscles where it colocalizes with REN. Expressed
CC in vascular structures and by syncytiotrophoblast cells in the mature
CC fetal placenta. {ECO:0000269|PubMed:12045255,
CC ECO:0000269|PubMed:15746149}.
CC -!- PTM: Phosphorylated. {ECO:0000269|PubMed:12045255}.
CC -!- PTM: Proteolytically cleaved by a furin-like convertase in the trans-
CC Golgi network to generate N- and C-terminal fragments.
CC {ECO:0000269|PubMed:29127204}.
CC -!- DISEASE: Intellectual developmental disorder, X-linked, syndromic,
CC Hedera type (MRXSH) [MIM:300423]: A disorder characterized by
CC significantly below average general intellectual functioning associated
CC with impairments in adaptive behavior and manifested during the
CC developmental period. MRXSH patients manifest mild to moderate
CC intellectual disability associated with epilepsy, delays in motor
CC milestones and speech acquisition in infancy.
CC {ECO:0000269|PubMed:15746149, ECO:0000269|PubMed:30985297}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Parkinsonism with spasticity, X-linked (XPDS) [MIM:300911]: A
CC syndrome characterized by parkinsonian features, such as cogwheel
CC rigidity, resting tremor and bradykinesia, and variably penetrant
CC spasticity. {ECO:0000269|PubMed:23595882}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- DISEASE: Congenital disorder of glycosylation 2R (CDG2R) [MIM:301045]:
CC A form of congenital disorder of glycosylation, a genetically
CC heterogeneous group of multisystem disorders caused by a defect in
CC glycoprotein biosynthesis and characterized by under-glycosylated serum
CC glycoproteins. Congenital disorders of glycosylation result in a wide
CC variety of clinical features, such as defects in the nervous system
CC development, psychomotor retardation, dysmorphic features, hypotonia,
CC coagulation disorders, and immunodeficiency. The broad spectrum of
CC features reflects the critical role of N-glycoproteins during embryonic
CC development, differentiation, and maintenance of cell functions. CDG2R
CC is an X-linked recessive disorder characterized by infantile onset of
CC liver failure, recurrent infections due to hypogammaglobulinemia, and
CC cutis laxa. Some patients may also have mild intellectual impairment
CC and dysmorphic features. {ECO:0000269|PubMed:29127204}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Note=Defects in ATP6AP2 may be involved in a glycosylation
CC disorder with autophagic defects characterized by serum protein
CC hypoglycosylation, immunodeficiency, liver disease, psychomotor
CC impairment, and cutis laxa. {ECO:0000269|PubMed:25944712}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH10395.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAQ13511.1; Type=Frameshift; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
CC Sequence=CAA76984.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF291814; AAM47531.1; -; mRNA.
DR EMBL; AY038990; AAK83467.1; -; mRNA.
DR EMBL; AF109363; AAQ13511.1; ALT_FRAME; mRNA.
DR EMBL; AF248966; AAG44564.1; -; mRNA.
DR EMBL; AK315948; BAH14319.1; -; mRNA.
DR EMBL; AK075382; BAC11582.1; -; mRNA.
DR EMBL; AC092473; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC010395; AAH10395.1; ALT_INIT; mRNA.
DR EMBL; BC084541; AAH84541.1; -; mRNA.
DR EMBL; AY429341; AAR06910.1; -; mRNA.
DR EMBL; AL049929; CAB43210.1; -; mRNA.
DR EMBL; Y17975; CAA76984.1; ALT_INIT; mRNA.
DR CCDS; CCDS14252.1; -. [O75787-1]
DR PIR; T08667; T08667.
DR RefSeq; NP_005756.2; NM_005765.2. [O75787-1]
DR PDB; 3LBS; X-ray; 2.15 A; A/B=333-350.
DR PDB; 3LC8; X-ray; 2.00 A; A/B=333-350.
DR PDB; 6WLW; EM; 3.00 A; V=1-350.
DR PDB; 6WM2; EM; 3.10 A; V=1-350.
DR PDB; 6WM3; EM; 3.40 A; V=1-350.
DR PDB; 6WM4; EM; 3.60 A; V=1-350.
DR PDBsum; 3LBS; -.
DR PDBsum; 3LC8; -.
DR PDBsum; 6WLW; -.
DR PDBsum; 6WM2; -.
DR PDBsum; 6WM3; -.
DR PDBsum; 6WM4; -.
DR AlphaFoldDB; O75787; -.
DR SMR; O75787; -.
DR BioGRID; 115461; 339.
DR ComplexPortal; CPX-2470; Vacuolar proton translocating ATPase complex, ATP6V0A1 variant.
DR ComplexPortal; CPX-6904; Vacuolar proton translocating ATPase complex, ATP6V0A2 variant.
DR ComplexPortal; CPX-6905; Vacuolar proton translocating ATPase complex, ATP6V0A3 variant.
DR ComplexPortal; CPX-6912; Vacuolar proton translocating ATPase complex, ATP6V0A4 variant.
DR IntAct; O75787; 128.
DR MINT; O75787; -.
DR STRING; 9606.ENSP00000367697; -.
DR TCDB; 8.A.80.1.1; the (pro)renin receptor (prr) family.
DR iPTMnet; O75787; -.
DR PhosphoSitePlus; O75787; -.
DR BioMuta; ATP6AP2; -.
DR EPD; O75787; -.
DR jPOST; O75787; -.
DR MassIVE; O75787; -.
DR MaxQB; O75787; -.
DR PaxDb; O75787; -.
DR PeptideAtlas; O75787; -.
DR PRIDE; O75787; -.
DR ProteomicsDB; 50195; -. [O75787-1]
DR ProteomicsDB; 7033; -.
DR TopDownProteomics; O75787-1; -. [O75787-1]
DR Antibodypedia; 556; 365 antibodies from 37 providers.
DR DNASU; 10159; -.
DR Ensembl; ENST00000636409.1; ENSP00000489819.1; ENSG00000182220.15. [O75787-2]
DR Ensembl; ENST00000636580.2; ENSP00000490083.1; ENSG00000182220.15. [O75787-1]
DR GeneID; 10159; -.
DR KEGG; hsa:10159; -.
DR MANE-Select; ENST00000636580.2; ENSP00000490083.1; NM_005765.3; NP_005756.2.
DR UCSC; uc004det.4; human. [O75787-1]
DR CTD; 10159; -.
DR DisGeNET; 10159; -.
DR GeneCards; ATP6AP2; -.
DR HGNC; HGNC:18305; ATP6AP2.
DR HPA; ENSG00000182220; Tissue enriched (parathyroid).
DR MalaCards; ATP6AP2; -.
DR MIM; 300423; phenotype.
DR MIM; 300556; gene.
DR MIM; 300911; phenotype.
DR MIM; 301045; phenotype.
DR neXtProt; NX_O75787; -.
DR OpenTargets; ENSG00000182220; -.
DR Orphanet; 93952; X-linked intellectual disability, Hedera type.
DR Orphanet; 363654; X-linked parkinsonism-spasticity syndrome.
DR PharmGKB; PA25148; -.
DR VEuPathDB; HostDB:ENSG00000182220; -.
DR eggNOG; KOG4737; Eukaryota.
DR GeneTree; ENSGT00390000008856; -.
DR HOGENOM; CLU_065819_0_0_1; -.
DR OMA; QYAVIFN; -.
DR OrthoDB; 1179410at2759; -.
DR PhylomeDB; O75787; -.
DR TreeFam; TF106137; -.
DR BioCyc; MetaCyc:MON66-34369; -.
DR PathwayCommons; O75787; -.
DR Reactome; R-HSA-2022377; Metabolism of Angiotensinogen to Angiotensins.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; O75787; -.
DR SIGNOR; O75787; -.
DR BioGRID-ORCS; 10159; 298 hits in 730 CRISPR screens.
DR ChiTaRS; ATP6AP2; human.
DR GeneWiki; ATP6AP2; -.
DR GenomeRNAi; 10159; -.
DR Pharos; O75787; Tbio.
DR PRO; PR:O75787; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; O75787; protein.
DR Bgee; ENSG00000182220; Expressed in visceral pleura and 211 other tissues.
DR ExpressionAtlas; O75787; baseline and differential.
DR Genevisible; O75787; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0000421; C:autophagosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0044297; C:cell body; IEA:Ensembl.
DR GO; GO:0030665; C:clathrin-coated vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0032591; C:dendritic spine membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; ISS:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:HGNC-UCL.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0101003; C:ficolin-1-rich granule membrane; TAS:Reactome.
DR GO; GO:0000139; C:Golgi membrane; IC:ComplexPortal.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:ComplexPortal.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-KW.
DR GO; GO:0033176; C:proton-transporting V-type ATPase complex; IC:ComplexPortal.
DR GO; GO:0030672; C:synaptic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070821; C:tertiary granule membrane; TAS:Reactome.
DR GO; GO:0016471; C:vacuolar proton-transporting V-type ATPase complex; IMP:UniProtKB.
DR GO; GO:0000220; C:vacuolar proton-transporting V-type ATPase, V0 domain; ISS:UniProtKB.
DR GO; GO:0038023; F:signaling receptor activity; IEA:InterPro.
DR GO; GO:0002003; P:angiotensin maturation; IDA:HGNC-UCL.
DR GO; GO:0021626; P:central nervous system maturation; IMP:UniProtKB.
DR GO; GO:0048388; P:endosomal lumen acidification; IC:ComplexPortal.
DR GO; GO:0048069; P:eye pigmentation; IMP:UniProtKB.
DR GO; GO:0061795; P:Golgi lumen acidification; IC:ComplexPortal.
DR GO; GO:0060323; P:head morphogenesis; IMP:UniProtKB.
DR GO; GO:0051452; P:intracellular pH reduction; IC:ComplexPortal.
DR GO; GO:0007042; P:lysosomal lumen acidification; IMP:UniProtKB.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0032914; P:positive regulation of transforming growth factor beta1 production; IDA:HGNC-UCL.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:1902600; P:proton transmembrane transport; IC:ComplexPortal.
DR GO; GO:0043408; P:regulation of MAPK cascade; IDA:HGNC-UCL.
DR GO; GO:0021903; P:rostrocaudal neural tube patterning; IMP:UniProtKB.
DR GO; GO:0007035; P:vacuolar acidification; IC:ComplexPortal.
DR InterPro; IPR012493; Renin_rcpt.
DR PANTHER; PTHR13351; PTHR13351; 1.
DR Pfam; PF07850; Renin_r; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Cell projection;
KW Cleavage on pair of basic residues; Congenital disorder of glycosylation;
KW Cytoplasmic vesicle; Disease variant; Endoplasmic reticulum; Endosome;
KW Epilepsy; Intellectual disability; Lysosome; Membrane; Neurodegeneration;
KW Parkinsonism; Phosphoprotein; Postsynaptic cell membrane; Receptor;
KW Reference proteome; Signal; Synapse; Transmembrane; Transmembrane helix.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..350
FT /note="Renin receptor"
FT /id="PRO_0000022203"
FT CHAIN 17..275
FT /note="Renin receptor N-terminal fragment"
FT /evidence="ECO:0000305"
FT /id="PRO_0000447864"
FT CHAIN 278..350
FT /note="Renin receptor C-terminal fragment"
FT /evidence="ECO:0000305"
FT /id="PRO_0000447865"
FT TOPO_DOM 17..302
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 303..323
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 324..350
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOTIF 346..350
FT /note="Mediates retrograde transport to the ER"
FT /evidence="ECO:0000269|PubMed:29127204"
FT SITE 275..276
FT /note="Cleavage; by furin-like protease"
FT /evidence="ECO:0000305|PubMed:29127204"
FT SITE 277..278
FT /note="Cleavage; by furin-like protease"
FT /evidence="ECO:0000305|PubMed:29127204"
FT VAR_SEQ 101..132
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056910"
FT VARIANT 71
FT /note="R -> H (in CDG2R; increases degradation rate via the
FT ER-associated degradation pathway; loss of interaction with
FT ATP6AP1; dbSNP:rs1057523485)"
FT /evidence="ECO:0000269|PubMed:29127204"
FT /id="VAR_082052"
FT VARIANT 90
FT /note="P -> A (in dbSNP:rs9014)"
FT /id="VAR_051313"
FT VARIANT 98
FT /note="L -> S (in CDG2R; impairs export from the ER and
FT cleavage, increases N-glycosylation post-translational
FT modification which targets the misfolded protein to
FT degradation via the ER-associated degradation pathway,
FT results in loss of interaction with ATP6AP1)"
FT /evidence="ECO:0000269|PubMed:29127204"
FT /id="VAR_082053"
FT VARIANT 290
FT /note="A -> P (in dbSNP:rs35798522)"
FT /id="VAR_051314"
FT MUTAGEN 346
FT /note="K->Q: Increases cleavage and stability enhancing
FT localization to the Golgi; when associated with Q-348."
FT /evidence="ECO:0000269|PubMed:29127204"
FT MUTAGEN 348
FT /note="R->Q: Increases cleavage and stability and enhancing
FT localization to the Golgi; when associated with Q-346."
FT /evidence="ECO:0000269|PubMed:29127204"
FT CONFLICT 138
FT /note="G -> W (in Ref. 2; AAK83467)"
FT /evidence="ECO:0000305"
FT CONFLICT 153..154
FT /note="QL -> HV (in Ref. 2; AAK83467)"
FT /evidence="ECO:0000305"
FT CONFLICT 258
FT /note="N -> K (in Ref. 6; BAC11582)"
FT /evidence="ECO:0000305"
FT CONFLICT 285
FT /note="Q -> R (in Ref. 4 and 10)"
FT /evidence="ECO:0000305"
FT CONFLICT 287
FT /note="Missing (in Ref. 8; AAH10395)"
FT /evidence="ECO:0000305"
FT HELIX 303..329
FT /evidence="ECO:0007829|PDB:6WLW"
FT TURN 334..337
FT /evidence="ECO:0007829|PDB:3LC8"
FT HELIX 338..340
FT /evidence="ECO:0007829|PDB:3LBS"
SQ SEQUENCE 350 AA; 39008 MW; 84084A4ACE9C5DE8 CRC64;
MAVFVVLLAL VAGVLGNEFS ILKSPGSVVF RNGNWPIPGE RIPDVAALSM GFSVKEDLSW
PGLAVGNLFH RPRATVMVMV KGVNKLALPP GSVISYPLEN AVPFSLDSVA NSIHSLFSEE
TPVVLQLAPS EERVYMVGKA NSVFEDLSVT LRQLRNRLFQ ENSVLSSLPL NSLSRNNEVD
LLFLSELQVL HDISSLLSRH KHLAKDHSPD LYSLELAGLD EIGKRYGEDS EQFRDASKIL
VDALQKFADD MYSLYGGNAV VELVTVKSFD TSLIRKTRTI LEAKQAKNPA SPYNLAYKYN
FEYSVVFNMV LWIMIALALA VIITSYNIWN MDPGYDSIIY RMTNQKIRMD
