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 28-JAN-2026, entry version 203. 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:30374053, PubMed:33065002). 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=4; 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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 PDB; 7U4T; EM; 3.60 A; V=1-350. DR PDB; 9CF8; EM; 3.46 A; V=1-350. DR PDB; 9CFC; EM; 3.47 A; V=1-350. DR PDB; 9DET; EM; 3.00 A; p=1-350. DR PDBsum; 3LBS; -. DR PDBsum; 3LC8; -. DR PDBsum; 6WLW; -. DR PDBsum; 6WM2; -. DR PDBsum; 6WM3; -. DR PDBsum; 6WM4; -. DR PDBsum; 7U4T; -. DR PDBsum; 9CF8; -. DR PDBsum; 9CFC; -. DR PDBsum; 9DET; -. DR AlphaFoldDB; O75787; -. DR EMDB; EMD-21844; -. DR EMDB; EMD-21847; -. DR EMDB; EMD-21848; -. DR EMDB; EMD-21849; -. DR EMDB; EMD-26334; -. DR EMDB; EMD-45533; -. DR EMDB; EMD-45536; -. DR SMR; O75787; -. DR BioGRID; 115461; 367. 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 CORUM; O75787; -. DR FunCoup; O75787; 1050. DR IntAct; O75787; 242. DR MINT; O75787; -. DR STRING; 9606.ENSP00000490083; -. DR TCDB; 8.A.80.1.1; the (pro)renin receptor (prr) family. DR iPTMnet; O75787; -. DR PhosphoSitePlus; O75787; -. DR BioMuta; ATP6AP2; -. DR jPOST; O75787; -. DR MassIVE; O75787; -. DR PaxDb; 9606-ENSP00000367697; -. DR PeptideAtlas; O75787; -. DR ProteomicsDB; 50195; -. [O75787-1] DR ProteomicsDB; 7033; -. DR Pumba; O75787; -. DR TopDownProteomics; O75787-1; -. [O75787-1] DR Antibodypedia; 556; 361 antibodies from 37 providers. DR DNASU; 10159; -. DR Ensembl; ENST00000636409.1; ENSP00000489819.1; ENSG00000182220.16. [O75787-2] DR Ensembl; ENST00000636580.2; ENSP00000490083.1; ENSG00000182220.16. [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 AGR; HGNC:18305; -. DR ClinPGx; PA25148; -. 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 OpenTargets; ENSG00000182220; -. DR Orphanet; 93952; X-linked intellectual disability, Hedera type. DR Orphanet; 363654; X-linked parkinsonism-spasticity syndrome. DR VEuPathDB; HostDB:ENSG00000182220; -. DR eggNOG; KOG4737; Eukaryota. DR GeneTree; ENSGT00390000008856; -. DR HOGENOM; CLU_065819_0_0_1; -. DR InParanoid; O75787; -. DR OMA; QYAVIFN; -. DR OrthoDB; 7866065at2759; -. DR PAN-GO; O75787; 2 GO annotations based on evolutionary models. DR PhylomeDB; O75787; -. DR BioCyc; MetaCyc:MONOMER66-34369; -. 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 Agora; ENSG00000182220; -. DR BioGRID-ORCS; 10159; 326 hits in 822 CRISPR screens. DR ChiTaRS; ATP6AP2; human. DR EvolutionaryTrace; O75787; -. 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 213 other cell types or tissues. DR ExpressionAtlas; O75787; baseline and differential. DR GO; GO:0000421; C:autophagosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell. 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; NAS:ComplexPortal. 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:0033176; C:proton-transporting V-type ATPase complex; NAS: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; NAS:ComplexPortal. DR GO; GO:0048069; P:eye pigmentation; IMP:UniProtKB. DR GO; GO:0061795; P:Golgi lumen acidification; NAS:ComplexPortal. DR GO; GO:0060323; P:head morphogenesis; IMP:UniProtKB. DR GO; GO:0051452; P:intracellular pH reduction; NAS: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; NAS: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:0097401; P:synaptic vesicle lumen acidification; IEA:Ensembl. DR GO; GO:0007035; P:vacuolar acidification; NAS:ComplexPortal. DR InterPro; IPR056780; Renin_r_C. DR InterPro; IPR012493; Renin_rcpt. DR InterPro; IPR057318; RENR_N. DR PANTHER; PTHR13351; RENIN RECEPTOR; 1. DR PANTHER; PTHR13351:SF5; RENIN RECEPTOR; 1. DR Pfam; PF07850; Renin_r; 1. DR Pfam; PF25294; RENR_N; 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; KW Proteomics identification; Receptor; Reference proteome; Signal; Synapse; KW 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 dbSNP:rs1926621737)" 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 //