RENR_MOUSE
ID RENR_MOUSE Reviewed; 350 AA.
AC Q9CYN9; A2BDN5; Q8BVU6; Q91YU5;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 2.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Renin receptor;
DE AltName: Full=ATPase H(+)-transporting lysosomal accessory protein 2;
DE AltName: Full=ATPase H(+)-transporting lysosomal-interacting protein 2;
DE AltName: Full=Renin/prorenin receptor;
DE Contains:
DE RecName: Full=Renin receptor extracellular fragment {ECO:0000305};
DE Contains:
DE RecName: Full=Renin receptor cytoplasmic fragment {ECO:0000305};
DE Flags: Precursor;
GN Name=Atp6ap2 {ECO:0000312|MGI:MGI:1917745}; Synonyms=Atp6ip2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo, and Head;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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].
RC TISSUE=Brain, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=26376863; DOI=10.1093/hmg/ddv380;
RA Dubos A., Castells-Nobau A., Meziane H., Oortveld M.A., Houbaert X.,
RA Iacono G., Martin C., Mittelhaeuser C., Lalanne V., Kramer J.M., Bhukel A.,
RA Quentin C., Slabbert J., Verstreken P., Sigrist S.J., Messaddeq N.,
RA Birling M.C., Selloum M., Stunnenberg H.G., Humeau Y., Schenck A.,
RA Herault Y.;
RT "Conditional depletion of intellectual disability and Parkinsonism
RT candidate gene ATP6AP2 in fly and mouse induces cognitive impairment and
RT neurodegeneration.";
RL Hum. Mol. Genet. 24:6736-6755(2015).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
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 [7]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
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).
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 (By similarity). May mediate renin-dependent
CC cellular responses by activating ERK1 and ERK2 (By similarity). By
CC increasing the catalytic efficiency of renin in AGT/angiotensinogen
CC conversion to angiotensin I, may also play a role in the renin-
CC angiotensin system (RAS) (By similarity). Through its function in V-
CC type ATPase (v-ATPase) assembly and acidification of the lysosome it
CC regulates protein degradation and may control different signaling
CC pathways important for proper brain development, synapse morphology and
CC synaptic transmission (PubMed:26376863, PubMed:29127204,
CC PubMed:30985297). {ECO:0000250|UniProtKB:O75787,
CC ECO:0000269|PubMed:26376863, ECO:0000269|PubMed:29127204,
CC ECO:0000269|PubMed:30985297}.
CC -!- SUBUNIT: Interacts with renin. Accessory component of the multisubunit
CC proton-transporting vacuolar (V)-ATPase protein pump. Interacts (via N-
CC terminus) with ATP6AP1 (via N-terminus). Interacts with ATP6V0D1;
CC ATP6V0D1 is a V-ATPase complex subunit and the interaction promotes V-
CC ATPase complex assembly. Interacts with TMEM9; TMEM9 is a V-ATPase
CC assembly regulator and the interaction induces the interaction with
CC ATP6V0D1. Interacts with VMA21 (via N-terminus); VMA21 is a V-ATPase
CC accessory component. {ECO:0000250|UniProtKB:O75787}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:26376863}; Single-pass type I membrane protein
CC {ECO:0000305}. Lysosome membrane {ECO:0000269|PubMed:26376863,
CC ECO:0000269|PubMed:30985297}; Single-pass type I membrane protein
CC {ECO:0000305}. Cytoplasmic vesicle, autophagosome membrane
CC {ECO:0000269|PubMed:26376863}; Single-pass type I membrane protein
CC {ECO:0000305}. Cell projection, dendritic spine membrane
CC {ECO:0000269|PubMed:26376863}; Single-pass type I membrane protein
CC {ECO:0000305}. Cell projection, axon {ECO:0000269|PubMed:26376863}.
CC Endosome membrane {ECO:0000269|PubMed:30985297}; Single-pass type I
CC membrane protein {ECO:0000305}. Cytoplasmic vesicle, clathrin-coated
CC vesicle membrane {ECO:0000250|UniProtKB:Q6AXS4}; Single-pass type I
CC membrane protein {ECO:0000305}. Cytoplasmic vesicle, secretory vesicle,
CC synaptic vesicle membrane {ECO:0000250|UniProtKB:Q6AXS4}; Single-pass
CC type I membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in glutamatergic and GABAergic neurons
CC with highest levels in the cortex, the hippocampus, the medial
CC habenular nucleus, the cerebellum, the medulla and the olfactory bulb
CC (at protein level). {ECO:0000269|PubMed:26376863}.
CC -!- DEVELOPMENTAL STAGE: Expressed at 12 dpc throughout the developing
CC cortex with notable apical enrichment in radial glial cells (RGCs)
CC along the ventricular surface. {ECO:0000269|PubMed:30985297}.
CC -!- PTM: Phosphorylated. {ECO:0000250|UniProtKB:O75787}.
CC -!- PTM: Proteolytically cleaved by a furin-like convertase in the trans-
CC Golgi network to generate N- and C-terminal fragments.
CC {ECO:0000250|UniProtKB:O75787}.
CC -!- DISRUPTION PHENOTYPE: Conditional knockout mice lacking Atp6ap2 in
CC glutamatergic neurons display increased spontaneous locomotor activity
CC and altered fear memory; show abnormal number and morphology of
CC synapses, presynaptic transmission and autophagy defects that lead to
CC axonal and neuronal degeneration in the cortex and hippocampus
CC (PubMed:26376863). Conditional knockout mice lacking Atp6ap2 in the
CC liver display liver damage, hypoglycosylation of serum proteins and
CC autophagy defects (PubMed:29127204, PubMed:26376863). Conditional
CC knockout mice lacking Atp6ap2 in cortical neurons die around 4 weeks of
CC age (PubMed:30985297). It is associated with a flattened forehead and
CC deficits in neural cell generation and/or survival compared to
CC controls. Mutant embryonic cortex shows reduced proliferation of
CC progenitor neural cells with premature exit of the cell cycle,
CC premature differentiation, and apoptosis. There is also evidence of
CC lysosomal dysfunction, impaired protein degradation in
CC autophagolysosomes, and dysregulation of the mTOR kinase pathway.
CC {ECO:0000269|PubMed:26376863, ECO:0000269|PubMed:29127204,
CC ECO:0000269|PubMed:30985297}.
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DR EMBL; AK017482; BAB30766.2; -; mRNA.
DR EMBL; AK029405; BAC26436.1; -; mRNA.
DR EMBL; AK076495; BAC36365.1; -; mRNA.
DR EMBL; BX000537; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC014706; AAH14706.1; -; mRNA.
DR CCDS; CCDS30023.1; -.
DR RefSeq; NP_081715.1; NM_027439.4.
DR AlphaFoldDB; Q9CYN9; -.
DR SMR; Q9CYN9; -.
DR BioGRID; 214094; 2.
DR STRING; 10090.ENSMUSP00000033313; -.
DR iPTMnet; Q9CYN9; -.
DR PhosphoSitePlus; Q9CYN9; -.
DR EPD; Q9CYN9; -.
DR jPOST; Q9CYN9; -.
DR MaxQB; Q9CYN9; -.
DR PaxDb; Q9CYN9; -.
DR PeptideAtlas; Q9CYN9; -.
DR PRIDE; Q9CYN9; -.
DR ProteomicsDB; 253208; -.
DR TopDownProteomics; Q9CYN9; -.
DR Antibodypedia; 556; 365 antibodies from 37 providers.
DR Ensembl; ENSMUST00000033313; ENSMUSP00000033313; ENSMUSG00000031007.
DR GeneID; 70495; -.
DR KEGG; mmu:70495; -.
DR UCSC; uc009sqx.2; mouse.
DR CTD; 10159; -.
DR MGI; MGI:1917745; Atp6ap2.
DR VEuPathDB; HostDB:ENSMUSG00000031007; -.
DR eggNOG; KOG4737; Eukaryota.
DR GeneTree; ENSGT00390000008856; -.
DR HOGENOM; CLU_065819_0_0_1; -.
DR InParanoid; Q9CYN9; -.
DR OMA; QYAVIFN; -.
DR OrthoDB; 1179410at2759; -.
DR PhylomeDB; Q9CYN9; -.
DR TreeFam; TF106137; -.
DR Reactome; R-MMU-2022377; Metabolism of Angiotensinogen to Angiotensins.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 70495; 20 hits in 71 CRISPR screens.
DR ChiTaRS; Atp6ap2; mouse.
DR PRO; PR:Q9CYN9; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q9CYN9; protein.
DR Bgee; ENSMUSG00000031007; Expressed in choroid plexus epithelium and 250 other tissues.
DR ExpressionAtlas; Q9CYN9; baseline and differential.
DR Genevisible; Q9CYN9; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
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; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-KW.
DR GO; GO:0030672; C:synaptic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016471; C:vacuolar proton-transporting V-type ATPase complex; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0021626; P:central nervous system maturation; IMP:UniProtKB.
DR GO; GO:0048069; P:eye pigmentation; ISO:MGI.
DR GO; GO:0060323; P:head morphogenesis; ISO:MGI.
DR GO; GO:0007042; P:lysosomal lumen acidification; ISS:UniProtKB.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0032914; P:positive regulation of transforming growth factor beta1 production; ISO:MGI.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0043408; P:regulation of MAPK cascade; ISO:MGI.
DR GO; GO:0021903; P:rostrocaudal neural tube patterning; ISO:MGI.
DR InterPro; IPR012493; Renin_rcpt.
DR PANTHER; PTHR13351; PTHR13351; 1.
DR Pfam; PF07850; Renin_r; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Cleavage on pair of basic residues;
KW Cytoplasmic vesicle; Endoplasmic reticulum; Endosome; Lysosome; Membrane;
KW Phosphoprotein; Postsynaptic cell membrane; Receptor; Reference proteome;
KW Signal; Synapse; Transmembrane; Transmembrane helix.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..350
FT /note="Renin receptor"
FT /id="PRO_0000022204"
FT CHAIN 18..276
FT /note="Renin receptor extracellular fragment"
FT /evidence="ECO:0000305"
FT /id="PRO_0000447866"
FT CHAIN 279..350
FT /note="Renin receptor cytoplasmic fragment"
FT /evidence="ECO:0000305"
FT /id="PRO_0000447867"
FT TOPO_DOM 18..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:0000250|UniProtKB:O75787"
FT SITE 276..277
FT /note="Cleavage; by furin-like protease"
FT /evidence="ECO:0000250|UniProtKB:O75787"
FT SITE 278..279
FT /note="Cleavage; by furin-like protease"
FT /evidence="ECO:0000250|UniProtKB:O75787"
FT CONFLICT 157
FT /note="N -> K (in Ref. 1; BAC36365)"
FT /evidence="ECO:0000305"
FT CONFLICT 169
FT /note="L -> H (in Ref. 1; BAC36365)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 350 AA; 39092 MW; 3A90E0C586E7BAC7 CRC64;
MAVLVVLLFF LVAGALGNEF SILRSPGSVV FRNGNWPIPG DRIPDVAALS MGFSVKEDLS
WPGLAVGNLF HRPRATIMVM VKGVDKLALP AGSVISYPLE NAVPFSLDSV ANSIHSLFSE
ETPVVLQLAP SEERVYMVGK ANSVFEDLSV TLRQLRNRLF QENSLLNSLP LNSLSRNNEV
DLLFLSELQV LHDISSLLSR HKHLAKDHSP DLYSLELAGL DELGKRYGED SEQFRDASKI
LVDALQKFAD DMYSLYGGNA VVELVTVKSF DTSLVRKSRT ILEAKQENTQ SPYNLAYKYN
LEYSVVFNLV LWIMIGLALA VIITSYNIWN MDPGYDSIIY RMTNQKIRID
