RENR_RAT
ID RENR_RAT Reviewed; 350 AA.
AC Q6AXS4;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 1.
DT 03-AUG-2022, entry version 117.
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; Synonyms=Atp6ip2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=15489960; DOI=10.1172/jci200421398;
RA Ichihara A., Hayashi M., Kaneshiro Y., Suzuki F., Nakagawa T., Tada Y.,
RA Koura Y., Nishiyama A., Okada H., Uddin M.N., Nabi A.H.M.N., Ishida Y.,
RA Inagami T., Saruta T.;
RT "Inhibition of diabetic nephropathy by a decoy peptide corresponding to the
RT 'handle' region for nonproteolytic activation of prorenin.";
RL J. Clin. Invest. 114:1128-1135(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 [3] {ECO:0007744|PDB:6VQ6, ECO:0007744|PDB:6VQ7, ECO:0007744|PDB:6VQ8, ECO:0007744|PDB:6VQC, ECO:0007744|PDB:6VQG, ECO:0007744|PDB:6VQH}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.80 ANGSTROMS) IN COMPLEX WITH THE
RP V-ATPASE, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP TISSUE SPECIFICITY.
RX PubMed=32165585; DOI=10.1126/science.aaz2924;
RA Abbas Y.M., Wu D., Bueler S.A., Robinson C.V., Rubinstein J.L.;
RT "Structure of V-ATPase from the mammalian brain.";
RL Science 367:1240-1246(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 (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 (By similarity). {ECO:0000250|UniProtKB:O75787,
CC ECO:0000250|UniProtKB:Q9CYN9}.
CC -!- SUBUNIT: Interacts with renin (By similarity). Accessory component of
CC the multisubunit proton-transporting vacuolar (V)-ATPase protein pump
CC (PubMed:32165585). Interacts (via N-terminus) with ATP6AP1 (via N-
CC terminus) (PubMed:32165585). Interacts with ATP6V0D1; ATP6V0D1 is a V-
CC ATPase complex subunit and the interaction promotes V-ATPase complex
CC assembly (PubMed:32165585). Interacts with TMEM9; TMEM9 is a V-ATPase
CC assembly regulator and the interaction induces the interaction with
CC ATP6V0D1 (By similarity). Interacts with VMA21 (via N-terminus); VMA21
CC is a V-ATPase accessory component (By similarity).
CC {ECO:0000250|UniProtKB:O75787, ECO:0000269|PubMed:32165585}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9CYN9}; Single-pass type I membrane protein
CC {ECO:0000305}. Lysosome membrane {ECO:0000250|UniProtKB:Q9CYN9};
CC Single-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}. Cytoplasmic vesicle, clathrin-coated
CC vesicle membrane {ECO:0000269|PubMed:32165585}; Single-pass type I
CC membrane protein {ECO:0000305}. Cytoplasmic vesicle, secretory vesicle,
CC synaptic vesicle membrane {ECO:0000269|PubMed:32165585}; Single-pass
CC type I membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in the brain.
CC {ECO:0000269|PubMed:32165585}.
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}.
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DR EMBL; AB188298; BAD67178.1; -; mRNA.
DR EMBL; BC079339; AAH79339.1; -; mRNA.
DR RefSeq; NP_001007092.1; NM_001007091.1.
DR PDB; 6VQ6; EM; 3.90 A; p=1-350.
DR PDB; 6VQ7; EM; 4.00 A; p=1-350.
DR PDB; 6VQ8; EM; 3.90 A; p=1-350.
DR PDB; 6VQC; EM; 3.80 A; p=1-350.
DR PDB; 6VQG; EM; 4.20 A; p=1-350.
DR PDB; 6VQH; EM; 4.40 A; p=1-350.
DR PDBsum; 6VQ6; -.
DR PDBsum; 6VQ7; -.
DR PDBsum; 6VQ8; -.
DR PDBsum; 6VQC; -.
DR PDBsum; 6VQG; -.
DR PDBsum; 6VQH; -.
DR AlphaFoldDB; Q6AXS4; -.
DR SMR; Q6AXS4; -.
DR IntAct; Q6AXS4; 1.
DR STRING; 10116.ENSRNOP00000005138; -.
DR jPOST; Q6AXS4; -.
DR PaxDb; Q6AXS4; -.
DR PRIDE; Q6AXS4; -.
DR GeneID; 302526; -.
DR KEGG; rno:302526; -.
DR UCSC; RGD:1561269; rat.
DR CTD; 10159; -.
DR RGD; 1561269; Atp6ap2.
DR VEuPathDB; HostDB:ENSRNOG00000003858; -.
DR eggNOG; KOG4737; Eukaryota.
DR HOGENOM; CLU_065819_0_0_1; -.
DR InParanoid; Q6AXS4; -.
DR OMA; QYAVIFN; -.
DR OrthoDB; 1179410at2759; -.
DR PhylomeDB; Q6AXS4; -.
DR TreeFam; TF106137; -.
DR Reactome; R-RNO-2022377; Metabolism of Angiotensinogen to Angiotensins.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR PRO; PR:Q6AXS4; -.
DR Proteomes; UP000002494; Chromosome X.
DR Bgee; ENSRNOG00000003858; Expressed in cerebellum and 19 other tissues.
DR Genevisible; Q6AXS4; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0016324; C:apical plasma membrane; IDA:RGD.
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; IDA:RGD.
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:RGD.
DR GO; GO:0010008; C:endosome membrane; ISS:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
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; ISO:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
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; ISS: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; ISO:RGD.
DR GO; GO:0021626; P:central nervous system maturation; ISS:UniProtKB.
DR GO; GO:0048069; P:eye pigmentation; ISO:RGD.
DR GO; GO:0060323; P:head morphogenesis; ISO:RGD.
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:RGD.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; ISO:RGD.
DR GO; GO:0043408; P:regulation of MAPK cascade; ISO:RGD.
DR GO; GO:0021903; P:rostrocaudal neural tube patterning; ISO:RGD.
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; Cell membrane; Cell projection;
KW Cleavage on pair of basic residues; Cytoplasmic vesicle;
KW Endoplasmic reticulum; Endosome; Lysosome; Membrane; Phosphoprotein;
KW Postsynaptic cell membrane; Receptor; Reference proteome; Signal; Synapse;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..350
FT /note="Renin receptor"
FT /id="PRO_0000022206"
FT CHAIN 18..276
FT /note="Renin receptor extracellular fragment"
FT /evidence="ECO:0000305"
FT /id="PRO_0000447870"
FT CHAIN 279..350
FT /note="Renin receptor cytoplasmic fragment"
FT /evidence="ECO:0000305"
FT /id="PRO_0000447871"
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"
SQ SEQUENCE 350 AA; 39082 MW; 9845898BC3E260CF CRC64;
MAVLVVLLSS LVSSALANEF SILRSPGSVV FRNGNWPIPG DRIPDVAALS MGFSVKEDLS
WPGLAVGNLF HRPRATIMVT VKGVDKLALP TGSVISYPLE NAVPFSLDSV ANSIHSLFSE
ETPVVLQLAP SEERVYMVGK ANSVFEDLSV TLRQLRNRLF QENSVLNSLP LNSLSRNNEV
DLLFLSELQV LHDISSLLSR HKHLAKDHSP DLYSLELAGL DELGKRYGED SEQFRDASRI
LVDALQKFAD DMYSLYGGNA VVELVTVKSF DTSLVRKSRT ILETKQENTQ SPYNLAYKYN
LEYSVVFNLV LWIMTGLALA VIITSYNIWN MDPGYDSIIY RMTNQKIRMD
