RNK_HUMAN
ID RNK_HUMAN Reviewed; 137 AA.
AC Q6P5S7; G3V1Z9; Q502Z2;
DT 22-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2013, sequence version 2.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Ribonuclease kappa;
DE Short=RNase K;
DE Short=RNase kappa;
DE EC=3.1.-.- {ECO:0000269|PubMed:17881363};
DE AltName: Full=V-type proton ATPase subunit f {ECO:0000303|PubMed:33065002};
DE Short=V-ATPase subunit f {ECO:0000303|PubMed:33065002};
GN Name=RNASEK;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 24-137 (ISOFORM 1).
RC TISSUE=Hippocampus;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 26-137 (ISOFORM 1), AND
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 27-137 (ISOFORM 2).
RC TISSUE=Adrenal cortex, 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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 29-137 (ISOFORM 1), FUNCTION, CATALYTIC
RP ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=17881363; DOI=10.1093/nar/gkm718;
RA Economopoulou M.-A., Fragoulis E.G., Sideris D.C.;
RT "Molecular cloning and characterization of the human RNase kappa, an
RT ortholog of Cc RNase.";
RL Nucleic Acids Res. 35:6389-6398(2007).
RN [6]
RP FUNCTION, FUNCTION (MICROBIAL INFECTION), INTERACTION WITH ATP6AP1, AND
RP SUBCELLULAR LOCATION.
RX PubMed=26212330; DOI=10.1016/j.celrep.2015.06.076;
RA Perreira J.M., Aker A.M., Savidis G., Chin C.R., McDougall W.M.,
RA Portmann J.M., Meraner P., Smith M.C., Rahman M., Baker R.E., Gauthier A.,
RA Franti M., Brass A.L.;
RT "RNASEK Is a V-ATPase-Associated Factor Required for Endocytosis and the
RT Replication of Rhinovirus, Influenza A Virus, and Dengue Virus.";
RL Cell Rep. 12:850-863(2015).
RN [7]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=26056282; DOI=10.1073/pnas.1424098112;
RA Hackett B.A., Yasunaga A., Panda D., Tartell M.A., Hopkins K.C.,
RA Hensley S.E., Cherry S.;
RT "RNASEK is required for internalization of diverse acid-dependent
RT viruses.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:7797-7802(2015).
RN [8] {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 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: Endoribonuclease which preferentially cleaves ApU and ApG
CC phosphodiester bonds. Hydrolyzes UpU bonds at a lower rate
CC (PubMed:17881363). Regulates the activity of vacuolar (H+)-ATPase (V-
CC ATPase) which is responsible for acidifying and maintaining the pH of
CC intracellular compartments (PubMed:26212330). Required at an early
CC stage of receptor-mediated endocytosis (PubMed:26212330).
CC {ECO:0000269|PubMed:17881363, ECO:0000269|PubMed:26212330}.
CC -!- FUNCTION: (Microbial infection) Required at an early stage of both
CC clathrin-mediated and clathrin-independent endocytic uptake of a
CC diverse set of viruses, including dengue, West Nile, Sindbis, Rift
CC Valley Fever, influenza, and human rhinoviruses (PubMed:26056282,
CC PubMed:26212330). {ECO:0000269|PubMed:26056282,
CC ECO:0000269|PubMed:26212330}.
CC -!- SUBUNIT: Interacts with the proton translocation complex V0 of the V-
CC ATPase (PubMed:33065002). Interacts with ATP6AP1 (PubMed:26212330).
CC {ECO:0000269|PubMed:26212330, ECO:0000269|PubMed:33065002}.
CC -!- INTERACTION:
CC Q6P5S7; Q9H2C2: ARV1; NbExp=3; IntAct=EBI-18397230, EBI-11724186;
CC Q6P5S7; Q9HD20-3: ATP13A1; NbExp=3; IntAct=EBI-18397230, EBI-12069500;
CC Q6P5S7; Q12983: BNIP3; NbExp=3; IntAct=EBI-18397230, EBI-749464;
CC Q6P5S7; Q9Y3D6: FIS1; NbExp=3; IntAct=EBI-18397230, EBI-3385283;
CC Q6P5S7; Q9H0Q3: FXYD6; NbExp=3; IntAct=EBI-18397230, EBI-713304;
CC Q6P5S7; Q96F15: GIMAP5; NbExp=3; IntAct=EBI-18397230, EBI-6166686;
CC Q6P5S7; P30519: HMOX2; NbExp=3; IntAct=EBI-18397230, EBI-712096;
CC Q6P5S7; O75427: LRCH4; NbExp=3; IntAct=EBI-18397230, EBI-718707;
CC Q6P5S7; Q9NZG7: NINJ2; NbExp=3; IntAct=EBI-18397230, EBI-10317425;
CC Q6P5S7; Q5QGT7: RTP2; NbExp=3; IntAct=EBI-18397230, EBI-10244780;
CC Q6P5S7; Q96IW7: SEC22A; NbExp=3; IntAct=EBI-18397230, EBI-8652744;
CC Q6P5S7; O75920: SERF1B; NbExp=3; IntAct=EBI-18397230, EBI-2115181;
CC Q6P5S7; Q8N6R1: SERP2; NbExp=3; IntAct=EBI-18397230, EBI-749270;
CC Q6P5S7; Q0VAQ4: SMAGP; NbExp=3; IntAct=EBI-18397230, EBI-10226799;
CC Q6P5S7; Q9UNK0: STX8; NbExp=3; IntAct=EBI-18397230, EBI-727240;
CC Q6P5S7; O14925: TIMM23; NbExp=3; IntAct=EBI-18397230, EBI-1047996;
CC Q6P5S7; Q969S6: TMEM203; NbExp=3; IntAct=EBI-18397230, EBI-12274070;
CC Q6P5S7; Q9H0R3: TMEM222; NbExp=3; IntAct=EBI-18397230, EBI-347385;
CC Q6P5S7; Q9H2L4: TMEM60; NbExp=3; IntAct=EBI-18397230, EBI-2852148;
CC Q6P5S7; Q9NSU2-1: TREX1; NbExp=3; IntAct=EBI-18397230, EBI-16746122;
CC Q6P5S7; O95292: VAPB; NbExp=3; IntAct=EBI-18397230, EBI-1188298;
CC Q6P5S7; Q9UEU0: VTI1B; NbExp=3; IntAct=EBI-18397230, EBI-723716;
CC Q6P5S7; Q8IVQ6: ZDHHC21; NbExp=3; IntAct=EBI-18397230, EBI-2849773;
CC -!- SUBCELLULAR LOCATION: Endomembrane system
CC {ECO:0000269|PubMed:26212330}; Multi-pass membrane protein
CC {ECO:0000255}. Cytoplasmic vesicle, clathrin-coated vesicle membrane
CC {ECO:0000250|UniProtKB:Q3ZC23}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6P5S7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6P5S7-2; Sequence=VSP_046496;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:17881363}.
CC -!- SIMILARITY: Belongs to the RNase K family. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-40 is the initiator.
CC Orthologous sequences cannot be extended. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH51802.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH62705.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAF82619.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAN89245.1; 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; AC040977; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471108; EAW90275.1; -; Genomic_DNA.
DR EMBL; AK289930; BAF82619.1; ALT_INIT; mRNA.
DR EMBL; BC051802; AAH51802.1; ALT_INIT; mRNA.
DR EMBL; BC062705; AAH62705.1; ALT_INIT; mRNA.
DR EMBL; BC095436; AAH95436.1; -; mRNA.
DR EMBL; AM746459; CAN89245.1; ALT_INIT; mRNA.
DR RefSeq; NP_001004333.2; NM_001004333.4.
DR PDB; 6WLW; EM; 3.00 A; T=1-137.
DR PDB; 6WM2; EM; 3.10 A; T=1-137.
DR PDB; 6WM3; EM; 3.40 A; T=1-137.
DR PDB; 6WM4; EM; 3.60 A; T=1-137.
DR PDBsum; 6WLW; -.
DR PDBsum; 6WM2; -.
DR PDBsum; 6WM3; -.
DR PDBsum; 6WM4; -.
DR AlphaFoldDB; Q6P5S7; -.
DR SMR; Q6P5S7; -.
DR BioGRID; 136544; 27.
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; Q6P5S7; 26.
DR MINT; Q6P5S7; -.
DR STRING; 9606.ENSP00000449500; -.
DR TCDB; 3.A.2.2.4; the h(+)- or na(+)-translocating f-type, v-type and a-type atpase (f-atpase) superfamily.
DR iPTMnet; Q6P5S7; -.
DR PhosphoSitePlus; Q6P5S7; -.
DR SwissPalm; Q6P5S7; -.
DR BioMuta; RNASEK; -.
DR DMDM; 485956029; -.
DR MassIVE; Q6P5S7; -.
DR PaxDb; Q6P5S7; -.
DR PeptideAtlas; Q6P5S7; -.
DR PRIDE; Q6P5S7; -.
DR ProteomicsDB; 67004; -. [Q6P5S7-1]
DR Antibodypedia; 48096; 56 antibodies from 12 providers.
DR DNASU; 440400; -.
DR Ensembl; ENST00000548577.5; ENSP00000449500.1; ENSG00000219200.12. [Q6P5S7-1]
DR GeneID; 440400; -.
DR KEGG; hsa:440400; -.
DR UCSC; uc002gea.5; human. [Q6P5S7-1]
DR CTD; 440400; -.
DR DisGeNET; 440400; -.
DR GeneCards; RNASEK; -.
DR HGNC; HGNC:33911; RNASEK.
DR HPA; ENSG00000219200; Low tissue specificity.
DR neXtProt; NX_Q6P5S7; -.
DR OpenTargets; ENSG00000219200; -.
DR PharmGKB; PA162401458; -.
DR VEuPathDB; HostDB:ENSG00000219200; -.
DR eggNOG; ENOG502S351; Eukaryota.
DR GeneTree; ENSGT00390000009664; -.
DR InParanoid; Q6P5S7; -.
DR OrthoDB; 1615928at2759; -.
DR PhylomeDB; Q6P5S7; -.
DR TreeFam; TF300182; -.
DR PathwayCommons; Q6P5S7; -.
DR SignaLink; Q6P5S7; -.
DR BioGRID-ORCS; 440400; 184 hits in 1080 CRISPR screens.
DR GenomeRNAi; 440400; -.
DR Pharos; Q6P5S7; Tbio.
DR PRO; PR:Q6P5S7; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q6P5S7; protein.
DR Bgee; ENSG00000219200; Expressed in right adrenal gland cortex and 96 other tissues.
DR ExpressionAtlas; Q6P5S7; baseline and differential.
DR Genevisible; Q6P5S7; HS.
DR GO; GO:0030665; C:clathrin-coated vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0010008; C:endosome membrane; IC:ComplexPortal.
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; IC:ComplexPortal.
DR GO; GO:0016020; C:membrane; IDA:ComplexPortal.
DR GO; GO:0005886; C:plasma membrane; IC:ComplexPortal.
DR GO; GO:0033176; C:proton-transporting V-type ATPase complex; IC:ComplexPortal.
DR GO; GO:0000220; C:vacuolar proton-transporting V-type ATPase, V0 domain; ISS:UniProtKB.
DR GO; GO:0004521; F:endoribonuclease activity; IDA:UniProtKB.
DR GO; GO:0048388; P:endosomal lumen acidification; IPI:UniProtKB.
DR GO; GO:0061795; P:Golgi lumen acidification; IC:ComplexPortal.
DR GO; GO:0051452; P:intracellular pH reduction; IC:ComplexPortal.
DR GO; GO:0007042; P:lysosomal lumen acidification; IC:ComplexPortal.
DR GO; GO:1902600; P:proton transmembrane transport; IPI:UniProtKB.
DR GO; GO:0006898; P:receptor-mediated endocytosis; IMP:UniProtKB.
DR GO; GO:0019065; P:receptor-mediated endocytosis of virus by host cell; IMP:UniProtKB.
DR GO; GO:0007035; P:vacuolar acidification; IC:ComplexPortal.
DR InterPro; IPR026770; RNase_K.
DR PANTHER; PTHR31733; PTHR31733; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasmic vesicle; Endocytosis;
KW Endonuclease; Hydrogen ion transport; Hydrolase; Ion transport; Membrane;
KW Nuclease; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..137
FT /note="Ribonuclease kappa"
FT /id="PRO_0000344221"
FT TRANSMEM 52..72
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 104..124
FT /note="Helical"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..65
FT /note="MGWLRPGPRPLCPPARASWAFSHRFPSPLAPRRSPTPFFMASLLCCGPKLAA
FT CGIVLSAWGVIML -> MVEAGATPPLPPCEGILGFLPPLSEPACTSAIPDSLLYGVAP
FT VLWAEAGRLRHRPQRLGSDH (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_046496"
FT CONFLICT 26..27
FT /note="PS -> GG (in Ref. 4; AAH62705)"
FT /evidence="ECO:0000305"
FT HELIX 50..73
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 80..82
FT /evidence="ECO:0007829|PDB:6WLW"
FT STRAND 89..93
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 95..127
FT /evidence="ECO:0007829|PDB:6WLW"
SQ SEQUENCE 137 AA; 15420 MW; 1E8DD4A350DCCC4F CRC64;
MGWLRPGPRP LCPPARASWA FSHRFPSPLA PRRSPTPFFM ASLLCCGPKL AACGIVLSAW
GVIMLIMLGI FFNVHSAVLI EDVPFTEKDF ENGPQNIYNL YEQVSYNCFI AAGLYLLLGG
FSFCQVRLNK RKEYMVR
