KCJ16_HUMAN
ID KCJ16_HUMAN Reviewed; 418 AA.
AC Q9NPI9;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Inward rectifier potassium channel 16;
DE AltName: Full=Inward rectifier K(+) channel Kir5.1;
DE AltName: Full=Potassium channel, inwardly rectifying subfamily J member 16;
GN Name=KCNJ16;
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], AND TISSUE SPECIFICITY.
RX PubMed=11060447; DOI=10.1159/000015662;
RA Liu Y., McKenna E., Figueroa D.J., Blevins R., Austin C.P., Bennett P.B.,
RA Swanson R.;
RT "The human inward rectifier K(+) channel subunit kir5.1 (KCNJ16) maps to
RT chromosome 17q25 and is expressed in kidney and pancreas.";
RL Cytogenet. Cell Genet. 90:60-63(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], TISSUE SPECIFICITY, SUBCELLULAR
RP LOCATION, AND INTERACTION WITH KCNJ2.
RC TISSUE=Kidney, and Parathyroid;
RX PubMed=11240146; DOI=10.1016/s0014-5793(01)02202-5;
RA Derst C., Karschin C., Wischmeyer E., Hirsch J.R., Preisig-Muller R.,
RA Rajan S., Engel H., Grzeschik K., Daut J., Karschin A.;
RT "Genetic and functional linkage of Kir5.1 and Kir2.1 channel subunits.";
RL FEBS Lett. 491:305-311(2001).
RN [3]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH KCNJ10 AND
RP MAGI1.
RX PubMed=24561201; DOI=10.1016/j.febslet.2014.02.024;
RA Tanemoto M., Abe T., Uchida S., Kawahara K.;
RT "Mislocalization of K+ channels causes the renal salt wasting in
RT EAST/SeSAME syndrome.";
RL FEBS Lett. 588:899-905(2014).
RN [4]
RP VARIANTS HKTD ILE-64; ARG-132; ALA-135; CYS-137; 176-ARG--MET-418 DEL AND
RP LEU-250, INVOLVEMENT IN HKTD, AND CHARACTERIZATION OF VARIANTS HKTD ILE-64;
RP ARG-132; CYS-137; 176-ARG--MET-418 DEL AND LEU-250.
RX PubMed=33811157; DOI=10.1681/asn.2020111587;
RA Schlingmann K.P., Renigunta A., Hoorn E.J., Forst A.L., Renigunta V.,
RA Atanasov V., Mahendran S., Barakat T.S., Gillion V., Godefroid N.,
RA Brooks A.S., Lugtenberg D., Lake J., Debaix H., Rudin C., Knebelmann B.,
RA Tellier S., Rousset-Rouviere C., Viering D., de Baaij J.H.F., Weber S.,
RA Palygin O., Staruschenko A., Kleta R., Houillier P., Bockenhauer D.,
RA Devuyst O., Vargas-Poussou R., Warth R., Zdebik A.A., Konrad M.;
RT "Defects in KCNJ16 cause a novel tubulopathy with hypokalemia, salt
RT wasting, disturbed acid-base homeostasis, and sensorineural deafness.";
RL J. Am. Soc. Nephrol. 32:1498-1512(2021).
CC -!- FUNCTION: Inward rectifier potassium channels are characterized by a
CC greater tendency to allow potassium to flow into the cell rather than
CC out of it. Their voltage dependence is regulated by the concentration
CC of extracellular potassium; as external potassium is raised, the
CC voltage range of the channel opening shifts to more positive voltages.
CC The inward rectification is mainly due to the blockage of outward
CC current by internal magnesium. KCNJ16 may be involved in the regulation
CC of fluid and pH balance. In the kidney, together with KCNJ10, mediates
CC basolateral K(+) recycling in distal tubules; this process is critical
CC for Na(+) reabsorption at the tubules (PubMed:24561201).
CC {ECO:0000305|PubMed:24561201}.
CC -!- SUBUNIT: Heterodimer with Kir4.1/KCNJ10; this interaction is required
CC for KCNJ16 localization to the basolateral membrane in kidney cells. As
CC a heterodimer with KCNJ10, may interact with MAGI1; this interaction
CC may facilitate KCNJ10/KCNJ16 potassium channel expression at the
CC basolateral membrane in kidney cells (PubMed:24561201). May form
CC heterodimers with Kir2.1/KCNJ2 (Probable).
CC {ECO:0000269|PubMed:24561201, ECO:0000305|PubMed:11240146}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:24561201}; Multi-
CC pass membrane protein. Basolateral cell membrane
CC {ECO:0000269|PubMed:24561201}. Note=In kidney distal convoluted
CC tubules, located in the basolateral membrane in the presence of KCNJ10.
CC {ECO:0000269|PubMed:24561201}.
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest levels in adult and
CC fetal kidney (at protein level). In the kidney, expressed in the
CC proximal and distal convoluted tubules, but not in glomeruli nor
CC collecting ducts. {ECO:0000269|PubMed:11060447,
CC ECO:0000269|PubMed:11240146, ECO:0000269|PubMed:24561201}.
CC -!- DISEASE: Hypokalemic tubulopathy and deafness (HKTD) [MIM:619406]: An
CC autosomal recessive disease characterized by renal tubulopathy with
CC hypokalemia, salt wasting, disturbed acid-base homeostasis, and
CC sensorineural deafness. {ECO:0000269|PubMed:33811157}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the inward rectifier-type potassium channel (TC
CC 1.A.2.1) family. KCNJ16 subfamily. {ECO:0000305}.
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DR EMBL; AF179353; AAG09401.1; -; mRNA.
DR EMBL; AF153814; AAF73244.1; -; Genomic_DNA.
DR EMBL; AF153815; AAF73238.1; -; mRNA.
DR EMBL; AF153816; AAF73239.1; -; mRNA.
DR EMBL; AF153817; AAF73240.1; -; mRNA.
DR CCDS; CCDS11687.1; -.
DR CCDS; CCDS74141.1; -.
DR RefSeq; NP_001257351.1; NM_001270422.1.
DR RefSeq; NP_001278551.1; NM_001291622.1.
DR RefSeq; NP_001278552.1; NM_001291623.1.
DR RefSeq; NP_001278553.1; NM_001291624.1.
DR RefSeq; NP_001278554.1; NM_001291625.1.
DR RefSeq; NP_061128.2; NM_018658.2.
DR RefSeq; NP_733937.2; NM_170741.2.
DR RefSeq; NP_733938.2; NM_170742.2.
DR RefSeq; XP_011523083.1; XM_011524781.2.
DR RefSeq; XP_016880102.1; XM_017024613.1.
DR AlphaFoldDB; Q9NPI9; -.
DR SMR; Q9NPI9; -.
DR BioGRID; 109975; 1.
DR IntAct; Q9NPI9; 2.
DR MINT; Q9NPI9; -.
DR STRING; 9606.ENSP00000465295; -.
DR TCDB; 1.A.2.1.11; the inward rectifier k(+) channel (irk-c) family.
DR PhosphoSitePlus; Q9NPI9; -.
DR BioMuta; KCNJ16; -.
DR DMDM; 13878562; -.
DR MassIVE; Q9NPI9; -.
DR PaxDb; Q9NPI9; -.
DR PeptideAtlas; Q9NPI9; -.
DR PRIDE; Q9NPI9; -.
DR Antibodypedia; 31886; 174 antibodies from 29 providers.
DR DNASU; 3773; -.
DR Ensembl; ENST00000283936.5; ENSP00000283936.1; ENSG00000153822.15.
DR Ensembl; ENST00000392670.5; ENSP00000376438.1; ENSG00000153822.15.
DR Ensembl; ENST00000392671.6; ENSP00000376439.1; ENSG00000153822.15.
DR Ensembl; ENST00000589377.1; ENSP00000465967.1; ENSG00000153822.15.
DR Ensembl; ENST00000615244.4; ENSP00000479817.1; ENSG00000153822.15.
DR GeneID; 3773; -.
DR KEGG; hsa:3773; -.
DR MANE-Select; ENST00000392671.6; ENSP00000376439.1; NM_170741.4; NP_733937.3.
DR UCSC; uc002jin.5; human.
DR CTD; 3773; -.
DR DisGeNET; 3773; -.
DR GeneCards; KCNJ16; -.
DR HGNC; HGNC:6262; KCNJ16.
DR HPA; ENSG00000153822; Group enriched (kidney, parathyroid gland, thyroid gland).
DR MIM; 605722; gene.
DR MIM; 619406; phenotype.
DR neXtProt; NX_Q9NPI9; -.
DR OpenTargets; ENSG00000153822; -.
DR PharmGKB; PA30047; -.
DR VEuPathDB; HostDB:ENSG00000153822; -.
DR eggNOG; KOG3827; Eukaryota.
DR GeneTree; ENSGT01030000234586; -.
DR HOGENOM; CLU_022738_3_2_1; -.
DR InParanoid; Q9NPI9; -.
DR OMA; HIFGEWE; -.
DR PhylomeDB; Q9NPI9; -.
DR TreeFam; TF313676; -.
DR PathwayCommons; Q9NPI9; -.
DR Reactome; R-HSA-1296041; Activation of G protein gated Potassium channels.
DR Reactome; R-HSA-1296067; Potassium transport channels.
DR Reactome; R-HSA-997272; Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits.
DR SignaLink; Q9NPI9; -.
DR BioGRID-ORCS; 3773; 14 hits in 1063 CRISPR screens.
DR GeneWiki; KCNJ16; -.
DR GenomeRNAi; 3773; -.
DR Pharos; Q9NPI9; Tbio.
DR PRO; PR:Q9NPI9; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9NPI9; protein.
DR Bgee; ENSG00000153822; Expressed in renal medulla and 147 other tissues.
DR ExpressionAtlas; Q9NPI9; baseline and differential.
DR Genevisible; Q9NPI9; HS.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; NAS:UniProtKB.
DR GO; GO:0005242; F:inward rectifier potassium channel activity; IBA:GO_Central.
DR GO; GO:1990573; P:potassium ion import across plasma membrane; IBA:GO_Central.
DR GO; GO:0006813; P:potassium ion transport; NAS:UniProtKB.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IBA:GO_Central.
DR Gene3D; 2.60.40.1400; -; 1.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR041647; IRK_C.
DR InterPro; IPR016449; K_chnl_inward-rec_Kir.
DR InterPro; IPR008061; K_chnl_inward-rec_Kir5.
DR InterPro; IPR013518; K_chnl_inward-rec_Kir_cyto.
DR InterPro; IPR040445; Kir_TM.
DR PANTHER; PTHR11767; PTHR11767; 1.
DR PANTHER; PTHR11767:SF24; PTHR11767:SF24; 1.
DR Pfam; PF01007; IRK; 1.
DR Pfam; PF17655; IRK_C; 1.
DR PIRSF; PIRSF005465; GIRK_kir; 1.
DR PRINTS; PR01678; KIR5CHANNEL.
DR PRINTS; PR01320; KIRCHANNEL.
DR SUPFAM; SSF81296; SSF81296; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Deafness; Disease variant; Ion channel; Ion transport;
KW Membrane; Phosphoprotein; Potassium; Potassium transport;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport;
KW Voltage-gated channel.
FT CHAIN 1..418
FT /note="Inward rectifier potassium channel 16"
FT /id="PRO_0000154975"
FT TOPO_DOM 1..70
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 71..95
FT /note="Helical; Name=M1"
FT /evidence="ECO:0000250"
FT TOPO_DOM 96..117
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT INTRAMEM 118..129
FT /note="Helical; Pore-forming; Name=H5"
FT /evidence="ECO:0000250"
FT INTRAMEM 130..136
FT /note="Pore-forming"
FT /evidence="ECO:0000250"
FT TOPO_DOM 137..145
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 146..167
FT /note="Helical; Name=M2"
FT /evidence="ECO:0000250"
FT TOPO_DOM 168..418
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT MOTIF 131..136
FT /note="Selectivity filter"
FT /evidence="ECO:0000250"
FT SITE 161
FT /note="Role in the control of polyamine-mediated channel
FT gating and in the blocking by intracellular magnesium"
FT /evidence="ECO:0000250"
FT MOD_RES 373
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z307"
FT MOD_RES 375
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z307"
FT VARIANT 11
FT /note="I -> V (in dbSNP:rs9302912)"
FT /id="VAR_024510"
FT VARIANT 64
FT /note="T -> I (in HKTD; when coexpressed with KCNJ10 or
FT KCNJ15 in Xenopus oocytes, it results in decreased channel
FT expression at the surface and reduced potassium current
FT amplitude compared to the wild-type)"
FT /evidence="ECO:0000269|PubMed:33811157"
FT /id="VAR_085941"
FT VARIANT 132
FT /note="I -> R (in HKTD; when coexpressed with KCNJ10 in
FT Xenopus oocytes, it results in decreased channel expression
FT at the surface and reduced potassium current amplitude
FT compared to the wild-type)"
FT /evidence="ECO:0000269|PubMed:33811157"
FT /id="VAR_085942"
FT VARIANT 135
FT /note="G -> A (in HKTD)"
FT /evidence="ECO:0000269|PubMed:33811157"
FT /id="VAR_085943"
FT VARIANT 137
FT /note="R -> C (in HKTD; when coexpressed with KCNJ10 or
FT KCNJ15 in Xenopus oocytes, it results in decreased channel
FT expression at the surface and reduced potassium current
FT amplitude compared to the wild-type)"
FT /evidence="ECO:0000269|PubMed:33811157"
FT /id="VAR_085944"
FT VARIANT 176..418
FT /note="Missing (in HKTD; when coexpressed with KCNJ10 or
FT KCNJ15 in Xenopus oocytes, it results in decreased channel
FT expression at the surface and reduced potassium current
FT amplitude compared to the wild-type)"
FT /evidence="ECO:0000269|PubMed:33811157"
FT /id="VAR_085945"
FT VARIANT 250
FT /note="P -> L (in HKTD; when coexpressed with KCNJ10 in
FT Xenopus oocytes, it results in decreased channel expression
FT at the surface and reduced potassium current amplitude
FT compared to the wild-type)"
FT /evidence="ECO:0000269|PubMed:33811157"
FT /id="VAR_085946"
SQ SEQUENCE 418 AA; 47949 MW; 1E241B4C15CBD264 CRC64;
MSYYGSSYHI INADAKYPGY PPEHIIAEKR RARRRLLHKD GSCNVYFKHI FGEWGSYVVD
IFTTLVDTKW RHMFVIFSLS YILSWLIFGS VFWLIAFHHG DLLNDPDITP CVDNVHSFTG
AFLFSLETQT TIGYGYRCVT EECSVAVLMV ILQSILSCII NTFIIGAALA KMATARKRAQ
TIRFSYFALI GMRDGKLCLM WRIGDFRPNH VVEGTVRAQL LRYTEDSEGR MTMAFKDLKL
VNDQIILVTP VTIVHEIDHE SPLYALDRKA VAKDNFEILV TFIYTGDSTG TSHQSRSSYV
PREILWGHRF NDVLEVKRKY YKVNCLQFEG SVEVYAPFCS AKQLDWKDQQ LHIEKAPPVR
ESCTSDTKAR RRSFSAVAIV SSCENPEETT TSATHEYRET PYQKALLTLN RISVESQM
