PK1L3_HUMAN
ID PK1L3_HUMAN Reviewed; 1732 AA.
AC Q7Z443;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Polycystic kidney disease protein 1-like 3;
DE AltName: Full=PC1-like 3 protein;
DE AltName: Full=Polycystin-1L3;
DE Flags: Precursor;
GN Name=PKD1L3;
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], FUNCTION, ALTERNATIVE SPLICING, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=12782129; DOI=10.1016/s0888-7543(03)00048-x;
RA Li A., Tian X., Sung S.-W., Somlo S.;
RT "Identification of two novel polycystic kidney disease-1-like genes in
RT human and mouse genomes.";
RL Genomics 81:596-608(2003).
RN [2]
RP ERRATUM OF PUBMED:12782129.
RA Li A., Tian X., Sung S.-W., Somlo S.;
RL Genomics 82:498-500(2003).
RN [3]
RP ACTIVITY REGULATION, AND SUBCELLULAR LOCATION.
RX PubMed=18535624; DOI=10.1038/embor.2008.89;
RA Inada H., Kawabata F., Ishimaru Y., Fushiki T., Matsunami H., Tominaga M.;
RT "Off-response property of an acid-activated cation channel complex PKD1L3-
RT PKD2L1.";
RL EMBO Rep. 9:690-697(2008).
RN [4]
RP ACTIVITY REGULATION.
RX PubMed=19464260; DOI=10.1016/j.bbrc.2009.05.069;
RA Ishii S., Misaka T., Kishi M., Kaga T., Ishimaru Y., Abe K.;
RT "Acetic acid activates PKD1L3-PKD2L1 channel--a candidate sour taste
RT receptor.";
RL Biochem. Biophys. Res. Commun. 385:346-350(2009).
RN [5]
RP FUNCTION.
RX PubMed=19812697; DOI=10.1371/journal.pone.0007347;
RA Huque T., Cowart B.J., Dankulich-Nagrudny L., Pribitkin E.A., Bayley D.L.,
RA Spielman A.I., Feldman R.S., Mackler S.A., Brand J.G.;
RT "Sour ageusia in two individuals implicates ion channels of the ASIC and
RT PKD families in human sour taste perception at the anterior tongue.";
RL PLoS ONE 4:E7347-E7347(2009).
RN [6]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH PKD2L1.
RX PubMed=20538909; DOI=10.1096/fj.10-162925;
RA Ishimaru Y., Katano Y., Yamamoto K., Akiba M., Misaka T., Roberts R.W.,
RA Asakura T., Matsunami H., Abe K.;
RT "Interaction between PKD1L3 and PKD2L1 through their transmembrane domains
RT is required for localization of PKD2L1 at taste pores in taste cells of
RT circumvallate and foliate papillae.";
RL FASEB J. 24:4058-4067(2010).
RN [7]
RP ACTIVITY REGULATION.
RX PubMed=22420714; DOI=10.1111/j.1742-4658.2012.08566.x;
RA Ishii S., Kurokawa A., Kishi M., Yamagami K., Okada S., Ishimaru Y.,
RA Misaka T.;
RT "The response of PKD1L3/PKD2L1 to acid stimuli is inhibited by capsaicin
RT and its pungent analogs.";
RL FEBS J. 279:1857-1870(2012).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23212381; DOI=10.1038/ncomms2257;
RA Yu Y., Ulbrich M.H., Li M.H., Dobbins S., Zhang W.K., Tong L.,
RA Isacoff E.Y., Yang J.;
RT "Molecular mechanism of the assembly of an acid-sensing receptor ion
RT channel complex.";
RL Nat. Commun. 3:1252-1252(2012).
CC -!- FUNCTION: Component of a calcium channel. May act as a sour taste
CC receptor by forming a calcium channel with PKD1L3 in gustatory cells;
CC however, its contribution to sour taste perception is unclear in vivo
CC and may be indirect. {ECO:0000269|PubMed:12782129,
CC ECO:0000269|PubMed:19812697, ECO:0000269|PubMed:23212381}.
CC -!- ACTIVITY REGULATION: The calcium channel is gated following an off-
CC response property by acid: gated open after the removal of acid
CC stimulus, but not during acid application.
CC {ECO:0000269|PubMed:18535624, ECO:0000269|PubMed:19464260,
CC ECO:0000269|PubMed:22420714}.
CC -!- SUBUNIT: Calcium channels are probably composed of 3 subunit of PKD2L1
CC and 1 subunit of PKD1L3.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18535624,
CC ECO:0000269|PubMed:20538909, ECO:0000269|PubMed:23212381}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:18535624,
CC ECO:0000269|PubMed:20538909, ECO:0000269|PubMed:23212381}.
CC Note=Interaction with PKD2L1 is required for localization to the cell
CC membrane.
CC -!- TISSUE SPECIFICITY: Highly expressed in placenta, weakly in heart and
CC lung. {ECO:0000269|PubMed:12782129}.
CC -!- SIMILARITY: Belongs to the polycystin family. {ECO:0000305}.
CC -!- CAUTION: PKD1L3 and PKD2L1 have been defined as sour taste receptor in
CC gustatory cells based on a number of indirect evidences in mouse. Some
CC data confirm this hypothesis in human: in 2 patients with sour ageusia
CC that are unresponsive to sour stimuli, but show normal responses to
CC bitter, sweet, and salty stimuli, expression of PKD1L3 and PKD2L1 is
CC absent in the anterior part of the tongue (PubMed:19812697). However, a
CC number of experiments have recently shown that the sour taste receptor
CC activity is probably indirect. {ECO:0000305|PubMed:19812697}.
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DR EMBL; AY164485; AAO32798.1; -; mRNA.
DR CCDS; CCDS73912.1; -.
DR RefSeq; NP_853514.1; NM_181536.1.
DR AlphaFoldDB; Q7Z443; -.
DR SMR; Q7Z443; -.
DR BioGRID; 131173; 3.
DR IntAct; Q7Z443; 2.
DR MINT; Q7Z443; -.
DR STRING; 9606.ENSP00000480090; -.
DR DrugBank; DB11093; Calcium citrate.
DR DrugBank; DB11348; Calcium Phosphate.
DR DrugBank; DB14481; Calcium phosphate dihydrate.
DR MEROPS; P02.039; -.
DR TCDB; 1.A.5.1.2; the polycystin cation channel (pcc) family.
DR GlyGen; Q7Z443; 5 sites.
DR iPTMnet; Q7Z443; -.
DR PhosphoSitePlus; Q7Z443; -.
DR BioMuta; PKD1L3; -.
DR DMDM; 74713456; -.
DR EPD; Q7Z443; -.
DR MaxQB; Q7Z443; -.
DR PeptideAtlas; Q7Z443; -.
DR PRIDE; Q7Z443; -.
DR ProteomicsDB; 69147; -.
DR Antibodypedia; 72636; 50 antibodies from 7 providers.
DR DNASU; 342372; -.
DR Ensembl; ENST00000620267.2; ENSP00000480090.1; ENSG00000277481.2.
DR GeneID; 342372; -.
DR KEGG; hsa:342372; -.
DR MANE-Select; ENST00000620267.2; ENSP00000480090.1; NM_181536.2; NP_853514.1.
DR UCSC; uc059wxm.1; human.
DR CTD; 342372; -.
DR DisGeNET; 342372; -.
DR GeneCards; PKD1L3; -.
DR HGNC; HGNC:21716; PKD1L3.
DR HPA; ENSG00000277481; Tissue enhanced (liver).
DR MIM; 607895; gene.
DR neXtProt; NX_Q7Z443; -.
DR OpenTargets; ENSG00000277481; -.
DR VEuPathDB; HostDB:ENSG00000277481; -.
DR eggNOG; KOG3272; Eukaryota.
DR eggNOG; KOG3599; Eukaryota.
DR GeneTree; ENSGT00940000162813; -.
DR HOGENOM; CLU_000913_1_0_1; -.
DR InParanoid; Q7Z443; -.
DR OMA; QKWRFFT; -.
DR OrthoDB; 1276906at2759; -.
DR PhylomeDB; Q7Z443; -.
DR PathwayCommons; Q7Z443; -.
DR SignaLink; Q7Z443; -.
DR BioGRID-ORCS; 342372; 6 hits in 199 CRISPR screens.
DR ChiTaRS; PKD1L3; human.
DR GenomeRNAi; 342372; -.
DR Pharos; Q7Z443; Tbio.
DR PRO; PR:Q7Z443; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q7Z443; protein.
DR Bgee; ENSG00000277481; Expressed in right lobe of liver and 30 other tissues.
DR GO; GO:0034703; C:cation channel complex; ISS:BHF-UCL.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0043235; C:receptor complex; ISS:BHF-UCL.
DR GO; GO:0005262; F:calcium channel activity; IBA:GO_Central.
DR GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW.
DR GO; GO:0006812; P:cation transport; ISS:BHF-UCL.
DR GO; GO:0071468; P:cellular response to acidic pH; ISS:BHF-UCL.
DR GO; GO:0001581; P:detection of chemical stimulus involved in sensory perception of sour taste; ISS:BHF-UCL.
DR GO; GO:0050982; P:detection of mechanical stimulus; IBA:GO_Central.
DR GO; GO:0001822; P:kidney development; IEA:InterPro.
DR GO; GO:0050915; P:sensory perception of sour taste; IMP:UniProtKB.
DR CDD; cd01752; PLAT_polycystin; 1.
DR Gene3D; 2.60.220.50; -; 1.
DR Gene3D; 3.10.100.10; -; 1.
DR InterPro; IPR001304; C-type_lectin-like.
DR InterPro; IPR016186; C-type_lectin-like/link_sf.
DR InterPro; IPR016187; CTDL_fold.
DR InterPro; IPR046338; GAIN_dom_sf.
DR InterPro; IPR000203; GPS.
DR InterPro; IPR000434; PC1.
DR InterPro; IPR013122; PKD1_2_channel.
DR InterPro; IPR001024; PLAT/LH2_dom.
DR InterPro; IPR036392; PLAT/LH2_dom_sf.
DR InterPro; IPR042060; PLAT_polycystin1.
DR Pfam; PF01825; GPS; 1.
DR Pfam; PF00059; Lectin_C; 1.
DR Pfam; PF08016; PKD_channel; 1.
DR Pfam; PF01477; PLAT; 1.
DR PRINTS; PR00500; POLYCYSTIN1.
DR SMART; SM00303; GPS; 1.
DR SMART; SM00308; LH2; 1.
DR SUPFAM; SSF49723; SSF49723; 1.
DR SUPFAM; SSF56436; SSF56436; 1.
DR PROSITE; PS50221; GPS; 1.
DR PROSITE; PS50095; PLAT; 1.
PE 1: Evidence at protein level;
KW Calcium; Calcium channel; Calcium transport; Cell membrane; Disulfide bond;
KW Glycoprotein; Ion channel; Ion transport; Lectin; Membrane;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..1732
FT /note="Polycystic kidney disease protein 1-like 3"
FT /id="PRO_0000322578"
FT TOPO_DOM 24..697
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 698..718
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 719..905
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 906..926
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 927..939
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 940..960
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 961..1154
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1155..1175
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1176..1198
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1199..1219
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1220..1280
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1281..1301
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1302..1462
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1463..1483
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1484..1501
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1502..1522
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1523..1550
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1551..1571
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1572..1592
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1593..1613
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1614..1625
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1626..1646
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1647..1658
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1659..1679
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1680..1732
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 30..138
FT /note="C-type lectin"
FT DOMAIN 632..681
FT /note="GPS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00098"
FT DOMAIN 743..860
FT /note="PLAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT REGION 1613..1651
FT /note="Channel pore-region"
FT CARBOHYD 286
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 363
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 515
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 537
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 575
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 51..137
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT DISULFID 112..129
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT VARIANT 120
FT /note="I -> F (in dbSNP:rs16973585)"
FT /id="VAR_039453"
FT VARIANT 211
FT /note="S -> P (in dbSNP:rs4788591)"
FT /id="VAR_039454"
FT VARIANT 274
FT /note="K -> E (in dbSNP:rs12708923)"
FT /id="VAR_039455"
FT VARIANT 429
FT /note="T -> S (in dbSNP:rs7185272)"
FT /id="VAR_039456"
FT VARIANT 471
FT /note="A -> D (in dbSNP:rs16973537)"
FT /id="VAR_039457"
FT VARIANT 571
FT /note="H -> Q (in dbSNP:rs1559401)"
FT /id="VAR_039458"
FT VARIANT 593
FT /note="V -> M (in dbSNP:rs9925415)"
FT /id="VAR_039459"
FT VARIANT 903
FT /note="V -> I (in dbSNP:rs9921412)"
FT /id="VAR_039460"
FT VARIANT 1176
FT /note="S -> R (in dbSNP:rs1035543)"
FT /id="VAR_039461"
FT VARIANT 1474
FT /note="Y -> C (in dbSNP:rs13335617)"
FT /id="VAR_039462"
SQ SEQUENCE 1732 AA; 195894 MW; 64847A1C8BE5A6A1 CRC64;
MFFKGGSWLW LYIRTSIILG SELNSPAPHG QNNCYQLNRF QCSFEEAQHY CHVQRGFLAH
IWNKEVQDLI RDYLEEGKKW WIGQNVMPLK KHQDNKYPAD VAANGPPKPL SCTYLSRNFI
RISSKGDKCL LKYYFICQTG DFLDGDAHYE RNGNNSHLYQ RHKKTKRGVA IARDKMPPGP
GHLPTTCHYP LPAHLSKTLC HPISQFPSVL SSITSQVTSA ASEPSSQPLP VITQLTMPVS
VTHAGQSLAE TTSSPKEEGH PNTFTSYLQV SLQKASGQVI DEIAGNFSRA VHGLQALNKL
QEACEFLQKL TALTPRFSKP AQVNLINSLI YLSEELLRIP FQNNNSLGFK VPPTVCPFHS
LNNVTKAGEG SWLESKRHTE PVEDILEMSL VEFGNIGEAF LEQNQSPESS VTLTSANATL
LLSRQNISTL PLSSYTLGHP APVRLGFPSA LALKELLNKH PGVNVQITGL AFNPFKDLDN
RNIVGSIGSV LLSANRKLLQ VHDLMEDIEI MLWRNVSLET HPTSLNMSTH QLTITVNVTS
LEKSLIVSID PDSPLLMTLY LGFQYQPNCT HFHLNITLPK DKVWQKDEEY TWVLNPEHLQ
HGIGTYYITA VLSERQEGAQ QTPSLVSVIT AVTQCYYWEI HNQTWSSAGC QVGPQSTILR
TQCLCNHLTF FASDFFVVPR TVNVEDTIKL FLRVTNNPVG VSLLASLLGF YVITVVWARK
KDQADMQKVK VTVLADNDPS AQFHYLIQVY TGYRRSAATT AKVVITLYGS EGRSEPHHLC
DPQKTVFERG GLDVFLLTTW TSLGNLHSLR LWHDNSGVSP SWYVSQVIVC DMAVKRKWHF
LCNCWLAVDL GDCELDRVFI PVSKRELFSF RHLFSSMIVE KFTQDYLWLS IATRHPWNQF
TRVQRLSCCM TLLLCNMVIN VMFWKINSTT AKRDEQMRPF AVAWSELLVS IHTAVILFPI
NLVIGRLFPL IEPQETLPLF PPIQASCLSD ASVEPLSATM VVEELKETVR FLLRRNTYLL
SKCEQPPWSS WDITKLVKLL SSLVSSHLEG QGCHQQGERH WARVVPENHH HFCCYLHRVL
QRLKSHLGTL GLTQGHQSCD FLDAASQLQK LQELLETHIL PTEQEPSREV TSFAILSSEE
GKKPISNGLS KWLTSVCWLL LGFTSLASAF FTALYSLELS KDQATSWMIS IILSVLQNIF
ISQPVKVVFF TFLYSLMMSR MPRLNKENEQ QTKRILALLA KCSSSVPGSR DKNNPVYVAP
AINSPTKHPE RTLKKKKLFK LTGDILVQIL FLTLLMTAIY SAKNSNRFYL HQAIWKTFSH
QFSEIKLLQD FYPWANHILL PSLYGDYRGK NAVLEPSHCK CGVQLIFQIP RTKTYEKVDE
GQLAFCDNGH TCGRPKSLFP GLHLRRFSYI CSPRPMVLIP TDELHERLTS KNENGFSYIM
RGAFFTSLRL ESFTSLQMSK KGCVWSIISQ VIYYLLVCYY AFIQGCQLKQ QKWRFFTGKR
NILDTSIILI SFILLGLDMK SISLHKKNMA RYRDDQDRFI SFYEAVKVNS AATHLVGFPV
LLATVQLWNL LRHSPRLRVI SRTLSRAWDE VVGFLLIILI LLTGYAIAFN LLFGCSISDY
RTFFSSAVTV VGLLMGISHQ EEVFALDPVL GTFLILTSVI LMVLVVINLF VSAILMAFGK
ERKSLKKEAA LIDTLLQKLS NLLGISWPQK TSSEQAATTA VGSDTEVLDE LP
