1.A.5.1.3
Heteromeric polycystic kidney disease proteins 1 and 2-like 1 (PKD1L1/PKD2L1/PC2) cation (calcium) channel of kidney primary cilia (DeCaen et al. 2013). PKD2L1 is probably orthologous to mouse TC# 1.A.5.2.2. The voltage dependence of PKD2L1 may reflect the charge state of the S4 domain (Numata et al. 2017). PKD2L1, (TRPP3) is involved in the sour sensation and other pH-dependent processes and is a nonselective cation channel that can be regulated by voltage, protons, and calcium. The 3-d structure has been determined by cryoEM at 3.4 Å resolution (Su et al. 2018). Unlike its ortholog PKD2, the pore helix and TMS6, which are involved in upper and lower-gate opening, adopt an open conformation. The pore domain dilation is coupled to conformational changes of voltage-sensing domains via a series of pi-pi interactions, suggesting a potential PKD2L1 gating mechanism (Su et al. 2018). Autosomal dominant polycystic kidney disease is caused by mutations in PKD1 or PKD2 genes; the latter encodes polycystin-2 (PC2, also known as TRPP2), a member of the transient receptor potential (TRP) ion channel family. Despite most pathogenic mutations in PKD2 being truncation variants, there are many point mutations, which cause small changes in protein sequences but dramatic changes in the in vivo function of PC2. Conformational consequences of these mutations based on the cryo-EM structures of PC2 provide insight into the structure and function of PC2 and the molecular mechanism of pathogenesis caused by these mutations (Wang et al. 2023). Polycystin-1 interacting protein-1 (CU062) interacts with the ectodomain of polycystin-1 (PC1) (Lea et al. 2023).
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| Accession Number: | Q8TDX9 |
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| Protein Name: | Polycystic kidney disease protein 1-like 1 |
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| Length: | 2849 |
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| Molecular Weight: | 315435.00 |
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| Species: | Homo sapiens (Human) [9606] |
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| Number of TMSs: | 12 |
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| Location1 / Topology2 / Orientation3: |
Membrane1 / Multi-pass membrane protein2 |
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| Substrate |
cation, calcium(2+) |
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1: MAEEAAQNIS DDQERCLQAA CCLSFGGELS VSTDKSWGLH LCSCSPPGGG LWVEVYANHV
61: LLMSDGKCGC PWCALNGKAE DRESQSPSSS ASRQKNIWKT TSEAALSVVN EKTQAVVNEK
121: TQAPLDCDNS ADRIPHKPFI IIARAWSSGG PRFHHRRLCA TGTADSTFSA LLQLQGTTSA
181: AAPCSLKMEA SCCVLRLLCC AEDVATGLLP GTVTMETPTK VARPTQTSSQ RVPLWPISHF
241: PTSPRSSHGL PPGIPRTPSF TASQSGSEIL YPPTQHPPVA ILARNSDNFM NPVLNCSLEV
301: EARAPPNLGF RVHMASGEAL CLMMDFGDSS GVEMRLHNMS EAMAVTAYHQ YSKGIFFHLL
361: HFQLDMSTYK EAETQNTTLN VYLCQSENSC LEDSDPSNLG YELISAFVTK GVYMLKAVIY
421: NEFHGTEVEL GPYYVEIGHE AVSAFMNSSS VHEDEVLVFA DSQVNQKSTV VIHHFPSIPS
481: YNVSFISQTQ VGDSQAWHSM TVWYKMQSVS VYTNGTVFAT DTDITFTAVT KETIPLEFEW
541: YFGEDPPVRT TSRSIKKRLS IPQWYRVMVK ASNRMSSVVS EPHVIRVQKK IVANRLTSPS
601: SALVNASVAF ECWINFGTDV AYLWDFGDGT VSLGSSSSSH VYSREGEFTV EVLAFNNVSA
661: STLRQQLFIV CEPCQPPLVK NMGPGKVQIW RSQPVRLGVT FEAAVFCDIS QGLSYTWNLM
721: DSEGLPVSLP AAVDTHRQTL ILPSHTLEYG NYTALAKVQI EGSVVYSNYC VGLEVRAQAP
781: VSVISEGTHL FFSRTTSSPI VLRGTQSFDP DDPGATLRYH WECATAGSPA HPCFDSSTAH
841: QLDAAAPTVS FEAQWLSDSY DQFLVMLRVS SGGRNSSETR VFLSPYPDSA FRFVHISWVS
901: FKDTFVNWND ELSLQAMCED CSEIPNLSYS WDLFLVNATE KNRIEVPFCR VVGLLGSLGL
961: GAISESSQLN LLPTEPGTAD PDATTTPFSR EPSPVTLGQP ATSAPRGTPT EPMTGVYWIP
1021: PAGDSAVLGE APEEGSLDLE PGPQSKGSLM TGRSERSQPT HSPDPHLSDF EAYYSDIQEA
1081: IPSGGRQPAK DTSFPGSGPS LSAEESPGDG DNLVDPSLSA GRAEPVLMID WPKALLGRAV
1141: FQGYSSSGIT EQTVTIKPYS LSSGETYVLQ VSVASKHGLL GKAQLYLTVN PAPRDMACQV
1201: QPHHGLEAHT VFSVFCMSGK PDFHYEFSYQ IGNTSKHTLY HGRDTQYYFV LPAGEHLDNY
1261: KVMVSTEITD GKGSKVQPCT VVVTVLPRYH GNDCLGEDLY NSSLKNLSTL QLMGSYTEIR
1321: NYITVITRIL SRLSKEDKTA SCNQWSRIQD ALISSVCRLA FVDQEEMIGS VLMLRDLVSF
1381: SNKLGFMSAV LILKYTRALL AQGQFSGPFV IDKGVRLELI GLISRVWEVS EQENSKEEVY
1441: RHEEGITVIS DLLLGCLSLN HVSTGQMEFR TLLHYNLQSS VQSLGSVQVH LPGDLAGHSP
1501: AGAETQSPCY ISQLILFKKN PYPGSQAPGQ IGGVVGLNLY TCSSRRPINR QWLRKPVMVE
1561: FGEEDGLDNR RNKTTFVLLR DKVNLHQFTE LSENPQESLQ IEIEFSKPVT RAFPVMLLVR
1621: FSEKPTPSDF LVKQIYFWDE SIVQIYIPAA SQKDASVGYL SLLDADYDRK PPNRYLAKAV
1681: NYTVHFQWIR CLFWDKREWK SERFSPQPGT SPEKVNCSYH RLAAFALLRR KLKASFEVSD
1741: ISKLQSHPEN LLPSIFIMGS VILYGFLVAK SRQVDHHEKK KAGYIFLQEA SLPGHQLYAV
1801: VIDTGFRAPA RLTSKVYIVL CGDNGLSETK ELSCPEKPLF ERNSRHTFIL SAPAQLGLLR
1861: KIRLWHDSRG PSPGWFISHV MVKELHTGQG WFFPAQCWLS AGRHDGRVER ELTCLQGGLG
1921: FRKLFYCKFT EYLEDFHVWL SVYSRPSSSR YLHTPRLTVS FSLLCVYACL TALVAAGGQE
1981: QPHLDVSPTL GSFRVGLLCT LLASPGAQLL SLLFRLSKEA PGSARVEPHS PLRGGAQTEA
2041: PHGPNSWGRI PDAQEPRKQP ASAILSGSGR AQRKAASDNG TACPAPKLQV HGADHSRTSL
2101: MGKSHCCPPH TQAPSSGLEG LMPQWSRALQ PWWSSAVWAI CGTASLACSL GTGFLAYRFG
2161: QEQCVQWLHL LSLSVVCCIF ITQPLMVCLM ALGFAWKRRA DNHFFTESLC EATRDLDSEL
2221: AERSWTRLPF SSSCSIPDCA GEVEKVLAAR QQARHLRWAH PPSKAQLRGT RQRMRRESRT
2281: RAALRDISMD ILMLLLLLCV IYGRFSQDEY SLNQAIRKEF TRNARNCLGG LRNIADWWDW
2341: SLTTLLDGLY PGGTPSARVP GAQPGALGGK CYLIGSSVIR QLKVFPRHLC KPPRPFSALI
2401: EDSIPTCSPE VGGPENPYLI DPENQNVTLN GPGGCGTRED CVLSLGRTRT EAHTALSRLR
2461: ASMWIDRSTR AVSVHFTLYN PPTQLFTSVS LRVEILPTGS LVPSSLVESF SIFRSDSALQ
2521: YHLMLPQLVF LALSLIHLCV QLYRMMDKGV LSYWRKPRNW LELSVVGVSL TYYAVSGHLV
2581: TLAGDVTNQF HRGLCRAFMD LTLMASWNQR ARWLRGILLF LFTLKCVYLP GIQNTMASCS
2641: SMMRHSLPSI FVAGLVGALM LAALSHLHRF LLSMWVLPPG TFTDAFPGLL FHFPRRSQKD
2701: CLLGLSKSDQ RAMACYFGIL LIVSATLCFG MLRGFLMTLP QKRKSFQSKS FVRLKDVTAY
2761: MWEKVLTFLR LETPKLEEAE MVENHNYYLD EFANLLDELL MKINGLSDSL QLPLLEKTSN
2821: NTGEARTEES PLVDISSYQA AEPADIKDF