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1.A.5.1.1
Polycystin 1 (PKD1 or PC1) assembles with TRPP2 (Q86VP3) in a stoichiometry of 3TRPP2: 1PKD1, forming the receptor/ion channel complex (Yu et al., 2009). The C-terminal coiled-coil complex is critical for proper assembly (Zhu et al., 2011).  Missense mutations have been identified that affect membrane topogenesis (Nims et al. 2011). Biomarkers for polycystic kidney diseases have been identified (Hogan et al. 2015).  Extracellular divalent ions, including Ca2+, inhibit permeation of monovalent ions by directly blocking the TRPP2 channel pore. D643, a negatively charged amino acid in the pore, is crucial for channel permeability (Arif Pavel et al. 2016). Polycystin (TRPP/PKD) complexes, made of transient receptor potential channel polycystin (TRPP)4 and polycystic kidney disease (PKD) proteins, play key roles in coupling extracellular stimuli with intracellular Ca2+ signals. PKD1 and PKD2 form a complex, the structure of which has been solved in 3-dimensions at high resolution.  The complex consists of PKD1:PKD2 = 3:1. PKD1 consists of a voltage-gated ion channel fold that interacts with PKD2 to complete a domain-swapped TRP architecture with unique features (Su et al. 2018; Su et al. 2018). The C-terminal tail of PKD1 may play a role in the prognosis of renal disease (Higashihara et al. 2018).

Accession Number:P98161
Protein Name:PKD1
Length:4303
Molecular Weight:462529.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:11
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate cations

Cross database links:

Genevestigator: P98161
HEGENOM: HBG445104
RefSeq: NP_000287.3    NP_001009944.2   
Entrez Gene ID: 5310   
Pfam: PF01825    PF00059    PF01462    PF00801    PF08016    PF01477    PF02010    PF01822   
OMIM: 173900  phenotype
601313  gene+phenotype
KEGG: hsa:5310   

Gene Ontology

GO:0005887 C:integral to plasma membrane
GO:0005515 F:protein binding
GO:0005529 F:sugar binding
GO:0007161 P:calcium-independent cell-matrix adhesion
GO:0007156 P:homophilic cell adhesion
GO:0007218 P:neuropeptide signaling pathway

References (40)

[1] “Polycystic kidney disease: the complete structure of the PKD1 gene and its protein.”  Gluecksmann-Kuis M.A.et.al.   7736581
[2] “The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains.”  Hughes J.et.al.   7663510
[3] “The sequence and analysis of duplication-rich human chromosome 16.”  Martin J.et.al.   15616553
[4] “The polycystic kidney disease 1 gene encodes a 14 kb transcript and lies within a duplicated region on chromosome 16.”  Ward C.J.et.al.   8004675
[5] “”  Ward C.J.et.al.   8069919
[6] “Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.”  Olsen J.V.et.al.   17081983
[7] “The structure of a PKD domain from polycystin-1: implications for polycystic kidney disease.”  Bycroft M.et.al.   9889186
[8] “Polycystin channels and kidney disease.”  Stayner C.et.al.   11698076
[9] “Screening the 3' region of the polycystic kidney disease 1 (PKD1) gene reveals six novel mutations.”  Peral B.et.al.   8554072
[10] “Identification of mutations in the duplicated region of the polycystic kidney disease 1 gene (PKD1) by a novel approach.”  Peral B.et.al.   9199561
[11] “New amino acid polymorphism, Ala/Val4058, in exon 45 of the polycystic kidney disease 1 gene: evolution of alleles.”  Constantinides R.et.al.   9150733
[12] “An unusual pattern of mutation in the duplicated portion of PKD1 is revealed by use of a novel strategy for mutation detection.”  Watnick T.J.et.al.   9285784
[13] “Three novel mutations of the PKD1 gene in Italian families with autosomal dominant polycystic kidney disease.”  Turco A.E.et.al.   9259200
[14] “Novel and recurrent mutations in the PKD1 (polycystic kidney disease) gene.”  Daniells C.et.al.   9521593
[15] “Loss of heterozygosity in polycystic kidney disease with a missense mutation in the repeated region of PKD1.”  Koptides M.et.al.   9921908
[16] “Identification of mutations in the repeated part of the autosomal dominant polycystic kidney disease type 1 gene, PKD1, by long-range PCR.”  Thomas R.L.et.al.   10364515
[17] “Mutation detection of PKD1 identifies a novel mutation common to three families with aneurysms and/or very-early-onset disease.”  Watnick T.et.al.   10577909
[18] “DGGE screening of PKD1 gene reveals novel mutations in a large cohort of 146 unrelated patients.”  Perrichot R.A.et.al.   10987650
[19] “Novel mutations in the 3 region of the polycystic kidney disease 1 (PKD1) gene.”  Afzal A.R.et.al.   10647901
[20] “Mutational analysis within the 3' region of the PKD1 gene.”  Badenas C.et.al.   10200984
[21] “Novel mutations in the duplicated region of PKD1 gene.”  Perrichot R.et.al.   10854095
[22] “Novel mutations in the duplicated region of the polycystic kidney disease 1 (PKD1) gene provides supporting evidence for gene conversion.”  Afzal A.R.et.al.   11216660
[23] “Screening of the PKD1 duplicated region reveals multiple single nucleotide polymorphisms and a de novo mutation in Hellenic polycystic kidney disease families.”  Koptides M.et.al.   10923040
[24] “Novel splicing and missense mutations in autosomal dominant polycystic kidney disease 1 (PKD1) gene: expression of mutated genes.”  Aguiari G.et.al.   11058904
[25] “Thirteen novel mutations of the replicated region of PKD1 in an Asian population.”  Phakdeekitcharoen B.et.al.   11012875
[26] “Novel mutations of the PKD1 gene in Korean patients with autosomal dominant polycystic kidney disease.”  Kim U.K.et.al.   10729710
[27] “Mutation analysis of the entire PKD1 gene: genetic and diagnostic implications.”  Rossetti S.et.al.   11115377
[28] “Novel PKD1 deletions and missense variants in a cohort of Hellenic polycystic kidney disease families.”  Bouba I.et.al.   11571556
[29] “Mutation analysis of the entire replicated portion of PKD1 using genomic DNA samples.”  Phakdeekitcharoen B.et.al.   11316854
[30] “Mutations of the PKD1 gene among Japanese autosomal dominant polycystic kidney disease patients, including one heterozygous mutation identified in members of the same family.”  Mizoguchi M.et.al.   11558899
[31] “Mutational analysis within the 3' region of the PKD1 gene in Japanese families.”  Tsuchiya K.et.al.   11691639
[32] “Three novel mutations of the PKD1 gene in Korean patients with autosomal dominant polycystic kidney disease.”  Eo H.-S.et.al.   12220456
[33] “Mutation detection in the duplicated region of the polycystic kidney disease 1 (PKD1) gene in PKD1-linked Australian families.”  McCluskey M.et.al.   11857740
[34] “Mutation analysis in PKD1 of Japanese autosomal dominant polycystic kidney disease patients.”  Inoue S.et.al.   12007219
[35] “Mutation screening of the PKD1 transcript by RT-PCR.”  Burtey S.et.al.   12070253
[36] “A complete mutation screen of the ADPKD genes by DHPLC.”  Rossetti S.et.al.   11967008
[37] “Novel mutations of PKD1 gene in Chinese patients with autosomal dominant polycystic kidney disease.”  Ding L.et.al.   11773467
[38] “Association of mutation position in polycystic kidney disease 1 (PKD1) gene and development of a vascular phenotype.”  Rossetti S.et.al.   12842373
[39] “Genetics and phenotypic characteristics of autosomal dominant polycystic kidney disease in Finns.”  Peltola P.et.al.   15772804
[40] “Novel method for genomic analysis of PKD1 and PKD2 mutations in autosomal dominant polycystic kidney disease.”  Tan Y.-C.et.al.   18837007
Structure:
1B4R     

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MPPAAPARLA LALGLGLWLG ALAGGPGRGC GPCEPPCLCG PAPGAACRVN CSGRGLRTLG 
61:	PALRIPADAT ALDVSHNLLR ALDVGLLANL SALAELDISN NKISTLEEGI FANLFNLSEI 
121:	NLSGNPFECD CGLAWLPRWA EEQQVRVVQP EAATCAGPGS LAGQPLLGIP LLDSGCGEEY 
181:	VACLPDNSSG TVAAVSFSAA HEGLLQPEAC SAFCFSTGQG LAALSEQGWC LCGAAQPSSA 
241:	SFACLSLCSG PPPPPAPTCR GPTLLQHVFP ASPGATLVGP HGPLASGQLA AFHIAAPLPV 
301:	TATRWDFGDG SAEVDAAGPA ASHRYVLPGR YHVTAVLALG AGSALLGTDV QVEAAPAALE 
361:	LVCPSSVQSD ESLDLSIQNR GGSGLEAAYS IVALGEEPAR AVHPLCPSDT EIFPGNGHCY 
421:	RLVVEKAAWL QAQEQCQAWA GAALAMVDSP AVQRFLVSRV TRSLDVWIGF STVQGVEVGP 
481:	APQGEAFSLE SCQNWLPGEP HPATAEHCVR LGPTGWCNTD LCSAPHSYVC ELQPGGPVQD 
541:	AENLLVGAPS GDLQGPLTPL AQQDGLSAPH EPVEVMVFPG LRLSREAFLT TAEFGTQELR 
601:	RPAQLRLQVY RLLSTAGTPE NGSEPESRSP DNRTQLAPAC MPGGRWCPGA NICLPLDASC 
661:	HPQACANGCT SGPGLPGAPY ALWREFLFSV PAGPPAQYSV TLHGQDVLML PGDLVGLQHD 
721:	AGPGALLHCS PAPGHPGPRA PYLSANASSW LPHLPAQLEG TWACPACALR LLAATEQLTV 
781:	LLGLRPNPGL RLPGRYEVRA EVGNGVSRHN LSCSFDVVSP VAGLRVIYPA PRDGRLYVPT 
841:	NGSALVLQVD SGANATATAR WPGGSVSARF ENVCPALVAT FVPGCPWETN DTLFSVVALP 
901:	WLSEGEHVVD VVVENSASRA NLSLRVTAEE PICGLRATPS PEARVLQGVL VRYSPVVEAG 
961:	SDMVFRWTIN DKQSLTFQNV VFNVIYQSAA VFKLSLTASN HVSNVTVNYN VTVERMNRMQ 
1021:	GLQVSTVPAV LSPNATLALT AGVLVDSAVE VAFLWTFGDG EQALHQFQPP YNESFPVPDP 
1081:	SVAQVLVEHN VMHTYAAPGE YLLTVLASNA FENLTQQVPV SVRASLPSVA VGVSDGVLVA 
1141:	GRPVTFYPHP LPSPGGVLYT WDFGDGSPVL TQSQPAANHT YASRGTYHVR LEVNNTVSGA 
1201:	AAQADVRVFE ELRGLSVDMS LAVEQGAPVV VSAAVQTGDN ITWTFDMGDG TVLSGPEATV 
1261:	EHVYLRAQNC TVTVGAASPA GHLARSLHVL VFVLEVLRVE PAACIPTQPD ARLTAYVTGN 
1321:	PAHYLFDWTF GDGSSNTTVR GCPTVTHNFT RSGTFPLALV LSSRVNRAHY FTSICVEPEV 
1381:	GNVTLQPERQ FVQLGDEAWL VACAWPPFPY RYTWDFGTEE AAPTRARGPE VTFIYRDPGS 
1441:	YLVTVTASNN ISAANDSALV EVQEPVLVTS IKVNGSLGLE LQQPYLFSAV GRGRPASYLW 
1501:	DLGDGGWLEG PEVTHAYNST GDFTVRVAGW NEVSRSEAWL NVTVKRRVRG LVVNASRTVV 
1561:	PLNGSVSFST SLEAGSDVRY SWVLCDRCTP IPGGPTISYT FRSVGTFNII VTAENEVGSA 
1621:	QDSIFVYVLQ LIEGLQVVGG GRYFPTNHTV QLQAVVRDGT NVSYSWTAWR DRGPALAGSG 
1681:	KGFSLTVLEA GTYHVQLRAT NMLGSAWADC TMDFVEPVGW LMVAASPNPA AVNTSVTLSA 
1741:	ELAGGSGVVY TWSLEEGLSW ETSEPFTTHS FPTPGLHLVT MTAGNPLGSA NATVEVDVQV 
1801:	PVSGLSIRAS EPGGSFVAAG SSVPFWGQLA TGTNVSWCWA VPGGSSKRGP HVTMVFPDAG 
1861:	TFSIRLNASN AVSWVSATYN LTAEEPIVGL VLWASSKVVA PGQLVHFQIL LAAGSAVTFR 
1921:	LQVGGANPEV LPGPRFSHSF PRVGDHVVSV RGKNHVSWAQ AQVRIVVLEA VSGLQVPNCC 
1981:	EPGIATGTER NFTARVQRGS RVAYAWYFSL QKVQGDSLVI LSGRDVTYTP VAAGLLEIQV 
2041:	RAFNALGSEN RTLVLEVQDA VQYVALQSGP CFTNRSAQFE AATSPSPRRV AYHWDFGDGS 
2101:	PGQDTDEPRA EHSYLRPGDY RVQVNASNLV SFFVAQATVT VQVLACREPE VDVVLPLQVL 
2161:	MRRSQRNYLE AHVDLRDCVT YQTEYRWEVY RTASCQRPGR PARVALPGVD VSRPRLVLPR 
2221:	LALPVGHYCF VFVVSFGDTP LTQSIQANVT VAPERLVPII EGGSYRVWSD TRDLVLDGSE 
2281:	SYDPNLEDGD QTPLSFHWAC VASTQREAGG CALNFGPRGS STVTIPRERL AAGVEYTFSL 
2341:	TVWKAGRKEE ATNQTVLIRS GRVPIVSLEC VSCKAQAVYE VSRSSYVYLE GRCLNCSSGS 
2401:	KRGRWAARTF SNKTLVLDET TTSTGSAGMR LVLRRGVLRD GEGYTFTLTV LGRSGEEEGC 
2461:	ASIRLSPNRP PLGGSCRLFP LGAVHALTTK VHFECTGWHD AEDAGAPLVY ALLLRRCRQG 
2521:	HCEEFCVYKG SLSSYGAVLP PGFRPHFEVG LAVVVQDQLG AAVVALNRSL AITLPEPNGS 
2581:	ATGLTVWLHG LTASVLPGLL RQADPQHVIE YSLALVTVLN EYERALDVAA EPKHERQHRA 
2641:	QIRKNITETL VSLRVHTVDD IQQIAAALAQ CMGPSRELVC RSCLKQTLHK LEAMMLILQA 
2701:	ETTAGTVTPT AIGDSILNIT GDLIHLASSD VRAPQPSELG AESPSRMVAS QAYNLTSALM 
2761:	RILMRSRVLN EEPLTLAGEE IVAQGKRSDP RSLLCYGGAP GPGCHFSIPE AFSGALANLS 
2821:	DVVQLIFLVD SNPFPFGYIS NYTVSTKVAS MAFQTQAGAQ IPIERLASER AITVKVPNNS 
2881:	DWAARGHRSS ANSANSVVVQ PQASVGAVVT LDSSNPAAGL HLQLNYTLLD GHYLSEEPEP 
2941:	YLAVYLHSEP RPNEHNCSAS RRIRPESLQG ADHRPYTFFI SPGSRDPAGS YHLNLSSHFR 
3001:	WSALQVSVGL YTSLCQYFSE EDMVWRTEGL LPLEETSPRQ AVCLTRHLTA FGASLFVPPS 
3061:	HVRFVFPEPT ADVNYIVMLT CAVCLVTYMV MAAILHKLDQ LDASRGRAIP FCGQRGRFKY 
3121:	EILVKTGWGR GSGTTAHVGI MLYGVDSRSG HRHLDGDRAF HRNSLDIFRI ATPHSLGSVW 
3181:	KIRVWHDNKG LSPAWFLQHV IVRDLQTARS AFFLVNDWLS VETEANGGLV EKEVLAASDA 
3241:	ALLRFRRLLV AELQRGFFDK HIWLSIWDRP PRSRFTRIQR ATCCVLLICL FLGANAVWYG 
3301:	AVGDSAYSTG HVSRLSPLSV DTVAVGLVSS VVVYPVYLAI LFLFRMSRSK VAGSPSPTPA 
3361:	GQQVLDIDSC LDSSVLDSSF LTFSGLHAEQ AFVGQMKSDL FLDDSKSLVC WPSGEGTLSW 
3421:	PDLLSDPSIV GSNLRQLARG QAGHGLGPEE DGFSLASPYS PAKSFSASDE DLIQQVLAEG 
3481:	VSSPAPTQDT HMETDLLSSL SSTPGEKTET LALQRLGELG PPSPGLNWEQ PQAARLSRTG 
3541:	LVEGLRKRLL PAWCASLAHG LSLLLVAVAV AVSGWVGASF PPGVSVAWLL SSSASFLASF 
3601:	LGWEPLKVLL EALYFSLVAK RLHPDEDDTL VESPAVTPVS ARVPRVRPPH GFALFLAKEE 
3661:	ARKVKRLHGM LRSLLVYMLF LLVTLLASYG DASCHGHAYR LQSAIKQELH SRAFLAITRS 
3721:	EELWPWMAHV LLPYVHGNQS SPELGPPRLR QVRLQEALYP DPPGPRVHTC SAAGGFSTSD 
3781:	YDVGWESPHN GSGTWAYSAP DLLGAWSWGS CAVYDSGGYV QELGLSLEES RDRLRFLQLH 
3841:	NWLDNRSRAV FLELTRYSPA VGLHAAVTLR LEFPAAGRAL AALSVRPFAL RRLSAGLSLP 
3901:	LLTSVCLLLF AVHFAVAEAR TWHREGRWRV LRLGAWARWL LVALTAATAL VRLAQLGAAD 
3961:	RQWTRFVRGR PRRFTSFDQV AQLSSAARGL AASLLFLLLV KAAQQLRFVR QWSVFGKTLC 
4021:	RALPELLGVT LGLVVLGVAY AQLAILLVSS CVDSLWSVAQ ALLVLCPGTG LSTLCPAESW 
4081:	HLSPLLCVGL WALRLWGALR LGAVILRWRY HALRGELYRP AWEPQDYEMV ELFLRRLRLW 
4141:	MGLSKVKEFR HKVRFEGMEP LPSRSSRGSK VSPDVPPPSA GSDASHPSTS SSQLDGLSVS 
4201:	LGRLGTRCEP EPSRLQAVFE ALLTQFDRLN QATEDVYQLE QQLHSLQGRR SSRAPAGSSR 
4261:	GPSPGLRPAL PSRLARASRG VDLATGPSRT PLRAKNKVHP SST