PKHD1_MOUSE
ID PKHD1_MOUSE Reviewed; 4059 AA.
AC E9PZ36;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=Fibrocystin {ECO:0000305};
DE AltName: Full=Polycystic kidney and hepatic disease 1 protein;
DE AltName: Full=Polyductin;
DE Flags: Precursor;
GN Name=Pkhd1 {ECO:0000312|MGI:MGI:2155808};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP INTERACTION WITH CAMLG.
RX PubMed=16243292; DOI=10.1016/j.bbrc.2005.10.022;
RA Nagano J., Kitamura K., Hujer K.M., Ward C.J., Bram R.J., Hopfer U.,
RA Tomita K., Huang C., Miller R.T.;
RT "Fibrocystin interacts with CAML, a protein involved in Ca2+ signaling.";
RL Biochem. Biophys. Res. Commun. 338:880-889(2005).
RN [3]
RP PROTEOLYTIC PROCESSING, SUBCELLULAR LOCATION, AND REGION.
RX PubMed=16956880; DOI=10.1074/jbc.m606740200;
RA Hiesberger T., Gourley E., Erickson A., Koulen P., Ward C.J., Masyuk T.V.,
RA Larusso N.F., Harris P.C., Igarashi P.;
RT "Proteolytic cleavage and nuclear translocation of fibrocystin is regulated
RT by intracellular Ca2+ and activation of protein kinase C.";
RL J. Biol. Chem. 281:34357-34364(2006).
RN [4]
RP SHEDDING, AND SUBCELLULAR LOCATION.
RX PubMed=17470460; DOI=10.1093/hmg/ddm039;
RA Kaimori J.Y., Nagasawa Y., Menezes L.F., Garcia-Gonzalez M.A., Deng J.,
RA Imai E., Onuchic L.F., Guay-Woodford L.M., Germino G.G.;
RT "Polyductin undergoes notch-like processing and regulated release from
RT primary cilia.";
RL Hum. Mol. Genet. 16:942-956(2007).
RN [5]
RP DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=18202188; DOI=10.2353/ajpath.2008.070381;
RA Gallagher A.R., Esquivel E.L., Briere T.S., Tian X., Mitobe M.,
RA Menezes L.F., Markowitz G.S., Jain D., Onuchic L.F., Somlo S.;
RT "Biliary and pancreatic dysgenesis in mice harboring a mutation in Pkhd1.";
RL Am. J. Pathol. 172:417-429(2008).
RN [6]
RP DISRUPTION PHENOTYPE, FUNCTION, AND INTERACTION WITH PKD2.
RX PubMed=18235088; DOI=10.1681/asn.2007070770;
RA Kim I., Fu Y., Hui K., Moeckel G., Mai W., Li C., Liang D., Zhao P., Ma J.,
RA Chen X.Z., George A.L. Jr., Coffey R.J., Feng Z.P., Wu G.;
RT "Fibrocystin/polyductin modulates renal tubular formation by regulating
RT polycystin-2 expression and function.";
RL J. Am. Soc. Nephrol. 19:455-468(2008).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=18286309; DOI=10.1007/s00467-007-0735-4;
RA Williams S.S., Cobo-Stark P., James L.R., Somlo S., Igarashi P.;
RT "Kidney cysts, pancreatic cysts, and biliary disease in a mouse model of
RT autosomal recessive polycystic kidney disease.";
RL Pediatr. Nephrol. 23:733-741(2008).
RN [8] {ECO:0007744|PubMed:21183079}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP FUNCTION.
RX PubMed=19959710; DOI=10.1681/asn.2009060603;
RA Nishio S., Tian X., Gallagher A.R., Yu Z., Patel V., Igarashi P., Somlo S.;
RT "Loss of oriented cell division does not initiate cyst formation.";
RL J. Am. Soc. Nephrol. 21:295-302(2010).
RN [10]
RP SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-3869; 3870-LEU-VAL-3871;
RP 3872-CYS-CYS-3873; 3874-TRP-PHE-3875; 3876-LYS--SER-3878;
RP 3879-LYS--LYS-3882 AND 3883-ILE--PRO-3885, PALMITOYLATION, INTERACTION WITH
RP RAB8A, AND REGION.
RX PubMed=20048263; DOI=10.1083/jcb.200910096;
RA Follit J.A., Li L., Vucica Y., Pazour G.J.;
RT "The cytoplasmic tail of fibrocystin contains a ciliary targeting
RT sequence.";
RL J. Cell Biol. 188:21-28(2010).
RN [11]
RP FUNCTION.
RX PubMed=20875407; DOI=10.1016/j.yexcr.2010.09.012;
RA Hu B., He X., Li A., Qiu Q., Li C., Liang D., Zhao P., Ma J., Coffey R.J.,
RA Zhan Q., Wu G.;
RT "Cystogenesis in ARPKD results from increased apoptosis in collecting duct
RT epithelial cells of Pkhd1 mutant kidneys.";
RL Exp. Cell Res. 317:173-187(2011).
RN [12]
RP DISRUPTION PHENOTYPE, GLYCOSYLATION, PROTEOLYTIC PROCESSING, AND
RP SUBCELLULAR LOCATION.
RX PubMed=22021705; DOI=10.1681/asn.2010111173;
RA Bakeberg J.L., Tammachote R., Woollard J.R., Hogan M.C., Tuan H.F., Li M.,
RA van Deursen J.M., Wu Y., Huang B.Q., Torres V.E., Harris P.C., Ward C.J.;
RT "Epitope-tagged Pkhd1 tracks the processing, secretion, and localization of
RT fibrocystin.";
RL J. Am. Soc. Nephrol. 22:2266-2277(2011).
RN [13]
RP INTERACTION WITH ARF4, AND MUTAGENESIS OF CYS-3869; 3870-LEU-VAL-3871;
RP 3872-CYS-CYS-3873; 3879-LYS--LYS-3882 AND 3883-ILE--PRO-3885.
RX PubMed=24586199; DOI=10.1371/journal.pgen.1004170;
RA Follit J.A., San Agustin J.T., Jonassen J.A., Huang T., Rivera-Perez J.A.,
RA Tremblay K.D., Pazour G.J.;
RT "Arf4 is required for Mammalian development but dispensable for ciliary
RT assembly.";
RL PLoS Genet. 10:e1004170-e1004170(2014).
RN [14]
RP SUBCELLULAR LOCATION, MUTAGENESIS OF 3879-LYS--PRO-3885, AND INTERACTION
RP WITH TULP3.
RX PubMed=28154160; DOI=10.1083/jcb.201607095;
RA Badgandi H.B., Hwang S.H., Shimada I.S., Loriot E., Mukhopadhyay S.;
RT "Tubby family proteins are adapters for ciliary trafficking of integral
RT membrane proteins.";
RL J. Cell Biol. 216:743-760(2017).
RN [15]
RP TISSUE SPECIFICITY, PROTEOLYTIC PROCESSING, SUBCELLULAR LOCATION, AND
RP GLYCOSYLATION.
RX PubMed=28729032; DOI=10.1016/j.kint.2017.04.027;
RA Outeda P., Menezes L., Hartung E.A., Bridges S., Zhou F., Zhu X., Xu H.,
RA Huang Q., Yao Q., Qian F., Germino G.G., Watnick T.;
RT "A novel model of autosomal recessive polycystic kidney questions the role
RT of the fibrocystin C-terminus in disease mechanism.";
RL Kidney Int. 92:1130-1144(2017).
CC -!- FUNCTION: Promotes ciliogenesis in renal epithelial cells and therefore
CC participates in the tubules formation and/or ensures the maintenance of
CC the architecture of the lumen of the kidney (PubMed:18235088,
CC PubMed:20875407). Has an impact on cellular symmetry by ensuring
CC correct bipolar cell division through the regulation of centrosome
CC duplication and mitotic spindle assembly and by maintaining oriented
CC cell division (OCD) during tubular elongation through planar cell
CC polarity (PCP) pathway (PubMed:19959710). During epithelial cell
CC morphogenesis regulates also cell-cell and cell-matrix adhesion and
CC participates in cell motility (By similarity). Promotes cell-cell
CC contact through the positive regulation of PTK2 kinase activity leading
CC to either positive regulation of epithelial cell proliferation through
CC the HRAS/RAF1 pathways, or negative regulation of apoptosis through the
CC PDK1/AKT1 pathway (PubMed:20875407). May act in collecting-duct and
CC biliary differentiation (By similarity). May participate in the
CC regulation of the cholangiocytes proliferation and the CCN2 production
CC in an CXCL8-dependent manner (By similarity).
CC {ECO:0000250|UniProtKB:E2RK30, ECO:0000250|UniProtKB:P08F94,
CC ECO:0000269|PubMed:18235088, ECO:0000269|PubMed:19959710,
CC ECO:0000269|PubMed:20875407}.
CC -!- SUBUNIT: Interacts with CAMLG (PubMed:16243292). Interacts with PKD2
CC (PubMed:18235088). Interacts (via CST) with ARF4; this interaction
CC allows an efficient PKHD1 trafficking to the cilium (PubMed:24586199).
CC Interacts (via CST) with RAB8A; this interaction controls trafficking
CC through the endomembrane systeme and to the cilium (PubMed:20048263).
CC Interacts (via CST) with TULP3; this interaction allows PKHD1
CC trafficking to the cilium (PubMed:28154160).
CC {ECO:0000269|PubMed:16243292, ECO:0000269|PubMed:18235088,
CC ECO:0000269|PubMed:20048263, ECO:0000269|PubMed:24586199,
CC ECO:0000269|PubMed:28154160}.
CC -!- INTERACTION:
CC E9PZ36; P49069: CAMLG; Xeno; NbExp=4; IntAct=EBI-11693075, EBI-1748958;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P08F94};
CC Single-pass membrane protein {ECO:0000255}. Cytoplasm
CC {ECO:0000250|UniProtKB:P08F94}. Apical cell membrane
CC {ECO:0000269|PubMed:18202188}. Cytoplasm, cytoskeleton, cilium basal
CC body {ECO:0000250|UniProtKB:P08F94}. Cell projection, cilium
CC {ECO:0000269|PubMed:17470460, ECO:0000269|PubMed:18202188,
CC ECO:0000269|PubMed:20048263, ECO:0000269|PubMed:22021705,
CC ECO:0000269|PubMed:28154160}. Cytoplasm, cytoskeleton, spindle
CC {ECO:0000250|UniProtKB:P08F94}. Chromosome, centromere
CC {ECO:0000250|UniProtKB:P08F94}. Nucleus {ECO:0000269|PubMed:16956880}.
CC Secreted, extracellular exosome {ECO:0000269|PubMed:22021705,
CC ECO:0000269|PubMed:28729032}. Secreted {ECO:0000269|PubMed:22021705,
CC ECO:0000269|PubMed:28729032}. Endoplasmic reticulum
CC {ECO:0000269|PubMed:28729032}. Golgi apparatus
CC {ECO:0000269|PubMed:28729032}. Note=The intra-cellular C-terminal
CC fragment (ICD) translocates to the nucleus and is not detected in
CC primary cilia (PubMed:16956880, PubMed:28729032). The extracellular
CC domain (PECD) traffics beyond the mid-Golgi and localizes on exosome
CC like vesicles (ELVs) attached to the primary cilium (PubMed:22021705,
CC PubMed:28729032). In the urine, the extracellular domain (PECD) exists
CC as an highly abundant secreted form and a less abundant PECD form that
CC is either tethered to or shed with the C-terminal fragment (PTM) in
CC ELVs (PubMed:28729032). The majority of full length PKHD1 protein
CC resides at the endoplasmic reticulum and cannot pass beyond the mid-
CC Golgi apparatus and is not detected in primary cilia (PubMed:28729032).
CC {ECO:0000269|PubMed:16956880, ECO:0000269|PubMed:22021705,
CC ECO:0000269|PubMed:28729032}.
CC -!- TISSUE SPECIFICITY: Expressed in bile ducts and distal nephron segments
CC but is absent from the proximal tubule (PubMed:18202188). Expressed in
CC pancreas and kidney but also in the liver (PubMed:28729032). Expressed
CC primarily in the distal tubule and thick ascending limb of the loop of
CC Henle, and at low-level in the proximal tubule before renal development
CC is complete at P0 (PubMed:28729032). {ECO:0000269|PubMed:18202188,
CC ECO:0000269|PubMed:28729032}.
CC -!- PTM: Palmitoylated (PubMed:20048263). Palmitoylation facilitates the
CC trafficking to the cilia and membrane targeting (PubMed:20048263).
CC {ECO:0000269|PubMed:20048263}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:22021705,
CC ECO:0000269|PubMed:28729032}.
CC -!- PTM: Several proteolytic cleavages occur within the extracellular
CC domain, whereas at least one cleavage occurs within the cytoplasmic
CC domain (PubMed:16956880). Cleaved by a probable proprotein convertase
CC which produces an extracellular domain (polyductin extracellular
CC domain, (PECD)) and a C-terminal fragment (polyductin transmembrane
CC fragment (PTM)) which are tethered together by disulfide bonds
CC (PubMed:17470460, PubMed:28729032). This extracellular domain (PECD) is
CC then shed from the primary cilium by activation of a member of the ADAM
CC metalloproteinase disintegrins family, resulting in concomitant release
CC of an intra-cellular C-terminal fragment (ICD) via a gamma-secretase-
CC dependent process (PubMed:17470460, PubMed:28729032). The proteolytic
CC cleavage of the C-terminal intracellular fragment (ICD) is controlled
CC by cytosolic calcium concentration and activation of PKC
CC (PubMed:16956880). {ECO:0000269|PubMed:16956880,
CC ECO:0000269|PubMed:17470460, ECO:0000269|PubMed:28729032}.
CC -!- DISRUPTION PHENOTYPE: A mouse model, for human autosomal recessive
CC polycystic kidney disease (ARPKD), where homozygous knockout mice for
CC the Pkhd1 gene are born at a frequency lower than the expected
CC Mendelian ratio (PubMed:18235088). Homozygous mice may lead to
CC embryonic lethality (PubMed:18235088). Mice that escape embryonic
CC lethality and survive into adulthood exhibit mild to severe tubular
CC dilation or cyst formation in the kidney and liver accompanied by
CC fibrosis and necrosis (PubMed:18235088). Homozygous mice for the Pkhd1
CC gene develop cysts and fibrosis in the liver at 1 month of age, and
CC females develop proximal tubule (PT) dilation at 6 months of age
CC whereas male mice never develop PT dilation (PubMed:22021705). Both
CC male and female homozygous mice develop liver cysts and fibrosis at 3
CC months of age and this worsens with age until the liver is completely
CC replaced by cysts at 12 mo of age (PubMed:22021705). A new mouse model,
CC for ARPKD, where homozygous knockout mice for the Pkhd1 gene develop
CC biliary dysgenesis accompanied by periportal fibrosis. Despite the
CC progressive liver disease, these mice are viable at 12 months of age
CC with no apparent decline in synthetic liver function. These mice also
CC develop extrahepatic phenotypes involving the pancreas, extrahepatic
CC bile ducts, and spleen, which occur in a more variable manner
CC (PubMed:18202188). An other model, for ARPKD, where homozygous knockout
CC mice for the Pkhd1 gene develop progressive renal cystic disease
CC involving the proximal tubules, collecting ducts, and glomeruli. In the
CC liver, mice show dilatation of the bile ducts and periportal fibrosis.
CC Dilatation of pancreatic exocrine ducts is uniformly seen, with
CC pancreatic cysts arising less frequently (PubMed:18286309).
CC {ECO:0000269|PubMed:18202188, ECO:0000269|PubMed:18235088,
CC ECO:0000269|PubMed:18286309, ECO:0000269|PubMed:22021705}.
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DR EMBL; AC101729; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC101789; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC161178; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC166488; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC166770; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS14841.1; -.
DR RefSeq; NP_694819.2; NM_153179.3.
DR CORUM; E9PZ36; -.
DR IntAct; E9PZ36; 1.
DR STRING; 10090.ENSMUSP00000085794; -.
DR GlyGen; E9PZ36; 51 sites.
DR PhosphoSitePlus; E9PZ36; -.
DR SwissPalm; E9PZ36; -.
DR MaxQB; E9PZ36; -.
DR PaxDb; E9PZ36; -.
DR PRIDE; E9PZ36; -.
DR ProteomicsDB; 363285; -.
DR Antibodypedia; 30875; 167 antibodies from 13 providers.
DR DNASU; 241035; -.
DR Ensembl; ENSMUST00000088448; ENSMUSP00000085794; ENSMUSG00000043760.
DR GeneID; 241035; -.
DR KEGG; mmu:241035; -.
DR UCSC; uc007akv.1; mouse.
DR CTD; 5314; -.
DR MGI; MGI:2155808; Pkhd1.
DR VEuPathDB; HostDB:ENSMUSG00000043760; -.
DR eggNOG; ENOG502QR85; Eukaryota.
DR GeneTree; ENSGT00940000160697; -.
DR HOGENOM; CLU_000057_1_0_1; -.
DR InParanoid; E9PZ36; -.
DR OMA; ETVHNAD; -.
DR OrthoDB; 323806at2759; -.
DR PhylomeDB; E9PZ36; -.
DR TreeFam; TF329582; -.
DR BioGRID-ORCS; 241035; 1 hit in 70 CRISPR screens.
DR ChiTaRS; Pkhd1; mouse.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; E9PZ36; protein.
DR Bgee; ENSMUSG00000043760; Expressed in urinary bladder urothelium and 68 other tissues.
DR Genevisible; E9PZ36; MM.
DR GO; GO:0097731; C:9+0 non-motile cilium; IDA:MGI.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0005813; C:centrosome; ISO:MGI.
DR GO; GO:0000775; C:chromosome, centromeric region; IEA:UniProtKB-SubCell.
DR GO; GO:0036064; C:ciliary basal body; ISO:MGI.
DR GO; GO:0005929; C:cilium; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0072686; C:mitotic spindle; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; IMP:UniProtKB.
DR GO; GO:0045216; P:cell-cell junction organization; IMP:UniProtKB.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISO:MGI.
DR GO; GO:0060271; P:cilium assembly; IMP:MGI.
DR GO; GO:0003382; P:epithelial cell morphogenesis; ISS:UniProtKB.
DR GO; GO:0051660; P:establishment of centrosome localization; ISS:UniProtKB.
DR GO; GO:0000132; P:establishment of mitotic spindle orientation; IMP:UniProtKB.
DR GO; GO:0001822; P:kidney development; IDA:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:1904036; P:negative regulation of epithelial cell apoptotic process; IMP:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:UniProtKB.
DR GO; GO:0030155; P:regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:0022407; P:regulation of cell-cell adhesion; ISS:UniProtKB.
DR GO; GO:0001952; P:regulation of cell-matrix adhesion; ISS:UniProtKB.
DR GO; GO:0010824; P:regulation of centrosome duplication; ISO:MGI.
DR GO; GO:1904054; P:regulation of cholangiocyte proliferation; ISS:UniProtKB.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:0090175; P:regulation of establishment of planar polarity; IMP:UniProtKB.
DR GO; GO:0032006; P:regulation of TOR signaling; ISO:MGI.
DR Gene3D; 2.160.20.10; -; 1.
DR Gene3D; 2.60.40.10; -; 5.
DR InterPro; IPR039448; Beta_helix.
DR InterPro; IPR019316; G8_domain.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR002909; IPT_dom.
DR InterPro; IPR037524; PA14/GLEYA.
DR InterPro; IPR006626; PbH1.
DR InterPro; IPR012334; Pectin_lyas_fold.
DR InterPro; IPR011050; Pectin_lyase_fold/virulence.
DR InterPro; IPR028839; PKHD1.
DR PANTHER; PTHR46769:SF1; PTHR46769:SF1; 1.
DR Pfam; PF13229; Beta_helix; 2.
DR Pfam; PF10162; G8; 2.
DR Pfam; PF01833; TIG; 6.
DR SMART; SM01225; G8; 2.
DR SMART; SM00429; IPT; 6.
DR SMART; SM00710; PbH1; 8.
DR SUPFAM; SSF51126; SSF51126; 2.
DR SUPFAM; SSF81296; SSF81296; 6.
DR PROSITE; PS51484; G8; 2.
DR PROSITE; PS51820; PA14; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Centromere; Chromosome; Cytoplasm;
KW Cytoskeleton; Endoplasmic reticulum; Glycoprotein; Golgi apparatus;
KW Membrane; Nucleus; Reference proteome; Repeat; Secreted; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..4059
FT /note="Fibrocystin"
FT /evidence="ECO:0000255"
FT /id="PRO_5003243036"
FT TOPO_DOM 19..3851
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 3852..3872
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 3873..4059
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 25..109
FT /note="IPT/TIG 1; atypical"
FT /evidence="ECO:0000250|UniProtKB:P08F94"
FT DOMAIN 135..230
FT /note="IPT/TIG 2"
FT /evidence="ECO:0000250|UniProtKB:P08F94"
FT DOMAIN 257..333
FT /note="IPT/TIG 3"
FT /evidence="ECO:0000255"
FT DOMAIN 323..483
FT /note="PA14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01164"
FT DOMAIN 945..997
FT /note="IPT/TIG 4"
FT /evidence="ECO:0000255"
FT DOMAIN 1017..1100
FT /note="IPT/TIG 5"
FT /evidence="ECO:0000255"
FT DOMAIN 1106..1190
FT /note="IPT/TIG 6; atypical"
FT /evidence="ECO:0000250|UniProtKB:P08F94"
FT DOMAIN 1198..1266
FT /note="IPT/TIG 7"
FT /evidence="ECO:0000255"
FT DOMAIN 1297..1378
FT /note="IPT/TIG 8; atypical"
FT /evidence="ECO:0000250|UniProtKB:P08F94"
FT DOMAIN 1385..1466
FT /note="IPT/TIG 9"
FT /evidence="ECO:0000255"
FT DOMAIN 1482..1566
FT /note="IPT/TIG 10"
FT /evidence="ECO:0000250|UniProtKB:P08F94"
FT DOMAIN 1569..1637
FT /note="IPT/TIG 11"
FT /evidence="ECO:0000255"
FT DOMAIN 1654..1738
FT /note="IPT/TIG 12; atypical"
FT /evidence="ECO:0000250|UniProtKB:P08F94"
FT DOMAIN 1928..2049
FT /note="G8 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00817"
FT REPEAT 2244..2266
FT /note="PbH1 1"
FT /evidence="ECO:0000255"
FT REPEAT 2287..2321
FT /note="PbH1 2"
FT /evidence="ECO:0000255"
FT REPEAT 2404..2426
FT /note="PbH1 3"
FT /evidence="ECO:0000255"
FT REPEAT 2459..2481
FT /note="PbH1 4"
FT /evidence="ECO:0000255"
FT DOMAIN 2741..2867
FT /note="G8 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00817"
FT REPEAT 3004..3026
FT /note="PbH1 5"
FT /evidence="ECO:0000255"
FT REPEAT 3027..3049
FT /note="PbH1 6"
FT /evidence="ECO:0000255"
FT REPEAT 3080..3102
FT /note="PbH1 7"
FT /evidence="ECO:0000255"
FT REPEAT 3188..3212
FT /note="PbH1 8"
FT /evidence="ECO:0000255"
FT REGION 3869..3886
FT /note="Ciliary targeting sequence (CST)"
FT /evidence="ECO:0000269|PubMed:20048263"
FT REGION 3885..3915
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3946..3970
FT /note="Nuclear localization signal (NLS)"
FT /evidence="ECO:0000269|PubMed:16956880"
FT REGION 4015..4038
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3885..3902
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 3613..3614
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:P08F94"
FT CARBOHYD 55
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 224
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 355
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 385
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 518
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 527
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 620
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 639
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 709
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 867
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 965
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 975
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1082
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1114
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1133
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1239
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1273
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1308
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1319
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1344
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1373
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1456
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1471
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1528
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1613
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1627
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1694
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1760
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1775
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1875
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1879
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1915
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1955
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 2030
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 2139
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 2380
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 2466
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 2503
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 2529
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 2547
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 2581
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 2589
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 2627
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 2747
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 2762
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 3051
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 3133
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 3162
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 3218
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 3719
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 3831
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT MUTAGEN 3869
FT /note="C->A: Almost completely blocks the ability to
FT traffic to the cilia; when associated with 3872-A-A-3873.
FT Affects palmitoylation; when associated with 3872-A-A-3873.
FT Disrupts interaction with RAB8A; when associated with 3872-
FT A-A-3873. Disrupts interaction with ARF4; when associated
FT with 3872-A-A-3873."
FT /evidence="ECO:0000269|PubMed:20048263,
FT ECO:0000269|PubMed:24586199"
FT MUTAGEN 3870..3871
FT /note="LV->AA: Little affects the ability to traffic to the
FT cilia. Does not affect interaction with RAB8A. Does not
FT affect interaction with ARF4."
FT /evidence="ECO:0000269|PubMed:20048263,
FT ECO:0000269|PubMed:24586199"
FT MUTAGEN 3872..3873
FT /note="CC->AA: Almost completely blocks the ability to
FT traffic to the cilia; when associated with A-3869. Affetcs
FT palmitoylation; when associated with A-3869. Disrupts
FT interaction with RAB8A; when associated with A-3869.
FT Disrupts interaction with ARF4; when associated with A-
FT 3869."
FT /evidence="ECO:0000269|PubMed:20048263,
FT ECO:0000269|PubMed:24586199"
FT MUTAGEN 3874..3875
FT /note="WF->AA: Reduces the ability to traffic to the cilia.
FT Reduces interaction with RAB8A."
FT /evidence="ECO:0000269|PubMed:20048263"
FT MUTAGEN 3876..3878
FT /note="KKS->AAA: Reduces the ability to traffic to the
FT cilia."
FT /evidence="ECO:0000269|PubMed:20048263"
FT MUTAGEN 3879..3885
FT /note="KTRKIKP->AAAAAAA: Prevents ciliary localizytion."
FT /evidence="ECO:0000269|PubMed:28154160"
FT MUTAGEN 3879..3882
FT /note="KTRK->AAAA: Almost completely blocks the ability to
FT traffic to cilia. Disrupts interaction with RAB8A. Disrupts
FT interaction with ARF4."
FT /evidence="ECO:0000269|PubMed:20048263,
FT ECO:0000269|PubMed:24586199"
FT MUTAGEN 3883..3885
FT /note="IKP->AAA: Reduces the ability to traffic to the
FT cilia. Reduces interaction with RAB8A. Does not affect
FT interaction with ARF4."
FT /evidence="ECO:0000269|PubMed:20048263,
FT ECO:0000269|PubMed:24586199"
SQ SEQUENCE 4059 AA; 444882 MW; E36B773589027AC2 CRC64;
MMLAWLVSLL SMEVLLLAKP YSSFQFEPAE GSLAGGTWIT VVFDGLDRSI LYPNNGSQLQ
IDLVSVAIPT LRIPCDVSPA FVDLPVVTCQ TRSLPSEADA GPYSLEMRSG EQVLGTPCPG
SLDSCTFKFS KDQTPVLYQV YPASGVPGEV VSVYGRVITT WLETFDPDVD YIESPLILEA
REDKWLTPCS LINRQTGSCF PIQEEHGLGN VQCRVEGDYI GSQNVSFSVF NKGRSMVHKE
AWLISAKQEL FLYQTYPEIL SVFPKVGSLG GRTDIIITGD FFDPSARVTI AGIPCDIRYV
SPRKIECTTR APGNEARLTA PQAGNRGLRF EVGDATKDVE LTEATPGYRW QIVPNASSPS
GFWSKEGRPF RARLSGFFVA PQTNNYTFWI QADSQASLCF SSSEEPRTKV EVASVGVGTA
DWFDSWEQIG NEGSWHQKTT KLELQGGAKY YLEAEQHGIA PSRGMRIGVQ IHNTWLNPDV
VNTYLLEKHQ IRARAQRLPE IQVLHVSGKG NFFLTWGNVS SQPVPANATA QQIQTTIEEL
LVVKCNLAPF SAHVLLRLGF EQGLEGSRSD GVRTSSTEPF CGRFSLGQLG HLILIPEAAD
KGYQLDRYPY LCLAYRGHMN KTLDMTVSFL FGFQTIMKNI TCDWSLTDPH PESWQFTCIN
LWDTCLCHSE DIQSSLANTP LLAHRIDIRP VVPEAGLLYV DEIILADTNV TVSQADSGRA
CPGGNVVESV SVVGVPPVYS ISSWLAGCGS ELPLITACSV STEGTGDGSE LIEVTAQRLQ
RTSPPLGGHF FLYLSDTVIP DVPVRMSARQ LHKLLQDSAD ESTSGYLNAG DFTVTEDLNS
CYEHVWTLSW TTQTGDLPNF IRVSDQNLTG VNPTVTARVV YDGGVFLGPI FGDMLATANQ
QTQVAVQVND IPAYCSGSCS FQYQQESTPS VDHVWYSLGS DVNLLVHFTG TGFPRDTQFL
QVTVNKTSCE VLFSNETNVA CELALLPVGV HQIFMLVIPS GLAVHASGED LLLHVEPRLD
AVEPSTAAEI GGRWVTLRGS SLEGVSLVLF GTQSCVIDAI RSNSQQIQCK VPPRGKDGYT
VNVTVISGDH STVLARAFTY VSSLNPVIVS LSRNRSSIAG GEILFLGMSL LVNYTDLDVQ
IHVQDTSAQV LSQTAWGLEV VLPPLVPGIH VISAFINGVS IRSQGVDLYI QYLTEVFSVE
PCSGSLLGGT LLSLLGTGLG RDPALIRVLV DNHPCDIVNL TEVNIWCETP PAVLPPRADV
LTVLASVEIW AGNTSFFHGP SLVGKGFTFT YEAAATPVVT AMWGEFRNNS VRFYVEGSNI
SDSVILLGSL KCELEVQFFG DSMNLSGCFF PLHSLEAGVY TLQVRHKRMG FANMSVVPQK
FELSPQIIAI FPTHGSKCGG TVLTVKGMAF SSRKRSVHVD ISGPFACMIL SLEDHTVLCQ
TRFVGDQFSE ASLALNITVL VNGLTSKCKG NCTLFIEEAA TPIVDALTIS ISGSLTMVLM
RGRRLATTAD EPIAFVDDQL PCHTTFFNTS HVACQIRDLA PGFHYLSAVH TSAGYACLNS
VSRNFFIVPQ VLDYFPKDFS IHGGSLLTIK GTALRGWKAT VVYVGRQACL TVNFSSDFIQ
CIVPAGNGSA ALEIDVNGVL YHIGLVDYSS IFTPELLSVS RSQDILTFTV ARISGAANVD
IFIGTSPCLG VAGNRTVLQC MVPLLPAGEY LVTGYDHSRG WASSTLILVL RATVTSVTKN
YGCLGGRLLH VLGAGFSPGN ISAAVCGAPC QVLANATVSA FSCLVLPLHV SLAFLCDLRH
AEDSCKVRSS TYLRCDLTVS MGTERLPGSW PYVYLCEESS LCLFEPDHWT ESVFPSFSGL
FLSPKVERDE VLIYNSSCNI TMETEAEMEC EMPNQPITAK ITEIQKSWGQ NTQGNFSFQF
CRRWSRPHSW FPQRVPHDGD SVTVETGHLL LLDANTSFLN SLHIKGGKLI FMDPGPIELR
AHSILITDGG ELHIGSEEKP FQGKARIKIY GSVHSTPFFP YGVKFLAVRN GTLSLHGSVP
EVTVTYLQAA AHAGDKVLTL GEAVDWKPGD EAVITSGMTV AGAEATEVVV VETVHNADLH
LRNPLRYSYD FRENWVAGEN PILKPTVALL SRNIIIQGNF TLERVKLLNS CQEANTAKGN
LKHCLYSKSE KMLGARDLGA RVIIQSFPEE PSFVKLKGVQ FRDLGQAFHK HLSSLALVGA
MRGSYIQSCS VWNSFSRGLS MHRTWGLKVD SNVFYKIVGH ALLLGSYLDG RFSTSETVTG
RKNGWWEQGS TIRNNVIISV SAAEGLSGSE MLAPAGIYTF SPTNVMEGNR VCAAGYGYVF
HLVTSQTLQA PLLSFNWNTA HSCTRYGLLV YPKFQPPWNN DTGFTLFQNF MVWGSAGGAQ
IFRSNNLHLK NFQVYACRDF GIDILESDAN TLITDSFLLG HFTHKGSLCM SAGIKTPQRW
ELTISNTTFV NFDGNCVAIR TCSGCFQGQG GYTVKTRQLK FVNSSNLVAF PFPHAAVLED
LDGSLSGKNG SHVLASMETL SDTCLTNASF SQIVPGSVCG EAVLFHRMSI ALANSLDVPK
NLTITDISNK TITVNYVEDT LSNYYGWMAL LLDQETYSLQ FESPWMNRSL QYSATFDSFA
PGNYLLIMHR DLPPYPDILL RCGSQVGHSL PFHPLPSQDR ACDWFFNRQL RQLTYLVSGE
GQVKVFLQLK PGVPPSVSAS TSVPESASRW SLPETWQDVE KGWGGYNHTI PGPGDDVLIL
PNKTVLVDTD LPVLRCLYVM GTLEFPVDRS NVLSVACLLI AGGELKVGTL ENPLEKDQRL
LIFLRASEEV VCDYFEGIHV DPGTIGVYGK LRLHSAYPKK SWVHLGADIA PGNERIIVHN
AVDWQPHDTI VLSSSSYEAH EAEVLTVKEV KGHHIRIYER LKHRHIGSTH TMEDGQQVHL
AAEVGLLTRN IRIQPDSSCR GRLLVGSFRK SSGEDFSGVL QLLNVEIQNM GLPLYSSIEF
TGVSAGSWVI SSTVHQSCSV GIHASSSHGV ILTDNVVFGT NGHGIDVEGQ NYSLTNNLVI
LTMQSANSSP WVAGIKVNYA EDIILHGNVV AGSERLGFHV GGHGCSSEVL WSDNVVHSSL
HGLHLYKKHE SNNCTGVSGF MAFKNFDYGA MVQTENSVDI QNITLVDNTV GLLAITYVSS
ALLSSVSTVQ ITLRNSVIVA TSSSFDCIHD RKAPQSANWT STDRAPSNPR GGRIGILWPV
SASEPNAWPQ EPWHKVRSRH SVPGIMKLQD VTFSSFVKSC YSNDLDVCIL PNEYSTGVMY
PITAERTRML GIKDKNKFYF PVLQSSKDLV GTICPTLVCE YPRKYLFTDL DGRTLGLPPP
VSVFPRTEEE WTGSFLNTGI FREEQKCTFR AMNQGFFCKQ TEHAVLILDN VDATWTIPKS
HPLVSVTNGF VDTFSIVKDS DLCPPTSSLS TFYSILPTRQ MTKVCFPEQT PPFLRFLLLG
NQRASKLILA VFYNEIQSPH VFLDKSFIPP TPLESAFSLL AEPSGANYFD IMNNLLYVVL
QGEEPVEIHS SVSIHLALTV TFSVLEKGWE RAMLESLSDF FQIDPNQIRL TLEMPGNKET
LEAIANSERK RKRNCPSVTC GGPSIRYGQR RPLMAEMTSL KITPATTLET FSKVIVIEVG
DLPNIRNSEP IQSLPSNRLQ RLVNQVITAQ QTGALENVLG MTVGALLVTQ SKGVTGYRNA
SSLITGNLIY TRPSELSILV QPSDGEVGIE LPVQPRLVFL DEKNERVESL GLPSEPWIIS
VSLEGASESV LKGCTLAETR DGYVTFSRLA VLISGSNWHL FFTVISPPGT NFTARSRTFV
VLPVASKERS TIILALSLCS VASWVALSCL VCCWFKKSKT RKIKPEDISE SQAKEQKKNT
HNSSKPRGLQ AKTAKENTLM GEDMRMKVMQ GMQSQFPQHS MDGVSKRKVS RLAVTEERTT
TPAPKIPRIT CVPGSLAQQL TLQEPGNWQE AQQQLLRYQL AGRNQLLLLR PDLRQERKQG
QEPSQLDKGS DCTGLSQEKA TCIPTETFSL HTAPPETIQ
