FRITZ_HUMAN
ID FRITZ_HUMAN Reviewed; 746 AA.
AC O95876; Q53RW4; Q7Z2Z3;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAR-2008, sequence version 2.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=WD repeat-containing and planar cell polarity effector protein fritz homolog;
DE Short=hFRTZ;
DE AltName: Full=Bardet-Biedl syndrome 15 protein;
DE AltName: Full=WD repeat-containing and planar cell polarity effector protein;
GN Name=WDPCP; Synonyms=BBS15, C2orf86, FRITZ;
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 [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RA Mei G., Yu W., Gibbs R.A.;
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Fetal brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP INVOLVEMENT IN BBS15, INVOLVEMENT IN MECKEL SYNDROME, AND VARIANTS LYS-55;
RP PHE-205 AND PHE-708.
RX PubMed=20671153; DOI=10.1126/science.1191184;
RA Kim S.K., Shindo A., Park T.J., Oh E.C., Ghosh S., Gray R.S., Lewis R.A.,
RA Johnson C.A., Attie-Bittach T., Katsanis N., Wallingford J.B.;
RT "Planar cell polarity acts through septins to control collective cell
RT movement and ciliogenesis.";
RL Science 329:1337-1340(2010).
RN [6]
RP INVOLVEMENT IN CHDTHP, AND VARIANT CHDTHP ASN-54.
RX PubMed=25427950; DOI=10.1002/ajmg.a.36852;
RA Saari J., Lovell M.A., Yu H.C., Bellus G.A.;
RT "Compound heterozygosity for a frame shift mutation and a likely pathogenic
RT sequence variant in the planar cell polarity-ciliogenesis gene WDPCP in a
RT girl with polysyndactyly, coarctation of the aorta, and tongue
RT hamartomas.";
RL Am. J. Med. Genet. A 167:421-427(2015).
RN [7]
RP VARIANT CHDTHP ASN-54, AND CHARACTERIZATION OF VARIANT CHDTHP ASN-54.
RX PubMed=27158779; DOI=10.1038/ng.3558;
RA Toriyama M., Lee C., Taylor S.P., Duran I., Cohn D.H., Bruel A.L.,
RA Tabler J.M., Drew K., Kelly M.R., Kim S., Park T.J., Braun D.A.,
RA Pierquin G., Biver A., Wagner K., Malfroot A., Panigrahi I., Franco B.,
RA Al-Lami H.A., Yeung Y., Choi Y.J., Duffourd Y., Faivre L., Riviere J.B.,
RA Chen J., Liu K.J., Marcotte E.M., Hildebrandt F., Thauvin-Robinet C.,
RA Krakow D., Jackson P.K., Wallingford J.B.;
RT "The ciliopathy-associated CPLANE proteins direct basal body recruitment of
RT intraflagellar transport machinery.";
RL Nat. Genet. 48:648-656(2016).
CC -!- FUNCTION: Probable effector of the planar cell polarity signaling
CC pathway which regulates the septin cytoskeleton in both ciliogenesis
CC and collective cell movements. Together with FUZ and WDPCP proposed to
CC function as core component of the CPLANE (ciliogenesis and planar
CC polarity effectors) complex involved in the recruitment of peripheral
CC IFT-A proteins to basal bodies (By similarity).
CC {ECO:0000250|UniProtKB:Q32NR9, ECO:0000250|UniProtKB:Q8C456}.
CC -!- SUBUNIT: Interacts with CPLANE1. Interacts with INTU and FUZ; FUZ, INTU
CC and WDPCP probably form the core CPLANE (ciliogenesis and planar
CC polarity effectors) complex. {ECO:0000250|UniProtKB:Q8C456}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q32NR9}.
CC Cytoplasm, cytoskeleton, cilium axoneme {ECO:0000250|UniProtKB:Q32NR9}.
CC Cytoplasm, cytoskeleton, cilium basal body
CC {ECO:0000250|UniProtKB:Q32NR9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O95876-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95876-2; Sequence=VSP_032409, VSP_032410;
CC Name=3;
CC IsoId=O95876-3; Sequence=VSP_032408;
CC -!- DISEASE: Bardet-Biedl syndrome 15 (BBS15) [MIM:615992]: A syndrome
CC characterized by usually severe pigmentary retinopathy, early-onset
CC obesity, polydactyly, hypogenitalism, renal malformation and
CC intellectual disability. Secondary features include diabetes mellitus,
CC hypertension and congenital heart disease. Bardet-Biedl syndrome
CC inheritance is autosomal recessive, but three mutated alleles (two at
CC one locus, and a third at a second locus) may be required for clinical
CC manifestation of some forms of the disease.
CC {ECO:0000269|PubMed:20671153}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Congenital heart defects, hamartomas of tongue, and
CC polysyndactyly (CHDTHP) [MIM:217085]: A disease characterized by a
CC constellation of anomalies including tongue hamartomas, polysyndactyly,
CC and congenital heart defects such as atrioventricular canal and
CC coarctation of the aorta. {ECO:0000269|PubMed:25427950,
CC ECO:0000269|PubMed:27158779}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Note=Mutations in WDPCP may act as modifiers of the phenotypic
CC expression of Bardet-Biedl syndrome and Meckel syndrome by interacting
CC in trans with primary BBS and MKS loci. {ECO:0000269|PubMed:20671153}.
CC -!- SIMILARITY: Belongs to the WD repeat fritz family. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-34 is the initiator.
CC {ECO:0000305}.
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DR EMBL; AF131737; AAD20026.1; -; mRNA.
DR EMBL; BX538331; CAD98100.1; -; mRNA.
DR EMBL; AC079353; AAY24034.1; -; Genomic_DNA.
DR EMBL; AC009501; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC067953; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC074367; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC093752; AAH93752.1; -; mRNA.
DR EMBL; BC093754; AAH93754.1; -; mRNA.
DR CCDS; CCDS42688.1; -. [O95876-1]
DR CCDS; CCDS46301.1; -. [O95876-3]
DR RefSeq; NP_001036157.1; NM_001042692.2. [O95876-3]
DR RefSeq; NP_056994.3; NM_015910.5. [O95876-1]
DR PDB; 7Q3D; EM; 3.35 A; A=2-746.
DR PDBsum; 7Q3D; -.
DR AlphaFoldDB; O95876; -.
DR BioGRID; 119249; 1.
DR ComplexPortal; CPX-5001; CPLANE complex.
DR IntAct; O95876; 1.
DR STRING; 9606.ENSP00000272321; -.
DR iPTMnet; O95876; -.
DR PhosphoSitePlus; O95876; -.
DR BioMuta; WDPCP; -.
DR jPOST; O95876; -.
DR MassIVE; O95876; -.
DR PaxDb; O95876; -.
DR PeptideAtlas; O95876; -.
DR PRIDE; O95876; -.
DR Antibodypedia; 47438; 113 antibodies from 20 providers.
DR DNASU; 51057; -.
DR Ensembl; ENST00000272321.12; ENSP00000272321.7; ENSG00000143951.16. [O95876-1]
DR Ensembl; ENST00000398544.7; ENSP00000381552.3; ENSG00000143951.16. [O95876-3]
DR Ensembl; ENST00000409562.7; ENSP00000387222.3; ENSG00000143951.16. [O95876-2]
DR GeneID; 51057; -.
DR KEGG; hsa:51057; -.
DR MANE-Select; ENST00000272321.12; ENSP00000272321.7; NM_015910.7; NP_056994.3.
DR UCSC; uc002scf.4; human. [O95876-1]
DR CTD; 51057; -.
DR DisGeNET; 51057; -.
DR GeneCards; WDPCP; -.
DR GeneReviews; WDPCP; -.
DR HGNC; HGNC:28027; WDPCP.
DR HPA; ENSG00000143951; Tissue enhanced (brain).
DR MalaCards; WDPCP; -.
DR MIM; 217085; phenotype.
DR MIM; 613580; gene.
DR MIM; 615992; phenotype.
DR neXtProt; NX_O95876; -.
DR OpenTargets; ENSG00000143951; -.
DR Orphanet; 110; Bardet-Biedl syndrome.
DR Orphanet; 1338; Heart defect-tongue hamartoma-polysyndactyly syndrome.
DR PharmGKB; PA164717186; -.
DR VEuPathDB; HostDB:ENSG00000143951; -.
DR eggNOG; ENOG502QR8Y; Eukaryota.
DR GeneTree; ENSGT00390000016551; -.
DR HOGENOM; CLU_004917_1_0_1; -.
DR InParanoid; O95876; -.
DR OMA; LCFIQFA; -.
DR OrthoDB; 692945at2759; -.
DR PhylomeDB; O95876; -.
DR TreeFam; TF323483; -.
DR PathwayCommons; O95876; -.
DR SignaLink; O95876; -.
DR BioGRID-ORCS; 51057; 5 hits in 1067 CRISPR screens.
DR ChiTaRS; WDPCP; human.
DR GenomeRNAi; 51057; -.
DR Pharos; O95876; Tbio.
DR PRO; PR:O95876; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; O95876; protein.
DR Bgee; ENSG00000143951; Expressed in kidney epithelium and 196 other tissues.
DR ExpressionAtlas; O95876; baseline and differential.
DR Genevisible; O95876; HS.
DR GO; GO:0097541; C:axonemal basal plate; IBA:GO_Central.
DR GO; GO:0005930; C:axoneme; ISS:UniProtKB.
DR GO; GO:0005929; C:cilium; IC:ComplexPortal.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0002093; P:auditory receptor cell morphogenesis; IEA:Ensembl.
DR GO; GO:0043010; P:camera-type eye development; IEA:Ensembl.
DR GO; GO:0060271; P:cilium assembly; ISS:UniProtKB.
DR GO; GO:0044782; P:cilium organization; IBA:GO_Central.
DR GO; GO:0072359; P:circulatory system development; IEA:Ensembl.
DR GO; GO:0055123; P:digestive system development; IEA:Ensembl.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IMP:GO_Central.
DR GO; GO:0001736; P:establishment of planar polarity; IC:ComplexPortal.
DR GO; GO:0045184; P:establishment of protein localization; IBA:GO_Central.
DR GO; GO:0042073; P:intraciliary transport; IC:ComplexPortal.
DR GO; GO:0001822; P:kidney development; IEA:Ensembl.
DR GO; GO:0007399; P:nervous system development; IBA:GO_Central.
DR GO; GO:0021915; P:neural tube development; IC:ComplexPortal.
DR GO; GO:0090521; P:podocyte cell migration; IEA:Ensembl.
DR GO; GO:1902017; P:regulation of cilium assembly; IC:ComplexPortal.
DR GO; GO:0016476; P:regulation of embryonic cell shape; ISS:UniProtKB.
DR GO; GO:2000114; P:regulation of establishment of cell polarity; IEA:Ensembl.
DR GO; GO:0010762; P:regulation of fibroblast migration; IEA:Ensembl.
DR GO; GO:0051893; P:regulation of focal adhesion assembly; IEA:Ensembl.
DR GO; GO:0032880; P:regulation of protein localization; ISS:UniProtKB.
DR GO; GO:1900027; P:regulation of ruffle assembly; IEA:Ensembl.
DR GO; GO:0060541; P:respiratory system development; IEA:Ensembl.
DR GO; GO:0060021; P:roof of mouth development; IMP:GO_Central.
DR GO; GO:0032185; P:septin cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0007224; P:smoothened signaling pathway; IEA:Ensembl.
DR GO; GO:0043587; P:tongue morphogenesis; IMP:GO_Central.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR024511; Frtz.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR13667; PTHR13667; 1.
DR Pfam; PF11768; Frtz; 1.
DR SUPFAM; SSF50978; SSF50978; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Bardet-Biedl syndrome; Cell membrane;
KW Cell projection; Ciliopathy; Cilium; Cilium biogenesis/degradation;
KW Cytoplasm; Cytoskeleton; Disease variant; Intellectual disability;
KW Membrane; Obesity; Reference proteome; Repeat; WD repeat.
FT CHAIN 1..746
FT /note="WD repeat-containing and planar cell polarity
FT effector protein fritz homolog"
FT /id="PRO_0000325802"
FT REPEAT 326..374
FT /note="WD 1"
FT REPEAT 375..414
FT /note="WD 2"
FT VAR_SEQ 1..166
FT /note="MRREFCWDAYSKAAGSRASSPLPRQDRDSFCHQMSFCLTELHLWSLKNTLHI
FT ADRDIGIYQYYDKKDPPATEHGNLEKKQKLAESRDYPWTLKNRRPEKLRDSLKELEELM
FT QNSRCVLSKWKNKYVCQLLFGSGVLVSLSLSGPQLEKVVIDRSLVGKLISDTISD ->
FT MFSSLHS (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.1"
FT /id="VSP_032408"
FT VAR_SEQ 605..618
FT /note="DIHYLALDKGELAL -> ASCYLTSNYTTRLQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_032409"
FT VAR_SEQ 619..746
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_032410"
FT VARIANT 54
FT /note="D -> N (in CHDTHP; impairs protein stability;
FT dbSNP:rs200322968)"
FT /evidence="ECO:0000269|PubMed:25427950,
FT ECO:0000269|PubMed:27158779"
FT /id="VAR_073251"
FT VARIANT 55
FT /note="R -> K (in a patient with Meckel syndrome compound
FT heterozygous for mutations in CC2D2A; dbSNP:rs267606693)"
FT /evidence="ECO:0000269|PubMed:20671153"
FT /id="VAR_064770"
FT VARIANT 205
FT /note="L -> F (in a patient with Bardet-Biedl syndrome
FT compound heterozygous for mutations in BBS12)"
FT /evidence="ECO:0000269|PubMed:20671153"
FT /id="VAR_064771"
FT VARIANT 268
FT /note="G -> S (in dbSNP:rs17617459)"
FT /id="VAR_039919"
FT VARIANT 708
FT /note="S -> F"
FT /evidence="ECO:0000269|PubMed:20671153"
FT /id="VAR_064772"
SQ SEQUENCE 746 AA; 85084 MW; 585EFED0D93EB3D4 CRC64;
MRREFCWDAY SKAAGSRASS PLPRQDRDSF CHQMSFCLTE LHLWSLKNTL HIADRDIGIY
QYYDKKDPPA TEHGNLEKKQ KLAESRDYPW TLKNRRPEKL RDSLKELEEL MQNSRCVLSK
WKNKYVCQLL FGSGVLVSLS LSGPQLEKVV IDRSLVGKLI SDTISDALLT DSFIILSFLA
QNKLCFIQFT KKMESSDVNK RLEKLSALDY KIFYYEIPGP INKTTERHLA INCVHDRVVC
WWPLVNDDAW PWAPISSEKD RANLLLLGYA QGRLEVLSSV RTEWDPLDVR FGTKQPYQVF
TVEHSVSVDK EPMADSCIYE CIRNKIQCVS VTRIPLKSKA ISCCRNVTED KLILGCEDSS
LILYETHRRV TLLAQTELLP SLISCHPSGA ILLVGSNQGE LQIFDMALSP INIQLLAEDR
LPRETLQFSK LFDASSSLVQ MQWIAPQVVS QKGEGSDIYD LLFLRFERGP LGVLLFKLGV
FTRGQLGLID IIFQYIHCDE IYEAINILSS MNWDTLGHQC FISMSAIVNH LLRQKLTPER
EAQLETSLGT FYAPTRPLLD STILEYRDQI SKYARRFFHH LLRYQRFEKA FLLAVDVGAR
DLFMDIHYLA LDKGELALAE VARKRASDID AESITSGVEL LGPLDRGDML NEAFIGLSLA
PQGEDSFPDN LPPSCPTHRH ILQQRILNGS SNRQIIDRRN ELEKDICSGF LMTNTCNAED
GELREDGREQ EIRDGGSLKM IHFGLV
