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WD repeat-containing and planar cell polarity effector protein fritz homolog (hFRTZ) (Bardet-Biedl syndrome 15 protein) (WD repeat-containing and planar cell polarity effector protein)

 FRITZ_HUMAN             Reviewed;         746 AA.
O95876; Q53RW4; Q7Z2Z3;
18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
18-MAR-2008, sequence version 2.
10-OCT-2018, entry version 122.
RecName: Full=WD repeat-containing and planar cell polarity effector protein fritz homolog;
Short=hFRTZ;
AltName: Full=Bardet-Biedl syndrome 15 protein;
AltName: Full=WD repeat-containing and planar cell polarity effector protein;
Name=WDPCP; Synonyms=BBS15, C2orf86, FRITZ;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
TISSUE=Brain;
Mei G., Yu W., Gibbs R.A.;
Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
TISSUE=Fetal brain;
PubMed=17974005; DOI=10.1186/1471-2164-8-399;
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
"The full-ORF clone resource of the German cDNA consortium.";
BMC Genomics 8:399-399(2007).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=15815621; DOI=10.1038/nature03466;
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
Waterston R.H., Wilson R.K.;
"Generation and annotation of the DNA sequences of human chromosomes 2
and 4.";
Nature 434:724-731(2005).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
TISSUE=Brain;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
INVOLVEMENT IN BBS15, INVOLVEMENT IN MECKEL SYNDROME, AND VARIANTS
LYS-55; PHE-205 AND PHE-708.
PubMed=20671153; DOI=10.1126/science.1191184;
Kim S.K., Shindo A., Park T.J., Oh E.C., Ghosh S., Gray R.S.,
Lewis R.A., Johnson C.A., Attie-Bittach T., Katsanis N.,
Wallingford J.B.;
"Planar cell polarity acts through septins to control collective cell
movement and ciliogenesis.";
Science 329:1337-1340(2010).
[6]
INVOLVEMENT IN CHDTHP, AND VARIANT CHDTHP ASN-54.
PubMed=25427950; DOI=10.1002/ajmg.a.36852;
Saari J., Lovell M.A., Yu H.C., Bellus G.A.;
"Compound heterozygosity for a frame shift mutation and a likely
pathogenic sequence variant in the planar cell polarity-ciliogenesis
gene WDPCP in a girl with polysyndactyly, coarctation of the aorta,
and tongue hamartomas.";
Am. J. Med. Genet. A 167:421-427(2015).
[7]
VARIANT CHDTHP ASN-54, AND CHARACTERIZATION OF VARIANT CHDTHP ASN-54.
PubMed=27158779; DOI=10.1038/ng.3558;
Toriyama M., Lee C., Taylor S.P., Duran I., Cohn D.H., Bruel A.L.,
Tabler J.M., Drew K., Kelly M.R., Kim S., Park T.J., Braun D.A.,
Pierquin G., Biver A., Wagner K., Malfroot A., Panigrahi I.,
Franco B., Al-Lami H.A., Yeung Y., Choi Y.J., Duffourd Y., Faivre L.,
Riviere J.B., Chen J., Liu K.J., Marcotte E.M., Hildebrandt F.,
Thauvin-Robinet C., Krakow D., Jackson P.K., Wallingford J.B.;
"The ciliopathy-associated CPLANE proteins direct basal body
recruitment of intraflagellar transport machinery.";
Nat. Genet. 48:648-656(2016).
-!- FUNCTION: Probable effector of the planar cell polarity signaling
pathway which regulates the septin cytoskeleton in both
ciliogenesis and collective cell movements. Together with FUZ and
WDPCP proposed to function as core component of the CPLANE
(ciliogenesis and planar polarity effectors) complex involved in
the recruitment of peripheral IFT-A proteins to basal bodies (By
similarity). {ECO:0000250|UniProtKB:Q32NR9,
ECO:0000250|UniProtKB:Q8C456}.
-!- SUBUNIT: Interacts with CPLANE1. Interacts with INTU and FUZ; FUZ,
INTU and WDPCP probably form the core CPLANE (ciliogenesis and
planar polarity effectors) complex.
{ECO:0000250|UniProtKB:Q8C456}.
-!- SUBCELLULAR LOCATION: Cell membrane
{ECO:0000250|UniProtKB:Q32NR9}. Cytoplasm, cytoskeleton, cilium
axoneme {ECO:0000250|UniProtKB:Q32NR9}. Cytoplasm, cytoskeleton,
cilium basal body {ECO:0000250|UniProtKB:Q32NR9}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=3;
Name=1;
IsoId=O95876-1; Sequence=Displayed;
Name=2;
IsoId=O95876-2; Sequence=VSP_032409, VSP_032410;
Name=3;
IsoId=O95876-3; Sequence=VSP_032408;
-!- DISEASE: Bardet-Biedl syndrome 15 (BBS15) [MIM:615992]: A syndrome
characterized by usually severe pigmentary retinopathy, early-
onset obesity, polydactyly, hypogenitalism, renal malformation and
mental retardation. Secondary features include diabetes mellitus,
hypertension and congenital heart disease. Bardet-Biedl syndrome
inheritance is autosomal recessive, but three mutated alleles (two
at one locus, and a third at a second locus) may be required for
clinical manifestation of some forms of the disease.
{ECO:0000269|PubMed:20671153}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- DISEASE: Congenital heart defects, hamartomas of tongue, and
polysyndactyly (CHDTHP) [MIM:217085]: A disease characterized by a
constellation of anomalies including tongue hamartomas,
polysyndactyly, and congenital heart defects such as
atrioventricular canal and coarctation of the aorta.
{ECO:0000269|PubMed:25427950, ECO:0000269|PubMed:27158779}.
Note=The disease is caused by mutations affecting the gene
represented in this entry.
-!- DISEASE: Note=Mutations in WDPCP may act as modifiers of the
phenotypic expression of Bardet-Biedl syndrome and Meckel syndrome
by interacting in trans with primary BBS and MKS loci.
{ECO:0000269|PubMed:20671153}.
-!- SIMILARITY: Belongs to the WD repeat fritz family. {ECO:0000305}.
-!- CAUTION: It is uncertain whether Met-1 or Met-34 is the initiator.
{ECO:0000305}.
-----------------------------------------------------------------------
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EMBL; AF131737; AAD20026.1; -; mRNA.
EMBL; BX538331; CAD98100.1; -; mRNA.
EMBL; AC079353; AAY24034.1; -; Genomic_DNA.
EMBL; AC009501; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AC067953; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AC074367; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; BC093752; AAH93752.1; -; mRNA.
EMBL; BC093754; AAH93754.1; -; mRNA.
CCDS; CCDS42688.1; -. [O95876-1]
CCDS; CCDS46301.1; -. [O95876-3]
RefSeq; NP_001036157.1; NM_001042692.2. [O95876-3]
RefSeq; NP_056994.3; NM_015910.5. [O95876-1]
UniGene; Hs.414952; -.
UniGene; Hs.682428; -.
UniGene; Hs.737299; -.
ProteinModelPortal; O95876; -.
BioGrid; 119249; 1.
IntAct; O95876; 1.
STRING; 9606.ENSP00000272321; -.
iPTMnet; O95876; -.
PhosphoSitePlus; O95876; -.
BioMuta; WDPCP; -.
PaxDb; O95876; -.
PeptideAtlas; O95876; -.
PRIDE; O95876; -.
ProteomicsDB; 51114; -.
ProteomicsDB; 51115; -. [O95876-2]
ProteomicsDB; 51116; -. [O95876-3]
Ensembl; ENST00000272321; ENSP00000272321; ENSG00000143951. [O95876-1]
Ensembl; ENST00000398544; ENSP00000381552; ENSG00000143951. [O95876-3]
Ensembl; ENST00000409562; ENSP00000387222; ENSG00000143951. [O95876-2]
GeneID; 51057; -.
KEGG; hsa:51057; -.
UCSC; uc002scf.4; human. [O95876-1]
CTD; 51057; -.
DisGeNET; 51057; -.
EuPathDB; HostDB:ENSG00000143951.15; -.
GeneCards; WDPCP; -.
GeneReviews; WDPCP; -.
H-InvDB; HIX0002091; -.
HGNC; HGNC:28027; WDPCP.
HPA; HPA044144; -.
MalaCards; WDPCP; -.
MIM; 217085; phenotype.
MIM; 613580; gene.
MIM; 615992; phenotype.
neXtProt; NX_O95876; -.
OpenTargets; ENSG00000143951; -.
Orphanet; 110; Bardet-Biedl syndrome.
Orphanet; 564; Meckel syndrome.
PharmGKB; PA164717186; -.
eggNOG; ENOG410IGAV; Eukaryota.
eggNOG; ENOG410Y1HY; LUCA.
GeneTree; ENSGT00390000016551; -.
InParanoid; O95876; -.
KO; K22863; -.
OMA; PMADSCI; -.
OrthoDB; EOG091G03ZZ; -.
PhylomeDB; O95876; -.
TreeFam; TF323483; -.
ChiTaRS; WDPCP; human.
GenomeRNAi; 51057; -.
PRO; PR:O95876; -.
Proteomes; UP000005640; Chromosome 2.
Bgee; ENSG00000143951; Expressed in 208 organ(s), highest expression level in nasal cavity epithelium.
ExpressionAtlas; O95876; baseline and differential.
Genevisible; O95876; HS.
GO; GO:0097541; C:axonemal basal plate; IEA:Ensembl.
GO; GO:0005930; C:axoneme; ISS:UniProtKB.
GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
GO; GO:0002093; P:auditory receptor cell morphogenesis; IEA:Ensembl.
GO; GO:0043010; P:camera-type eye development; IEA:Ensembl.
GO; GO:0072358; P:cardiovascular system development; IEA:Ensembl.
GO; GO:0060271; P:cilium assembly; ISS:UniProtKB.
GO; GO:0055123; P:digestive system development; IEA:Ensembl.
GO; GO:0042733; P:embryonic digit morphogenesis; IEA:Ensembl.
GO; GO:0045184; P:establishment of protein localization; IEA:Ensembl.
GO; GO:0090521; P:glomerular visceral epithelial cell migration; IEA:Ensembl.
GO; GO:0001822; P:kidney development; IEA:Ensembl.
GO; GO:0016476; P:regulation of embryonic cell shape; ISS:UniProtKB.
GO; GO:2000114; P:regulation of establishment of cell polarity; IEA:Ensembl.
GO; GO:0010762; P:regulation of fibroblast migration; IEA:Ensembl.
GO; GO:0051893; P:regulation of focal adhesion assembly; IEA:Ensembl.
GO; GO:0032880; P:regulation of protein localization; ISS:UniProtKB.
GO; GO:1900027; P:regulation of ruffle assembly; IEA:Ensembl.
GO; GO:0060541; P:respiratory system development; IEA:Ensembl.
GO; GO:0060021; P:roof of mouth development; IEA:Ensembl.
GO; GO:0032185; P:septin cytoskeleton organization; ISS:UniProtKB.
GO; GO:0007224; P:smoothened signaling pathway; IEA:Ensembl.
Gene3D; 2.130.10.10; -; 1.
InterPro; IPR024511; Frtz.
InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
InterPro; IPR036322; WD40_repeat_dom_sf.
PANTHER; PTHR13667; PTHR13667; 1.
Pfam; PF11768; Frtz; 1.
SUPFAM; SSF50978; SSF50978; 1.
1: Evidence at protein level;
Alternative splicing; Bardet-Biedl syndrome; Cell membrane;
Cell projection; Ciliopathy; Cilium; Cilium biogenesis/degradation;
Complete proteome; Cytoplasm; Cytoskeleton; Disease mutation;
Membrane; Mental retardation; Obesity; Polymorphism;
Reference proteome; Repeat; WD repeat.
CHAIN 1 746 WD repeat-containing and planar cell
polarity effector protein fritz homolog.
/FTId=PRO_0000325802.
REPEAT 326 374 WD 1.
REPEAT 375 414 WD 2.
VAR_SEQ 1 166 MRREFCWDAYSKAAGSRASSPLPRQDRDSFCHQMSFCLTEL
HLWSLKNTLHIADRDIGIYQYYDKKDPPATEHGNLEKKQKL
AESRDYPWTLKNRRPEKLRDSLKELEELMQNSRCVLSKWKN
KYVCQLLFGSGVLVSLSLSGPQLEKVVIDRSLVGKLISDTI
SD -> MFSSLHS (in isoform 3).
{ECO:0000303|PubMed:15489334,
ECO:0000303|Ref.1}.
/FTId=VSP_032408.
VAR_SEQ 605 618 DIHYLALDKGELAL -> ASCYLTSNYTTRLQ (in
isoform 2).
{ECO:0000303|PubMed:17974005}.
/FTId=VSP_032409.
VAR_SEQ 619 746 Missing (in isoform 2).
{ECO:0000303|PubMed:17974005}.
/FTId=VSP_032410.
VARIANT 54 54 D -> N (in CHDTHP; impairs protein
stability; dbSNP:rs200322968).
{ECO:0000269|PubMed:25427950,
ECO:0000269|PubMed:27158779}.
/FTId=VAR_073251.
VARIANT 55 55 R -> K (in a patient with Meckel syndrome
compound heterozygous for mutations in
CC2D2A; dbSNP:rs267606693).
{ECO:0000269|PubMed:20671153}.
/FTId=VAR_064770.
VARIANT 205 205 L -> F (in a patient with Bardet-Biedl
syndrome compound heterozygous for
mutations in BBS12).
{ECO:0000269|PubMed:20671153}.
/FTId=VAR_064771.
VARIANT 268 268 G -> S (in dbSNP:rs17617459).
/FTId=VAR_039919.
VARIANT 708 708 S -> F. {ECO:0000269|PubMed:20671153}.
/FTId=VAR_064772.
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


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