ID   CF298_HUMAN             Reviewed;         290 AA.
AC   P57076; Q53FH0;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2000, sequence version 1.
DT   02-SEP-2026, entry version 168.
DE   RecName: Full=Cilia- and flagella-associated protein 298 {ECO:0000305};
DE   AltName: Full=Protein kurly homolog {ECO:0000305};
GN   Name=CFAP298 {ECO:0000312|HGNC:HGNC:1301};
GN   Synonyms=C21orf48, C21orf59;
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 [MRNA].
RA   Lutfalla G.;
RL   Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Thymus;
RA   Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA   Tanaka A., Yokoyama S.;
RL   Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=10830953; DOI=10.1038/35012518;
RA   Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA   Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA   Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA   Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA   Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA   Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA   Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA   Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA   Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA   Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA   Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT   "The DNA sequence of human chromosome 21.";
RL   Nature 405:311-319(2000).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Placenta;
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   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-264, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=15592455; DOI=10.1038/nbt1046;
RA   Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA   Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT   "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL   Nat. Biotechnol. 23:94-101(2005).
RN   [6]
RP   FUNCTION, INVOLVEMENT IN CILD26, AND VARIANTS TRP-33; GLY-141 AND TYR-173.
RX   PubMed=24094744; DOI=10.1016/j.ajhg.2013.08.015;
RA   Austin-Tse C., Halbritter J., Zariwala M.A., Gilberti R.M., Gee H.Y.,
RA   Hellman N., Pathak N., Liu Y., Panizzi J.R., Patel-King R.S.,
RA   Tritschler D., Bower R., O'Toole E., Porath J.D., Hurd T.W., Chaki M.,
RA   Diaz K.A., Kohl S., Lovric S., Hwang D.Y., Braun D.A., Schueler M.,
RA   Airik R., Otto E.A., Leigh M.W., Noone P.G., Carson J.L., Davis S.D.,
RA   Pittman J.E., Ferkol T.W., Atkinson J.J., Olivier K.N., Sagel S.D.,
RA   Dell S.D., Rosenfeld M., Milla C.E., Loges N.T., Omran H., Porter M.E.,
RA   King S.M., Knowles M.R., Drummond I.A., Hildebrandt F.;
RT   "Zebrafish ciliopathy screen plus human mutational analysis identifies
RT   C21orf59 and CCDC65 defects as causing primary ciliary dyskinesia.";
RL   Am. J. Hum. Genet. 93:672-686(2013).
RN   [7]
RP   INTERACTION WITH ZMYND10, AND SUBCELLULAR LOCATION.
RX   PubMed=29601588; DOI=10.1371/journal.pgen.1007316;
RA   Cho K.J., Noh S.H., Han S.M., Choi W.I., Kim H.Y., Yu S., Lee J.S.,
RA   Rim J.H., Lee M.G., Hildebrandt F., Gee H.Y.;
RT   "ZMYND10 stabilizes intermediate chain proteins in the cytoplasmic pre-
RT   assembly of dynein arms.";
RL   PLoS Genet. 14:E1007316-E1007316(2018).
CC   -!- FUNCTION: Plays a role in motile cilium function, possibly by acting on
CC       outer dynein arm assembly (PubMed:24094744). Seems to be important for
CC       initiation rather than maintenance of cilium motility (By similarity).
CC       Required for correct positioning of the cilium at the apical cell
CC       surface, suggesting an additional role in the planar cell polarity
CC       (PCP) pathway (By similarity). May suppress canonical Wnt signaling
CC       activity (By similarity). {ECO:0000250|UniProtKB:Q6DRC3,
CC       ECO:0000269|PubMed:24094744}.
CC   -!- SUBUNIT: Interacts with ZMYND10. {ECO:0000269|PubMed:29601588}.
CC   -!- INTERACTION:
CC       P57076; O00628: PEX7; NbExp=3; IntAct=EBI-7205010, EBI-5238811;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:29601588}.
CC       Cytoplasm, cytoskeleton, cilium basal body
CC       {ECO:0000250|UniProtKB:A0A1L8HCK2}. Note=Partially colocalized with
CC       SASS6 in cytoplasmic puncta, suggesting a centrosomal localization.
CC       {ECO:0000250|UniProtKB:Q5U3Z0}.
CC   -!- DISEASE: Ciliary dyskinesia, primary, 26 (CILD26) [MIM:615500]: A
CC       disorder characterized by abnormalities of motile cilia. Respiratory
CC       infections leading to chronic inflammation and bronchiectasis are
CC       recurrent, due to defects in the respiratory cilia. Patients may
CC       exhibit randomization of left-right body asymmetry and situs inversus,
CC       due to dysfunction of monocilia at the embryonic node. Primary ciliary
CC       dyskinesia associated with situs inversus is referred to as Kartagener
CC       syndrome. {ECO:0000269|PubMed:24094744}. Note=The disease is caused by
CC       variants affecting the gene represented in this entry. Cilia in nasal
CC       epithelia show the absence of both outer and inner dynein-arm
CC       components and complete paralysis.
CC   -!- SIMILARITY: Belongs to the CFAP298 family. {ECO:0000305}.
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DR   EMBL; AF282851; AAG00496.1; -; mRNA.
DR   EMBL; AK223318; BAD97038.1; -; mRNA.
DR   EMBL; AP000275; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC000709; AAH00709.1; -; mRNA.
DR   CCDS; CCDS13617.1; -.
DR   RefSeq; NP_067077.1; NM_021254.4.
DR   AlphaFoldDB; P57076; -.
DR   BioGRID; 121187; 88.
DR   CORUM; P57076; -.
DR   FunCoup; P57076; 2392.
DR   IntAct; P57076; 70.
DR   MINT; P57076; -.
DR   STRING; 9606.ENSP00000290155; -.
DR   GlyGen; P57076; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P57076; -.
DR   PhosphoSitePlus; P57076; -.
DR   BioMuta; C21orf59; -.
DR   DMDM; 10719917; -.
DR   jPOST; P57076; -.
DR   MassIVE; P57076; -.
DR   PaxDb; 9606-ENSP00000290155; -.
DR   PeptideAtlas; P57076; -.
DR   ProteomicsDB; 56984; -.
DR   Pumba; P57076; -.
DR   Antibodypedia; 6941; 196 antibodies from 20 providers.
DR   DNASU; 56683; -.
DR   Ensembl; ENST00000290155.8; ENSP00000290155.3; ENSG00000159079.20.
DR   GeneID; 56683; -.
DR   KEGG; hsa:56683; -.
DR   MANE-Select; ENST00000290155.8; ENSP00000290155.3; NM_021254.4; NP_067077.1.
DR   UCSC; uc002yqc.4; human.
DR   AGR; HGNC:1301; -.
DR   ClinPGx; PA25854; -.
DR   CTD; 56683; -.
DR   DisGeNET; 56683; -.
DR   GeneCards; CFAP298; -.
DR   HGNC; HGNC:1301; CFAP298.
DR   HPA; ENSG00000159079; Low tissue specificity.
DR   MalaCards; CFAP298; -.
DR   MIM; 615494; gene.
DR   MIM; 615500; phenotype.
DR   OpenTargets; ENSG00000159079; -.
DR   Orphanet; 244; Primary ciliary dyskinesia.
DR   VEuPathDB; HostDB:ENSG00000159079; -.
DR   eggNOG; ENOG502QQ3Z; Eukaryota.
DR   GeneTree; ENSGT00390000006278; -.
DR   HOGENOM; CLU_064854_0_0_1; -.
DR   InParanoid; P57076; -.
DR   OMA; YRKQEEW; -.
DR   OrthoDB; 276065at2759; -.
DR   PAN-GO; P57076; 0 GO annotations based on evolutionary models.
DR   PhylomeDB; P57076; -.
DR   PathwayCommons; P57076; -.
DR   SignaLink; P57076; -.
DR   Agora; ENSG00000159079; -.
DR   BioGRID-ORCS; 56683; 800 hits in 1138 CRISPR screens.
DR   ChiTaRS; C21orf59; human.
DR   GeneWiki; C21orf59; -.
DR   GenomeRNAi; 56683; -.
DR   Pharos; P57076; Tbio.
DR   PRO; PR:P57076; -.
DR   Proteomes; UP000005640; Chromosome 21.
DR   RNAct; P57076; protein.
DR   Bgee; ENSG00000159079; Expressed in right uterine tube and 108 other cell types or tissues.
DR   ExpressionAtlas; P57076; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; EXP:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR   GO; GO:0060271; P:cilium assembly; IMP:UniProtKB.
DR   GO; GO:0003352; P:regulation of cilium movement; IMP:UniProtKB.
DR   InterPro; IPR021298; CFAP298.
DR   PANTHER; PTHR13238:SF0; CILIA- AND FLAGELLA-ASSOCIATED PROTEIN 298; 1.
DR   PANTHER; PTHR13238; PROTEIN C21ORF59; 1.
DR   Pfam; PF11069; CFAP298; 1.
PE   1: Evidence at protein level;
KW   Cell projection; Ciliopathy; Cilium; Cytoplasm; Cytoskeleton;
KW   Kartagener syndrome; Phosphoprotein; Primary ciliary dyskinesia;
KW   Proteomics identification; Reference proteome.
FT   CHAIN           1..290
FT                   /note="Cilia- and flagella-associated protein 298"
FT                   /id="PRO_0000079523"
FT   MOD_RES         264
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0007744|PubMed:15592455"
FT   VARIANT         33
FT                   /note="R -> W (in dbSNP:rs753786167)"
FT                   /evidence="ECO:0000269|PubMed:24094744"
FT                   /id="VAR_070200"
FT   VARIANT         141
FT                   /note="D -> G (in CILD26; uncertain significance;
FT                   hypomorphic mutation; dbSNP:rs140727644)"
FT                   /evidence="ECO:0000269|PubMed:24094744"
FT                   /id="VAR_070201"
FT   VARIANT         173
FT                   /note="D -> Y (in dbSNP:rs540473945)"
FT                   /evidence="ECO:0000269|PubMed:24094744"
FT                   /id="VAR_070202"
FT   CONFLICT        176
FT                   /note="G -> E (in Ref. 2; BAD97038)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   290 AA;  33224 MW;  4C56A8C989B108DD CRC64;
     MVLLHVKRGD ESQFLLQAPG STELEELTVQ VARVYNGRLK VQRLCSEMEE LAEHGIFLPP
     NMQGLTDDQI EELKLKDEWG EKCVPSGGAV FKKDDIGRRN GQAPNEKMKQ VLKKTIEEAK
     AIISKKQVEA GVCVTMEMVK DALDQLRGAV MIVYPMGLPP YDPIRMEFEN KEDLSGTQAG
     LNVIKEAEAQ LWWAAKELRR TKKLSDYVGK NEKTKIIAKI QQRGQGAPAR EPIISSEEQK
     QLMLYYHRRQ EELKRLEEND DDAYLNSPWA DNTALKRHFH GVKDIKWRPR
//