ID DAA11_HUMAN Reviewed; 466 AA. AC Q86X45; Q13648; Q4G183; DT 11-OCT-2005, integrated into UniProtKB/Swiss-Prot. DT 20-MAR-2007, sequence version 3. DT 24-JAN-2024, entry version 168. DE RecName: Full=Dynein axonemal assembly factor 11 {ECO:0000305}; DE Short=DNAAF11 {ECO:0000305}; DE AltName: Full=Leucine-rich repeat-containing protein 6 {ECO:0000303|PubMed:23527195, ECO:0000303|PubMed:33403504}; DE AltName: Full=Leucine-rich testis-specific protein; DE AltName: Full=Protein tilB homolog; DE AltName: Full=Testis-specific leucine-rich repeat protein; GN Name=DNAAF11 {ECO:0000312|HGNC:HGNC:16725}; GN Synonyms=LRRC6 {ECO:0000303|PubMed:23122589, GN ECO:0000303|PubMed:23527195, ECO:0000303|PubMed:23891469, GN ECO:0000303|PubMed:33403504}, LRTP, TSLRP; 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] (ISOFORM 1), AND VARIANT ILE-232. RA O'Hern P.A., Yavetz H., Moy T., Yavetz B., Liang Z.G., Wang G.Y., RA Goldberg E.; RL Submitted (JUN-1996) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Brain, and Testis; 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 [3] RP INTERACTION WITH ZMYND10. 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). RN [4] RP VARIANTS CILD19 PRO-74; HIS-146 AND 192-GLN--ILE-466 DEL, FUNCTION, RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=23122589; DOI=10.1016/j.ajhg.2012.10.003; RA Kott E., Duquesnoy P., Copin B., Legendre M., Dastot-Le Moal F., RA Montantin G., Jeanson L., Tamalet A., Papon J.F., Siffroi J.P., Rives N., RA Mitchell V., de Blic J., Coste A., Clement A., Escalier D., Toure A., RA Escudier E., Amselem S.; RT "Loss-of-function mutations in LRRC6, a gene essential for proper axonemal RT assembly of inner and outer dynein arms, cause primary ciliary RT dyskinesia."; RL Am. J. Hum. Genet. 91:958-964(2012). RN [5] RP INTERACTION WITH ZMYND10, INVOLVEMENT IN CILD19, VARIANTS CILD19 ARG-87 AND RP 188-GLN--ILE-466 DEL, AND CHARACTERIZATION OF VARIANTS CILD19 ARG-87; RP HIS-146 AND 188-GLN--ILE-466 DEL. RX PubMed=23891469; DOI=10.1016/j.ajhg.2013.06.007; RA Zariwala M.A., Gee H.Y., Kurkowiak M., Al-Mutairi D.A., Leigh M.W., RA Hurd T.W., Hjeij R., Dell S.D., Chaki M., Dougherty G.W., Adan M., RA Spear P.C., Esteve-Rudd J., Loges N.T., Rosenfeld M., Diaz K.A., RA Olbrich H., Wolf W.E., Sheridan E., Batten T.F., Halbritter J., RA Porath J.D., Kohl S., Lovric S., Hwang D.Y., Pittman J.E., Burns K.A., RA Ferkol T.W., Sagel S.D., Olivier K.N., Morgan L.C., Werner C., Raidt J., RA Pennekamp P., Sun Z., Zhou W., Airik R., Natarajan S., Allen S.J., RA Amirav I., Wieczorek D., Landwehr K., Nielsen K., Schwerk N., Sertic J., RA Kohler G., Washburn J., Levy S., Fan S., Koerner-Rettberg C., Amselem S., RA Williams D.S., Mitchell B.J., Drummond I.A., Otto E.A., Omran H., RA Knowles M.R., Hildebrandt F.; RT "ZMYND10 is mutated in primary ciliary dyskinesia and interacts with RT LRRC6."; RL Am. J. Hum. Genet. 93:336-345(2013). RN [6] RP VARIANT CILD19 HIS-146, CHARACTERIZATION OF VARIANT CILD19 HIS-146, RP SUBCELLULAR LOCATION, FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=23527195; DOI=10.1371/journal.pone.0059436; RA Horani A., Ferkol T.W., Shoseyov D., Wasserman M.G., Oren Y.S., Kerem B., RA Amirav I., Cohen-Cymberknoh M., Dutcher S.K., Brody S.L., Elpeleg O., RA Kerem E.; RT "LRRC6 mutation causes primary ciliary dyskinesia with dynein arm RT defects."; RL PLoS ONE 8:e59436-e59436(2013). RN [7] RP INVOLVEMENT IN CILD19. RX PubMed=25186273; DOI=10.1183/09031936.00052014; RA Raidt J., Wallmeier J., Hjeij R., Onnebrink J.G., Pennekamp P., Loges N.T., RA Olbrich H., Haeffner K., Dougherty G.W., Omran H., Werner C.; RT "Ciliary beat pattern and frequency in genetic variants of primary ciliary RT dyskinesia."; RL Eur. Respir. J. 44:1579-1588(2014). RN [8] RP VARIANT CILD19 LYS-61. RX PubMed=29511670; DOI=10.1155/2018/1854269; RA Liu L., Luo H.; RT "Whole-Exome Sequencing Identified a Novel Compound Heterozygous Mutation RT of LRRC6 in a Chinese Primary Ciliary Dyskinesia Patient."; RL Biomed. Res. Int. 2018:1854269-1854269(2018). RN [9] RP VARIANT CILD19 250-TRP--ILE-466 DEL, CHARACTERIZATION OF VARIANT CILD19 RP 250-TRP--ILE-466 DEL, TISSUE SPECIFICITY, FUNCTION, SUBCELLULAR LOCATION, RP AND DEVELOPMENTAL STAGE. RX PubMed=33403504; DOI=10.1007/s10815-020-02036-6; RA Li Y., Jiang C., Zhang X., Liu M., Sun Y., Yang Y., Shen Y.; RT "The effect of a novel LRRC6 mutation on the flagellar ultrastructure in a RT primary ciliary dyskinesia patient."; RL J. Assist. Reprod. Genet. 38:689-696(2021). CC -!- FUNCTION: Involved in dynein arm assembly, is important for expression CC and transporting outer dynein arm (ODA) proteins from the cytoplasm to CC the cilia (PubMed:23122589, PubMed:23527195, PubMed:33403504). Acts as CC a crucial component in the formation and motility of spermatozoal CC flagella (PubMed:33403504). {ECO:0000269|PubMed:23122589, CC ECO:0000269|PubMed:23527195, ECO:0000269|PubMed:33403504}. CC -!- SUBUNIT: Interacts (via CS domain) with ZMYND10 (via C-terminus). CC {ECO:0000269|PubMed:23891469, ECO:0000269|PubMed:29601588}. CC -!- INTERACTION: CC Q86X45; P26196: DDX6; NbExp=3; IntAct=EBI-9379658, EBI-351257; CC Q86X45; Q96II8-3: LRCH3; NbExp=3; IntAct=EBI-9379658, EBI-17658306; CC Q86X45; Q9Y333: LSM2; NbExp=3; IntAct=EBI-9379658, EBI-347416; CC Q86X45; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-9379658, EBI-16439278; CC Q86X45; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-9379658, EBI-742388; CC Q86X45; Q7Z5L7-3: PODN; NbExp=3; IntAct=EBI-9379658, EBI-23806733; CC Q86X45; Q7RTT5: SSX7; NbExp=3; IntAct=EBI-9379658, EBI-12879730; CC Q86X45; P54274-2: TERF1; NbExp=3; IntAct=EBI-9379658, EBI-711018; CC Q86X45; Q6PF05: TTC23L; NbExp=3; IntAct=EBI-9379658, EBI-8656864; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23122589, CC ECO:0000269|PubMed:23527195, ECO:0000269|PubMed:33403504}. Cell CC projection, cilium {ECO:0000269|PubMed:23122589}. Dynein axonemal CC particle {ECO:0000250|UniProtKB:A0A1L8G016}. Cell projection, cilium, CC flagellum {ECO:0000269|PubMed:33403504}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q86X45-1; Sequence=Displayed; CC Name=2; CC IsoId=Q86X45-2; Sequence=VSP_015862, VSP_015863; CC -!- TISSUE SPECIFICITY: Expressed predominantly in testis and in nasal CC epithelial cells. {ECO:0000269|PubMed:23122589, CC ECO:0000269|PubMed:23527195, ECO:0000269|PubMed:33403504}. CC -!- DEVELOPMENTAL STAGE: Localized in the cytoplasm of early spermatogonia CC and spermatids of different spermatogenic stages and in the flagella of CC mature epididymal spermatozoa. {ECO:0000269|PubMed:33403504}. CC -!- DISEASE: Ciliary dyskinesia, primary, 19 (CILD19) [MIM:614935]: 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; reduced fertility CC is often observed in male patients due to abnormalities of sperm tails. CC Half of the patients exhibit randomization of left-right body asymmetry CC and situs inversus, due to dysfunction of monocilia at the embryonic CC node. Primary ciliary dyskinesia associated with situs inversus is CC referred to as Kartagener syndrome. {ECO:0000269|PubMed:23122589, CC ECO:0000269|PubMed:23527195, ECO:0000269|PubMed:23891469, CC ECO:0000269|PubMed:25186273, ECO:0000269|PubMed:29511670, CC ECO:0000269|PubMed:33403504}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the tilB family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U60666; AAB02976.1; -; mRNA. DR EMBL; BC027589; AAH27589.1; -; mRNA. DR EMBL; BC047286; AAH47286.1; -; mRNA. DR CCDS; CCDS6365.1; -. [Q86X45-1] DR RefSeq; NP_001308890.1; NM_001321961.1. DR RefSeq; NP_001308891.1; NM_001321962.1. DR RefSeq; NP_001308892.1; NM_001321963.1. DR RefSeq; NP_001308893.1; NM_001321964.1. DR RefSeq; NP_001308894.1; NM_001321965.1. DR RefSeq; NP_001308895.1; NM_001321966.1. DR RefSeq; NP_036604.2; NM_012472.5. [Q86X45-1] DR AlphaFoldDB; Q86X45; -. DR SMR; Q86X45; -. DR BioGRID; 117167; 18. DR IntAct; Q86X45; 19. DR MINT; Q86X45; -. DR STRING; 9606.ENSP00000484634; -. DR GlyGen; Q86X45; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q86X45; -. DR PhosphoSitePlus; Q86X45; -. DR BioMuta; LRRC6; -. DR DMDM; 134047813; -. DR MassIVE; Q86X45; -. DR PaxDb; 9606-ENSP00000484634; -. DR PeptideAtlas; Q86X45; -. DR ProteomicsDB; 70236; -. [Q86X45-1] DR ProteomicsDB; 70237; -. [Q86X45-2] DR Antibodypedia; 14134; 287 antibodies from 21 providers. DR DNASU; 23639; -. DR Ensembl; ENST00000519595.5; ENSP00000429791.1; ENSG00000129295.10. [Q86X45-1] DR Ensembl; ENST00000620350.5; ENSP00000484634.1; ENSG00000129295.10. [Q86X45-1] DR GeneID; 23639; -. DR KEGG; hsa:23639; -. DR MANE-Select; ENST00000620350.5; ENSP00000484634.1; NM_012472.6; NP_036604.2. DR UCSC; uc003ytk.5; human. [Q86X45-1] DR AGR; HGNC:16725; -. DR CTD; 23639; -. DR DisGeNET; 23639; -. DR GeneCards; DNAAF11; -. DR GeneReviews; DNAAF11; -. DR HGNC; HGNC:16725; DNAAF11. DR HPA; ENSG00000129295; Tissue enhanced (choroid plexus, testis). DR MalaCards; DNAAF11; -. DR MIM; 614930; gene. DR MIM; 614935; phenotype. DR neXtProt; NX_Q86X45; -. DR OpenTargets; ENSG00000129295; -. DR Orphanet; 244; Primary ciliary dyskinesia. DR VEuPathDB; HostDB:ENSG00000129295; -. DR eggNOG; KOG0531; Eukaryota. DR GeneTree; ENSGT00940000158506; -. DR InParanoid; Q86X45; -. DR OMA; QHRAVIV; -. DR OrthoDB; 5476364at2759; -. DR PhylomeDB; Q86X45; -. DR TreeFam; TF324815; -. DR PathwayCommons; Q86X45; -. DR SignaLink; Q86X45; -. DR BioGRID-ORCS; 23639; 11 hits in 1133 CRISPR screens. DR ChiTaRS; LRRC6; human. DR GenomeRNAi; 23639; -. DR Pharos; Q86X45; Tbio. DR PRO; PR:Q86X45; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q86X45; Protein. DR Bgee; ENSG00000129295; Expressed in right uterine tube and 141 other cell types or tissues. DR ExpressionAtlas; Q86X45; baseline and differential. DR GO; GO:0090651; C:apical cytoplasm; IEA:Ensembl. DR GO; GO:0005929; C:cilium; IDA:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0120293; C:dynein axonemal particle; ISS:UniProtKB. DR GO; GO:0005576; C:extracellular region; IEA:GOC. DR GO; GO:0031514; C:motile cilium; IEA:UniProtKB-SubCell. DR GO; GO:0070286; P:axonemal dynein complex assembly; IMP:UniProtKB. DR GO; GO:0090660; P:cerebrospinal fluid circulation; ISS:UniProtKB. DR GO; GO:0003341; P:cilium movement; IMP:BHF-UCL. DR GO; GO:0060287; P:epithelial cilium movement involved in determination of left/right asymmetry; IMP:BHF-UCL. DR GO; GO:0003351; P:epithelial cilium movement involved in extracellular fluid movement; ISS:UniProtKB. DR GO; GO:0051649; P:establishment of localization in cell; ISS:UniProtKB. DR GO; GO:0030317; P:flagellated sperm motility; IMP:BHF-UCL. DR GO; GO:0036159; P:inner dynein arm assembly; IMP:BHF-UCL. DR GO; GO:0008584; P:male gonad development; ISS:BHF-UCL. DR GO; GO:0044458; P:motile cilium assembly; IMP:BHF-UCL. DR GO; GO:0036158; P:outer dynein arm assembly; IMP:BHF-UCL. DR GO; GO:0061512; P:protein localization to cilium; ISS:UniProtKB. DR GO; GO:0120229; P:protein localization to motile cilium; IMP:UniProtKB. DR GO; GO:0061458; P:reproductive system development; IMP:BHF-UCL. DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 1. DR InterPro; IPR007052; CS_dom. DR InterPro; IPR001611; Leu-rich_rpt. DR InterPro; IPR032675; LRR_dom_sf. DR InterPro; IPR003603; U2A'_phosphoprotein32A_C. DR PANTHER; PTHR18849:SF0; CILIA- AND FLAGELLA-ASSOCIATED PROTEIN 410-RELATED; 1. DR PANTHER; PTHR18849; LEUCINE RICH REPEAT PROTEIN; 1. DR Pfam; PF14580; LRR_9; 1. DR SMART; SM00365; LRR_SD22; 3. DR SMART; SM00446; LRRcap; 1. DR SUPFAM; SSF52058; L domain-like; 1. DR PROSITE; PS51203; CS; 1. DR PROSITE; PS51450; LRR; 5. DR Genevisible; Q86X45; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cell projection; Ciliopathy; Cilium; Coiled coil; KW Cytoplasm; Disease variant; Flagellum; Kartagener syndrome; KW Leucine-rich repeat; Primary ciliary dyskinesia; Reference proteome; KW Repeat. FT CHAIN 1..466 FT /note="Dynein axonemal assembly factor 11" FT /id="PRO_0000084496" FT REPEAT 22..43 FT /note="LRR 1" FT REPEAT 45..66 FT /note="LRR 2" FT REPEAT 67..88 FT /note="LRR 3" FT REPEAT 89..110 FT /note="LRR 4" FT DOMAIN 123..161 FT /note="LRRCT" FT DOMAIN 301..396 FT /note="CS" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00547" FT REGION 185..206 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 268..288 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 391..466 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 178..204 FT /evidence="ECO:0000255" FT COMPBIAS 396..422 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 429..453 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 409..414 FT /note="RSKHME -> SYSTGF (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_015862" FT VAR_SEQ 415..466 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_015863" FT VARIANT 61 FT /note="N -> K (in CILD19; uncertain significance)" FT /evidence="ECO:0000269|PubMed:29511670" FT /id="VAR_084433" FT VARIANT 74 FT /note="A -> P (in CILD19; uncertain significance; FT dbSNP:rs397514596)" FT /evidence="ECO:0000269|PubMed:23122589" FT /id="VAR_069038" FT VARIANT 87 FT /note="C -> R (in CILD19; no effect on interaction with FT ZMYND10)" FT /evidence="ECO:0000269|PubMed:23891469" FT /id="VAR_084434" FT VARIANT 146 FT /note="D -> H (in CILD19; no effect on interaction with FT ZMYND10; reduced expression in cytoplasm; decreased FT expression of inner and outer dynein proteins; mislocation FT of inner and outer dynein proteins; dbSNP:rs200321595)" FT /evidence="ECO:0000269|PubMed:23122589, FT ECO:0000269|PubMed:23527195, ECO:0000269|PubMed:23891469" FT /id="VAR_069039" FT VARIANT 188..466 FT /note="Missing (in CILD19; loss of interaction with FT ZMYND10)" FT /evidence="ECO:0000269|PubMed:23891469" FT /id="VAR_084435" FT VARIANT 192..466 FT /note="Missing (in CILD19)" FT /evidence="ECO:0000269|PubMed:23122589" FT /id="VAR_084436" FT VARIANT 232 FT /note="T -> I (in dbSNP:rs2293979)" FT /evidence="ECO:0000269|Ref.1" FT /id="VAR_023603" FT VARIANT 250..466 FT /note="Missing (in CILD19; loss of protein expression)" FT /evidence="ECO:0000269|PubMed:33403504" FT /id="VAR_084437" FT VARIANT 466 FT /note="I -> T (in dbSNP:rs9297853)" FT /id="VAR_031223" FT CONFLICT 242..244 FT /note="Missing (in Ref. 1; AAB02976)" FT /evidence="ECO:0000305" FT CONFLICT 349..351 FT /note="Missing (in Ref. 2; AAH27589)" FT /evidence="ECO:0000305" SQ SEQUENCE 466 AA; 54255 MW; 4A3DBF849D5621C7 CRC64; MGWITEDLIR RNAEHNDCVI FSLEELSLHQ QEIERLEHID KWCRDLKILY LQNNLIGKIE NVSKLKKLEY LNLALNNIEK IENLEGCEEL AKLDLTVNFI GELSSIKNLQ HNIHLKELFL MGNPCASFDH YREFVVATLP QLKWLDGKEI EPSERIKALQ DYSVIEPQIR EQEKDHCLKR AKLKEEAQRK HQEEDKNEDK RSNAGFDGRW YTDINATLSS LESKDHLQAP DTEEHNTKKL DNSEDDLEFW NKPCLFTPES RLETLRHMEK QRKKQEKLSE KKKKVKPPRT LITEDGKALN VNEPKIDFSL KDNEKQIILD LAVYRYMDTS LIDVDVQPTY VRVMIKGKPF QLVLPAEVKP DSSSAKRSQT TGHLVICMPK VGEVITGGQR AFKSMKTTSD RSREQTNTRS KHMEKLEVDP SKHSFPDVTN IVQEKKHTPR RRPEPKIIPS EEDPTFEDNP EVPPLI //