DAA11_HUMAN
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 03-AUG-2022, entry version 160.
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, ECO:0000303|PubMed:23527195,
GN ECO:0000303|PubMed:23891469, 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}.
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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 iPTMnet; Q86X45; -.
DR PhosphoSitePlus; Q86X45; -.
DR BioMuta; LRRC6; -.
DR DMDM; 134047813; -.
DR MassIVE; Q86X45; -.
DR PaxDb; Q86X45; -.
DR PeptideAtlas; Q86X45; -.
DR PRIDE; Q86X45; -.
DR ProteomicsDB; 70236; -. [Q86X45-1]
DR ProteomicsDB; 70237; -. [Q86X45-2]
DR Antibodypedia; 14134; 243 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 CTD; 23639; -.
DR DisGeNET; 23639; -.
DR GeneCards; DNAAF11; -.
DR GeneReviews; DNAAF11; -.
DR HGNC; HGNC:16725; DNAAF11.
DR HPA; ENSG00000129295; Tissue enhanced (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; 800324at2759; -.
DR PhylomeDB; Q86X45; -.
DR TreeFam; TF324815; -.
DR PathwayCommons; Q86X45; -.
DR SignaLink; Q86X45; -.
DR BioGRID-ORCS; 23639; 10 hits in 1054 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 139 other tissues.
DR ExpressionAtlas; Q86X45; baseline and differential.
DR Genevisible; Q86X45; HS.
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:0043393; P:regulation of protein binding; IEA:Ensembl.
DR GO; GO:0061458; P:reproductive system development; IMP:BHF-UCL.
DR Gene3D; 3.80.10.10; -; 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 SMART; SM00446; LRRcap; 1.
DR PROSITE; PS51203; CS; 1.
DR PROSITE; PS51450; LRR; 5.
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; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:29511670"
FT /id="VAR_084433"
FT VARIANT 74
FT /note="A -> P (in CILD19; unknown pathological
FT significance; 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
