DAAF6_HUMAN
ID DAAF6_HUMAN Reviewed; 214 AA.
AC Q9NQM4; D3DUX5; Q86WE1;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Dynein axonemal assembly factor 6 {ECO:0000312|HGNC:HGNC:28570};
DE AltName: Full=PIH1 domain-containing protein 3 {ECO:0000312|HGNC:HGNC:28570};
DE AltName: Full=Sarcoma antigen NY-SAR-97;
GN Name=DNAAF6 {ECO:0000312|HGNC:HGNC:28570};
GN Synonyms=CXorf41 {ECO:0000312|HGNC:HGNC:28570},
GN PIH1D3 {ECO:0000312|HGNC:HGNC:28570};
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 GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Lung, 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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-195, AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=12601173; DOI=10.1073/pnas.0437972100;
RA Lee S.-Y., Obata Y., Yoshida M., Stockert E., Williamson B.,
RA Jungbluth A.A., Chen Y.-T., Old L.J., Scanlan M.J.;
RT "Immunomic analysis of human sarcoma.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:2651-2656(2003).
RN [5]
RP INVOLVEMENT IN CILD36, VARIANT CILD36 119-GLN--PHE-214 DEL,
RP CHARACTERIZATION OF VARIANT CILD36 119-GLN--PHE-214 DEL, FUNCTION, AND
RP INTERACTION WITH DNAAF2 AND DNAAF4.
RX PubMed=28041644; DOI=10.1016/j.ajhg.2016.11.019;
RA Paff T., Loges N.T., Aprea I., Wu K., Bakey Z., Haarman E.G., Daniels J.M.,
RA Sistermans E.A., Bogunovic N., Dougherty G.W., Hoeben I.M.,
RA Grosse-Onnebrink J., Matter A., Olbrich H., Werner C., Pals G.,
RA Schmidts M., Omran H., Micha D.;
RT "Mutations in PIH1D3 Cause X-Linked Primary Ciliary Dyskinesia with Outer
RT and Inner Dynein Arm Defects.";
RL Am. J. Hum. Genet. 100:160-168(2017).
RN [6]
RP INVOLVEMENT IN CILD36, VARIANTS CILD36 43-GLU--PHE-214 DEL; 89-TRP--PHE-214
RP DEL; TYR-133 AND 171-GLN--PHE-214 DEL, CHARACTERIZATION OF VARIANTS CILD36
RP 43-GLU--PHE-214 DEL; 89-TRP--PHE-214 DEL; TYR-133 AND 171-GLN--PHE-214,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH DNAI2, AND
RP FUNCTION.
RX PubMed=28176794; DOI=10.1038/ncomms14279;
RG UK10K Rare Group;
RA Olcese C., Patel M.P., Shoemark A., Kiviluoto S., Legendre M.,
RA Williams H.J., Vaughan C.K., Hayward J., Goldenberg A., Emes R.D.,
RA Munye M.M., Dyer L., Cahill T., Bevillard J., Gehrig C., Guipponi M.,
RA Chantot S., Duquesnoy P., Thomas L., Jeanson L., Copin B., Tamalet A.,
RA Thauvin-Robinet C., Papon J.F., Garin A., Pin I., Vera G., Aurora P.,
RA Fassad M.R., Jenkins L., Boustred C., Cullup T., Dixon M., Onoufriadis A.,
RA Bush A., Chung E.M., Antonarakis S.E., Loebinger M.R., Wilson R.,
RA Armengot M., Escudier E., Hogg C., Amselem S., Sun Z., Bartoloni L.,
RA Blouin J.L., Mitchison H.M.;
RT "X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic
RT axonemal dynein assembly factor PIH1D3.";
RL Nat. Commun. 8:14279-14279(2017).
CC -!- FUNCTION: Plays a role in cytoplasmic pre-assembly of axonemal dynein.
CC {ECO:0000269|PubMed:28041644, ECO:0000269|PubMed:28176794}.
CC -!- SUBUNIT: Interacts with HSPA1A/B and HSP90AA1 (By similarity).
CC Interacts with DNAAF2 and DNAAF4 (PubMed:28041644). Interacts wuth
CC DNAI2 (PubMed:28176794). {ECO:0000250|UniProtKB:Q3KNI6,
CC ECO:0000269|PubMed:28041644, ECO:0000269|PubMed:28176794}.
CC -!- INTERACTION:
CC Q9NQM4; Q4LE39-3: ARID4B; NbExp=3; IntAct=EBI-10239299, EBI-11957452;
CC Q9NQM4; Q2M1V9: BTAF1; NbExp=3; IntAct=EBI-10239299, EBI-10239305;
CC Q9NQM4; Q8IX12: CCAR1; NbExp=3; IntAct=EBI-10239299, EBI-356265;
CC Q9NQM4; Q8IVW4: CDKL3; NbExp=3; IntAct=EBI-10239299, EBI-3919850;
CC Q9NQM4; Q8NHY3: GAS2L2; NbExp=4; IntAct=EBI-10239299, EBI-7960826;
CC Q9NQM4; Q92993: KAT5; NbExp=6; IntAct=EBI-10239299, EBI-399080;
CC Q9NQM4; Q9H1H9: KIF13A; NbExp=3; IntAct=EBI-10239299, EBI-1759129;
CC Q9NQM4; Q99571: P2RX4; NbExp=3; IntAct=EBI-10239299, EBI-2828248;
CC Q9NQM4; Q7Z2X4-3: PID1; NbExp=3; IntAct=EBI-10239299, EBI-11953174;
CC Q9NQM4; Q9Y2S7: POLDIP2; NbExp=3; IntAct=EBI-10239299, EBI-713000;
CC Q9NQM4; P54646: PRKAA2; NbExp=3; IntAct=EBI-10239299, EBI-1383852;
CC Q9NQM4; Q2TAL8: QRICH1; NbExp=3; IntAct=EBI-10239299, EBI-2798044;
CC Q9NQM4; Q9H2S5: RNF39; NbExp=3; IntAct=EBI-10239299, EBI-12235180;
CC Q9NQM4; Q8WW01: TSEN15; NbExp=3; IntAct=EBI-10239299, EBI-372432;
CC Q9NQM4; Q8IY57-5: YAF2; NbExp=3; IntAct=EBI-10239299, EBI-12111538;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:28176794}. Golgi
CC apparatus, trans-Golgi network {ECO:0000269|PubMed:28176794}.
CC Note=Localized to the cytoplasm of spermatogenic cells.
CC {ECO:0000250|UniProtKB:Q3KNI6}.
CC -!- TISSUE SPECIFICITY: Expressed in testis, small intestine, prostate,
CC adrenal gland, spleen, lung, bladder, breast and ovary. Expressed in
CC ciliated epithelial cells (PubMed:28176794).
CC {ECO:0000269|PubMed:12601173, ECO:0000269|PubMed:28176794}.
CC -!- DISEASE: Ciliary dyskinesia, primary, 36, X-linked (CILD36)
CC [MIM:300991]: A form of primary ciliary dyskinesia, a disorder
CC characterized by abnormalities of motile cilia. Respiratory infections
CC leading to chronic inflammation and bronchiectasis are recurrent, due
CC to defects in the respiratory cilia. Some patients exhibit
CC randomization of left-right body asymmetry and situs inversus. Primary
CC ciliary dyskinesia associated with situs inversus is referred to as
CC Kartagener syndrome. CILD36 inheritance is X-linked recessive. About
CC half of CILD36 patients have laterality defects due to ciliary
CC dysfunction at the embryonic node. {ECO:0000269|PubMed:28041644,
CC ECO:0000269|PubMed:28176794}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the PIH1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAO65181.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AL136112; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471120; EAX02716.1; -; Genomic_DNA.
DR EMBL; CH471120; EAX02717.1; -; Genomic_DNA.
DR EMBL; BC033510; AAH33510.1; -; mRNA.
DR EMBL; AY211928; AAO65181.1; ALT_FRAME; mRNA.
DR CCDS; CCDS14528.1; -.
DR RefSeq; NP_001162625.1; NM_001169154.1.
DR RefSeq; NP_775765.1; NM_173494.1.
DR RefSeq; XP_011529157.1; XM_011530855.2.
DR AlphaFoldDB; Q9NQM4; -.
DR SMR; Q9NQM4; -.
DR BioGRID; 126551; 16.
DR IntAct; Q9NQM4; 15.
DR STRING; 9606.ENSP00000441930; -.
DR iPTMnet; Q9NQM4; -.
DR PhosphoSitePlus; Q9NQM4; -.
DR BioMuta; PIH1D3; -.
DR DMDM; 71153251; -.
DR MassIVE; Q9NQM4; -.
DR PaxDb; Q9NQM4; -.
DR PeptideAtlas; Q9NQM4; -.
DR PRIDE; Q9NQM4; -.
DR ProteomicsDB; 82164; -.
DR Antibodypedia; 63940; 51 antibodies from 15 providers.
DR DNASU; 139212; -.
DR Ensembl; ENST00000336387.4; ENSP00000337757.4; ENSG00000080572.14.
DR Ensembl; ENST00000372453.8; ENSP00000361531.3; ENSG00000080572.14.
DR Ensembl; ENST00000535523.6; ENSP00000441930.1; ENSG00000080572.14.
DR GeneID; 139212; -.
DR KEGG; hsa:139212; -.
DR MANE-Select; ENST00000372453.8; ENSP00000361531.3; NM_173494.2; NP_775765.1.
DR UCSC; uc004enc.3; human.
DR CTD; 139212; -.
DR DisGeNET; 139212; -.
DR GeneCards; DNAAF6; -.
DR HGNC; HGNC:28570; DNAAF6.
DR HPA; ENSG00000080572; Group enriched (fallopian tube, testis).
DR MalaCards; DNAAF6; -.
DR MIM; 300933; gene.
DR MIM; 300991; phenotype.
DR neXtProt; NX_Q9NQM4; -.
DR OpenTargets; ENSG00000080572; -.
DR Orphanet; 244; Primary ciliary dyskinesia.
DR VEuPathDB; HostDB:ENSG00000080572; -.
DR eggNOG; ENOG502RZWX; Eukaryota.
DR GeneTree; ENSGT00390000015219; -.
DR HOGENOM; CLU_106090_1_0_1; -.
DR InParanoid; Q9NQM4; -.
DR OMA; ESMVVHK; -.
DR OrthoDB; 1561656at2759; -.
DR PhylomeDB; Q9NQM4; -.
DR TreeFam; TF325677; -.
DR PathwayCommons; Q9NQM4; -.
DR SignaLink; Q9NQM4; -.
DR BioGRID-ORCS; 139212; 6 hits in 687 CRISPR screens.
DR GenomeRNAi; 139212; -.
DR Pharos; Q9NQM4; Tbio.
DR PRO; PR:Q9NQM4; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q9NQM4; protein.
DR Bgee; ENSG00000080572; Expressed in bronchial epithelial cell and 57 other tissues.
DR ExpressionAtlas; Q9NQM4; baseline and differential.
DR Genevisible; Q9NQM4; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005802; C:trans-Golgi network; IDA:UniProtKB.
DR GO; GO:0051087; F:chaperone binding; ISS:UniProtKB.
DR GO; GO:0045505; F:dynein intermediate chain binding; IMP:UniProtKB.
DR GO; GO:0070286; P:axonemal dynein complex assembly; IMP:UniProtKB.
DR GO; GO:0003341; P:cilium movement; IMP:UniProtKB.
DR GO; GO:0030317; P:flagellated sperm motility; IMP:UniProtKB.
DR GO; GO:0036159; P:inner dynein arm assembly; IMP:UniProtKB.
DR GO; GO:0036158; P:outer dynein arm assembly; IMP:UniProtKB.
DR InterPro; IPR026697; DNAAF6.
DR InterPro; IPR041442; PIH1D1/2/3_CS-like.
DR PANTHER; PTHR21083; PTHR21083; 1.
DR Pfam; PF18201; PIH1_CS; 1.
PE 1: Evidence at protein level;
KW Ciliopathy; Cytoplasm; Disease variant; Golgi apparatus;
KW Kartagener syndrome; Primary ciliary dyskinesia; Reference proteome.
FT CHAIN 1..214
FT /note="Dynein axonemal assembly factor 6"
FT /id="PRO_0000079736"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 34..68
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 43..214
FT /note="Missing (in CILD36; strongly decreased expression at
FT protein level; almost complete loss of outer dynein arms
FT and less loss of inner dynein arms in motor cilia;
FT decreased cilia movement; no effect on trans-Golgi network
FT location; abolishes interaction with DNAI2)"
FT /evidence="ECO:0000269|PubMed:28176794"
FT /id="VAR_083176"
FT VARIANT 89..214
FT /note="Missing (in CILD36; almost complete loss of inner
FT dynein arms and less loss of outer dynein arms in motor
FT cilia; immotile cilia; abolishes interaction with DNAI2)"
FT /evidence="ECO:0000269|PubMed:28176794"
FT /id="VAR_083177"
FT VARIANT 119..214
FT /note="Missing (in CILD36; defective preassembly of outer
FT and inner dynein arms)"
FT /evidence="ECO:0000269|PubMed:28041644"
FT /id="VAR_078066"
FT VARIANT 133
FT /note="D -> Y (in CILD36; no effect on expression at
FT protein level; almost complete loss of outer dynein arms
FT and inner dynein arms in motor cilia; immotile cilia;
FT abolishes interaction with DNAI2)"
FT /evidence="ECO:0000269|PubMed:28176794"
FT /id="VAR_083178"
FT VARIANT 171..214
FT /note="Missing (in CILD36; almost complete loss of outer
FT dynein arms and inner dynein arms in motor cilia; immotile
FT cilia)"
FT /evidence="ECO:0000269|PubMed:28176794"
FT /id="VAR_083179"
SQ SEQUENCE 214 AA; 24069 MW; F86B2E210BBC06F6 CRC64;
MESENMDSEN MKTENMESQN VDFESVSSVT ALEALSKLLN PEEEDDSDYG QTNGLSTIGA
MGPGNIGPPQ IEELKVIPET SEENNEDIWN SEEIPEGAEY DDMWDVREIP EYEIIFRQQV
GTEDIFLGLS KKDSSTGCCS ELVAKIKLPN TNPSDIQIDI QETILDLRTP QKKLLITLPE
LVECTSAKAF YIPETETLEI TMTMKRELDI ANFF
