DNAI2_HUMAN
ID DNAI2_HUMAN Reviewed; 605 AA.
AC Q9GZS0; C9J0S6; Q8IUW4; Q9H179; Q9NT53;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2010, sequence version 2.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Dynein axonemal intermediate chain 2 {ECO:0000305};
DE AltName: Full=Axonemal dynein intermediate chain 2;
GN Name=DNAI2 {ECO:0000312|HGNC:HGNC:18744};
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 [GENOMIC DNA / MRNA] (ISOFORM 1), AND VARIANT THR-558.
RC TISSUE=Testis;
RX PubMed=11153919; DOI=10.1007/s004390000427;
RA Pennarun G., Chapelin C., Escudier E., Bridoux A.-M., Dastot F.,
RA Cacheux V., Goossens M., Amselem S., Duriez B.;
RT "The human dynein intermediate chain 2 gene (DNAI2): cloning, mapping,
RT expression pattern, and evaluation as a candidate for primary ciliary
RT dyskinesia.";
RL Hum. Genet. 107:642-649(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT THR-558.
RC TISSUE=Testis;
RA Bartoloni L., Mitchison H., Pazour G.J., Meeks M., Chung E., Dickert B.L.,
RA Spiden S., Gehrig C., Rossier C., DeLozier-Blanchet C.D., Blouin J.-L.,
RA Witman G.B., Gardiner R.M., Antonarakis S.E.;
RT "No deleterious mutations were found in three genes (HFH4, LC8, DNAI2) on
RT human chromosome 17q in patients with primary ciliary dyskinesia.";
RL Eur. J. Hum. Genet. 8:126-126(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT THR-558.
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT THR-558.
RC TISSUE=Brain;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 330-605, AND VARIANT THR-558.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP INVOLVEMENT IN CILD9.
RX PubMed=18950741; DOI=10.1016/j.ajhg.2008.10.001;
RA Loges N.T., Olbrich H., Fenske L., Mussaffi H., Horvath J., Fliegauf M.,
RA Kuhl H., Baktai G., Peterffy E., Chodhari R., Chung E.M., Rutman A.,
RA O'Callaghan C., Blau H., Tiszlavicz L., Voelkel K., Witt M.,
RA Zietkiewicz E., Neesen J., Reinhardt R., Mitchison H.M., Omran H.;
RT "DNAI2 mutations cause primary ciliary dyskinesia with defects in the outer
RT dynein arm.";
RL Am. J. Hum. Genet. 83:547-558(2008).
RN [8]
RP INTERACTION WITH HEATR2.
RX PubMed=25232951; DOI=10.1371/journal.pgen.1004577;
RA Diggle C.P., Moore D.J., Mali G., zur Lage P., Ait-Lounis A., Schmidts M.,
RA Shoemark A., Garcia Munoz A., Halachev M.R., Gautier P., Yeyati P.L.,
RA Bonthron D.T., Carr I.M., Hayward B., Markham A.F., Hope J.E.,
RA von Kriegsheim A., Mitchison H.M., Jackson I.J., Durand B., Reith W.,
RA Sheridan E., Jarman A.P., Mill P.;
RT "HEATR2 plays a conserved role in assembly of the ciliary motile
RT apparatus.";
RL PLoS Genet. 10:E1004577-E1004577(2014).
RN [9]
RP INVOLVEMENT IN CILD9.
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 [10]
RP INTERACTION WITH DNAAF6.
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).
RN [11]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=33139725; DOI=10.1038/s41467-020-19113-0;
RA Dougherty G.W., Mizuno K., Noethe-Menchen T., Ikawa Y., Boldt K.,
RA Ta-Shma A., Aprea I., Minegishi K., Pang Y.P., Pennekamp P., Loges N.T.,
RA Raidt J., Hjeij R., Wallmeier J., Mussaffi H., Perles Z., Elpeleg O.,
RA Rabert F., Shiratori H., Letteboer S.J., Horn N., Young S., Struenker T.,
RA Stumme F., Werner C., Olbrich H., Takaoka K., Ide T., Twan W.K.,
RA Biebach L., Grosse-Onnebrink J., Klinkenbusch J.A., Praveen K.,
RA Bracht D.C., Hoeben I.M., Junger K., Guetzlaff J., Cindric S., Aviram M.,
RA Kaiser T., Memari Y., Dzeja P.P., Dworniczak B., Ueffing M., Roepman R.,
RA Bartscherer K., Katsanis N., Davis E.E., Amirav I., Hamada H., Omran H.;
RT "CFAP45 deficiency causes situs abnormalities and asthenospermia by
RT disrupting an axonemal adenine nucleotide homeostasis module.";
RL Nat. Commun. 11:5520-5520(2020).
CC -!- FUNCTION: Part of the dynein complex of respiratory cilia.
CC -!- SUBUNIT: Consists of at least two heavy chains and a number of
CC intermediate and light chains (Probable). Interacts with DNAAF2 (By
CC similarity). Interacts with DNAAF6/PIH1D3 (PubMed:28176794). Interacts
CC with HEATR2; probably involved in outer arm dynein assembly
CC (PubMed:25232951). {ECO:0000250|UniProtKB:A2AC93,
CC ECO:0000269|PubMed:25232951, ECO:0000269|PubMed:28176794, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium axoneme
CC {ECO:0000269|PubMed:33139725}. Dynein axonemal particle
CC {ECO:0000250|UniProtKB:Q4QR00}. Note=Located in the proximal region of
CC respiratory cilia. {ECO:0000269|PubMed:33139725}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9GZS0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9GZS0-2; Sequence=VSP_036541;
CC -!- TISSUE SPECIFICITY: Highly expressed in trachea and testis. Expressed
CC in respiratory ciliated cells (at protein level) (PubMed:33139725).
CC {ECO:0000269|PubMed:33139725}.
CC -!- DISEASE: Ciliary dyskinesia, primary, 9 (CILD9) [MIM:612444]: 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:18950741,
CC ECO:0000269|PubMed:25186273}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the dynein intermediate chain family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAB70790.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
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DR EMBL; AF250288; AAG38489.1; -; mRNA.
DR EMBL; AF253097; AAG38000.1; -; Genomic_DNA.
DR EMBL; AF253087; AAG38000.1; JOINED; Genomic_DNA.
DR EMBL; AF253088; AAG38000.1; JOINED; Genomic_DNA.
DR EMBL; AF253089; AAG38000.1; JOINED; Genomic_DNA.
DR EMBL; AF260782; AAG38000.1; JOINED; Genomic_DNA.
DR EMBL; AF253090; AAG38000.1; JOINED; Genomic_DNA.
DR EMBL; AF253091; AAG38000.1; JOINED; Genomic_DNA.
DR EMBL; AF253092; AAG38000.1; JOINED; Genomic_DNA.
DR EMBL; AF253093; AAG38000.1; JOINED; Genomic_DNA.
DR EMBL; AF253094; AAG38000.1; JOINED; Genomic_DNA.
DR EMBL; AF253095; AAG38000.1; JOINED; Genomic_DNA.
DR EMBL; AF253096; AAG38000.1; JOINED; Genomic_DNA.
DR EMBL; AJ295276; CAC17464.1; -; mRNA.
DR EMBL; AC103809; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471099; EAW89146.1; -; Genomic_DNA.
DR EMBL; BC039582; AAH39582.1; -; mRNA.
DR EMBL; AL137526; CAB70790.1; ALT_SEQ; mRNA.
DR CCDS; CCDS11697.1; -. [Q9GZS0-1]
DR CCDS; CCDS58589.1; -. [Q9GZS0-2]
DR PIR; T46370; T46370.
DR RefSeq; NP_001166281.1; NM_001172810.1. [Q9GZS0-2]
DR RefSeq; NP_075462.3; NM_023036.4. [Q9GZS0-1]
DR AlphaFoldDB; Q9GZS0; -.
DR SMR; Q9GZS0; -.
DR BioGRID; 122183; 91.
DR IntAct; Q9GZS0; 10.
DR STRING; 9606.ENSP00000400252; -.
DR iPTMnet; Q9GZS0; -.
DR PhosphoSitePlus; Q9GZS0; -.
DR BioMuta; DNAI2; -.
DR DMDM; 311033373; -.
DR jPOST; Q9GZS0; -.
DR MassIVE; Q9GZS0; -.
DR PaxDb; Q9GZS0; -.
DR PeptideAtlas; Q9GZS0; -.
DR PRIDE; Q9GZS0; -.
DR ProteomicsDB; 80122; -. [Q9GZS0-1]
DR ProteomicsDB; 80123; -. [Q9GZS0-2]
DR Antibodypedia; 31949; 220 antibodies from 29 providers.
DR DNASU; 64446; -.
DR Ensembl; ENST00000311014.11; ENSP00000308312.6; ENSG00000171595.14. [Q9GZS0-1]
DR Ensembl; ENST00000446837.2; ENSP00000400252.2; ENSG00000171595.14. [Q9GZS0-1]
DR Ensembl; ENST00000582036.5; ENSP00000461950.1; ENSG00000171595.14. [Q9GZS0-2]
DR GeneID; 64446; -.
DR KEGG; hsa:64446; -.
DR MANE-Select; ENST00000311014.11; ENSP00000308312.6; NM_023036.6; NP_075462.3.
DR UCSC; uc002jkf.4; human. [Q9GZS0-1]
DR CTD; 64446; -.
DR DisGeNET; 64446; -.
DR GeneCards; DNAI2; -.
DR GeneReviews; DNAI2; -.
DR HGNC; HGNC:18744; DNAI2.
DR HPA; ENSG00000171595; Group enriched (fallopian tube, testis).
DR MalaCards; DNAI2; -.
DR MIM; 605483; gene.
DR MIM; 612444; phenotype.
DR neXtProt; NX_Q9GZS0; -.
DR OpenTargets; ENSG00000171595; -.
DR Orphanet; 244; Primary ciliary dyskinesia.
DR PharmGKB; PA38669; -.
DR VEuPathDB; HostDB:ENSG00000171595; -.
DR eggNOG; KOG1587; Eukaryota.
DR GeneTree; ENSGT00940000161939; -.
DR HOGENOM; CLU_022406_1_0_1; -.
DR InParanoid; Q9GZS0; -.
DR OMA; WDFFYRQ; -.
DR OrthoDB; 297526at2759; -.
DR PhylomeDB; Q9GZS0; -.
DR TreeFam; TF300553; -.
DR PathwayCommons; Q9GZS0; -.
DR SignaLink; Q9GZS0; -.
DR BioGRID-ORCS; 64446; 15 hits in 1074 CRISPR screens.
DR GeneWiki; DNAI2; -.
DR GenomeRNAi; 64446; -.
DR Pharos; Q9GZS0; Tbio.
DR PRO; PR:Q9GZS0; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9GZS0; protein.
DR Bgee; ENSG00000171595; Expressed in right uterine tube and 95 other tissues.
DR ExpressionAtlas; Q9GZS0; baseline and differential.
DR Genevisible; Q9GZS0; HS.
DR GO; GO:0005858; C:axonemal dynein complex; IMP:MGI.
DR GO; GO:0005930; C:axoneme; IDA:SYSCILIA_CCNET.
DR GO; GO:0120293; C:dynein axonemal particle; ISS:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0036157; C:outer dynein arm; IMP:SYSCILIA_CCNET.
DR GO; GO:0036126; C:sperm flagellum; IDA:SYSCILIA_CCNET.
DR GO; GO:0045504; F:dynein heavy chain binding; IBA:GO_Central.
DR GO; GO:0045503; F:dynein light chain binding; IBA:GO_Central.
DR GO; GO:0003777; F:microtubule motor activity; IMP:MGI.
DR GO; GO:0060271; P:cilium assembly; IMP:MGI.
DR GO; GO:0003341; P:cilium movement; IMP:SYSCILIA_CCNET.
DR GO; GO:0007368; P:determination of left/right symmetry; IMP:SYSCILIA_CCNET.
DR GO; GO:0007018; P:microtubule-based movement; IBA:GO_Central.
DR GO; GO:0036158; P:outer dynein arm assembly; IMP:SYSCILIA_CCNET.
DR Gene3D; 2.130.10.10; -; 2.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR SMART; SM00320; WD40; 5.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Ciliopathy; Cilium;
KW Cilium biogenesis/degradation; Cytoplasm; Cytoskeleton; Dynein;
KW Kartagener syndrome; Microtubule; Motor protein;
KW Primary ciliary dyskinesia; Reference proteome; Repeat; WD repeat.
FT CHAIN 1..605
FT /note="Dynein axonemal intermediate chain 2"
FT /id="PRO_0000114659"
FT REPEAT 150..203
FT /note="WD 1"
FT REPEAT 208..246
FT /note="WD 2"
FT REPEAT 253..294
FT /note="WD 3"
FT REPEAT 301..347
FT /note="WD 4"
FT REPEAT 355..393
FT /note="WD 5"
FT REPEAT 399..437
FT /note="WD 5"
FT REPEAT 443..481
FT /note="WD 5"
FT REGION 568..605
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 582..605
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 450..461
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_036541"
FT VARIANT 495
FT /note="V -> I (in dbSNP:rs28725418)"
FT /id="VAR_061140"
FT VARIANT 558
FT /note="A -> T (in dbSNP:rs1979370)"
FT /evidence="ECO:0000269|PubMed:11153919,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17974005,
FT ECO:0000269|Ref.2, ECO:0000269|Ref.4"
FT /id="VAR_033880"
FT CONFLICT 70
FT /note="E -> K (in Ref. 2; CAC17464)"
FT /evidence="ECO:0000305"
FT CONFLICT 593
FT /note="G -> E (in Ref. 2; CAC17464)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 605 AA; 68821 MW; ACD0CB1D7FBB64EA CRC64;
MEIVYVYVKK RSEFGKQCNF SDRQAELNID IMPNPELAEQ FVERNPVDTG IQCSISMSEH
EANSERFEME TRGVNHVEGG WPKDVNPLEL EQTIRFRKKV EKDENYVNAI MQLGSIMEHC
IKQNNAIDIY EEYFNDEEAM EVMEEDPSAK TINVFRDPQE IKRAATHLSW HPDGNRKLAV
AYSCLDFQRA PVGMSSDSYI WDLENPNKPE LALKPSSPLV TLEFNPKDSH VLLGGCYNGQ
IACWDTRKGS LVAELSTIES SHRDPVYGTI WLQSKTGTEC FSASTDGQVM WWDIRKMSEP
TEVVILDITK KEQLENALGA ISLEFESTLP TKFMVGTEQG IVISCNRKAK TSAEKIVCTF
PGHHGPIYAL QRNPFYPKNF LTVGDWTARI WSEDSRESSI MWTKYHMAYL TDAAWSPVRP
TVFFTTRMDG TLDIWDFMFE QCDPTLSLKV CDEALFCLRV QDNGCLIACG SQLGTTTLLE
VSPGLSTLQR NEKNVASSMF ERETRREKIL EARHREMRLK EKGKAEGRDE EQTDEELAVD
LEALVSKAEE EFFDIIFAEL KKKEADAIKL TPVPQQPSPE EDQVVEEGEE AAGEEGDEEV
EEDLA
