ID DNAI3_HUMAN Reviewed; 891 AA.
AC Q8IWG1; A8K988; Q96L72; Q96NU4;
DT 02-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 24-JAN-2024, entry version 169.
DE RecName: Full=Dynein axonemal intermediate chain 3 {ECO:0000305};
DE AltName: Full=Testis development protein NYD-SP29;
DE AltName: Full=WD repeat-containing protein 63;
GN Name=DNAI3 {ECO:0000312|HGNC:HGNC:30711}; Synonyms=WDR63;
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).
RC TISSUE=Testis;
RA Sha J.H.;
RT "NYD-SP29: a new gene related to testis development.";
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Astrocyte, and Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 NOMENCLATURE.
RX PubMed=21953912; DOI=10.1002/cm.20533;
RA Hom E.F., Witman G.B., Harris E.H., Dutcher S.K., Kamiya R., Mitchell D.R.,
RA Pazour G.J., Porter M.E., Sale W.S., Wirschell M., Yagi T., King S.M.;
RT "A unified taxonomy for ciliary dyneins.";
RL Cytoskeleton 68:555-565(2011).
RN [7]
RP POSSIBLE INVOLVEMENT IN DISEASE.
RX PubMed=29285825; DOI=10.1002/humu.23388;
RA Hofmeister W., Pettersson M., Kurtoglu D., Armenio M., Eisfeldt J.,
RA Papadogiannakis N., Gustavsson P., Lindstrand A.;
RT "Targeted copy number screening highlights an intragenic deletion of WDR63
RT as the likely cause of human occipital encephalocele and abnormal CNS
RT development in zebrafish.";
RL Hum. Mutat. 39:495-505(2018).
RN [8]
RP SUBCELLULAR LOCATION, INTERACTION WITH ACTR2, FUNCTION, AND INDUCTION.
RX PubMed=32128961; DOI=10.15252/embr.201949269;
RA Zhao K., Wang D., Zhao X., Wang C., Gao Y., Liu K., Wang F., Wu X.,
RA Wang X., Sun L., Zang J., Mei Y.;
RT "WDR63 inhibits Arp2/3-dependent actin polymerization and mediates the
RT function of p53 in suppressing metastasis.";
RL EMBO Rep. 21:e49269-e49269(2020).
CC -!- FUNCTION: Acts as a negative regulator of cell migration, invasion, and
CC metastasis downstream of p53/TP53, through inhibition of Arp2/3
CC complex-mediated actin polymerization (PubMed:32128961). Via its
CC association with the multisubunit axonemal dynein complex, is
CC potentially involved in the regulation of cilia function (By
CC similarity). May play a role in osteogenesis of dental tissue-derived
CC mesenchymal stem cells (By similarity). {ECO:0000250|UniProtKB:B2RY71,
CC ECO:0000269|PubMed:32128961}.
CC -!- SUBUNIT: Interacts with ACTR2; this interaction reduces binding of the
CC Arp2/3 complex to the VCA domain of nucleation promoting factors
CC (PubMed:32128961). Part of the multisubunit axonemal dynein complex
CC formed at least of two heavy chains and a number of intermediate and
CC light chains. Found in a associated with the catalytic heavy chain
CC DNAH2, the intermediate chain DNAI4, and the light chain DYNLT1 (By
CC similarity). {ECO:0000250|UniProtKB:B2RY71,
CC ECO:0000269|PubMed:32128961}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:32128961}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8IWG1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IWG1-2; Sequence=VSP_018080;
CC -!- INDUCTION: Up-regulated at the transcriptional level by TP53.
CC {ECO:0000269|PubMed:32128961}.
CC -!- DISEASE: Note=A rare heterozygous in-frame DNAI3 deletion encompassing
CC exons 14-17 has been found in a fetus with encephalocele.
CC Overexpression of human DNAI3 RNA lacking exons 14-17 in zebrafish
CC embryos also results in similar brain malformations, suggesting that
CC DNAI3 defects might be involved in encephalocele formation.
CC {ECO:0000269|PubMed:29285825}.
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DR EMBL; AY049724; AAL06239.1; -; mRNA.
DR EMBL; AK054629; BAB70778.1; -; mRNA.
DR EMBL; AK292603; BAF85292.1; -; mRNA.
DR EMBL; AL358789; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471097; EAW73212.1; -; Genomic_DNA.
DR EMBL; BC040265; AAH40265.1; -; mRNA.
DR CCDS; CCDS702.1; -. [Q8IWG1-1]
DR CCDS; CCDS72818.1; -. [Q8IWG1-2]
DR RefSeq; NP_001275492.1; NM_001288563.1. [Q8IWG1-2]
DR RefSeq; NP_660155.2; NM_145172.4. [Q8IWG1-1]
DR PDB; 8J07; EM; 4.10 A; k1=1-891.
DR PDBsum; 8J07; -.
DR AlphaFoldDB; Q8IWG1; -.
DR EMDB; EMD-35888; -.
DR SMR; Q8IWG1; -.
DR BioGRID; 126018; 3.
DR STRING; 9606.ENSP00000294664; -.
DR GlyGen; Q8IWG1; 1 site, 2 O-linked glycans (1 site).
DR iPTMnet; Q8IWG1; -.
DR PhosphoSitePlus; Q8IWG1; -.
DR BioMuta; WDR63; -.
DR DMDM; 74759634; -.
DR MassIVE; Q8IWG1; -.
DR MaxQB; Q8IWG1; -.
DR PaxDb; 9606-ENSP00000294664; -.
DR PeptideAtlas; Q8IWG1; -.
DR ProteomicsDB; 70858; -. [Q8IWG1-1]
DR ProteomicsDB; 70859; -. [Q8IWG1-2]
DR Antibodypedia; 33558; 32 antibodies from 15 providers.
DR DNASU; 126820; -.
DR Ensembl; ENST00000294664.11; ENSP00000294664.6; ENSG00000162643.13. [Q8IWG1-1]
DR Ensembl; ENST00000326813.12; ENSP00000317463.8; ENSG00000162643.13. [Q8IWG1-2]
DR Ensembl; ENST00000370596.5; ENSP00000359628.1; ENSG00000162643.13. [Q8IWG1-2]
DR GeneID; 126820; -.
DR KEGG; hsa:126820; -.
DR MANE-Select; ENST00000294664.11; ENSP00000294664.6; NM_145172.5; NP_660155.2.
DR UCSC; uc001dkt.5; human. [Q8IWG1-1]
DR AGR; HGNC:30711; -.
DR CTD; 126820; -.
DR DisGeNET; 126820; -.
DR GeneCards; DNAI3; -.
DR HGNC; HGNC:30711; DNAI3.
DR HPA; ENSG00000162643; Group enriched (adrenal gland, choroid plexus, fallopian tube, testis).
DR MIM; 617968; gene.
DR neXtProt; NX_Q8IWG1; -.
DR OpenTargets; ENSG00000162643; -.
DR VEuPathDB; HostDB:ENSG00000162643; -.
DR eggNOG; KOG1587; Eukaryota.
DR GeneTree; ENSGT00940000156924; -.
DR HOGENOM; CLU_009390_1_0_1; -.
DR InParanoid; Q8IWG1; -.
DR OMA; EFICFAN; -.
DR OrthoDB; 5474766at2759; -.
DR PhylomeDB; Q8IWG1; -.
DR TreeFam; TF326991; -.
DR PathwayCommons; Q8IWG1; -.
DR SignaLink; Q8IWG1; -.
DR BioGRID-ORCS; 126820; 14 hits in 1140 CRISPR screens.
DR GenomeRNAi; 126820; -.
DR Pharos; Q8IWG1; Tdark.
DR PRO; PR:Q8IWG1; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q8IWG1; Protein.
DR Bgee; ENSG00000162643; Expressed in bronchial epithelial cell and 107 other cell types or tissues.
DR ExpressionAtlas; Q8IWG1; baseline and differential.
DR Genevisible; Q8IWG1; HS.
DR GO; GO:0005858; C:axonemal dynein complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0036156; C:inner dynein arm; IBA:GO_Central.
DR GO; GO:0071933; F:Arp2/3 complex binding; IDA:UniProtKB.
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:0060294; P:cilium movement involved in cell motility; IBA:GO_Central.
DR GO; GO:0036159; P:inner dynein arm assembly; IBA:GO_Central.
DR GO; GO:0034316; P:negative regulation of Arp2/3 complex-mediated actin nucleation; IMP:UniProtKB.
DR GO; GO:0030336; P:negative regulation of cell migration; IMP:UniProtKB.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISS:UniProtKB.
DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 2.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR InterPro; IPR001680; WD40_rpt.
DR PANTHER; PTHR12442:SF5; DYNEIN AXONEMAL INTERMEDIATE CHAIN 3; 1.
DR PANTHER; PTHR12442; DYNEIN INTERMEDIATE CHAIN; 1.
DR SMART; SM00320; WD40; 3.
DR SUPFAM; SSF50978; WD40 repeat-like; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Coiled coil; Cytoplasm;
KW Reference proteome; Repeat; WD repeat.
FT CHAIN 1..891
FT /note="Dynein axonemal intermediate chain 3"
FT /id="PRO_0000233162"
FT REPEAT 395..435
FT /note="WD 1"
FT /evidence="ECO:0000255"
FT REPEAT 477..533
FT /note="WD 2"
FT /evidence="ECO:0000255"
FT REPEAT 670..709
FT /note="WD 3"
FT /evidence="ECO:0000255"
FT REPEAT 713..753
FT /note="WD 4"
FT /evidence="ECO:0000255"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 818..861
FT /evidence="ECO:0000255"
FT COMPBIAS 1..15
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 247..286
FT /note="WTYPKNATTQYYPREFSEEEKETLKQSKPLVDFLNNASIS -> C (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_018080"
FT VARIANT 674
FT /note="T -> A (in dbSNP:rs17121745)"
FT /id="VAR_057630"
FT VARIANT 798
FT /note="R -> H (in dbSNP:rs709783)"
FT /id="VAR_057631"
FT CONFLICT 108
FT /note="K -> E (in Ref. 1; AAL06239)"
FT /evidence="ECO:0000305"
FT CONFLICT 441
FT /note="G -> D (in Ref. 1; AAL06239)"
FT /evidence="ECO:0000305"
FT CONFLICT 496
FT /note="R -> G (in Ref. 1; AAL06239)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 891 AA; 102935 MW; 982EA7B814BCC1F1 CRC64;
MAPKQKKKTS RGKKRLKPVL AASEDMEPVN MESMGHPEIY PLVLTTKTQE IFNCRIDEDV
TDEQPYKLIN KEDIFEDLRN RAAVSDFHPV KKIVQEYPGN ELLLVYDKDF KYGLNFYLIA
TEEGKENYLN PPEVPEEQEE YKEHIPEDVY IYKPPVSKPW VSLGSEKEIE EESVTESTKQ
ITYMISRKRS EFGAPIKFSD QNASSVKDAY IECTAYPDKN FTLKQLEKDV GMQVIPQIKD
ISTQTKWTYP KNATTQYYPR EFSEEEKETL KQSKPLVDFL NNASISVEIA LQQNEIMNTF
IDDWKYLAEE EGTFGDKTDT HLKEYQSFTD LHSPTEKMIT CVSWHPTIYG LIAVSVAVRL
SFEDRVHFSG KLLLQPSLIL FWSFSDPIHP QLMLESPDDI FCFKFCPSDP NIIAGGCING
QIVMWDITAH ADRIENIKAG GSRSKRATLK PMFLLEPESN KEAMYIRHCA VSSIENGHKK
VITDIHWLSD TFEINRMGSV FENRSGICCQ LVTCSADCTI CFWDIRPQKP LTPQTTEKKK
EESIEIPFDV PSTFLHLDLS WKPLTKVRLS KGETSLDHCP TKISLNEDHL LCKTQDKMLA
QSKTEKAEEM NPYHNLESGM ANLLKPIDDF CTKFFVGTEE GEVIYTDWKM EKDPETGRLM
SKKPVSHHTI HDGTVHTIQR SPFYNDIILT VGGWNVAIWK EGVMTGPLLQ SCCAPKRYTS
GHWSLTRPGV FYIGREDGYI DIWDLLEKTH EPAQSQNICI TMITYIKPWI FSSKQQFIAT
ADYYGTLHIL EIPWTLSRPS TNEMASVNHY FEREVKHLEY VEQRKKIREQ EKKEMELEMA
KKKVKTYQKS KEQMQAELKM DYESYLELEK TVLINLGLIK VTEKGSYMEV M
//
