DC2I2_MOUSE
ID DC2I2_MOUSE Reviewed; 537 AA.
AC Q5U4F6; A2BE91;
DT 21-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 07-OCT-2020, sequence version 3.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Cytoplasmic dynein 2 intermediate chain 2;
DE AltName: Full=Dynein 2 intermediate chain 2;
DE AltName: Full=WD repeat-containing protein 34;
GN Name=Dync2i2; Synonyms=Wdr34;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 16-537.
RC STRAIN=C57BL/6J; TISSUE=Embryonic germ cell;
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 TISSUE SPECIFICITY.
RX PubMed=19521662; DOI=10.1007/s00018-009-0059-6;
RA Gao D., Wang R., Li B., Yang Y., Zhai Z., Chen D.Y.;
RT "WDR34 is a novel TAK1-associated suppressor of the IL-1R/TLR3/TLR4-induced
RT NF-kappaB activation pathway.";
RL Cell. Mol. Life Sci. 66:2573-2584(2009).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Kidney, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=24183451; DOI=10.1016/j.ajhg.2013.10.003;
RA Schmidts M., Vodopiutz J., Christou-Savina S., Cortes C.R.,
RA McInerney-Leo A.M., Emes R.D., Arts H.H., Tuysuz B., D'Silva J., Leo P.J.,
RA Giles T.C., Oud M.M., Harris J.A., Koopmans M., Marshall M., Elcioglu N.,
RA Kuechler A., Bockenhauer D., Moore A.T., Wilson L.C., Janecke A.R.,
RA Hurles M.E., Emmet W., Gardiner B., Streubel B., Dopita B., Zankl A.,
RA Kayserili H., Scambler P.J., Brown M.A., Beales P.L., Wicking C.,
RA Duncan E.L., Mitchison H.M.;
RT "Mutations in the gene encoding IFT dynein complex component WDR34 cause
RT Jeune asphyxiating thoracic dystrophy.";
RL Am. J. Hum. Genet. 93:932-944(2013).
RN [6]
RP DISRUPTION PHENOTYPE, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=28379358; DOI=10.1093/hmg/ddx127;
RA Wu C., Li J., Peterson A., Tao K., Wang B.;
RT "Loss of dynein-2 intermediate chain Wdr34 results in defects in retrograde
RT ciliary protein trafficking and Hedgehog signaling in the mouse.";
RL Hum. Mol. Genet. 26:2386-2397(2017).
CC -!- FUNCTION: Acts as one of several non-catalytic accessory components of
CC the cytoplasmic dynein 2 complex (dynein-2 complex), a motor protein
CC complex that drives the movement of cargos along microtubules within
CC cilia and flagella in concert with the intraflagellar transport (IFT)
CC system. DYNC2I2 plays a major role in retrograde ciliary protein
CC trafficking and in ciliogenesis (PubMed:28379358). Required also to
CC maintain a functional transition zone (By similarity).
CC {ECO:0000250|UniProtKB:Q96EX3, ECO:0000269|PubMed:28379358}.
CC -!- FUNCTION: Acts as a negative regulator of the Toll-like and IL-1R
CC receptor signaling pathways. Inhibits the MAP3K7-induced NF-kappa-B
CC activation pathway. Inhibits MAP3K7 phosphorylation at 'Thr-184' and
CC 'Thr-187' upon Il-1 beta stimulation. {ECO:0000250|UniProtKB:Q96EX3}.
CC -!- SUBUNIT: The cytoplasmic dynein 2 complex consists of two catalytic
CC heavy chains (HCs) and a number of non-catalytic subunits presented by
CC intermediate chains (ICs), light intermediate chains (LICs) and light
CC chains (LCs). Among them, a heavy chain (DYNC2H1), two intermediate
CC chains (DYNC2I2 and DYNC2I1), a light intermediate chain (DYNC2LI1),
CC and a light chain (DYNLT2B) are unique to the cytoplasmic dynein
CC complex 2, but a subset of the light chains are also shared by dynein-1
CC and dynein-2 complexes. Interacts with DYNC2I1; their C-terminal
CC domains each bind a copy of the heavy chain, and their extended N-
CC terminal regions are held together by an array of light chain dimers.
CC Interacts with DYNLL2; this interaction is essential for dynein-2-
CC mediated retrograde trafficking of ciliary proteins. Interacts with
CC DYNLRB1; this interaction is essential for dynein-2-mediated retrograde
CC trafficking of ciliary proteins. Interacts (via the WD domains) with
CC MAP3K7 and TAB3. Interacts (via WD domains) with TAB2 (via C-terminus).
CC Interacts (via WD domains) with TRAF6 (via TRAF-type domains).
CC {ECO:0000250|UniProtKB:Q96EX3}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q96EX3}.
CC Cytoplasm, cytoskeleton, cilium basal body
CC {ECO:0000269|PubMed:24183451}. Cytoplasm, cytoskeleton, cilium axoneme
CC {ECO:0000269|PubMed:24183451}. Cell projection, cilium
CC {ECO:0000269|PubMed:28379358}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250|UniProtKB:Q96EX3}. Cell
CC projection, filopodium {ECO:0000269|PubMed:28379358}. Note=Concentrates
CC around the centrioles and basal bodies also showing axonemal staining.
CC {ECO:0000269|PubMed:24183451}.
CC -!- TISSUE SPECIFICITY: Expressed in brain, thymus, heart, lung, liver,
CC spleen, kidney, testis and intestine. {ECO:0000269|PubMed:19521662}.
CC -!- DISRUPTION PHENOTYPE: The majority of deficient mice die in
CC midgestation from 10.5 dpc to 12.5 dpc. The mutant embryos exhibit open
CC brain, spinal bifida, microphthalmia, and polydactyly. Inactivation of
CC the protein results also in short and stumpy cilia with an abnormal
CC accumulation of ciliary proteins and defects in Sonic hedgehog
CC signaling. {ECO:0000269|PubMed:28379358}.
CC -!- SIMILARITY: Belongs to the dynein light intermediate chain family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH85113.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; BX005298; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL928926; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC085113; AAH85113.1; ALT_INIT; mRNA.
DR CCDS; CCDS15865.2; -.
DR RefSeq; NP_001008498.2; NM_001008498.2.
DR AlphaFoldDB; Q5U4F6; -.
DR SMR; Q5U4F6; -.
DR BioGRID; 214952; 3.
DR IntAct; Q5U4F6; 2.
DR MINT; Q5U4F6; -.
DR STRING; 10090.ENSMUSP00000109340; -.
DR iPTMnet; Q5U4F6; -.
DR PhosphoSitePlus; Q5U4F6; -.
DR MaxQB; Q5U4F6; -.
DR PaxDb; Q5U4F6; -.
DR PRIDE; Q5U4F6; -.
DR ProteomicsDB; 297943; -.
DR ProteomicsDB; 333076; -.
DR Antibodypedia; 31223; 120 antibodies from 18 providers.
DR DNASU; 71820; -.
DR Ensembl; ENSMUST00000113711; ENSMUSP00000109340; ENSMUSG00000039715.
DR GeneID; 71820; -.
DR KEGG; mmu:71820; -.
DR CTD; 89891; -.
DR MGI; MGI:1919070; Dync2i2.
DR VEuPathDB; HostDB:ENSMUSG00000039715; -.
DR eggNOG; KOG1587; Eukaryota.
DR GeneTree; ENSGT00940000158483; -.
DR HOGENOM; CLU_031167_1_0_1; -.
DR InParanoid; Q5U4F6; -.
DR OMA; KKYLFCV; -.
DR OrthoDB; 1453532at2759; -.
DR TreeFam; TF300553; -.
DR Reactome; R-MMU-5620924; Intraflagellar transport.
DR BioGRID-ORCS; 71820; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Wdr34; mouse.
DR PRO; PR:Q5U4F6; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q5U4F6; protein.
DR Bgee; ENSMUSG00000039715; Expressed in spermatocyte and 187 other tissues.
DR GO; GO:0005930; C:axoneme; IDA:UniProtKB.
DR GO; GO:0005814; C:centriole; IDA:UniProtKB.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0036064; C:ciliary basal body; IDA:UniProtKB.
DR GO; GO:0097014; C:ciliary plasm; IBA:GO_Central.
DR GO; GO:0005929; C:cilium; IMP:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005868; C:cytoplasmic dynein complex; IPI:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030175; C:filopodium; IMP:UniProtKB.
DR GO; GO:0045504; F:dynein heavy chain binding; IBA:GO_Central.
DR GO; GO:0045503; F:dynein light chain binding; ISO:MGI.
DR GO; GO:0060271; P:cilium assembly; IDA:UniProtKB.
DR GO; GO:0035721; P:intraciliary retrograde transport; IMP:UniProtKB.
DR GO; GO:0042073; P:intraciliary transport; IBA:GO_Central.
DR GO; GO:0007018; P:microtubule-based movement; IBA:GO_Central.
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 Pfam; PF00400; WD40; 2.
DR SMART; SM00320; WD40; 5.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW Cell projection; Cytoplasm; Cytoskeleton; Phosphoprotein;
KW Reference proteome; Repeat; WD repeat.
FT CHAIN 1..537
FT /note="Cytoplasmic dynein 2 intermediate chain 2"
FT /id="PRO_0000223621"
FT REPEAT 216..256
FT /note="WD 1"
FT /evidence="ECO:0000255"
FT REPEAT 265..309
FT /note="WD 2"
FT /evidence="ECO:0000255"
FT REPEAT 391..431
FT /note="WD 3"
FT /evidence="ECO:0000255"
FT REPEAT 434..474
FT /note="WD 4"
FT /evidence="ECO:0000255"
FT REPEAT 481..521
FT /note="WD 5"
FT /evidence="ECO:0000255"
FT REGION 80..93
FT /note="DYNLL2 binding"
FT /evidence="ECO:0000250|UniProtKB:Q96EX3"
FT REGION 107..132
FT /note="DYNLRB1 binding"
FT /evidence="ECO:0000250|UniProtKB:Q96EX3"
FT MOD_RES 15
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 537 AA; 58174 MW; 5F73AA6DB7E536F6 CRC64;
MAMCASPRPF RRVGSAGAAA LAAGGAGGAE RRGRPAPLQD ETLGVASVPS QWRSVQGIRG
ETKSCQTAGI ATAESSAQAR THADAQVQTE APEEPAAMAP VSQYDTLRLE AFLRRVEAMV
IRELNNNWQS HAFDGYEVNW TEQQQTVSCL HTLVYPLAQG QGLHVTGISW NSTGSVLACA
YGRLDDGDWS TLKSYVCTWN LDRQGLNPQQ PSVVVEVPSA VMCLAFHPTQ PSHIAGGLYS
GEVLVWDMSR PEDPLLWRTG LTDDTHTDPV YQVLWLPEPR HSHRFQVLSA ATDGKVLLWR
GSGAGQLRLT KGFALAVQQL PRSTKLKKPP RGETEVGVTS VAFSSFDSSL FVLGTEGGFP
LKCSLASEVA ALTRMPSSVP LRAPVQFTFS PHGGPVYSVS CSPFHRNLFL SAGTDGHVHL
YSMLQAQPLT SLQLSHKYLF AVRWSPVRPL VFAAASGEGD VQLFDLQKSS QKPTVSITQT
QDGSPVYCLE FNSQQTQLLA AGDAKGMVKV WQLSTAFTEQ GPREVEDLDQ LEAEITT
