DRC2_HUMAN
ID DRC2_HUMAN Reviewed; 484 AA.
AC Q8IXS2; A6NJG5; B2RBE2; Q8N7G4; Q8NA91; Q96JA0;
DT 17-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Dynein regulatory complex subunit 2 {ECO:0000303|PubMed:24094744};
DE AltName: Full=Coiled-coil domain-containing protein 65;
DE AltName: Full=Testis development protein NYD-SP28;
GN Name=CCDC65; Synonyms=DRC2 {ECO:0000303|PubMed:24094744};
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 TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=17089017;
RA Zheng Y., Zhang J., Wang L., Zhou Z., Xu M., Li J., Sha J.-H.;
RT "Cloning and characterization of a novel sperm tail protein, NYD-SP28.";
RL Int. J. Mol. Med. 18:1119-1125(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 181-484 (ISOFORM 2).
RC TISSUE=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=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=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 [6]
RP FUNCTION, AND INVOLVEMENT IN CILD27.
RX PubMed=24094744; DOI=10.1016/j.ajhg.2013.08.015;
RA Austin-Tse C., Halbritter J., Zariwala M.A., Gilberti R.M., Gee H.Y.,
RA Hellman N., Pathak N., Liu Y., Panizzi J.R., Patel-King R.S.,
RA Tritschler D., Bower R., O'Toole E., Porath J.D., Hurd T.W., Chaki M.,
RA Diaz K.A., Kohl S., Lovric S., Hwang D.Y., Braun D.A., Schueler M.,
RA Airik R., Otto E.A., Leigh M.W., Noone P.G., Carson J.L., Davis S.D.,
RA Pittman J.E., Ferkol T.W., Atkinson J.J., Olivier K.N., Sagel S.D.,
RA Dell S.D., Rosenfeld M., Milla C.E., Loges N.T., Omran H., Porter M.E.,
RA King S.M., Knowles M.R., Drummond I.A., Hildebrandt F.;
RT "Zebrafish ciliopathy screen plus human mutational analysis identifies
RT C21orf59 and CCDC65 defects as causing primary ciliary dyskinesia.";
RL Am. J. Hum. Genet. 93:672-686(2013).
CC -!- FUNCTION: Component of the nexin-dynein regulatory complex (N-DRC), a
CC key regulator of ciliary/flagellar motility which maintains the
CC alignment and integrity of the distal axoneme and regulates microtubule
CC sliding in motile axonemes (By similarity). Plays a critical role in
CC the assembly of N-DRC and also stabilizes the assembly of multiple
CC inner dynein arms and radial spokes. Coassembles with DRC1 to form a
CC central scaffold needed for assembly of the N-DRC and its attachment to
CC the outer doublet microtubules (PubMed:24094744).
CC {ECO:0000250|UniProtKB:A8JB22, ECO:0000269|PubMed:24094744}.
CC -!- SUBUNIT: Component of the nexin-dynein regulatory complex (N-DRC).
CC {ECO:0000250|UniProtKB:A8JB22}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, flagellum basal body
CC {ECO:0000250|UniProtKB:A8JB22}. Cell projection, cilium, flagellum
CC {ECO:0000250|UniProtKB:A8JB22}. Cytoplasm, cytoskeleton, flagellum
CC axoneme {ECO:0000250|UniProtKB:A8JB22}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8IXS2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IXS2-2; Sequence=VSP_024644;
CC -!- TISSUE SPECIFICITY: Highly expressed in adult testis, in spermatocytes
CC and spermatids. Also observed in spermatogonia. Not detected in Leydig
CC cells, nor in fetal testis (at protein level).
CC {ECO:0000269|PubMed:17089017}.
CC -!- DISEASE: Ciliary dyskinesia, primary, 27 (CILD27) [MIM:615504]: 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. Patients may
CC exhibit randomization of left-right body asymmetry and situs inversus,
CC due to dysfunction of monocilia at the embryonic node. Primary ciliary
CC dyskinesia associated with situs inversus is referred to as Kartagener
CC syndrome. {ECO:0000269|PubMed:24094744}. Note=The disease is caused by
CC variants affecting the gene represented in this entry. Cilia
CC ultrastructure show normal outer dynein arms, radial spokes and central
CC pairs, but a reduction in inner dynein arms and nexin links. In 5%-15%
CC of cilia, microtubules are disorganized. Nasal epithelial cilia reveal
CC a stiff, dyskinetic cilia waveform.
CC -!- SIMILARITY: Belongs to the DRC2 family.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC05324.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF382188; AAK60542.1; -; mRNA.
DR EMBL; AK093051; BAC04035.1; -; mRNA.
DR EMBL; AK098529; BAC05324.1; ALT_INIT; mRNA.
DR EMBL; AK314623; BAG37189.1; -; mRNA.
DR EMBL; AC073610; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471111; EAW58020.1; -; Genomic_DNA.
DR EMBL; CH471111; EAW58021.1; -; Genomic_DNA.
DR EMBL; BC039317; AAH39317.2; -; mRNA.
DR CCDS; CCDS8772.1; -. [Q8IXS2-1]
DR RefSeq; NP_149115.2; NM_033124.4. [Q8IXS2-1]
DR AlphaFoldDB; Q8IXS2; -.
DR SMR; Q8IXS2; -.
DR BioGRID; 124553; 10.
DR IntAct; Q8IXS2; 8.
DR STRING; 9606.ENSP00000312706; -.
DR iPTMnet; Q8IXS2; -.
DR PhosphoSitePlus; Q8IXS2; -.
DR BioMuta; CCDC65; -.
DR DMDM; 74728229; -.
DR MassIVE; Q8IXS2; -.
DR MaxQB; Q8IXS2; -.
DR PaxDb; Q8IXS2; -.
DR PeptideAtlas; Q8IXS2; -.
DR PRIDE; Q8IXS2; -.
DR ProteomicsDB; 71055; -. [Q8IXS2-1]
DR ProteomicsDB; 71056; -. [Q8IXS2-2]
DR Antibodypedia; 48594; 57 antibodies from 13 providers.
DR DNASU; 85478; -.
DR Ensembl; ENST00000266984.9; ENSP00000266984.5; ENSG00000139537.11. [Q8IXS2-2]
DR Ensembl; ENST00000320516.5; ENSP00000312706.4; ENSG00000139537.11. [Q8IXS2-1]
DR GeneID; 85478; -.
DR KEGG; hsa:85478; -.
DR MANE-Select; ENST00000320516.5; ENSP00000312706.4; NM_033124.5; NP_149115.2.
DR UCSC; uc001rso.4; human. [Q8IXS2-1]
DR CTD; 85478; -.
DR DisGeNET; 85478; -.
DR GeneCards; CCDC65; -.
DR GeneReviews; CCDC65; -.
DR HGNC; HGNC:29937; CCDC65.
DR HPA; ENSG00000139537; Group enriched (fallopian tube, testis).
DR MalaCards; CCDC65; -.
DR MIM; 611088; gene.
DR MIM; 615504; phenotype.
DR neXtProt; NX_Q8IXS2; -.
DR OpenTargets; ENSG00000139537; -.
DR Orphanet; 244; Primary ciliary dyskinesia.
DR PharmGKB; PA143485417; -.
DR VEuPathDB; HostDB:ENSG00000139537; -.
DR eggNOG; ENOG502QQDD; Eukaryota.
DR GeneTree; ENSGT00940000153804; -.
DR HOGENOM; CLU_026536_1_0_1; -.
DR InParanoid; Q8IXS2; -.
DR OMA; QNHERDV; -.
DR OrthoDB; 815240at2759; -.
DR PhylomeDB; Q8IXS2; -.
DR TreeFam; TF326074; -.
DR PathwayCommons; Q8IXS2; -.
DR SignaLink; Q8IXS2; -.
DR BioGRID-ORCS; 85478; 17 hits in 1069 CRISPR screens.
DR ChiTaRS; CCDC65; human.
DR GenomeRNAi; 85478; -.
DR Pharos; Q8IXS2; Tdark.
DR PRO; PR:Q8IXS2; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q8IXS2; protein.
DR Bgee; ENSG00000139537; Expressed in right uterine tube and 106 other tissues.
DR ExpressionAtlas; Q8IXS2; baseline and differential.
DR Genevisible; Q8IXS2; HS.
DR GO; GO:0005858; C:axonemal dynein complex; IEA:InterPro.
DR GO; GO:0005930; C:axoneme; IBA:GO_Central.
DR GO; GO:0036064; C:ciliary basal body; IDA:GO_Central.
DR GO; GO:0031514; C:motile cilium; IEA:UniProtKB-SubCell.
DR GO; GO:0070286; P:axonemal dynein complex assembly; IBA:GO_Central.
DR GO; GO:0060271; P:cilium assembly; IMP:UniProtKB.
DR GO; GO:0060285; P:cilium-dependent cell motility; IBA:GO_Central.
DR GO; GO:0003352; P:regulation of cilium movement; IMP:UniProtKB.
DR InterPro; IPR039505; DRC1/2_N.
DR InterPro; IPR039750; DRC1/DRC2.
DR PANTHER; PTHR21625; PTHR21625; 1.
DR Pfam; PF14772; NYD-SP28; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Ciliopathy; Cilium; Coiled coil;
KW Cytoplasm; Cytoskeleton; Flagellum; Kartagener syndrome;
KW Primary ciliary dyskinesia; Reference proteome.
FT CHAIN 1..484
FT /note="Dynein regulatory complex subunit 2"
FT /id="PRO_0000284778"
FT COILED 92..160
FT /evidence="ECO:0000255"
FT COILED 374..403
FT /evidence="ECO:0000255"
FT VAR_SEQ 478..484
FT /note="DKQHPTT -> STSPSAPWRDQRRSFFLGSS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_024644"
FT VARIANT 133
FT /note="H -> R (in dbSNP:rs10747556)"
FT /id="VAR_056780"
FT VARIANT 408
FT /note="Y -> C (in dbSNP:rs4760600)"
FT /id="VAR_056781"
FT CONFLICT 164
FT /note="H -> R (in Ref. 2; BAC04035)"
FT /evidence="ECO:0000305"
FT CONFLICT 202
FT /note="N -> D (in Ref. 1; AAK60542)"
FT /evidence="ECO:0000305"
FT CONFLICT 242
FT /note="A -> T (in Ref. 1; AAK60542)"
FT /evidence="ECO:0000305"
FT CONFLICT 308
FT /note="K -> E (in Ref. 2; BAC05324)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 484 AA; 57297 MW; 8B3E8E676512AAF2 CRC64;
MPKKEKMAKT PLSDEKQLLL FQQKLLAEEE MAKKKERLLS QFLKDKLAKE EHNSALNLNK
INTQWRTVLR EVKTRELHKD IEILSQTFER VVDCKDNVIK SLAKDLSEAE EQYAHALRSH
LHNVDQLLAL QRHRLSLLEE SYNMELEALT KEFETERKTI IDQHEKEIHY LQDIFMAMEQ
NYIDSEYESK LEFQSMWNDL KNMNLEEKHF LRLHLENRVE DLWRKFQDVL KNYTDATEDR
KAAFETLQVK DEKSSKEIEV QMKKIQKLQD AITISKGKIM IHSRESEDEN RYIRNDKELV
LVQLRKLKAQ RTQARAASQK NLVRLTLESN ATLKALRKIV DKGEKILKLA EICRKFETEE
EKVLPFYSSV LTPKEQEGIQ KNNLEELTEE LTKVMVDYIG MENFWKRYNK VKLEQLSLQH
RRAQLLDING KLREMLKQYL DGISVSDEVL SQLNPLFIVN YQSNLLQPLS IRIAHPGDKQ
HPTT
