TT21A_MOUSE
ID TT21A_MOUSE Reviewed; 1314 AA.
AC Q8C0S4; Q0HA37; Q3V0A2; Q9D5Q9;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 26-JUN-2007, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Tetratricopeptide repeat protein 21A;
DE Short=TPR repeat protein 21A;
DE AltName: Full=Tetratricopeptide repeat-containing hedgehog modulator 2;
GN Name=Ttc21a; Synonyms=Thm2;
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 [MRNA] (ISOFORM 1).
RC STRAIN=A/J;
RA Tran P.V., Herron B.J., Scherz P.J., Qiu H., Turbe-Doan A., Parker K.,
RA Beier D.R.;
RT "Thm1 is a novel negative regulator of mouse Sonic hedgehog signaling.";
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30929735; DOI=10.1016/j.ajhg.2019.02.020;
RA Liu W., He X., Yang S., Zouari R., Wang J., Wu H., Kherraf Z.E., Liu C.,
RA Coutton C., Zhao R., Tang D., Tang S., Lv M., Fang Y., Li W., Li H.,
RA Zhao J., Wang X., Zhao S., Zhang J., Arnoult C., Jin L., Zhang Z.,
RA Ray P.F., Cao Y., Zhang F.;
RT "Bi-allelic mutations in TTC21A induce asthenoteratospermia in humans and
RT mice.";
RL Am. J. Hum. Genet. 104:738-748(2019).
CC -!- FUNCTION: Intraflagellar transport (IFT)-associated protein required
CC for spermatogenesis (PubMed:30929735). Required for sperm flagellar
CC formation and intraflagellar transport (PubMed:30929735).
CC {ECO:0000269|PubMed:30929735}.
CC -!- SUBUNIT: Interacts with IFT20. Interacts with IFT52. Interacts with
CC IFT140. {ECO:0000250|UniProtKB:Q8NDW8}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8C0S4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8C0S4-2; Sequence=VSP_026304, VSP_026305;
CC -!- DISRUPTION PHENOTYPE: Male mice display strongly reduced fertility
CC (PubMed:30929735). Spermatozoa show significantly reduced motility and
CC morphologic abnormalities are observed, such as primarily tailless
CC spermatozoa with an abnormal head-tail junction, as well as short and
CC coiled flagella (PubMed:30929735). Structural abnormalities of the
CC connecting piece are observed during spermiogenesis and multiple
CC structural defects of the flagella, with a greatly increased percentage
CC of flagella exhibiting abnormal principal pieces and end pieces
CC (PubMed:30929735). Axonemal structural abnormalities, such as abnormal
CC bulges, extra peripheral microtubule doublets, lack of central-pair
CC microtubules, absent dynein arms, and abnormal arrangement of the 9
CC peripheral microtubule doubles, are also frequently observed
CC (PubMed:30929735). {ECO:0000269|PubMed:30929735}.
CC -!- SIMILARITY: Belongs to the TTC21 family. {ECO:0000305}.
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DR EMBL; DQ011665; AAY78492.1; -; mRNA.
DR EMBL; AK015017; BAB29674.1; -; mRNA.
DR EMBL; AK029952; BAC26695.1; -; mRNA.
DR EMBL; AK133304; BAE21602.1; -; mRNA.
DR EMBL; BC133699; AAI33700.1; -; mRNA.
DR CCDS; CCDS40805.1; -. [Q8C0S4-1]
DR RefSeq; NP_083011.2; NM_028735.3. [Q8C0S4-1]
DR AlphaFoldDB; Q8C0S4; -.
DR BioGRID; 216453; 2.
DR STRING; 10090.ENSMUSP00000035100; -.
DR iPTMnet; Q8C0S4; -.
DR PhosphoSitePlus; Q8C0S4; -.
DR MaxQB; Q8C0S4; -.
DR PaxDb; Q8C0S4; -.
DR PRIDE; Q8C0S4; -.
DR ProteomicsDB; 297731; -. [Q8C0S4-1]
DR ProteomicsDB; 297732; -. [Q8C0S4-2]
DR Antibodypedia; 50732; 7 antibodies from 6 providers.
DR DNASU; 74052; -.
DR Ensembl; ENSMUST00000035100; ENSMUSP00000035100; ENSMUSG00000032514. [Q8C0S4-1]
DR GeneID; 74052; -.
DR KEGG; mmu:74052; -.
DR UCSC; uc009sbs.1; mouse. [Q8C0S4-2]
DR UCSC; uc009sbt.1; mouse. [Q8C0S4-1]
DR CTD; 199223; -.
DR MGI; MGI:1921302; Ttc21a.
DR VEuPathDB; HostDB:ENSMUSG00000032514; -.
DR eggNOG; ENOG502QQAB; Eukaryota.
DR GeneTree; ENSGT00390000005979; -.
DR HOGENOM; CLU_006149_0_0_1; -.
DR InParanoid; Q8C0S4; -.
DR OMA; QCPCLAG; -.
DR OrthoDB; 45918at2759; -.
DR PhylomeDB; Q8C0S4; -.
DR TreeFam; TF314664; -.
DR BioGRID-ORCS; 74052; 2 hits in 71 CRISPR screens.
DR PRO; PR:Q8C0S4; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q8C0S4; protein.
DR Bgee; ENSMUSG00000032514; Expressed in otolith organ and 42 other tissues.
DR Genevisible; Q8C0S4; MM.
DR GO; GO:0005929; C:cilium; IEA:GOC.
DR GO; GO:0030991; C:intraciliary transport particle A; IBA:GO_Central.
DR GO; GO:0030317; P:flagellated sperm motility; IMP:UniProtKB.
DR GO; GO:0035721; P:intraciliary retrograde transport; IBA:GO_Central.
DR GO; GO:0061512; P:protein localization to cilium; IBA:GO_Central.
DR GO; GO:0007286; P:spermatid development; IMP:UniProtKB.
DR Gene3D; 1.25.40.10; -; 6.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR019734; TPR_repeat.
DR InterPro; IPR040364; TTC21A/TTC21B.
DR PANTHER; PTHR14699; PTHR14699; 1.
DR Pfam; PF13176; TPR_7; 1.
DR Pfam; PF13181; TPR_8; 1.
DR SMART; SM00028; TPR; 14.
DR SUPFAM; SSF48452; SSF48452; 4.
DR PROSITE; PS50005; TPR; 11.
DR PROSITE; PS50293; TPR_REGION; 4.
PE 1: Evidence at protein level;
KW Alternative splicing; Differentiation; Reference proteome; Repeat;
KW Spermatogenesis; TPR repeat.
FT CHAIN 1..1314
FT /note="Tetratricopeptide repeat protein 21A"
FT /id="PRO_0000291916"
FT REPEAT 110..143
FT /note="TPR 1"
FT REPEAT 214..247
FT /note="TPR 2"
FT REPEAT 326..359
FT /note="TPR 3"
FT REPEAT 494..527
FT /note="TPR 4"
FT REPEAT 529..561
FT /note="TPR 5"
FT REPEAT 565..598
FT /note="TPR 6"
FT REPEAT 616..649
FT /note="TPR 7"
FT REPEAT 721..754
FT /note="TPR 8"
FT REPEAT 755..788
FT /note="TPR 9"
FT REPEAT 790..821
FT /note="TPR 10"
FT REPEAT 831..863
FT /note="TPR 11"
FT REPEAT 883..916
FT /note="TPR 12"
FT REPEAT 918..950
FT /note="TPR 13"
FT REPEAT 951..984
FT /note="TPR 14"
FT REPEAT 986..1018
FT /note="TPR 15"
FT REPEAT 1022..1055
FT /note="TPR 16"
FT REPEAT 1195..1228
FT /note="TPR 17"
FT REPEAT 1230..1262
FT /note="TPR 18"
FT REPEAT 1264..1297
FT /note="TPR 19"
FT VAR_SEQ 1227..1233
FT /note="SCCRAYE -> AKLTSLG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_026304"
FT VAR_SEQ 1234..1314
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_026305"
FT CONFLICT 16
FT /note="S -> N (in Ref. 2; BAB29674)"
FT /evidence="ECO:0000305"
FT CONFLICT 208
FT /note="L -> M (in Ref. 2; BAC26695)"
FT /evidence="ECO:0000305"
FT CONFLICT 650
FT /note="P -> L (in Ref. 1; AAY78492 and 3; AAI33700)"
FT /evidence="ECO:0000305"
FT CONFLICT 1037
FT /note="Q -> K (in Ref. 2; BAE21602)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1314 AA; 148617 MW; A1790B1DA679883B CRC64;
MSSDDSSLMA SIIYYSQEKY FHHVLQAANV GLERYSSDPA LQFFRAYGIL GEDHIHDAIS
ELEGIQSHPD TSLCAVIALL SAHKSCDTID IEAVQELESS LKEIRRSASS TALYYASLFL
WFMGHHDKAR EYVDHMLKVS SGSKEGYVLK GWVDLTSSKP HVVKKSIKYL EQGTQDTKDV
LGLMGKATYF MTQQNFSGAL EVANQVTLAC SNFLPALVLK MKLFLARQDW DQTIETGQRI
LEKDENNIDA WQILAVHELV KEGNTDRAAD RVRNLIKALE TGEPHNPNLH LKKILVISRL
CGRHQVVHRL VSGFLERIFM ATPSCALVAT ELGYLFILHQ QVKEACLWYK EAMKLEENRL
AALAGSIWCQ ILQGQLEEAA HQLEFLKEVQ QSLGKSELLV FLQALVAAKK QRLEQEATAL
LKEAVEVHFS SMQGLALSPE YFEKLDPLFL VCIAKEYLHF CPKQPRSPGQ LVSPLLKQVA
MILSPVVKVA PAMMEPLYVT AQVKFLSGEL ENAQSTLQRC LELDPTFVDA HLLMSQIYLA
QGNFAMCSHC LELGVSHNFQ VRDHPLYHFI KARALNKTGD YAEAIKTLKM IIKVPTSKAE
EGRKSQSPSV RPSERASILL ELVEALRLNG ELHEATKIMQ DAINEFSGTP EEMRITVANV
DLALSKGNVD LALNMLRGIT PKQPCYTEAK EKMASIYLHT RKDVRLYIGC YVELCEHLPG
PHSSLLLGDA FMNIQEPEKA LEVYDEAYRK NPHDASLVSR IGQAYVKTHQ YAKAINYYEA
AQKISGQDFL CCELAELLLK LKKYHKAEKV LKQALERDSG VKDIPSMINE VKCLLLLAKV
YKSHKKEEVM ETLNLALDLQ SRILKRVPLE QSEMIPFQNQ LAASICIQIG EHHLAEKDYD
SALKSYKDAL AYSPTDSKVV LELAHLYLLL GQLDLCEQRC APLLEMEQTH ERAAVMLADL
MFRRQNYETA INLYHQVLEK APDNFLVLNK LVDLLRRSGK LEEAPAFFEL AKKVSSRVPL
EPGFNYCQGI YFWHIGQPNE ALRFLNKARK DSTWGQLATC YMVQICLNPD NEIVGGEAFE
SLVGDSNSAS RKESQQHGVR TAEKLLREFY PHSESGQTQL RLLQNLCLLA TREKANVEVA
LGAFIEMAQA EKDSIPALLA MAQAYILLKQ VPKARTQLKR LAKVPWTVDE AEDLEKSWLL
LADIYCQGGK FDLALELLRR CLQYNKSCCR AYEYMGFIME KEQSYKDAAT NYELAWKYSH
QANPAIGFKL AFNYLKDKKF VDAIEVCHSV LTEHPKYPKI REEILEKAQG SLRP
