ID TT21A_HUMAN Reviewed; 1320 AA. AC Q8NDW8; A1L388; B4DYF6; B4DYJ3; D3YTE7; D4PHA5; Q6P5W8; Q8N7G5; Q8NA02; DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 3. DT 28-JUN-2023, entry version 157. DE RecName: Full=Tetratricopeptide repeat protein 21A {ECO:0000303|PubMed:30929735}; DE Short=TPR repeat protein 21A {ECO:0000303|PubMed:30929735}; DE AltName: Full=Stress-inducible protein 2 {ECO:0000303|PubMed:12543795}; GN Name=TTC21A {ECO:0000303|PubMed:30929735, ECO:0000312|HGNC:HGNC:30761}; GN Synonyms=STI2 {ECO:0000303|PubMed:12543795}; 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), TISSUE SPECIFICITY, AND VARIANT RP LYS-1316. RC TISSUE=Pancreas; RX PubMed=12543795; RA Protopopov A., Kashuba V., Zabarovska V.I., Muravenko O.V., Lerman M.I., RA Klein G., Zabarovsky E.R.; RT "An integrated physical and gene map of the 3.5-Mb chromosome 3p21.3 (AP20) RT region implicated in major human epithelial malignancies."; RL Cancer Res. 63:404-412(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] (ISOFORM 5), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF RP 440-1320 (ISOFORMS 5/6/7), AND VARIANT LEU-1055. 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=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [4] RP INVOLVEMENT IN SPGF37, VARIANTS SPGF37 CYS-114 AND 777-GLN--PRO-1320 DEL, RP FUNCTION, DEVELOPMENTAL STAGE, AND INTERACTION WITH IFT20; IFT52 AND RP IFT140. 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 (PubMed:30929735). Interacts with IFT52 CC (PubMed:30929735). Interacts with IFT140 (PubMed:30929735). CC {ECO:0000269|PubMed:30929735}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=Q8NDW8-1; Sequence=Displayed; CC Name=3; CC IsoId=Q8NDW8-3; Sequence=VSP_026297; CC Name=5; CC IsoId=Q8NDW8-5; Sequence=VSP_038429, VSP_038430, VSP_038431; CC Name=6; CC IsoId=Q8NDW8-6; Sequence=VSP_038428, VSP_038429, VSP_038431; CC Name=7; CC IsoId=Q8NDW8-7; Sequence=VSP_038431; CC -!- TISSUE SPECIFICITY: Strongly expressed in testis. CC {ECO:0000269|PubMed:12543795}. CC -!- DEVELOPMENTAL STAGE: Expressed in preleptotene spermatocytes, pachytene CC spermatocytes, round spermatids and elongated spermatids (at protein CC level). {ECO:0000269|PubMed:30929735}. CC -!- DISEASE: Spermatogenic failure 37 (SPGF37) [MIM:618429]: An autosomal CC recessive infertility disorder characterized by CC asthenoteratozoospermia. Spermatozoa exhibit multiple morphologic CC abnormalities, primarily consisting of short or absent flagella, and CC neck defects at the head-tail junction. {ECO:0000269|PubMed:30929735}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the TTC21 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAC04129.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AJ487015; CAD31647.1; -; mRNA. DR EMBL; AK093313; BAC04129.1; ALT_INIT; mRNA. DR EMBL; AK098528; BAC05323.1; -; mRNA. DR EMBL; AK302408; BAG63718.1; -; mRNA. DR EMBL; AK302465; BAG63755.1; -; mRNA. DR EMBL; AC092053; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC138124; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS43068.2; -. [Q8NDW8-6] DR CCDS; CCDS46800.1; -. [Q8NDW8-1] DR RefSeq; NP_001098983.2; NM_001105513.2. [Q8NDW8-6] DR RefSeq; NP_665698.2; NM_145755.2. [Q8NDW8-1] DR AlphaFoldDB; Q8NDW8; -. DR SMR; Q8NDW8; -. DR BioGRID; 128260; 11. DR IntAct; Q8NDW8; 7. DR STRING; 9606.ENSP00000398211; -. DR iPTMnet; Q8NDW8; -. DR PhosphoSitePlus; Q8NDW8; -. DR BioMuta; TTC21A; -. DR DMDM; 296453007; -. DR jPOST; Q8NDW8; -. DR MassIVE; Q8NDW8; -. DR PaxDb; Q8NDW8; -. DR PeptideAtlas; Q8NDW8; -. DR ProteomicsDB; 73070; -. [Q8NDW8-1] DR ProteomicsDB; 73071; -. [Q8NDW8-3] DR ProteomicsDB; 73072; -. [Q8NDW8-5] DR ProteomicsDB; 73073; -. [Q8NDW8-6] DR ProteomicsDB; 73074; -. [Q8NDW8-7] DR TopDownProteomics; Q8NDW8-6; -. [Q8NDW8-6] DR Antibodypedia; 50732; 8 antibodies from 7 providers. DR DNASU; 199223; -. DR Ensembl; ENST00000431162.6; ENSP00000398211.2; ENSG00000168026.19. [Q8NDW8-1] DR Ensembl; ENST00000440121.1; ENSP00000410882.1; ENSG00000168026.19. [Q8NDW8-6] DR GeneID; 199223; -. DR KEGG; hsa:199223; -. DR UCSC; uc003cjc.3; human. [Q8NDW8-1] DR AGR; HGNC:30761; -. DR CTD; 199223; -. DR DisGeNET; 199223; -. DR GeneCards; TTC21A; -. DR HGNC; HGNC:30761; TTC21A. DR HPA; ENSG00000168026; Tissue enriched (testis). DR MalaCards; TTC21A; -. DR MIM; 611430; gene. DR MIM; 618429; phenotype. DR neXtProt; NX_Q8NDW8; -. DR OpenTargets; ENSG00000168026; -. DR Orphanet; 276234; Non-syndromic male infertility due to sperm motility disorder. DR PharmGKB; PA134915959; -. DR VEuPathDB; HostDB:ENSG00000168026; -. DR eggNOG; ENOG502QQAB; Eukaryota. DR GeneTree; ENSGT00390000005979; -. DR HOGENOM; CLU_006149_0_0_1; -. DR InParanoid; Q8NDW8; -. DR OMA; QCPCLAG; -. DR OrthoDB; 121960at2759; -. DR PhylomeDB; Q8NDW8; -. DR TreeFam; TF314664; -. DR PathwayCommons; Q8NDW8; -. DR SignaLink; Q8NDW8; -. DR BioGRID-ORCS; 199223; 10 hits in 1146 CRISPR screens. DR ChiTaRS; TTC21A; human. DR GenomeRNAi; 199223; -. DR Pharos; Q8NDW8; Tdark. DR PRO; PR:Q8NDW8; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q8NDW8; protein. DR Bgee; ENSG00000168026; Expressed in right uterine tube and 106 other tissues. DR ExpressionAtlas; Q8NDW8; baseline and differential. DR Genevisible; Q8NDW8; HS. 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; Tetratricopeptide repeat domain; 6. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR InterPro; IPR019734; TPR_repeat. DR InterPro; IPR040364; TTC21A/TTC21B. DR PANTHER; PTHR14699; STI2 PROTEIN-RELATED; 1. DR PANTHER; PTHR14699:SF2; TETRATRICOPEPTIDE REPEAT PROTEIN 21A; 1. DR Pfam; PF13432; TPR_16; 1. DR Pfam; PF13174; TPR_6; 1. DR Pfam; PF13181; TPR_8; 1. DR SMART; SM00028; TPR; 13. DR SUPFAM; SSF48452; TPR-like; 4. DR PROSITE; PS50005; TPR; 9. DR PROSITE; PS50293; TPR_REGION; 4. PE 1: Evidence at protein level; KW Alternative splicing; Differentiation; Disease variant; Reference proteome; KW Repeat; Spermatogenesis; TPR repeat. FT CHAIN 1..1320 FT /note="Tetratricopeptide repeat protein 21A" FT /id="PRO_0000291915" FT REPEAT 4..38 FT /note="TPR 1" FT REPEAT 110..143 FT /note="TPR 2" FT REPEAT 146..180 FT /note="TPR 3" FT REPEAT 181..213 FT /note="TPR 4" FT REPEAT 215..247 FT /note="TPR 5" FT REPEAT 334..367 FT /note="TPR 6" FT REPEAT 502..534 FT /note="TPR 7" FT REPEAT 572..605 FT /note="TPR 8" FT REPEAT 728..761 FT /note="TPR 9" FT REPEAT 762..795 FT /note="TPR 10" FT REPEAT 797..828 FT /note="TPR 11" FT REPEAT 837..869 FT /note="TPR 12" FT REPEAT 889..922 FT /note="TPR 13" FT REPEAT 924..956 FT /note="TPR 14" FT REPEAT 957..990 FT /note="TPR 15" FT REPEAT 1028..1061 FT /note="TPR 16" FT REPEAT 1201..1234 FT /note="TPR 17" FT REPEAT 1236..1268 FT /note="TPR 18" FT REPEAT 1270..1303 FT /note="TPR 19" FT VAR_SEQ 1..879 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_026297" FT VAR_SEQ 147..187 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000305" FT /id="VSP_038428" FT VAR_SEQ 268..275 FT /note="Missing (in isoform 5 and isoform 6)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_038429" FT VAR_SEQ 386..396 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_038430" FT VAR_SEQ 515 FT /note="S -> SG (in isoform 5, isoform 6 and isoform 7)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_038431" FT VARIANT 91 FT /note="R -> Q (in dbSNP:rs1112438)" FT /id="VAR_032879" FT VARIANT 108 FT /note="V -> L (in dbSNP:rs17855763)" FT /id="VAR_032880" FT VARIANT 114 FT /note="Y -> C (in SPGF37; dbSNP:rs750057655)" FT /evidence="ECO:0000269|PubMed:30929735" FT /id="VAR_082207" FT VARIANT 290 FT /note="R -> K (in dbSNP:rs1274972)" FT /id="VAR_032881" FT VARIANT 293 FT /note="E -> K (in dbSNP:rs1274971)" FT /id="VAR_032882" FT VARIANT 622 FT /note="R -> W (in dbSNP:rs35581078)" FT /id="VAR_032883" FT VARIANT 719 FT /note="R -> H (in dbSNP:rs9861353)" FT /id="VAR_059861" FT VARIANT 719 FT /note="R -> Q (in dbSNP:rs9861353)" FT /id="VAR_032884" FT VARIANT 777..1320 FT /note="Missing (in SPGF37)" FT /evidence="ECO:0000269|PubMed:30929735" FT /id="VAR_082208" FT VARIANT 1055 FT /note="R -> L (in dbSNP:rs35934336)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_032885" FT VARIANT 1160 FT /note="S -> R (in dbSNP:rs34201693)" FT /id="VAR_032886" FT VARIANT 1316 FT /note="R -> K (in dbSNP:rs704959)" FT /evidence="ECO:0000269|PubMed:12543795" FT /id="VAR_032887" FT CONFLICT 153 FT /note="V -> G (in Ref. 1; CAD31647)" FT /evidence="ECO:0000305" FT CONFLICT 174 FT /note="I -> T (in Ref. 2; BAG63718)" FT /evidence="ECO:0000305" FT CONFLICT 802 FT /note="G -> D (in Ref. 2; BAG63755)" FT /evidence="ECO:0000305" FT CONFLICT 803 FT /note="K -> E (in Ref. 1; CAD31647)" FT /evidence="ECO:0000305" FT CONFLICT 838 FT /note="K -> R (in Ref. 2; BAG63718)" FT /evidence="ECO:0000305" FT CONFLICT 1095 FT /note="M -> T (in Ref. 1; CAD31647)" FT /evidence="ECO:0000305" FT CONFLICT 1165 FT /note="L -> P (in Ref. 2; BAC04129)" FT /evidence="ECO:0000305" FT CONFLICT 1291 FT /note="E -> K (in Ref. 2; BAG63755)" FT /evidence="ECO:0000305" SQ SEQUENCE 1320 AA; 150944 MW; CFB949A8E2B702DE CRC64; MSSNDSSLMA GIIYYSQEKY FHHVQQAAAV GLEKFSNDPV LKFFKAYGVL KEEHIQDAIS DLESIRHHPD VSLCSTMALI YAHKRCEIID REAIQELEYS LKEIRKTVSG TALYYAGLFL WLIGRHDKAK EYIDRMLKIS RGFREAYVLR GWVDLTSDKP HTAKKAIEYL EQGIQDTKDV LGLMGKAMYF MMQQNYSEAL EVVNQITVTS GSFLPALVLK MQLFLARQDW EQTVEMGHRI LEKDESNIDA CQILTVHELA REGNMTTVSS LKTQKATNHV RNLIKALETR EPENPSLHLK KIIVVSRLCG SHQVILGLVC SFIERTFMAT PSYVHVATEL GYLFILKNQV KEALLWYSEA MKLDKDGMAG LTGIILCHIL EGHLEEAEYR LEFLKEVQKS LGKSEVLIFL QALLMSRKHK GEEETTALLK EAVELHFSSM QGIPLGSEYF EKLDPYFLVC IAKEYLLFCP KQPRLPGQIV SPLLKQVAVI LNPVVKAAPA LIDPLYLMAQ VRYYSELENA QSILQRCLEL DPASVDAHLL MCQIYLAQGN FGMCFHCLEL GVSHNFQVRD HPLYHLIKAR ALNKAGDYPE AIKTLKMVIK LPALKKEEGR KFLRPSVQPS QRASILLELV EALRLNGELH EATKVMQDTI NEFGGTPEEN RITIANVDLV LSKGNVDVAL NMLRNILPKQ SCYMEAREKM ANIYLQTLRD RRLYIRCYRE LCEHLPGPHT SLLLGDALMS ILEPEKALEV YDEAYRQNPH DASLASRIGH AYVKAHQYTE AIEYYEAAQK INGQDFLCCD LGKLLLKLKK VNKAEKVLKQ ALEHDIVQDI PSMMNDVKCL LLLAKVYKSH KKEAVIETLN KALDLQSRIL KRVPLEQPEM IPSQKQLAAS ICIQFAEHYL AEKEYDKAVQ SYKDVFSYLP TDNKVMLELA QLYLLQGHLD LCEQHCAILL QTEQNHETAS VLMADLMFRK QKHEAAINLY HQVLEKAPDN FLVLHKLIDL LRRSGKLEDI PAFFELAKKV SSRVPLEPGF NYCRGIYCWH IGQPNEALKF LNKARKDSTW GQSAIYHMVQ ICLNPDNEVV GGEAFENQGA ESNYMEKKEL EQQGVSTAEK LLREFYPHSD SSQTQLRLLQ GLCRLATREK ANMEAALGSF IQIAQAEKDS VPALLALAQA YVFLKQIPKA RMQLKRLAKT PWVLSEAEDL EKSWLLLADI YCQGSKFDLA LELLRRCVQY NKSCYKAYEY MGFIMEKEQS YKDAVTNYKL AWKYSHHANP AIGFKLAFNY LKDKKFVEAI EICNDVLREH PDYPKIREEI LEKARRSLRP //