TT21A_HUMAN
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 03-AUG-2022, entry version 154.
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};
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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 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 PRIDE; 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; 7 antibodies from 6 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 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; 45918at2759; -.
DR PhylomeDB; Q8NDW8; -.
DR TreeFam; TF314664; -.
DR PathwayCommons; Q8NDW8; -.
DR SignaLink; Q8NDW8; -.
DR BioGRID-ORCS; 199223; 10 hits in 1068 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; -; 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; PF13174; TPR_6; 1.
DR Pfam; PF13181; TPR_8; 1.
DR SMART; SM00028; TPR; 13.
DR SUPFAM; SSF48452; SSF48452; 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
