TTC12_HUMAN
ID TTC12_HUMAN Reviewed; 705 AA.
AC Q9H892; Q8N5H9; Q9NWY3;
DT 15-DEC-2003, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 2.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Tetratricopeptide repeat protein 12;
DE Short=TPR repeat protein 12;
GN Name=TTC12;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Thyroid;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT LEU-73.
RC TISSUE=Blood;
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 INVOLVEMENT IN CILD45, VARIANTS CILD45 203-ILE--SER-705 DEL;
RP 560-ARG--SER-705 DEL AND ARG-567, CHARACTERIZATION OF VARIANTS CILD45
RP 203-ILE--SER-705 DEL; 560-ARG--SER-705 DEL AND ARG-567, FUNCTION,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=31978331; DOI=10.1016/j.ajhg.2019.12.010;
RA Thomas L., Bouhouche K., Whitfield M., Thouvenin G., Coste A., Louis B.,
RA Szymanski C., Bequignon E., Papon J.F., Castelli M., Lemullois M.,
RA Dhalluin X., Drouin-Garraud V., Montantin G., Tissier S., Duquesnoy P.,
RA Copin B., Dastot F., Couvet S., Barbotin A.L., Faucon C., Honore I.,
RA Maitre B., Beydon N., Tamalet A., Rives N., Koll F., Escudier E.,
RA Tassin A.M., Toure A., Mitchell V., Amselem S., Legendre M.;
RT "TTC12 Loss-of-function mutations cause primary ciliary dyskinesia and
RT unveil distinct dynein assembly mechanisms in motile cilia versus
RT flagella.";
RL Am. J. Hum. Genet. 106:153-169(2020).
CC -!- FUNCTION: Cytoplasmic protein that plays a role in the proper assembly
CC of dynein arm complexes in motile cilia in both respiratory cells and
CC sperm flagella. {ECO:0000269|PubMed:31978331}.
CC -!- INTERACTION:
CC Q9H892-2; Q9NX04: C1orf109; NbExp=3; IntAct=EBI-10274410, EBI-8643161;
CC Q9H892-2; Q9UM19: HPCAL4; NbExp=3; IntAct=EBI-10274410, EBI-744820;
CC Q9H892-2; Q8TD10: MIPOL1; NbExp=6; IntAct=EBI-10274410, EBI-2548751;
CC Q9H892-2; Q13153: PAK1; NbExp=3; IntAct=EBI-10274410, EBI-1307;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:31978331}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H892-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H892-2; Sequence=VSP_009119;
CC -!- TISSUE SPECIFICITY: Expressed in testis and in epithelial cells of
CC trachea and bronchial tube. {ECO:0000269|PubMed:31978331}.
CC -!- DISEASE: Ciliary dyskinesia, primary, 45 (CILD45) [MIM:618801]: A form
CC of primary ciliary dyskinesia, a disorder characterized by
CC abnormalities of motile cilia. Respiratory infections leading to
CC chronic inflammation and bronchiectasis are recurrent, due to defects
CC in the respiratory cilia. CILD45 is an autosomal recessive form
CC characterized by onset of symptoms in infancy or early childhood. Male
CC patients have infertility due to immotile sperm.
CC {ECO:0000269|PubMed:31978331}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA91242.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK000542; BAA91242.1; ALT_INIT; mRNA.
DR EMBL; AK023921; BAB14725.1; -; mRNA.
DR EMBL; AP000880; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP002840; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC032355; AAH32355.1; -; mRNA.
DR CCDS; CCDS8360.2; -. [Q9H892-1]
DR RefSeq; NP_001305462.1; NM_001318533.1.
DR RefSeq; NP_060338.3; NM_017868.3. [Q9H892-1]
DR AlphaFoldDB; Q9H892; -.
DR SMR; Q9H892; -.
DR BioGRID; 120307; 23.
DR IntAct; Q9H892; 9.
DR MINT; Q9H892; -.
DR STRING; 9606.ENSP00000433757; -.
DR iPTMnet; Q9H892; -.
DR PhosphoSitePlus; Q9H892; -.
DR BioMuta; TTC12; -.
DR DMDM; 317373286; -.
DR EPD; Q9H892; -.
DR jPOST; Q9H892; -.
DR MassIVE; Q9H892; -.
DR MaxQB; Q9H892; -.
DR PaxDb; Q9H892; -.
DR PeptideAtlas; Q9H892; -.
DR PRIDE; Q9H892; -.
DR ProteomicsDB; 81198; -. [Q9H892-1]
DR ProteomicsDB; 81199; -. [Q9H892-2]
DR Antibodypedia; 32178; 81 antibodies from 17 providers.
DR DNASU; 54970; -.
DR Ensembl; ENST00000314756.7; ENSP00000315160.3; ENSG00000149292.17. [Q9H892-2]
DR Ensembl; ENST00000494714.5; ENSP00000435291.1; ENSG00000149292.17. [Q9H892-2]
DR Ensembl; ENST00000529221.6; ENSP00000433757.1; ENSG00000149292.17. [Q9H892-1]
DR GeneID; 54970; -.
DR KEGG; hsa:54970; -.
DR MANE-Select; ENST00000529221.6; ENSP00000433757.1; NM_017868.4; NP_060338.3.
DR UCSC; uc001pnu.3; human. [Q9H892-1]
DR CTD; 54970; -.
DR DisGeNET; 54970; -.
DR GeneCards; TTC12; -.
DR HGNC; HGNC:23700; TTC12.
DR HPA; ENSG00000149292; Tissue enhanced (testis).
DR MalaCards; TTC12; -.
DR MIM; 610732; gene.
DR MIM; 618801; phenotype.
DR neXtProt; NX_Q9H892; -.
DR OpenTargets; ENSG00000149292; -.
DR Orphanet; 244; Primary ciliary dyskinesia.
DR PharmGKB; PA134886066; -.
DR VEuPathDB; HostDB:ENSG00000149292; -.
DR eggNOG; KOG0548; Eukaryota.
DR GeneTree; ENSGT00940000161758; -.
DR InParanoid; Q9H892; -.
DR OMA; TAVKCYS; -.
DR OrthoDB; 731085at2759; -.
DR PhylomeDB; Q9H892; -.
DR TreeFam; TF332406; -.
DR PathwayCommons; Q9H892; -.
DR SignaLink; Q9H892; -.
DR BioGRID-ORCS; 54970; 7 hits in 1078 CRISPR screens.
DR ChiTaRS; TTC12; human.
DR GenomeRNAi; 54970; -.
DR Pharos; Q9H892; Tbio.
DR PRO; PR:Q9H892; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9H892; protein.
DR Bgee; ENSG00000149292; Expressed in sperm and 135 other tissues.
DR ExpressionAtlas; Q9H892; baseline and differential.
DR Genevisible; Q9H892; HS.
DR GO; GO:0005813; C:centrosome; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0070286; P:axonemal dynein complex assembly; IMP:UniProtKB.
DR GO; GO:0007288; P:sperm axoneme assembly; IMP:UniProtKB.
DR Gene3D; 1.25.10.10; -; 1.
DR Gene3D; 1.25.40.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR001440; TPR_1.
DR InterPro; IPR019734; TPR_repeat.
DR InterPro; IPR043195; TTC12.
DR PANTHER; PTHR46540; PTHR46540; 1.
DR Pfam; PF00515; TPR_1; 1.
DR Pfam; PF13181; TPR_8; 1.
DR SMART; SM00028; TPR; 3.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF48452; SSF48452; 1.
DR PROSITE; PS50005; TPR; 3.
DR PROSITE; PS50293; TPR_REGION; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Ciliopathy; Cilium biogenesis/degradation; Cytoplasm;
KW Disease variant; Phosphoprotein; Primary ciliary dyskinesia;
KW Reference proteome; Repeat; TPR repeat.
FT CHAIN 1..705
FT /note="Tetratricopeptide repeat protein 12"
FT /id="PRO_0000106395"
FT REPEAT 106..139
FT /note="TPR 1"
FT REPEAT 140..173
FT /note="TPR 2"
FT REPEAT 174..207
FT /note="TPR 3"
FT MOD_RES 71
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8BW49"
FT VAR_SEQ 682..705
FT /note="FAAQLRKLHGLEILNSTMKYISDS -> VPAESSHLQFGRESAAPEALSPRR
FT WEEMFHMLVFSLSSVDPPPPPPQTCYP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009119"
FT VARIANT 73
FT /note="M -> L (in dbSNP:rs723077)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_031431"
FT VARIANT 203..705
FT /note="Missing (in CILD45; reduced protein abundance;
FT changed axonemal dynein complex assembly)"
FT /evidence="ECO:0000269|PubMed:31978331"
FT /id="VAR_083923"
FT VARIANT 468
FT /note="M -> L (in dbSNP:rs35852218)"
FT /id="VAR_031432"
FT VARIANT 560..705
FT /note="Missing (in CILD45; reduced protein abundance;
FT changed axonemal dynein complex assembly)"
FT /evidence="ECO:0000269|PubMed:31978331"
FT /id="VAR_083924"
FT VARIANT 563
FT /note="V -> A (in dbSNP:rs35303225)"
FT /id="VAR_061903"
FT VARIANT 567
FT /note="M -> R (in CILD45; reduced protein abundance;
FT changed axonemal dynein complex assembly; loss of sperm
FT axoneme assembly; dbSNP:rs372955658)"
FT /evidence="ECO:0000269|PubMed:31978331"
FT /id="VAR_083925"
FT CONFLICT 361
FT /note="F -> Y (in Ref. 1; BAA91242)"
FT /evidence="ECO:0000305"
FT CONFLICT 649
FT /note="Q -> R (in Ref. 1; BAA91242)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 705 AA; 78756 MW; 2775D30CC9D83C2E CRC64;
MDADKEKDLQ KFLKNVDEIS NLIQEMNSDD PVVQQKAVLE TEKRLLLMEE DQEEDECRTT
LNKTMISPPQ TAMKSAEEIN SEAFLASVEK DAKERAKRRR ENKVLADALK EKGNEAFAEG
NYETAILRYS EGLEKLKDMK VLYTNRAQAY MKLEDYEKAL VDCEWALKCD EKCTKAYFHM
GKANLALKNY SVSRECYKKI LEINPKLQTQ VKGYLNQVDL QEKADLQEKE AHELLDSGKN
TAVTTKNLLE TLSKPDQIPL FYAGGIEILT EMINECTEQT LFRMHNGFSI ISDNEVIRRC
FSTAGNDAVE EMVCVSVLKL WQAVCSRNEE NQRVLVIHHD RARLLAALLS SKVLAIRQQS
FALLLHLAQT ESGRSLIINH LDLTRLLEAL VSFLDFSDKE ANTAMGLFTD LALEERFQVW
FQANLPGVLP ALTGVLKTDP KVSSSSALCQ CIAIMGNLSA EPTTRRHMAA CEEFGDGCLS
LLARCEEDVD LFREVIYTLL GLMMNLCLQA PFVSEVWAVE VSRRCLSLLN SQDGGILTRA
AGVLSRTLSS SLKIVEEALR AGVVKKMMKF LKTGGETASR YAIKILAICT NSYHEAREEV
IRLDKKLSVM MKLLSSEDEV LVGNAALCLG NCMEVPNVAS SLLKTDLLQV LLKLAGSDTQ
KTAVQVNAGI ALGKLCTAEP RFAAQLRKLH GLEILNSTMK YISDS
