TTC3_HUMAN
ID TTC3_HUMAN Reviewed; 2025 AA.
AC P53804; A8K7H7; B2RPA7; D3DSG9; D3DSH2; D3DSH3; O60767; P78476; P78477;
AC Q569I2; Q6P578; Q9UEK4;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 2.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=E3 ubiquitin-protein ligase TTC3;
DE EC=2.3.2.27 {ECO:0000269|PubMed:20059950, ECO:0000269|PubMed:30696809};
DE AltName: Full=Protein DCRR1;
DE AltName: Full=RING finger protein 105;
DE AltName: Full=RING-type E3 ubiquitin transferase TTC3 {ECO:0000305};
DE AltName: Full=TPR repeat protein D;
DE AltName: Full=Tetratricopeptide repeat protein 3;
DE Short=TPR repeat protein 3;
GN Name=TTC3; Synonyms=DCRR1, RNF105, TPRD;
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 TPRDI), AND VARIANT HIS-1751.
RC TISSUE=Brain;
RX PubMed=8724848; DOI=10.1093/dnares/3.1.9;
RA Ohira M., Ootsuyama A., Suzuki E., Ichikawa H., Seki N., Nagase T.,
RA Nomura N., Ohki M.;
RT "Identification of a novel human gene containing the tetratricopeptide
RT repeat domain from the Down syndrome region of chromosome 21.";
RL DNA Res. 3:9-16(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS TPRDI; TPRDII AND TPRDIII), AND
RP VARIANT HIS-1751.
RC TISSUE=Fetal brain, and Placenta;
RX PubMed=8947847; DOI=10.1093/oxfordjournals.jbchem.a021485;
RA Tsukahara F., Hattori M., Muraki T., Sakaki Y.;
RT "Identification and cloning of a novel cDNA belonging to tetratricopeptide
RT repeat gene family from Down syndrome-critical region 21q22.2.";
RL J. Biochem. 120:820-827(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10830953; DOI=10.1038/35012518;
RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT "The DNA sequence of human chromosome 21.";
RL Nature 405:311-319(2000).
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM TPRDI).
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-627 (ISOFORM TPRDI).
RC TISSUE=Small intestine;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 85-2025 (ISOFORM TPRDI), AND VARIANT THR-840.
RX PubMed=9254009; DOI=10.3109/10425179709034031;
RA Eki T., Abe M., Naitou M., Sasanuma S.I., Nohata J., Kawashima K.,
RA Ahmad I., Hanaoka F., Murakami Y.;
RT "Cloning and characterization of novel gene, DCRR1, expressed from Down's
RT syndrome critical region of human chromosome 21q22.2.";
RL DNA Seq. 7:153-164(1997).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 121-616 (ISOFORM TPRDI).
RC TISSUE=Fetal brain;
RX PubMed=9503011; DOI=10.1006/geno.1997.5146;
RA Dahmane N., Ait-Ghezala G., Gosset P., Chamoun Z., Dufresne-Zacharia M.-C.,
RA Lopes C., Rabatel N., Gassanova-Maugenre S., Chettouh Z., Abramowski V.,
RA Fayet E., Yaspo M.-L., Korn B., Blouin J.-L., Lehrach H., Poustka A.,
RA Antonarakis S.E., Sinet P.-M., Creau N., Delabar J.-M.;
RT "Transcriptional map of the 2.5-Mb CBR-ERG region of chromosome 21 involved
RT in Down syndrome.";
RL Genomics 48:12-23(1998).
RN [9]
RP FUNCTION, AND INTERACTION WITH CIT.
RX PubMed=17488780; DOI=10.1242/jcs.000703;
RA Berto G., Camera P., Fusco C., Imarisio S., Ambrogio C., Chiarle R.,
RA Silengo L., Di Cunto F.;
RT "The Down syndrome critical region protein TTC3 inhibits neuronal
RT differentiation via RhoA and Citron kinase.";
RL J. Cell Sci. 120:1859-1867(2007).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, INTERACTION
RP WITH AKT1; AKT2 AND AKT3, PHOSPHORYLATION AT SER-378, AND MUTAGENESIS OF
RP SER-378.
RX PubMed=20059950; DOI=10.1016/j.devcel.2009.09.007;
RA Suizu F., Hiramuki Y., Okumura F., Matsuda M., Okumura A.J., Hirata N.,
RA Narita M., Kohno T., Yokota J., Bohgaki M., Obuse C., Hatakeyama S.,
RA Obata T., Noguchi M.;
RT "The E3 ligase TTC3 facilitates ubiquitination and degradation of
RT phosphorylated Akt.";
RL Dev. Cell 17:800-810(2009).
RN [11]
RP FUNCTION.
RX PubMed=24695496; DOI=10.1371/journal.pone.0093721;
RA Berto G.E., Iobbi C., Camera P., Scarpa E., Iampietro C., Bianchi F.,
RA Gai M., Sgro F., Cristofani F., Gaertner A., Dotti C.G., Di Cunto F.;
RT "The DCR protein TTC3 affects differentiation and Golgi compactness in
RT neurons through specific actin-regulating pathways.";
RL PLoS ONE 9:E93721-E93721(2014).
RN [12]
RP INTERACTION WITH POLG AND HSP70.
RX PubMed=29290964; DOI=10.18632/oncotarget.22476;
RA Gong Y., Wang X., Shang X., Xiao S.P., Li W., Shang Y., Dou F.;
RT "Tetratricopeptide repeat domain 3 overexpression tends to form aggregates
RT and inhibit ubiquitination and degradation of DNA polymerase gamma.";
RL Oncotarget 8:106475-106485(2017).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, INTERACTION WITH SMURF2, AND
RP INDUCTION BY TGFB1.
RX PubMed=30696809; DOI=10.1038/s41419-019-1308-8;
RA Kim J.H., Ham S., Lee Y., Suh G.Y., Lee Y.S.;
RT "TTC3 contributes to TGF-beta1-induced epithelial-mesenchymal transition
RT and myofibroblast differentiation, potentially through SMURF2
RT ubiquitylation and degradation.";
RL Cell Death Dis. 10:92-92(2019).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=30203323; DOI=10.1007/s12017-018-8509-7;
RA Gong Y., Wang K., Xiao S.P., Mi P., Li W., Shang Y., Dou F.;
RT "Overexpressed TTC3 Protein Tends to be Cleaved into Fragments and Form
RT Aggregates in the Nucleus.";
RL NeuroMolecular Med. 21:85-96(2019).
RN [15]
RP VARIANT [LARGE SCALE ANALYSIS] MET-1289.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [16]
RP VARIANT CYS-1038.
RX PubMed=27066578; DOI=10.1212/nxg.0000000000000041;
RA Kohli M.A., Cukier H.N., Hamilton-Nelson K.L., Rolati S., Kunkle B.W.,
RA Whitehead P.L., Zuechner S.L., Farrer L.A., Martin E.R., Beecham G.W.,
RA Haines J.L., Vance J.M., Cuccaro M.L., Gilbert J.R., Schellenberg G.D.,
RA Carney R.M., Pericak-Vance M.A.;
RT "Segregation of a rare TTC3 variant in an extended family with late-onset
RT Alzheimer disease.";
RL Neurol. Genet. 2:E41-E41(2016).
CC -!- FUNCTION: E3 ubiquitin-protein ligase which catalyzes the formation of
CC 'Lys-48'-polyubiquitin chains (PubMed:20059950, PubMed:30696809).
CC Mediates the ubiquitination and subsequent degradation of
CC phosphorylated Akt (AKT1, AKT2 and AKT3) in the nucleus
CC (PubMed:20059950). Acts as a terminal regulator of Akt signaling after
CC activation; its phosphorylation by Akt, which is a prerequisite for
CC ubiquitin ligase activity, suggests the existence of a regulation
CC mechanism required to control Akt levels after activation
CC (PubMed:20059950). Positively regulates TGFB1-induced epithelial-
CC mesenchymal transition and myofibroblast differentiation by mediating
CC the ubiquitination and subsequent degradation of SMURF2
CC (PubMed:30696809). Regulates neuronal differentiation by regulating
CC actin remodeling and Golgi organization via a signaling cascade
CC involving RHOA, CIT and ROCK (PubMed:17488780, PubMed:24695496).
CC Inhibits cell proliferation (PubMed:30203323).
CC {ECO:0000269|PubMed:17488780, ECO:0000269|PubMed:20059950,
CC ECO:0000269|PubMed:24695496, ECO:0000269|PubMed:30203323,
CC ECO:0000269|PubMed:30696809}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:20059950,
CC ECO:0000269|PubMed:30696809};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:20059950, ECO:0000269|PubMed:30696809}.
CC -!- SUBUNIT: Interacts (when phosphorylated on Ser-378) with AKT1, AKT2 and
CC AKT3 (when phosphorylated) (PubMed:20059950). Interacts with CIT
CC (PubMed:17488780). Interacts with POLG (PubMed:29290964). Interacts
CC with HSP70 (PubMed:29290964). Interacts with SMURF2 (PubMed:30696809).
CC {ECO:0000269|PubMed:17488780, ECO:0000269|PubMed:20059950,
CC ECO:0000269|PubMed:29290964, ECO:0000269|PubMed:30696809}.
CC -!- INTERACTION:
CC P53804; P31749: AKT1; NbExp=4; IntAct=EBI-2681313, EBI-296087;
CC P53804; P31751: AKT2; NbExp=5; IntAct=EBI-2681313, EBI-296058;
CC P53804; Q9Y243: AKT3; NbExp=2; IntAct=EBI-2681313, EBI-296115;
CC P53804; Q9HAU4: SMURF2; NbExp=2; IntAct=EBI-2681313, EBI-396727;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20059950,
CC ECO:0000269|PubMed:30203323}. Cytoplasm {ECO:0000269|PubMed:30203323}.
CC Golgi apparatus {ECO:0000250|UniProtKB:D3ZSP7}. Note=Nuclear
CC localization may be dependent on the proteolytic cleavage of full
CC length protein in the cytoplasm (PubMed:30203323). This cleavage may
CC reveal an N-terminal nuclear localization signal, allowing N-terminal
CC fragments to enter the nucleus (PubMed:30203323).
CC {ECO:0000269|PubMed:30203323}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=TPRDI;
CC IsoId=P53804-1; Sequence=Displayed;
CC Name=TPRDII;
CC IsoId=P53804-2; Sequence=VSP_006554;
CC Name=TPRDIII;
CC IsoId=P53804-3; Sequence=VSP_006555;
CC -!- TISSUE SPECIFICITY: Found in all tissues examined.
CC -!- INDUCTION: Up-regulated by TGFB1 signaling.
CC {ECO:0000269|PubMed:30696809}.
CC -!- PTM: Phosphorylation on Ser-378 by Akt is required for ubiquitin ligase
CC activity. {ECO:0000269|PubMed:20059950}.
CC -!- PTM: Proteolytically cleaved into differently sized N- and C-terminal
CC fragments. {ECO:0000269|PubMed:30203323}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH63033.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=AAH92466.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
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DR EMBL; D83077; BAA11769.1; -; mRNA.
DR EMBL; D84294; BAA12301.1; -; mRNA.
DR EMBL; D84295; BAA12302.1; -; mRNA.
DR EMBL; D84296; BAA12303.1; -; mRNA.
DR EMBL; AP001429; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP001432; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471079; EAX09716.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09717.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09718.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09719.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09720.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09721.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09722.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09723.1; -; Genomic_DNA.
DR EMBL; BC063033; AAH63033.1; ALT_SEQ; mRNA.
DR EMBL; BC092466; AAH92466.1; ALT_SEQ; mRNA.
DR EMBL; BC137345; AAI37346.1; -; mRNA.
DR EMBL; AK291992; BAF84681.1; -; mRNA.
DR EMBL; D83327; BAA23666.1; -; mRNA.
DR EMBL; AJ001866; CAA05057.1; -; mRNA.
DR CCDS; CCDS13651.1; -. [P53804-1]
DR PIR; JC5020; JC5020.
DR RefSeq; NP_001001894.1; NM_001001894.2. [P53804-1]
DR RefSeq; NP_001307633.1; NM_001320704.1.
DR RefSeq; NP_001317610.1; NM_001330681.1. [P53804-3]
DR RefSeq; NP_001317611.1; NM_001330682.1. [P53804-3]
DR RefSeq; NP_001317612.1; NM_001330683.1. [P53804-1]
DR RefSeq; NP_003307.3; NM_003316.3. [P53804-1]
DR RefSeq; XP_011528042.1; XM_011529740.2. [P53804-2]
DR AlphaFoldDB; P53804; -.
DR BioGRID; 113118; 60.
DR ELM; P53804; -.
DR IntAct; P53804; 38.
DR MINT; P53804; -.
DR STRING; 9606.ENSP00000381981; -.
DR iPTMnet; P53804; -.
DR PhosphoSitePlus; P53804; -.
DR BioMuta; TTC3; -.
DR DMDM; 313104040; -.
DR EPD; P53804; -.
DR jPOST; P53804; -.
DR MassIVE; P53804; -.
DR MaxQB; P53804; -.
DR PaxDb; P53804; -.
DR PeptideAtlas; P53804; -.
DR PRIDE; P53804; -.
DR ProteomicsDB; 56623; -. [P53804-1]
DR ProteomicsDB; 56624; -. [P53804-2]
DR ProteomicsDB; 56625; -. [P53804-3]
DR Antibodypedia; 8442; 73 antibodies from 18 providers.
DR DNASU; 7267; -.
DR Ensembl; ENST00000354749.6; ENSP00000346791.2; ENSG00000182670.13. [P53804-1]
DR Ensembl; ENST00000355666.5; ENSP00000347889.1; ENSG00000182670.13. [P53804-1]
DR Ensembl; ENST00000399017.6; ENSP00000381981.2; ENSG00000182670.13. [P53804-1]
DR GeneID; 7267; -.
DR KEGG; hsa:7267; -.
DR UCSC; uc002yvz.4; human. [P53804-1]
DR CTD; 7267; -.
DR DisGeNET; 7267; -.
DR GeneCards; TTC3; -.
DR HGNC; HGNC:12393; TTC3.
DR HPA; ENSG00000182670; Low tissue specificity.
DR MIM; 602259; gene.
DR neXtProt; NX_P53804; -.
DR OpenTargets; ENSG00000182670; -.
DR PharmGKB; PA37058; -.
DR VEuPathDB; HostDB:ENSG00000182670; -.
DR eggNOG; KOG0800; Eukaryota.
DR GeneTree; ENSGT00940000154465; -.
DR HOGENOM; CLU_001829_1_0_1; -.
DR InParanoid; P53804; -.
DR OMA; HDDQGLV; -.
DR OrthoDB; 16272at2759; -.
DR PhylomeDB; P53804; -.
DR TreeFam; TF333981; -.
DR PathwayCommons; P53804; -.
DR SignaLink; P53804; -.
DR SIGNOR; P53804; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 7267; 8 hits in 1119 CRISPR screens.
DR ChiTaRS; TTC3; human.
DR GeneWiki; TTC3; -.
DR GenomeRNAi; 7267; -.
DR Pharos; P53804; Tbio.
DR PRO; PR:P53804; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; P53804; protein.
DR Bgee; ENSG00000182670; Expressed in cortical plate and 208 other tissues.
DR ExpressionAtlas; P53804; baseline and differential.
DR Genevisible; P53804; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 1.25.40.10; -; 2.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR019734; TPR_repeat.
DR InterPro; IPR043866; TTC3/DZIP3_dom.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF19179; DUF5861; 1.
DR Pfam; PF13639; zf-RING_2; 1.
DR SMART; SM00184; RING; 1.
DR SMART; SM00028; TPR; 4.
DR SUPFAM; SSF48452; SSF48452; 2.
DR PROSITE; PS50005; TPR; 2.
DR PROSITE; PS50293; TPR_REGION; 2.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Golgi apparatus; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; TPR repeat; Transferase;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..2025
FT /note="E3 ubiquitin-protein ligase TTC3"
FT /id="PRO_0000106378"
FT REPEAT 231..264
FT /note="TPR 1"
FT REPEAT 266..298
FT /note="TPR 2"
FT REPEAT 536..572
FT /note="TPR 3"
FT REPEAT 576..609
FT /note="TPR 4"
FT ZN_FING 1957..1997
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 1..230
FT /note="Interaction with POLG"
FT /evidence="ECO:0000269|PubMed:29290964"
FT REGION 423..458
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 786..805
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1012..1068
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1215..1295
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1773..1842
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1894..1944
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2004..2025
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1035..1064
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1258..1283
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1894..1909
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1914..1934
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2008..2025
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 378
FT /note="Phosphoserine; by PKB/AKT2"
FT /evidence="ECO:0000269|PubMed:20059950"
FT MOD_RES 1009
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88196"
FT MOD_RES 1061
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88196"
FT VAR_SEQ 1..310
FT /note="Missing (in isoform TPRDIII)"
FT /evidence="ECO:0000303|PubMed:8947847"
FT /id="VSP_006555"
FT VAR_SEQ 1..233
FT /note="Missing (in isoform TPRDII)"
FT /evidence="ECO:0000303|PubMed:8947847"
FT /id="VSP_006554"
FT VARIANT 840
FT /note="M -> T (in dbSNP:rs1053808)"
FT /evidence="ECO:0000269|PubMed:9254009"
FT /id="VAR_020312"
FT VARIANT 1038
FT /note="S -> C (in an extended family with high risk of
FT late-onset Alzheimer Disease; dbSNP:rs377155188)"
FT /evidence="ECO:0000269|PubMed:27066578"
FT /id="VAR_082645"
FT VARIANT 1154
FT /note="P -> S (in dbSNP:rs1053840)"
FT /id="VAR_044428"
FT VARIANT 1289
FT /note="K -> M (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035868"
FT VARIANT 1751
FT /note="D -> H (in dbSNP:rs1053966)"
FT /evidence="ECO:0000269|PubMed:8724848,
FT ECO:0000269|PubMed:8947847"
FT /id="VAR_024676"
FT MUTAGEN 378
FT /note="S->A: Abolishes phosphorylation by Akt and impairs
FT ubiquitin ligase activity on Akt."
FT /evidence="ECO:0000269|PubMed:20059950"
FT CONFLICT 9
FT /note="F -> Y (in Ref. 5; AAH92466)"
FT /evidence="ECO:0000305"
FT CONFLICT 121
FT /note="N -> D (in Ref. 8; CAA05057)"
FT /evidence="ECO:0000305"
FT CONFLICT 139
FT /note="K -> R (in Ref. 8; CAA05057)"
FT /evidence="ECO:0000305"
FT CONFLICT 232
FT /note="E -> G (in Ref. 8; CAA05057)"
FT /evidence="ECO:0000305"
FT CONFLICT 276
FT /note="L -> P (in Ref. 8; CAA05057)"
FT /evidence="ECO:0000305"
FT CONFLICT 437
FT /note="K -> Q (in Ref. 5; AAH63033)"
FT /evidence="ECO:0000305"
FT CONFLICT 495
FT /note="Q -> P (in Ref. 7; BAA23666)"
FT /evidence="ECO:0000305"
FT CONFLICT 1700
FT /note="E -> V (in Ref. 7; BAA23666)"
FT /evidence="ECO:0000305"
FT CONFLICT 1822
FT /note="A -> T (in Ref. 7; BAA23666)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2025 AA; 229869 MW; C80BC8E1970B6725 CRC64;
MDNFAEGDFT VADYALLEDC PHVDDCVFAA EFMSNDYVRV TQLYCDGVGV QYKDYIQSER
NLEFDICSIW CSKPISVLQD YCDAIKINIF WPLLFQHQNS SVISRLHPCV DANNSRASEI
NLKKLQHLEL MEDIVDLAKK VANDSFLIGG LLRIGCKIEN KILAMEEALN WIKYAGDVTI
LTKLGSIDNC WPMLSIFFTE YKYHITKIVM EDCNLLEELK TQSCMDCIEE GELMKMKGNE
EFSKERFDIA IIYYTRAIEY RPENYLLYGN RALCFLRTGQ FRNALGDGKR ATILKNTWPK
GHYRYCDALS MLGEYDWALQ ANIKAQKLCK NDPEGIKDLI QQHVKLQKQI EDLQGRTANK
DPIKAFYENR AYTPRSLSAP IFTTSLNFVE KERDFRKINH EMANGGNQNL KVADEALKVD
DCDCHPEFSP PSSQPPKHKG KQKSRNNESE KFSSSSPLTL PADLKNILEK QFSKSSRAAH
QDFANIMKML RSLIQDGYMA LLEQRCRSAA QAFTELLNGL DPQKIKQLNL AMINYVLVVY
GLAISLLGIG QPEELSEAEN QFKRIIEHYP SEGLDCLAYC GIGKVYLKKN RFLEALNHFE
KARTLIYRLP GVLTWPTSNV IIEESQPQKI KMLLEKFVEE CKFPPVPDAI CCYQKCHGYS
KIQIYITDPD FKGFIRISCC QYCKIEFHMN CWKKLKTTTF NDKIDKDFLQ GICLTPDCEG
VISKIIIFSS GGEVKCEFEH KVIKEKVPPR PILKQKCSSL EKLRLKEDKK LKRKIQKKEA
KKLAQERMEE DLRESNPPKN EEQKETVDNV QRCQFLDDRI LQCIKQYADK IKSGIQNTAM
LLKELLSWKV LSTEDYTTCF SSRNFLNEAV DYVIRHLIQE NNRVKTRIFL HVLSELKEVE
PKLAAWIQKL NSFGLDATGT FFSRYGASLK LLDFSIMTFL WNEKYGHKLD SIEGKQLDYF
SEPASLKEAR CLIWLLEEHR DKFPALHSAL DEFFDIMDSR CTVLRKQDSG EAPFSSTKVK
NKSKKKKPKD SKPMLVGSGT TSVTSNNEII TSSEDHSNRN SDSAGPFAVP DHLRQDVEEF
EALYDQHSNE YVVRNKKLWD MNPKQKCSTL YDYFSQFLEE HGPLDMSNKM FSAEYEFFPE
ETRQILEKAG GLKPFLLGCP RFVVIDNCIA LKKVASRLKK KRKKKNIKTK VEEISKAGEY
VRVKLQLNPA AREFKPDVKS KPVSDSSSAP AFENVKPKPV SANSPKPACE DVKAKPVSDN
SSRQVSEDGQ PKGVSSNSPK PGSEDANYKR VSCNSPKPVL EDVKPTYWAQ SHLVTGYCTY
LPFQRFDITQ TPPAYINVLP GLPQYTSIYT PLASLSPEYQ LPRSVPVVPS FVANDRADKN
AAAYFEGHHL NAENVAGHQI ASETQILEGS LGISVKSHCS TGDAHTVLSE SNRNDEHCGN
SNNKCEVIPE STSAVTNIPH VQMVAIQVSW NIIHQEVNTE PYNPFEERQG EISRIEKEHQ
VLQDQLQEVY ENYEQIKLKG LEETRDLEEK LKRHLEENKI SKTELDWFLQ DLEREIKKWQ
QEKKEIQERL KSLKKKIKKV SNASEMYTQK NDGKEKEHEL HLDQSLEISN TLTNEKMKIE
EYIKKGKEDY EESHQRAVAA EVSVLENWKE SEVYKLQIME SQAEAFLKKL GLISRDPAAY
PDMESDIRSW ELFLSNVTKE IEKAKSQFEE QIKAIKNGSR LSELSKVQIS ELSFPACNTV
HPELLPESSG DDGQGLVTSA SDVTGNHAAL HRDPSVFSAG DSPGEAPSAL LPGPPPGQPE
ATQLTGPKRA GQAALSERSP VADRKQPVPP GRAARSSQSP KKPFNSIIEH LSVVFPCYNS
TELAGFIKKV RSKNKNSLSG LSIDEIVQRV TEHILDEQKK KKPNPGKDKR TYEPSSATPV
TRSSQGSPSV VVAPSPKTKG QKAEDVPVRI ALGASSCEIC HEVFKSKNVR VLKCGHKYHK
GCFKQWLKGQ SACPACQGRD LLTEESPSGR GWPSQNQELP SCSSR
