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   27-MAR-2024, entry version 207.
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   CCDS; CCDS93096.1; -. [P53804-3]
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.
DR   AlphaFoldDB; P53804; -.
DR   BioGRID; 113118; 66.
DR   ELM; P53804; -.
DR   IntAct; P53804; 98.
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; 9606-ENSP00000381981; -.
DR   PeptideAtlas; P53804; -.
DR   ProteomicsDB; 56623; -. [P53804-1]
DR   ProteomicsDB; 56624; -. [P53804-2]
DR   ProteomicsDB; 56625; -. [P53804-3]
DR   Pumba; P53804; -.
DR   Antibodypedia; 8442; 84 antibodies from 19 providers.
DR   DNASU; 7267; -.
DR   Ensembl; ENST00000354749.6; ENSP00000346791.2; ENSG00000182670.14. [P53804-1]
DR   Ensembl; ENST00000399017.6; ENSP00000381981.2; ENSG00000182670.14. [P53804-1]
DR   Ensembl; ENST00000418766.6; ENSP00000403943.2; ENSG00000182670.14. [P53804-1]
DR   Ensembl; ENST00000450533.6; ENSP00000408456.2; ENSG00000182670.14. [P53804-1]
DR   Ensembl; ENST00000463216.6; ENSP00000512893.1; ENSG00000182670.14. [P53804-3]
DR   Ensembl; ENST00000492275.6; ENSP00000512889.1; ENSG00000182670.14. [P53804-3]
DR   GeneID; 7267; -.
DR   KEGG; hsa:7267; -.
DR   MANE-Select; ENST00000418766.6; ENSP00000403943.2; NM_001330683.2; NP_001317612.1.
DR   UCSC; uc002yvz.4; human. [P53804-1]
DR   AGR; HGNC:12393; -.
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; CEDVRAK; -.
DR   OrthoDB; 5354896at2759; -.
DR   PhylomeDB; P53804; -.
DR   TreeFam; TF333981; -.
DR   PathwayCommons; P53804; -.
DR   SignaLink; P53804; -.
DR   SIGNOR; P53804; -.
DR   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 7267; 10 hits in 1195 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 210 other cell types or tissues.
DR   ExpressionAtlas; P53804; baseline and differential.
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   CDD; cd16481; RING-H2_TTC3; 1.
DR   Gene3D; 1.10.533.10; Death Domain, Fas; 1.
DR   Gene3D; 1.25.40.10; Tetratricopeptide repeat domain; 2.
DR   Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 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   PANTHER; PTHR17550; E3 UBIQUITIN-PROTEIN LIGASE TTC3; 1.
DR   PANTHER; PTHR17550:SF6; E3 UBIQUITIN-PROTEIN LIGASE TTC3; 1.
DR   Pfam; PF19179; TTC3_DZIP3_dom; 1.
DR   Pfam; PF13639; zf-RING_2; 1.
DR   SMART; SM00184; RING; 1.
DR   SMART; SM00028; TPR; 4.
DR   SUPFAM; SSF57850; RING/U-box; 1.
DR   SUPFAM; SSF48452; TPR-like; 2.
DR   PROSITE; PS50005; TPR; 2.
DR   PROSITE; PS50293; TPR_REGION; 2.
DR   PROSITE; PS50089; ZF_RING_2; 1.
DR   Genevisible; P53804; HS.
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
//