TTC3_RAT
ID TTC3_RAT Reviewed; 2000 AA.
AC D3ZSP7;
DT 11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2015, sequence version 3.
DT 03-AUG-2022, entry version 76.
DE RecName: Full=E3 ubiquitin-protein ligase TTC3 {ECO:0000250|UniProtKB:P53804};
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:P53804};
DE AltName: Full=RING-type E3 ubiquitin transferase TTC3 {ECO:0000305};
DE AltName: Full=TPR repeat protein D {ECO:0000250|UniProtKB:P53804};
GN Name=Ttc3 {ECO:0000312|RGD:1308654};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116 {ECO:0000312|Proteomes:UP000002494};
RN [1] {ECO:0000312|Proteomes:UP000002494}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2] {ECO:0000305}
RP FUNCTION, AND SUBCELLULAR LOCATION.
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).
CC -!- FUNCTION: E3 ubiquitin-protein ligase which catalyzes the formation of
CC 'Lys-48'-polyubiquitin chains (By similarity). Mediates the
CC ubiquitination and subsequent degradation of phosphorylated Akt (AKT1,
CC AKT2 and AKT3) in the nucleus (By similarity). Acts as a terminal
CC regulator of Akt signaling after activation; its phosphorylation by
CC Akt, which is a prerequisite for ubiquitin ligase activity, suggests
CC the existence of a regulation mechanism required to control Akt levels
CC after activation (By similarity). Positively regulates TGFB1-induced
CC epithelial-mesenchymal transition and myofibroblast differentiation by
CC mediating the ubiquitination and subsequent degradation of SMURF2 (By
CC similarity). Regulates neuronal differentiation by regulating actin
CC remodeling and Golgi organization via a signaling cascade involving
CC RHOA, CIT and ROCK (PubMed:24695496). Inhibits cell proliferation (By
CC similarity). {ECO:0000250|UniProtKB:P53804,
CC ECO:0000269|PubMed:24695496}.
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:0000250|UniProtKB:P53804};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:P53804}.
CC -!- SUBUNIT: Interacts (when phosphorylated on Ser-397) with AKT1, AKT2 and
CC AKT3 (when phosphorylated) (By similarity). Interacts with CIT (By
CC similarity). Interacts with POLG (By similarity). Interacts with HSP70
CC (By similarity). Interacts with SMURF2 (By similarity).
CC {ECO:0000250|UniProtKB:P53804}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P53804}. Cytoplasm
CC {ECO:0000269|PubMed:24695496}. Golgi apparatus
CC {ECO:0000269|PubMed:24695496}. Note=Nuclear localization may be
CC dependent on the proteolytic cleavage of full length protein in the
CC cytoplasm (By similarity). This cleavage may reveal an N-terminal
CC nuclear localization signal, allowing N-terminal fragments to enter the
CC nucleus (By similarity). {ECO:0000250|UniProtKB:P53804}.
CC -!- PTM: Phosphorylation on Ser-397 by Akt is required for ubiquitin ligase
CC activity. {ECO:0000250|UniProtKB:P53804}.
CC -!- PTM: Proteolytically cleaved into differently sized N- and C-terminal
CC fragments. {ECO:0000250|UniProtKB:P53804}.
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DR EMBL; AABR07033674; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07033675; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07033676; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; D3ZSP7; -.
DR SMR; D3ZSP7; -.
DR STRING; 10116.ENSRNOP00000059742; -.
DR jPOST; D3ZSP7; -.
DR PaxDb; D3ZSP7; -.
DR PeptideAtlas; D3ZSP7; -.
DR PRIDE; D3ZSP7; -.
DR RGD; 1308654; Ttc3.
DR VEuPathDB; HostDB:ENSRNOG00000001682; -.
DR eggNOG; KOG0800; Eukaryota.
DR HOGENOM; CLU_001829_1_0_1; -.
DR InParanoid; D3ZSP7; -.
DR OMA; HDDQGLV; -.
DR UniPathway; UPA00143; -.
DR PRO; PR:D3ZSP7; -.
DR Proteomes; UP000002494; Chromosome 11.
DR Bgee; ENSRNOG00000001682; Expressed in Ammon's horn and 19 other tissues.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0005773; C:vacuole; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISO:RGD.
DR GO; GO:0010771; P:negative regulation of cell morphogenesis involved in differentiation; ISO:RGD.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; ISO:RGD.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; ISO:RGD.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISO:RGD.
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; 3.
DR PROSITE; PS50293; TPR_REGION; 2.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 3: Inferred from homology;
KW Cytoplasm; Golgi apparatus; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; TPR repeat; Transferase; Zinc; Zinc-finger.
FT CHAIN 1..2000
FT /note="E3 ubiquitin-protein ligase TTC3"
FT /id="PRO_0000448697"
FT REPEAT 250..283
FT /note="TPR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00339"
FT REPEAT 284..317
FT /note="TPR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00339"
FT REPEAT 556..592
FT /note="TPR 3"
FT /evidence="ECO:0000255"
FT REPEAT 596..629
FT /note="TPR 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00339"
FT ZN_FING 1952..1991
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 20..249
FT /note="Interaction with POLG"
FT /evidence="ECO:0000250|UniProtKB:P53804"
FT REGION 442..478
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 804..828
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1041..1087
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1233..1308
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1423..1448
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1806..1839
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1894..1947
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 804..826
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1266..1280
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1808..1839
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1894..1913
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 397
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P53804"
FT MOD_RES 1029
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88196"
FT MOD_RES 1080
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88196"
SQ SEQUENCE 2000 AA; 225783 MW; 2716C704140F51AE CRC64;
MPGHRGAPHL PPWVCGLCSM DDFAEGGLSL ADDILLEDYP YEDDCICTPD FTTDDYVRVT
QLYYEGVGMQ YKDYAQSEKN LEYDICNIWC SKPLSILQDY CDAIKLYIFW PLLFQHQHSS
IISRLHPCVE AIRSRAAEIS LKKLQHLELM EDIVDLAKKV ANDSFLIEGL LKIGYKIENK
ILAMEDALNW IKYTGDVTIL PKLGSVDSGW PMLSIFFTEY KYHITRVVTE NCNLLEEFRR
HSCMQCVKQG ELMKMRGNEE FAKEKFEIAV IYYTRAIEYR PENHLLYGNR ALCFLRMGQF
RNALSDGKRA IVLKNTWPKG HYRYCDALSM LGEYDWALQA NIKAQKLCKN DPEGIKDLIQ
QHIKLQKQIE DLQGRTSNRN PIKAFYESRA YIPRNSSAPA FRTSLNFVET ERGFRKTKYR
MANGGGHQNQ KVADEALKGD DCDCHPEFLP PPSQPPRHKG KQKSRNNESE KPSSNSQVTL
QVDLKSILEK QFSKSSRAAH QDFANIMKML RSLIQDGYTA LLEQRCRSAA QAFTELLNGL
DPQKIKQLNL AMINYVLVVY GLAVSLLGIG RPEELSEAEN QFKRIIEHYP NEGLDCLAYC
GIGKVYLKKN RFLEALNHFE KAKTLICRLP GILTWPTSNV IIEESKPEKV KVMLEKFVEE
CKFPPVPDAV CCYQKCRGFS KIQIYLTDPD FKGFIRISCC QYCKVEFHMN CWKKLKTTTF
NDKIDKDFLQ GICLTPDCEG IISKIIIFSS GGQVKCEFEH KVVKEKAPSR PVLKQKCSSL
EKLRLKEDKK LKRKIQKQEA KKLAQERMEE DLRESNPPKP EEPEETVESA QSCQFLDDRI
LQCIKQNADK IKSVVLNTST LLKELLSWKV LSTEDYTTCF SSKNFVHEAV DYVIGHLIQE
KNRVKTRIFL HVLSELKELD PKLAPWIQRL NSFGLDATGP FFTRYGASLK ELDFNIVTFL
WSEKYGHKLG SIEGKQLDYF CEPASVMEAR CLIWLLEEHR DKFPALHSAL DEFFDIMDSR
CTVLRKQDSD EMPFGCIKVK NKGKKKKPKD SKPMLVGSGT ASVTPSSETV TPEDHNRRNS
DSAGPFAVPD HLRQDVEEFE ALYDQHSSEY VVRNKKLWDI NPKQKCSTLY DYFSQLLEEH
GPLDMSDRMF SEEYEFFPEE TRQILEKAGG LKSFLLGCPR FVVIDNCIAL KKVASRLKKK
RKKKNIKTKV EEISKTGEYL RVKLPLNPTA REFQPDVKSE AAAEDVTSIP GPADSSAPAA
EDLKPQLDSD SSSGSASEDS RLEVVSPDLP TPLCEDASPS PTPAPEDAKP TYWTQSHLVT
GFCTYLPFQG FGIAQSRPAY INMVPSLSQF TSIYTPLANI SSEYPMPRSM PVVPSFVASE
RADGNAAAYF ESHRLNTENA SDDHTASETQ ILEGPLGMCV KSQSSTADAR TALSEPEGNS
RHSGSSDSLW EASLENVSGI TDVPPAPSVA IQVSRSLIHQ EVNTEPYAPF ERQQGDLSQK
EKECHLLREQ LQVACEECEQ MELRSSQETR DLEEKLQRHA EENKVSLPEL QWALGKLDRE
IKKWHQEKKE IQERLKALKK KIKKVINTSD MSAQKNDGLD KECESQPDQS LGISSALTDE
KAKVEESVRK GKELYEESQQ RAVAAEVSVL ENWKEREVCK LQGVATQAEA CLKSLKLMNS
DSAAYPDVEC DILSWETFLS TVTEEIENTK CQFEEQIKAI KSGSRLSDLS SVQVSELLFP
ACSMIHPQLL SESSRHEDHG LVACVDSMTG AVLNDPYVGP DSGCSEEVPE LSLGSPTHHP
EGAQQLEVKK ASQVSPSEQN PEADEKPSGQ ATRSSQSQKN PFNSIIEHLS VIFPCYASSE
LSGFIKKVRN KSKNSFSGLS IEEIVERVTE HIVEEQKKKK PNPGKDKKTS EAHPAASVSK
SSPSPPLAAA GPSAKTKGQK KDDVPAPDGN SCQICHEIFK SKNMRVLKCG HKFHKGCFKQ
WLKGQSTCPT CGSSDLLSEE
