TTL12_MOUSE
ID TTL12_MOUSE Reviewed; 639 AA.
AC Q3UDE2; Q7TPC3;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Tubulin--tyrosine ligase-like protein 12;
DE AltName: Full=Inactive tubulin--tyrosine ligase-like protein 12 {ECO:0000305};
GN Name=Ttll12 {ECO:0000312|MGI:MGI:3039573};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1] {ECO:0000305, ECO:0000312|EMBL:CAM84333.1}
RP NUCLEOTIDE SEQUENCE [MRNA], LACK OF POLYGLUTAMASE ACTIVITY, AND TISSUE
RP SPECIFICITY.
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:CAM84333.1};
RC TISSUE=Brain {ECO:0000312|EMBL:CAM84333.1};
RX PubMed=17499049; DOI=10.1016/j.molcel.2007.04.012;
RA van Dijk J., Rogowski K., Miro J., Lacroix B., Edde B., Janke C.;
RT "A targeted multienzyme mechanism for selective microtubule
RT polyglutamylation.";
RL Mol. Cell 26:437-448(2007).
RN [2] {ECO:0000312|EMBL:BAE29319.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAE29319.1};
RC TISSUE=Bone marrow {ECO:0000312|EMBL:BAE29319.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4] {ECO:0000312|EMBL:AAH55368.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C3H/He {ECO:0000312|EMBL:AAH55368.1};
RC TISSUE=Osteoblast {ECO:0000312|EMBL:AAH55368.1};
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Negatively regulates post-translational modifications of
CC tubulin, including detyrosination of the C-terminus and
CC polyglutamylation of glutamate residues. Also, indirectly promotes
CC histone H4 trimethylation at 'Lys-20' (H4K20me3). Probably by
CC controlling tubulin and/or histone H4 post-translational modifications,
CC plays a role in mitosis and in maintaining chromosome number stability.
CC During RNA virus-mediated infection, acts as a negative regulator of
CC the DDX58/RIG-I pathway by preventing MAVS binding to TBK1 and IKBKE.
CC {ECO:0000250|UniProtKB:Q14166}.
CC -!- SUBUNIT: Interacts with MAVS; the interaction prevents MAVS binding to
CC TBK1 and IKBKE. Interacts (via N-terminus) with TBK1 (via protein
CC kinase domain). Interacts (via TTL domain) with IKBKE (via protein
CC kinase domain). Interacts with tubulin alpha. Interacts with histone H3
CC and histone H4 (when trimethylated at 'Lys-20' (H4K20me3)). Interacts
CC with CBX3. {ECO:0000250|UniProtKB:Q14166}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q14166}. Midbody
CC {ECO:0000250|UniProtKB:Q14166}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250|UniProtKB:Q14166}.
CC Cytoplasm, cytoskeleton, spindle {ECO:0000250|UniProtKB:Q14166}.
CC Nucleus {ECO:0000250|UniProtKB:Q14166}. Note=Predominantly localizes in
CC the cytoplasm. {ECO:0000250|UniProtKB:Q14166}.
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels in brain,
CC kidney, liver, lung, muscle and testis. {ECO:0000269|PubMed:17499049}.
CC -!- SIMILARITY: Belongs to the tubulin--tyrosine ligase family.
CC {ECO:0000305}.
CC -!- CAUTION: Although it belongs to the tubulin--tyrosine ligase family,
CC the TTL domain lacks some of the ATP binding sites predicted to be
CC essential for TTL activity (By similarity). Lacks tyrosine ligase
CC activity in vitro (By similarity). Lacks glutamylation activity in
CC vitro (PubMed:17499049). Although TTLL12 contains a potential SET-like
CC domain in the N-terminus, it does not have lysine methyltransferase
CC activity towards histone in vitro (By similarity).
CC {ECO:0000250|UniProtKB:Q14166, ECO:0000269|PubMed:17499049}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AM690756; CAM84333.1; -; mRNA.
DR EMBL; AK150116; BAE29319.1; -; mRNA.
DR EMBL; AL583887; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC055368; AAH55368.1; -; mRNA.
DR CCDS; CCDS27706.1; -.
DR RefSeq; NP_898838.2; NM_183017.2.
DR AlphaFoldDB; Q3UDE2; -.
DR SMR; Q3UDE2; -.
DR BioGRID; 230183; 22.
DR IntAct; Q3UDE2; 17.
DR MINT; Q3UDE2; -.
DR STRING; 10090.ENSMUSP00000016901; -.
DR iPTMnet; Q3UDE2; -.
DR PhosphoSitePlus; Q3UDE2; -.
DR EPD; Q3UDE2; -.
DR jPOST; Q3UDE2; -.
DR MaxQB; Q3UDE2; -.
DR PaxDb; Q3UDE2; -.
DR PeptideAtlas; Q3UDE2; -.
DR PRIDE; Q3UDE2; -.
DR ProteomicsDB; 297751; -.
DR Antibodypedia; 27494; 265 antibodies from 17 providers.
DR Ensembl; ENSMUST00000016901; ENSMUSP00000016901; ENSMUSG00000016757.
DR GeneID; 223723; -.
DR KEGG; mmu:223723; -.
DR UCSC; uc007xbh.2; mouse.
DR CTD; 23170; -.
DR MGI; MGI:3039573; Ttll12.
DR VEuPathDB; HostDB:ENSMUSG00000016757; -.
DR eggNOG; KOG2155; Eukaryota.
DR GeneTree; ENSGT00390000006760; -.
DR HOGENOM; CLU_018324_0_0_1; -.
DR InParanoid; Q3UDE2; -.
DR OMA; CKRACDY; -.
DR OrthoDB; 611643at2759; -.
DR PhylomeDB; Q3UDE2; -.
DR TreeFam; TF313037; -.
DR Reactome; R-MMU-8955332; Carboxyterminal post-translational modifications of tubulin.
DR BioGRID-ORCS; 223723; 4 hits in 72 CRISPR screens.
DR ChiTaRS; Ttll12; mouse.
DR PRO; PR:Q3UDE2; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q3UDE2; protein.
DR Bgee; ENSMUSG00000016757; Expressed in ectoplacental cone and 224 other tissues.
DR ExpressionAtlas; Q3UDE2; baseline and differential.
DR Genevisible; Q3UDE2; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0030496; C:midbody; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell.
DR GO; GO:0016881; F:acid-amino acid ligase activity; IEA:UniProt.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:1990889; F:H4K20me3 modified histone binding; ISO:MGI.
DR GO; GO:0015631; F:tubulin binding; ISO:MGI.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0060339; P:negative regulation of type I interferon-mediated signaling pathway; ISO:MGI.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; ISO:MGI.
DR InterPro; IPR004344; TTL/TTLL_fam.
DR InterPro; IPR027749; TTLL12.
DR PANTHER; PTHR46088; PTHR46088; 1.
DR Pfam; PF03133; TTL; 1.
DR PROSITE; PS51221; TTL; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cytoplasm; Cytoskeleton; Immunity; Innate immunity;
KW Nucleotide-binding; Nucleus; Reference proteome.
FT CHAIN 1..639
FT /note="Tubulin--tyrosine ligase-like protein 12"
FT /id="PRO_0000326166"
FT DOMAIN 295..639
FT /note="TTL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00568"
FT BINDING 445..448
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q6ZT98"
FT BINDING 463
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q6ZT98"
FT BINDING 465
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q6ZT98"
FT CONFLICT 65
FT /note="M -> K (in Ref. 4; AAH55368)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 639 AA; 74043 MW; 584D72AA05BCA837 CRC64;
MEIQSGPQPG SPGRAERLNA RLLDEFVSLH GPTLRASGVP ERLWGRLLHK LEHEVFDAGE
MFGIMQVEEV EEAEDEAARE AQRKQPNPGG ELCYKVIVTS ESGVRADDPN SIFLIDHAWT
CRVEHARKQL QQVPGLLHRM ANLMGIEFHG EVPSPEVVAL VLEEMWKFNQ TYQLAHGTAE
EKVPVWYIMD EFGSRIQHSD MPSFATAPFF YMPQQVAYTL LWPLRDLDTG EEVTRDFAYG
EADPLIRKCM LLPWAPADML DLSFSTPEPP AKYYQAILEE NKEKLPLAIS PVARPQGHVF
RVHCDVQQVL GHLTHPRFTF TDSEADADIF FHFSHFKDYM KLSQESPQVL LNQFPCENLL
TVKDCLASIA RRAGGPEGPP WLPRTFNLRT ELPQFVSYFQ HRERRGEDNH WICKPWNLAR
SLDTHVTNNL HSIIRHREST PKVVSKYIES PVLFLREDVG NVKFDIRYIV LLRSVRPLRL
FAYDVFWLRF SNRPFALDDL DDYEKHFTVM NYDPDVVLKQ VHYNEFIPQF EKQYPEFPWS
DVQAEIFKAF TELFQVACAK PPPMGLCDYP SSRAMYAIDL MLNWDNHPDG KRVMQPQILE
VNFNPDCERA CRYHPSFFND VFSTLFLDET DNCHVTRII
