TTLL2_MOUSE
ID TTLL2_MOUSE Reviewed; 540 AA.
AC A4Q9E4;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2007, sequence version 1.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=Probable tubulin polyglutamylase TTLL2;
DE EC=6.-.-.-;
DE AltName: Full=Tubulin--tyrosine ligase-like protein 2;
GN Name=Ttll2 {ECO:0000312|MGI:MGI:3644030};
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:CAM84322.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:CAM84322.1};
RC TISSUE=Testis {ECO:0000312|EMBL:CAM84322.1};
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]
RP FUNCTION.
RA Mahalingan K.K., Keith Keenan E., Strickland M., Li Y., Liu Y., Ball H.L.,
RA Tanner M.E., Tjandra N., Roll-Mecak A.;
RT "Structural basis for polyglutamate chain initiation and elongation by TTLL
RT family enzymes.";
RL Nat. Struct. Mol. Biol. 27:802-813(2020).
CC -!- FUNCTION: Probable tubulin polyglutamylase that generates side chains
CC of glutamate on the gamma-carboxyl group of specific glutamate residues
CC within the C-terminal tail of target proteins (PubMed:17499049).
CC Similar to TTLL1, may acquire enzymatic activity only in complex with
CC other proteins as it is most likely lacking domains important for
CC autonomous activity (By similarity). Probably involved in the side-
CC chain initiation step of the polyglutamylation reaction rather than the
CC elongation step (Probable). {ECO:0000250|UniProtKB:Q91V51,
CC ECO:0000269|PubMed:17499049, ECO:0000305|Ref.2}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:A4Q9E8};
CC -!- TISSUE SPECIFICITY: Highly expressed in brain, kidney, liver and testis
CC (PubMed:17499049). Expressed in heart, lung, muscle and spleen
CC (PubMed:17499049). {ECO:0000269|PubMed:17499049}.
CC -!- DOMAIN: Arg-175 is the main determinant for regioselectivity, which
CC segregates between initiases and elongases in all tubulin--tyrosine
CC ligase family. A glutamine residue at this position is found in
CC elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-
CC chain elongation, whereas an arginine residue is found in initiases
CC TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation.
CC {ECO:0000305|Ref.2}.
CC -!- SIMILARITY: Belongs to the tubulin--tyrosine ligase family.
CC {ECO:0000255}.
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DR EMBL; AM690745; CAM84322.1; -; mRNA.
DR CCDS; CCDS49941.1; -.
DR RefSeq; NP_001091737.1; NM_001098267.1.
DR RefSeq; XP_011244474.1; XM_011246172.2.
DR RefSeq; XP_011244476.1; XM_011246174.2.
DR RefSeq; XP_011244477.1; XM_011246175.2.
DR AlphaFoldDB; A4Q9E4; -.
DR SMR; A4Q9E4; -.
DR BioGRID; 950147; 1.
DR STRING; 10090.ENSMUSP00000111413; -.
DR PhosphoSitePlus; A4Q9E4; -.
DR PaxDb; A4Q9E4; -.
DR PRIDE; A4Q9E4; -.
DR ProteomicsDB; 298337; -.
DR Antibodypedia; 20063; 33 antibodies from 8 providers.
DR Ensembl; ENSMUST00000115747; ENSMUSP00000111413; ENSMUSG00000079722.
DR GeneID; 100216474; -.
DR KEGG; mmu:100216474; -.
DR UCSC; uc008ain.1; mouse.
DR CTD; 83887; -.
DR MGI; MGI:3644030; Ttll2.
DR VEuPathDB; HostDB:ENSMUSG00000079722; -.
DR eggNOG; KOG2157; Eukaryota.
DR GeneTree; ENSGT00940000162752; -.
DR HOGENOM; CLU_010131_9_0_1; -.
DR InParanoid; A4Q9E4; -.
DR OMA; SDHGKAP; -.
DR OrthoDB; 626048at2759; -.
DR PhylomeDB; A4Q9E4; -.
DR TreeFam; TF313087; -.
DR Reactome; R-MMU-8955332; Carboxyterminal post-translational modifications of tubulin.
DR BioGRID-ORCS; 100216474; 6 hits in 72 CRISPR screens.
DR ChiTaRS; Ttll2; mouse.
DR PRO; PR:A4Q9E4; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; A4Q9E4; protein.
DR Bgee; ENSMUSG00000079722; Expressed in testis and 14 other tissues.
DR GO; GO:0005929; C:cilium; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0015631; F:tubulin binding; IBA:GO_Central.
DR GO; GO:0070740; F:tubulin-glutamic acid ligase activity; IBA:GO_Central.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0018095; P:protein polyglutamylation; IBA:GO_Central.
DR InterPro; IPR004344; TTL/TTLL_fam.
DR Pfam; PF03133; TTL; 1.
DR PROSITE; PS51221; TTL; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Ligase; Magnesium; Metal-binding; Nucleotide-binding;
KW Reference proteome.
FT CHAIN 1..540
FT /note="Probable tubulin polyglutamylase TTLL2"
FT /id="PRO_0000326158"
FT DOMAIN 41..384
FT /note="TTL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00568"
FT REGION 257..258
FT /note="L-glutamate"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT REGION 479..499
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 169
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 175..176
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 175
FT /ligand="a protein"
FT /ligand_id="ChEBI:CHEBI:16541"
FT /ligand_part="L-glutamate residue"
FT /ligand_part_id="ChEBI:CHEBI:29973"
FT /ligand_part_note="L-glutamate acceptor residue in protein
FT target"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 197..200
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 210..212
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 236
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 255..256
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 278
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 330
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 343
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 343
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 345
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 361
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT SITE 175
FT /note="Essential for specifying initiation versus
FT elongation step of the polyglutamylase activity"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
SQ SEQUENCE 540 AA; 62109 MW; 0704DE5937B2838A CRC64;
MDGLQSLGDV TAEIFGLPLE GHSVQESKPL KTEDEPQGAP LKPLVFRVDE STPGLVQSVL
LERGWDKFDE QRQDVEDWNL YWRSSSFRRA EYVNVKPWQR LNHHPGMTNL TRKDCLAKHL
ARMRSRYGES LYEFTPLTFI MPTDYTKFVA KYFKEKQDLG TKPSYWICKP AELSRGRGII
IFSDIRDLMF KGTYVVQKYI CNPLLVGRYK CDLRIYVCIT GFKPLTIYMY QEGLVRFATE
KFDLRNLEDY YSHLTNSSIN KLGASYQKIK EVVGQGCKWT LSRFFSYLRN WDVDDLLLRQ
KISHMVILTV LAMAPSVPVT YNCFELFGFD ILIDDNLKPW LLEVNYNPAL TLDCSTDESV
KRSLVHDVIE LLYLNGLRSE EKKCGRTSPG NSVVSLARSH HHEFCATPNS SSYASLIEFT
TGSKSDPAVQ NICPKHTRTS QLREMMSRRD RLLTKEAAKS KPRHKAWHLP RKMVFPYASQ
SQPHKMKGPA GDLPEAGSTP NDHAGNFVLI FPFNKATFRA SRNGLNVKRI IQELQKLMNK
