ID TTLL5_HUMAN Reviewed; 1281 AA.
AC Q6EMB2; B9EGH8; B9EGH9; Q9BUB0; Q9H0G4; Q9H7W2; Q9P1V5; Q9UPZ4;
DT 21-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 16-JUN-2009, sequence version 3.
DT 27-MAR-2024, entry version 148.
DE RecName: Full=Tubulin polyglutamylase TTLL5 {ECO:0000250|UniProtKB:Q8CHB8};
DE EC=6.3.2.- {ECO:0000250|UniProtKB:Q8CHB8};
DE AltName: Full=SRC1 and TIF2-associated modulatory protein {ECO:0000303|PubMed:17116691};
DE Short=STAMP protein {ECO:0000303|PubMed:17116691};
DE AltName: Full=Tubulin--tyrosine ligase-like protein 5;
GN Name=TTLL5 {ECO:0000312|HGNC:HGNC:19963};
GN Synonyms=KIAA0998, STAMP {ECO:0000303|PubMed:17116691};
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 1), FUNCTION, SUBCELLULAR LOCATION,
RP INTERACTION WITH NCOA1 AND NCOA2, TISSUE SPECIFICITY, AND VARIANTS VAL-149
RP AND SER-1267.
RC TISSUE=Testis;
RX PubMed=17116691; DOI=10.1128/mcb.01360-06;
RA He Y., Simons S.S. Jr.;
RT "STAMP, a novel predicted factor assisting TIF2 actions in glucocorticoid
RT receptor-mediated induction and repression.";
RL Mol. Cell. Biol. 27:1467-1485(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT VAL-149.
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT
RP VAL-149.
RC TISSUE=Brain, Testis, and Uterus;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 24-1281 (ISOFORM 3).
RC TISSUE=Teratocarcinoma;
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 56-1281 (ISOFORM 1), AND VARIANTS
RP VAL-149 AND SER-1267.
RC TISSUE=Brain;
RX PubMed=10231032; DOI=10.1093/dnares/6.1.63;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:63-70(1999).
RN [9]
RP FUNCTION.
RX PubMed=22493317; DOI=10.1091/mbc.e11-11-0931;
RA Backer C.B., Gutzman J.H., Pearson C.G., Cheeseman I.M.;
RT "CSAP localizes to polyglutamylated microtubules and promotes proper cilia
RT function and zebrafish development.";
RL Mol. Biol. Cell 23:2122-2130(2012).
RN [10]
RP INVOLVEMENT IN CORD19, VARIANT CORD19 LYS-543, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=24791901; DOI=10.1016/j.ajhg.2014.04.003;
RG UCL-Exomes Consortium;
RA Sergouniotis P.I., Chakarova C., Murphy C., Becker M., Lenassi E., Arno G.,
RA Lek M., MacArthur D.G., Bhattacharya S.S., Moore A.T., Holder G.E.,
RA Robson A.G., Wolfrum U., Webster A.R., Plagnol V.;
RT "Biallelic variants in TTLL5, encoding a tubulin glutamylase, cause retinal
RT dystrophy.";
RL Am. J. Hum. Genet. 94:760-769(2014).
RN [11]
RP DOMAIN, AND MUTAGENESIS OF 467-LYS--LYS-473.
RX PubMed=25959773; DOI=10.1016/j.cell.2015.04.003;
RA Garnham C.P., Vemu A., Wilson-Kubalek E.M., Yu I., Szyk A., Lander G.C.,
RA Milligan R.A., Roll-Mecak A.;
RT "Multivalent microtubule recognition by tubulin tyrosine ligase-like family
RT glutamylases.";
RL Cell 161:1112-1123(2015).
CC -!- FUNCTION: Polyglutamylase which modifies tubulin, generating
CC polyglutamate side chains on the gamma-carboxyl group of specific
CC glutamate residues within the C-terminal tail of tubulin.
CC Preferentially mediates ATP-dependent initiation step of the
CC polyglutamylation reaction over the elongation step. Preferentially
CC modifies the alpha-tubulin tail over a beta-tail (By similarity).
CC Required for CCSAP localization to both polyglutamylated spindle and
CC cilia microtubules (PubMed:22493317). Increases the effects of
CC transcriptional coactivator NCOA2/TIF2 in glucocorticoid receptor-
CC mediated repression and induction and in androgen receptor-mediated
CC induction (PubMed:17116691). {ECO:0000250|UniProtKB:Q8CHB8,
CC ECO:0000269|PubMed:17116691, ECO:0000269|PubMed:22493317}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-glutamate + L-glutamyl-[protein] = ADP + gamma-L-
CC glutamyl-L-glutamyl-[protein] + H(+) + phosphate;
CC Xref=Rhea:RHEA:60144, Rhea:RHEA-COMP:10208, Rhea:RHEA-COMP:15517,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29973, ChEBI:CHEBI:29985,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:143622,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:Q8CHB8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60145;
CC Evidence={ECO:0000250|UniProtKB:Q8CHB8};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(L-glutamyl)(n)-gamma-L-glutamyl-L-glutamyl-[protein] + ATP +
CC L-glutamate = (L-glutamyl)(n+1)-gamma-L-glutamyl-L-glutamyl-[protein]
CC + ADP + H(+) + phosphate; Xref=Rhea:RHEA:60148, Rhea:RHEA-COMP:15519,
CC Rhea:RHEA-COMP:15675, ChEBI:CHEBI:15378, ChEBI:CHEBI:29985,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:143623,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:Q8CHB8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60149;
CC Evidence={ECO:0000250|UniProtKB:Q8CHB8};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:A4Q9E8};
CC -!- SUBUNIT: Interacts with the transcriptional coactivators NCOA1/SRC-1
CC and NCOA2/TIF2. {ECO:0000269|PubMed:17116691}.
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium
CC {ECO:0000269|PubMed:24791901}. Cytoplasm, cytoskeleton, cilium basal
CC body {ECO:0000250|UniProtKB:Q8CHB8}. Nucleus
CC {ECO:0000269|PubMed:17116691}. Cytoplasm {ECO:0000269|PubMed:17116691}.
CC Note=Localized to the base of the connecting cilium between the basal
CC body and the adjacent daughter centriole of the cilium. In osteosarcoma
CC cells, found in both cytoplasm and nucleus in the absence of steroid
CC but located exclusively in the nucleus in the presence of steroid.
CC {ECO:0000250|UniProtKB:Q8CHB8, ECO:0000269|PubMed:24791901}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6EMB2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6EMB2-2; Sequence=VSP_037453, VSP_037456, VSP_037457;
CC Name=3;
CC IsoId=Q6EMB2-3; Sequence=VSP_037454, VSP_037455;
CC -!- TISSUE SPECIFICITY: Expressed in the retina, found in the rod and cone
CC photoreceptors (at protein level). Widely expressed with highest levels
CC in heart and skeletal muscle and low levels in other tissues.
CC {ECO:0000269|PubMed:17116691, ECO:0000269|PubMed:24791901}.
CC -!- DOMAIN: The flexible c-MTBD (cationic microtubule binding domain)
CC region mediates binding to microtubules. It is positively charged and
CC becomes ordered when bound to microtubules: it interacts with a
CC negatively charged patch on tubulin. The presence of positive charges
CC in the c-MTBD region is essential for proper binding.
CC {ECO:0000250|UniProtKB:Q6ZT98, ECO:0000269|PubMed:25959773}.
CC -!- DOMAIN: Arg-186 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:0000250|UniProtKB:A4Q9E8}.
CC -!- DISEASE: Cone-rod dystrophy 19 (CORD19) [MIM:615860]: A form of cone-
CC rod dystrophy, an inherited retinal dystrophy characterized by retinal
CC pigment deposits visible on fundus examination, predominantly in the
CC macular region, and initial loss of cone photoreceptors followed by rod
CC degeneration. This leads to decreased visual acuity and sensitivity in
CC the central visual field, followed by loss of peripheral vision. Severe
CC loss of vision occurs earlier than in retinitis pigmentosa, due to cone
CC photoreceptors degenerating at a higher rate than rod photoreceptors.
CC {ECO:0000269|PubMed:24791901}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the tubulin--tyrosine ligase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF23275.2; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=AAP75557.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY237126; AAP75557.1; ALT_INIT; mRNA.
DR EMBL; AC007182; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC009399; AAF23275.2; ALT_SEQ; Genomic_DNA.
DR EMBL; AF107885; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471061; EAW81247.1; -; Genomic_DNA.
DR EMBL; CR533554; CAG38585.1; -; mRNA.
DR EMBL; AL136808; CAB66742.1; -; mRNA.
DR EMBL; BC002766; AAH02766.2; -; mRNA.
DR EMBL; BC136472; AAI36473.1; -; mRNA.
DR EMBL; BC136473; AAI36474.1; -; mRNA.
DR EMBL; AK024259; BAB14862.1; -; mRNA.
DR EMBL; AB023215; BAA76842.1; -; mRNA.
DR CCDS; CCDS32124.1; -. [Q6EMB2-1]
DR RefSeq; NP_055887.3; NM_015072.4. [Q6EMB2-1]
DR AlphaFoldDB; Q6EMB2; -.
DR SMR; Q6EMB2; -.
DR BioGRID; 116721; 55.
DR IntAct; Q6EMB2; 25.
DR MINT; Q6EMB2; -.
DR STRING; 9606.ENSP00000298832; -.
DR GlyCosmos; Q6EMB2; 1 site, 1 glycan.
DR GlyGen; Q6EMB2; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q6EMB2; -.
DR PhosphoSitePlus; Q6EMB2; -.
DR BioMuta; TTLL5; -.
DR DMDM; 239938834; -.
DR EPD; Q6EMB2; -.
DR jPOST; Q6EMB2; -.
DR MassIVE; Q6EMB2; -.
DR MaxQB; Q6EMB2; -.
DR PaxDb; 9606-ENSP00000298832; -.
DR PeptideAtlas; Q6EMB2; -.
DR ProteomicsDB; 66285; -. [Q6EMB2-1]
DR ProteomicsDB; 66286; -. [Q6EMB2-2]
DR ProteomicsDB; 66287; -. [Q6EMB2-3]
DR Pumba; Q6EMB2; -.
DR Antibodypedia; 25856; 70 antibodies from 13 providers.
DR DNASU; 23093; -.
DR Ensembl; ENST00000286650.9; ENSP00000286650.5; ENSG00000119685.20. [Q6EMB2-3]
DR Ensembl; ENST00000298832.14; ENSP00000298832.9; ENSG00000119685.20. [Q6EMB2-1]
DR Ensembl; ENST00000556893.5; ENSP00000452524.1; ENSG00000119685.20. [Q6EMB2-2]
DR GeneID; 23093; -.
DR KEGG; hsa:23093; -.
DR MANE-Select; ENST00000298832.14; ENSP00000298832.9; NM_015072.5; NP_055887.3.
DR UCSC; uc001xrw.3; human. [Q6EMB2-1]
DR AGR; HGNC:19963; -.
DR CTD; 23093; -.
DR DisGeNET; 23093; -.
DR GeneCards; TTLL5; -.
DR HGNC; HGNC:19963; TTLL5.
DR HPA; ENSG00000119685; Tissue enhanced (testis).
DR MalaCards; TTLL5; -.
DR MIM; 612268; gene.
DR MIM; 615860; phenotype.
DR neXtProt; NX_Q6EMB2; -.
DR OpenTargets; ENSG00000119685; -.
DR Orphanet; 1872; Cone rod dystrophy.
DR PharmGKB; PA164742694; -.
DR VEuPathDB; HostDB:ENSG00000119685; -.
DR eggNOG; KOG2156; Eukaryota.
DR eggNOG; KOG2157; Eukaryota.
DR GeneTree; ENSGT00940000162939; -.
DR HOGENOM; CLU_1034260_0_0_1; -.
DR InParanoid; Q6EMB2; -.
DR OrthoDB; 7265at2759; -.
DR PhylomeDB; Q6EMB2; -.
DR TreeFam; TF313087; -.
DR PathwayCommons; Q6EMB2; -.
DR Reactome; R-HSA-8955332; Carboxyterminal post-translational modifications of tubulin.
DR SignaLink; Q6EMB2; -.
DR BioGRID-ORCS; 23093; 16 hits in 1159 CRISPR screens.
DR ChiTaRS; TTLL5; human.
DR GenomeRNAi; 23093; -.
DR Pharos; Q6EMB2; Tbio.
DR PRO; PR:Q6EMB2; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q6EMB2; Protein.
DR Bgee; ENSG00000119685; Expressed in left testis and 207 other cell types or tissues.
DR ExpressionAtlas; Q6EMB2; baseline and differential.
DR Genevisible; Q6EMB2; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005929; C:cilium; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
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; ISS:UniProtKB.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0036211; P:protein modification process; IEA:InterPro.
DR GO; GO:0060041; P:retina development in camera-type eye; IMP:MGI.
DR Gene3D; 3.30.470.20; ATP-grasp fold, B domain; 1.
DR InterPro; IPR004344; TTL/TTLL_fam.
DR PANTHER; PTHR12241; TUBULIN POLYGLUTAMYLASE; 1.
DR PANTHER; PTHR12241:SF145; TUBULIN POLYGLUTAMYLASE TTLL5; 1.
DR Pfam; PF03133; TTL; 1.
DR SUPFAM; SSF56059; Glutathione synthetase ATP-binding domain-like; 1.
DR PROSITE; PS51221; TTL; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cell projection; Cilium;
KW Cone-rod dystrophy; Cytoplasm; Cytoskeleton; Disease variant; Ligase;
KW Magnesium; Metal-binding; Microtubule; Nucleotide-binding; Nucleus;
KW Reference proteome; Transcription.
FT CHAIN 1..1281
FT /note="Tubulin polyglutamylase TTLL5"
FT /id="PRO_0000223341"
FT DOMAIN 62..407
FT /note="TTL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00568"
FT REGION 378..488
FT /note="c-MTBD region"
FT /evidence="ECO:0000269|PubMed:25959773"
FT REGION 577..614
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1072..1114
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1199..1281
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 582..604
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1072..1112
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1236..1281
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 180
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 186..187
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 186
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 208..211
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 221..223
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 247
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 268..269
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 270
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 271
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 293
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 353
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 366
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 366
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 368
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 384
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT SITE 186
FT /note="Essential for specifying initiation versus
FT elongation step of the polyglutamylase activity"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT VAR_SEQ 1..462
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11230166, ECO:0000303|Ref.5"
FT /id="VSP_037453"
FT VAR_SEQ 248..269
FT /note="FATVRYDQGAKNIRNQFMHLTN -> KCNWKMGNTMDKRRLPIYVQVL (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_037454"
FT VAR_SEQ 270..1281
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_037455"
FT VAR_SEQ 516
FT /note="D -> DRGNPRRSLLTGRT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11230166, ECO:0000303|Ref.5"
FT /id="VSP_037456"
FT VAR_SEQ 1247..1281
FT /note="KGSSAEGQLNGLQSSLNPAAFVPITSSTDPAHTKI -> NTRFRSSFQNYLW
FT YFFQAVS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11230166, ECO:0000303|Ref.5"
FT /id="VSP_037457"
FT VARIANT 149
FT /note="A -> V (in dbSNP:rs2303345)"
FT /evidence="ECO:0000269|PubMed:10231032,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17116691,
FT ECO:0000269|Ref.3"
FT /id="VAR_057895"
FT VARIANT 203
FT /note="E -> D (in dbSNP:rs17856074)"
FT /id="VAR_057896"
FT VARIANT 543
FT /note="E -> K (in CORD19; dbSNP:rs199882533)"
FT /evidence="ECO:0000269|PubMed:24791901"
FT /id="VAR_071327"
FT VARIANT 592
FT /note="A -> T (in dbSNP:rs11848004)"
FT /id="VAR_057897"
FT VARIANT 1223
FT /note="A -> S (in dbSNP:rs10130991)"
FT /id="VAR_057898"
FT VARIANT 1231
FT /note="P -> T (in dbSNP:rs11844617)"
FT /id="VAR_057899"
FT VARIANT 1267
FT /note="F -> S (in dbSNP:rs1133834)"
FT /evidence="ECO:0000269|PubMed:10231032,
FT ECO:0000269|PubMed:17116691"
FT /id="VAR_057900"
FT MUTAGEN 467..473
FT /note="KVLRRVK->DVLDDVD: Decreased binding to microtubules
FT and polyglutamylase activity."
FT /evidence="ECO:0000269|PubMed:25959773"
SQ SEQUENCE 1281 AA; 143577 MW; 01441AFE6925AEDF CRC64;
MPIVMARDLE ETASSSEDEE VISQEDHPCI MWTGGCRRIP VLVFHADAIL TKDNNIRVIG
ERYHLSYKIV RTDSRLVRSI LTAHGFHEVH PSSTDYNLMW TGSHLKPFLL RTLSEAQKVN
HFPRSYELTR KDRLYKNIIR MQHTHGFKAF HILPQTFLLP AEYAEFCNSY SKDRGPWIVK
PVASSRGRGV YLINNPNQIS LEENILVSRY INNPLLIDDF KFDVRLYVLV TSYDPLVIYL
YEEGLARFAT VRYDQGAKNI RNQFMHLTNY SVNKKSGDYV SCDDPEVEDY GNKWSMSAML
RYLKQEGRDT TALMAHVEDL IIKTIISAEL AIATACKTFV PHRSSCFELY GFDVLIDSTL
KPWLLEVNLS PSLACDAPLD LKIKASMISD MFTVVGFVCQ DPAQRASTRP IYPTFESSRR
NPFQKPQRCR PLSASDAEMK NLVGSAREKG PGKLGGSVLG LSMEEIKVLR RVKEENDRRG
GFIRIFPTSE TWEIYGSYLE HKTSMNYMLA TRLFQDRMTA DGAPELKIES LNSKAKLHAA
LYERKLLSLE VRKRRRRSSR LRAMRPKYPV ITQPAEMNVK TETESEEEEE VALDNEDEEQ
EASQEESAGF LRENQAKYTP SLTALVENTP KENSMKVREW NNKGGHCCKL ETQELEPKFN
LMQILQDNGN LSKMQARIAF SAYLQHVQIR LMKDSGGQTF SASWAAKEDE QMELVVRFLK
RASNNLQHSL RMVLPSRRLA LLERRRILAH QLGDFIIVYN KETEQMAEKK SKKKVEEEEE
DGVNMENFQE FIRQASEAEL EEVLTFYTQK NKSASVFLGT HSKISKNNNN YSDSGAKGDH
PETIMEEVKI KPPKQQQTTE IHSDKLSRFT TSAEKEAKLV YSNSSSGPTA TLQKIPNTHL
SSVTTSDLSP GPCHHSSLSQ IPSAIPSMPH QPTILLNTVS ASASPCLHPG AQNIPSPTGL
PRCRSGSHTI GPFSSFQSAA HIYSQKLSRP SSAKAGSCYL NKHHSGIAKT QKEGEDASLY
SKRYNQSMVT AELQRLAEKQ AARQYSPSSH INLLTQQVTN LNLATGIINR SSASAPPTLR
PIISPSGPTW STQSDPQAPE NHSSSPGSRS LQTGGFAWEG EVENNVYSQA TGVVPQHKYH
PTAGSYQLQF ALQQLEQQKL QSRQLLDQSR ARHQAIFGSQ TLPNSNLWTM NNGAGCRISS
ATASGQKPTT LPQKVVPPPS SCASLVPKPP PNHEQVLRRA TSQKASKGSS AEGQLNGLQS
SLNPAAFVPI TSSTDPAHTK I
//
