TTLL2_HUMAN
ID TTLL2_HUMAN Reviewed; 592 AA.
AC Q9BWV7; B2RB11; B3KS77; Q7Z6R8; Q86X22;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 3.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Probable tubulin polyglutamylase TTLL2;
DE EC=6.-.-.-;
DE AltName: Full=Testis-specific protein NYD-TSPG;
DE AltName: Full=Tubulin--tyrosine ligase-like protein 2;
GN Name=TTLL2 {ECO:0000312|HGNC:HGNC:21211}; Synonyms=C6orf104;
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], AND VARIANT GLY-425.
RC TISSUE=Testis;
RA Sha J.H.;
RT "Cloning of a novel testis specific gene from human testes.";
RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-425.
RC TISSUE=Testis;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLY-425.
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
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], AND VARIANTS ALA-127 AND GLY-425.
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).
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 (By similarity). Similar
CC to TTLL1, may acquire enzymatic activity only in complex with other
CC proteins as it is most likely lacking domains important for autonomous
CC activity (By similarity). Probably involved in the side-chain
CC initiation step of the polyglutamylation reaction rather than the
CC elongation step (By similarity). {ECO:0000250|UniProtKB:A4Q9E4,
CC ECO:0000250|UniProtKB:Q91V51}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:A4Q9E8};
CC -!- TISSUE SPECIFICITY: Testis. {ECO:0000305|Ref.1}.
CC -!- DOMAIN: Arg-218 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:A4Q9E4}.
CC -!- SIMILARITY: Belongs to the tubulin--tyrosine ligase family.
CC {ECO:0000305}.
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DR EMBL; AY026506; AAK20169.1; -; mRNA.
DR EMBL; AK093039; BAG52639.1; -; mRNA.
DR EMBL; AK314450; BAG37058.1; -; mRNA.
DR EMBL; AL021331; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW47498.1; -; Genomic_DNA.
DR EMBL; BC030650; AAH30650.1; -; mRNA.
DR EMBL; BC047411; AAH47411.1; -; mRNA.
DR CCDS; CCDS5301.1; -.
DR RefSeq; NP_114155.4; NM_031949.4.
DR AlphaFoldDB; Q9BWV7; -.
DR SMR; Q9BWV7; -.
DR BioGRID; 123798; 5.
DR IntAct; Q9BWV7; 1.
DR STRING; 9606.ENSP00000239587; -.
DR iPTMnet; Q9BWV7; -.
DR PhosphoSitePlus; Q9BWV7; -.
DR BioMuta; TTLL2; -.
DR DMDM; 313104264; -.
DR jPOST; Q9BWV7; -.
DR MassIVE; Q9BWV7; -.
DR PaxDb; Q9BWV7; -.
DR PeptideAtlas; Q9BWV7; -.
DR PRIDE; Q9BWV7; -.
DR ProteomicsDB; 79329; -.
DR Antibodypedia; 20063; 33 antibodies from 8 providers.
DR DNASU; 83887; -.
DR Ensembl; ENST00000239587.10; ENSP00000239587.5; ENSG00000120440.15.
DR Ensembl; ENST00000515138.1; ENSP00000424130.1; ENSG00000120440.15.
DR GeneID; 83887; -.
DR KEGG; hsa:83887; -.
DR MANE-Select; ENST00000239587.10; ENSP00000239587.5; NM_031949.5; NP_114155.4.
DR UCSC; uc003qvs.2; human.
DR CTD; 83887; -.
DR GeneCards; TTLL2; -.
DR HGNC; HGNC:21211; TTLL2.
DR HPA; ENSG00000120440; Tissue enriched (testis).
DR neXtProt; NX_Q9BWV7; -.
DR OpenTargets; ENSG00000120440; -.
DR PharmGKB; PA134888799; -.
DR VEuPathDB; HostDB:ENSG00000120440; -.
DR eggNOG; KOG2157; Eukaryota.
DR GeneTree; ENSGT00940000162752; -.
DR HOGENOM; CLU_010131_9_0_1; -.
DR InParanoid; Q9BWV7; -.
DR OMA; SDHGKAP; -.
DR OrthoDB; 626048at2759; -.
DR PhylomeDB; Q9BWV7; -.
DR TreeFam; TF313087; -.
DR PathwayCommons; Q9BWV7; -.
DR Reactome; R-HSA-8955332; Carboxyterminal post-translational modifications of tubulin.
DR SignaLink; Q9BWV7; -.
DR BioGRID-ORCS; 83887; 12 hits in 1072 CRISPR screens.
DR ChiTaRS; TTLL2; human.
DR GenomeRNAi; 83887; -.
DR Pharos; Q9BWV7; Tdark.
DR PRO; PR:Q9BWV7; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9BWV7; protein.
DR Bgee; ENSG00000120440; Expressed in sperm and 70 other tissues.
DR ExpressionAtlas; Q9BWV7; baseline and differential.
DR Genevisible; Q9BWV7; HS.
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..592
FT /note="Probable tubulin polyglutamylase TTLL2"
FT /id="PRO_0000212440"
FT DOMAIN 84..427
FT /note="TTL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00568"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 51..77
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 300..301
FT /note="L-glutamate"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 212
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 218..219
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 218
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 240..243
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 253..255
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 279
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 298..299
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 321
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 373
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 386
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 386
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 388
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT BINDING 404
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT SITE 218
FT /note="Essential for specifying initiation versus
FT elongation step of the polyglutamylase activity"
FT /evidence="ECO:0000250|UniProtKB:A4Q9E8"
FT VARIANT 3
FT /note="G -> R (in dbSNP:rs12526094)"
FT /id="VAR_028119"
FT VARIANT 63
FT /note="P -> S (in dbSNP:rs34350976)"
FT /id="VAR_057312"
FT VARIANT 127
FT /note="T -> A (in dbSNP:rs11540664)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_028120"
FT VARIANT 202
FT /note="L -> P (in dbSNP:rs6936639)"
FT /id="VAR_028121"
FT VARIANT 356
FT /note="I -> V (in dbSNP:rs34286114)"
FT /id="VAR_057313"
FT VARIANT 425
FT /note="R -> G (in dbSNP:rs909545)"
FT /evidence="ECO:0000269|PubMed:14574404,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|Ref.1"
FT /id="VAR_028122"
FT VARIANT 441
FT /note="K -> T (in dbSNP:rs41266331)"
FT /id="VAR_061866"
FT VARIANT 445
FT /note="G -> S (in dbSNP:rs9457304)"
FT /id="VAR_028123"
FT VARIANT 529
FT /note="Q -> H (in dbSNP:rs12528714)"
FT /id="VAR_028124"
FT VARIANT 559
FT /note="V -> I (in dbSNP:rs34931196)"
FT /id="VAR_057314"
FT CONFLICT 377
FT /note="D -> N (in Ref. 1; AAK20169)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 592 AA; 67336 MW; 43F7741950AFE70D CRC64;
MRGRDLCSST QSQALGSLRT TTPAFTLNIP SEANHTEQPP AGLGARLQEA GVSIPPRRGR
PTPTLEKKKK PHLMAEDEPS GALLKPLVFR VDETTPAVVQ SVLLERGWNK FDKQEQNAED
WNLYWRTSSF RMTEHNSVKP WQQLNHHPGT TKLTRKDCLA KHLKHMRRMY GTSLYQFIPL
TFVMPNDYTK FVAEYFQERQ MLGTKHSYWI CKPAELSRGR GILIFSDFKD FIFDDMYIVQ
KYISNPLLIG RYKCDLRIYV CVTGFKPLTI YVYQEGLVRF ATEKFDLSNL QNNYAHLTNS
SINKSGASYE KIKEVIGHGC KWTLSRFFSY LRSWDVDDLL LWKKIHRMVI LTILAIAPSV
PFAANCFELF GFDILIDDNL KPWLLEVNYS PALTLDCSTD VLVKRKLVHD IIDLIYLNGL
RNEGREASNA THGNSNIDAA KSDRGGLDAP DCLPYDSLSF TSRMYNEDDS VVEKAVSVRP
EAAPASQLEG EMSGQDFHLS TREMPQSKPK LRSRHTPHKT LMPYASLFQS HSCKTKTSPC
VLSDRGKAPD PQAGNFVLVF PFNEATLGAS RNGLNVKRII QELQKLMNKQ HS
