ID   TTLL1_HUMAN             Reviewed;         423 AA.
AC   O95922; B2RDS7; Q9BR27; Q9NRS9; Q9UMU0;
DT   02-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   07-APR-2021, entry version 166.
DE   RecName: Full=Probable tubulin polyglutamylase TTLL1;
DE            EC=6.-.-.-;
DE   AltName: Full=Tubulin polyglutamylase complex subunit 3;
DE            Short=PGs3;
DE   AltName: Full=Tubulin--tyrosine ligase-like protein 1;
GN   Name=TTLL1; Synonyms=C22orf7;
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] (ISOFORMS A AND B), AND TISSUE SPECIFICITY.
RX   PubMed=11054573; DOI=10.1016/s0378-1119(00)00383-8;
RA   Trichet V., Ruault M., Roizes G., De Sario A.;
RT   "Characterization of the human tubulin tyrosine ligase-like 1 gene (TTLL1)
RT   mapping to 22q13.1.";
RL   Gene 257:109-117(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC   TISSUE=Brain;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A; B AND 4).
RX   PubMed=12529303; DOI=10.1101/gr.695703;
RA   Collins J.E., Goward M.E., Cole C.G., Smink L.J., Huckle E.J., Knowles S.,
RA   Bye J.M., Beare D.M., Dunham I.;
RT   "Reevaluating human gene annotation: a second-generation analysis of
RT   chromosome 22.";
RL   Genome Res. 13:27-36(2003).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RX   PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA   Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA   Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA   Beare D.M., Dunham I.;
RT   "A genome annotation-driven approach to cloning the human ORFeome.";
RL   Genome Biol. 5:R84.1-R84.11(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
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   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=10591208; DOI=10.1038/990031;
RA   Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA   Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA   Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA   Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA   Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA   Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA   Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA   Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA   Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA   Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA   Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA   Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA   Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA   Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA   Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA   Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA   Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA   Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA   Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA   Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA   Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA   Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA   Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA   Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA   Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA   Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA   Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA   Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA   Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA   Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA   Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA   Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA   Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA   McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA   Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA   Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA   Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA   Wright H.;
RT   "The DNA sequence of human chromosome 22.";
RL   Nature 402:489-495(1999).
RN   [7]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC   TISSUE=Eye;
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: Catalytic subunit of the neuronal tubulin polyglutamylase
CC       complex. Modifies alpha- and beta-tubulin, generating side chains of
CC       glutamate on the gamma-carboxyl groups of specific glutamate residues
CC       within the C-terminal tail of alpha- and beta-tubulin (By similarity).
CC       {ECO:0000250}.
CC   -!- SUBUNIT: Part of the neuronal tubulin polyglutamylase complex which
CC       contains TPGS1, TPGS2, TTLL1, LRRC49 and NICN1. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC         Comment=Additional isoforms seem to exist.;
CC       Name=A; Synonyms=TTLL1a;
CC         IsoId=O95922-1; Sequence=Displayed;
CC       Name=B; Synonyms=TTLL1b, Truncated;
CC         IsoId=O95922-2; Sequence=VSP_006671, VSP_006672;
CC       Name=4;
CC         IsoId=O95922-4; Sequence=VSP_011825;
CC   -!- TISSUE SPECIFICITY: Expressed in a wide range of tissues. Has a
CC       stronger expression in heart, brain and testis.
CC       {ECO:0000269|PubMed:11054573}.
CC   -!- MISCELLANEOUS: [Isoform B]: May be produced at very low levels due to a
CC       premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC       decay. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the tubulin polyglutamylase family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAB51423.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305};
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DR   EMBL; AF104927; AAG29879.1; -; mRNA.
DR   EMBL; AF173935; AAF91088.1; -; mRNA.
DR   EMBL; AL136687; CAB66622.1; -; mRNA.
DR   EMBL; AL096883; CAB51423.1; ALT_SEQ; mRNA.
DR   EMBL; AL096886; CAB51469.1; -; mRNA.
DR   EMBL; AL589867; CAC34478.1; -; mRNA.
DR   EMBL; CR456599; CAG30485.1; -; mRNA.
DR   EMBL; AK315658; BAG38024.1; -; mRNA.
DR   EMBL; AL022476; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471138; EAW73279.1; -; Genomic_DNA.
DR   EMBL; BC014968; AAH14968.1; -; mRNA.
DR   CCDS; CCDS14043.1; -. [O95922-1]
DR   RefSeq; NP_036395.1; NM_012263.4. [O95922-1]
DR   RefSeq; XP_011528410.1; XM_011530108.2.
DR   RefSeq; XP_016884240.1; XM_017028751.1. [O95922-1]
DR   RefSeq; XP_016884241.1; XM_017028752.1. [O95922-1]
DR   RefSeq; XP_016884242.1; XM_017028753.1.
DR   SMR; O95922; -.
DR   BioGRID; 117340; 24.
DR   IntAct; O95922; 20.
DR   STRING; 9606.ENSP00000266254; -.
DR   iPTMnet; O95922; -.
DR   PhosphoSitePlus; O95922; -.
DR   BioMuta; TTLL1; -.
DR   jPOST; O95922; -.
DR   MassIVE; O95922; -.
DR   PaxDb; O95922; -.
DR   PeptideAtlas; O95922; -.
DR   PRIDE; O95922; -.
DR   ProteomicsDB; 51124; -. [O95922-1]
DR   ProteomicsDB; 51125; -. [O95922-2]
DR   ProteomicsDB; 51126; -. [O95922-4]
DR   Antibodypedia; 27458; 41 antibodies.
DR   DNASU; 25809; -.
DR   Ensembl; ENST00000266254; ENSP00000266254; ENSG00000100271. [O95922-1]
DR   Ensembl; ENST00000331018; ENSP00000333734; ENSG00000100271. [O95922-4]
DR   Ensembl; ENST00000439248; ENSP00000401518; ENSG00000100271. [O95922-2]
DR   Ensembl; ENST00000440761; ENSP00000403332; ENSG00000100271. [O95922-2]
DR   GeneID; 25809; -.
DR   KEGG; hsa:25809; -.
DR   UCSC; uc003bdi.5; human. [O95922-1]
DR   CTD; 25809; -.
DR   DisGeNET; 25809; -.
DR   GeneCards; TTLL1; -.
DR   HGNC; HGNC:1312; TTLL1.
DR   HPA; ENSG00000100271; Low tissue specificity.
DR   MIM; 608955; gene.
DR   neXtProt; NX_O95922; -.
DR   OpenTargets; ENSG00000100271; -.
DR   PharmGKB; PA35030; -.
DR   VEuPathDB; HostDB:ENSG00000100271.16; -.
DR   eggNOG; KOG2157; Eukaryota.
DR   GeneTree; ENSGT00940000156720; -.
DR   HOGENOM; CLU_2960116_0_0_1; -.
DR   InParanoid; O95922; -.
DR   OMA; DVRWNKV; -.
DR   PhylomeDB; O95922; -.
DR   TreeFam; TF313087; -.
DR   PathwayCommons; O95922; -.
DR   Reactome; R-HSA-8955332; Carboxyterminal post-translational modifications of tubulin.
DR   BioGRID-ORCS; 25809; 7 hits in 984 CRISPR screens.
DR   ChiTaRS; TTLL1; human.
DR   GeneWiki; TTLL1; -.
DR   GenomeRNAi; 25809; -.
DR   Pharos; O95922; Tdark.
DR   PRO; PR:O95922; -.
DR   Proteomes; UP000005640; Chromosome 22.
DR   RNAct; O95922; protein.
DR   Bgee; ENSG00000100271; Expressed in cortical plate and 201 other tissues.
DR   ExpressionAtlas; O95922; baseline and differential.
DR   Genevisible; O95922; HS.
DR   GO; GO:0036064; C:ciliary basal body; IEA:Ensembl.
DR   GO; GO:0005929; C:cilium; IBA:GO_Central.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR   GO; GO:0005576; C:extracellular region; IEA:GOC.
DR   GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR   GO; GO:0005524; F:ATP 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:0021702; P:cerebellar Purkinje cell differentiation; IEA:Ensembl.
DR   GO; GO:0002395; P:immune response in nasopharyngeal-associated lymphoid tissue; IEA:Ensembl.
DR   GO; GO:0000226; P:microtubule cytoskeleton organization; IBA:GO_Central.
DR   GO; GO:0120197; P:mucociliary clearance; IEA:Ensembl.
DR   GO; GO:0018095; P:protein polyglutamylation; IBA:GO_Central.
DR   GO; GO:0120222; P:regulation of blastocyst development; IEA:Ensembl.
DR   GO; GO:0007288; P:sperm axoneme assembly; IEA:Ensembl.
DR   Gene3D; 3.30.1490.20; -; 1.
DR   InterPro; IPR013815; ATP_grasp_subdomain_1.
DR   InterPro; IPR004344; TTL/TTLL_fam.
DR   InterPro; IPR027750; TTLL1.
DR   PANTHER; PTHR12241:SF31; PTHR12241:SF31; 1.
DR   Pfam; PF03133; TTL; 1.
DR   PROSITE; PS51221; TTL; 1.
PE   2: Evidence at transcript level;
KW   Alternative splicing; ATP-binding; Cytoplasm; Cytoskeleton; Ligase;
KW   Microtubule; Nucleotide-binding; Reference proteome.
FT   CHAIN           1..423
FT                   /note="Probable tubulin polyglutamylase TTLL1"
FT                   /id="PRO_0000212438"
FT   DOMAIN          1..367
FT                   /note="TTL"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00568"
FT   NP_BIND         181..184
FT                   /note="ATP binding"
FT                   /evidence="ECO:0000250|UniProtKB:Q6ZT98"
FT   BINDING         194
FT                   /note="ATP"
FT                   /evidence="ECO:0000250|UniProtKB:Q6ZT98"
FT   BINDING         196
FT                   /note="ATP"
FT                   /evidence="ECO:0000250|UniProtKB:Q6ZT98"
FT   VAR_SEQ         39..59
FT                   /note="MSVQTIRNVFSVEAGYRLSDD -> LLDLPEFRYRSCLNEFPDFRV (in
FT                   isoform B)"
FT                   /evidence="ECO:0000303|PubMed:11054573,
FT                   ECO:0000303|PubMed:12529303"
FT                   /id="VSP_006671"
FT   VAR_SEQ         60..423
FT                   /note="Missing (in isoform B)"
FT                   /evidence="ECO:0000303|PubMed:11054573,
FT                   ECO:0000303|PubMed:12529303"
FT                   /id="VSP_006672"
FT   VAR_SEQ         298..326
FT                   /note="Missing (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:12529303"
FT                   /id="VSP_011825"
FT   VARIANT         168
FT                   /note="S -> L (in dbSNP:rs6003030)"
FT                   /id="VAR_052409"
SQ   SEQUENCE   423 AA;  48988 MW;  AFFDEEE008D2E655 CRC64;
     MAGKVKWVTD IEKSVLINNF EKRGWVQVTE NEDWNFYWMS VQTIRNVFSV EAGYRLSDDQ
     IVNHFPNHYE LTRKDLMVKN IKRYRKELEK EGSPLAEKDE NGKYLYLDFV PVTYMLPADY
     NLFVEEFRKS PSSTWIMKPC GKAQGKGIFL INKLSQIKKW SRDSKTSSFV SQSNKEAYVI
     SLYINNPLLI GGRKFDLRLY VLVSTYRPLR CYMYKLGFCR FCTVKYTPST SELDNMFVHL
     TNVAIQKHGE DYNHIHGGKW TVSNLRLYLE STRGKEVTSK LFDEIHWIIV QSLKAVAPVM
     NNDKHCFECY GYDIIIDDKL KPWLIEVNAS PSLTSSTAND RILKYNLIND TLNIAVPNGE
     IPDCKWNKSP PKEVLGNYEI LYDEELAQGD GADRELRSRQ GQSLGPRAGR SRDSGRAVLT
     TWK
//