5J2U


Conserved Protein Domain Family
TTL

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pfam03133: TTL 
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Tubulin-tyrosine ligase family
Tubulins and microtubules are subjected to several post-translational modifications of which the reversible detyrosination/tyrosination of the carboxy-terminal end of most alpha-tubulins has been extensively analysed. This modification cycle involves a specific carboxypeptidase and the activity of the tubulin-tyrosine ligase (TTL). The true physiological function of TTL has so far not been established. Tubulin-tyrosine ligase (TTL) catalyzes the ATP-dependent post-translational addition of a tyrosine to the carboxy terminal end of detyrosinated alpha-tubulin. In normally cycling cells, the tyrosinated form of tubulin predominates. However, in breast cancer cells, the detyrosinated form frequently predominates, with a correlation to tumor aggressiveness. On the other hand, 3-nitrotyrosine has been shown to be incorporated, by TTL, into the carboxy terminal end of detyrosinated alpha-tubulin. This reaction is not reversible by the carboxypeptidase enzyme. Cells cultured in 3-nitrotyrosine rich medium showed evidence of altered microtubule structure and function, including altered cell morphology, epithelial barrier dysfunction, and apoptosis. Bacterial homologs of TTL are predicted to form peptide tags. Some of these are fused to a 2-oxoglutarate Fe(II)-dependent dioxygenase domain.
Statistics
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PSSM-Id: 397308
Aligned: 20 rows
Threshold Bit Score: 234.152
Threshold Setting Gi: 1723548
Created: 11-May-2020
Updated: 7-Aug-2020
Structure
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Program:
Drawing:
Aligned Rows:
PubMed ReferencesClick to see Conserved Features Help

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
5J2U_F  81 IKTSPEL--SESCTWFPESYVIYPTN-LKTPVAPAQNGIRHLI--------NNTRTDEREVFLAAYNRRREGREG----- 144 cattle
Q9VGW2 126 ANLKNLGq-HQVVNHYPGCGYLTNKV---D------LCTTQLP--------FLPRAFRLPAEREEFLDYARENPQ----- 182 fruit fly
Q9VM92 325 VRHAEHYslDDARIKPPTPAEIVENQtFMVQSTDVLKSNAKFKvse---kvMAEYARLAGLYLDQIESLRPDYRWdg--- 398 fruit fly
Q9Y4R7 213 MDIDKD---LEAPLYLTPEGWSLFLQ-RYYQVVHEGAELRHLDt------qVQRCEDILQQLQAVVPQIDMEGDR----- 277 human
Q4Q4Y1 122 iTLKSSM--VTALLKHHNYNWNTLGD-YLPMSFKLTPCQSSRD----------ERQQLLATLKGRMRPLHEGDEP----- 183 Leishmania major
Q09512 370 QLSEENP--CGMINQFPFESCITVKD-LLAACAMRDPAKNDWY----------QLTYNLNTQLPEFVARFQNRELng--- 433 Caenorhabditis elegans
Q14166 346 KLSQERP--GVLLNQFPCENLLTVKD-CLASIARRAGGPEGPP--------WLPRTFNLRTELPQFVSYFQQRERwg--- 411 human
P38254 388 EQLDMDKl-MELPNNYFTNSYIYRKAlIRKHFLSHTIQTYTAKnpesilkkAYLESFTIDLDYAEFLDDALDENWelrqe 466 Saccharomyces cerevis...
Q10438 119 SLMEA----YELRQELEENATKNISE-KQWYILKPSMCDRAQG----------IRLFSTIEELQAIFDSFDDEES----- 178 Schizosaccharomyces p...
Q9VB58 190 FKNMKR---FQQINHFPGMIEICRKD-LLSRNLNRMLKIFPQDy------kIFPKTWMLPADYGDAMNYALNHKR----- 254 fruit fly
5J2U_F 145 -------NVWIAKSSAGAKGEGILISSEASELLDFi-------------------------------dE--QGQVHVIQK 184 cattle
Q9VGW2 183 --------ALFVQKHNEHRHIKVRAPADIAFGS----------------------------------------NDSFVQE 214 fruit fly
Q9VM92 399 -----srNLWILKPGYQSRGIGIVIRSSLDDILQWt--------------------------------SnnQNKKYIVQK 441 fruit fly
Q9Y4R7 278 -------NIWIVKPGAKSRGRGIMCMDHLEEMLKLvng----------------------------npVvmKDGKWVVQK 322 human
Q4Q4Y1 184 -------CLWIAKSSAGCHGDNIEIFRGDYRGILKllr---------------------------fidSqhGSQPWIAQQ 229 Leishmania major
Q09512 434 -----qhNVWIVKPWNLARGMDMTVTEDLNQIIRm-----------------------------------iETGPKIVCE 473 Caenorhabditis elegans
Q14166 412 -----edNHWICKPWNLARSLDTHVTKSLHSIIRh-----------------------------------rESTPKVVSK 451 human
P38254 467 lenesqdKWWIVKPSMSDKGQGIRVFKTIEDLQAIfdsfddedseaeesgndddaddvngefmdnnkvNisQLRHFIIQE 546 Saccharomyces cerevis...
Q10438 179 ---------ESEEAGLEEKGDITVAFNNKIVIS--------------------------------------QIRNFLVQK 211 Schizosaccharomyces p...
Q9VB58 255 --------TFILKPDSGAQGRGIWLTNDLKTIG--------------------------------------PHERLICQT 288 fruit fly
5J2U_F 185 YLEKPLLLEPg----hRKFDIRSWVLVD---HLYNIYLYREG-VLRTSSEPYN--------SANFQDKTCHLTNHCIQKE 248 cattle
Q9VGW2 215 FVQRPYLVDG------HKFDIGVYVVITs-vNPLRVYIYTGDvLFRYCPVKYHp--------FDAENVDKYIVGDDYLPT 279 fruit fly
Q9VM92 442 YIERPLLIYR------TKFDIRQYMLLTitdTKVSIWTYRDC-YLRFSSQEFT---------MDDLRESIHLTNNSVQKR 505 fruit fly
Q9Y4R7 323 YIERPLLIFG------TKFDLRQWFLVTd-wNPLTVWFYRDS-YIRFSTQPFS---------LKNLDNSVHLCNNSIQKH 385 human
Q4Q4Y1 230 YVDRPLLYHK------RKFDIRCWALLLr--DMYEIYVHEEL-VMRTSSVPYNres---atSKTPTGRLAHITNHCVQET 297 Leishmania major
Q09512 474 YIPRPLLFPRpdngnkVKFDLRYIVFLNg-iAPVTAYVYNRF-WIRFAINEFS--------LSNFEDVETHFTVFNYLDK 543 Caenorhabditis elegans
Q14166 452 YIESPVLFLRedv-gkVKFDIRYIVLLRs-vRPLRLFVYDVF-WLRFSNRAFA--------LNDLDDYEKHFTVMNYDPD 520 human
P38254 547 YLTNPLLLASmd---nRKFHIRCYVVCRg---DLQVFVYDRM-LALFAAKPFVpldpyaysVTDLKDLECHLTNTCLQSK 619 Saccharomyces cerevis...
Q10438 212 YISKPLLLDH------RKFHIRAYVLATg---ALSVYLFNEM-LCLLARDKYKk------pTPDPDLLFSHLSNTCLQGD 275 Schizosaccharomyces p...
Q9VB58 289 YIHRPLLIDG------YKFDLRVYTLITs-vDPLRIFVYNEG-LARFATNKYVep-----tPGNANDLYMHLTNYSVNKR 355 fruit fly
5J2U_F 249 ys--knYGRYEEGNEMFFEEFNQYLMDALn-TTLENSILLQIKHIIRSCLMC-------IEPAISTKHLHYQSFQLFGFD 318 cattle
Q9VGW2 280 wevpslRKYYNRFGGSMRTVFEAYVRDQG--KDPAQIWPQVEHIVRTTIAAKe-----kDIVNILRSYRTHNFFDLMRFD 352 fruit fly
Q9VM92 506 ykn-ktNRDSRLPKNNMWSLDQFKNYLRIm-GAPDGSWSKTYNGFKQNLVAV-------VMASLDETELLQNAFELYGCD 576 fruit fly
Q9Y4R7 386 len-scHRHPLLPPDNMWSSQRFQAHLQE--MGAPNAWSTIIVPGMKDAVIHa------LQTSQDTVQCRKASFELYGAD 456 human
Q4Q4Y1 298 skmyslYEESNELWREHLDGLIRYKGTVRaaKLKQEKYTPLCSPRPQEPNRGd------VPYPTRYSNDSRESLYPIREA 371 Leishmania major
Q09512 544 --------EKILQMKCENFIETIEKAYPR--IQWSEVQKDINLTIRKAIEAAa------KEEAPRGVAPNVQSRAMYGVD 607 Caenorhabditis elegans
Q14166 521 --------VVLKQVHCEEFIPEFEKQYPE--FPWTDVQAEIFRAFTELFQVAc------AKPPPLGLCDYPSSRAMYAVD 584 human
P38254 620 ------------KKDKDSSVLEFDSIEEIpnERKSNIKEQIHSITNDVFLAA-------VNVNRLNFQPLPNAFETYGVD 680 Saccharomyces cerevis...
Q10438 276 -------------NVEQSSIRDFWNTSIE---NKDDIFKSILNIIGDVFEAA-------ATTQGIHFQPLENCFEIFGVD 332 Schizosaccharomyces p...
Q9VB58 356 nshyelCDNDDCGSKRKLSAINNWMRRHN--YDVEEFWSNVDDVIIKTVLSAwpvlkhnYHACFPGHDKIQACFEILGFD 433 fruit fly
5J2U_F 319 FMV--------DEELKVWLIEVNGAP---ACAQKLYAELCQGIVDVAIS---SVFPLADTGQK 367 cattle
Q9VGW2 353 LFI--------DEDLKVFLMEANMSPnlsSAHFKPNSLLYEQVLYSVFNlvgIRPLTSTSGAL 407 fruit fly
Q9VM92 577 FML--------DEHYNPILIEINSTPd-lSPSTEITARICPMVLKDCIR-----VVVDLPKNP 625 fruit fly
Q9Y4R7 457 FVF--------GEDFQPWLIEINASPt-mAPSTAVTARLCAGVQADTLR-----VVIDRMLDR 505 human
Q4Q4Y1 372 YRG--------DSTTAPRFVSVRDEPt-tITLDNHVMPQIHFIIRDSLLaarSHVPGEpaipp 425 Leishmania major
Q09512 608 IMLqh----gdNDVIKSTLLEINFMPd-tTRACQYYPDFADTVFETLFL---DEIDPTKVTPI 662 Caenorhabditis elegans
Q14166 585 LMLkwdngpdgRRVMQPQILEVNFNPd-cERACRYHPTFFNDVFSTLFL---D-QPGGCHVTC 642 human
P38254 681 FLI--------DSNYEVKLLEINAFPd-fKQTGKDLKNLIDELFDDTVKy--CVTPIFNENRN 732 Saccharomyces cerevisiae S288C
Q10438 333 FLV--------DCESQVYLLEVNSYPd-fKQTGKNLSNIIENLFSAVVE---TAIIPFFESST 383 Schizosaccharomyces pombe 972h-
Q9VB58 434 ILV--------DWKLKPYILEVNHSPs-fHTNEQVDREVKRPLIRDTLNl-vSTVLADKRQIL 486 fruit fly
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