Conserved Protein Domain Family
TTL

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pfam03133: TTL 
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 tumour 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: 281171
View PSSM: pfam03133
Aligned: 20 rows
Threshold Bit Score: 234.15
Threshold Setting Gi: 1723548
Created: 23-Jun-2015
Updated: 5-Aug-2015
Structure
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Aligned Rows:
PubMed ReferencesClick to see Conserved Features Help

pfam03133 is a member of the superfamily cl17255.
Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74871827  119 FSVDSGYrmhdNQMINHFPNHYELSRKD-LLVKNIKRYRKDLERDgnplaektesnnssgtrylyLDFVPTTFVLPADYN 197
gi 74869013  126 ANLKNLGq---HQVVNHYPGCGYLTNKV---D------LCTTQLP----------------------FLPRAFRLPAERE 171
gi 257096967 325 VRHAEHYs--lDDARIKPPTPAEIVENQtFMVQSTDVLKSNAKFKvs-----------------eKVMAEYARLAGLYLD 385
gi 172046606 213 MDIDKD-----LEAPLYLTPEGWSLFLQ-RYYQVVHEGAELRHLD--------------------TQVQRCEDILQQLQA 266
gi 74869876  342 IDSCQHN----DIDFEDPPKIWEHDWDA-FLFQHQQLVNEDGRIQhd----------------ggQRLEPMVKSCLSLVD 400
gi 586134     81 IKTSPEL----AESCTWFPESYVIYPTN-LKTPVAPAQDGIHPPL----------------------HSSRTDEREFFLA 133
gi 6686247   370 QLSEENP----CGMINQFPFESCITVKD-LLAACAMRDPAKNDWY------------------------QLTYNLNTQLP 420
gi 20455527  346 KLSQERP----GVLLNQFPCENLLTVKD-CLASIARRAGGPEGPP----------------------WLPRTFNLRTELP 398
gi 342187090 388 EQLDMDKl---MELPNNYFTNSYIYRKAlIRKHFLSHTIQTYTAKnpe--------------silKKAYLESFTIDLDYA 450
gi 1723548   119 SLMEA------YELRQELEENATKNISE-KQWYILKPSMCDRAQG------------------------IRLFSTIEELQ 167
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74871827  198 MFVEEYRKFPL------------STWIMKPCGKSQGAGIFLINKLSKLKKwsreak------------------------ 241
gi 74869013  172 EFLDYARENPQ-------------ALFVQKHNEHRHIKVRAPADIAFGS------------------------------- 207
gi 257096967 386 QIESLRPDYRWdg--------srNLWILKPGYQSRGIGIVIRSSLDDILQwt---------------------------- 429
gi 172046606 267 VVPQIDMEGDR------------NIWIVKPGAKSRGRGIMCMDHLEEMLKlvng-------------------------- 308
gi 74869876  401 KMKVHWPQYSLdg--------yqNMWIVKPANKCRGRGIILMDNLKKILGvvn--------------------------- 445
gi 586134    134 SYNRKKEEGEG------------NVWIAKSSAGAKGEGILISSDATELLDfi---------------------------- 173
gi 6686247   421 EFVARFQNRELng--------qhNVWIVKPWNLARGMDMTVTEDLNQIIR------------------------------ 462
gi 20455527  399 QFVSYFQQRERwg--------edNHWICKPWNLARSLDTHVTKSLHSIIR------------------------------ 440
gi 342187090 451 EFLDDALDENWelrqelenesqdKWWIVKPSMSDKGQGIRVFKTIEDLQAifdsfddedseaeesgndddaddvngefmd 530
gi 1723548   168 AIFDSFDDEES--------------ESEEAGLEEKGDITVAFNNKIVIS------------------------------- 202
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74871827  242 gpfhpQIAKESYVISRYIDNPLLIGG------KKFDLRLYVLVASF-RPLKAYLFKQG-FCRFCTVKYDt------sVTE 307
gi 74869013  208 ---------NDSFVQEFVQRPYLVDG------HKFDIGVYVVITSV-NPLRVYIYTGDvLFRYCPVKYHp--------FD 263
gi 257096967 430 ----sNNQNKKYIVQKYIERPLLIYR------TKFDIRQYMLLTITdTKVSIWTYRDC-YLRFSSQEFT---------MD 489
gi 172046606 309 --npvVMKDGKWVVQKYIERPLLIFG------TKFDLRQWFLVTDW-NPLTVWFYRDS-YIRFSTQPFS---------LK 369
gi 74869876  446 ---lsIASKSRYVVQKYIERPLILFQ------TKFDIRQWFLITNT-QPLVVWFYRES-YLRFSSQEYS---------LS 505
gi 586134    174 -----dnQGQVHVIQKYLERPLLLEPg----hRKFDIRSWVLVD---HQFNIYLYREG-VLRTASEPYH--------MDN 232
gi 6686247   463 -----MIETGPKIVCEYIPRPLLFPRpdngnkVKFDLRYIVFLNGI-APVTAYVYNRF-WIRFAINEFS--------LSN 527
gi 20455527  441 -----HRESTPKVVSKYIESPVLFLRedv-gkVKFDIRYIVLLRSV-RPLRLFVYDVF-WLRFSNRAFA--------LND 504
gi 342187090 531 nnkvnISQLRHFIIQEYLTNPLLLASmd---nRKFHIRCYVVCRG---DLQVFVYDRM-LALFAAKPFVpldpyaysVTD 603
gi 1723548   203 -------QIRNFLVQKYISKPLLLDH------RKFHIRAYVLATG---ALSVYLFNEM-LCLLARDKYKk------pTPD 259
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74871827  308 LDNMYVHLTNVSVQKH------GGEYNTLHGGKWSVQNLALYLEG--TRGKEVTDRLFGAISWLIVHS--LRAVAPVMAS 377
gi 74869013  264 AENVDKYIVGDDYLPTwevpslRKYYNRFGGSMRTVFEAYVRDQG--KDPAQIWPQVEHIVRTTIAAKekDIVNILRSYR 341
gi 257096967 490 DLRESIHLTNNSVQKRykn-ktNRDSRLPKNNMWSLDQFKNYLRIm-GAPDGSWSKTYNGFKQNLVAV--VMASLDETEL 565
gi 172046606 370 NLDNSVHLCNNSIQKHlen-scHRHPLLPPDNMWSSQRFQAHLQE--MGAPNAWSTIIVPGMKDAVIHa-LQTSQDTVQC 445
gi 74869876  506 NHHESVHLTNYAIQKKyt--ngKRDKRLPSENMWDCYSFQAYLRQ--IGKYNMWLERIFPGMRKAIVGc-MLASQENMDR 580
gi 586134    233 FQDKTCHLTNHCIQKEys--knYGKYEEGNEMFFEAFNRYLTSALn-ITLESSILLQIKHIIRSCLMS--VEPAISTKHL 307
gi 6686247   528 FEDVETHFTVFNYLDK--------EKILQMKCENFIETIEKAYPR--IQWSEVQKDINLTIRKAIEAAa-KEEAPRGVAP 596
gi 20455527  505 LDDYEKHFTVMNYDPD--------VVLKQVHCEEFIPEFEKQYPE--FPWTDVQAEIFRAFTELFQVAc-AKPPPLGLCD 573
gi 342187090 604 LKDLECHLTNTCLQSK------------KKDKDSSVLEFDSIEEIpnERKSNIKEQIHSITNDVFLAA--VNVNRLNFQP 669
gi 1723548   260 PDLLFSHLSNTCLQGD-------------NVEQSSIRDFWNTSIE---NKDDIFKSILNIIGDVFEAA--ATTQGIHFQP 321
                        330       340       350       360       370       380       390
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 74871827  378 DRHCFECYGYDIII--------DNALKPWLVEVNASPSL-TSTTVNDRILKYKLIDNILS---VVLPPDGVPDV 439
gi 74869013  342 THNFFDLMRFDLFI--------DEDLKVFLMEANMSPNLsSAHFKPNSLLYEQVLYSVFNlvgIRPLTSTSGAL 407
gi 257096967 566 LQNAFELYGCDFML--------DEHYNPILIEINSTPDL-SPSTEITARICPMVLKDCIR-----VVVDLPKNP 625
gi 172046606 446 RKASFELYGADFVF--------GEDFQPWLIEINASPTM-APSTAVTARLCAGVQADTLR-----VVIDRMLDR 505
gi 74869876  581 RPNTFELFGADFMI--------CENFYPWLIEINSSPDL-GATTSVTARMCPQCLEDVVK-----VVIDRRTDP 640
gi 586134    308 PYQSFQLFGFDFMV--------DEELKVWLIEVNGAP---ACAQKLYAELCQGIVDIAIA---SVFPPPDAEQQ 367
gi 6686247   597 NVQSRAMYGVDIMLqh----gdNDVIKSTLLEINFMPDT-TRACQYYPDFADTVFETLFL---DEIDPTKVTPI 662
gi 20455527  574 YPSSRAMYAVDLMLkwdngpdgRRVMQPQILEVNFNPDC-ERACRYHPTFFNDVFSTLFL---D-QPGGCHVTC 642
gi 342187090 670 LPNAFETYGVDFLI--------DSNYEVKLLEINAFPDF-KQTGKDLKNLIDELFDDTVKy--CVTPIFNENRN 732
gi 1723548   322 LENCFEIFGVDFLV--------DCESQVYLLEVNSYPDF-KQTGKNLSNIIENLFSAVVE---TAIIPFFESST 383
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