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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) catalyses 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: 251749
View PSSM: pfam03133
Aligned: 22 rows
Threshold Bit Score: 224.89
Threshold Setting Gi: 1723548
Created: 28-Mar-2013
Updated: 4-Apr-2013
Structure
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Program:
Drawing:
Aligned Rows:

pfam03133 is a member of the superfamily cl18406.
Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4I4T_F        81 IKTSPEl--SESCTWFPESYVIYPTN-LKTPVAPAQNGIRH--------LINNTRTDEREVFLAAYNRRREGREG----- 144
gi 257096967 325 VRHAEHyslDDARIKPPTPAEIVENQtFMVQSTDVLKSNAKfkv---seKVMAEYARLAGLYLDQIESLRPDYRWdg--- 398
gi 172046606 213 MDIDKD---LEAPLYLTPEGWSLFLQ-RYYQVVHEGAELRHl------dTQVQRCEDILQQLQAVVPQIDMEGDR----- 277
gi 74869876  342 IDSCQHn--DIDFEDPPKIWEHDWDA-FLFQHQQLVNEDGRiqh--dggQRLEPMVKSCLSLVDKMKVHWPQYSLdg--- 413
gi 586134     81 IKTSPEl--AESCTWFPESYVIYPTN-LKTPVAPAQDGIHPp--------lHSSRTDEREFFLASYNRKKEEGEG----- 144
gi 20455327   81 VKTSPEl--SESCSWFPESYVIHPTN-LKTPVAPAQNGIQLp--------vSNSRTDEREFFLASYNRKKEDGEG----- 144
gi 6686247   370 QLSEENp--CGMINQFPFESCITVKD-LLAACAMRDPAKNDw----------yQLTYNLNTQLPEFVARFQNRELng--- 433
gi 20455527  346 KLSQERp--GVLLNQFPCENLLTVKD-CLASIARRAGGPEGp--------pWLPRTFNLRTELPQFVSYFQQRERwg--- 411
gi 342187090 388 EQLDMDk-lMELPNNYFTNSYIYRKAlIRKHFLSHTIQTYTaknpesilKKAYLESFTIDLDYAEFLDDALDENWelrqe 466
gi 1723548   119 SLMEA----YELRQELEENATKNISE-KQWYILKPSMCDRAq----------gIRLFSTIEELQAIFDSFDDEES----- 178
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4I4T_F       145 -------NVWIAKSSAGAKGEGILISSEASELLdfi---------------------------------deQGQVHVIQK 184
gi 257096967 399 -----srNLWILKPGYQSRGIGIVIRSSLDDILqwt--------------------------------snnQNKKYIVQK 441
gi 172046606 278 -------NIWIVKPGAKSRGRGIMCMDHLEEMLklvng----------------------------npvvmKDGKWVVQK 322
gi 74869876  414 -----yqNMWIVKPANKCRGRGIILMDNLKKILgvvn------------------------------lsiaSKSRYVVQK 458
gi 586134    145 -------NVWIAKSSAGAKGEGILISSDATELLdfi---------------------------------dnQGQVHVIQK 184
gi 20455327  145 -------NVWIAKSSAGAKGEGILISSEASELLdfi---------------------------------dnQGQVHVIQK 184
gi 6686247   434 -----qhNVWIVKPWNLARGMDMTVTEDLNQIIrm-----------------------------------iETGPKIVCE 473
gi 20455527  412 -----edNHWICKPWNLARSLDTHVTKSLHSIIrh-----------------------------------rESTPKVVSK 451
gi 342187090 467 lenesqdKWWIVKPSMSDKGQGIRVFKTIEDLQaifdsfddedseaeesgndddaddvngefmdnnkvnisQLRHFIIQE 546
gi 1723548   179 ---------ESEEAGLEEKGDITVAFNNKIVIS--------------------------------------QIRNFLVQK 211
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4I4T_F       185 YLEKPLLLepGH------RKFDIRSWVLVD---HLYNIYLYREGVLRTSSEPYNS------A--NFQDKTCHLTNHCIQK 247
gi 257096967 442 YIERPLLI--YR------TKFDIRQYMLLTitdTKVSIWTYRDCYLRFSSQEFTm---------DDLRESIHLTNNSVQK 504
gi 172046606 323 YIERPLLI--FG------TKFDLRQWFLVTd-wNPLTVWFYRDSYIRFSTQPFSl---------KNLDNSVHLCNNSIQK 384
gi 74869876  459 YIERPLIL--FQ------TKFDIRQWFLITn-tQPLVVWFYRESYLRFSSQEYSl---------SNHHESVHLTNYAIQK 520
gi 586134    185 YLERPLLL--EPg----hRKFDIRSWVLVD---HQFNIYLYREGVLRTASEPYHm--------dNFQDKTCHLTNHCIQK 247
gi 20455327  185 YLEHPLLL--EPg----hRKFDIRSWVLVD---HQYNIYLYREGVLRTASEPYHv--------dNFQDKTCHLTNHCIQK 247
gi 6686247   474 YIPRPLLF--PRpdngnkVKFDLRYIVFLNg-iAPVTAYVYNRFWIRFAINEFSl--------sNFEDVETHFTVFNYLD 542
gi 20455527  452 YIESPVLF--LRedv-gkVKFDIRYIVLLRs-vRPLRLFVYDVFWLRFSNRAFAl--------nDLDDYEKHFTVMNYDP 519
gi 342187090 547 YLTNPLLL--ASmd---nRKFHIRCYVVCRg---DLQVFVYDRMLALFAAKPFVPldpyaySvtDLKDLECHLTNTCLQS 618
gi 1723548   212 YISKPLLL--DH------RKFHIRAYVLATg---ALSVYLFNEMLCLLARDKYKK------PtpDPDLLFSHLSNTCLQG 274
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4I4T_F       248 Eys-knYGRYEEGNEMFFEEFNQYLMDAlN--TTLENSILLQIKHIIRSCLMc-IEPAISTKHLHYQSFQLFGFDFMV-- 321
gi 257096967 505 RyknktNRDSRLPKNNMWSLDQFKNYLR-Im-GAPDGSWSKTYNGFKQNLVAv-VMASLDETELLQNAFELYGCDFML-- 579
gi 172046606 385 HlenscHRHPLLPPDNMWSSQRFQAHLQ-E--MGAPNAWSTIIVPGMKDAVIhaLQTSQDTVQCRKASFELYGADFVF-- 459
gi 74869876  521 Kyt-ngKRDKRLPSENMWDCYSFQAYLR-Q--IGKYNMWLERIFPGMRKAIVgcMLASQENMDRRPNTFELFGADFMI-- 594
gi 586134    248 Eys-knYGKYEEGNEMFFEAFNRYLTSA-Ln-ITLESSILLQIKHIIRSCLMs-VEPAISTKHLPYQSFQLFGFDFMV-- 321
gi 20455327  248 Eys-knYGKYEEGNEMFFEEFNQYLTSA-Ln-ITLENSILLQIKHIIRSCLMs-VEPAISTKHLPYQSFQLLGFDFMV-- 321
gi 6686247   543 K-------EKILQMKCENFIETIEKAYP-R--IQWSEVQKDINLTIRKAIEAaaKEEAPRGVAPNVQSRAMYGVDIMLqh 612
gi 20455527  520 D-------VVLKQVHCEEFIPEFEKQYP-E--FPWTDVQAEIFRAFTELFQVacAKPPPLGLCDYPSSRAMYAVDLMLkw 589
gi 342187090 619 K-----------KKDKDSSVLEFDSIEE-IpnERKSNIKEQIHSITNDVFLAa-VNVNRLNFQPLPNAFETYGVDFLI-- 683
gi 1723548   275 D------------NVEQSSIRDFWNTSI-E---NKDDIFKSILNIIGDVFEAa-ATTQGIHFQPLENCFEIFGVDFLV-- 335
                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....*...
4I4T_F       322 ------DEELKVWLIEVNGAP--ACAQKLYAELCQGIVDVAIS-SVFP 360
gi 257096967 580 ------DEHYNPILIEINSTPdlSPSTEITARICPMVLKDCIR---VV 618
gi 172046606 460 ------GEDFQPWLIEINASPtmAPSTAVTARLCAGVQADTLR---VV 498
gi 74869876  595 ------CENFYPWLIEINSSPdlGATTSVTARMCPQCLEDVVK---VV 633
gi 586134    322 ------DEELKVWLIEVNGAP--ACAQKLYAELCQGIVDIAIA-SVFP 360
gi 20455327  322 ------DEELKVWLIEVNGAP--ACAQKLYAELCQGIVDIAIS-SVFP 360
gi 6686247   613 ----gdNDVIKSTLLEINFMPdtTRACQYYPDFADTVFETLFL-DEID 655
gi 20455527  590 dngpdgRRVMQPQILEVNFNPdcERACRYHPTFFNDVFSTLFL-D-QP 635
gi 342187090 684 ------DSNYEVKLLEINAFPdfKQTGKDLKNLIDELFDDTVKyCVTP 725
gi 1723548   336 ------DCESQVYLLEVNSYPdfKQTGKNLSNIIENLFSAVVE-TAII 376
Citing CDD
Marchler-Bauer A et al. (2013), "CDD: conserved domains and protein three-dimensional structure.", Nucleic Acids Res. 41(D1):D384-52.
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