Spt5 C-terminal nonapeptide repeat binding Spt4; The C-terminal domain of the transcription elongation factor protein Spt5 is necessary for binding to Spt4 to form the functional complex that regulates early transcription elongation by RNA polymerase II. The complex may be involved in pre-mRNA processing through its association with mRNA capping enzymes. This CTD domain carries a regular nonapeptide repeat that can be present in up to 18 copies, as in S. pombe. The repeat has a characteristic TPA motif.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149056473   627 GSQTPMYG-SGSRTPMYGSQTP----LQDGSRTPHYGSQTPLHDG--SRTPAQSGAWdPNNPNTPSRAEEEYEYAFDDEP 699
Cdd:smart01104   1 GGRTPAWGaSGSKTPAWGSRTPgtaaGGAPTARGGSGSRTPAWGGagSRTPAWGGAG-PTGSRTPAWGGASAWGNKSSEG 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 149056473   700 TPSPQA--YGGTPNPQTPGYpdpssPQVNPQYNPQTPGTPAMYNTDQ 744
Cdd:smart01104  80 SASSWAagPGGAYGAPTPGY-----GGTPSAYGPATPGGGAMAGSAS 121

KOW domain of Spt5, repeat 2; Spt5, an eukaryotic ortholog of NusG, contains multiple KOW motifs at its C-terminus. Spt5 is involved in transcription elongation and termination. KOW domain is known as an RNA-binding motif that is shared so far among some families of ribosomal proteins, the essential bacterial transcriptional elongation factor NusG, the eukaryotic chromatin elongation factor Spt5, the higher eukaryotic KIN17 proteins and Mtr4. KOW_Spt5 domains play critical roles in recruitment of multiple other eukaryotic transcription elongation and RNA biogenesis factors and additionally are involved in the binding of the eukaryotic Spt5 proteins to RNA polymerases.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 149056473 279 FQPGDNVEVCEGELINLQGKVLSVDGNKITIMPKHEDLKDMLEFPAQELRK 329
Cdd:cd06082    1 FQPGDNVEVIEGELKGLQGKVESVDGDIVTIMPKHEDLKEPLEFPAKELRK 51

KOW domain of Spt5, repeat 6; Spt5, an eukaryotic ortholog of NusG, contains multiple KOW motifs at its C-terminus. Spt5 is involved in transcription elongation and termination. KOW domain is known as an RNA-binding motif that is shared so far among some families of ribosomal proteins, the essential bacterial transcriptional elongation factor NusG, the eukaryotic chromatin elongation factor Spt5, the higher eukaryotic KIN17 proteins and Mtr4. KOW_Spt5 domains play critical roles in recruitment of multiple other eukaryotic transcription elongation and RNA biogenesis factors and additionally are involved in the binding of the eukaryotic Spt5 proteins to RNA polymerases.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 149056473 883 EHLEPITPTKNNKVKVILGEDREATGVLLSIDGEDGIIRMDlEDQQIKILNLRFLGKL 940
Cdd:cd06086    1 EHLEPVPPEKGDRVKVIKGEDRGSTGELISIDGADGIVKMD-SDGDIKILPMNFLAKL 57

KOW domain of Spt5, repeat 1; Spt5, an eukaryotic ortholog of NusG, contains multiple KOW motifs at its C-terminus. Spt5 is involved in transcription elongation and termination. KOW domain is known as an RNA-binding motif that is shared so far among some families of ribosomal proteins, the essential bacterial transcriptional elongation factor NusG, the eukaryotic chromatin elongation factor Spt5, the higher eukaryotic KIN17 proteins and Mtr4. KOW_Spt5 domains play critical roles in recruitment of multiple other eukaryotic transcription elongation and RNA biogenesis factors and additionally are involved in the binding of the eukaryotic Spt5 proteins to RNA polymerases.

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 149056473 135 KSWVRLKRGIYKDDIAQVDYVEPSQNTISLKMIPRIDY 172
Cdd:cd06081    1 GSWVRIKRGIYKGDLAQVDEVDENGNRVVVKLIPRIDY 38

Early transcription elongation factor of RNA pol II, NGN section; Spt5p and prokaryotic NusG are shown to contain a novel 'NGN' domain. The combined NGN and KOW motif regions of Spt5 form the binding domain with Spt4. Spt5 complexes with Spt4 as a 1:1 heterodimer snf this Spt5-Spt4 complex regulates early transcription elongation by RNA polymerase II and has an imputed role in pre-mRNA processing via its physical association with mRNA capping enzymes. The Schizosaccharomyces pombe core Spt5-Spt4 complex is a heterodimer bearing a trypsin-resistant Spt4-binding domain within the Spt5 subunit.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149056473   37 NLWTVKCKIGEERATAISLMRKFIAYQfTDTPLQIKSVVAPEHVKGYIYVEAYKQTHVKQAIEGVGNLRLGywNQQMVPI 116
Cdd:pfam03439   1 KIWAVKCTPGQEREVALSLMRKILALA-KTNNLGIYSVFAPDGLKGYIYVEADRQAAVKRALEGIPNVRGL--VPGLVPI 77

                  ....*..
gi 149056473  117 KEMTDVL 123
Cdd:pfam03439  78 KEMEHLL 84

KOW domain of Spt5, repeat 3; Spt5, an eukaryotic ortholog of NusG, contains multiple KOW motifs at its C-terminus. Spt5 is involved in transcription elongation and termination. KOW domain is known as an RNA-binding motif that is shared so far among some families of ribosomal proteins, the essential bacterial transcriptional elongation factor NusG, the eukaryotic chromatin elongation factor Spt5, the higher eukaryotic KIN17 proteins and Mtr4. KOW_Spt5 domains play critical roles in recruitment of multiple other eukaryotic transcription elongation and RNA biogenesis factors and additionally are involved in the binding of the eukaryotic Spt5 proteins to RNA polymerases.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 149056473 330 YFKMGDHVKVIAGRFEGDTGLIVRVEENFVILFSDLTMHELKVLPRDLQLC 380
Cdd:cd06083    1 HFKVGDHVKVISGRHEGETGLVVKVEDDVVTVFSDLTMRELKVFPRDLQLS 51

KOW domain of Spt5, repeat 5; Spt5, an eukaryotic ortholog of NusG, contains multiple KOW motifs at its C-terminus. Spt5 is involved in transcription elongation and termination. KOW domain is known as an RNA-binding motif that is shared so far among some families of ribosomal proteins, the essential bacterial transcriptional elongation factor NusG, the eukaryotic chromatin elongation factor Spt5, the higher eukaryotic KIN17 proteins and Mtr4. KOW_Spt5 domains play critical roles in recruitment of multiple other eukaryotic transcription elongation and RNA biogenesis factors and additionally are involved in the binding of the eukaryotic Spt5 proteins to RNA polymerases.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 149056473 557 DNELIGQTVRISQGPYKGYIGVVKDATESTARVELHSTCQTISVDRQRLT 606
Cdd:cd06085    2 RDPLIGKTVRIRKGPYKGYIGIVKDATGTTARVELHSKNKTITVDRSRLA 51

KOW domain of Spt5, repeat 4; Spt5, an eukaryotic ortholog of NusG, contains multiple KOW motifs at its C-terminus. Spt5 is involved in transcription elongation and termination. KOW domain is known as an RNA-binding motif that is shared so far among some families of ribosomal proteins, the essential bacterial transcriptional elongation factor NusG, the eukaryotic chromatin elongation factor Spt5, the higher eukaryotic KIN17 proteins and Mtr4. KOW_Spt5 domains play critical roles in recruitment of multiple other eukaryotic transcription elongation and RNA biogenesis factors and additionally are involved in the binding of the eukaryotic Spt5 proteins to RNA polymerases.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 149056473 456 KDIVKVIDGPHSGREGEIRHLYRSFAFLHCKKLVENGGMFVCK 498
Cdd:cd06084    1 GDTVKVVDGPYKGRQGTVLHIYRGTLFLHSREVTENGGIFVVR 43

Spt5 C-terminal nonapeptide repeat binding Spt4; The C-terminal domain of the transcription elongation factor protein Spt5 is necessary for binding to Spt4 to form the functional complex that regulates early transcription elongation by RNA polymerase II. The complex may be involved in pre-mRNA processing through its association with mRNA capping enzymes. This CTD domain carries a regular nonapeptide repeat that can be present in up to 18 copies, as in S. pombe. The repeat has a characteriztic TPA motif.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149056473  627 GSQTPMYGS--GSRTPMY---GSQTPL--QDGSRTPHY--GSQTPLHD--GSRTPAQSGAWDPnnPNTPS 685
Cdd:pfam12815   1 GSRTPAYNSagGSRTPAWgadGSRTPAygGAGGRTPAYnqGGKTPAWGgaGSRTPAYYGAWGG--SRTPA 68

In Spt5p, this domain may confer affinity for Spt4p. It possesses a RNP-like fold; In Spt5p, this domain may confer affinity for Spt4p.Spt4p

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149056473    37 NLWTVKCKIGEERATAISLMRKFIAYQFTDtplQIKSVVAP-EHVK----------------GYIYVEAYKQTHVKQAIE 99
Cdd:smart00738   1 NWYAVRTTSGQEKRVAENLERKAEALGLED---KIVSILVPtEEVKeirrgkkkvverklfpGYIFVEADLEDEVWTAIR 77

                           90       100       110
                   ....*....|....*....|....*....|
gi 149056473   100 GV----GNLRLGYWnQQMVPIKEMTDVLKV 125
Cdd:smart00738  78 GTpgvrGFVGGGGK-PTPVPDDEIEKILKP 106

transcription elongation factor Spt5; This protein contains a KOW domain, shared by bacterial NusG and the uL24 (previously L24p/L26e) family of ribosomal proteins. The most recent papers and crystal structures make this a transcription elongation factor rather than a ribosomal protein.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149056473   39 WTVKCKIGEERATAislmrKFIAYQFTDTPLQIKSVVAPEHVKGYIYVEAYKQTHVKQAIEGVGNLRlgywnqQMVP--- 115
Cdd:TIGR00405   1 FAVKTSVGQEKNVA-----RLMARKARKSGLEVYSILAPESLKGYILVEAETKIDMRNPIIGVPHVR------GVVEgei 69

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 149056473  116 -IKEMTDVLKVVKEVANLKPKSWVRLKRGIYKDDIAQVDYVEPSQNTISLKMI 167
Cdd:TIGR00405  70 dFEEIERFLTPKKIIESIKKGDIVEIISGPFKGERAKVIRVDESKEEVTLELI 122

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149056473  699 PTPSPQAYGGTPNPQTPGYPDPSSPQVN-PQYNPQTPGTP--AMYNTDQFSPYAAPSPQGSYQPSPSPQSYHQVAPSPAG 775
Cdd:pfam03154 188 PPGTTQAATAGPTPSAPSVPPQGSPATSqPPNQTQSTAAPhtLIQQTPTLHPQRLPSPHPPLQPMTQPPPPSQVSPQPLP 267

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 149056473  776 YQNTHSPASYHP---------TPSPMAYQASPSPSPVGYSPMTPG----APSPGGYNPHTPGS 825
Cdd:pfam03154 268 QPSLHGQMPPMPhslqtgpshMQHPVPPQPFPLTPQSSQSQVPPGpspaAPGQSQQRIHTPPS 330

N-terminal domain of transcription factor Specificity Protein (SP) 7; Specificity Proteins (SPs) are transcription factors that are involved in many cellular processes, including cell differentiation, cell growth, apoptosis, immune responses, response to DNA damage, and chromatin remodeling. SP7, also called Osterix (Osx) in humans, is highly conserved among bone-forming vertebrates. It plays a major role, along with Runx2 and Dlx5 in driving the differentiation of mesenchymal precursor cells into osteoblasts and eventually osteocytes. SP7 also plays a regulatory role by inhibiting chondrocyte differentiation, maintaining the balance between differentiation of mesenchymal precursor cells into ossified bone or cartilage. Mutations of this gene have been associated with multiple dysfunctional bone phenotypes in vertebrates. SP7 is thought to play a role in diseases such as Osteogenesis imperfecta. SP7 belongs to a family of proteins, called the SP/Kruppel or Krueppel-like Factor (KLF) family, characterized by a C-terminal DNA-binding domain of 81 amino acids consisting of three Kruppel-like C2H2 zinc fingers. These factors bind to a loose consensus motif, namely NNRCRCCYY (where N is any nucleotide; R is A/G, and Y is C/T), such as the recurring motifs in GC and GT boxes (5'-GGGGCGGGG-3' and 5-GGTGTGGGG-3') that are present in promoters and more distal regulatory elements of mammalian genes. SP factors preferentially bind GC boxes, while KLFs bind CACCC boxes. Another characteristic hallmark of SP factors is the presence of the Buttonhead (BTD) box CXCPXC, just N-terminal to the zinc fingers. The function of the BTD box is unknown, but it is thought to play an important physiological role. Another feature of most SP factors is the presence of a conserved amino acid stretch, the so-called SP box, located close to the N-terminus. SP factors may be separated into three groups based on their domain architecture and the similarity of their N-terminal transactivation domains: SP1-4, SP5, and SP6-9. The transactivation domains between the three groups are not homologous to one another. This model represents the N-terminal domain of SP7.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149056473 657 YGSQTPLHDgSRTPAQSGAWDPNNPNTP--------SRAEE----EYEYAFDD-----EPTPSPQA---YGGTPNPQTPG 716
Cdd:cd22542   26 FGGSSPIRD-SATPGKPGNNPGKKPYSLgsdlssakSRSSElmgdSYTATFSSgnglmSPSGSPQAsttYGNDYNPFSHS 104

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149056473 717 YPDPSSPQ----VNPQYNPQTPGTPAMYNT-DQFSPY-----AAPSPQGSYQPSPSPQSYHQVAPSPAGYQNTHSPASYH 786
Cdd:cd22542  105 FPTSSGSQdpslLVSKGHPSADCLPSVYTSlDMAHPYgswykTGIHPGISSSSTNATASWWDMHSNTNWLSAQGQPDGLQ 184

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 149056473 787 PTPSPMAYQASPSPSPVGYSPMTPgaPSPGGYNPHTPGS 825
Cdd:cd22542  185 ASLQPVPAQTPLNPQLPSYTEFTT--LNPAPYPAVGISS 221

KOW motif; This family has been extended to coincide with ref. The KOW (Kyprides, Ouzounis, Woese) motif is found in a variety of ribosomal proteins and NusG.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 149056473  561 IGQTVRISQGPYKGYIGVVKDATESTARVELH 592
Cdd:pfam00467   1 KGDVVRVIAGPFKGKVGKVVEVDDKKNRVLVE 32

KOW motif; This family has been extended to coincide with ref. The KOW (Kyprides, Ouzounis, Woese) motif is found in a variety of ribosomal proteins and NusG.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 149056473  334 GDHVKVIAGRFEGDTGLIVRVEE--NFVILF 362
Cdd:pfam00467   2 GDVVRVIAGPFKGKVGKVVEVDDkkNRVLVE 32

pneumococcal surface protein PspC, LPXTG-anchored form; The pneumococcal surface protein PspC, as described in Streptococcus pneumoniae, is a repetitive and highly variable protein, recognized by a conserved N-terminal domain and also by genomic location. This form, subgroup 2, is anchored covalently after cleavage by sortase at a C-terminal LPXTG site. The other form, subgroup 1, has variable numbers of a choline-binding repeat in the C-terminal region, and is also known as choline-binding protein A.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149056473 697 DEPTPSPQAYGGTPNPQTPGYPDPSSPQVNPQynPQTPGTPAMYNTDQFSPYAAPSPQ-GSYQPSPSPQSYH-QVAPSPA 774
Cdd:NF033839 370 EKPKPEVKPQPETPKPEVKPQPEKPKPEVKPQ--PEKPKPEVKPQPEKPKPEVKPQPEkPKPEVKPQPEKPKpEVKPQPE 447

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 149056473 775 GYQNTHSPASYHPTPSPMAYQASPSPSpVGYSPMTP----GAPSPGGYNPHTP 823
Cdd:NF033839 448 KPKPEVKPQPETPKPEVKPQPEKPKPE-VKPQPEKPkpdnSKPQADDKKPSTP 499

Early transcription elongation factor of RNA pol II, NGN section; Spt5p and prokaryotic NusG are shown to contain a novel 'NGN' domain. The combined NGN and KOW motif regions of Spt5 form the binding domain with Spt4. Spt5 complexes with Spt4 as a 1:1 heterodimer snf this Spt5-Spt4 complex regulates early transcription elongation by RNA polymerase II and has an imputed role in pre-mRNA processing via its physical association with mRNA capping enzymes. The Schizosaccharomyces pombe core Spt5-Spt4 complex is a heterodimer bearing a trypsin-resistant Spt4-binding domain within the Spt5 subunit.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149056473   37 NLWTVKCKIGEERATAISLMRKFIAYQfTDTPLQIKSVVAPEHVKGYIYVEAYKQTHVKQAIEGVGNLRLGywNQQMVPI 116
Cdd:pfam03439   1 KIWAVKCTPGQEREVALSLMRKILALA-KTNNLGIYSVFAPDGLKGYIYVEADRQAAVKRALEGIPNVRGL--VPGLVPI 77

                  ....*..
gi 149056473  117 KEMTDVL 123
Cdd:pfam03439  78 KEMEHLL 84

KOW domain of Spt5, repeat 3; Spt5, an eukaryotic ortholog of NusG, contains multiple KOW motifs at its C-terminus. Spt5 is involved in transcription elongation and termination. KOW domain is known as an RNA-binding motif that is shared so far among some families of ribosomal proteins, the essential bacterial transcriptional elongation factor NusG, the eukaryotic chromatin elongation factor Spt5, the higher eukaryotic KIN17 proteins and Mtr4. KOW_Spt5 domains play critical roles in recruitment of multiple other eukaryotic transcription elongation and RNA biogenesis factors and additionally are involved in the binding of the eukaryotic Spt5 proteins to RNA polymerases.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 149056473 330 YFKMGDHVKVIAGRFEGDTGLIVRVEENFVILFSDLTMHELKVLPRDLQLC 380
Cdd:cd06083    1 HFKVGDHVKVISGRHEGETGLVVKVEDDVVTVFSDLTMRELKVFPRDLQLS 51

KOW domain of Spt5, repeat 5; Spt5, an eukaryotic ortholog of NusG, contains multiple KOW motifs at its C-terminus. Spt5 is involved in transcription elongation and termination. KOW domain is known as an RNA-binding motif that is shared so far among some families of ribosomal proteins, the essential bacterial transcriptional elongation factor NusG, the eukaryotic chromatin elongation factor Spt5, the higher eukaryotic KIN17 proteins and Mtr4. KOW_Spt5 domains play critical roles in recruitment of multiple other eukaryotic transcription elongation and RNA biogenesis factors and additionally are involved in the binding of the eukaryotic Spt5 proteins to RNA polymerases.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 149056473 557 DNELIGQTVRISQGPYKGYIGVVKDATESTARVELHSTCQTISVDRQRLT 606
Cdd:cd06085    2 RDPLIGKTVRIRKGPYKGYIGIVKDATGTTARVELHSKNKTITVDRSRLA 51

KOW domain of Spt5, repeat 4; Spt5, an eukaryotic ortholog of NusG, contains multiple KOW motifs at its C-terminus. Spt5 is involved in transcription elongation and termination. KOW domain is known as an RNA-binding motif that is shared so far among some families of ribosomal proteins, the essential bacterial transcriptional elongation factor NusG, the eukaryotic chromatin elongation factor Spt5, the higher eukaryotic KIN17 proteins and Mtr4. KOW_Spt5 domains play critical roles in recruitment of multiple other eukaryotic transcription elongation and RNA biogenesis factors and additionally are involved in the binding of the eukaryotic Spt5 proteins to RNA polymerases.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 149056473 456 KDIVKVIDGPHSGREGEIRHLYRSFAFLHCKKLVENGGMFVCK 498
Cdd:cd06084    1 GDTVKVVDGPYKGRQGTVLHIYRGTLFLHSREVTENGGIFVVR 43

Spt5 C-terminal nonapeptide repeat binding Spt4; The C-terminal domain of the transcription elongation factor protein Spt5 is necessary for binding to Spt4 to form the functional complex that regulates early transcription elongation by RNA polymerase II. The complex may be involved in pre-mRNA processing through its association with mRNA capping enzymes. This CTD domain carries a regular nonapeptide repeat that can be present in up to 18 copies, as in S. pombe. The repeat has a characteriztic TPA motif.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149056473  627 GSQTPMYGS--GSRTPMY---GSQTPL--QDGSRTPHY--GSQTPLHD--GSRTPAQSGAWDPnnPNTPS 685
Cdd:pfam12815   1 GSRTPAYNSagGSRTPAWgadGSRTPAygGAGGRTPAYnqGGKTPAWGgaGSRTPAYYGAWGG--SRTPA 68

N-Utilization Substance G (NusG) N-terminal (NGN) domain Superfamily; The N-Utilization Substance G (NusG) and its eukaryotic homolog Spt5 are involved in transcription elongation and termination. NusG contains an NGN domain at its N-terminus and Kyrpides Ouzounis and Woese (KOW) repeats at its C-terminus in bacteria and archaea. The eukaryotic ortholog, Spt5, is a large protein composed of an acidic N-terminus, an NGN domain, and multiple KOW motifs at its C-terminus. Spt5 forms a Spt4-Spt5 complex that is an essential RNA Polymerase II elongation factor. NusG was originally discovered as an N-dependent antitermination enhancing activity in Escherichia coli and has a variety of functions, such as being involved in RNA polymerase elongation and Rho-termination in bacteria. Orthologs of the NusG gene exist in all bacteria, but its functions and requirements are different. The diverse activities suggest that, after diverging from a common ancestor, NusG proteins became specialized in different bacteria.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149056473  37 NLWTVKCKIGEERATAISLMRKFIA---------YQFTDTPLQIKSVVAPEHVKGYIYVEAYKQTHVKQAIEGVGNLRLG 107
Cdd:cd08000    1 NWYVLFVKTGREEKVEKLLEKRFEAndieafvpkKEVPERKRGKIEEVIKPLFPGYVFVETDLSPELYELIREVPGVIGI 80

                         90
                 ....*....|....*....
gi 149056473 108 YWN---QQMVPIKEMTDVL 123
Cdd:cd08000   81 LGNgeePSPVSDEEIEMIL 99

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149056473  644 SQTPLQDGSRTPHYGSQTPLHDgsrtPAQSGAWDPNNPNTPSRAEEEYEYAFDDEPtPSPQAYGGTPNPQTPGYPdPSSP 723
Cdd:pfam03154 259 SQVSPQPLPQPSLHGQMPPMPH----SLQTGPSHMQHPVPPQPFPLTPQSSQSQVP-PGPSPAAPGQSQQRIHTP-PSQS 332

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149056473  724 QVNPQYNP-QTPGTPAMYNTdqfsPYAAPSPQGSYQPSPSPQSY----HQVAPSPagYQ-----------------NTHS 781
Cdd:pfam03154 333 QLQSQQPPrEQPLPPAPLSM----PHIKPPPTTPIPQLPNPQSHkhppHLSGPSP--FQmnsnlppppalkplsslSTHH 406

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 149056473  782 PASYHPTPSPMAYQASPSPSPVGYSPM---TPGAPSPGGYNPHTPGS 825
Cdd:pfam03154 407 PPSAHPPPLQLMPQSQQLPPPPAQPPVltqSQSLPPPAASHPPTSGL 453

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149056473  631 PMYGSGSRTPMYGSQTPLQDGSRTPHYGSQTPLHDGSRTPAQSGAWDPNNPNTPsrAEEEYEYAFDDEPTPSPQayggTP 710
Cdd:pfam03154 294 PPQPFPLTPQSSQSQVPPGPSPAAPGQSQQRIHTPPSQSQLQSQQPPREQPLPP--APLSMPHIKPPPTTPIPQ----LP 367

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149056473  711 NPQTPGYPDPSSPQVNPQYNPQTPGTPAMYNTDQFSPYAAPSPQgsyqPSP---SPQSyHQVAPSPAG------YQNTHS 781
Cdd:pfam03154 368 NPQSHKHPPHLSGPSPFQMNSNLPPPPALKPLSSLSTHHPPSAH----PPPlqlMPQS-QQLPPPPAQppvltqSQSLPP 442

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 149056473  782 PASYHPTPSpmAYQASPSPSPVGYSPMTPGAP----SPGGYNPHTP--GSGIEQNSS 832
Cdd:pfam03154 443 PAASHPPTS--GLHQVPSQSPFPQHPFVPGGPppitPPSGPPTSTSsaMPGIQPPSS 497

Spt5 C-terminal nonapeptide repeat binding Spt4; The C-terminal domain of the transcription elongation factor protein Spt5 is necessary for binding to Spt4 to form the functional complex that regulates early transcription elongation by RNA polymerase II. The complex may be involved in pre-mRNA processing through its association with mRNA capping enzymes. This CTD domain carries a regular nonapeptide repeat that can be present in up to 18 copies, as in S. pombe. The repeat has a characteriztic TPA motif.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 149056473  614 GGMTSTYG----RTPMYG---SQTPMYGSGSRTPMYGsqtplQDGSRTPHYGSQTplhDGSRTPAQSG 674
Cdd:pfam12815  12 GSRTPAWGadgsRTPAYGgagGRTPAYNQGGKTPAWG-----GAGSRTPAYYGAW---GGSRTPAYGG 71

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149056473  652 SRTPHYGSQTPLHDGSRTPAQSGAWDPNNPNTPsraeeeyeyafddePTPSPQAYGGTPN----PQTPGYPDPSSPQVNP 727
Cdd:PHA03247 2710 PAPHALVSATPLPPGPAAARQASPALPAAPAPP--------------AVPAGPATPGGPArparPPTTAGPPAPAPPAAP 2775

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149056473  728 QYNPQTPGTPAMYNTDQFSPYAAPSPqgsyqPSPSPQSYHQVAPSPAgYQNTHSPASYHPTPsPMAYQASPSPSPVGYSP 807
Cdd:PHA03247 2776 AAGPPRRLTRPAVASLSESRESLPSP-----WDPADPPAAVLAPAAA-LPPAASPAGPLPPP-TSAQPTAPPPPPGPPPP 2848

                         170
                  ....*....|..
gi 149056473  808 MTP--GAPSPGG 817
Cdd:PHA03247 2849 SLPlgGSVAPGG 2860

Archaeal N-Utilization Substance G (NusG) N-terminal (NGN) domain; The N-Utilization Substance G (NusG) protein and its eukaryotic homolog, Spt5, are involved in transcription elongation and termination. Transcription in archaea has a eukaryotic-type transcription apparatus, but contains bacterial-type transcription factors. NusG is one of the few archaeal transcription factors that has orthologs in both bacteria and eukaryotes. Archaeal NusG is similar to bacterial NusG, composed of an NGN domain and a Kyrpides Ouzounis and Woese (KOW) repeat. The eukaryotic ortholog, Spt5, is a large protein composed of an acidic N-terminus, an NGN domain, and multiple KOW motifs at its C-terminus. NusG was originally discovered as a N-dependent antitermination enhancing activity in Escherichia coli and has a variety of functions, such as being involved in RNA polymerase elongation and Rho-termination in bacteria. Archaeal NusG forms a complex with DNA-directed RNA polymerase subunit E (rpoE) that is similar to the Spt5-Spt4 complex in eukaryotes.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 149056473  38 LWTVKCKIGEERATAISLMRKFiayqfTDTPLQIKSVVAPEHVKGYIYVEAYKQTHVKQAIEGVGNLR 105
Cdd:cd09887    2 IYAVKTTAGQERNVADLLAMRA-----EKENLDVYSILVPEELKGYVFVEAEDPDRVEELIRGIPHVR 64

EBNA-3C; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149056473  593 STCQTISVDRQRLTTVDSQRPGGMTSTygrTPMYGSQTPMYgSGSRTPMYGSQTPLQD---GSRTPHYGSQTPLHDGSRT 669
Cdd:PHA03377  686 SVFVLPSVDAGRAQPSEESHLSSMSPT---QPISHEEQPRY-EDPDDPLDLSLHPDQApppSHQAPYSGHEEPQAQQAPY 761

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149056473  670 PaqsGAWDPNNPNTPSRAEEEyeyafddeptpsPQAYGGTPNpQTPGY--PDPSSPQvNPQY--------------NPQT 733
Cdd:PHA03377  762 P---GYWEPRPPQAPYLGYQE------------PQAQGVQVS-SYPGYagPWGLRAQ-HPRYrhswaywsqypghgHPQG 824

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149056473  734 PGTP-AMYNTDQFSPYAAP-----SPQGSYQPSPSP----QSYHQVAPSPAGYQNTHSPASYHPTPS----PMAYQASPS 799
Cdd:PHA03377  825 PWAPrPPHLPPQWDGSAGHgqdqvSQFPHLQSETGPprlqLSQVPQLPYSQTLVSSSAPSWSSPQPRapirPIPTRFPPP 904

                         250       260
                  ....*....|....*....|....
gi 149056473  800 PSPVGYSpMTPGAPSPGGYNPHTP 823
Cdd:PHA03377  905 PMPLQDS-MAVGCDSSGTACPSMP 927