Eukaryotic N-Utilization Substance G (NusG) N-terminal (NGN) domain, including plant KTF1 (KOW domain-containing Transcription Factor 1); The N-Utilization Substance G (NusG) protein 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. Spt5 forms an 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 its involvement in RNA polymerase elongation and Rho-termination in bacteria. Orthologs of the NusG gene exist in all bacteria, but their functions and requirements are different. Spt5-like is homologous to the Spt5 proteins present in all eukaryotes, which is unique as it encodes a protein with an additional long carboxy-terminal extension that contains WG/GW motifs. Spt5-like, or KTF1 (KOW domain-containing Transcription Factor 1), is a RNA-directed DNA methylation (RdDM) pathway effector in plants.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388490406  178 NLWTVKCKIGEERATAISLMRKFIAYQFTDTPLQIKSVVAPEHVKGYIYVEAYKQTHVKQAIEGVGNLRLgyWNQQMVPI 257
Cdd:cd09888     1 KLWAVKCKPGKEREIVISLMRKFLDLQRTGNPLGIKSVFARDGLKGYIYIEARKEAHVKDAIEGLRGVYL--NTIKLVPI 78

                  ....*...
gi 388490406  258 KEMTDVLK 265
Cdd:cd09888    79 KEMPDVLS 86

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 388490406  471 YFKMGDHVKVIAGRFEGDTGLIVRVEENFVILFSDLTMHELKVLPRDLQLC 521
Cdd:cd06083     1 HFKVGDHVKVISGRHEGETGLVVKVEDDVVTVFSDLTMRELKVFPRDLQLS 51

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 388490406  420 FQPGDNVEVCEGELINLQGKILSVDGNKITIMPKHEDLKDMLEFPAQELRK 470
Cdd:cd06082     1 FQPGDNVEVIEGELKGLQGKVESVDGDIVTIMPKHEDLKEPLEFPAKELRK 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 388490406  597 KDIVKVIDGPHSGREGEIRHLFRSFAFLHCKKLVENGGMFVCK 639
Cdd:cd06084     1 GDTVKVVDGPYKGRQGTVLHIYRGTLFLHSREVTENGGIFVVR 43

Spt5 transcription elongation factor, acidic N-terminal; This is the very acidic N-terminal region of the early transcription elongation factor Spt5. The 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 actual function of this N-terminal domain is not known although it is dispensable for binding to Spt4.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388490406    93 EDGAEDILEKEEIEASNIDNVVLDEDRSGARRLQNLWRDQREEELGEYYMKKYAKSSvgETVYGGSDElsDDITQQQLLP 172
Cdd:pfam11942   22 EDGADDFIEDDEEDEDEEDGRRDDRRHRELDRRRELEEDEDAEEIAEYLKERYGRSS--SDAYRGDAE--EGVPQRLLLP 97

Eukaryotic N-Utilization Substance G (NusG) N-terminal (NGN) domain, including plant KTF1 (KOW domain-containing Transcription Factor 1); The N-Utilization Substance G (NusG) protein 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. Spt5 forms an 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 its involvement in RNA polymerase elongation and Rho-termination in bacteria. Orthologs of the NusG gene exist in all bacteria, but their functions and requirements are different. Spt5-like is homologous to the Spt5 proteins present in all eukaryotes, which is unique as it encodes a protein with an additional long carboxy-terminal extension that contains WG/GW motifs. Spt5-like, or KTF1 (KOW domain-containing Transcription Factor 1), is a RNA-directed DNA methylation (RdDM) pathway effector in plants.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388490406  178 NLWTVKCKIGEERATAISLMRKFIAYQFTDTPLQIKSVVAPEHVKGYIYVEAYKQTHVKQAIEGVGNLRLgyWNQQMVPI 257
Cdd:cd09888     1 KLWAVKCKPGKEREIVISLMRKFLDLQRTGNPLGIKSVFARDGLKGYIYIEARKEAHVKDAIEGLRGVYL--NTIKLVPI 78

                  ....*...
gi 388490406  258 KEMTDVLK 265
Cdd:cd09888    79 KEMPDVLS 86

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 388490406    772 GSQTPMYG-SGSRTPMYGSQTP----LQDGSRTPHYGSQTPLHDG--SRTPAQSGAWdPNNPNTPSRAEEEYEYAFDDEP 844
Cdd:smart01104    1 GGRTPAWGaSGSKTPAWGSRTPgtaaGGAPTARGGSGSRTPAWGGagSRTPAWGGAG-PTGSRTPAWGGASAWGNKSSEG 79

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*..
gi 388490406    845 TPSPQA--YGGTPNPQTPGYpdpssPQVNPQYNPQTPGTPAMYNTDQ 889
Cdd:smart01104   80 SASSWAagPGGAYGAPTPGY-----GGTPSAYGPATPGGGAMAGSAS 121

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 388490406 1028 EHLEPITPTKNNKVKVILGEDREATGVLLSIDGEDGIVRMDLDEQLKILNLRFLGKL 1084
Cdd:cd06086     1 EHLEPVPPEKGDRVKVIKGEDRGSTGELISIDGADGIVKMDSDGDIKILPMNFLAKL 57

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 388490406  702 DNELIGQTVRISQGPYKGYIGVVKDATESTARVELHSTCQTISVDRQRLT 751
Cdd:cd06085     2 RDPLIGKTVRIRKGPYKGYIGIVKDATGTTARVELHSKNKTITVDRSRLA 51

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 388490406  276 KSWVRLKRGIYKDDIAQVDYVEPSQNTISLKMIPRIDY 313
Cdd:cd06081     1 GSWVRIKRGIYKGDLAQVDEVDENGNRVVVKLIPRIDY 38

Spt5 transcription elongation factor, acidic N-terminal; This is the very acidic N-terminal region of the early transcription elongation factor Spt5. The 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 actual function of this N-terminal domain is not known although it is dispensable for binding to Spt4.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388490406    93 EDGAEDILEKEEIEASNIDNVVLDEDRSGARRLQNLWRDQREEELGEYYMKKYAKSSvgETVYGGSDElsDDITQQQLLP 172
Cdd:pfam11942   22 EDGADDFIEDDEEDEDEEDGRRDDRRHRELDRRRELEEDEDAEEIAEYLKERYGRSS--SDAYRGDAE--EGVPQRLLLP 97

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 388490406    178 NLWTVKCKIGEERATAISLMRKFIAYQFTDtplQIKSVVAP-EHVK----------------GYIYVEAYKQTHVKQAIE 240
Cdd:smart00738    1 NWYAVRTTSGQEKRVAENLERKAEALGLED---KIVSILVPtEEVKeirrgkkkvverklfpGYIFVEADLEDEVWTAIR 77

                            90       100       110
                    ....*....|....*....|....*....|
gi 388490406    241 GV----GNLRLGYWnQQMVPIKEMTDVLKV 266
Cdd:smart00738   78 GTpgvrGFVGGGGK-PTPVPDDEIEKILKP 106

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388490406  745 VDRQRLTTVGSRRPGGMTSTYGRTPMYGSQTPMYGSGSRTPMYGSQTPlqdGSRTPHYGSQTPLHDGSRTPAQSGAWDPN 824
Cdd:PHA03247 2661 VSRPRRARRLGRAAQASSPPQRPRRRAARPTVGSLTSLADPPPPPPTP---EPAPHALVSATPLPPGPAAARQASPALPA 2737

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388490406  825 NPNTPsraeeeyeyafddePTPSPQAYGGTPN----PQTPGYPDPSSPQVNPQYNPQTPGTPAMYNTDQFSPYAAPSPqg 900
Cdd:PHA03247 2738 APAPP--------------AVPAGPATPGGPArparPPTTAGPPAPAPPAAPAAGPPRRLTRPAVASLSESRESLPSP-- 2801

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 388490406  901 syqPSPSPQSYHQVAPSPAgYQNTHSPASYHPTPSPMAYQASPSPSPVGYSPMTP-GAPSPGG 962
Cdd:PHA03247 2802 ---WDPADPPAAVLAPAAA-LPPAASPAGPLPPPTSAQPTAPPPPPGPPPPSLPLgGSVAPGG 2860

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 388490406   844 PTPSPQAYGGTPNPQTPGYPDPSSPQVN-PQYNPQTPGTP--AMYNTDQFSPYAAPSPQGSYQPSPSPQSYHQVAPSPAG 920
Cdd:pfam03154  188 PPGTTQAATAGPTPSAPSVPPQGSPATSqPPNQTQSTAAPhtLIQQTPTLHPQRLPSPHPPLQPMTQPPPPSQVSPQPLP 267

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 388490406   921 YQNTHSPASYHP---------TPSPMAYQASPSPSPVGYSPMTPG----APSPGGYNPHTPGS 970
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 388490406  802 YGSQTPLHDgSRTPAQSGAWDPNNPNTP--------SRAEE----EYEYAFDD-----EPTPSPQA---YGGTPNPQTPG 861
Cdd:cd22542    26 FGGSSPIRD-SATPGKPGNNPGKKPYSLgsdlssakSRSSElmgdSYTATFSSgnglmSPSGSPQAsttYGNDYNPFSHS 104

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388490406  862 YPDPSSPQ----VNPQYNPQTPGTPAMYNT-DQFSPY-----AAPSPQGSYQPSPSPQSYHQVAPSPAGYQNTHSPASYH 931
Cdd:cd22542   105 FPTSSGSQdpslLVSKGHPSADCLPSVYTSlDMAHPYgswykTGIHPGISSSSTNATASWWDMHSNTNWLSAQGQPDGLQ 184

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 388490406  932 PTPSPMAYQASPSPSPVGYSPMTPgaPSPGGYNPHTPGS 970
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 388490406   706 IGQTVRISQGPYKGYIGVVKDATESTARVELH 737
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 388490406   475 GDHVKVIAGRFEGDTGLIVRVEE--NFVILF 503
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 388490406  842 DEPTPSPQAYGGTPNPQTPGYPDPSSPQVNPQynPQTPGTPAMYNTDQFSPYAAPSPQ-GSYQPSPSPQSYH-QVAPSPA 919
Cdd:NF033839  370 EKPKPEVKPQPETPKPEVKPQPEKPKPEVKPQ--PEKPKPEVKPQPEKPKPEVKPQPEkPKPEVKPQPEKPKpEVKPQPE 447

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 388490406  920 GYQNTHSPASYHPTPSPMAYQASPSPSpVGYSPMTP----GAPSPGGYNPHTP 968
Cdd:NF033839  448 KPKPEVKPQPETPKPEVKPQPEKPKPE-VKPQPEKPkpdnSKPQADDKKPSTP 499

Amelogenins, cell adhesion proteins, play a role in the biomineralisation of teeth; They seem to regulate formation of crystallites during the secretory stage of tooth enamel development and are thought to play a major role in the structural organisation and mineralisation of developing enamel. The extracellular matrix of the developing enamel comprises two major classes of protein: the hydrophobic amelogenins and the acidic enamelins. Circular dichroism studies of porcine amelogenin have shown that the protein consists of 3 discrete folding units: the N-terminal region appears to contain beta-strand structures, while the C-terminal region displays characteristics of a random coil conformation. Subsequent studies on the bovine protein have indicated the amelogenin structure to contain a repetitive beta-turn segment and a "beta-spiral" between Gln112 and Leu138, which sequester a (Pro, Leu, Gln) rich region. The beta-spiral offers a probable site for interactions with Ca2+ ions. Muatations in the human amelogenin gene (AMGX) cause X-linked hypoplastic amelogenesis imperfecta, a disease characterised by defective enamel. A 9bp deletion in exon 2 of AMGX results in the loss of codons for Ile5, Leu6, Phe7 and Ala8, and replacement by a new threonine codon, disrupting the 16-residue (Met1-Ala16) amelogenin signal peptide.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388490406    855 PNPQTPGYPDPSSPQVNPQYNPQTPGTPAMyntdQFSPYAAPSPQGSYQPSPSPQSYHQVAPSPAGYQNTHSPASYHPTP 934
Cdd:smart00818   45 QHPPTHTLQPHHHIPVLPAQQPVVPQQPLM----PVPGQHSMTPTQHHQPNLPQPAQQPFQPQPLQPPQPQQPMQPQPPV 120

                            90       100
                    ....*....|....*....|....*.
gi 388490406    935 SPMAYQASPSPSPvgysPMTPGAPSP 960
Cdd:smart00818  121 HPIPPLPPQPPLP----PMFPMQPLP 142

Eukaryotic N-Utilization Substance G (NusG) N-terminal (NGN) domain, including plant KTF1 (KOW domain-containing Transcription Factor 1); The N-Utilization Substance G (NusG) protein 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. Spt5 forms an 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 its involvement in RNA polymerase elongation and Rho-termination in bacteria. Orthologs of the NusG gene exist in all bacteria, but their functions and requirements are different. Spt5-like is homologous to the Spt5 proteins present in all eukaryotes, which is unique as it encodes a protein with an additional long carboxy-terminal extension that contains WG/GW motifs. Spt5-like, or KTF1 (KOW domain-containing Transcription Factor 1), is a RNA-directed DNA methylation (RdDM) pathway effector in plants.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388490406  178 NLWTVKCKIGEERATAISLMRKFIAYQFTDTPLQIKSVVAPEHVKGYIYVEAYKQTHVKQAIEGVGNLRLgyWNQQMVPI 257
Cdd:cd09888     1 KLWAVKCKPGKEREIVISLMRKFLDLQRTGNPLGIKSVFARDGLKGYIYIEARKEAHVKDAIEGLRGVYL--NTIKLVPI 78

                  ....*...
gi 388490406  258 KEMTDVLK 265
Cdd:cd09888    79 KEMPDVLS 86

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 388490406    772 GSQTPMYG-SGSRTPMYGSQTP----LQDGSRTPHYGSQTPLHDG--SRTPAQSGAWdPNNPNTPSRAEEEYEYAFDDEP 844
Cdd:smart01104    1 GGRTPAWGaSGSKTPAWGSRTPgtaaGGAPTARGGSGSRTPAWGGagSRTPAWGGAG-PTGSRTPAWGGASAWGNKSSEG 79

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*..
gi 388490406    845 TPSPQA--YGGTPNPQTPGYpdpssPQVNPQYNPQTPGTPAMYNTDQ 889
Cdd:smart01104   80 SASSWAagPGGAYGAPTPGY-----GGTPSAYGPATPGGGAMAGSAS 121

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 388490406 1028 EHLEPITPTKNNKVKVILGEDREATGVLLSIDGEDGIVRMDLDEQLKILNLRFLGKL 1084
Cdd:cd06086     1 EHLEPVPPEKGDRVKVIKGEDRGSTGELISIDGADGIVKMDSDGDIKILPMNFLAKL 57

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 388490406  702 DNELIGQTVRISQGPYKGYIGVVKDATESTARVELHSTCQTISVDRQRLT 751
Cdd:cd06085     2 RDPLIGKTVRIRKGPYKGYIGIVKDATGTTARVELHSKNKTITVDRSRLA 51

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 388490406  276 KSWVRLKRGIYKDDIAQVDYVEPSQNTISLKMIPRIDY 313
Cdd:cd06081     1 GSWVRIKRGIYKGDLAQVDEVDENGNRVVVKLIPRIDY 38

Spt5 transcription elongation factor, acidic N-terminal; This is the very acidic N-terminal region of the early transcription elongation factor Spt5. The 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 actual function of this N-terminal domain is not known although it is dispensable for binding to Spt4.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388490406    93 EDGAEDILEKEEIEASNIDNVVLDEDRSGARRLQNLWRDQREEELGEYYMKKYAKSSvgETVYGGSDElsDDITQQQLLP 172
Cdd:pfam11942   22 EDGADDFIEDDEEDEDEEDGRRDDRRHRELDRRRELEEDEDAEEIAEYLKERYGRSS--SDAYRGDAE--EGVPQRLLLP 97

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 388490406  178 NLWTVKCKIGEERATAISLMRKFIA---------YQFTDTPLQIKSVVAPEHVKGYIYVEAYKQTHVKQAIEGVGNLRLG 248
Cdd:cd08000     1 NWYVLFVKTGREEKVEKLLEKRFEAndieafvpkKEVPERKRGKIEEVIKPLFPGYVFVETDLSPELYELIREVPGVIGI 80

                          90
                  ....*....|....*....
gi 388490406  249 YWN---QQMVPIKEMTDVL 264
Cdd:cd08000    81 LGNgeePSPVSDEEIEMIL 99

Family of unknown function (DUF5585); This is a family of unknown function found in chordata.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388490406   727 ATESTARVELHSTCQTISvdrqrlTTVGSRRPGGMTSTYGRT--PMYGSQTPMYGSGsrTPMYGSQTPlQDGSRTPHYGS 804
Cdd:pfam17823  170 AASPAPRTAASSTTAASS------TTAASSAPTTAASSAPATltPARGISTAATATG--HPAAGTALA-AVGNSSPAAGT 240

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388490406   805 QTPLhDGSRTPAQSGawdpnnpnTPSRAEEEYEYAFDDEPTPSPQAYGGTPNPQTPGypDPSSPQVNPQYNPQTPGTPAM 884
Cdd:pfam17823  241 VTAA-VGTVTPAALA--------TLAAAAGTVASAAGTINMGDPHARRLSPAKHMPS--DTMARNPAAPMGAQAQGPIIQ 309

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388490406   885 YNTDQfsPYAAPSPqgsyQPSPSPQSYHQVAPSPAGYQNTHSPASyhPTPSPMAYQASPSPSPVGYSPMTPGA------- 957
Cdd:pfam17823  310 VSTDQ--PVHNTAG----EPTPSPSNTTLEPNTPKSVASTNLAVV--TTTKAQAKEPSASPVPVLHTSMIPEVeatsptt 381

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388490406   958 -PSPGGYNPHTPGSGIEQNSSdwvttdiQVKVRDTyLDTQVVGQT----GVIRSVTGGMCSVYLKDSEKVVSIssehlEP 1032
Cdd:pfam17823  382 qPSPLLPTQGAAGPGILLAPE-------QVATEAT-AGTASAGPTprssGDPKTLAMASCQLSTQGQYLVVTT-----DP 448

                          330
                   ....*....|....*...
gi 388490406  1033 ITPTKNNK----VKVILG 1046
Cdd:pfam17823  449 LTPALVDKmfllVVLILG 466

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 388490406   754 GSRRPGGMTSTYGRTPMY-------------GSQTPMYGSGSRTPMYGsqtplQDGSRTPHYGSQTplhDGSRTPAQSG 819
Cdd:pfam12815    1 GSRTPAYNSAGGSRTPAWgadgsrtpayggaGGRTPAYNQGGKTPAWG-----GAGSRTPAYYGAW---GGSRTPAYGG 71

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 388490406   776 PMYGSGSRTPMYGSQTPLQDGSRTPHYGSQTPLHDGSRTPAQSGAWDPNNPNTPsrAEEEYEYAFDDEPTPSPQayggTP 855
Cdd:pfam03154  294 PPQPFPLTPQSSQSQVPPGPSPAAPGQSQQRIHTPPSQSQLQSQQPPREQPLPP--APLSMPHIKPPPTTPIPQ----LP 367

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388490406   856 NPQTPGYPDPSSPQVNPQYNPQTPGTPAMYNTDQFSPYAAPSPQgsyqPSP---SPQSyHQVAPSPAG------YQNTHS 926
Cdd:pfam03154  368 NPQSHKHPPHLSGPSPFQMNSNLPPPPALKPLSSLSTHHPPSAH----PPPlqlMPQS-QQLPPPPAQppvltqSQSLPP 442

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 388490406   927 PASYHPTPSpmAYQASPSPSPVGYSPMTPGAP----SPGGYNPHTP--GSGIEQNSS 977
Cdd:pfam03154  443 PAASHPPTS--GLHQVPSQSPFPQHPFVPGGPppitPPSGPPTSTSsaMPGIQPPSS 497

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 388490406   180 WTVKCKIGEERATAislmrKFIAYQFTDTPLQIKSVVAPEHVKGYIYVEAYKQTHVKQAIEGVGNLRlgywnqQMVP--- 256
Cdd:TIGR00405    1 FAVKTSVGQEKNVA-----RLMARKARKSGLEVYSILAPESLKGYILVEAETKIDMRNPIIGVPHVR------GVVEgei 69

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 388490406   257 -IKEMTDVLKVVKEVANLKPKSWVRLKRGIYKDDIAQVDYVEPSQNTISLKMI 308
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 388490406   844 PTPSPQAYGGTPNPQTPGYPDPSSPQVN-PQYNPQTPGTP--AMYNTDQFSPYAAPSPQGSYQPSPSPQSYHQVAPSPAG 920
Cdd:pfam03154  188 PPGTTQAATAGPTPSAPSVPPQGSPATSqPPNQTQSTAAPhtLIQQTPTLHPQRLPSPHPPLQPMTQPPPPSQVSPQPLP 267

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 388490406   921 YQNTHSPASYHP---------TPSPMAYQASPSPSPVGYSPMTPG----APSPGGYNPHTPGS 970
Cdd:pfam03154  268 QPSLHGQMPPMPhslqtgpshMQHPVPPQPFPLTPQSSQSQVPPGpspaAPGQSQQRIHTPPS 330