Protein Family Models

This entry represents the N-terminal domain of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), which is arranged in four supersecondary alpha-helical structures, N1 to N4, that resemble HEAT repeats. Therefore, this domain is also known as N-HEAT. This domain likely mediates DNA binding and, together with the Circular Cradle, forms a ring through which Ku70/80 may present DNA for repair. DNA-PKcs is involved in DNA nonhomologous end joining (NHEJ), required for double-strand break (DSB) repair [1-4]. It is recruited by Ku70/80 heterodimer to DNA ends. [1]. 28154079. DNA-PKcs structure suggests an allosteric mechanism modulating. DNA double-strand break repair.. Sibanda BL, Chirgadze DY, Ascher DB, Blundell TL;. Science. 2017;355:520-524.. [2]. 28652322. Cryo-EM structure of the DNA-PK holoenzyme.. Sharif H, Li Y, Dong Y, Dong L, Wang WL, Mao Y, Wu H;. Proc Natl Acad Sci U S A. 2017;114:7367-7372.. [3]. 28840859. Cryo-EM structure of human DNA-PK holoenzyme.. Yin X, Liu M, Tian Y, Wang J, Xu Y;. Cell Res. 2017;27:1341-1350.. [4]. 33077952. Dimers of DNA-PK create a stage for DNA double-strand break. repair.. Chaplin AK, Hardwick SW, Liang S, Kefala Stavridi A, Hnizda A,. Cooper LR, De Oliveira TM, Chirgadze DY, Blundell TL;. Nat Struct Mol Biol. 2021;28:13-19. (from Pfam)

Date:

2024-08-14

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is involved in DNA nonhomologous end joining (NHEJ) which is recruited by Ku70/80 heterodimer to DNA ends and required for double-strand break (DSB) repair. It folds into three well-defined large structural units, consisting of a N-terminal region, the Circular Cradle (consisting of five supersecondary alpha-helical structures CC1 to CC5), and the C-terminal Head (comprising FAT, FRB, kinase, and FATC). The N-terminal and CCs regions resemble HEAT repeats, and thus, they are also referred to as N-HEAT and M-HEAT ('middle'), respectively. The CCs form a curved elliptical ring that serves as a scaffold to maintain the integrity of the whole complex. This entry represents CC1 and CC2, which contain the Highly conserved region I (HCR-I) [1-4]. [1]. 28154079. DNA-PKcs structure suggests an allosteric mechanism modulating. DNA double-strand break repair.. Sibanda BL, Chirgadze DY, Ascher DB, Blundell TL;. Science. 2017;355:520-524.. [2]. 28652322. Cryo-EM structure of the DNA-PK holoenzyme.. Sharif H, Li Y, Dong Y, Dong L, Wang WL, Mao Y, Wu H;. Proc Natl Acad Sci U S A. 2017;114:7367-7372.. [3]. 28840859. Cryo-EM structure of human DNA-PK holoenzyme.. Yin X, Liu M, Tian Y, Wang J, Xu Y;. Cell Res. 2017;27:1341-1350.. [4]. 33077952. Dimers of DNA-PK create a stage for DNA double-strand break. repair.. Chaplin AK, Hardwick SW, Liang S, Kefala Stavridi A, Hnizda A,. Cooper LR, De Oliveira TM, Chirgadze DY, Blundell TL;. Nat Struct Mol Biol. 2021;28:13-19. (from Pfam)

Date:

2024-08-14

This is the C-terminal domain of BclA (Bacillus collagen-like protein of anthracis) which is expressed on spores of Bacillus species. Trimers of the C-terminal domain (CTD) form the tips of the spore's hair-like nap and are the immunodominant target of vertebrate antibodies and drive trimerization [1]. Structure analysis indicate the C-terminal region of the peptide folding into an all-beta structure with a jelly-fold topology, similar to the first human complement C1q, a member of the tumor necrosis factor (TNF)-like family. The C-terminal globular domain has been shown to be located on the exterior of the exosporium, and therefore is critical in determining the immunogenicity of the spore in a mammalian host [2]. [1]. 22405006. Variable lymphocyte receptor recognition of the immunodominant. glycoprotein of Bacillus anthracis spores.. Kirchdoerfer RN, Herrin BR, Han BW, Turnbough CL Jr, Cooper MD,. Wilson IA;. Structure. 2012;20:479-486.. [2]. 17879302. Construction, crystal structure and application of a recombinant. protein that lacks the collagen-like region of BclA from. Bacillus anthracis spores.. Liu CQ, Nuttall SD, Tran H, Wilkins M, Streltsov VA, Alderton. MR;. Biotechnol Bioeng. 2008;99:774-782. (from Pfam)

Date:

2024-08-14

Soti is a post-meiotically transcribed gene that is required in late spermiogenesis for normal spermatid individualisation. Besides, it is expressed in primary spermatocytes and round spermatids [1]. [1]. 18434411. Post-meiotic transcription in Drosophila testes.. Barreau C, Benson E, Gudmannsdottir E, Newton F, White-Cooper H;. Development. 2008;135:1897-1902. (from Pfam)

Date:

2024-08-14

This family represents the C-terminal domain of the putative Leucine Rich Repeat Containing protein 37A or protein 37B (LRRC37A/B) found in eukaryotes. The Leucine Rich Repeats (LRR) lies in the central region. The gene that encodes this protein is found in the chromosomal position 17q11.2, and its microdeletion results in the disease, neurofibromatosis type-1 (NF1) [1]. The function of the protein, LRRC37B is unknown, however experimental data shows expression in the aorta, heart, skeletal muscle, liver and brain during gestation [2]. [1]. 20506354. A novel third type of recurrent NF1 microdeletion mediated by. nonallelic homologous recombination between LRRC37B-containing. low-copy repeats in 17q11.2.. Bengesser K, Cooper DN, Steinmann K, Kluwe L, Chuzhanova NA,. Wimmer K, Tatagiba M, Tinschert S, Mautner VF, Kehrer-Sawatzki. H;. Hum Mutat. 2010;31:742-751.. [2]. 16138909. Evidence by expression analysis of candidate genes for. congenital heart defects in the NF1 microdeletion interval.. Venturin M, Bentivegna A, Moroni R, Larizza L, Riva P;. Ann Hum Genet. 2005;69:508-516. (from Pfam)

Date:

2024-08-14

Telomere repeat binding factor (TRF) family proteins are important for the regulation of telomere stability. The two related human TRF proteins hTRF1 and hTRF2 form homodimers and bind directly to telomeric TTAGGG repeats via the myb DNA binding domain Pfam:PF00249 at the carboxy terminus [1]. TRF1 is implicated in telomere length regulation and TRF2 in telomere protection [1]. Other telomere complex associated proteins are recruited through their interaction with either TRF1 or TRF2. The fission yeast protein Taz1p (telomere-associated in Schizosaccharomyces pombe) has similarity to both hTRF1 and hTRF2 and may perform the dual functions of TRF1 and TRF2 at fission yeast telomeres [2]. This domain is composed of multiple alpha helices [3] arranged in a solenoid conformation similar to TPR repeats. The fungal members have now also been found to carry two double strand telomeric repeat binding factors [4]. [1]. 15316005. TIN2 binds TRF1 and TRF2 simultaneously and stabilizes the TRF2. complex on telomeres.. Ye JZ, Donigian JR, van Overbeek M, Loayza D, Luo Y, Krutchinsky. AN, Chait BT, de Lange T;. J Biol Chem 2004;279:47264-47271.. [2]. 9034194. Regulation of telomere length and function by a Myb-domain. protein in fission yeast.. Cooper JP, Nimmo ER, Allshire RC, Cech TR;. Nature 1997;385:744-747.. [3]. 11545737. Structure of the TRFH dimerization domain of the human telomeric. proteins TRF1 and TRF2.. Fairall L, Chapman L, Moss H, de Lange T, Rhodes D;. Mol Cell 2001;8:351-361.. [4]. 17977837. Identification and characterization of an essential telomeric. repeat binding factor in fission yeast.. Pitt CW, Valente LP, Rhod. TRUNCATED at 1650 bytes (from Pfam)

Date:

2024-08-14

This family includes lipoprotein GfcB (YmcC), involved in group 4 capsule polysaccharide formation [1]. YjbF is a family of Gram-negative bacterial outer-membrane lipoproteins, predicted to be a beta-barrel and possibly a porin that is one of four gene-products expressed from an operon, yjbEFGH, which is regulated by the Rcs phosphorelay in a RcsA-dependent manner, similar to that of other exopolysaccharide biosynthetic pathways. It is highly possible that the yjbEFGH operon encodes a system involved in EPS secretion since none of the products is predicted to have enzymic activity, the products are all secreted and YbjF and H are predicted to be beta-barrel lipoproteins similar to porins. It may be that the operon products play some role in biofilm formation and/or matrix production [1]. [1]. 16030220. Identification of an Escherichia coli operon required for. formation of the O-antigen capsule.. Peleg A, Shifrin Y, Ilan O, Nadler-Yona C, Nov S, Koby S, Baruch. K, Altuvia S, Elgrably-Weiss M, Abe CM, Knutton S, Saper MA,. Rosenshine I;. J Bacteriol. 2005;187:5259-5266.. [2]. 17379715. The yjbEFGH locus in Escherichia coli K-12 is an operon encoding. proteins involved in exopolysaccharide production.. Ferrieres L, Aslam SN, Cooper RM, Clarke DJ;. Microbiology. 2007;153:1070-1080.. [3]. 21449614. Crystal structure of E. coli group 4 capsule protein GfcC. reveals a domain organization resembling Wza.. Sathiyamoorthy K, Mills E, Franzmann TM, Rosenshine I, Saper MA;. Biochemistry 2011;0:0-0. (from Pfam)

Date:

2024-08-14

Members of this family have serine hydrolase activity. They contain a conserved serine hydrolase motif, GXSXG/A, where the serine is a putative nucleophile [1]. This family has an alpha-beta hydrolase fold [2,3]. Eukaryotic members of this family have a conserved LXCXE motif, which binds to retinoblastomas. This motif is absent from prokaryotic members of this family [3]. [1]. 20080647. RBBP9: a tumor-associated serine hydrolase activity required for. pancreatic neoplasia.. Shields DJ, Niessen S, Murphy EA, Mielgo A, Desgrosellier JS,. Lau SK, Barnes LA, Lesperance J, Bouvet M, Tarin D, Cravatt BF,. Cheresh DA;. Proc Natl Acad Sci U S A. 2010;107:2189-2194.. [2]. 15159570. Harvesting the high-hanging fruit: the structure of the YdeN. gene product from Bacillus subtilis at 1.8 angstroms resolution.. Janda I, Devedjiev Y, Cooper D, Chruszcz M, Derewenda U, Gabrys. A, Minor W, Joachimiak A, Derewenda ZS;. Acta Crystallogr D Biol Crystallogr 2004;60:1101-1107.. [3]. 19004028. Crystal structure of human retinoblastoma binding protein 9.. Vorobiev SM, Su M, Seetharaman J, Huang YJ, Chen CX, Maglaqui M,. Janjua H, Proudfoot M, Yakunin A, Xiao R, Acton TB, Montelione. GT, Tong L;. Proteins. 2009;74:526-529. (from Pfam)

Date:

2024-08-14

DIRP (Domain in Rb-related Pathway) is postulated to be involved in the Rb-related pathway, which is encoded by multiple eukaryotic genomes and is present in proteins including lin-9 of Caenorhabditis elegans, aly of fruit fly and mustard weed. Studies of lin-9 and aly of fruit fly proteins containing DIRP suggest that this domain might be involved in development. Aly, lin-9, act in parallel to, or downstream of, activation of MAPK by the RTK-Ras signalling pathway. [1]. 11076766. Transcription of meiotic cell cycle and terminal differentiation. genes depends on a conserved chromatin associated protein, whose. nuclear localisation is regulated.. White-Cooper H, Leroy D, MacQueen A, Fuller MT;. Development 2000;127:5463-5473. (from Pfam)

Date:

2024-08-14

This family represents an N-terminal conserved region found in several huntingtin-associated protein 1 (HAP1) homologues. HAP1 binds to huntingtin in a polyglutamine repeat-length-dependent manner. However, its possible role in the pathogenesis of Huntington's disease is unclear [1-3]. This family also includes a similar N-terminal conserved region from hypothetical protein products of ALS2CR3 genes found in the human juvenile amyotrophic lateral sclerosis critical region 2q33-2q34 [4]. [1]. 7477378. A huntingtin-associated protein enriched in brain with. implications for pathology.. Li XJ, Li SH, Sharp AH, Nucifora FC Jr, Schilling G, Lanahan A,. Worley P, Snyder SH, Ross CA;. Nature 1995;378:398-402.. [2]. 9599014. HAP1-huntingtin interactions do not contribute to the molecular. pathology in Huntington's disease transgenic mice.. Bertaux F, Sharp AH, Ross CA, Lehrach H, Bates GP, Wanker E;. FEBS Lett 1998;426:229-232.. [3]. 9285789. Huntingtin-associated protein 1 (HAP1) binds to a Trio-like. polypeptide, with a rac1 guanine nucleotide exchange factor. domain.. Colomer V, Engelender S, Sharp AH, Duan K, Cooper JK, Lanahan A,. Lyford G, Worley P, Ross CA;. Hum Mol Genet 1997;6:1519-1525.. [4]. 11161814. Cloning and characterization of three novel genes, ALS2CR1,. ALS2CR2, and ALS2CR3, in the juvenile amyotrophic lateral. sclerosis (ALS2) critical region at chromosome 2q33-q34:. candidate genes for ALS2.. Hadano S, Yanagisawa Y, Skaug J, Fichter K, Nasir J, Martindale. D, Koop BF, Scherer SW, Nicholson DW, Rouleau GA, Ikeda J,. Hayden MR;. Genomics 2001;71:200-213. (from Pfam)

Date:

2024-08-14

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 [1,2]. 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 characteristic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity [2]. [1]. 9647693. Atrophin-1, the DRPLA gene product, interacts with two families. of WW domain-containing proteins.. Wood JD, Yuan J, Margolis RL, Colomer V, Duan K, Kushi J,. Kaminsky Z, Kleiderlein JJ, Sharp AH, Ross CA;. Mol Cell Neurosci 1998;11:149-160.. [2]. 11264541. Interference by huntingtin and atrophin-1 with cbp-mediated. transcription leading to cellular toxicity.. Nucifora FC Jr, Sasaki M, Peters MF, Huang H, Cooper JK, Yamada. M, Takahashi H, Tsuji S, Troncoso J, Dawson VL, Dawson TM, Ross. CA;. Science 2001;291:2423-2428. (from Pfam)

Date:

2024-08-14