Protein Family Models

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2024-08-14

This is the second domain on the N-terminal region found on the alpha C protein (ACP). ACP is found in Streptococcus and acts as an invasin which plays a role in the internalisation and translocation of the organism across human epithelial surfaces [1]. Group B Streptococcus is the leading cause of diseases including bacterial pneumonia, sepsis and meningitis. ACP consists of an N-terminal domain (NtACP; 170 amino acids) followed by a variable number of tandem repeats (82 amino acids each) and a C-terminal domain (45 amino acids) containing an LPXTG peptidoglycan-anchoring motif. The NtACP, contains two structural domains, D1 and D2. D1, the more distal (amino-terminal) portion Pfam:PF08829 and consists of a beta sandwich with strong structural homology to fibronectin's integrin-binding region (FnIII10). This entry, D2 (connects distally to Domain 1 and proximally to the repeat region) [1] consists of three antiparallel alpha helix coils [2]. It is suggested that the GAG-binding region of ACP may extend from Domain 2 into the repeat region [3]. [1]. 15753100. Crystal structure of the N-terminal domain of the group B. streptococcus alpha C protein.. Auperin TC, Bolduc GR, Baron MJ, Heroux A, Filman DJ, Madoff LC,. Hogle JM;. J Biol Chem. 2005;280:18245-18252.. [2]. 18048918. The group B streptococcal alpha C protein binds. alpha1beta1-integrin through a novel KTD motif that promotes. internalization of GBS within human epithelial cells.. Bolduc GR, Madoff LC;. Microbiology. 2007;153:4039-4049.. [3]. 17259175. Identification of a glycosaminoglycan binding region of the. alpha C protein that mediates entry of group B Strept. TRUNCATED at 1650 bytes (from Pfam)

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2024-08-14

Type IIS restriction endonuclease FokI is a member of an unusual class of bipartite restriction enzymes that recognises the double- stranded DNA sequence 5'-GGATG-3' and cleave DNA phosphodiester groups 9 base pairs away on this strand and 13 base pairs away on the complementary strand [1,2]. FokI contains amino- and carboxy- terminal domains corresponding to the DNA-recognition and cleavage functions, respectively. The recognition domain is made of three smaller subdomains (D1, D2 and D3) which are evolutionarily related to the helix-turn-helix-containing DNA-binding domain of the catabolite gene activator protein CAP [1]. This is the D3 domain which is most similar to CAP and related proteins such as histone H5, HNF-3gamma and the biotin operon repressor (BirA). Despite its similarity, D3 barely touches the DNA [1]. [1]. 9214510. Structure of the multimodular endonuclease FokI bound to DNA.. Wah DA, Hirsch JA, Dorner LF, Schildkraut I, Aggarwal AK;. Nature. 1997;388:97-100.. [2]. 9724743. Structure of FokI has implications for DNA cleavage.. Wah DA, Bitinaite J, Schildkraut I, Aggarwal AK;. Proc Natl Acad Sci U S A. 1998;95:10564-10569. (from Pfam)

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Many bacteria are covered in a layer of surface-associated polysaccharide called the capsule. These capsules can be divided into four groups depending upon the organisation of genes responsible for capsule assembly, the assembly pathway and regulation [1]. This family plays a role in group 4 capsule biosynthesis [2]. These proteins have a beta-grasp fold [3]. Two beta-grasp domains, D2 and D3, are arranged in tandem. There is a C-terminal amphipathic helix which packs against D3. A helical hairpin insert in D2 binds to D3 and constrains its position, a conserved arginine residue at the end of this hairpin is essential for structural integrity [4]. This entry represents D2 domain found at the N-terminal [4]. [1]. 10200953. Structure, assembly and regulation of expression of capsules in. Escherichia coli.. Whitfield C, Roberts IS;. Mol Microbiol. 1999;31:1307-1319.. [2]. 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.. [3]. 17250770. A novel superfamily containing the beta-grasp fold involved in. binding diverse soluble ligands.. Burroughs AM, Balaji S, Iyer LM, Aravind L;. Biol Direct. 2007;2:4-4.. [4]. 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)

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2024-08-14

This is the C-terminal domain found in hemagglutinin component such as HA70 found in Clostridium botulinum. HA is a component of the large botulinum neurotoxin complex and is critical for its oral toxicity. HA plays multiple roles in toxin penetration in the gastrointestinal tract, including protection from the digestive environment, binding to the intestinal mucosal surface, and disruption of the epithelial barrier [1]. HA consists of three different proteins, designated HA70 (also known as HA3), HA33 (HA1), and HA17 (HA2) based on molecular mass [2]. HA70 consists of three domains (D1-3). The D1 and D2 domains, which adopt similar structures, mediate the trimerization of HA70 with each protomer. The D3 domain, sitting at the tip of the trimer, is composed of two similar jelly-roll-like beta-sandwich structures [3]. Furthermore, crystal structures of HA70 in a complex with alpha2,3- or alpha2,6-SiaLac (alpha2,6-sialyllactose), show that alpha2,3- and alpha2,6-SiaLac bound to the same region in the D3 domain of HA70. This domain is the D3 domain found in HA3/HA70 which has been shown to be involved in binding to carbohydrate of glycoproteins from epithelial cells in the infection process [2]. [1]. 24948737. Molecular basis for disruption of E-cadherin adhesion by. botulinum neurotoxin A complex.. Lee K, Zhong X, Gu S, Kruel AM, Dorner MB, Perry K, Rummel A,. Dong M, Jin R;. Science. 2014;344:1405-1410.. [2]. 22684008. Carbohydrate recognition mechanism of HA70 from Clostridium. botulinum deduced from X-ray structures in complexes with. sialylated oligosaccharides.. Yamashita S, Yoshida H, Uchiyama N, Nakakita Y, Nakakita S. TRUNCATED at 1650 bytes (from Pfam)

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2024-08-14

This domain is found in Interleukin-7 receptor subunit alpha (IL-7Ralpha), which together IL-7 form a complex crucial to several signalling cascades leading to the development and homeostasis of T and B cells. IL-7Ralpha carries a 219 residue ectodomain on the N-terminal region which is crucial for T and B-cell development. Mutations in the IL-7Ralpha ectodomain inhibits T and B cell development, resulting in patients with a form of severe combined immunodeficiency (SCID). The ectodomain folds into two fibronectin type III (FNIII) domains connected by a 310-helical linker. This entry comprises the first of the two FNIII domains, D1 while D2 domain is Pfam:PF00041. In the D1 domain of IL-7Ralpha, a disulfide bond (C22R-C37R) conserved among cytokine receptor class I (CRH I) family members bridges two beta strands [1]. [1]. 19141282. Structural and biophysical studies of the human IL-7/IL-7Ralpha. complex.. McElroy CA, Dohm JA, Walsh ST;. Structure. 2009;17:54-65.. [2]. 22308406. Structural reorganization of the interleukin-7 signaling. complex.. McElroy CA, Holland PJ, Zhao P, Lim JM, Wells L, Eisenstein E,. Walsh ST;. Proc Natl Acad Sci U S A. 2012;109:2503-2508.. [3]. 24632570. Structural basis of the proinflammatory signaling complex. mediated by TSLP.. Verstraete K, van Schie L, Vyncke L, Bloch Y, Tavernier J,. Pauwels E, Peelman F, Savvides SN;. Nat Struct Mol Biol. 2014;21:375-382. (from Pfam)

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HlyD_D23 is the combined domains 2 and 3 of the membrane-fusion proteins CusB and HlyD, which forms a barrel-sandwich. CusB and HlyD proteins are membrane fusion proteins of the CusCFBA copper efflux system in E.coli and related bacteria. The whole molecule hinges between D2 and D3. Efflux systems of this resistance-nodulation-division group - RND - have been developed to excrete poisonous metal ions, and in E.coli the only one that deals with silver and copper is the CusA transporter. The transporter CusA works in conjunction with a periplasmic component that is a membrane fusion protein, eg CusB, and an outer-membrane channel component CusC in a CusABC complex driven by import of protons. [1]. 19695261. Crystal structure of the membrane fusion protein CusB from. Escherichia coli.. Su CC, Yang F, Long F, Reyon D, Routh MD, Kuo DW, Mokhtari AK,. Van Ornam JD, Rabe KL, Hoy JA, Lee YJ, Rajashankar KR, Yu EW;. J Mol Biol. 2009;393:342-355. (from Pfam)

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This domain can be found in 5' to 3' exoribonuclease 1 (XRN1) which belong to a family of conserved enzymes in eukaryotes and have important functions in transcription, RNA metabolism, and RNA interference. Xrn1 in fungi and animals is primarily cytosolic, involved in degradation of decapped mRNAs, nonsense mediated decay, microRNA decay and is essential for proper development. The Xrn1 homolog in Drosophila, known as Pacman, is required for male fertility [1]. This entry relates to domain 2 and 3 combined which can be found in the 510-residue C-terminal extension found in XRN1 and not in XRN2/Rat1. Domain D2 is formed by two stretches of Xrn1, residues 915-960 and 1134-1151. The presence of domain (D3) is suggested based on structure. This domain is formed by residues 979-1109, in the insert of domain D2. It is suggested that domains D2-D4 may help maintain domain D1 Pfam:PF18332 in the correct conformation, thereby indirectly stabilising the conformation of the N-terminal segment Pfam:PF03159 [1]. [1]. 21297639. Structural and biochemical studies of the 5'-->3'. exoribonuclease Xrn1.. Chang JH, Xiang S, Xiang K, Manley JL, Tong L;. Nat Struct Mol Biol. 2011;18:270-276. (from Pfam)

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2024-08-14

IL-2Rbeta is a member of the class I cytokine receptor superfamily [1]. It carries a cytokine-binding homology region, which is divided in two fibronectin type-III (FN-III) domains termed D1 and D2. Each domain contains seven beta-strands that form a sandwich of two antiparallel beta-sheets. The N-terminal D1 domain of IL-2Rbeta includes two highly conserved disulfide bridges [2]. This entry describes D1 of the N-terminal region of IL2Rbeta. [1]. 16293754. Structure of the quaternary complex of interleukin-2 with its. alpha, beta, and gammac receptors.. Wang X, Rickert M, Garcia KC;. Science. 2005;310:1159-1163.. [2]. 16477002. Crystal structure of the IL-2 signaling complex: paradigm for a. heterotrimeric cytokine receptor.. Stauber DJ, Debler EW, Horton PA, Smith KA, Wilson IA;. Proc Natl Acad Sci U S A. 2006;103:2788-2793. (from Pfam)

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This is the D2 domain in cytokine-binding module 1 (CBM1) found in Leukemia inhibitory factor receptor (LIFR) and OSM receptors (OSMR). LIFR has an extracellular region with a modular structure containing two cytokine-binding modules (CBM) separated by an Ig-like domain and followed by three membrane-proximal fibronectin type-III (FNIII) domains. The D2 domain in CBM1 shows structural similarity to the corresponding CBM domains of both gp130 and IL-6Ralpha because it contains conserved structural features like the WSXWS motif [1] [2]. The WSXWS motif in cytokine receptors is a molecular switch involved in receptor activation [3]. [1]. 18775332. Structural organization of a full-length gp130/LIF-R cytokine. receptor transmembrane complex.. Skiniotis G, Lupardus PJ, Martick M, Walz T, Garcia KC;. Mol Cell. 2008;31:737-748.. [2]. 17652170. An unusual cytokine:Ig-domain interaction revealed in the. crystal structure of leukemia inhibitory factor (LIF) in complex. with the LIF receptor.. Huyton T, Zhang JG, Luo CS, Lou MZ, Hilton DJ, Nicola NA,. Garrett TP;. Proc Natl Acad Sci U S A. 2007;104:12737-12742.. [3]. 22325776. The WSXWS motif in cytokine receptors is a molecular switch. involved in receptor activation: insight from structures of the. prolactin receptor.. Dagil R, Knudsen MJ, Olsen JG, O'Shea C, Franzmann M, Goffin V,. Teilum K, Breinholt J, Kragelund BB;. Structure. 2012;20:270-282. (from Pfam)

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This entry represents a C-terminal winged Helix-Turn-Helix domain. CNDH2_C is the C-terminal domain of the H2 subunit of the condensin II complex, found in eukaryotes but not fungi. Eukaryotes carry at least two condensin complexes, I and II, each made up of five subunits. The functions of the two complexes are collaborative but non-overlapping. CI appears to be functional in G2 phase in the cytoplasm beginning the process of chromosomal lateral compaction while the CII are concentrated in the nucleus, possibly to counteract the activity of cohesion at this stage. In prophase, CII contributes to axial shortening of chromatids while CI continues to bring about lateral chromatid compaction, during which time the sister chromatids are joined centrally by cohesins. There appears to be just one condensin complex in fungi. CI and CII each contain SMC2 and SMC4 (structural maintenance of chromosomes) subunits, then CI has non-SMC CAP-D2 (CND1), CAP-G (CND3), and CAP-H (CND2). CII has, in addition to the two SMCs, CAP-D3, CAPG2 and CAP-H2. All four of the CAP-D and CAP-G subunits have degenerate HEAT repeats, whereas the CAP-H are kleisins or SMC-interacting proteins (ie they bind directly to the SMC subunits in the complex). The SMC molecules are each long with a small hinge-like knob at the free end of a longish strand, articulating with each other at the hinge. Each strand ends in a knob-like head that binds to one or other end of the CAP-H subunit. The HEAT-repeat containing D and G subunits bind side-by-side between the ends of the H subunit. Activity of the various parts of the complex seem to be triggered by extensive. TRUNCATED at 1650 bytes (from Pfam)

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This family of proteins of unknown function gets its name from its position in the mammalian genome: Fanconi anemia group D2 protein opposite strand transcript protein. (from Pfam)

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CNDH2_M is the middle domain of the H2 subunit of the condensin II complex, found in eukaryotes but not fungi. Eukaryotes carry at least two condensin complexes, I and II, each made up of five subunits. The functions of the two complexes are collaborative but non-overlapping. CI appears to be functional in G2 phase in the cytoplasm beginning the process of chromosomal lateral compaction while the CII are concentrated in the nucleus, possibly to counteract the activity of cohesion at this stage. In prophase, CII contributes to axial shortening of chromatids while CI continues to bring about lateral chromatid compaction, during which time the sister chromatids are joined centrally by cohesins. There appears to be just one condensin complex in fungi. CI and CII each contain SMC2 and SMC4 (structural maintenance of chromosomes) subunits, then CI has non-SMC CAP-D2 (CND1), CAP-G (CND3), and CAP-H (CND2). CII has, in addition to the two SMCs, CAP-D3, CAPG2 and CAP-H2. All four of the CAP-D and CAP-G subunits have degenerate HEAT repeats, whereas the CAP-H are kleisins or SMC-interacting proteins (ie they bind directly to the SMC subunits in the complex). The SMC molecules are each long with a small hinge-like knob at the free end of a longish strand, articulating with each other at the hinge. Each strand ends in a knob-like head that binds to one or other end of the CAP-H subunit. The HEAT-repeat containing D and G subunits bind side-by-side between the ends of the H subunit. Activity of the various parts of the complex seem to be triggered by extensive phosphorylations, eg, entry of the complex, in Sch.pombe, into the nucl. TRUNCATED at 1650 bytes (from Pfam)

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