Protein Family Models

This entry represents the RZ type zinc finger domain, found in NFX1-type zinc finger-containing protein 1 (ZNFX1) and E3 ubiquitin-protein ligase RNF213 from humans. It contains two conserved histidine residues and four conserved cysteine residues in a CHC3H motif. It can bind divalent transition metals, with a preference for Zn2+. ZNFX1 is an RNA-binding protein that initiates the antiviral response and is required to restrict the replication of RNA viruses [1,2]. RNF213 is a giant E3 ubiquitin ligase that can catalyse ubiquitination of both proteins and lipids, which is involved in various processes, such as lipid metabolism, angiogenesis and cell-autonomous immunity. It functions as a key immune sensor by catalysing ubiquitination of the lipid A moiety of bacterial LPS via its RZ-type zinc-finger and restricts the proliferation of cytosolic bacteria [3,4]. RNF213 is a major susceptibility factor of Moyamoya disease [5]. [1]. 31685995. Mitochondria-localised ZNFX1 functions as a dsRNA sensor to. initiate antiviral responses through MAVS.. Wang Y, Yuan S, Jia X, Ge Y, Ling T, Nie M, Lan X, Chen S, Xu A;. Nat Cell Biol. 2019;21:1346-1356.. [2]. 33872655. Multisystem inflammation and susceptibility to viral infections. in human ZNFX1 deficiency.. Vavassori S, Chou J, Faletti LE, Haunerdinger V, Opitz L, Joset. P, Fraser CJ, Prader S, Gao X, Schuch LA, Wagner M, Hoefele J,. Maccari ME, Zhu Y, Elakis G, Gabbett MT, Forstner M, Omran H,. Kaiser T, Kessler C, Olbrich H, Frosk P, Almutairi A, Platt CD,. Elkins M, Weeks S, Rubin T, Planas R, Marchetti T, Koovely D,. Klambt V, Soliman NA, von Hardenberg S, Klemann C, Baumann U,. L. TRUNCATED at 1650 bytes (from Pfam)

Date:

2024-08-14

This entry represents an alpha-helical domain found in 5-hmdU DNA kinase (HMUDK), a P-loop nucleotide kinase that phosphorylates 5-hydroxymethyluracil (5hmdU) into 5-phosphomethyl-2'-deoxyuridine (5-PmdU) on DNA as a step in the pathway leading to thymidine hypermodifications in the viral genome [2]. HMUDK also transfers glutamate to 5-pyrophosphoryloxymethyldeoxyuridine (5-PPmdU) to produce 5-Nalpha-glyutamylthymidine (Nalpha-GluT) [2,3]. These modifications probably prevent degradation of viral genome by the host restriction-modification antiviral defense system [1,2]. Members of this entry (formerly known as aGPT-Pplase1) are found in phages with hypermodified bases and eukaryotes such as fungi and stramenopiles [1,2]. [1]. 23814188. Computational identification of novel biochemical systems. involved in oxidation, glycosylation and other complex. modifications of bases in DNA.. Iyer LM, Zhang D, Burroughs AM, Aravind L;. Nucleic Acids Res. 2013;41:7635-7655.. [2]. 34522950. Pathways of thymidine hypermodification.. Lee YJ, Dai N, Muller SI, Guan C, Parker MJ, Fraser ME, Walsh. SE, Sridar J, Mulholland A, Nayak K, Sun Z, Lin YC, Comb DG,. Marks K, Gonzalez R, Dowling DP, Bandarian V, Saleh L, Correa. IR, Weigele PR;. Nucleic Acids Res. 2022;50:3001-3017.. [3]. 29555775. Identification and biosynthesis of thymidine hypermodifications. in the genomic DNA of widespread bacterial viruses.. Lee YJ, Dai N, Walsh SE, Muller S, Fraser ME, Kauffman KM, Guan. C, Correa IR Jr, Weigele PR;. Proc Natl Acad Sci U S A. 2018;115:E3116. (from Pfam)

Date:

2024-08-14

5-hmdU DNA kinase (HMUDK) and 5-hmdU DNA kinase 1 (HDMU1) are P-loop nucleotide kinases that phosphorylates 5-hydroxymethyluracil (5hmdU) into 5-phosphomethyl-2'-deoxyuridine (5-PmdU) on DNA as a step in the pathway leading to thymidine hypermodifications in the viral genome [2]. HMUDK also transfers glutamate to 5-pyrophosphoryloxymethyldeoxyuridine (5-PPmdU) to produce 5-Nalpha-glyutamylthymidine (Nalpha-GluT) [2,3]. These modifications probably prevent degradation of viral genome by the host restriction-modification antiviral defense system [1,3]. [1]. 23814188. Computational identification of novel biochemical systems. involved in oxidation, glycosylation and other complex. modifications of bases in DNA.. Iyer LM, Zhang D, Burroughs AM, Aravind L;. Nucleic Acids Res. 2013;41:7635-7655.. [2]. 34522950. Pathways of thymidine hypermodification.. Lee YJ, Dai N, Muller SI, Guan C, Parker MJ, Fraser ME, Walsh. SE, Sridar J, Mulholland A, Nayak K, Sun Z, Lin YC, Comb DG,. Marks K, Gonzalez R, Dowling DP, Bandarian V, Saleh L, Correa. IR, Weigele PR;. Nucleic Acids Res. 2022;50:3001-3017.. [3]. 29555775. Identification and biosynthesis of thymidine hypermodifications. in the genomic DNA of widespread bacterial viruses.. Lee YJ, Dai N, Walsh SE, Muller S, Fraser ME, Kauffman KM, Guan. C, Correa IR Jr, Weigele PR;. Proc Natl Acad Sci U S A. 2018;115:E3116. (from Pfam)

Date:

2024-08-14

This family features the C-terminal regions of various plexins (e.g. Swiss:P51805). Plexins are receptors for semaphorins, and plexin signalling is important in path finding and patterning of both neurons and developing blood vessels [1,2]. The cytoplasmic region, which has been called a SEX domain in some members of this family [3], is involved in downstream signalling pathways, by interaction with proteins such as Rac1, RhoD, Rnd1 and other plexins [4]. This domain acts as a RasGAP domain [5]. [1]. 15239959. Semaphorin-plexin signaling guides patterning of the developing. vasculature.. Torres-Vazquez J, Gitler AD, Fraser SD, Berk JD, Van N Pham,. Fishman MC, Childs S, Epstein JA, Weinstein BM;. Dev Cell 2004;7:117-123.. [2]. 11959816. Caenorhabditis elegans PlexinA, PLX-1, interacts with. transmembrane semaphorins and regulates epidermal morphogenesis.. Fujii T, Nakao F, Shibata Y, Shioi G, Kodama E, Fujisawa H,. Takagi S;. Development 2002;129:2053-2063.. [3]. 8570614. A family of transmembrane proteins with homology to the. MET-hepatocyte growth factor receptor.. Maestrini E, Tamagnone L, Longati P, Cremona O, Gulisano M,. Bione S, Tamanini F, Neel BG, Toniolo D, Comoglio PM;. Proc Natl Acad Sci U S A 1996;93:674-678.. [4]. 12559962. Plexin-A1 and plexin-B1 specifically interact at their. cytoplasmic domains.. Usui H, Taniguchi M, Yokomizo T, Shimizu T;. Biochem Biophys Res Commun 2003;300:927-931.. [5]. 11108845. The semaphorin 3A receptor may directly regulate the activity of. small GTPases.. Rohm B, Rahim B, Kleiber B, Hovatta I, Puschel AW;. FEBS Lett. 2000;486:68-72. (from Pfam)

Date:

2024-08-14

Several members of this family are Borrelia burgdorferi plasmid proteins of uncharacterized function. [1]. 10672174. A bacterial genome in flux: the twelve linear and nine circular. extrachromosomal DNAs in an infectious isolate of the Lyme. disease spirochete Borrelia burgdorferi.. Casjens S, Palmer N, van Vugt R, Huang WM, Stevenson B, Rosa P,. Lathigra R, Sutton G, Peterson J, Dodson RJ, Haft D, Hickey E,. Gwinn M, White O, Fraser CM;. Mol Microbiol 2000;35:490-516. (from Pfam)

Date:

2024-08-14

Thymidylate synthase complementing protein (Thy1) complements the thymidine growth requirement of the organisms in which it is found, but shows no homology to thymidylate synthase. The bacterial members of this family at least are flavin-dependent thymidylate synthases [2,3,4]. [1]. 9665876. Complete genome sequence of Treponema pallidum, the syphilis. spirochete [see comments]. Fraser CM, Norris SJ, Weinstock GM, White O, Sutton GG, Dodson. R, Gwinn M, Hickey EK, Clayton R, Ketchum KA, Sodergren E,. Hardham JM, McLeod MP, Salzberg S, Peterson J, Khalak H,. Richardson D, Howell JK, Chidambaram M, Utterback T, McDonald L,. Artiach P,. Science 1998;281:375-388.. [2]. 12029065. An alternative flavin-dependent mechanism for thymidylate. synthesis.. Myllykallio H, Lipowski G, Leduc D, Filee J, Forterre P, Liebl. U;. Science. 2002;297:105-107.. [3]. 15046578. Two distinct pathways for thymidylate (dTMP) synthesis in. (hyper)thermophilic Bacteria and Archaea.. Leduc D, Graziani S, Meslet-Cladiere L, Sodolescu A, Liebl U,. Myllykallio H;. Biochem Soc Trans. 2004;32:231-235.. [4]. 17890305. Flavin-dependent thymidylate synthase ThyX activity:. implications for the folate cycle in bacteria.. Leduc D, Escartin F, Nijhout HF, Reed MC, Liebl U, Skouloubris. S, Myllykallio H;. J Bacteriol. 2007;189:8537-8545. (from Pfam)

Date:

2024-08-14