Protein Family Models

C-terminal jelly roll/Ig-like domain (C-JID) was defined in cryogenic electron microscopy (cryoEM) structures of plant intracellular immune receptors containing Toll/interleukin-1 receptor (TIR, PF01582), nucleotide-binding (NB-ARC, PF00931) and leucine-rich repeat (LRR) domains (TIR-NLRs) [1,2]. Structurally, the C-JID core is represented by a beta-sandwich made up of 8 to 9 beta-strands. C-JID matches the so-called post-LRR or C-terminal non-LRR domain detected earlier via MEME and BLAST searches [3,7]. The domain showed a strong distribution bias towards TIR-NLRs of dicotyledonous plant species despite broader taxonomic distribution of TIR-NLR in plant groups [1-7]. Structure-function analyses of cryoEM structures suggest that C-JID domains play a role in substrate recognition, such as binding to effector proteins from pathogens, and thus are involved in the initiation of signaling by TIR-NLR receptors [1,2]. Presence of C-JID (or post-LRR) and its importance for the function of Arabidopsis TIR-NLR RPS4 that partners with RRS1 for effector recognition suggest that C-JID has additional functions [4-6]. [1]. 33273074. Structure of the activated ROQ1 resistosome directly recognizing. the pathogen effector XopQ.. Martin R, Qi T, Zhang H, Liu F, King M, Toth C, Nogales E,. Staskawicz BJ;. Science. 2020; [Epub ahead of print]. [2]. 33273071. Direct pathogen-induced assembly of an NLR immune receptor. complex to form a holoenzyme.. Ma S, Lapin D, Liu L, Sun Y, Song W, Zhang X, Logemann E, Yu D,. Wang J, Jirschitzka J, Han Z, Schulze-Lefert P, Parker JE, Chai. J;. Science. 2020; [Epub ahead of print]. [3]. 27129402. TNL genes i. TRUNCATED at 1650 bytes (from Pfam)

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2024-08-14

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0000877) is described by MIBiG as an example of the following biosynthetic class, other (unspecified), in particular the polyoxin A biosynthetic gene cluster from Streptomyces cacaoi subsp. asoensis [1]. This family appears to be predominantly found in Actinobacteria. [1]. 19233844. Characterization of the polyoxin biosynthetic gene cluster from. Streptomyces cacaoi and engineered production of polyoxin H.. Chen W, Huang T, He X, Meng Q, You D, Bai L, Li J, Wu M, Li R,. Xie Z, Zhou H, Zhou X, Tan H, Deng Z;. J Biol Chem. 2009;284:10627-10638.. [2]. 19383687. polR, a pathway-specific transcriptional regulatory gene,. positively controls polyoxin biosynthesis in Streptomyces cacaoi. subsp. asoensis.. Li R, Xie Z, Tian Y, Yang H, Chen W, You D, Liu G, Deng Z, Tan. H;. Microbiology (Reading). 2009;155:1819-1831. (from Pfam)

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2024-08-14

This entry represents the C-terminal domain of coronavirus non-structural protein 15 (NSP15 or nsp15). NSP15 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. This domain exhibits endoribonuclease activity designated EndoU, highly conserved in all known CoVs and is part of the replicase-transcriptase complex that plays important roles in virus replication and transcription [1, 2, 3]. NSP15 is a Uridylate-specific endoribonuclease that cleaves the 5'-polyuridines from negative-sense viral RNA, termed PUN RNA either upstream or downstream of uridylates, at GUU or GU to produce molecules with 2',3'-cyclic phosphate ends [2, 3]. PUN RNA is a CoV MDA5-dependent pathogen-associated molecular pattern (PAMP) [3]. [1]. 16873248. New antiviral target revealed by the hexameric structure of. mouse hepatitis virus nonstructural protein nsp15.. Xu X, Zhai Y, Sun F, Lou Z, Su D, Xu Y, Zhang R, Joachimiak A,. Zhang XC, Bartlam M, Rao Z;. J Virol. 2006;80:7909-7917.. [2]. 29307596. An "Old" protein with a new story: Coronavirus endoribonuclease. is important for evading host antiviral defenses.. Deng X, Baker SC;. Virology. 2018;517:157-163.. [3]. 32198201. Coronavirus endoribonuclease targets viral polyuridine sequences. to evade activating host sensors.. Hackbart M, Deng X, Baker SC;. Proc Natl Acad Sci U S A. 2020 Mar 20. pii: 1921; [Epub ahead of print] (from Pfam)

Date:

2024-08-14

Heparinase II (HepII) is an 85-kDa dimeric enzyme that depolymerizes both heparin and heparan sulfate glycosaminoglycans [1]. The protein is composed of three domains: an N-terminal alpha-helical domain, a central two-layered beta-sheet domain, and a C-terminal domain forming a two-layered beta-sheet. The C-terminal domain contains nine beta-strands packed together in a manner resembling a beta-barrel [2]. [1]. 20404324. Catalytic mechanism of heparinase II investigated by. site-directed mutagenesis and the crystal structure with its. substrate.. Shaya D, Zhao W, Garron ML, Xiao Z, Cui Q, Zhang Z, Sulea T,. Linhardt RJ, Cygler M;. J Biol Chem. 2010;285:20051-20061.. [2]. 16565082. Crystal structure of heparinase II from Pedobacter heparinus and. its complex with a disaccharide product.. Shaya D, Tocilj A, Li Y, Myette J, Venkataraman G, Sasisekharan. R, Cygler M;. J Biol Chem. 2006;281:15525-15535. (from Pfam)

Date:

2024-08-14

The activity of RING finger ubiquitin ligases (E3) is dependent on their ability to facilitate transfer of ubiquitin from ubiquitin-conjugating enzymes (E2) to substrates. The G2BR domain within the E3 gp78 binds selectively and with high affinity to the E2 Ube2g2. Binding to the G2BR results in conformational changes in Ube2g2 that affect ubiquitin loading. The Ube2g2-G2BR interaction also causes a 50-fold increase in affinity between the E2 and RING finger. Hence, the Ube2g2-binding region (G2BR) is required for the function of gp78. In yeast, Ubc7p, the ortholog of Ube2g2, is recruited by Cue1p to the ER membrane. Cue1p directly binds Ubc7p through a stretch of 50 aa domain analogous to G2BR, i.e. suggesting that this domain which activates ERAD and Hrd1p stimulating ubiquitylation, might be the yeast equivalent of the G2BR domain [1-3]. [1]. 23942235. Allosteric regulation of E2:E3 interactions promote a processive. ubiquitination machine.. Das R, Liang YH, Mariano J, Li J, Huang T, King A, Tarasov SG,. Weissman AM, Ji X, Byrd RA;. EMBO J. 2013;32:2504-2516.. [2]. 19223579. Mechanistic insights into active site-associated. polyubiquitination by the ubiquitin-conjugating enzyme Ube2g2.. Li W, Tu D, Li L, Wollert T, Ghirlando R, Brunger AT, Ye Y;. Proc Natl Acad Sci U S A. 2009;106:3722-3727.. [3]. 19560420. Allosteric activation of E2-RING finger-mediated ubiquitylation. by a structurally defined specific E2-binding region of gp78.. Das R, Mariano J, Tsai YC, Kalathur RC, Kostova Z, Li J, Tarasov. SG, McFeeters RL, Altieri AS, Ji X, Byrd RA, Weissman AM;. Mol Cell. 2009;34:674-685. (from Pfam)

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2024-08-14

Catalyses cleavage and ligation of DNA [1-2]. [1]. 22593158. The structure of an archaeal viral integrase reveals an. evolutionarily conserved catalytic core yet supports a. mechanism of DNA cleavage in trans.. Eilers BJ, Young MJ, Lawrence CM;. J Virol. 2012;86:8309-8313.. [2]. 22683788. Structural and functional characterization of the C-terminal. catalytic domain of SSV1 integrase.. Zhan Z, Ouyang S, Liang W, Zhang Z, Liu ZJ, Huang L;. Acta Crystallogr D Biol Crystallogr. 2012;68:659-670. (from Pfam)

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2024-08-14

Apc1 is the largest of the subunits of the anaphase-promoting complex or cyclosome. The anaphase-promoting complex is a multiprotein subunit E3 ubiquitin ligase complex that controls segregation of chromosomes and exit from mitosis in eukaryotes. Apc1 consists of a N-terminal WD40 beta-propeller domain, followed by the middle domain (Mid-N), a PC domain and the C-terminal domain (MidC). This entry represents the middle domain of Apc1, MidN (also referred to as the first helical domain), that coaleses with the C-terminal domain to form Apc1Mid that connects Apc1WD40 with Apc1PC [1,2]. Apc1Mid consists of an alpha-solenoid capped by a beta-sandwich [2]. [1]. 27601667. WD40 domain of Apc1 is critical for the coactivator-induced. allosteric transition that stimulates APC/C catalytic activity.. Li Q, Chang L, Aibara S, Yang J, Zhang Z, Barford D;. Proc Natl Acad Sci U S A. 2016;113:10547-10552.. [2]. 26083744. Atomic structure of the APC/C and its mechanism of protein. ubiquitination.. Chang L, Zhang Z, Yang J, McLaughlin SH, Barford D;. Nature. 2015;522:450-454. (from Pfam)

Date:

2024-08-14

DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange factors (GEFs) that activate some small GTPases, such as Rac or Cdc42, by exchanging bound GDP for free GTP to control cell migration, morphogenesis, and phagocytosis. These proteins share a DOCK-type C2 domain (also termed the DOCK-homology region (DHR)-1) at the N-terminal, and the DHR-2 domain (also termed the DOCKER domain) at the C-terminal. DHR-2 is the GEF catalytic domain organised into three lobes A, B and C, with the Rho-family binding site and catalytic centre generated entirely from lobes B and C. This entry represents Lobe B which adopts an unusual architecture of two antiparallel beta sheets disposed in a loosely packed orthogonal arrangement. This lobe changes its position relative to lobe C and the bound GTPase, which suggests that lobe B distinguishes between the switch 1 conformations of Rac1 and Cdc42 [2]. [1]. 32651375. Structure of the DOCK2-ELMO1 complex provides insights into. regulation of the auto-inhibited state.. Chang L, Yang J, Jo CH, Boland A, Zhang Z, McLaughlin SH,. Abu-Thuraia A, Killoran RC, Smith MJ, Cote JF, Barford D;. Nat Commun. 2020;11:3464.. [2]. 30853411. Structural Basis for the Dual Substrate Specificity of DOCK7. Guanine Nucleotide Exchange Factor.. Kukimoto-Niino M, Tsuda K, Ihara K, Mishima-Tsumagari C, Honda. K, Ohsawa N, Shirouzu M;. Structure. 2019;27:741-748. (from Pfam)

Date:

2024-08-14

This entry represents the non-catalytic middle domain from coronavirus non-structural protein 15 (NSP15). NSP15 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. This domain is formed by ten beta strands organised into three beta hairpins [1, 2]. [1]. 16873248. New antiviral target revealed by the hexameric structure of. mouse hepatitis virus nonstructural protein nsp15.. Xu X, Zhai Y, Sun F, Lou Z, Su D, Xu Y, Zhang R, Joachimiak A,. Zhang XC, Bartlam M, Rao Z;. J Virol. 2006;80:7909-7917.. [2]. 29307596. An "Old" protein with a new story: Coronavirus endoribonuclease. is important for evading host antiviral defenses.. Deng X, Baker SC;. Virology. 2018;517:157-163. (from Pfam)

Date:

2024-08-14

In the pneumococcus cell division, MapZ (Midcell Anchored Protein Z) locates at the division site before FtsZ and guides septum positioning. MapZ forms ring structures at the cell equator and moves apart as the cell elongates, therefore behaving as a permanent beacon of division sites. MapZ then positions the FtsZ-ring through direct protein-protein interactions [1]. Structural analysis indicate that it displays a bi-modular structure composed of two subdomains separated by a flexible serine-rich linker. The extracellular C-terminal domain carries a conserved patch of amino acids which plays a crucial function in binding peptidoglycan and positioning MapZ at the cell equator [2]. [1]. 25470041. MapZ marks the division sites and positions FtsZ rings in. Streptococcus pneumoniae.. Fleurie A, Lesterlin C, Manuse S, Zhao C, Cluzel C, Lavergne JP,. Franz-Wachtel M, Macek B, Combet C, Kuru E, VanNieuwenhze MS,. Brun YV, Sherratt D, Grangeasse C;. Nature. 2014;516:259-262.. [2]. 27346279. Structure-function analysis of the extracellular domain of the. pneumococcal cell division site positioning protein MapZ.. Manuse S, Jean NL, Guinot M, Lavergne JP, Laguri C, Bougault CM,. VanNieuwenhze MS, Grangeasse C, Simorre JP;. Nat Commun. 2016;7:12071. (from Pfam)

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2024-08-14

This is the N-terminal domain found in trehalose-6-phosphate phosphatase (T6PP, EC 3.1.3.12) from parasitic nematodes such as Brugia malayi. In the model nematode Caenorhabditis elegans, T6PP is essential for survival due to the toxic effect(s) of the accumulation of trehalose 6-phosphate. T6PP has also been shown to be essential in Mycobacterium tuberculosis. The N-terminal domain composed of a three-helix bundle is similar in topology to the Microtubule Interacting and Transport (MIT) domains of the Vps4-like ATPases from Sulfolobus acidocaldarius. MIT domains are protein-interacting domains typically associated with multivesicular body formation, cytokinetic abscission, or viral budding. Mutational analysis indicate that deletion or mutation of the MIT-like domain is highly destabilizing to the enzyme [1]. [1]. 24992307. Structure of the trehalose-6-phosphate phosphatase from Brugia. malayi reveals key design principles for anthelmintic drugs.. Farelli JD, Galvin BD, Li Z, Liu C, Aono M, Garland M, Hallett. OE, Causey TB, Ali-Reynolds A, Saltzberg DJ, Carlow CK,. Dunaway-Mariano D, Allen KN;. PLoS Pathog. 2014;10:e1004245. (from Pfam)

Date:

2024-08-14

This is the N-terminal domain found in Escherichia coli RimK proteins (Ribosomal protein S6-L-glutamate ligase). This domain precedes the ATP-grasp domain Pfam:PF08443 [1]. [1]. 23609986. Structure and function of Escherichia coli RimK, an ATP-grasp. fold, L-glutamyl ligase enzyme.. Zhao G, Jin Z, Wang Y, Allewell NM, Tuchman M, Shi D;. Proteins. 2013;81:1847-1854. (from Pfam)

Date:

2024-08-14

This entry represents a helical domain found in the NLRC4 protein [2] and NOD2 protein [1]. [1]. 27283905. Crystal structure of NOD2 and its implications in human disease.. Maekawa S, Ohto U, Shibata T, Miyake K, Shimizu T;. Nat Commun. 2016;7:11813.. [2]. 23765277. Crystal structure of NLRC4 reveals its autoinhibition mechanism.. Hu Z, Yan C, Liu P, Huang Z, Ma R, Zhang C, Wang R, Zhang Y,. Martinon F, Miao D, Deng H, Wang J, Chang J, Chai J;. Science. 2013;341:172-175. (from Pfam)

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2024-08-14

In Drosophila QUIVER (also known as SLEEPLESS protein or SSS) is a (GPI)-anchored protein required for homoeostatic regulation of sleep under normal conditions and following sleep deprivation [1]. It is a novel potassium channel subunit that modulates the Shaker (Sh) potassium channel which regulates the sleep [2,3]. Besides the Sh modulation, SSS also antagonises nicotinic acetylcholine receptors (nAChRs) to reduce synaptic transmission and promote sleep [4]. [1]. 18635795. Identification of SLEEPLESS, a sleep-promoting factor.. Koh K, Joiner WJ, Wu MN, Yue Z, Smith CJ, Sehgal A;. Science. 2008;321:372-376.. [2]. 21813698. Drosophila QVR/SSS modulates the activation and C-type. inactivation kinetics of Shaker K(+) channels.. Dean T, Xu R, Joiner W, Sehgal A, Hoshi T;. J Neurosci. 2011;31:11387-11395.. [3]. 20010822. SLEEPLESS, a Ly-6/neurotoxin family member, regulates the. levels, localization and activity of Shaker.. Wu MN, Joiner WJ, Dean T, Yue Z, Smith CJ, Chen D, Hoshi T,. Sehgal A, Koh K;. Nat Neurosci. 2010;13:69-75.. [4]. 24613312. SLEEPLESS is a bifunctional regulator of excitability and. cholinergic synaptic transmission.. Wu M, Robinson JE, Joiner WJ;. Curr Biol. 2014;24:621-629. (from Pfam)

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2024-08-14

CBM60 is a family of xylan-binding modules found in conjunction with xylanase enzymes in many bacterial species that attack plant cell walls. Xylan is the major hemicellulose component of most plant cell walls, and is one of the most complex carbohydrates targeted by CBMs. CBM60 modules are evolutionarily related to CBM36 domains as both show circular permutation in the beta-barrel folds. CBM60 targets xylan but is also able to bind cellulose and galactan and thus contribute towards breakdown of the plant cell wall. Recognition of the ligand is conferred primarily through the polar interactions of O2 (oxygen) and O3 of a single sugar with a protein-bound calcium ion [1]. [1]. 20659893. Circular permutation provides an evolutionary link between two. families of calcium-dependent carbohydrate binding modules.. Montanier C, Flint JE, Bolam DN, Xie H, Liu Z, Rogowski A,. Weiner DP, Ratnaparkhe S, Nurizzo D, Roberts SM, Turkenburg JP,. Davies GJ, Gilbert HJ;. J Biol Chem. 2010;285:31742-31754. (from Pfam)

Date:

2024-08-14

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0001203) is described by MIBiG as an example of the following biosynthetic classes, NRP (non-ribosomal peptide) and polyketide, in particular the clarexpoxcin biosynthetic gene cluster from uncultured bacterium AR_456 [1]. This family appears to be predominantly found in Actinobacteria. [1]. 25831524. Multiplexed metagenome mining using short DNA sequence tags. facilitates targeted discovery of epoxyketone proteasome. inhibitors.. Owen JG, Charlop-Powers Z, Smith AG, Ternei MA, Calle PY, Reddy. BV, Montiel D, Brady SF;. Proc Natl Acad Sci U S A. 2015;112:4221-4226. (from Pfam)

Date:

2024-08-14

This family, interleukin 23 subunit alpha, is a heterodimer consisting of a 40 kDa subunit - p40 - that is shared with IL12 and a unique 19 kDa subunit - p19. IL23 is a pro-inflammatory cytokine that binds to adnectins and thus plays a key role in the pathogenesis of several autoimmune and inflammatory diseases. IL23 signalling on the cell membrane works through the interaction of four proteins, two of which are shared with the IL12-receptor complex; signalling through the cell membrane involves the combined aggregation of at least two receptor components and then the subsequent activation of the Jak/Tyk tyrosine kinases and the family of STAT transcription factors [1,2,3]. [1]. 18680750. The structure of interleukin-23 reveals the molecular basis of. p40 subunit sharing with interleukin-12.. Lupardus PJ, Garcia KC;. J Mol Biol. 2008;382:931-941.. [2]. 18708069. Crystal structures of the pro-inflammatory cytokine. interleukin-23 and its complex with a high-affinity neutralizing. antibody.. Beyer BM, Ingram R, Ramanathan L, Reichert P, Le HV, Madison V,. Orth P;. J Mol Biol. 2008;382:942-955.. [3]. 22325775. Structures of adnectin/protein complexes reveal an expanded. binding footprint.. Ramamurthy V, Krystek SR Jr, Bush A, Wei A, Emanuel SL, Das. Gupta R, Janjua A, Cheng L, Murdock M, Abramczyk B, Cohen D, Lin. Z, Morin P, Davis JH, Dabritz M, McLaughlin DC, Russo KA, Chao. G, Wright MC, Jenny VA, Engle LJ, Furfine E, Sheriff S;. Structure. 2012;20:259-269. (from Pfam)

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2024-08-14

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0001774) is described by MIBiG as an example of the following biosynthetic class, other (unspecified). It includes a member from the MS-271 biosynthetic gene cluster from Streptomyces sp [1]. This family appears to be predominantly found in Actinobacteria. Some members of this family have been identified as putative cholesterol esterases. [1]. 29974638. Biosynthetic Gene Cluster of a d-Tryptophan-Containing Lasso. Peptide, MS-271.. Feng Z, Ogasawara Y, Nomura S, Dairi T;. Chembiochem. 2018;19:2045-2048. (from Pfam)

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2024-08-14

This domain is the ubiquitin-binding zinc-finger of the Fanconi anaemia-associated protein of 20 kDa [1-4]. [1]. 22343915. FAAP20: a novel ubiquitin-binding FA nuclear core-complex. protein required for functional integrity of the FA-BRCA DNA. repair pathway.. Ali AM, Pradhan A, Singh TR, Du C, Li J, Wahengbam K, Grassman. E, Auerbach AD, Pang Q, Meetei AR;. Blood. 2012;119:3285-3294.. [2]. 22266823. Regulation of Rev1 by the Fanconi anemia core complex.. Kim H, Yang K, Dejsuphong D, D'Andrea AD;. Nat Struct Mol Biol. 2012;19:164-170.. [3]. 22396592. Fanconi anemia (FA) binding protein FAAP20 stabilizes FA. complementation group A (FANCA) and participates in interstrand. cross-link repair.. Leung JW, Wang Y, Fong KW, Huen MS, Li L, Chen J;. Proc Natl Acad Sci U S A. 2012;109:4491-4496.. [4]. 22705371. A ubiquitin-binding protein, FAAP20, links RNF8-mediated. ubiquitination to the Fanconi anemia DNA repair network.. Yan Z, Guo R, Paramasivam M, Shen W, Ling C, Fox D 3rd, Wang Y,. Oostra AB, Kuehl J, Lee DY, Takata M, Hoatlin ME, Schindler D,. Joenje H, de Winter JP, Li L, Seidman MM, Wang W;. Mol Cell. 2012;47:61-75. (from Pfam)

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2024-08-14

5-hmdU DNA kinase 2 from phages which 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 [1-3], probably prevent degradation of viral by the host restriction-modification antiviral defense system [2,3]. [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