Protein Family Models

This repeat is a family of repeating regions of eukaryotic vacuolar sorting-associated 13 proteins. This repeating region shares a common core element that includes a well-conserved P-x4-P-x13-17-G sequence. This region contains a FFAT motif which mediates VAMP binding and tethering of the ER [1,2]. VPS13 proteins have been implicated in processes including vesicle fusion, autophagy, and actin regulation. They bind phospholipids and act as channels that mediate the transfer of lipids between membranes at organelle contact sites [3,4,5]. Members of this entry belong to the RBG (repeating beta-groove) superfamily. They have a long hydrophobic grooves made of multiple repeating modules that consist of five beta-sheets followed by a loop [6]. [1]. 15498460. Analysis of the human VPS13 gene family.. Velayos-Baeza A, Vettori A, Copley RR, Dobson-Stone C, Monaco. AP;. Genomics. 2004;84:536-549.. [2]. 21764909. Vacuolar protein sorting protein 13A, TtVPS13A, localizes to the. tetrahymena thermophila phagosome membrane and is required for. efficient phagocytosis.. Samaranayake HS, Cowan AE, Klobutcher LA;. Eukaryot Cell. 2011;10:1207-1218.. [3]. 34830155. The GTPase Arf1 Is a Determinant of Yeast Vps13 Localization to. the Golgi Apparatus.. Kolakowski D, Rzepnikowska W, Kaniak-Golik A, Zoladek T,. Kaminska J;. Int J Mol Sci. 2021; [Epub ahead of print]. [4]. 30741634. Human VPS13A is associated with multiple organelles and. influences mitochondrial morphology and lipid droplet motility.. Yeshaw WM, van der Zwaag M, Pinto F, Lahaye LL, Faber AI,. Gomez-Sanchez R, Dolga AM, Poland C, Monaco AP, van IJzendoorn. SC, Grzeschik NA, Vela. TRUNCATED at 1650 bytes (from Pfam)

Date:

2024-08-14

Cadherin_tail is the cytoplasmic domain at the C-terminus of cadherin proteins [1]. This domain binds p120 catenin, an action critical for the surface stability of cadherin-catenin cell-cell adhesion complexes [2]. [1]. 9865466. A common protocadherin tail: multiple protocadherins share the. same sequence in their cytoplasmic domains and are expressed in. different regions of brain.. Obata S, Sago H, Mori N, Davidson M, St John T, Suzuki ST;. Cell Adhes Commun. 1998;6:323-333.. [2]. 20371349. Dynamic and static interactions between p120 catenin and. E-cadherin regulate the stability of cell-cell adhesion.. Ishiyama N, Lee SH, Liu S, Li GY, Smith MJ, Reichardt LF, Ikura. M;. Cell. 2010;141:117-128. (from Pfam)

Date:

2024-08-14

Brca1 C-terminal (BRCT) domains are a common protein-protein interaction regions in proteins involved in the DNA damage response and DNA repair [1,2]. For example 53BP1 which plays multiple roles in mammalian DNA damage repair, has a C-terminal tandem BRCT domain (BRCT2), which in its orthologs, Saccharomyces cerevisiae Rad9p and Schizosaccharomyces pombe Crb2, mediates binding to the equivalents of gammaH2AX. Structural and functional studies indicate that the 53BP1-BRCT2 domain is a competent binding module for phosphorylated peptides with a clear specificity for the DNA-damage marker gammaH2AX, and in isolation from other parts of 53BP1 is sufficient for localization to sites of DNA damage in cells associated with gammaH2AX [3]. [1]. 12110597. Crystal structure of human 53BP1 BRCT domains bound to p53. tumour suppressor.. Derbyshire DJ, Basu BP, Serpell LC, Joo WS, Date T, Iwabuchi K,. Doherty AJ;. EMBO J. 2002;21:3863-3872.. [2]. 11877378. Structure of the 53BP1 BRCT region bound to p53 and its. comparison to the Brca1 BRCT structure.. Joo WS, Jeffrey PD, Cantor SB, Finnin MS, Livingston DM,. Pavletich NP;. Genes Dev. 2002;16:583-593.. [3]. 26628370. ATM Localization and Heterochromatin Repair Depend on Direct. Interaction of the 53BP1-BRCT2 Domain with gammaH2AX.. Baldock RA, Day M, Wilkinson OJ, Cloney R, Jeggo PA, Oliver AW,. Watts FZ, Pearl LH;. Cell Rep. 2015;13:2081-2089. (from Pfam)

Date:

2024-08-14

Bee venom contains a variety of peptides such as melittin, apamin, adolapin and mast cell degranulating peptide [1]. Bee venom has been used in the treatment of major neurodegenerative disorders, including Alzheimer's Disease, Parkinson's Disease, Epilepsy, Multiple Sclerosis and Amyotrophic Lateral Sclerosis [2]. Secondary structure analysis of apamin, mast cell degranulating peptide, tertiapin and secapin have been studied. The predicted structure for mast cell degranulating peptide is almost spherical with the eight positive centres evenly distributed over the surface. It has also been suggested that these four peptides share a common folding pattern, which is centred on a beta-turn covalently linked to an alpha-helical segment by two disulphide links. It is further suggested that apamin, mast cell degranulating peptide and tertiapin form a single molecular class [3]. This family includes apamin and mast cell degranulating peptide. Apamin, the most widely studied member of this family has been shown to be a selective blocker of small-conductance Ca2+-activated K+ (KCa2.X or SK) channels [1,4]. It is a promising anti neuroinflammatory agent that could be used to prevent and treat various neurological disorders [4]. Apamin also blocks Kv1.3 channels [5] and is able to inhibit neuromuscular transmission by a mechanism independent of the blockade of SK channels, which may involve the activation of inhibitory muscarinic M2 receptors on motor nerve terminals [6]. [1]. 27364758. Interactions between calcium channels and SK channels in. midbrain dopamine neurons and their impact on pacemaker. regularity: Contrasting roles of N. TRUNCATED at 1650 bytes (from Pfam)

Date:

2024-08-14

A member of the nucleic acid/nucleotide deaminase superfamily prototyped by Burkholderia BURPS668_1122 [1]. Members of this family are found as toxins in polymorphic toxin systems in a wide range of bacteria and in the eukaryote Perkinsus. Members of this family typically possess a DxE catalytic motif in Helix-2 of the core fold instead of the more common C[H]xE motif. The Perkinsus versions are predicted to be inactive [1]. [1]. 21890906. Evolution of the deaminase fold and multiple origins of. eukaryotic editing and mutagenic nucleic acid deaminases from. bacterial toxin systems.. Iyer LM, Zhang D, Rogozin IB, Aravind L;. Nucleic Acids Res. 2011; [Epub ahead of print] (from Pfam)

Date:

2024-08-14

This is the C-terminal domain found in S. cerevisiae Rpn2 (26S proteasome regulatory subunit RPN2) as well as other eukaryotic species. A study revealed that the C-terminal 52 residues of the Rpn2 C-terminal domain are responsible for mediating interactions with the ubiquitin-binding subunit Rpn13. Futhermore, the extreme C-terminal 20 or 21 residues of Rpn2 (926-945 or 925-945) of S. cerevisiae, were shown to be equally effective at binding Rpn13. Multiple sequence alignments indicate that Rpn2 orthologs are highly conserved in this C-terminal region and share characteristic acidic, aromatic, and proline residues, suggesting a common function. In the structure of Rpn2 from S. cerevisiae , this region is exposed and disordered, and is thus accessible for associating with Rpn13. The Rpn2 binding surface of human Rpn13 has been mapped by nuclear magnetic resonance titration to one surface of its Pru domain [1]. [1]. 22405010. The structure of the 26S proteasome subunit Rpn2 reveals its PC. repeat domain as a closed toroid of two concentric. alpha-helical rings.. He J, Kulkarni K, da Fonseca PC, Krutauz D, Glickman MH, Barford. D, Morris EP;. Structure. 2012;20:513-521.. [2]. 24706844. Deep classification of a large cryo-EM dataset defines the. conformational landscape of the 26S proteasome.. Unverdorben P, Beck F, Sledz P, Schweitzer A, Pfeifer G, Plitzko. JM, Baumeister W, Forster F;. Proc Natl Acad Sci U S A. 2014;111:5544-5549. (from Pfam)

Date:

2024-08-14

Desmoplakin (DP) is an integral part of desmosomes, where it links desmosomal cadherins to the intermediate filaments. The N-terminal region of DP contains a plakin domain common to members of the plakin family. Plakin domains contain multiple copies of spectrin repeats (SRs) Pfam:PF00435. Spectrin repeats (SRs) consist of three alpha-helices (A, B, and C) that form an antiparallel triple-helical bundle. This entry describes SR6 which has a divergent structure relative to the other SRs. SR6 shows significant deviations in helices A and B where they are significantly shorter than in other repeats. Structural comparison revealed that SR6 is more similar to other three-helix-bundle proteins, including target of Myb1 and the syntaxin Habc domain, than to other SR proteins. Due to these differences with other spectrin repeats, this region is termed spectrin-like repeat [1]. [1]. 21536047. Crystal structure of a rigid four-spectrin-repeat fragment of. the human desmoplakin plakin domain.. Choi HJ, Weis WI;. J Mol Biol. 2011;409:800-812. (from Pfam)

Date:

2024-08-14

This family of glycosyl hydrolases (GH) from CAZy family 18 is mainly found in Bacteroidetes, including the endoglycosidase BT1044 from Bacteroides thetaiotaomicron. This protein folds into the canonical (beta/alpha)8 barrel (TIM barrel) fold common to many GH structures [1]. [1]. 31160824. Complex N-glycan breakdown by gut Bacteroides involves an. extensive enzymatic apparatus encoded by multiple co-regulated. genetic loci.. Briliute J, Urbanowicz PA, Luis AS, Basle A, Paterson N, Rebello. O, Hendel J, Ndeh DA, Lowe EC, Martens EC, Spencer DIR, Bolam. DN, Crouch LI;. Nat Microbiol. 2019;4:1571-1581. (from Pfam)

Date:

2024-08-14

Interactions with ankyrin-G are crucial to the localisation of voltage-gated sodium channels (VGSCs) at the axon initial segment and for neurons to initiate action potentials. This conserved 9-amino acid motif ((V/A)P(I/L)AXXE(S/D)D) is required for ankyrin-G binding and functions to localise sodium channels to a variety of 'excitable' membrane domains both inside and outside of the nervous system [1]. This motif has also been identified in the potassium channel 6TM proteins KCNQ2 and KCNQ3 [2], that correspond to the M channels that exert a crucial influence over neuronal excitability. KCNQ2/KCNQ3 channels are preferentially localised to the surface of axons both at the axonal initial segment and more distally, and this axonal initial segment targeting of surface KCNQ channels is mediated by these ankyrin-G binding motifs of KCNQ2 and KCNQ3 [3]. KCNQ3 is a major determinant of M channel localisation to the AIS, rather than KCNQ2 [4]. Phylogenetic analysis reveals that anchor motifs evolved sequentially in chordates (NaV channel) and jawed vertebrates (KCNQ2/3) [5]. [1]. 12716895. Identification of a conserved ankyrin-binding motif in the. family of sodium channel alpha subunits.. Lemaillet G, Walker B, Lambert S;. J Biol Chem. 2003;278:27333-27339.. [2]. 16525039. A common ankyrin-G-based mechanism retains KCNQ and NaV channels. at electrically active domains of the axon.. Pan Z, Kao T, Horvath Z, Lemos J, Sul JY, Cranstoun SD, Bennett. V, Scherer SS, Cooper EC;. J Neurosci. 2006;26:2599-2613.. [3]. 16735477. Polarized axonal surface expression of neuronal KCNQ channels is. mediated by multiple signals in the KCNQ2 and KC. TRUNCATED at 1650 bytes (from Pfam)

Date:

2024-08-14

This eukaryotic family includes a number of plant organ-specific proteins. The predicted amino acid sequence suggests that these proteins could be exported and glycosylated [1]. Family members consist of an N-terminal region with no repeats and a C-terminal region which carries multiple tandem repeats. The N-terminal region ends before the repeats region and is defined as the area that extends from the end of the signal peptide to the start of the tandem repeat region. Its length varies considerably, ranging from 30 to 80 amino acids. Generally, these proteins vary in size where it is suggested that thirty-six percent of the sequences had fewer than 150 amino acids; 41% ranged from 150 to 250, and 23% had more than 250 amino acids. Accordingly, these proteins belong to category II of proteins having repeats in tandem; that is, those with the repeats ranging in length from 20 to 40 residues. The second region (C-terminal) in the mature protein is the tandem repeat oligopeptide area. The repeats start with a common hexapeptide (E/D)FEPRP and end with X4Y i .e. (D/E)FEPRPX4Y. Full-length sequences revealed considerable variability in the number of repeats, ranging from 2 to 17. The length of the repeats also varied, ranging from 12 amino acids to 34 amino acids [2]. [1]. 2102854. Differential expression of two related organ-specific genes in. pea.. Williams ME, Mundy J, Kay SA, Chua NH;. Plant Mol Biol. 1990;14:765-774.. [2]. 23134664. ST proteins, a new family of plant tandem repeat proteins with a. DUF2775 domain mainly found in Fabaceae and Asteraceae.. Albornos L, Martin I, Iglesias R, Jimenez T, Labrador E, Dopico. B;. B. TRUNCATED at 1650 bytes (from Pfam)

Date:

2024-08-14

The EXT family is a family of tumour suppressor genes. Mutations of EXT1 Swiss:Q16394 on 8q24.1, EXT2 Swiss:Q93063 on 11p11-13, and EXT3 on 19p have been associated with the autosomal dominant disorder known as hereditary multiple exostoses (HME). This is the most common known skeletal dysplasia. The chromosomal locations of other EXT genes suggest association with other forms of neoplasia. EXT1 and EXT2 have both been shown to encode a heparan sulphate polymerase with both D-glucuronyl (GlcA) and N-acetyl-D-glucosaminoglycan (GlcNAC) transferase activities [1]. The nature of the defect in heparan sulphate biosynthesis in HME is unclear. [1]. 9756849. The putative tumor suppressors EXT1 and EXT2 are. glycosyltransferases required for the biosynthesis of heparan. sulfate.. Lind T, Tufaro F, McCormick C, Lindahl U, Lidholt K;. J Biol Chem 1998;273:26265-26268. (from Pfam)

Date:

2024-08-14

Rpb7 bind to Rpb4 to form a heterodimer. This complex is thought to interact with the nascent RNA strand during RNA polymerase II elongation[1]. This family includes the homologs from RNA polymerase I and III. In RNA polymerase I, Rpa43 is at least one of the subunits contacted by the transcription factor TIF-IA [2]. The N terminus of Rpb7p/Rpc25p/MJ0397 has a SHS2 domain that is involved in protein-protein interaction [3]. [1]. 11741548. Structure of an archaeal homolog of the eukaryotic RNA. polymerase II RPB4/RPB7 complex.. Todone F, Brick P, Werner F, Weinzierl RO, Onesti S;. Mol Cell 2001;8:1137-1143.. [2]. 12393749. Multiple interactions between RNA polymerase I, TIF-IA and TAFI. subunits regulate preinitiation complex assembly at the. ribosomal gene promoter.. Yuan X, Zhao J, Zentgraf H, Hoffmann-Rohrer U, Grummt I;. 0;0:1-2.. [3]. 15281131. The SHS2 module is a common structural theme in functionally. diverse protein groups, like Rpb7p, FtsA, GyrI, and. MTH1598/TM1083 superfamilies.. Anantharaman V, Aravind L;. Proteins. 2004;56:795-807. (from Pfam)

Date:

2024-08-14

The DOMON (named after dopamine beta-monooxygenase N-terminal) domain is 110-125 residues long. It is predicted to form an all beta fold with up to 11 strands and is secreted to the extracellular compartment. The beta-strand folding produces a hydrophobic pocket which appears to bind soluble haem. This is consistent with the predominant architectures where the protein is associated with cytochromes or enzymatic domains whose activity involves redox or electron transfer reactions potentially as a direct participant in the electron transfer process. The DOMON domain superfamily, of which this is just one member, shows (1) multiple hydrophobic residues that contribute to the hydrophobic core of the strands of the beta-sandwich, and small residues found at the boundaries of strands and loops, (2) a strongly conserved charged residue (usually arginine/lysine) at the end of strand 9, which possibly stabilises the loop between 9 and 10, and (3) a polar residue (usually histidine, lysine or arginine), that interacts or coordinates with ligands [1]. The suggested superfamily includes both haem- and sugar-binding members: the haem-binding families being the ethyl-Benzoate dehydrogenase family EB_dh, Pfam:PF09459, the cellobiose dehydrogenase family CBDH and this family, and the sugar-binding families being the xylanases, CBM_4_9, Pfam:PF02018. The common feature of the superfamily is the 11-beta-strand structure, although the first and eleventh strands are not well conserved either within families or between families. [1]. 17878204. The DOMON domains are involved in heme and sugar recognition.. Iyer LM, Anantharaman V, Aravind L;. B. TRUNCATED at 1650 bytes (from Pfam)

Date:

2024-08-14

The four families of large eukaryotic DNA viruses, Poxviridae, Asfarviridae, Iridoviridae, and Phycodnaviridae, referred to collectively as nucleocytoplasmic large DNA viruses or NCLDV, have all been shown to have a lipid membrane, in spite of the major differences in virion structure. The paralogous genes L1R and F9L encode membrane proteins that have a conserved domain architecture, with a single, C-terminal transmembrane helix, and an N-terminal, multiple-disulfide-bonded domain. The conservation of the myristoylated, disulfide-bonded protein L1R/F9L in most of the NCLDV correlates with the conservation of the thiol-disulfide oxidoreductase E10R which, in vaccinia virus, is required for the formation of disulfide bonds in L1R and F9L [2]. [1]. 8938976. Sequence analysis of a Molluscum contagiosum virus DNA region. which includes the gene encoding protein kinase 2 and other. genes with unique organization.. Martin-Gallardo A, Moratilla M, Funes JM, Agromayor M, Nunez A,. Varas AJ, Collado M, Valencia A, Lopez-Estebaranz JL, Esteban M;. Virus Genes 1996;13:19-29.. [2]. 11689653. Common origin of four diverse families of large eukaryotic DNA. viruses.. Iyer LM, Aravind L, Koonin EV;. J Virol. 2001;75:11720-11734. (from Pfam)

Date:

2024-08-14

This cysteine rich domain is found in multiple copies in GNDF and GAS1 proteins. GDNF and neurturin (NTN) receptors are potent survival factors for sympathetic, sensory and central nervous system neurons [2]. GDNF and neurturin promote neuronal survival by signaling through similar multicomponent receptors that consist of a common receptor tyrosine kinase and a member of a GPI-linked family of receptors that determines ligand specificity [3]. [1]. 9576965. GFRalpha3 is an orphan member of the GDNF/neurturin/persephin. receptor family.. Baloh RH, Gorodinsky A, Golden JP, Tansey MG, Keck CL, Popescu. NC, Johnson EM Jr, Milbrandt J;. Proc Natl Acad Sci U S A 1998;95:5801-5806.. [2]. 9192898. A GPI-linked protein that interacts with Ret to form a candidate. neurturin receptor [published erratum appears in Nature 1998 Mar. 12;392(6672):210]. Klein RD, Sherman D, Ho WH, Stone D, Bennett GL, Moffat B,. Vandlen R, Simmons L, Gu Q, Hongo JA, Devaux B, Poulsen K,. Armanini M, Nozaki C, Asai N, Goddard A, Phillips H, Henderson. CE, Takahashi M, Rosenthal A;. Nature 1997;387:717-721.. [3]. 9192899. Neurturin responsiveness requires a GPI-linked receptor and the. Ret receptor tyrosine kinase.. Buj-Bello A, Adu J, Pinon LG, Horton A, Thompson J, Rosenthal A,. Chinchetru M, Buchman VL, Davies AM;. Nature 1997;387:721-724.. [4]. 16551639. GAS1 is related to the GDNF family receptors alpha and regulates. ret signaling.. Cabrera JR, Sanchez-Pulido L, Rojas AM, Valencia A, Manes S,. Naranjo JR, Mellstrom B;. J Biol Chem. 2006; [Epub ahead of print] (from Pfam)

Date:

2024-08-14

alpha-crystallin domain-containing protein similar to alpha-crystallin-type small heat shock proteins

Date:

2021-12-21

Glutaredoxins are thioltransferases (disulfide reductases) which utilize glutathione and NADPH as cofactors. Oxidized glutathione is regenerated by glutathione reductase. Together these components compose the glutathione system [1]. Glutaredoxins utilize the CXXC motif common to thioredoxins and are involved in multiple cellular processes including protection from redox stress, reduction of critical enzymes such as ribonucleotide reductase and the generation of reduced sulfur for iron sulfur cluster formation. Glutaredoxins are capable of reduction of mixed disulfides of glutathione as well as the formation of glutathione mixed disulfides. This model represents eukaryotic glutaredoxins and includes sequences from fungi, plants and metazoans as well as viruses.

Date:

2019-09-10

Glutaredoxins are thioltransferases (disulfide reductases) which utilize glutathione and NADPH as cofactors. Oxidized glutathione is regenerated by glutathione reductase. Together these components compose the glutathione system [1]. Glutaredoxins utilize the CXXC motif common to thioredoxins and are involved in multiple cellular processes including protection from redox stress, reduction of critical enzymes such as ribonucleotide reductase and the generation of reduced sulfur for iron sulfur cluster formation. Glutaredoxins are capable of reduction of mixed disulfides of glutathione as well as the formation of glutathione mixed disulfides. This model includes the E. coli glyutaredoxin GrxA which appears to have primary responsibility for the reduction of ribonucleotide reductase [2].

Date:

2024-05-30

Glutaredoxins are thioltransferases (disulfide reductases) which utilize glutathione and NADPH as cofactors. Oxidized glutathione is regenerated by glutathione reductase. Together these components compose the glutathione system [1]. Glutaredoxins utilize the CXXC motif common to thioredoxins and are involved in multiple cellular processes including protection from redox stress, reduction of critical enzymes such as ribonucleotide reductase and the generation of reduced sulfur for iron sulfur cluster formation. Glutaredoxins are capable of reduction of mixed disulfides of glutathione as well as the formation of glutathione mixed disulfides. This model includes the highly abundant E. coli GrxB (Grx2) glutaredoxin which is notably longer than either GrxA or GrxC. Unlike the other two E. coli glutaredoxins, GrxB appears to be unable to reduce ribonucleotide reductase [2], and may have more to do with resistance to redox stress [3].

Date:

2024-05-29

This HMM represents the less common of two related families of N-acetyl-gamma-glutamyl-phosphate reductase, an enzyme catalyzing the third step of Arg biosynthesis from Glu. The two families differ by phylogeny, similarity clustering, and gap architecture in a multiple sequence alignment.

Gene:

argC

Date:

2024-05-30