Protein Family Models

Proteins containing a galactose-binding domain-like fold can be found in several different protein families, in both eukaryotes and prokaryotes. The common function of these domains is to bind to specific ligands, such as cell-surface-attached carbohydrate substrates for galactose oxidase and sialidase [1], phospholipids on the outer side of the mammalian cell membrane for coagulation factor Va [2], membrane-anchored ephrin for the Eph family of receptor tyrosine kinases [3], and a complex of broken single-stranded DNA and DNA polymerase beta for XRCC1 [4]. The structure of the galactose-binding domain-like members consists of a beta-sandwich, in which the strands making up the sheets exhibit a jellyroll fold [5]. [1]. 2002850. Novel thioether bond revealed by a 1.7 A crystal structure of. galactose oxidase.. Ito N, Phillips SE, Stevens C, Ogel ZB, McPherson MJ, Keen JN,. Yadav KD, Knowles PF;. Nature 1991;350:87-90.. [2]. 10586886. Crystal structures of the membrane-binding C2 domain of human. coagulation factor V.. Macedo-Ribeiro S, Bode W, Huber R, Quinn-Allen MA, Kim SW, Ortel. TL, Bourenkov GP, Bartunik HD, Stubbs MT, Kane WH, Fuentes-Prior. P;. Nature. 1999;402:434-439.. [3]. 11780069. Crystal structure of an Eph receptor-ephrin complex.. Himanen JP, Rajashankar KR, Lackmann M, Cowan CA, Henkemeyer M,. Nikolov DB;. Nature. 2001;414:933-938.. [4]. 10467102. Solution structure of the single-strand break repair protein. XRCC1 N- terminal domain.. Marintchev A, Mullen MA, Maciejewski MW, Pan B, Gryk MR, Mullen. GP;. Nat Struct Biol 1999;6:884-893.. [5]. 18784084. The structural basis for T-antigen hydrolysis by Streptoc. TRUNCATED at 1650 bytes (from Pfam)

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2024-08-14

This is the C-terminal domain of retinitis pigmentosa G-protein regulator (RPGR) interacting protein-1 present in Homo sapiens. A mutation in RPGR interacting protein-1 can be observed in the eye disease Leber congenital amaurosis. The domain is commonly known as the RPGR-interacting domain (RID) and is thought to have a C2-like fold [1]. [1]. 24981858. C2 domains as protein-protein interaction modules in the ciliary. transition zone.. Remans K, Burger M, Vetter IR, Wittinghofer A;. Cell Rep. 2014;8:1-9. (from Pfam)

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2024-08-14

This is the second domain (C2) located in the C-terminal region found in antigen I/II type adhesin protein AspA from S. pyogenes. Together with C3, these two domains form an elongated structure, each domain adopts the DEv-IgG fold. Similar to the classical IgG folds, it is comprised of two major antiparallel beta-sheets, designated ABED and CFG. For the C2-domain, there are two additional strands on the CFG sheet. Furthermore, sheets ABED and CFG are interconnected by several cross-connecting loops and one alpha-helix (DH1). The side chains of D982 and N996 in the C2-domain are involved in hydrogen bonding with the side chains of R1264 and N1295 in the C3 domain. Main chain hydrogen bonding can also be observed between S992 in C2 and N1189/G1191 in C3, furthermore stabilizing the interaction between the domains. The C2 domain contains one bound metal ion, modeled as Ca2+, and both the C2- and C3-domains are stabilized by conserved isopeptide bonds, which connect the beta-sheets of the central DEv-IgG motifs [1].Other members of this family include Major cell-surface adhesin PAc from Streptococcus mutans and SspB from Streptococcus gordonii. [1]. 24918040. Structure of the C-terminal domain of AspA (antigen I/II-family). protein from Streptococcus pyogenes.. Hall M, Nylander S, Jenkinson HF, Persson K;. FEBS Open Bio. 2014;4:283-289. (from Pfam)

Date:

2024-08-14

SMP is a proposed lipid-binding module, ie a synaptotagmin-like mitochondrial-lipid-binding domain found in eukaryotes. The SMP domain has a beta-barrel structure like protein modules in the tubular-lipid-binding (TULIP) superfamily. It dimerises to form an approximately 90-Angstrom-long cylinder traversed by a channel lined entirely with hydrophobic residues. The following two C2 domains then form arched structures flexibly linked to the SMP domain. The SMP domain is a lipid-binding domain that links the ER with other lipid bilayer-membranes within the cell [1]. [1]. 24847877. Structure of a lipid-bound extended synaptotagmin indicates a. role in lipid transfer.. Schauder CM, Wu X, Saheki Y, Narayanaswamy P, Torta F, Wenk MR,. De Camilli P, Reinisch KM;. Nature. 2014;510:552-555. (from Pfam)

Date:

2024-08-14

Cation channel sperm-associated targeting subunit tau (CTSRT, also known as Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 11 and C2 calcium-dependent domain-containing protein 6) has been identified in mice as an auxiliary component of the CatSper complex, which is involved in sperm cell hyperactivation. Sperm cell hyperactivation is required for sperm motility, essential late in the preparation of sperm fertilisation [1]. This protein is key for CatSper flagellar targeting and trafficking into the quadrilinear nanodomains as it links the channel-carrying vesicles ans motor proteins in elongating flagella. [1]. 34998468. C2cd6-encoded CatSpertau targets sperm calcium channel to Ca(2+). signaling domains in the flagellar membrane.. Hwang JY, Wang H, Lu Y, Ikawa M, Chung JJ;. Cell Rep. 2022;38:110226. (from Pfam)

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2024-08-14

The VASt (VAD1 Analog of StAR-related lipid transfer) domain is conserved across eukaryotes and is structurally related to Bet v1-like domains, including START lipid-binding domains. The 190-amino acid VASt domain is predominantly associated with lipid binding domains such as GRAM Pfam:PF02893, C2 and PH domains. The VASt domain is likely to have a function in binding large hydrophobic ligands and may be specific for sterol [1, 2]. The predicted structure of the VASt domain is a two-layer sandwich alpha beta fold, also called 'helix grip fold', containing three alpha helices (alpha1 to 3), six beta-sheets (beta1 to 6) and two loops (omega1 and 2) numbered from N to C terminus [1]. Some proteins known to contain a VASt domain are : Plant vascular associated death1 (VAD1), a regulator of programmed cell death (PCD) harboring a GRAM putative lipid-binding domain. Yeast SNF1 Interacting Protein 3 (SIP3), may be involved in sterol transfer between intracellular membranes. Yeast Suicide Protein 1 (YSP1), a mitochondrial protein specifically required for the mitochondrial thread-grain transition, de-energization, and the cell death. May be involved in sterol transfer between intracellular membranes. Yeast Suicide Protein 2 (YSP2), a mitochondrial membrane protein involved in mitochondrial fragmentation and may be involved in sterol transfer between intracellular membranes.It is also found in human GramD1a-c. [1]. 24965341. Identification and phylogenetic analyses of VASt, an. uncharacterized protein domain associated with lipid-binding. domains in Eukaryotes.. Khafif M, Cottret L, Balague C, Raffaele S;. BMC Bioinformatics. 2014;. TRUNCATED at 1650 bytes (from Pfam)

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2024-08-14

A small family of bacterial proteins, found in several Bacteroides species. Structure determination (NMR and Xray) shows an immunoglobulin beta-barrel fold. Multiple homologues have been found in human gut metagenomics data sets. Structural experimentation shows it to share features with two well-established protein architectures in the SCOP database, ie, C2 (calcium/lipid-binding domain) of the Pfam PF00168 and PLAT/LH2 (lipase/lipooxigenase domain) of the Pfam PF01477. The C2 and PLAT/LH2 domains bind Ca2+ in their functions of targeting proteins to cell-membranes; this domain is also shown to bind Ca2+ as well as to be a novel fold [1]. [1]. 23681886. Structural representative of the protein family PF14466 has a. new fold and establishes links with the C2 and PLAT domains from. the widely distant Pfams PF00168 and PF01477.. Serrano P, Geralt M, Mohanty B, Wuthrich K;. Protein Sci. 2013;22:1000-1007. (from Pfam)

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2024-08-14

This is the C-terminal domain of the axin-interacting protein family, and is a distinct version of the C2 domain. This domain is critical for interactions with cytoskeletal in the context of cellular adhesion points [1], thus it is combined with diverse domains related to cytoskeletal functions. This domain has predominantly a beta-strand globular fold composed of an antiparallel beta-sandwich with two beta-sheets, and three short alpha-helices to stabilize the conformation [2]. [1]. 20713135. Identification of novel families and classification of the C2. domain superfamily elucidate the origin and evolution of. membrane targeting activities in eukaryotes.. Zhang D, Aravind L;. Gene. 2010;469:18-30.. [2]. 25117763. Structure and mechanism of the unique C2 domain of Aida.. Zheng LS, Liu YT, Chen L, Wang Y, Rui YN, Huang HZ, Lin SY, Wang. J, Wang ZX, Lin SC, Wu JW;. FEBS J. 2014;281:4622-4632. (from Pfam)

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2024-08-14

This family of proteins is functionally uncharacterised. This protein is found in bacteria and archaea. Proteins in this family are about 200 amino acids in length. The structure of protein Swiss:Q63J81 from B. pseudomallei has been solved. This protein contains two domains, domain I (1:31, 46:81) is a helical domain, domain II (32:45,82-193) is a mainly beta protein with a beta barrel. According to crystal contacts the proteins probably functions as a dimer. The gene neighbourhood analysis suggests that this protein may be functionally related to rubrerythrin and ferredoxin. The wedge surface between the two domains might be functionally important. The fold of this protein could best be described as a circularly permuted C2-like fold (details derived from TOPSAN). (from Pfam)

Date:

2024-08-14

MID1 is a yeast Saccharomyces cerevisiae gene encoding a plasma membrane protein required for Ca2+ influx induced by the mating pheromone, alpha-factor. Mid1 protein plays a crucial role in supplying Ca2+ during the mating process. Mid1 is composed of 548-amino-acid residues with four hydrophobic regions named H1, H2, H3 and H4, and two cysteine-rich regions (C1 and C2) at the C-terminal. This family contains the H3, H4, C1 and C2 regions. suggesting that H1 is a signal sequence responsible for the alpha-factor-induced Mid1 delivery to the plasma membrane. The region from H1 to H3 is required for the localisation of Mid1 in the plasma and ER membranes. Trafficking of Mid1-GFP to the plasma membrane is dependent on the N-glycosylation of Mid1 and the transporter protein Sec12. This findings suggests that the trafficking of Mid1-GFP to the plasma membrane requires a Sec12-dependent pathway from the ER to the Golgi, and that Mid1 is recruited via a Sec6- and Sec7-independent pathway from the Golgi to the plasma membrane. [1]. 16202999. Identification of functional domains of Mid1, a. stretch-activated channel component, necessary for localization. to the plasma membrane and Ca2+ permeation.. Ozeki-Miyawaki C, Moriya Y, Tatsumi H, Iida H, Sokabe M;. Exp Cell Res. 2005;311:84-95.. [2]. 11796727. Essential hydrophilic carboxyl-terminal regions including. cysteine residues of the yeast stretch-activated. calcium-permeable channel Mid1.. Maruoka T, Nagasoe Y, Inoue S, Mori Y, Goto J, Ikeda M, Iida H;. J Biol Chem. 2002;277:11645-11652.. [3]. 14697255. Phe356 in the yeast Ca2+ channel component Mid1 is a key residue. for viability . TRUNCATED at 1650 bytes (from Pfam)

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2024-08-14

The B9-C2 domain is found in proteins associated with the ciliary basal body. B9 domains were identified as a specific family of C2 domains [1]. There are three sub-families represented by this family, notably, Mks1-Xbx7, Stumpy-Tza1 and Tza2 groups of proteins. Mutations in human Mks1 result in the developmental disorder Mechler-Gruber syndrome [2]; mutations in mouse Stumpy lead to perinatal hydrocephalus and severe polycystic kidney disease [3]. All the three distinct types of B9-C2 proteins cooperatively localise to the basal body or centrosome of cilia. [1]. 20713135. Identification of novel families and classification of the C2. domain superfamily elucidate the origin and evolution of. membrane targeting activities in eukaryotes.. Zhang D, Aravind L;. Gene. 2010;469:18-30.. [2]. 16415886. MKS1, encoding a component of the flagellar apparatus basal body. proteome, is mutated in Meckel syndrome.. Kyttala M, Tallila J, Salonen R, Kopra O, Kohlschmidt N,. Paavola-Sakki P, Peltonen L, Kestila M;. Nat Genet. 2006;38:155-157.. [3]. 18287022. The stumpy gene is required for mammalian ciliogenesis.. Town T, Breunig JJ, Sarkisian MR, Spilianakis C, Ayoub AE, Liu. X, Ferrandino AF, Gallagher AR, Li MO, Rakic P, Flavell RA;. Proc Natl Acad Sci U S A. 2008;105:2853-2858. (from Pfam)

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2024-08-14

This domain is present in proteins of the Ferlin family. It is often located between two C2 domains [1]. [1]. 15112237. Insights into the evolution of the nucleolus by an analysis of. its protein domain repertoire.. Staub E, Fiziev P, Rosenthal A, Hinzmann B;. Bioessays 2004;26:567-581. (from Pfam)

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2024-08-14

This entry corresponds to the MUN domain [1] found in Munc13 proteins. These constitute a family of three highly homologous molecules (Munc13-1, Munc13-2 and Munc13-3) with homology to Caenorhabditis elegans unc-13p. Munc13 proteins contain a phorbol ester-binding C1 domain and two C2 domains, which are Ca2+/phospholipid binding domains. Sequence analyses have uncovered two regions called Munc13 homology domains 1 (MHD1) and 2 (MHD2) that are arranged between two flanking C2 domains. MHD1 and MHD2 domains are present in a wide variety of proteins from Arabidopsis thaliana, C. elegans, Drosophila melanogaster, mouse, rat and human, some of which may function in a Munc13-like manner to regulate membrane trafficking. Structural studies have defined MHD1 and MHD2 to be part of the larger MUN domain which forms an elongated structure composed of any pairs of alpha helices. [1]. 28177287. Mechanistic insights into neurotransmitter release and. presynaptic plasticity from the crystal structure of Munc13-1. C1C2BMUN.. Xu J, Camacho M, Xu Y, Esser V, Liu X, Trimbuch T, Pan YZ, Ma C,. Tomchick DR, Rosenmund C, Rizo J;. Elife. 2017; [Epub ahead of print] (from Pfam)

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2024-08-14

This entry represents the DM10 domain, which consists of approximately 105 residues whose function is unknown. It has been identified in nucleoside diphosphate kinases, namely Nucleoside diphosphate kinase 7 (NDK7), which contain a single copy of the DM10 domain [1,2], and in uncharacterised proteins including Rib72 from Chlamydomonas and EF-hand domain-containing protein 1/EF-hand domain-containing family member C2 (EFHC1/2) from mammals, which contain multiple copies of DM10 domains. In Chlamydomonas, and possibly mammals, DM10 domain-containing proteins are tightly bound to the flagellar doublet microtubules. This suggests that DM10 domains might act as flagellar NDK regulatory modules or as units specifically involved in axonemal targeting or assembly [3,4]. This domain have a PH-like fold which includes seven beta strands, with a short 3-4 residue helix after the first strand, and a more extended alpha helical region at the C terminus [2,3]. [1]. 19852809. Nme protein family evolutionary history, a vertebrate. perspective.. Desvignes T, Pontarotti P, Fauvel C, Bobe J;. BMC Evol Biol. 2009;9:256.. [2]. 21289087. Functional characterization of putative cilia genes by. high-content analysis.. Lai CK, Gupta N, Wen X, Rangell L, Chih B, Peterson AS, Bazan. JF, Li L, Scales SJ;. Mol Biol Cell. 2011;22:1104-1119.. [3]. 16572395. Axonemal protofilament ribbons, DM10 domains, and the link to. juvenile myoclonic epilepsy.. King SM;. Cell Motil Cytoskeleton. 2006;63:245-253.. [4]. 30349665. EF-hand domain containing 2 (Efhc2) is crucial for distal. segmentation of pronephros in zebrafish.. Barrodia P, Patra C, Swain RK;. Cell B. TRUNCATED at 1650 bytes (from Pfam)

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2024-08-14

This family consists of Lysophospholipase / phospholipase B EC:3.1.1.5 and cytosolic phospholipase A2 EC:3.1.4 which also has a C2 domain Pfam:PF00168. Phospholipase B enzymes catalyse the release of fatty acids from lysophsopholipids and are capable in vitro of hydrolysing all phospholipids extractable form yeast cells [1]. Cytosolic phospholipase A2 associates with natural membranes in response to physiological increases in Ca2+ and selectively hydrolyses arachidonyl phospholipids [2], the aligned region corresponds the the carboxy-terminal Ca2+-independent catalytic domain of the protein as discussed in [2]. [1]. 8027085. Delineation of two functionally distinct domains of cytosolic. phospholipase A2, a regulatory Ca(2+)-dependent lipid-binding. domain and a Ca(2+)-independent catalytic domain.. Nalefski EA, Sultzman LA, Martin DM, Kriz RW, Towler PS, Knopf. JL, Clark JD;. J Biol Chem 1994;269:18239-18249.. [2]. 8051052. The Saccharomyces cerevisiae PLB1 gene encodes a protein. required for lysophospholipase and phospholipase B activity.. Lee KS, Patton JL, Fido M, Hines LK, Kohlwein SD, Paltauf F,. Henry SA, Levin DE;. J Biol Chem 1994;269:19725-19730. (from Pfam)

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2024-08-14

ML domain - MD-2-related lipid recognition domain. This family consists of proteins from plants, animals and fungi, including dust mite allergen Der P 2 (Swiss:P49278). It has been implicate in lipid recognition, particularly in the recognition of pathogen related products. A mutation in Npc2 (Swiss:Q15668) causes a rare form of Niemann-Pick type C2 disease. This domain has a similar topology to immunoglobulin domains. [1]. 9737847. Tertiary structure of the major house dust mite allergen Der p. 2: sequential and structural homologies.. Mueller GA, Benjamin DC, Rule GS;. Biochemistry 1998;37:12707-12714. (from Pfam)

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2024-08-14

SMP (synaptotagmin-like mitochondrial-lipid-binding) domain-containing protein contains a barrel-like domain that can bind various types of glycerophospholipids in its interior and mediate their transfer between two adjacent bilayers

Date:

2023-12-19

extended synaptotagmin family protein is a membrane-trafficking protein containing SMP (synaptotagmin-like mitochondrial-lipid-binding) and C2 domains

Date:

2023-12-19

synaptotagmin family protein is a membrane-trafficking protein containing SMP (synaptotagmin-like mitochondrial-lipid-binding) and C2 domains, similar to Arabidopsis thaliana calcium-dependent lipid-binding protein

Date:

2023-12-19

synaptotagmin family protein is a membrane-trafficking protein containing SMP (synaptotagmin-like mitochondrial-lipid-binding) and C2 domains, similar to Arabidopsis thaliana calcium-dependent lipid-binding protein

Date:

2023-12-19