Protein Family Models

The spike glycoprotein is a corona viral transmembrane protein that mediates the binding of virions to the host cell receptor and is involved in membrane fusion. The torovirinae spike proteins appear distinct from other coronaviridae spike proteins, such as human SARS coronavirus [1]. This entry also includes some alloherpesvirus fusion glycoproteins. [1]. 15731234. B-cell responses in patients who have recovered from severe. acute respiratory syndrome target a dominant site in the S2. domain of the surface spike glycoprotein.. Zhong X, Yang H, Guo ZF, Sin WY, Chen W, Xu J, Fu L, Wu J, Mak. CK, Cheng CS, Yang Y, Cao S, Wong TY, Lai ST, Xie Y, Guo Z;. J Virol. 2005;79:3401-3408. (from Pfam)

Date:

2024-08-14

Mevalonate diphosphate decarboxylase (EC:4.1.1.33) catalyzes the ATP dependent decarboxylation of mevalonate 5-diphosphate (MVAPP) to form isopentenyl 5-diphosphate. The reaction is required for production of polyisoprenoids and sterols from acetyl-CoA. This entry represents the C-terminal domain of the mevalonate 5-diphosphate decarboxylase enzyme which is a member of the GHMP kinase superfamily. [1]. 11698677. Structural genomics of enzymes involved in sterol/isoprenoid. biosynthesis.. Bonanno JB, Edo C, Eswar N, Pieper U, Romanowski MJ, Ilyin V,. Gerchman SE, Kycia H, Studier FW, Sali A, Burley SK;. Proc Natl Acad Sci U S A. 2001;98:12896-12901.. [2]. 17583736. Crystal structures of Trypanosoma brucei and Staphylococcus. aureus mevalonate diphosphate decarboxylase inform on the. determinants of specificity and reactivity.. Byres E, Alphey MS, Smith TK, Hunter WN;. J Mol Biol. 2007;371:540-553.. [3]. 18823933. Human mevalonate diphosphate decarboxylase: characterization,. investigation of the mevalonate diphosphate binding site, and. crystal structure.. Voynova NE, Fu Z, Battaile KP, Herdendorf TJ, Kim JJ, Miziorko. HM;. Arch Biochem Biophys. 2008;480:58-67. (from Pfam)

Date:

2024-08-14

Synaptonemal complex protein 2 (SYCP2) N-terminal region contains two separate subdomains an ARLD (armadillo-repeat-like domain) and an SLD (Spt16M-like domain). The SLD structure is highly similar to the middle domain of the histone chaperone FACT. It consists of a twisted ten-stranded beta-sheet flanked by two helices. Since the SLD domain structurally resembles Spt16M, which is known as the well-recognized histone protein H2A-H2B; it is speculated that the SLD may be involved in chromatin binding [1]. [1]. 28150150. Synaptonemal complex protein 2 (SYCP2) mediates the association. of the centromere with the synaptonemal complex.. Feng J, Fu S, Cao X, Wu H, Lu J, Zeng M, Liu L, Yang X, Shen Y;. Protein Cell. 2017;8:538-543. (from Pfam)

Date:

2024-08-14

This entry represents the transmembrane domain from ER/Golgi membrane proteins including V0 complex accessory subunit Ac45 (ATP6AP1, also known as V-type proton ATPase subunit S1) from animals and the yeast homologue V0 assembly protein 1 (VOA1) which are essential for V0 ATPase assembly, stability and function [1,2]. In humans, mutations of ATP6AP1 cause immunodeficiency with hypogammaglobulinemia, hepatopathy and neurocognitive abnormalities [3]. This entry also includes ER membrane BIG1 proteins from yeast, involved in cell wall biogenesis. [1]. 33065002. Structures of a Complete Human V-ATPase Reveal Mechanisms of Its. Assembly.. Wang L, Wu D, Robinson CV, Wu H, Fu TM;. Mol Cell. 2020;80:501-511.. [2]. 18799613. Voa1p functions in V-ATPase assembly in the yeast endoplasmic. reticulum.. Ryan M, Graham LA, Stevens TH;. Mol Biol Cell. 2008;19:5131-5142.. [3]. 27231034. ATP6AP1 deficiency causes an immunodeficiency with hepatopathy,. cognitive impairment and abnormal protein glycosylation.. Jansen EJ, Timal S, Ryan M, Ashikov A, van Scherpenzeel M,. Graham LA, Mandel H, Hoischen A, Iancu TC, Raymond K,. Steenbergen G, Gilissen C, Huijben K, van Bakel NH, Maeda Y,. Rodenburg RJ, Adamowicz M, Crushell E, Koenen H, Adams D,. Vodopiutz J, Greber-Platzer S, Muller T, Dueckers G, Morava E,. Sykut-Cegielska J, Martens GJ, Wevers RA, Niehues T, Huynen MA,. Veltman JA, Stevens TH, Lefeber DJ;. Nat Commun. 2016;7:11600. (from Pfam)

Date:

2024-08-14

Synaptonemal complex protein 2 (SYCP2) N-terminal region contains two separate subdomains an ARLD (armadillo-repeat-like domain) and an SLD (Spt16M-like domain). The ARLD domain belongs to the armadillo-repeat protein family. Armadillo-repeat units often form a superhelix, which typically provides a platform for many protein partners that transduce Wnt signaling, such as beta-catenin. The ARLD of mouse SYCP2 was found to associate with different protein partners, including CENP J and CENP F. ARLD structure is highly similar to that of the 'required for cell differentiation (RCD-1)' protein [1]. [1]. 28150150. Synaptonemal complex protein 2 (SYCP2) mediates the association. of the centromere with the synaptonemal complex.. Feng J, Fu S, Cao X, Wu H, Lu J, Zeng M, Liu L, Yang X, Shen Y;. Protein Cell. 2017;8:538-543. (from Pfam)

Date:

2024-08-14

This family contains an OB-fold found within MCM proteins. This domain contains an insertion at the zinc binding motif [2]. [1]. 12548282. The structure and function of MCM from archaeal M.. Thermoautotrophicum.. Fletcher RJ, Bishop BE, Leon RP, Sclafani RA, Ogata CM, Chen XS;. Nat Struct Biol. 2003;10:160-167.. [2]. 24378617. The 1.8-A crystal structure of the N-terminal domain of an. archaeal MCM as a right-handed filament.. Fu Y, Slaymaker IM, Wang J, Wang G, Chen XS;. J Mol Biol. 2014;426:1512-1523. (from Pfam)

Date:

2024-08-14

This is the N-terminal domain found in archaeal actin homolog Ta0583 found in thermophilic archaeon Thermoplasma acidophilum. Structural analysis indicate that the fold of Ta0583 contains the core structure of actin indicating that it belongs to the actin/Hsp70 superfamily of ATPases. Furthermore,Ta0583 co-crystallised with ADP shows that the nucleotide binds at the interface between the subdomains of Ta0583 in a manner similar to that of actin. It has been suggested that Ta0583 might function in the cellular organisation of T. acidophilum [1]. Other family members include ParM another actin-like protein found in Staphylococcus aureus. Crystal structure co-ordinates revealed that this protein is most structurally related to the chromosomally encoded Actin-like proteins (Alp) Ta0583 from the archaea Thermoplasma acidophilum. Furthermore, biophysical analyses have suggested that ParM filaments undergo a treadmilling-like mechanism of motion in vitro similar to that of F-actin. The recruitment of ParM to the segrosome complex, was shown to be required for the conversion of static ParM filaments to a dynamic form proficient for active segregation and facilitated by the C-terminus of ParR [2] [1]. 16500678. Crystal structure of an archaeal actin homolog.. Roeben A, Kofler C, Nagy I, Nickell S, Hartl FU, Bracher A;. J Mol Biol. 2006;358:145-156.. [2]. 27310470. Dynamic Filament Formation by a Divergent Bacterial Actin-Like. ParM Protein.. Brzoska AJ, Jensen SO, Barton DA, Davies DS, Overall RL, Skurray. RA, Firth N;. PLoS One. 2016;11:e0156944. (from Pfam)

Date:

2024-08-14

The endoplasmic reticulum-mitochondria encounter structure (ERMES) complex creates contact sites between the endoplasmic reticulum and mitochondria, playing crucial roles in interorganelle communication, mitochondrial fission, mtDNA inheritance, lipid transfer, and autophagy. Emr1, also known as Mco6 in budding yeasts, mediates the formation ERMES foci, thereby contributing to the formation of ER-mitochondrial contact sites [1]. [1]. 33483504. Emr1 regulates the number of foci of the endoplasmic. reticulum-mitochondria encounter structure complex.. Rasul F, Zheng F, Dong F, He J, Liu L, Liu W, Cheema JY, Wei W,. Fu C;. Nat Commun. 2021;12:521. (from Pfam)

Date:

2024-08-14

This coiled-coil domain found in Synphilin-1 is responsible for binding to alpha-Synuclein [1]. [1]. 19762560. Interaction with synphilin-1 promotes inclusion formation of. alpha-synuclein: mechanistic insights and pathological. implication.. Xie YY, Zhou CJ, Zhou ZR, Hong J, Che MX, Fu QS, Song AX, Lin. DH, Hu HY;. FASEB J. 2010;24:196-205. (from Pfam)

Date:

2024-08-14

This family contains the N-terminal domain of MCM proteins. [1]. 12548282. The structure and function of MCM from archaeal M.. Thermoautotrophicum.. Fletcher RJ, Bishop BE, Leon RP, Sclafani RA, Ogata CM, Chen XS;. Nat Struct Biol. 2003;10:160-167.. [2]. 24378617. The 1.8-A crystal structure of the N-terminal domain of an. archaeal MCM as a right-handed filament.. Fu Y, Slaymaker IM, Wang J, Wang G, Chen XS;. J Mol Biol. 2014;426:1512-1523. (from Pfam)

Date:

2024-08-14

A variety of different effector proteins interact specifically with GTP-bound Rab proteins and mediate their versatile roles in membrane trafficking, including budding of vesicles from a donor membrane, directed transport through the cell and finally tethering and fusion with a target membrane. The 'bivalent Mical/EHBP Rab binding' (bMERB) domain is a Rab effector domain that is present in proteins of the Mical and EHBP families, both known to act in endosomal trafficking. The bMERB domain displays a preference for Rab8 family proteins (Rab8, 10, 13 and 15) and at least some of the bMERB domains contain two separate binding sites for Rab-proteins, allowing Micals and EHBPs to bind two Rabs simultaneously. The strong similarity between the two binding sites within one bMRB domain strongly suggests an evolutionarily development via duplication of a common ancestor supersecondary structure element. The bMERB domain has a completely alpha-helical fold consisting of a central helix and N- and C-terminal helices folding back on this central helix [1]. [1]. 27552051. bMERB domains are bivalent Rab8 family effectors evolved by gene. duplication.. Rai A, Oprisko A, Campos J, Fu Y, Friese T, Itzen A, Goody RS,. Gazdag EM, Muller MP;. Elife. 2016; [Epub ahead of print] (from Pfam)

Date:

2024-08-14

This entry represents the Walker B domain of RAD50 from eukaryotes and the prokaryotic homologue SbcCD complex subunit C. RAD50-ATPase forms a complex with Mre11-nuclease that detects and processes diverse and obstructed DNA ends. This domain is separated of the Walker A domain by a long coiled-coil domain and forms the nucleotide-binding domain (NBD) when the coiled coils fold back on themselves and bring together Walker A and B domains [1,2,3,4]. Two RAD50-NBDs forms heterotetramers with a Mre11 nuclease dimer that assemble as catalytic head module that binds and cleaves DNA in an ATP-dependent reaction. Through secondary structural analysis, it has been suggested that there is a wide structural conservation in the Rad50/SMC protein family as seen in structural similarities between RAD50's hook and ABC-ATPase MukB's elbow region [4]. [1]. 26896444. Structural mechanism of ATP-dependent DNA binding and DNA end. bridging by eukaryotic Rad50.. Seifert FU, Lammens K, Stoehr G, Kessler B, Hopfner KP;. EMBO J. 2016;35:759-772.. [2]. 21892167. The Rad50 coiled-coil domain is indispensable for Mre11 complex. functions.. Hohl M, Kwon Y, Galvan SM, Xue X, Tous C, Aguilera A, Sung P,. Petrini JH;. Nat Struct Mol Biol. 2011;18:1124-1131.. [3]. 28134932. Eukaryotic Rad50 functions as a rod-shaped dimer.. Park YB, Hohl M, Padjasek M, Jeong E, Jin KS, Krezel A, Petrini. JH, Cho Y;. Nat Struct Mol Biol. 2017;24:248-257.. [4]. 31492634. Mechanism of DNA End Sensing and Processing by the Mre11-Rad50. Complex.. Kashammer L, Saathoff JH, Lammens K, Gut F, Bartho J, Alt A,. Kessler B, Hopfner KP;. Mol Cell. 2019;76:382-394. (from Pfam)

Date:

2024-08-14

This family of proteins is found in eukaryotes. Proteins in this family are typically between 77 and 1130 amino acids in length. The family is found in association with Pfam:PF00041. CD45 plays a critical role in T-cell receptor (TCR)-mediated signaling. CD45 interacts with SKAP55 which is a transcriptional activator of IL-2. [1]. 11909961. SKAP55 coupled with CD45 positively regulates T-cell. receptor-mediated gene transcription.. Wu L, Fu J, Shen SH;. Mol Cell Biol. 2002;22:2673-2686. (from Pfam)

Date:

2024-08-14

This domain family is found in eukaryotes, and is typically between 192 and 219 amino acids in length. The family is found in association with Pfam:PF05076. There is a conserved HGRHFT sequence motif. This family is the C terminal domain of the Suppressor of Fused protein (Su(fu)). Su(fu) is a repressor of the Gli and Ci transcription factors of the Hedgehog signalling cascade. It functions by binding these proteins and preventing their translocation to the nucleus. The C terminal domain is only found in eukaryotic Su(fu) proteins; it is not present in bacterial homologues. The C terminal domain binds to the N terminal of Gli/Ci while the N terminal of Su(fu) binds to the C terminal of Gli/Ci. This dual binding mechanism is likely an evolutionary advancement in this signalling cascade which is not present in bacterial homologues. [1]. 15367681. Suppressor of fused regulates Gli activity through a dual. binding mechanism.. Merchant M, Vajdos FF, Ultsch M, Maun HR, Wendt U, Cannon J,. Desmarais W, Lazarus RA, de Vos AM, de Sauvage FJ;. Mol Cell Biol. 2004;24:8627-8641. (from Pfam)

Date:

2024-08-14

This is a family of small, approximately 100 amino acid, proteins found from yeasts to humans. The majority of endogenous reactive oxygen species (ROS) in cells are produced by the mitochondrial respiratory chain. An increase or imbalance in ROS alters the intracellular redox homeostasis, triggers DNA damage, and may contribute to cancer development and progression [1]. Members of this family are mitochondrial reactive oxygen species modulator 1 (Romo1) proteins that are responsible for increasing the level of ROS in cells. Increased Romo1 expression can have a number of other effects including: inducing premature senescence of cultured human fibroblasts [2,3] and increased resistance to 5-fluorouracil [4]. [1]. 16842742. A novel protein, Romo1, induces ROS production in the. mitochondria.. Chung YM, Kim JS, Yoo YD;. Biochem Biophys Res Commun. 2006;347:649-655.. [2]. 18313394. A critical role for Romo1-derived ROS in cell proliferation.. Na AR, Chung YM, Lee SB, Park SH, Lee MS, Yoo YD;. Biochem Biophys Res Commun. 2008;369:672-678.. [3]. 18836179. Replicative senescence induced by Romo1-derived reactive oxygen. species.. Chung YM, Lee SB, Kim HJ, Park SH, Kim JJ, Chung JS, Yoo YD;. J Biol Chem. 2008;283:33763-33771.. [4]. 17537404. Drug resistance to 5-FU linked to reactive oxygen species. modulator 1.. Hwang IT, Chung YM, Kim JJ, Chung JS, Kim BS, Kim HJ, Kim JS,. Yoo YD;. Biochem Biophys Res Commun. 2007;359:304-310. (from Pfam)

Date:

2024-08-14

This is the C-terminal domain of Beta-carotene isomerase D27 that may contain an iron binding domain [1]. Beta-carotene isomerase D27 (also known as Protein DWARF-27) from plants is involved in strigolactones biosynthesis. It is a beta-carotene isomerase that converts all-trans-beta-carotene into 9-cis-beta-carotene, which is cleaved by CCD7 into a 9-cis-configured aldehyde [2,3]. This is an iron-containing protein that localises in chloroplasts and is expressed mainly in vascular cells of shoots and roots [1]. [1]. 19470589. DWARF27, an iron-containing protein required for the. biosynthesis of strigolactones, regulates rice tiller bud. outgrowth.. Lin H, Wang R, Qian Q, Yan M, Meng X, Fu Z, Yan C, Jiang B, Su. Z, Li J, Wang Y;. Plant Cell. 2009;21:1512-1525.. [2]. 22422982. The path from beta-carotene to carlactone, a strigolactone-like. plant hormone.. Alder A, Jamil M, Marzorati M, Bruno M, Vermathen M, Bigler P,. Ghisla S, Bouwmeester H, Beyer P, Al-Babili S;. Science. 2012;335:1348-1351.. [3]. 22623516. The Arabidopsis ortholog of rice DWARF27 acts upstream of MAX1. in the control of plant development by strigolactones.. Waters MT, Brewer PB, Bussell JD, Smith SM, Beveridge CA;. Plant Physiol. 2012;159:1073-1085. (from Pfam)

Date:

2024-08-14

C1ORF106 also known as INAVA (Innate Immune Activator), is identified as a risk factor for the chronic inflammatory bowel diseases (IBD). Mice lacking the protein show defects in intestinal barrier integrity at steady state and greater susceptibility to mucosal infection. INAVA carries CUPID (Cytohesin Ubiquitin Protein Inducing Domain). Three other human proteins contain CUPID: FRMD4A, FRMD4B, and CCDC120- proteins implicated in neurite outgrowth, and in human cancer, Alzheimer's, celiac, and heart disease. All appear to bind the ARF-GEF (guanine nucleotide-exchange factors) cytohesin family members, such as proteins (ARF 1-4), which regulate cell membrane and F-actin dynamics. INAVA-CUPID binds cytohesin 2 (also known as ARNO), targets the molecule to lateral membranes of epithelial monolayers, and enables ARNO to affect F-actin assembly that underlies cell-cell junctions and barrier function. In the case of inflammatory signalling, ARNO can coordinate CUPID function by binding and inhibiting CUPID activity of acting as an enhancer of TRAF6 dependent polyubiquitination. In other words, ARNO acts as a negative-regulator of inflammatory responses. In summary, INAVA-CUPID exhibits dual functions, coordinated directly by ARNO, that bridge epithelial barrier function with extracellular signals and inflammation [1]. [1]. 30355448. INAVA-ARNO complexes bridge mucosal barrier function with. inflammatory signaling.. Luong P, Hedl M, Yan J, Zuo T, Fu TM, Jiang X, Thiagarajah JR,. Hansen SH, Lesser CF, Wu H, Abraham C, Lencer WI;. Elife. 2018; [Epub ahead of print] (from Pfam)

Date:

2024-08-14

Nsp9 is a single-stranded RNA-binding viral protein involved in RNA synthesis [1]. Several crystallographic structures of nsp9 have shown that it is composed of seven beta strands and a single alpha helix. Nsp9 proteins have N-finger motifs and highly conserved GXXXG motifs that both play critical roles in dimerisation [2]. The conserved helix-helix dimer interface containing a GXXXG protein-protein interaction motif is biologically relevant to SARS-CoV replication. [1]. 15007178. The severe acute respiratory syndrome-coronavirus replicative. protein nsp9 is a single-stranded RNA-binding subunit unique in. the RNA virus world.. Egloff MP, Ferron F, Campanacci V, Longhi S, Rancurel C,. Dutartre H, Snijder EJ, Gorbalenya AE, Cambillau C, Canard B;. Proc Natl Acad Sci U S A. 2004;101:3792-3796.. [2]. 29925659. Dimerization of Coronavirus nsp9 with Diverse Modes Enhances Its. Nucleic Acid Binding Affinity.. Zeng Z, Deng F, Shi K, Ye G, Wang G, Fang L, Xiao S, Fu Z, Peng. G;. J Virol. 2018; [Epub ahead of print] (from Pfam)

Date:

2024-08-14

This entry describes a domain found in a number of GC-rich sequence DNA-binding factor proteins and homologues [1,2], as well as in a number of other proteins including Tuftelin-interacting protein 11 [3]. While the function of the domain is unknown, some of the proteins it is found in are reported to be involved in pre-mRNA splicing [3,4]. This domain is also found in Sip1, a septin interacting protein [5]. [1]. 24304693. Identification of a novel component C2ORF3 in the lariat-intron. complex: lack of C2ORF3 interferes with pre-mRNA splicing via. intron turnover pathway.. Yoshimoto R, Okawa K, Yoshida M, Ohno M, Kataoka N;. Genes Cells. 2014;19:78-87.. [2]. 22862948. Pax3/7BP is a Pax7- and Pax3-binding protein that regulates the. proliferation of muscle precursor cells by an epigenetic. mechanism.. Diao Y, Guo X, Li Y, Sun K, Lu L, Jiang L, Fu X, Zhu H, Sun H,. Wang H, Wu Z;. Cell Stem Cell. 2012;11:231-241.. [3]. 19103666. Isolation and characterization of post-splicing lariat-intron. complexes.. Yoshimoto R, Kataoka N, Okawa K, Ohno M;. Nucleic Acids Res. 2009;37:891-902.. [4]. 25568310. NTR1 is required for transcription elongation checkpoints at. alternative exons in Arabidopsis.. Dolata J, Guo Y, Kolowerzo A, Smolinski D, Brzyzek G,. Jarmolowski A, Swiezewski S;. EMBO J. 2015;34:544-558.. [5]. 11884525. Identification of septin-interacting proteins and. characterization of the Smt3/SUMO-conjugation system in. Drosophila.. Shih HP, Hales KG, Pringle JR, Peifer M;. J Cell Sci. 2002;115:1259-1271. (from Pfam)

Date:

2024-08-14

This entry consists of several animal specific latexin proteins. Latexin is a carboxypeptidase A inhibitor and is expressed in a cell type-specific manner in both central and peripheral nervous systems in the rat [1]. It consists of two cystatin-like domains, consisting of an alpha-helix enveloped by a curved beta-sheet [2,3]. These domains packed against each other, forming an interface to which the enzyme is bound. This is the N-terminal domain. [1]. 11455960. Cloning, tissue expression pattern and genomic organization of. latexin, a human homologue of rat carboxypeptidase A inhibitor.. Liu Q, Yu L, Gao J, Fu Q, Zhang J, Zhang P, Chen J, Zhao S;. Mol Biol Rep 2000;27:241-246.. [2]. 15698574. An inflammatory role for the mammalian carboxypeptidase. inhibitor latexin: relationship to cystatins and the tumor. suppressor TIG1.. Aagaard A, Listwan P, Cowieson N, Huber T, Ravasi T, Wells CA,. Flanagan JU, Kellie S, Hume DA, Kobe B, Martin JL;. Structure. 2005;13:309-317. (from Pfam)

Date:

2024-08-14