Protein Family Models

This domain is found towards the C-terminal the U3 small nucleolar RNA-associated protein 20 (UTP20) from yeast and its human homologue, also known as DRIM (Down-Regulated In Metastasis). DRIM is differentially expressed in metastatic and non-metastatic human breast carcinoma cells [1]. Proteins of this entry are involved in processing of non-coding RNA as components of the small-subunit (SSU) processome; SSU processome is involved in the biogenesis of the 18S rRNA [2,3]. UTP20 is a huge alpha-solenoid that functions as a scaffold [4,5]. [1]. 9673349. Differential gene expression in mammary carcinoma cell lines:. identification of DRIM, a new gene down-regulated in metastasis.. Schwirzke M, Gnirke A, Bork P, Tarin D, Weidle UH;. Anticancer Res 1998;18:1409-1421.. [2]. 12837249. A panoramic view of yeast noncoding RNA processing.. Peng WT, Robinson MD, Mnaimneh S, Krogan NJ, Cagney G, Morris Q,. Davierwala AP, Grigull J, Yang X, Zhang W, Mitsakakis N, Ryan. OW, Datta N, Jojic V, Pal C, Canadien V, Richards D, Beattie B,. Wu LF, Altschuler SJ, Roweis S, Frey BJ, Emili A, Greenblatt JF,. Cell 2003;113:919-933.. [3]. 17498821. Human 1A6/DRIM, the homolog of yeast Utp20, functions in the 18S. rRNA processing.. Wang Y, Liu J, Zhao H, Lu W, Zhao J, Yang L, Li N, Du X, Ke Y;. Biochim Biophys Acta. 2007;1773:863-868.. [4]. 31378463. Thermophile 90S Pre-ribosome Structures Reveal the Reverse Order. of Co-transcriptional 18S rRNA Subdomain Integration.. Cheng J, Bassler J, Fischer P, Lau B, Kellner N, Kunze R,. Griesel S, Kallas M, Berninghausen O, Strauss D, Beckmann R,. Hurt E;. Mol Cell. 2019;75:1256-1269.. [5]. 32943522. Cryo-EM . TRUNCATED at 1650 bytes (from Pfam)

Date:

2024-08-14

This entry represents the N-terminal domain of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), which is arranged in four supersecondary alpha-helical structures, N1 to N4, that resemble HEAT repeats. Therefore, this domain is also known as N-HEAT. This domain likely mediates DNA binding and, together with the Circular Cradle, forms a ring through which Ku70/80 may present DNA for repair. DNA-PKcs is involved in DNA nonhomologous end joining (NHEJ), required for double-strand break (DSB) repair [1-4]. It is recruited by Ku70/80 heterodimer to DNA ends. [1]. 28154079. DNA-PKcs structure suggests an allosteric mechanism modulating. DNA double-strand break repair.. Sibanda BL, Chirgadze DY, Ascher DB, Blundell TL;. Science. 2017;355:520-524.. [2]. 28652322. Cryo-EM structure of the DNA-PK holoenzyme.. Sharif H, Li Y, Dong Y, Dong L, Wang WL, Mao Y, Wu H;. Proc Natl Acad Sci U S A. 2017;114:7367-7372.. [3]. 28840859. Cryo-EM structure of human DNA-PK holoenzyme.. Yin X, Liu M, Tian Y, Wang J, Xu Y;. Cell Res. 2017;27:1341-1350.. [4]. 33077952. Dimers of DNA-PK create a stage for DNA double-strand break. repair.. Chaplin AK, Hardwick SW, Liang S, Kefala Stavridi A, Hnizda A,. Cooper LR, De Oliveira TM, Chirgadze DY, Blundell TL;. Nat Struct Mol Biol. 2021;28:13-19. (from Pfam)

Date:

2024-08-14

This family represents the C-terminal region of the E3 ubiquitin ligase RNF152 containing the hydrophobic transmembrane domain, responsible for the lysosomal localisation of the protein as well as its ubiquitination activity. This protein polyubiquitinates several proteins and itself, which leads to proteasome degradation. It has been shown that RNF152 has also pro-apoptotic activity, dependent on its RING finger and transmembrane domains [1]. In addition, the transmembrane domain of RNF152 is necessary for negative regulation of the mTORC1 pathway in an amino-acid-sensitive manner, as it mediates RNF152-RagA interaction and RagA ubiquitination [2]. [1]. 21203937. RNF152, a novel lysosome localized E3 ligase with pro-apoptotic. activities.. Zhang S, Wu W, Wu Y, Zheng J, Suo T, Tang H, Tang J;. Protein Cell. 2010;1:656-663.. [2]. 25936802. The ubiquitination of rag A GTPase by RNF152 negatively. regulates mTORC1 activation.. Deng L, Jiang C, Chen L, Jin J, Wei J, Zhao L, Chen M, Pan W, Xu. Y, Chu H, Wang X, Ge X, Li D, Liao L, Liu M, Li L, Wang P;. Mol Cell. 2015;58:804-818. (from Pfam)

Date:

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)

Date:

2024-08-14

LINC complexes are formed by coupling of KASH (Klarsicht, ANC-1, and Syne/Nesprin Homology) and SUN (Sad1 and UNC-84) proteins from the inner and outer nuclear membranes (INM and ONM, respectively). the formation of LINC complexes by KASH and SUN proteins at the nuclear envelope (NE) establishes the physical linkage between the cytoskeleton and nuclear lamina, which is instrumental for the mechanical force transmission from the cytoplasm to the nuclear interior, and is essential for cellular processes such as nuclear positioning and migration, centrosome-nucleus anchorage, and chromosome dynamics. This entry represents an HTH domain found in SUN2 that forms a three-helix bundle to lock the SUN domain in an inactive conformation acting as an inhibitory component. [1]. 26688217. Coiled-Coil Domains of SUN Proteins as Intrinsic Dynamic. Regulators.. Nie S, Ke H, Gao F, Ren J, Wang M, Huo L, Gong W, Feng W;. Structure. 2016;24:80-91.. [2]. 22170055. Structure of Sad1-UNC84 homology (SUN) domain defines features. of molecular bridge in nuclear envelope.. Zhou Z, Du X, Cai Z, Song X, Zhang H, Mizuno T, Suzuki E, Yee. MR, Berezov A, Murali R, Wu SL, Karger BL, Greene MI, Wang Q;. J Biol Chem. 2012;287:5317-5326. (from Pfam)

Date:

2024-08-14

AveC catalyzes the stereospecific spiroketalization of a dihydroxy-ketone polyketide intermediate in the biosynthetic pathway of Avermectin, a potent antiparasitic agent. Additionally, it has a unique dehydration activity that serves to determine the regiospecific saturation pattern for spiroketal diversity [1]. MeiC, the counterpart in the biosynthesis of AVE-like meilingmycin, also has spirocyclase activity, but lacks the dehydratase activity. [1]. 23294008. Spiroketal formation and modification in avermectin biosynthesis. involves a dual activity of AveC.. Sun P, Zhao Q, Yu F, Zhang H, Wu Z, Wang Y, Wang Y, Zhang Q, Liu. W;. J Am Chem Soc. 2013;135:1540-1548. (from Pfam)

Date:

2024-08-14

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

Melanoregulin is a family of proteins found in eukaryotes. It is a putative membrane fusion regulator. MREG forms a complex with peripherin-2 [1]. It is required for lysosome maturation and plays a role in intracellular trafficking [2]. It is a negative regulator of melanosome intercellular transfer [3] and it regulates intercellular melanosome transfer through palmitoylation [4]. [1]. 17260955. The tetraspanin protein peripherin-2 forms a complex with. melanoregulin, a putative membrane fusion regulator.. Boesze-Battaglia K, Song H, Sokolov M, Lillo C, Pankoski-Walker. L, Gretzula C, Gallagher B, Rachel RA, Jenkins NA, Copeland NG,. Morris F, Jacob J, Yeagle P, Williams DS, Damek-Poprawa M;. Biochemistry. 2007;46:1256-1272.. [2]. 19240024. Melanoregulin (MREG) modulates lysosome function in pigment. epithelial cells.. Damek-Poprawa M, Diemer T, Lopes VS, Lillo C, Harper DC, Marks. MS, Wu Y, Sparrow JR, Rachel RA, Williams DS, Boesze-Battaglia. K;. J Biol Chem. 2009;284:10877-10889.. [3]. 22753477. Melanoregulin regulates a shedding mechanism that drives. melanosome transfer from melanocytes to keratinocytes.. Wu XS, Masedunskas A, Weigert R, Copeland NG, Jenkins NA, Hammer. JA;. Proc Natl Acad Sci U S A. 2012;109:E2101-E2109.. [4]. 22940130. Melanoregulin is stably targeted to the melanosome membrane by. palmitoylation.. Wu XS, Martina JA, Hammer JA 3rd;. Biochem Biophys Res Commun. 2012;426:209-214. (from Pfam)

Date:

2024-08-14

This entry corresponds to a presumed domain found at the C-terminus of Coronavirus non-structural protein 2 (NSP2). NSP2 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein and its function is unclear. Viral-host protein interaction studies in SARS-CoV and SARS-CoV-2 found that this protein could interact with several host proteins, including prohibitin 1 (PHB1) and PHB2, which are implicated in a number of cellular functions, including cellular migration, differentiation and apoptosis [2,3]. This presumed domain is found in two copies in some viral NSP2 proteins. This domain is found in both alpha and betacoronaviruses. [1]. 16227261. The nsp2 replicase proteins of murine hepatitis virus and severe. acute respiratory syndrome coronavirus are dispensable for viral. replication.. Graham RL, Sims AC, Brockway SM, Baric RS, Denison MR;. J Virol. 2005;79:13399-13411.. [2]. 32586950. Structural insight into precursor ribosomal RNA processing by. ribonuclease MRP.. Lan P, Zhou B, Tan M, Li S, Cao M, Wu J, Lei M;. Science. 2020;369:656-663.. [3]. 34159380. Nsp2 has the potential to be a drug target revealed by global. identification of SARS-CoV-2 Nsp2-interacting proteins.. Zheng YX, Wang L, Kong WS, Chen H, Wang XN, Meng Q, Zhang HN,. Guo SJ, Jiang HW, Tao SC;. Acta Biochim Biophys Sin (Shanghai). 2021;53:1134-1141. (from Pfam)

Date:

2024-08-14

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is involved in DNA nonhomologous end joining (NHEJ) which is recruited by Ku70/80 heterodimer to DNA ends and required for double-strand break (DSB) repair. It folds into three well-defined large structural units, consisting of a N-terminal region, the Circular Cradle (consisting of five supersecondary alpha-helical structures CC1 to CC5), and the C-terminal Head (comprising FAT, FRB, kinase, and FATC). The N-terminal and CCs regions resemble HEAT repeats, and thus, they are also referred to as N-HEAT and M-HEAT ('middle'), respectively. The CCs form a curved elliptical ring that serves as a scaffold to maintain the integrity of the whole complex. This entry represents CC1 and CC2, which contain the Highly conserved region I (HCR-I) [1-4]. [1]. 28154079. DNA-PKcs structure suggests an allosteric mechanism modulating. DNA double-strand break repair.. Sibanda BL, Chirgadze DY, Ascher DB, Blundell TL;. Science. 2017;355:520-524.. [2]. 28652322. Cryo-EM structure of the DNA-PK holoenzyme.. Sharif H, Li Y, Dong Y, Dong L, Wang WL, Mao Y, Wu H;. Proc Natl Acad Sci U S A. 2017;114:7367-7372.. [3]. 28840859. Cryo-EM structure of human DNA-PK holoenzyme.. Yin X, Liu M, Tian Y, Wang J, Xu Y;. Cell Res. 2017;27:1341-1350.. [4]. 33077952. Dimers of DNA-PK create a stage for DNA double-strand break. repair.. Chaplin AK, Hardwick SW, Liang S, Kefala Stavridi A, Hnizda A,. Cooper LR, De Oliveira TM, Chirgadze DY, Blundell TL;. Nat Struct Mol Biol. 2021;28:13-19. (from Pfam)

Date:

2024-08-14

This is the N-terminal domain found in human spermine synthase (EC 2.5.1.22). The N-terminal domain, which forms the major part of the dimerization interface, shows a considerable structural similarity to the AdoMetDC-like fold (S-adenosylmethionine decarboxylase, the enzyme that forms the aminopropyl donor substrate), Pfam:PF02675 . Deletion of the N-terminal domain led to a complete loss of spermine synthase activity, suggesting that dimerization may be required for activity. The N-terminal domain (amino acids 1-117) includes seven beta-strands and two alpha-helices [1]. [1]. 18367445. Crystal structure of human spermine synthase: implications of. substrate binding and catalytic mechanism.. Wu H, Min J, Zeng H, McCloskey DE, Ikeguchi Y, Loppnau P,. Michael AJ, Pegg AE, Plotnikov AN;. J Biol Chem. 2008;283:16135-16146. (from Pfam)

Date:

2024-08-14

This family consists of the C-terminal region of several eukaryotic and archaeal RuvB-like 1 (Pontin or TIP49a) and RuvB-like 2 (Reptin or TIP49b) proteins. The N-terminal domain contains the Pfam:PF00004 domain. In zebrafish, the liebeskummer (lik) mutation, causes development of hyperplastic embryonic hearts. lik encodes Reptin, a component of a DNA-stimulated ATPase complex. Beta-catenin and Pontin, a DNA-stimulated ATPase that is often part of complexes with Reptin, are in the same genetic pathways. The Reptin/Pontin ratio serves to regulate heart growth during development, at least in part via the beta-catenin pathway [1]. TBP-interacting protein 49 (TIP49) was originally identified as a TBP-binding protein, and two related proteins are encoded by individual genes, tip49a and b. Although the function of this gene family has not been elucidated, they are supposed to play a critical role in nuclear events because they interact with various kinds of nuclear factors and have DNA helicase activities.TIP49a has been suggested to act as an autoantigen in some patients with autoimmune diseases [2]. [1]. 12464178. Reptin and pontin antagonistically regulate heart growth in. zebrafish embryos.. Rottbauer W, Saurin AJ, Lickert H, Shen X, Burns CG, Wo ZG,. Kemler R, Kingston R, Wu C, Fishman M;. Cell 2002;111:661-672.. [2]. 10902922. Chromosome mapping and expression of human tip49 family genes.. Makino Y, Kanemaki M, Koga A, Osano K, Matsu-Ura T, Kurokawa Y,. Kishimoto T, Tamura T;. DNA Seq 2000;11:145-148. (from Pfam)

Date:

2024-08-14

This is the fifth BRCT domain of regulator of Ty1 transposition protein 107 (RTT107). It is involved in binding phosphorylated histone H2A [1]. [1]. 22262834. Structure of C-terminal tandem BRCT repeats of Rtt107 protein. reveals critical role in interaction with phosphorylated histone. H2A during DNA damage repair.. Li X, Liu K, Li F, Wang J, Huang H, Wu J, Shi Y;. J Biol Chem. 2012;287:9137-9146. (from Pfam)

Date:

2024-08-14

Hydrogen gas-evolving membrane-bound hydrogenase (MBH) is a respiratory complex homologous to the quinone-reducing Complex I. Like Complex I, MBH has peripheral and membrane arms. MBH is made of 14 subunits (MbhA-N). MbhJ, K, L, N and M form the Membrane-anchored hydrogenase module. MbhJ, K, L, N are predicted to be exposed to the cytoplasm and form the peripheral arm. The remaining 10 subunits are predicted to be integral membrane proteins forming the membrane arm, made of 44 transmembrane helices (TMH) [2, 3]. MbhA, B, C and F form the Sodium translocation module. MbhD, E, G and H form the Proton translocation module. MbhI is the linker between the hydrogenase module and the proton-translocating membrane module. It anchors the discontinuous TMH7 of MbhH via its middle lateral helix and the C-terminal of TMH2, found in MbhE. MbhD and MbhE together are equivalent to Nqo10 of Complex I [1]. MbhE has two transmembrane helices: TMH1 and TMH2. Paper describing PDB structure 6cfw. [1]. 29754813. Structure of an Ancient Respiratory System.. Yu H, Wu CH, Schut GJ, Haja DK, Zhao G, Peters JW, Adams MWW, Li. H;. Cell. 2018;173:1636-1649.. [2]. 22713092. The modular respiratory complexes involved in hydrogen and. sulfur metabolism by heterotrophic hyperthermophilic archaea and. their evolutionary implications.. Schut GJ, Boyd ES, Peters JW, Adams MW;. FEMS Microbiol Rev. 2013;37:182-203.. [3]. 26808919. The role of geochemistry and energetics in the evolution of. modern respiratory complexes from a proton-reducing ancestor.. Schut GJ, Zadvornyy O, Wu CH, Peters JW, Boyd ES, Adams MW;. Biochim Biophys Acta. 2016;1857:958-97. TRUNCATED at 1650 bytes (from Pfam)

Gene:

mbhE

Date:

2024-08-14

This entry corresponds to the N-terminal region of coronavirus non-structural protein 2. NSP2 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. Viral-host protein interaction studies in SARS-CoV and SARS_CoV-2 found that this protein could interact with several host proteins including prohibitin 1 (PHB1) and PHB2, which are implicated in a number of cellular functions, including cellular migration, differentiation and apoptosis [2,3]. NSP2 structure from SARS-CoV-2 has been recently solved and revealed that it has three zinc fingers, covered in this entry, which may be involved in binding nucleic acids and regulating intracellular signalling pathways [2]. [1]. 16227261. The nsp2 replicase proteins of murine hepatitis virus and severe. acute respiratory syndrome coronavirus are dispensable for viral. replication.. Graham RL, Sims AC, Brockway SM, Baric RS, Denison MR;. J Virol. 2005;79:13399-13411.. [2]. 34398430. Structure and Function of N-Terminal Zinc Finger Domain of. SARS-CoV-2 NSP2.. Ma J, Chen Y, Wu W, Chen Z;. Virol Sin. 2021;36:1104-1112.. [3]. 34159380. Nsp2 has the potential to be a drug target revealed by global. identification of SARS-CoV-2 Nsp2-interacting proteins.. Zheng YX, Wang L, Kong WS, Chen H, Wang XN, Meng Q, Zhang HN,. Guo SJ, Jiang HW, Tao SC;. Acta Biochim Biophys Sin (Shanghai). 2021;53:1134-1141. (from Pfam)

Date:

2024-08-14

This family includes Cat eye syndrome critical region protein 6, a protein which has been identified in a screen for candidate genes for the developmental disorder Cat Eye Syndrome (CES) [1]. It also includes the TMEM121 transmembrane proteins. The function of this family is unknown. [1]. 11381032. Analysis of the cat eye syndrome critical region in humans and. the region of conserved synteny in mice: a search for candidate. genes at or near the human chromosome 22 pericentromere.. Footz TK, Brinkman-Mills P, Banting GS, Maier SA, Riazi MA,. Bridgland L, Hu S, Birren B, Minoshima S, Shimizu N, Pan H,. Nguyen T, Fang F, Fu Y, Ray L, Wu H, Shaull S, Phan S, Yao Z,. Chen F, Huan A, Hu P, Wang Q, Loh P, Qi S, Roe BA, McDermid HE;. Genome Res. 2001;11:1053-1070. (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 is the C-terminal hood domain found in Heterocyst differentiation control protein (HetR). HetR-C binds to PatS peptide. Two PatS6 peptides bind to the lateral clefts of HetR-Hood domain, and trigger significant conformational changes of the flap domain, resulting in dissociation of the auxiliary alpha-helix and eventually release of HetR from the DNA major grove and termination of transcription [1]. [1]. 26576507. Structural insights into HetR-PatS interaction involved in. cyanobacterial pattern formation.. Hu HX, Jiang YL, Zhao MX, Cai K, Liu S, Wen B, Lv P, Zhang Y,. Peng J, Zhong H, Yu HM, Ren YM, Zhang Z, Tian C, Wu Q, Oliveberg. M, Zhang CC, Chen Y, Zhou CZ;. Sci Rep. 2015;5:16470. (from Pfam)

Date:

2024-08-14

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0001735) is described by MIBiG as an example of the following biosynthetic class, other (unspecified), in particular the pentostatine biosynthetic gene cluster from Streptomyces antibioticus [1]. [1]. 28111097. An Unusual Protector-Protege Strategy for the Biosynthesis of. Purine Nucleoside Antibiotics.. Wu P, Wan D, Xu G, Wang G, Ma H, Wang T, Gao Y, Qi J, Chen X,. Zhu J, Li YQ, Deng Z, Chen W;. Cell Chem Biol. 2017;24:171-181. (from Pfam)

Date:

2024-08-14

This domain is found in the C-terminal region of Shikimate 5'-dehydrogenase (SDH) present in Methanocaldococcus jannaschii. SDH catalyses the NADPH-dependent reduction of 3-dehydroshikimate to shikimate in the shikimate pathway. The domain is found just after the C-terminal domain (Pfam:PF01488) which is responsible for NADP binding [1]. [1]. 19215302. X-ray crystallographic and enzymatic analyses of shikimate. dehydrogenase from Staphylococcus epidermidis.. Han C, Hu T, Wu D, Qu S, Zhou J, Ding J, Shen X, Qu D, Jiang H;. FEBS J. 2009;276:1125-1139. (from Pfam)

Date:

2024-08-14