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1Y74 Lichtarge Lab 2006 Pages 1–6 1y74 Evolutionary trace report by report maker September 25, 2008 5 Appendix 4 5.1 File formats 4 5.2 Color schemes used 5 5.3 Credits 5 5.3.1 Alistat 5 5.3.2 CE 5 5.3.3 DSSP 5 5.3.4 HSSP 5 5.3.5 LaTex 5 5.3.6 Muscle 5 5.3.7 Pymol 5 5.4 Note about ET Viewer 5 5.5 Citing this work 5 5.6 About report maker 5 5.7 Attachments 6 1 INTRODUCTION From the original Protein Data Bank entry (PDB id 1y74): Title: Solution structure of mlin-2/mlin-7 l27 domain complex Compound: Mol id: 1; molecule: lin 7 homolog b; chain: a, c; frag- ment: l27 domain; synonym: mlin-7/velis/mals; engineered: yes; mol id: 2; molecule: peripheral plasma membrane protein cask; chain: CONTENTS b, d; fragment: l27c domain; synonym: mlin-2/cask; ec: 2.7.1.-; engineered: yes 1 Introduction 1 Organism, scientific name: Mus Musculus; 1y74 contains unique chains 1y74A (57 residues) and 1y74D (50 2 Chain 1y74A 1 residues) 1y74C is a homologue of chain 1y74A. 1y74B is a homo- 2.1 Q9Z252 overview 1 logue of chain 1y74D. This is an NMR-determined structure – in this 2.2 Multiple sequence alignment for 1y74A 1 report the first model in the file was used. 2.3 Residue ranking in 1y74A 2 2.4 Top ranking residues in 1y74A and their position on 2 CHAIN 1Y74A the structure 2 2.4.1 Clustering of residues at 40% coverage. 2 2.1 Q9Z252 overview From SwissProt, id Q9Z252, 100% identical to 1y74A: 3 Chain 1y74D 3 Description: LIN-7 homolog B (LIN-7B) (Mammalian LIN-seven 3.1 Q9NYB2 overview 3 protein 2) (MALS-2) (Vertebrate LIN 7 homolog 2) (Veli-2 protein). 3.2 Multiple sequence alignment for 1y74D 3 Organism, scientific name: Rattus norvegicus (Rat). 3.3 Residue ranking in 1y74D 3 Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Verte- 3.4 Top ranking residues in 1y74D and their position on brata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; the structure 3 Rodentia; Sciurognathi; Muroidea; Muridae; Murinae; Rattus. 3.4.1 Clustering of residues at 94% coverage. 3 Function: Plays a role in establishing and maintaining the asymme- tric distribution of channels and receptors at the plasma membrane 4 Notes on using trace results 3 of polarized cells. Forms membrane-associated multiprotein com- 4.1 Coverage 3 plexes that may regulate delivery and recycling of proteins to the 4.2 Known substitutions 4 correct membrane domains. The tripartite complex composed of 4.3 Surface 4 LIN7 (LIN7A, LIN7B or LIN7C), CASK and APBA1 may have 4.4 Number of contacts 4 the potential to couple synaptic vesicle exocytosis to cell adhesion 4.5 Annotation 4 in brain. Ensures the proper localization of GRIN2B (subunit 2B 4.6 Mutation suggestions 4 of the NMDA receptor) to neuronal postsynaptic density and may 1 Lichtarge lab 2006 function in localizing synaptic vesicles at synapses where it is recrui- ted by beta-catenin and cadherin. Required to localize Kir2 channels, GABA transporter (SLC6A12) and EGFR/ERBB1, ERBB2, ERBB3 and ERBB4 to the basolateral membrane of epithelial cells. MPP5 via its L27 domain. Subunit: Forms two exclusive ternary complexes with CASK and APBA1 or CASKIN1. Can also interact with other modular proteins Fig. 1. Residues 17-73 in 1y74A colored by their relative importance. (See containing protein-protein interaction domains like MPP5, MPP6, Appendix, Fig.7, for the coloring scheme.) DLG1, DLG2 and DLG3 through its L27 domain. Interacts with DLG4 and GRIN2B as well as CDH1 and CTNNB1, the chan- Furthermore, 40% of residues show as conserved in this alignment. nels KCNJ12/Kir2.2, KCNJ4/Kir2.3 and probably KCNJ2/Kir2.1 The alignment consists of 88% eukaryotic ( 66% vertebrata, 22% and SLC6A12/BGT-1 via its PDZ domain. The association of LIN7A arthropoda) sequences. (Descriptions of some sequences were not with cadherin and beta- catenin is calcium-dependent, occurs at syn- readily available.) The file containing the sequence descriptions can aptic junctions and requires the actin cytoskeleton. Interacts with be found in the attachment, under the name 1y74A.descr. EGFR, ERBB2, ERBB3 and ERBB4 with both PDZ and KID domains. Associates with KIF17 via APBA1. 2.3 Residue ranking in 1y74A Subcellular location: Membrane-associated. Mainly basolateral The 1y74A sequence is shown in Fig. 1, with each residue colored in renal epithelial cells (By similarity). Localized to postsynaptic according to its estimated importance. The full listing of residues densities of neurons and epithelial cell-cell junctions. in 1y74A can be found in the file called 1y74A.ranks sorted in the Tissue specificity: Expressed only in brain. attachment. Induction: Up-regulated by cell depolarization and calcium entry through L-type calcium channels. 2.4 Top ranking residues in 1y74A and their position on Domain: The kinase interacting site is required for proper delivery the structure of ERBB2 to the basolateral membrane (By similarity). In the following we consider residues ranking among top 40% of resi- Domain: The PDZ domain regulates endocytosis and recycling of dues in the protein (the closest this analysis allows us to get to 25%). the receptor at the membrane (By similarity). Figure 2 shows residues in 1y74A colored by their importance: bright Domain: The L27 domain mediates interaction with CASK and is red and yellow indicate more conserved/important residues (see involved in the formation of multimeric complexes and the associa- Appendix for the coloring scheme). A Pymol script for producing tion of LIN7 to membranes (By similarity). this figure can be found in the attachment. Similarity: Belongs to the LIN7 family. Similarity: Contains 1 L27 domain. Similarity: Contains 1 PDZ (DHR) domain. About: This Swiss-Prot entry is copyright. It is produced through a collaboration between the Swiss Institute of Bioinformatics and the EMBL outstation - the European Bioinformatics Institute. There are no restrictions on its use as long as its content is in no way modified and this statement is not removed. 2.2 Multiple sequence alignment for 1y74A For the chain 1y74A, the alignment 1y74A.msf (attached) with 9 sequences was used. The alignment was assembled through combi- nation of BLAST searching on the UniProt database and alignment using Muscle program. It can be found in the attachment to this report, under the name of 1y74A.msf. Its statistics, from the alistat program are the following: Format: MSF Number of sequences: 9 Total number of residues: 513 Smallest: 57 Largest: 57 Average length: 57.0 Alignment length: 57 Fig. 2. Average identity: 67% Residues in 1y74A, colored by their relative importance. Clockwise: front, back, top and bottom views. Most related pair: 93% Most unrelated pair: 54% Most distant seq: 82% 2.4.1 Clustering of residues at 40% coverage. Fig. 3 shows the top 40% of all residues, this time colored according to clusters they 2 belong to. The clusters in Fig.3 are composed of the residues listed Fig. 4. Residues 83-132 in 1y74D colored by their relative importance. (See Appendix, Fig.7, for the coloring scheme.) using Muscle program. It can be found in the attachment to this report, under the name of 1y74D.msf. Its statistics, from the alistat program are the following: Format: MSF Number of sequences: 3 Total number of residues: 150 Smallest: 50 Largest: 50 Average length: 50.0 Alignment length: 50 Average identity: 96% Most related pair: 98% Most unrelated pair: 94% Most distant seq: 96% Furthermore, 94% of residues show as conserved in this alignment. Fig. 3. Residues in 1y74A, colored according to the cluster they belong to: The alignment consists of 66% eukaryotic ( 66% vertebrata) red, followed by blue and yellow are the largest clusters (see Appendix for sequences. (Descriptions of some sequences were not readily availa- the coloring scheme). Clockwise: front, back, top and bottom views. The ble.) The file containing the sequence descriptions can be found in corresponding Pymol script is attached. the attachment, under the name 1y74D.descr. 3.3 Residue ranking in 1y74D in Table 1. The 1y74D sequence is shown in Fig. 4, with each residue colored Table 1. according to its estimated importance. The full listing of residues cluster size member in 1y74D can be found in the file called 1y74D.ranks sorted in the color residues attachment. red 22 19,22,25,28,29,30,33,34,36 3.4 Top ranking residues in 1y74D and their position on 37,40,43,44,47,50,51,53,55 the structure 60,61,62,63 In the following we consider residues ranking among top 94% of resi- dues in the protein (the closest this analysis allows us to get to 25%). Table 1. Clusters of top ranking residues in 1y74A. Figure 5 shows residues in 1y74D colored by their importance: bright red and yellow indicate more conserved/important residues (see Appendix for the coloring scheme). A Pymol script for producing 3 CHAIN 1Y74D this figure can be found in the attachment. 3.1 Q9NYB2 overview 3.4.1 Clustering of residues at 94% coverage. Fig. 6 shows the From SwissProt, id Q9NYB2, 100% identical to 1y74D: top 94% of all residues, this time colored according to clusters they Description: Calcium/calmodulin-dependent serine protein kinase belong to. The clusters in Fig.6 are composed of the residues listed membrane-associated guanylate kinase (Fragment). in Table 2. Organism, scientific name: Homo sapiens (Human). Table 2. Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; cluster size member Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; color residues Catarrhini; Hominidae; Homo. red 47 83,84,85,86,87,88,89,90,91 Similarity: Contains 1 SH3 domain.
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