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J Mol Biol
2014 Feb 20;4264:945-61. doi: 10.1016/j.jmb.2013.11.009.
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Functional clustering of immunoglobulin superfamily proteins with protein-protein interaction information calibrated hidden Markov model sequence profiles.
Yap EH
,
Rosche T
,
Almo S
,
Fiser A
.
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Secreted and cell-surface-localized members of the immunoglobulin superfamily (IgSF) play central roles in regulating adaptive and innate immune responses and are prime targets for the development of protein-based therapeutics. An essential activity of the ectodomains of these proteins is the specific recognition of cognate ligands, which are often other members of the IgSF. In this work, we provide functional insight for this important class of proteins through the development of a clustering algorithm that groups together extracellular domains of the IgSF with similar binding preferences. Information from hidden Markov model-based sequence profiles and domain architecture is calibrated against manually curated protein interaction data to define functional families of IgSF proteins. The method is able to assign 82% of the 477 extracellular IgSF protein to a functional family, while the rest are either single proteins with unique function or proteins that could not be assigned with the current technology. The functional clustering of IgSF proteins generates hypotheses regarding the identification of new cognate receptor-ligand pairs and reduces the pool of possible interacting partners to a manageable level for experimental validation.
Altschul,
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
1997, Pubmed
Altschul,
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
1997,
Pubmed
Apweiler,
The InterPro database, an integrated documentation resource for protein families, domains and functional sites.
2001,
Pubmed
Arnaout,
Coming to grips with integrin binding to ligands.
2002,
Pubmed
Barclay,
Membrane proteins with immunoglobulin-like domains--a master superfamily of interaction molecules.
2003,
Pubmed
Barrow,
The extended human leukocyte receptor complex: diverse ways of modulating immune responses.
2008,
Pubmed
Bork,
Convergent evolution of similar enzymatic function on different protein folds: the hexokinase, ribokinase, and galactokinase families of sugar kinases.
1993,
Pubmed
Bottino,
Identification of PVR (CD155) and Nectin-2 (CD112) as cell surface ligands for the human DNAM-1 (CD226) activating molecule.
2003,
Pubmed
Boyden,
Skint1, the prototype of a newly identified immunoglobulin superfamily gene cluster, positively selects epidermal gammadelta T cells.
2008,
Pubmed
Brown,
Automated protein subfamily identification and classification.
2007,
Pubmed
Brümmendorf,
Cell adhesion molecules 1: immunoglobulin superfamily.
1995,
Pubmed
Calabrese,
Functional annotations improve the predictive score of human disease-related mutations in proteins.
2009,
Pubmed
Cohen,
The coxsackievirus and adenovirus receptor is a transmembrane component of the tight junction.
2001,
Pubmed
Eddy,
Profile hidden Markov models.
1998,
Pubmed
Edgar,
MUSCLE: multiple sequence alignment with high accuracy and high throughput.
2004,
Pubmed
Eguchi,
Identification of adipocyte adhesion molecule (ACAM), a novel CTX gene family, implicated in adipocyte maturation and development of obesity.
2005,
Pubmed
,
Xenbase
Engelhardt,
Genome-scale phylogenetic function annotation of large and diverse protein families.
2011,
Pubmed
Enright,
An efficient algorithm for large-scale detection of protein families.
2002,
Pubmed
Fahrig,
Characterization of binding properties of the myelin-associated glycoprotein to extracellular matrix constituents.
1987,
Pubmed
Fong,
Localization of leptin binding domain in the leptin receptor.
1998,
Pubmed
Friedlander,
The neuronal chondroitin sulfate proteoglycan neurocan binds to the neural cell adhesion molecules Ng-CAM/L1/NILE and N-CAM, and inhibits neuronal adhesion and neurite outgrowth.
1994,
Pubmed
Harada,
BT-IgSF, a novel immunoglobulin superfamily protein, functions as a cell adhesion molecule.
2005,
Pubmed
Hirata Ki,
Cloning of an immunoglobulin family adhesion molecule selectively expressed by endothelial cells.
2001,
Pubmed
Hlavin,
Molecular structure and functional testing of human L1CAM: an interspecies comparison.
1991,
Pubmed
Jones,
Protein secondary structure prediction based on position-specific scoring matrices.
1999,
Pubmed
Kaplan,
ProtoNet 4.0: a hierarchical classification of one million protein sequences.
2005,
Pubmed
Katoh,
Recent developments in the MAFFT multiple sequence alignment program.
2008,
Pubmed
Klickstein,
Localization of the binding site on intercellular adhesion molecule-3 (ICAM-3) for lymphocyte function-associated antigen 1 (LFA-1).
1996,
Pubmed
Krogh,
Hidden Markov models in computational biology. Applications to protein modeling.
1994,
Pubmed
Kulahin,
Modulation of the homophilic interaction between the first and second Ig modules of neural cell adhesion molecule by heparin.
2005,
Pubmed
Käll,
A combined transmembrane topology and signal peptide prediction method.
2004,
Pubmed
Lander,
Initial sequencing and analysis of the human genome.
2001,
Pubmed
Larkin,
Clustal W and Clustal X version 2.0.
2007,
Pubmed
Larsen,
Rational development of LEA29Y (belatacept), a high-affinity variant of CTLA4-Ig with potent immunosuppressive properties.
2005,
Pubmed
Lee,
Proteome analysis of human hair shaft: from protein identification to posttranslational modification.
2006,
Pubmed
Lee,
GeMMA: functional subfamily classification within superfamilies of predicted protein structural domains.
2010,
Pubmed
Lenschow,
CD28/B7 system of T cell costimulation.
1996,
Pubmed
Li,
Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences.
2006,
Pubmed
Marchler-Bauer,
CDD: a Conserved Domain Database for the functional annotation of proteins.
2011,
Pubmed
Meyer,
CD96 interaction with CD155 via its first Ig-like domain is modulated by alternative splicing or mutations in distal Ig-like domains.
2009,
Pubmed
Milev,
TAG-1/axonin-1 is a high-affinity ligand of neurocan, phosphacan/protein-tyrosine phosphatase-zeta/beta, and N-CAM.
1996,
Pubmed
Miley,
Biochemical features of the MHC-related protein 1 consistent with an immunological function.
2003,
Pubmed
Moreland,
Abatacept.
2006,
Pubmed
Mueller,
Recruitment of nectin-3 to cell-cell junctions through trans-heterophilic interaction with CD155, a vitronectin and poliovirus receptor that localizes to alpha(v)beta3 integrin-containing membrane microdomains.
2003,
Pubmed
Oleszewski,
Characterization of the L1-neurocan-binding site. Implications for L1-L1 homophilic binding.
2000,
Pubmed
Pegg,
Leveraging enzyme structure-function relationships for functional inference and experimental design: the structure-function linkage database.
2006,
Pubmed
Petersen,
SignalP 4.0: discriminating signal peptides from transmembrane regions.
2011,
Pubmed
Radivojac,
A large-scale evaluation of computational protein function prediction.
2013,
Pubmed
Rhodes,
The cluster of BTN genes in the extended major histocompatibility complex.
2001,
Pubmed
Rice,
Localization of hair shaft protein VSIG8 in the hair follicle, nail unit, and oral cavity.
2011,
Pubmed
Rost,
Protein structures sustain evolutionary drift.
1997,
Pubmed
Rubinstein,
Functional classification of immune regulatory proteins.
2013,
Pubmed
Sillitoe,
New functional families (FunFams) in CATH to improve the mapping of conserved functional sites to 3D structures.
2013,
Pubmed
Stajich,
The Bioperl toolkit: Perl modules for the life sciences.
2002,
Pubmed
Staunton,
The arrangement of the immunoglobulin-like domains of ICAM-1 and the binding sites for LFA-1 and rhinovirus.
1990,
Pubmed
Strenge,
Fibronectin is a binding partner for the myelin-associated glycoprotein (siglec-4a).
2001,
Pubmed
Szklarczyk,
The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored.
2011,
Pubmed
Söding,
Protein homology detection by HMM-HMM comparison.
2005,
Pubmed
Teglund,
The pregnancy-specific glycoprotein (PSG) gene cluster on human chromosome 19: fine structure of the 11 PSG genes and identification of 6 new genes forming a third subgroup within the carcinoembryonic antigen (CEA) family.
1994,
Pubmed
UniProt Consortium,
The Universal Protein Resource (UniProt) in 2010.
2010,
Pubmed
Wang,
VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses.
2011,
Pubmed
Weber,
Review: anti-CTLA-4 antibody ipilimumab: case studies of clinical response and immune-related adverse events.
2007,
Pubmed
Williams,
The immunoglobulin superfamily--domains for cell surface recognition.
1988,
Pubmed
Wu,
Convergent evolution of Trichomonas vaginalis lactate dehydrogenase from malate dehydrogenase.
1999,
Pubmed
Yu,
The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells.
2009,
Pubmed