Web interface

A relational database is a convenient and flexible way to store the data and to search it using complex queries. However, if data analysis and editing requires a consolidated view of the information, an interactive interface is needed. Based on the considerations outlined in the Tasks section, a web-based solution is most suitable.

Site menu: [classifications] [COGs] [Genes] [Products] Products menu: [list] [create] [edit] [delete] Asialoglycoprotein receptor I

hASGPR1 _{Homo sapiens (human)}

Transcript

One of 4 transcripts of gene hASGPR1

MTKEYQDLQH LDNEESDHHQ LRKGPPPPQP LLQRLCSGPR LLLLSLGLSL LLLVVVCVIG SQNSQLQEEL RGLRETFSNF TASTEAQVKG LSTQGGNVGR KMKSLESQLE KQQKDLSEDH SSLLLHVKQF VSDLRSLSCQ MAALQGNGSE RTCCPVNWVE HERSCYWFSR SGKAWADADN YCRLEDAHLV VVTSWEEQKF VQHHIGPVNT WMGLHDQNGP WKWVDGTDYE TGFKNWRPEQ PDDWYGHGLG GGEDCAHFTD DGRWNDDVCQ RPYRWVCETE LDKASQEPPL L

Function

Products of two genes ASGR1 and ASGR2 form respectively major and minor subunits of heterooligomeric asialoglycoprotein receptor (ASGPR). As shown in knockout mouse model, both subunits are required for receptor function [1], but the major subunit is required for stable expression of the receptor [2] and binds galactose ligands with higher specificity [3]. ASGPR, which is expressed exclusively on hepatic parenchimal cells, efficiently and specifically removes partially deglycosylated glycoproteins from plasma. Upon ligand binding, ASGPR is internalized to acidic-sorting organelle, where ligand dissociates. Receptor is then recirculated to the cell-

- surface [4]. Localized expression of ASGR1 and binding specificity make it a good target for site specific drug delivery [8206921, 7592600]. Another possible therapeutic use of ASGR1 is targeting NK cells transfected with this gene to tumor cells bearing b1-Gal Thomsen-Friedenreich (TF) antigen [5] . ASGPR binding to tumor cell glycans is also a cause of liver metastasis development [8219612, 3345610].

References

1. The reference was not found in the local database. Try Medline: [8702886] 2. The reference was not found in the local database. Try Medline: [11278827] 3. The reference was not found in the local database. Try Medline: [8877376] 4. The reference was not found in the local database. Try Medline: [6383714] 5. The reference was not found in the local database. Try Medline: [11776377]

[All references at NCBI]

Related Sequence Database Entries

GenPept : LNHU1, LNHU2A, NP_001662

SwissProt: LECH_HUMAN

TrEMBL : P07306

Classification

The product was included into the following classifications : Drickamer

1996

II Type II TM proteins with a single C-terminal CTLD Drickamer+

II Dendritic cell receptors, mono-ctld macrophage receptors, ASGR. CTLD length

Long long form

Domain structure

Alternative names

ASGPR- Asialoglycoprotein receptor

ASGPR-1 Hl- Hepatic lectin

References 1. Holland,E.C., Leung,J.O. and Drickamer,K. Rat liver asialoglycoprotein receptor lacks a cleavable NH2-terminal signal sequence //Proc. Natl. Acad. Sci. U.S.A. 81 (23), 7338-7342 (1984) [85063786]

2. Leung,J.O., Holland,E.C. and Drickamer,K. Characterization of the gene encoding the major rat liver

asialoglycoprotein receptor //J. Biol. Chem. 260 (23), 12523-12527 (1985) [86008335] 3. Paietta,E., Stockert,R.J. and Racevskis,J. Differences in the abundance of variably spliced transcripts for the second asialoglycoprotein receptor polypeptide, H2, in normal and transformed human liver //Hepatology 15 (3), 395-402 (1992) [92184202]

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(main access points) Object menu(page actions)

Controlled- vocabulary annotation Visualization of CTLD sequence features (see Figure 2-5) Free-text annotation (textwithrefs.inc) Object name Alternative nomenclature (akabox.inc) Bibliography (refbox.inc) Chapter 2 CTLD database

Figure 2-3 A screenshot of the prod.asp page displaying information about the ASGR1 protein

Chapter 2 CTLD database

Figure 2-4 COG page in a customized list mode (/COG.asp?action=splist&species=Fugu%20rubripes)

Site menu: [classifications] [COGs] [Genes] [Products] COG menu: [list] [create]

[<<][<]Showing records from 1 to 96 of 96[>][>>] Selected items. OK

Full name Title Number of genes

Afp Antifreeze protein

AFPL-F1 Antifreeze protein-like 1

AFPL-F2 Antifreeze protein-like 1

I Hyalectans

AGGRECAN Aggrecan 18

AGGRECAN-F1 Fugu aggrecan paralogue 2

BREVICAN Brevican 10

BREVICAN-F1 Fugu paralogue of Brevican 1

NEUROCAN Neurocan 9

NEUROCAN-F1 Fugu Neurocan paralogue 1

VERSICAN Versican 16

VERSICAN-F1 Fugu paralogue of versican (fragment containing EGF, CTLD and CCP domains) 3 VERSICAN-F2 Fugu versican paralogue (fragment containing link and Ig domains) 1

II Dendritic cell receptors, mono-ctld macrophage receptors, ASGR.

DC-SIGN-F1 Fugu DC-SIGN paralogue 1 1

DC-SIGN-F2 Fugu DC-SIGN paralogue 2 1

DC-SIGN-F3 Fugu DC-SIGN paralogue 3 1

DC-SIGN-F4 Fugu DC-SIGN paralogue 4 1

DC-SIGN-F5 Fugu DC-SIGN paralogue 5 2

DC-SIGN-F6 Fugu DC-SIGN paralogue 6 1

DC-SIGN-F7 Fugu DC-SIGN paralogue 7 1

DC-SIGN-F8 Fugu DC-SIGN paralogue 8 1

DC-SIGNR DCSIGN receptor 10

HML2 HML2 2

SRCL Scavenger receptor with C-type lectin 4 SRCL-F1 Putative Fugu paralogue of SRCL 1 XLCMCL eXtra Large Coiled coil region containing Membrane C-type Lectin 1

III Collectins COLEC10 COLEC10 5 MGC3279 MGC3279 5 IV Selectins SELECTIN-E E-Selectin 14 SELECTIN-L L-Selectin 10 SELECTIN-P P-Selectin 9

VI Multi-CTLD molecules. Macrophage Mannose Receptor (MMR) family.

DEC205 DEC205 6

Endo180 Endo180 3

MManR Macrophage mannose receptor 3

MManR-F1 Fugu macrophage mannose receptor paralogue (fragment) 1 MManR-F2 Fugu macrophage mannose receptor paralogue 1 MManR-F3 Fugu macrophage mannose receptor paralogue (fragment) 1 MManR-F4 Fugu macrophage mannose receptor paralogue (fragment) 1 MManR-F5 Fugu macrophage mannose receptor paralogue (fragment) 2

PLA2R Phosopholipase A2 receptor 6

VIII MT-75, layilin

LAYILIN Layilin 5

Chapter 2 CTLD database The initial version of the interface was implemented as a set of CGI scripts written in Perl, which provided a basic means for data access and modification. However, CGI scripting is not particularly suitable for generation of pages with complex structure, where the amount of static content is comparable with the amount of dynamically generated content. There are many Perl-based application servers and toolkits that solve the task much more efficiently by providing opportunities for embedding Perl code in HTML, templating, user session management, request caching etc. (see

http://perl.apache.org/products/app-server.html for a list of possibilities). I have chosen the Apache::ASP (http://www.apache-asp.org) for its power and simplicity.

The web-based interface provides several access points, which correspond to the primary annotation objects: /prod.asp1, /gene.asp and /cog.asp and to the classification object: /clasif.asp (Figure 2-3(a)). Each page associated with the primary annotation object has several modes of action: list,edit,show and create, which can be selected by

passing an appropriate value in the actionrequest parameter (e.g. /prod.asp?action=list

calls the product page in the list mode; Figure 2-3(b)). Some of the actions require

additional parameters. Theshow action (Figure 2-3) displays the information about a

single object, which can be specified by either id (database accession number) or fn

(object full name) parameters. The editaction works in a similar way and presents

object-related information in an editable HTML form. The listaction allows browsing

lists of objects presented as a table, in which each row is hyperlinked to the

corresponding object show page. The default behavior of the listpage is to display a list

of all the objects of the corresponding type that are available in the database. Currently there is no option to perform flexible database queries from the web interface and display the results using the list action. However, configuration can be done on the

server side and there are several pre-configured listing modes that output results of certain queries as a formatted list. For example, the cog.asp page accepts a special actionsplist. This action requires a species parameter, which can be set to a name of a

taxon of any level, and will produce a list of COGs that contain genes from species whose lineage includes the taxon passed to the script. The list is displayed with entries

Chapter 2 CTLD database grouped according to their position in Drickamer’s extended domain-based

classification (Figure 2-4).

The web interface has a modular structure, and several re-usable elements, located in the /asp/Gadgets directory, are included from multiple pages. The most important of such components is the list.inc module (as used for the query shown in Figure 2-4),

which is a customizable element lister. The number of fields in the list table can be specified in the argument list, and field text and the address linked to the field can be flexibly set by passing a reference to the delegate methods or subroutines. Another reusable module is called textwithrefs.inc (Figure 2-3 (c)). This module parses a string

of text containing references to literature indexed by PubMed, attempts to retrieve the full citation from the local database and displays the original text with formatted bibliography. These and other modules can be used for building other web interfaces based on Apache::ASP.

Finally, the web interface provides some simple sequence feature visualization

capabilities. The prod.asp page called in the showmode displays a diagram showing the

position of CTLDs in the sequences. Under this diagram each CTLD is drawn at a larger scale with the positions of conserved cysteines and WIGL domain indicated and exon/intron structure shown, if it is known (Figure 2-5).

Figure 2-5 Visualization of CTLDcp sequence features

The image was created by the web interface for human macrophage mannose receptor (MManR) sequence. At the top a diagram of MManR showing the positions of 8 CTLDs (green boxes). At the bottom each of the CTLDs is drawn at a larger scale with the positions of four cysteines (black dots) and the WIGL motif (black box) are shown. Alternating colors (green and pink) are used for exons, exon- intron boundaries are shown as grey vertical lines.