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MRC1 (mannose receptor, C type 1)

Written2010-01Silvia Rasi, Alessio Bruscaggin, Gianluca Gaidano
Division of Hematology, Department of Clinical, Experimental Medicine & Center of Biotechnologies for Applied Medical Research, Amedeo Avogadro University of Eastern Piedmont, Via Solaroli 17, 28100 Novara, Italy

(Note : for Links provided by Atlas : click)

Identity

Alias_namesMRC1L1
mannose receptor
Alias_symbol (synonym)CLEC13D
CD206
bA541I19.1
CLEC13DL
Other aliasMMR
HGNC (Hugo) MRC1
LocusID (NCBI) 4360
Atlas_Id 44561
Location 10p12.33  [Link to chromosome band 10p12]
Location_base_pair Starts at 17809343 and ends at 17911162 bp from pter ( according to hg19-Feb_2009)  [Mapping MRC1.png]
Local_order MRC1 is located on chromosome 10 on the short arm (forward strand), and lies between the FAM23B (family with sequence similarity 23, member B) and SLC39A12 (solute carrier family 39 - zinc transporter, member 12) genes. The gene loci including MRC1, MRC1L1 (mannose receptor, C type 1-like 1), FAM23B and LOC340893 consists of two nearly identical genomic regions, that probably are a part of a duplicated region.
 
  A. Chromosomal location of MRC1 gene.
B. Mapping of MRC1 gene and local order on genomic context of the chromosome 10.
Note MRC1 belongs to the mannose receptor (MR) family; all members of the MR family share a common extracellular domain structure but distinct ligand-binding properties and cell type expression patterns. The MR family comprises 4 members in mammals: MRC1, MRC2 (mannose receptor C, type 2), LY75 (lymphocyte antigen 75) and PLA2R1 (phospholipase A2 receptor 1).

DNA/RNA

 
  Exon-intron structure of MRC1 gene. The blue boxes correspond to protein coding sequences, while the white boxes correspond to non coding regions.
Description MRC1 is a functional gene of 101.74 kb comprising 30 exons and 29 introns. The 5' part of exon 1 and the 3' part of exon 30 are non coding.
Transcription Length of the transcript is 5171 bp.
Coding sequence: CDS 104-4474.
mRNA is mainly expressed in thyroid, spleen and blood.

Protein

 
  Representation of the MRC1 protein with localization of recognized domains. The ricin b-type lectin domain (RICIN) is shown in green, the fibronectin type-II domain (FN2) in yellow, the C-type lectin-like domains (CTLDs) in blue, while the transmembrane domain (TM) in red (UniProtKB/Swiss-Prot entry P22897).
Description Protein length of the unprocessed precursor: 1456 amino acids.
Molecular weight of the unprocessed precursor: 166 KDa.
The protein encoded by the MRC1 gene is classified as a type I transmembrane receptor since the protein COOH terminus is located on the cytoplasmic side of the membrane.
MRC1 is a membrane receptor containing:
- a ricin b-type lectin domain (RICIN), that is a cystein-rich (CysR) domain located at the extreme N-terminus and that can bind specific sulphated glycoproteins,
- a fibronectin type-II domain (FN2), that is the most conserved of the extracellular domains of the MR family and can bind several forms of collagen,
- 8 C-type lectin-like domains (CTLDs), that are Ca(2+)-dependent structural motifs. The fourth of these domains, CTLD4, is the only functional domain. In cooperation with CTLD5, CTLD4 is central to ligand binding by the receptor,
- a single transmembrane domain (TM),
- a short cytosolic domain that contains motifs capable of recognizing components of the endocytic pathway.
The first 3 exons of MRC1 gene encode the signal sequence, the RICIN domain and the FN2 domain, while exon 30 encodes the TM anchor and the cytoplasmic tail. The other 26 exons encode the 8 CTLD domains and intervening spacer elements.
Probably the MRC1 receptor acts with an alternation between bent and extended conformations, that might serve as a "conformational switch" to regulate ligand binding and receptor activity.
MRC1 interacts with CHEK2 (CHK2 checkpoint homolog - S. pombe) protein.
Expression MRC1 is commonly expressed on macrophages and endothelial cells.
Localisation Plasma membrane.
Function - MRC1 mediates the endocytosis of glyproteins by macrophages binding both sulfated and non-sulfated polysaccharide chains.
- MRC1 acts as a phagocytic receptor binding a range of pathogens, such as bacteria, viruses and fungi, through high-mannose structures that are in their surface.
- MRC1 is required for rapid clearance of a subset of mannose-bearing serum glycoproteins that are normally elevated during inflammation.
- MRC1 binds and internalises collagen and gelatin in a carbohydrate-independent mechanism.
- MRC1 can function as an antigen-acquisition system in a subset of dendritic cells.
- MRC1 is implicated in the regulation of macrophage migration during different stages of pathogenesis.
- MRC1 has an important role in binding and transmission of HIV-1 by macrophages.
Homology Ortholog to murine Mrc1, rat Mrc1, cow LOC787578, chimpanzee MLR1L1, canine LOC487114.
Paralog to MRC1L1, CD302, PLA2R1, MRC2.

Mutations

Note No mutations have been reported for MRC1 gene.

Implicated in

Note
  
Entity Pediatric acute lymphoblastic leukemia (ALL)
Disease ALL is a form of leukemia characterized by excess of lymphoblastic cells that is most common in childhood. The rate of cure in children is of nearly 80%, while only 30/40% of adults with ALL are cured.
It is a heterogeneous disease consisting of a number of genetically distinct leukemia subtypes that differ in the response to chemotherapy. These include B-lineage leukemias that contain t(9;22)[BCR-ABL], t(1;19)[E2A-PBX1], t(12;21)[TEL-AML1], rearrangements in the MLL gene on chromosome 11q23, or a hyperdiploid karyotype, and T-lineage leukemias (T-ALL).
Prognosis ALL is a heterogeneous disease and patients are assigned to specific risk groups. In fact, ALL prognosis differs among individuals and depends on several factors: sex, age and white blood cell count at diagnosis, leukemia spread to the central nervous system, morphological, immunological, and genetic subtypes, patient's response to initial treatment.
Various genetic alterations are correlated with prognosis in ALL. In particular ALLs with the presence of t(12;21)[TEL-AML1] and hyperdiploid karyotype have favorable prognosis, while ALLs with t(9;22)[BCR-ABL], t(1;19)[E2A-PBX1] or rearrangements in MLL (11q23) have a poor prognosis.
Oncogenesis In cases having ALL with MLL rearrangements, expression of MRC1 is lower than in normal cells, suggesting a putative involvement of MRC1 in MLL-mediated growth of leukemic cells.
  
  
Entity Acute monocytic leukemia (M5-AML)
Note In acute monocytic leukemia, a trimannose conjugate (TMC), with a high affinity for mannose-specific lectins, binds to MRC1 and this concatenation may play an important role in the activation of monocytic leukemia cells. TMC may be a good candidate to target MRC1 in leukemia cells.
Disease Acute monocytic leukemia is a type of acute myeloid leukemias (AML), characterized by a dominance of monocytes in the bone marrow.
  
  
Entity Cancer
Note MRC1 on lymphatic endothelial cells is involved in leukocyte trafficking and contributes to the metastatic behavior of cancer cells. Moreover, expression of the MRC1 gene is up-regulated in vascular endothelial cells during early development indicating that this gene is a potential regulator of vasculature formation.
Blocking of MRC1 may provide a new approach to controlling inflammation and cancer metastasis by targeting the lymphatic vasculature.
  
  
Entity Kaposi's sarcoma (KS)
Note KS cells express MRC1, since MRC1 is detected in more than 95% of KS cells in all of the major clinical forms of the disease. It is likely that KS lesions derive from tissue accumulation and local proliferation of a subset of macrophages with endotelial features.
Disease KS is a multicentric proliferative disease, involving cutaneous and visceral tissues. The etiology is unknown and the pathogenesis is unclear. KS lesions derive from local proliferation of spindleshaped cells (KS cells), that represent the histological hallmark of this disease.
  

Bibliography

The mannose receptor family.
East L, Isacke CM.
Biochim Biophys Acta. 2002 Sep 19;1572(2-3):364-86.
PMID 12223280
 
Assignment of the human macrophage mannose receptor gene (MRC1) to 10p13 by in situ hybridization and PCR-based somatic cell hybrid mapping.
Eichbaum Q, Clerc P, Bruns G, McKeon F, Ezekowitz RA.
Genomics. 1994 Aug;22(3):656-8.
PMID 8001982
 
Novel synthesized trimannose conjugate induces endocytosis and expression of immunostimulatory molecules in monocytic leukemia cells.
Kanbe E, Emi N, Abe A, Tanaka H, Kobayashi K, Saito H.
Int J Hematol. 2001 Oct;74(3):309-15.
PMID 11721968
 
Organization of the gene encoding the human macrophage mannose receptor (MRC1).
Kim SJ, Ruiz N, Bezouska K, Drickamer K.
Genomics. 1992 Nov;14(3):721-7.
PMID 1294118
 
Mannose receptor-mediated regulation of serum glycoprotein homeostasis.
Lee SJ, Evers S, Roeder D, Parlow AF, Risteli J, Risteli L, Lee YC, Feizi T, Langen H, Nussenzweig MC.
Science. 2002 Mar 8;295(5561):1898-901.
PMID 11884756
 
Extended and bent conformations of the mannose receptor family.
Llorca O.
Cell Mol Life Sci. 2008 May;65(9):1302-10. (REVIEW)
PMID 18193159
 
Carbohydrate-independent recognition of collagens by the macrophage mannose receptor.
Martinez-Pomares L, Wienke D, Stillion R, McKenzie EJ, Arnold JN, Harris J, McGreal E, Sim RB, Isacke CM, Gordon S.
Eur J Immunol. 2006 May;36(5):1074-82.
PMID 16619293
 
Macrophage mannose receptor on lymphatics controls cell trafficking.
Marttila-Ichihara F, Turja R, Miiluniemi M, Karikoski M, Maksimow M, Niemela J, Martinez-Pomares L, Salmi M, Jalkanen S.
Blood. 2008 Jul 1;112(1):64-72. Epub 2008 Apr 23.
PMID 18434610
 
Mannose receptor expression and function define a new population of murine dendritic cells.
McKenzie EJ, Taylor PR, Stillion RJ, Lucas AD, Harris J, Gordon S, Martinez-Pomares L.
J Immunol. 2007 Apr 15;178(8):4975-83.
PMID 17404279
 
Involvement of macrophage mannose receptor in the binding and transmission of HIV by macrophages.
Nguyen DG, Hildreth JE.
Eur J Immunol. 2003 Feb;33(2):483-93.
PMID 12645947
 
Acute lymphoblastic leukemia.
Pui CH, Evans WE.
N Engl J Med. 1998 Aug 27;339(9):605-15. (REVIEW)
PMID 9718381
 
Mannose receptor regulation of macrophage cell migration.
Sturge J, Todd SK, Kogianni G, McCarthy A, Isacke CM.
J Leukoc Biol. 2007 Sep;82(3):585-93. Epub 2007 Jun 27.
PMID 17596337
 
Primary structure of the mannose receptor contains multiple motifs resembling carbohydrate-recognition domains.
Taylor ME, Conary JT, Lennartz MR, Stahl PD, Drickamer K.
J Biol Chem. 1990 Jul 25;265(21):12156-62.
PMID 2373685
 
Kaposi's sarcoma cells express the macrophage-associated antigen mannose receptor and develop in peripheral blood cultures of Kaposi's sarcoma patients.
Uccini S, Sirianni MC, Vincenzi L, Topino S, Stoppacciaro A, Lesnoni La Parola I, Capuano M, Masini C, Cerimele D, Cella M, Lanzavecchia A, Allavena P, Mantovani A, Baroni CD, Ruco LP.
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PMID 9060831
 
Identification of vasculature-specific genes by microarray analysis of Etsrp/Etv2 overexpressing zebrafish embryos.
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Dev Dyn. 2009 Jul;238(7):1836-50.
PMID 19504456
 
Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling.
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Citation

This paper should be referenced as such :
Rasi, S ; Bruscaggin, A ; Gaidano, G
MRC1 (mannose receptor, C type 1)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(11):1016-1019.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/MRC1ID44561ch10p12.html


External links

Nomenclature
HGNC (Hugo)MRC1   7228
Cards
AtlasMRC1ID44561ch10p12
Entrez_Gene (NCBI)MRC1  4360  mannose receptor C-type 1
AliasesCD206; CLEC13D; CLEC13DL; MMR; 
MRC1L1; bA541I19.1; hMR
GeneCards (Weizmann)MRC1
Ensembl hg19 (Hinxton)ENSG00000260314 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000260314 [Gene_View]  chr10:17809343-17911162 [Contig_View]  MRC1 [Vega]
ICGC DataPortalENSG00000260314
TCGA cBioPortalMRC1
AceView (NCBI)MRC1
Genatlas (Paris)MRC1
WikiGenes4360
SOURCE (Princeton)MRC1
Genetics Home Reference (NIH)MRC1
Genomic and cartography
GoldenPath hg38 (UCSC)MRC1  -     chr10:17809343-17911162 +  10p12.33   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)MRC1  -     10p12.33   [Description]    (hg19-Feb_2009)
EnsemblMRC1 - 10p12.33 [CytoView hg19]  MRC1 - 10p12.33 [CytoView hg38]
Mapping of homologs : NCBIMRC1 [Mapview hg19]  MRC1 [Mapview hg38]
OMIM153618   
Gene and transcription
Genbank (Entrez)AK297044 AK308132 AK308167 AV659122 BC016003
RefSeq transcript (Entrez)NM_001009567 NM_002438
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)MRC1
Cluster EST : UnigeneHs.743903 [ NCBI ]
CGAP (NCI)Hs.743903
Alternative Splicing GalleryENSG00000260314
Gene ExpressionMRC1 [ NCBI-GEO ]   MRC1 [ EBI - ARRAY_EXPRESS ]   MRC1 [ SEEK ]   MRC1 [ MEM ]
Gene Expression Viewer (FireBrowse)MRC1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)4360
GTEX Portal (Tissue expression)MRC1
Protein : pattern, domain, 3D structure
UniProt/SwissProtP22897   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP22897  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP22897
Splice isoforms : SwissVarP22897
PhosPhoSitePlusP22897
Domaine pattern : Prosite (Expaxy)C_TYPE_LECTIN_1 (PS00615)    C_TYPE_LECTIN_2 (PS50041)    FN2_1 (PS00023)    FN2_2 (PS51092)    RICIN_B_LECTIN (PS50231)   
Domains : Interpro (EBI)C-type_lectin-like    C-type_lectin-like/link    C-type_lectin_CS    CTDL_fold    FN_type2_col-bd    Kringle-like    Ricin_B_lectin   
Domain families : Pfam (Sanger)fn2 (PF00040)    Lectin_C (PF00059)    Ricin_B_lectin (PF00652)   
Domain families : Pfam (NCBI)pfam00040    pfam00059    pfam00652   
Domain families : Smart (EMBL)CLECT (SM00034)  FN2 (SM00059)  RICIN (SM00458)  
Conserved Domain (NCBI)MRC1
DMDM Disease mutations4360
Blocks (Seattle)MRC1
PDB (SRS)1EGG    1EGI   
PDB (PDBSum)1EGG    1EGI   
PDB (IMB)1EGG    1EGI   
PDB (RSDB)1EGG    1EGI   
Structural Biology KnowledgeBase1EGG    1EGI   
SCOP (Structural Classification of Proteins)1EGG    1EGI   
CATH (Classification of proteins structures)1EGG    1EGI   
SuperfamilyP22897
Human Protein AtlasENSG00000260314
Peptide AtlasP22897
HPRD01089
IPIIPI00027848   IPI00890809   
Protein Interaction databases
DIP (DOE-UCLA)P22897
IntAct (EBI)P22897
FunCoupENSG00000260314
BioGRIDMRC1
STRING (EMBL)MRC1
ZODIACMRC1
Ontologies - Pathways
QuickGOP22897
Ontology : AmiGOvirus receptor activity  receptor activity  transmembrane signaling receptor activity  protein binding  mannose binding  plasma membrane  integral component of plasma membrane  receptor-mediated endocytosis  signal transduction  cell surface  endosome membrane  viral entry into host cell  cellular response to lipopolysaccharide  cellular response to interferon-gamma  cellular response to interleukin-4  
Ontology : EGO-EBIvirus receptor activity  receptor activity  transmembrane signaling receptor activity  protein binding  mannose binding  plasma membrane  integral component of plasma membrane  receptor-mediated endocytosis  signal transduction  cell surface  endosome membrane  viral entry into host cell  cellular response to lipopolysaccharide  cellular response to interferon-gamma  cellular response to interleukin-4  
Pathways : KEGGPhagosome    Tuberculosis   
REACTOMEP22897 [protein]
REACTOME PathwaysR-HSA-1236978 [pathway]   
NDEx NetworkMRC1
Atlas of Cancer Signalling NetworkMRC1
Wikipedia pathwaysMRC1
Orthology - Evolution
OrthoDB4360
GeneTree (enSembl)ENSG00000260314
Phylogenetic Trees/Animal Genes : TreeFamMRC1
HOVERGENP22897
HOGENOMP22897
Homologs : HomoloGeneMRC1
Homology/Alignments : Family Browser (UCSC)MRC1
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerMRC1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)MRC1
dbVarMRC1
ClinVarMRC1
1000_GenomesMRC1 
Exome Variant ServerMRC1
ExAC (Exome Aggregation Consortium)MRC1 (select the gene name)
Genetic variants : HAPMAP4360
Genomic Variants (DGV)MRC1 [DGVbeta]
DECIPHERMRC1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisMRC1 
Mutations
ICGC Data PortalMRC1 
TCGA Data PortalMRC1 
Broad Tumor PortalMRC1
OASIS PortalMRC1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICMRC1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDMRC1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch MRC1
DgiDB (Drug Gene Interaction Database)MRC1
DoCM (Curated mutations)MRC1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)MRC1 (select a term)
intoGenMRC1
NCG5 (London)MRC1
Cancer3DMRC1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM153618   
Orphanet
MedgenMRC1
Genetic Testing Registry MRC1
NextProtP22897 [Medical]
TSGene4360
GENETestsMRC1
Target ValidationMRC1
Huge Navigator MRC1 [HugePedia]
snp3D : Map Gene to Disease4360
BioCentury BCIQMRC1
ClinGenMRC1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD4360
Chemical/Pharm GKB GenePA30933
Clinical trialMRC1
Miscellaneous
canSAR (ICR)MRC1 (select the gene name)
Probes
Litterature
PubMed82 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineMRC1
EVEXMRC1
GoPubMedMRC1
iHOPMRC1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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