Blood group systems biosynthesis (Homo sapiens)

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1, 2, 9, 15, 18...483, 6, 11, 12, 38...26, 28, 3314, 16, 31, 44, 4617, 29, 39, 424341, 425, 27, 37453, 6, 11, 12, 38...14, 503, 6, 11, 12, 38...13, 21, 25, 29, 348, 22, 4810, 20, 40354236, 424, 74, 7, 28, 304, 73, 6, 11, 12, 38...Golgi lumennucleoluscytosolRHCE geneFUT3 FUT5 ABO-A:Mn2+H antigen-RBCCMP-Neu5AcPALM-C-Rhesus DproteinUDPFUT5 FUT3Lewis antigensST3GAL3 LeA GDP-FucLeARhesus C/E proteinMn2+ sABO-B:Mn2+LeX H antigen-secUDPsABO-A:Mn2+A antigen-secABO-A FUT3FUT10 ST3GAL3FUT9 GDPST3GAL4 B antigen-secLeX sLeA Type 2 MSGGSdaFUT6 LeYGDP-FucGDPsLeXType 1 chainB3GALTsB3GALT2 FUT2LeY Mn2+ GDP-FucGDP-FucFUT4,5,9(10,11)B4GALNT2FUT11 LeXLeB Type 1 DSGGUDP-GalNAcUDP-GalNAcFUT2dsLeA LeY A antigen-RBCsLeA FUT4 ABO-B:Mn2+GlcNAc-β1,3-Gal-RFUT7 ST6GALNAC6B3GALT5 B antigen-RBCUDP-GalGDPGDPsABO-B Sda CMPRHD geneFUT3,5,6,7LeB Mn2+ H antigen-secGDPSda GDP-FucABO-B Type 1 MSGGsLeAUDP-GalB3GALT1 UDPsABO-A Lewis antigensdsLeA CMPUDP-GalsLeX LeA ST3GAL3,4,6B3GALT4 sLeX UDPMn2+ ST3GAL6 LeBUDP-GalNAcdsLeAFUT1Type 2 chain1212


Description

The association between blood type and disease has been studied since the beginning of the 20th Century (Anstee 2010, Ewald & Sumner 2016). Landsteiner's discovery of blood groups in 1900 was based on agglutination patterns of red blood cells when blood types from different donors were mixed (Landsteiner 1931, Owen 2000, Tan & Graham 2013). His work is the basis of routine compatibility testing and transfusion practices today. The immune system of patients receiving blood transfusions will attack any donor red blood cells that contain antigens that differ from their self-antigens. Therefore, matching blood types is essential for safe blood transfusions. Landsteiner's classification of the ABO blood groups confirmed that antigens were inherited characteristics. In the 1940s, it was established that the specificity of blood group antigens was determined by their unique oligosaccharide structures. Since then, exponential advances in technology have resulted in the identification of over 300 blood group antigens, classified into more than 35 blood group systems by the International Society of Blood Transfusion (ISBT) (Storry et al. 2016).

Blood group antigens comprise either a protein portion or oligosaccharide sequence attached on a glycolipid or glycoprotein. The addition of one or more specific sugar molecules to this oligosaccharide sequence at specific positions by a variety of glycosyltransferases results in the formation of mature blood group antigens. The genes that code for glycosytransferases can contain genetic changes that produce antigenic differences, resulting in new antigens or loss of expression. Blood group antigens are found on red blood cells (RBCs), platelets, leukocytes, and plasma proteins and also exist in soluble form in bodily secretions such as breast milk, seminal fluid, saliva, sweat, gastric secretions and urine. Blood groups are implicated in many diseases such as those related to malignancy (Rummel & Ellsworth 2016), the cardiovascular system (Liumbruno & Franchini 2013), metabolism (Meo et al. 2016, Ewald & Sumner 2016) and infection (Rios & Bianco 2000, McCullough 2014). The most important and best-studied blood groups are the ABO, Lewis and Rhesus systems. The biosynthesis of the antigens in these systems is described in this section. View original pathway at Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 9033658
Reactome-version 
Reactome version: 73
Reactome Author 
Reactome Author: Jassal, Bijay

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Bibliography

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History

CompareRevisionActionTimeUserComment
114897view16:41, 25 January 2021ReactomeTeamReactome version 75
113343view11:41, 2 November 2020ReactomeTeamReactome version 74
112815view18:22, 9 October 2020DeSlOntology Term : 'homeostasis pathway' added !
112763view16:16, 9 October 2020ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
A antigen-RBCMetaboliteCHEBI:139352 (ChEBI)
A antigen-secMetaboliteCHEBI:140186 (ChEBI)
ABO-A ProteinP16442 (Uniprot-TrEMBL)
ABO-A:Mn2+ComplexR-HSA-9034067 (Reactome)
ABO-B ProteinP16442 (Uniprot-TrEMBL)
ABO-B:Mn2+ComplexR-HSA-9034077 (Reactome)
B antigen-RBCMetaboliteCHEBI:139353 (ChEBI)
B antigen-secMetaboliteCHEBI:140187 (ChEBI)
B3GALT1 ProteinQ9Y5Z6 (Uniprot-TrEMBL)
B3GALT2 ProteinO43825 (Uniprot-TrEMBL)
B3GALT4 ProteinO96024 (Uniprot-TrEMBL)
B3GALT5 ProteinQ9Y2C3 (Uniprot-TrEMBL)
B3GALTsComplexR-HSA-913717 (Reactome)
B4GALNT2ProteinQ8NHY0 (Uniprot-TrEMBL)
CMP-Neu5AcMetaboliteCHEBI:16556 (ChEBI)
CMPMetaboliteCHEBI:17361 (ChEBI)
FUT10 ProteinQ6P4F1 (Uniprot-TrEMBL)
FUT11 ProteinQ495W5 (Uniprot-TrEMBL)
FUT1ProteinP19526 (Uniprot-TrEMBL)
FUT2ProteinQ10981 (Uniprot-TrEMBL)
FUT3 ProteinP21217 (Uniprot-TrEMBL)
FUT3,5,6,7ComplexR-HSA-9605686 (Reactome)
FUT3ProteinP21217 (Uniprot-TrEMBL)
FUT4 ProteinP22083 (Uniprot-TrEMBL)
FUT4,5,9(10,11)ComplexR-HSA-9604002 (Reactome)
FUT5 ProteinQ11128 (Uniprot-TrEMBL)
FUT6 ProteinP51993 (Uniprot-TrEMBL)
FUT7 ProteinQ11130 (Uniprot-TrEMBL)
FUT9 ProteinQ9Y231 (Uniprot-TrEMBL)
GDP-FucMetaboliteCHEBI:17009 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GlcNAc-β1,3-Gal-RMetaboliteCHEBI:140876 (ChEBI)
H antigen-RBCMetaboliteCHEBI:139351 (ChEBI)
H antigen-secMetaboliteCHEBI:140180 (ChEBI)
LeA MetaboliteCHEBI:140878 (ChEBI)
LeAMetaboliteCHEBI:140878 (ChEBI)
LeB MetaboliteCHEBI:140910 (ChEBI)
LeBMetaboliteCHEBI:140910 (ChEBI)
LeX MetaboliteCHEBI:140911 (ChEBI)
LeXMetaboliteCHEBI:140911 (ChEBI)
LeY MetaboliteCHEBI:140912 (ChEBI)
LeYMetaboliteCHEBI:140912 (ChEBI)
Lewis antigensComplexR-ALL-9606394 (Reactome)
Lewis antigensComplexR-ALL-9606400 (Reactome)
Mn2+ MetaboliteCHEBI:29035 (ChEBI)
PALM-C-Rhesus D proteinProteinQ02161 (Uniprot-TrEMBL)
RHCE geneGeneProductENSG00000188672 (Ensembl)
RHD geneGeneProductENSG00000187010 (Ensembl)
Rhesus C/E proteinProteinP18577 (Uniprot-TrEMBL)
ST3GAL3 ProteinQ11203 (Uniprot-TrEMBL)
ST3GAL3,4,6ComplexR-HSA-9605640 (Reactome)
ST3GAL3ProteinQ11203 (Uniprot-TrEMBL)
ST3GAL4 ProteinQ11206 (Uniprot-TrEMBL)
ST3GAL6 ProteinQ9Y274 (Uniprot-TrEMBL)
ST6GALNAC6ProteinQ969X2 (Uniprot-TrEMBL)
Sda MetaboliteCHEBI:140913 (ChEBI)
SdaMetaboliteCHEBI:140913 (ChEBI)
Type 1 DSGGMetaboliteCHEBI:140919 (ChEBI)
Type 1 MSGGMetaboliteCHEBI:140917 (ChEBI)
Type 1 chainMetaboliteCHEBI:140162 (ChEBI)
Type 2 MSGGMetaboliteCHEBI:140918 (ChEBI)
Type 2 chainMetaboliteCHEBI:139350 (ChEBI)
UDP-GalMetaboliteCHEBI:18307 (ChEBI)
UDP-GalNAcMetaboliteCHEBI:16650 (ChEBI)
UDPMetaboliteCHEBI:17659 (ChEBI)
dsLeA MetaboliteCHEBI:140915 (ChEBI)
dsLeAMetaboliteCHEBI:140915 (ChEBI)
sABO-A ProteinP16442 (Uniprot-TrEMBL)
sABO-A:Mn2+ComplexR-HSA-9034047 (Reactome)
sABO-B ProteinP16442 (Uniprot-TrEMBL)
sABO-B:Mn2+ComplexR-HSA-9034031 (Reactome)
sLeA MetaboliteCHEBI:140914 (ChEBI)
sLeAMetaboliteCHEBI:140914 (ChEBI)
sLeX MetaboliteCHEBI:140916 (ChEBI)
sLeXMetaboliteCHEBI:140916 (ChEBI)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
A antigen-RBCArrowR-HSA-9033959 (Reactome)
A antigen-secArrowR-HSA-9034042 (Reactome)
ABO-A:Mn2+mim-catalysisR-HSA-9033959 (Reactome)
ABO-B:Mn2+mim-catalysisR-HSA-9033961 (Reactome)
B antigen-RBCArrowR-HSA-9033961 (Reactome)
B antigen-secArrowR-HSA-9034053 (Reactome)
B3GALTsmim-catalysisR-HSA-9603989 (Reactome)
B4GALNT2mim-catalysisR-HSA-9605700 (Reactome)
CMP-Neu5AcR-HSA-9603987 (Reactome)
CMP-Neu5AcR-HSA-9603991 (Reactome)
CMP-Neu5AcR-HSA-9605600 (Reactome)
CMPArrowR-HSA-9603987 (Reactome)
CMPArrowR-HSA-9603991 (Reactome)
CMPArrowR-HSA-9605600 (Reactome)
FUT1mim-catalysisR-HSA-9033949 (Reactome)
FUT2mim-catalysisR-HSA-9036987 (Reactome)
FUT2mim-catalysisR-HSA-9603982 (Reactome)
FUT2mim-catalysisR-HSA-9603983 (Reactome)
FUT3,5,6,7mim-catalysisR-HSA-9605682 (Reactome)
FUT3mim-catalysisR-HSA-9603986 (Reactome)
FUT3mim-catalysisR-HSA-9605609 (Reactome)
FUT3mim-catalysisR-HSA-9605644 (Reactome)
FUT4,5,9(10,11)mim-catalysisR-HSA-9603984 (Reactome)
GDP-FucR-HSA-9033949 (Reactome)
GDP-FucR-HSA-9036987 (Reactome)
GDP-FucR-HSA-9603982 (Reactome)
GDP-FucR-HSA-9603983 (Reactome)
GDP-FucR-HSA-9603984 (Reactome)
GDP-FucR-HSA-9603986 (Reactome)
GDP-FucR-HSA-9605609 (Reactome)
GDP-FucR-HSA-9605644 (Reactome)
GDP-FucR-HSA-9605682 (Reactome)
GDPArrowR-HSA-9033949 (Reactome)
GDPArrowR-HSA-9036987 (Reactome)
GDPArrowR-HSA-9603982 (Reactome)
GDPArrowR-HSA-9603983 (Reactome)
GDPArrowR-HSA-9603984 (Reactome)
GDPArrowR-HSA-9603986 (Reactome)
GDPArrowR-HSA-9605609 (Reactome)
GDPArrowR-HSA-9605644 (Reactome)
GDPArrowR-HSA-9605682 (Reactome)
GlcNAc-β1,3-Gal-RR-HSA-9603989 (Reactome)
H antigen-RBCArrowR-HSA-9033949 (Reactome)
H antigen-RBCR-HSA-9033959 (Reactome)
H antigen-RBCR-HSA-9033961 (Reactome)
H antigen-secArrowR-HSA-9036987 (Reactome)
H antigen-secArrowR-HSA-9037612 (Reactome)
H antigen-secR-HSA-9034042 (Reactome)
H antigen-secR-HSA-9034053 (Reactome)
H antigen-secR-HSA-9037612 (Reactome)
LeAArrowR-HSA-9603986 (Reactome)
LeAR-HSA-9603982 (Reactome)
LeBArrowR-HSA-9603982 (Reactome)
LeXArrowR-HSA-9603984 (Reactome)
LeXR-HSA-9603983 (Reactome)
LeYArrowR-HSA-9603983 (Reactome)
Lewis antigensArrowR-HSA-9606392 (Reactome)
Lewis antigensR-HSA-9606392 (Reactome)
PALM-C-Rhesus D proteinArrowR-HSA-9038658 (Reactome)
R-HSA-9033949 (Reactome) The H antigen is formed with the addition of a fucose (Fuc) sugar onto one of two precursor oligosaccharide sequences, Type 1 (RBCs) or Type 2 (secreted) chains. The FUT1 gene (aka H gene) found in hematopoietic cells produces galactoside 2-α-L-fucosyltransferase 1 (FUT1 aka α-1,2-fucosyltransferase 1) which mediates the transfer of a fucose (Fuc) sugar to the galactose (Gal) sugar of the Type 2 chain precursor Gal-β1,4-GlcNAc-β1,3-Gal-R (where R is a glycosphingolipid) to form the H antigen (Larsen et al. 1990). This is an essential step for subsequent formation of A and B antigens. Mutations that inactivate the FUT1 gene can result in the 'Bombay phenotype' where no A, B or H antigens are produced on RBCs (Koda et al 1997, Kaneko et al. 1997).
R-HSA-9033959 (Reactome) The histo-blood group ABO system transferase (ABO) is the basis of the ABO blood group system. A, B and AB individuals express a glycosyltransferase activity that converts the H antigen to the A antigen (by addition of GalNAc), to the B antigen (by addition of Gal) or to the AB antigen (by the addition of both GalNAc and Gal). O group individuals lack such activity. Differences in four critical amino acids (176, 235, 266 and 268) alter the specificity from an A to a B glycosyltransferase (Yamamoto et al. 1990, Yamamoto & McNeill 1996, Seto et al. 1999, Alfaro et al. 2008). The histo-blood group A transferase (ABO-A) utilises UDP-GalNAc to transfer N-acetylgalactosamine (GalNAc) to the H antigen formed via Type 2 chains to form the A antigen (Patenaude et al. 2002, Persson et al. 2007).
R-HSA-9033961 (Reactome) The histo-blood group ABO system transferase (ABO) is the basis of the ABO blood group system. A, B and AB individuals express glycosyltransferase activity that converts the H antigen to the A antigen (by addition of GalNAc), to the B antigen (by addition of Gal) or to the AB antigen (by the addition of both GalNAc and Gal). O group individuals lack such activity. Differences in four critical amino acids (176, 235, 266 and 268) alter the specificity from an A to a B glycosyltransferase (Yamamoto et al. 1990, Yamamoto & McNeill 1996, Seto et al. 1999, Alfaro et al. 2008). The histo-blood group B transferase (ABO-B) utilises UDP-Gal to transfer galactose (Gal) to the H antigen formed via Type 2 chains to form the B antigen (Patenaude et al. 2002, Persson et al. 2007).
R-HSA-9034042 (Reactome) As well as being a Golgi membrane resident, the histo-blood group ABO system transferase (ABO) can be proteolytically processed by an unknown protease into a soluble form, fucosylglycoprotein alpha-N-acetylgalactosaminyltransferase (sABO). A, B and AB individuals express glycosyltransferase activities that convert the H antigen to the A antigen (by addition of GalNAc), to the B antigen (by addition of Gal) or to the AB antigen (by the addition of both GalNAc and Gal). O group individuals lack such activity. Differences in four critical amino acids (176, 235, 266 and 268) alter the specificity from an A to a B glycosyltransferase (Yamamoto et al. 1990, Yamamoto & McNeill 1996, Seto et al. 1999, Alfaro et al. 2008). The soluble form of histo-blood group A transferase (sABO-A) utilises UDP-GalNAc to transfer N-acetylgalactosamine (GalNAc) to the H antigen formed via Type 1 chains to form the A antigen in secretors (A antigen-sec) (Patenaude et al. 2002, Persson et al. 2007).
R-HSA-9034053 (Reactome) As well as being a Golgi membrane resident, the histo-blood group ABO system transferase (ABO) can be proteolytically processed by an unknown protease into a soluble form, fucosylglycoprotein alpha-N-acetylgalactosaminyltransferase (sABO). A, B and AB individuals express glycosyltransferase activities that convert the H antigen to the A antigen (by addition of GalNAc), to the B antigen (by addition of Gal) or to the AB antigen (by the addition of both GalNAc and Gal). O group individuals lack such activity. Differences in four critical amino acids (176, 235, 266 and 268) alter the specificity from an A to a B glycosyltransferase (Yamamoto et al. 1990, Yamamoto & McNeill 1996, Seto et al. 1999, Alfaro et al. 2008). The soluble form of histo-blood group B transferase (sABO-B) utilises UDP-Gal to transfer galactose (Gal) to the H antigen formed via Type 1 chains to form the B antigen in secretors (B antigen-sec) (Patenaude et al. 2002, Persson et al. 2007).
R-HSA-9036987 (Reactome) The H antigen is formed by the addition of a fucose (Fuc) sugar onto one of two precursor oligosaccharide sequences; Type 1 or Type 2 chains. Type 2 chains are found on red blood cells (RBCs), epithelial cells and endothelial cells whereas Type 1 chains are primarily found in bodily secretions. The FUT2 gene (aka Se gene) is expressed in secretory epithelial cells in salivary glands and the gastrointestinal tract and produces galactoside 2-α-L-fucosyltransferase 2 (FUT2 aka α-1,2-fucosyltransferase 2) which mediates the transfer of a Fuc sugar to the galactose (Gal) sugar of the Type 1 chain precursor Gal-β1,3-GlcNAc-β1,3-Gal-R (where R is a glycoprotein) to form the H antigen (Kelly et al. 1995, Koda et al. 1997). This is an essential step for subsequent formation of A and B antigens. Mutations that inactivate the FUT2 gene can result in the 'Bombay phenotype' where no A, B or H antigens are produced in secretions (Koda et al 1997b, Kelly et al. 1994).
R-HSA-9037612 (Reactome) The H antigen in secretors (H antigen-sec) translocates from the Golgi lumen to the extracellular region by an unknown mechanism (Ewald & Sumner 2016). Here, it can be extended by the soluble forms of the histo-blood group ABO system transferase (sABO) enzymes.
R-HSA-9038653 (Reactome) The RHCE gene encodes the C/c and E/e proteins, presumably by alternative splicing of a pre messenger RNA (Bloy et al. 1998, Le Van Kim et al. 1992).
R-HSA-9038658 (Reactome) The RHD gene encodes the blood group Rh(D) polypeptide (Rhesus D protein, D antigen) (Bloy et al. 1988, Saboori et al. 1988, Avent et al. 1988). It is present only on the erythrocyte membrane as a post-translationally-modified palmitoylated protein (de Vetten & Agre 1988, Hartel-Schenk & Agre 1992).
R-HSA-9603982 (Reactome) The FUT2 gene (originally named the Se gene) expresses galactoside 2-alpha-L-fucosyltransferase 2 present on the Golgi membrane. FUT2 catalyses the α1,2 addition of fucose (Fuc) to Type 1 and Type 2 oligosaccharide chains, thereby playing a role in Lewis blood group determination (Kukowska-Latallo et al. 1990). Here, the addition of fucose to the terminal galactose (Gal) of the Lewis A antigen (LeA) in an α1,2 linkage forms the Lewis B antigen (LeB) (Kelly et al. 1995, Koda et al. 1997). LeB is found only in secretors in around 80% of Europeans. LeB is only formed when an individual inherits both FUT3 (Le) and FUT2 (Se) genes and around 80% of individuals inherit FUT2.
R-HSA-9603983 (Reactome) The FUT2 gene (originally named the Se gene) expresses galactoside 2-alpha-L-fucosyltransferase 2 present on the Golgi membrane. FUT2 catalyses the α1,2 addition of fucose (Fuc) to Type 1 and Type 2 oligosaccharide chains, thereby playing a role in Lewis blood group determination (Kukowska-Latallo et al. 1990). Here, the addition of fucose to the terminal galactose (Gal) of the Lewis X antigen (LeX) in an α1,2 linkage forms the Lewis Y antigen (LeY) (Kelly et al. 1995, Koda et al. 1997).
R-HSA-9603984 (Reactome) Analogous to FUT3 adding fucose to Type 1 chains to form LeA, alpha-(1,3)-fucosyltransferases 4, 5 and 9 (FUT4,5,9), resident on the Golgi membrane, mediate the transfer of fucose (Fuc) to Type 2 oligosaccharide chains in an α1,3 linkage to form the Lewis X antigen (LeX) (Goelz et al. 1990, Lowe et al. 1991, Weston et al. 1992, Toivonen et al. 2002). FUT10 and FUT11 also exhibit α1,3 fucosyltransferase activity (Mollicone et al. 2009).
R-HSA-9603986 (Reactome) The FUT3 gene (originally named the Le gene) expresses galactoside 3(4)-L-fucosyltransferase present on the Golgi membrane. FUT3 catalyses the α1,4 and α1,3 addition of fucose to Type 1 and Type 2 oligosaccharide chains respectively, thereby playing a role in Lewis blood group determination (Kukowska-Latallo et al. 1990). Here, the addition of fucose to the subterminal N-acetylglucosaminyl (GlcNAc) residue of Type 1 chains in an α1,4 linkage forms the Lewis A antigen (LeA). In Lewis negative (Le(a- b-)) individuals, FUT3 is inactivated by either of two mutations resulting in a single amino acid substitution in the catalytic region (Nishihara et al. 1993). LeA is found on red blood cells (~20%) and in saliva and other secretions (>90%) of Europeans. LeA is a water-soluble antigen and red blood cells acquire Lewis specificity by adsorbing it onto their surfaces from blood plasma.
R-HSA-9603987 (Reactome) CMP-N-acetylneuraminate-beta-1,4-galactoside alpha-2,3-sialyltransferase (ST3GAL3), located on the Golgi membrane, mediates the transfer of sialic acid (Neu5Ac, N-acetylneuraminic acid) in an α2,3 linkage to the terminal galactose of Gal-beta-1,3-GlcNAc- and Gal-beta-1,4-GalNAc- sequences found on glycoproteins and glycolipids (Kitagawa & Paulson 1993). The product, Type 1 monosialylgalactosylgloboside (Type 1 MSGG) is the precursor to sialyl Lewis a (sLeA) (also known as the CA19-9 antigen), a tumour marker that is used primarily in the management of pancreatic cancer. Increased sialylation has been observed to be associated with malignant transformation and metastasis.
R-HSA-9603989 (Reactome) The family of beta-1,3-galactosyltransferases (B3GALTs) transfer galactose (Gal) from UDP-alpha-D-galactose (UDP-Gal) to the β1,3 position of substrates with a terminal beta-N-acetylglucosamine (β-GlcNAc) residue. B3GALTs are involved in the biosynthesis of the carbohydrate moieties of glycolipids and glycoproteins. Here, five members of this family (B3GALT1-5) can mediate the transfer of Gal to GlcNAc-β1,3-Gal-R, the precursor to blood group Type 1 oligosaccharide chains found in bodily secretions (Amado et al. 1998, Isshiki et al. 1999; review Hennet 2002).
R-HSA-9603991 (Reactome) Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 6 (ST6GALNAC6), located on the Golgi membrane, mediates the transfer of sialic acid (Neu5Ac) to Type 1 monosialylgalactosylgloboside (Type 1 MSGG) to form Type 1 disialylgalactosylgloboside (Type 1 DSGG), the precursor for disialyl-Lewis A antigen (Senda et al. 2007). ST6GALNAC6 and DSGG are found in proximal tubule epithelial cells in normal kidney tissues and are both downregulated in renal cancer cell lines and cancer tissues (Senda et al. 2007).
R-HSA-9605600 (Reactome) The alpha-2,3-sialyltransferases ST3GAL3,4 and 6 (Kitagawa & Paulson 1993, Okajima et al. 1999, Kitagawa & Paulson 1994) located on the Golgi membrane, mediate the transfer of sialic acid (Neu5Ac, N-acetylneuraminic acid) in an α2,3 linkage to the terminal galactose of Gal-beta-1,4-GlcNAc- sequences found on glycoproteins and glycolipids to form Type 2 monosialylgalactosylgloboside (Type 2 MSGG).

Increased sialylation has been associated with malignant transformation and metastasis. ST3GAL6 is highly expressed in patients with multiple myeloma (MM). Knockdown of ST3GAL6 has been shown to prolong survival in mice (Glavey et al. 2014).
R-HSA-9605609 (Reactome) The FUT3 gene (originally named the Le gene) expresses galactoside 3(4)-L-fucosyltransferase present on the Golgi membrane. FUT3 catalyses the α1,4 and α1,3 addition of fucose to Type 1 and Type 2 oligosaccharide chains respectively, thereby playing a role in Lewis blood group determination (Kukowska-Latallo et al. 1990). Here, the addition of fucose to the subterminal N-acetylglucosaminyl (GlcNAc) residue of Type 1 monosialylgalactosylgloboside (Type 1 MSGG) in an α1,4 linkage forms the sialyl Lewis A antigen (sLeA), also known as the CA19-9 antigen, the most common tumour marker used primarily in the management of pancreatic and gastrointestinal cancers worldwide (Magnani 2004). If CA19-9 is initially elevated in pancreatic cancer, it may be requested several times during cancer treatment to monitor response and, on a regular basis following treatment, to help detect recurrence of the cancer.
R-HSA-9605644 (Reactome) The FUT3 gene (originally named the Le gene) expresses galactoside 3(4)-L-fucosyltransferase present on the Golgi membrane. FUT3 catalyses the α1,4 and α1,3 addition of fucose to Type 1 and Type 2 oligosaccharide chains respectively, thereby playing a role in Lewis blood group determination (Kukowska-Latallo et al. 1990). Here, the addition of fucose to the subterminal N-acetylglucosaminyl (GlcNAc) residue of Type 1 disialylgalactosylgloboside (Type 1 DSGG) in an α1,4 linkage forms the disialyl-Lewis A antigen (dsLeA).
R-HSA-9605682 (Reactome) Alpha-(1,3)-fucosyltransferases 3, 5, 6 and 7 (FUT3,5,6,7 respectively) mediate the transfer of fucose (Fuc) to glycan structures such as Type 2 monosialylgalactosylgloboside (Type 2 MSGG) to form the sialyl-Lewis X antigen (sLeX) (Kukowska-Latallo et al. 1990, Weston et al. 1992, Koszdin & Bowen 1992, Natsuka et al. 1994). The adhesion of sialyl-Lewis antigens to E-selectin on endothelial cell surfaces is a key step in the development of metastasis. Down-regulation of these FUTs may be a useful therapeutic approach in some cancers (Padro et al. 2011, Trinchera et al. 2011).
R-HSA-9605700 (Reactome) Beta-1,4 N-acetylgalactosaminyltransferase 2 (B4GALNT2), resident on the Golgi membrane, mediates the formation of the Sda antigen through the addition of an N-acetylgalactosamine (GalNAc) residue via a β1,4-linkage to the sub-terminal galactose residue substituted with an α2,3-linked sialic acid residue (Montiel et al. 2003, Lo Presti et al. 2003). The Sda antigen is a carbohydrate determinant expressed on erythrocytes and secretions of the vast majority of Caucasians and ethnic groups and its expression has an impact on the physiology and the pathology of several biological systems (Dall'Olio et al. 2014). In normal colon, B4GALNT2 levels are high and control the biosynthesis of Sda while at the same time inhibiting the formation of sialyl-Lewis X antigen (sLeX), involved in metastasis (Groux-Degroote et al. 2014).
R-HSA-9606392 (Reactome) Lewis antigens are components of exocrine epithelial secretions (Green 1989).
RHCE geneR-HSA-9038653 (Reactome)
RHD geneR-HSA-9038658 (Reactome)
Rhesus C/E proteinArrowR-HSA-9038653 (Reactome)
ST3GAL3,4,6mim-catalysisR-HSA-9605600 (Reactome)
ST3GAL3mim-catalysisR-HSA-9603987 (Reactome)
ST6GALNAC6mim-catalysisR-HSA-9603991 (Reactome)
SdaArrowR-HSA-9605700 (Reactome)
Type 1 DSGGArrowR-HSA-9603991 (Reactome)
Type 1 DSGGR-HSA-9605644 (Reactome)
Type 1 MSGGArrowR-HSA-9603987 (Reactome)
Type 1 MSGGR-HSA-9603991 (Reactome)
Type 1 MSGGR-HSA-9605609 (Reactome)
Type 1 chainArrowR-HSA-9603989 (Reactome)
Type 1 chainR-HSA-9036987 (Reactome)
Type 1 chainR-HSA-9603986 (Reactome)
Type 1 chainR-HSA-9603987 (Reactome)
Type 2 MSGGArrowR-HSA-9605600 (Reactome)
Type 2 MSGGR-HSA-9605682 (Reactome)
Type 2 MSGGR-HSA-9605700 (Reactome)
Type 2 chainR-HSA-9033949 (Reactome)
Type 2 chainR-HSA-9603984 (Reactome)
Type 2 chainR-HSA-9605600 (Reactome)
UDP-GalNAcR-HSA-9033959 (Reactome)
UDP-GalNAcR-HSA-9034042 (Reactome)
UDP-GalNAcR-HSA-9605700 (Reactome)
UDP-GalR-HSA-9033961 (Reactome)
UDP-GalR-HSA-9034053 (Reactome)
UDP-GalR-HSA-9603989 (Reactome)
UDPArrowR-HSA-9033959 (Reactome)
UDPArrowR-HSA-9033961 (Reactome)
UDPArrowR-HSA-9034042 (Reactome)
UDPArrowR-HSA-9034053 (Reactome)
UDPArrowR-HSA-9603989 (Reactome)
UDPArrowR-HSA-9605700 (Reactome)
dsLeAArrowR-HSA-9605644 (Reactome)
sABO-A:Mn2+mim-catalysisR-HSA-9034042 (Reactome)
sABO-B:Mn2+mim-catalysisR-HSA-9034053 (Reactome)
sLeAArrowR-HSA-9605609 (Reactome)
sLeXArrowR-HSA-9605682 (Reactome)
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