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Review

Human Lectins, Their Carbohydrate Affinities and Where to Find Them

by
Cláudia D. Raposo
1,*,
André B. Canelas
2 and
M. Teresa Barros
1
1
LAQV-Requimte, Department of Chemistry, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal
2
Glanbia-AgriChemWhey, Lisheen Mine, Killoran, Moyne, E41 R622 Tipperary, Ireland
*
Author to whom correspondence should be addressed.
Biomolecules 2021, 11(2), 188; https://doi.org/10.3390/biom11020188
Submission received: 4 November 2020 / Revised: 2 January 2021 / Accepted: 26 January 2021 / Published: 29 January 2021
Browse Figures
Versions Notes

Abstract

:
Lectins are a class of proteins responsible for several biological roles such as cell-cell interactions, signaling pathways, and several innate immune responses against pathogens. Since lectins are able to bind to carbohydrates, they can be a viable target for targeted drug delivery systems. In fact, several lectins were approved by Food and Drug Administration for that purpose. Information about specific carbohydrate recognition by lectin receptors was gathered herein, plus the specific organs where those lectins can be found within the human body.

1. Introduction

Lectins are an attractive class of proteins of non-immune origin that can either be free or linked to cell surfaces, and are involved in numerous biological processes, such as cell-cell interactions, signaling pathways, cell development, and immune responses [1]. Lectins selectively recognize carbohydrates and reversibly bind to them as long as the ligands are oriented in a specific manner. Some of the commonly occurring carbohydrates that are found in Nature are d-fructose, d-galactose, l-arabinose, d-xylose, d-mannose, d-glucose, d-glucosamine, d-galactosamine, l-fucose, various uronic acids, sialic acid, and their combinations to form other di- and oligosaccharides, or other biomolecules (Figure 1) [2].
Lectins in vertebrates can be classified either by their subcellular location, or by their structure. Division based on their location includes integral lectins located in membranes as structural components, or soluble lectins present in intra- and intercellular fluids, which can move freely.
Division according to lectin structure consists of several different types of lectins, such as C-type lectins (binding is Ca2+ dependent), I-type lectins (carbohydrate recognition domain is similar to immunoglobulins), galectin family (or S-type, which are thiol dependent), pentraxins (pentameric lectins) and P-type lectins (specific to glycoproteins containing mannose 6-phosphate) [3].
Different lectins have high similarity in the residues that bind to saccharides, most of which coordinate to metal ions, and water molecules. Nearly all animal lectins possess several pockets that recognize molecules other than carbohydrates, meaning that they are multivalent and can present 2 to 12 sites of interaction, allowing the binding of several ligands simultaneously. The specificity and affinity of the lectin-carbohydrate complex depends on the lectin, which can be very sensitive to the structure of the carbohydrate (e.g., mannose versus glucose, Figure 1), or to the orientation of the anomeric substituent (α versus β anomer, e.g., in Figure 2), or both. Lectin-carbohydrate interactions are achieved mainly through hydrogen bonds, van der Waals (steric interactions), and hydrophobic forces (example is given in Figure 3) [3,4].
It has been shown that the majority of lectins are conserved through evolution, suggesting that these proteins play a crucial role in the sugar-recognition activities necessary for the living process and development [5,6].
Although lectins are present in animals, plants, lichens, bacteria, and higher fungi [3], this review focuses only on human lectins for targeted drug delivery [7] purposes, their specificity towards carbohydrates and the organs where they are expressed. When referring to gene expression (or RNA expression), one means that those specific organs or cells have that specific gene coded. If active, it produces the respective protein, and one says that the protein is expressed in that organ or cell. In this review, we focus only on protein expression, since that information is the only relevant one for the development of targeted drug delivery systems. More information about carbohydrate-based nanocarriers for targeted drug delivery systems can be found elsewhere [8,9,10]. Since lectins are able to recognize and transport carbohydrates and their derivatives, lectin targeting can be relevant in the research and development of new medicines [7,11,12]. The metabolism of cancer cells, for example, is different from normal cells due to intense glycolytic activity (Warburg effect) [13]. Cancer cells require glutamine and/or glucose for cell growth, and glucose transporter isoforms 1 and 2 (gene symbols GLUT1 and GLUT2, respectively) showed an increase in activity in several tumors (gastrointestinal carcinoma, squamous cell carcinoma of the head and neck, breast carcinoma, renal cell carcinoma, gastric and ovarian cancer) [14,15].
The herein adopted lectin nomenclature is in accordance with the Human Genome Group (HUGO) Gene Nomenclature Committee. However, most common designated aliases (non-standard names) are also included (and appear first). The expression data for all lectin-coding genes was compiled from The Human Protein Atlas [16,17] and GeneCards [18] databases.

2. C-Type Lectins

C-type lectins are involved in the recognition of saccharides in a Ca2+-dependent manner but exhibit low affinities to carbohydrates, requiring multiple valencies of carbohydrate ligands to mediate signaling pathways, such as DC-SIGN2 which gene symbol is CLEC4M (Most genes carry the information to make proteins. The gene name is often used when referring to the corresponding protein). MINCLE (gene symbol CLEC4E), on the other hand, shows high affinity and can detect small numbers of glycolipids on fungal surfaces [19,20]. Most of the lectin-like domains contain some of the conserved residues required to establish the domain fold, but do not present the residues required for carbohydrate recognition [21]. The amino acid residues known to be involved in calcium-dependent sugar-binding are the EPN motif (mannose-binding), the QPD motif (for galactose binding), and the WND motif (for Ca2+binding) [22]. More information about glycan affinity and binding to proteins can be found elsewhere [23]. A comprehensive list of C-type lectins is presented in Table 1, divided by subfamilies that differ in the architecture of the domain [22,24], along with the carbohydrates that they recognize and the human tissues where they are expressed.

3. Chitolectins (or Chilectins)

There are two types of proteins that are able to recognize chitin: chitinases and chitolectins. The first ones are active proteins that bind and hydrolyze oligosaccharides, whereas the latter ones are able to bind oligosaccharides but do not hydrolyze them [76,77] and are presented in Table 2.

4. F-Type Lectins

F-type lectins, also called fucolectins, are characterized by an α-l-fucose recognition domain and display both unique carbohydrate- and calcium-binding sequence motifs [76]. F-type lectins are immune-recognition proteins and are presented in Table 3. Fucose is recognized by specific interactions with O5 (pyranose acetal oxygen), 3-OH and 4-OH [82], the reason why these atoms must be available to form these interactions after the synthesis of fucose derivatives.

5. F-Box Lectins

F-box proteins are the substrate-recognition subunits of the SCF (Skp1-Cul1-F-box protein) complex. They have an F-box domain that binds to S-phase kinase-associated protein 1 (Skp1) [84]. The F-box proteins were divided into three different classes: Fbws are those that contains WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs that have either different protein-protein interaction modules or no recognizable motifs [85]. Although F-box proteins are a superfamily of proteins, only five are known to recognize N-linked glycoproteins [84] as presented in Table 4.

6. Ficolins

Ficolins play an important role in innate immunity by recognizing and binding to carbohydrates present on the surface of Gram-positive and Gram-negative bacteria [89]. There are three human ficolins and they are presented in Table 5.

7. I-Type Lectins

I-type lectins are a subset of the immunoglobulin superfamily that specifically recognizes sialic acids and other carbohydrate ligands. Most of the members of this group of lectins are siglecs, which are type I transmembrane proteins, and can be divided into two groups: the CD33-related group that includes CD33 (siglec3) siglecs5–11, and siglec14 while the other group includes siglec1, CD22 (siglec2), MAG (siglec4) and Siglec15 [90,91]. CD33-related groups possess between 1 and 4 C-set domains and feature cytoplasmic tyrosine-based motifs involved in signaling and endocytosis. Siglec1 possesses 16 C-set domains, CD22 has 6 C-set domains and MAG presents 4 C-set domains. MAG is the only siglec not found on cells of the immune system. Members of this I-type superfamily are presented in Table 6 along with their carbohydrate ligands and protein expression. An example of a drug delivery system was developed by Spence, Greene and co-workers who developed polymeric nanoparticles of poly(lactic-co-glycolic acid) decorated with sialic acid [92,93].

8. L-Type Lectins

L-type lectins are distinguished from other lectins on the basis of tertiary structure, not the primary sequence, and are composed of antiparallel β-sheets connected by short loops and β-bends, usually lacking any α-helices [115]. Members of this family of lectins present different glycan-binding specificities as presented in Table 7. L-type superfamily includes Pentraxins [116,117] that require Ca2+ ions for ligand binding. Both LMAN1 and LMAN2 also require Ca2+ ions for their binding activity [115].

9. M-Type Lectins

M-type family of lectins consists of α-mannosidases, which are proteins involved in both the maturation and the degradation of Asn-linked oligosaccharides [127]. Members of this family, their binding affinities and protein expression are presented in Table 8.

10. P-Type Lectins

P-type lectins constitute a two-member family of mannose-6-phosphate receptors (Table 9) that play an essential role in the generation of functional lysosomes. The phosphate group is key to high-affinity ligand recognition by these proteins. Furthermore, optimal ligand-binding ability of M6PR is achieved in the presence of divalent cations, particularly Mn2+ cation [130,131].

11. R-Type Lectins

R-type lectins are protein-UDP acetylgalactosaminyltransferases that contain an R-type carbohydrate recognition domain, which is conserved between animal and bacterial lectins [135]. Members of this superfamily recognize Gal/GalNAc residues and are expressed in several tissues as presented in Table 10.

12. S-Type Lectins

S-type lectins are known nowadays as galectins and are a superfamily of proteins that show a high affinity for β-galactoside sugars (Table 11). Formerly called S-type lectins because of their sulfhydryl dependency, galectins are the most widely expressed class of lectins in all organisms. Human galectins have been classified into three major groups according to their structure: prototypical, chimeric and tandem-repeat [151,152,153].
Galectins play important roles in immune responses and promoting inflammation. They are also known for having a crucial role in cancer-causing tumor invasion, progression, metastasis and angiogenesis [154,155,156].
Table
Table 11. Human S-type lectins, their carbohydrate ligands and protein epression in the organs.
Table 11. Human S-type lectins, their carbohydrate ligands and protein epression in the organs.
Common Name
(HUGO Name if Different) 		Gene Symbol Carbohydrate Preferential Affinity Protein Expression in the Organs
Galectin 1
Galectin 1LGALS1β-d-galactosides, poly-N-acetyllactosamine-enriched glycoconjugates [157,158]Bone marrow, brain, cervix (uterine), endometrium, lymph node, ovary, parathyroid gland, placenta, smooth muscle, skin, spleen, testis, tonsil, vagina
Galectin 2LGALS2β-d-galactosides, lactose [159]Appendix, colon, duodenum, gallbladder, kidney, liver, lymph node, pancreas, rectum, small intestine, spleen, tonsil
Galectin 3
Galectin 3LGALS3β-d-galactosides, LacNAc [160]Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
Galectin 3 binding proteinLGALS3BPβ-d-galactosides, lactose [161]Adipose and soft tissue, bone marrow and lymphoid tissues, brain, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, proximal digestive tract, skin
Galectin 4LGALS4β-d-galactosides, lactose [162]Appendix, colon, duodenum, gallbladder, pancreas, rectum, small intestine, stomach
Galectin 7LGALS7Gal, GalNAc, Lac, LacNAc [163]Cervix (uterine), esophagus, oral mucosa, salivary gland, skin, tonsil, vagina
Galectin 8LGALS8β-d-galactosides. Preferentially binds to 3′-O-sialylated and 3′-O-sulfated glycans [164]Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
Galectin 9LGALS9β-d-galactosides. Forssman pentasaccharide, lactose, N-acetyllactosamine [165]Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
Galectin 9BLGALS9Bβ-d-galactosides [166]Appendix, bone marrow, breast, lymph node, spleen, tonsil
Galectin 9CLGALS9Cβ-d-galactosides [166]Appendix, bronchus, colon, duodenum, gallbladder, lung, pancreas, spleen, stomach, tonsil
Galectin 10 (Charcot-Leyden crystal galectin, CLC)LGALS10Binds weakly to lactose, N-acetyl-d-glucosamine and d-mannose [167]Lymph node, spleen, tonsil
Galectin 12LGALS12β-d-galactose and lactose [168,169]a)
Galectin 13LGALS13N-acetyl-lactosamine, mannose and N-acetyl-galactosamine [170]. Contrary to other galectins, Galectin 13 does not bind β-d-galactosides [171]Kidney, placenta, spleen, urinary bladder
Placental Protein 13 (Galectin 14)LGALS14N-acetyl-lactosamine [172]Adrenal gland, colon, kidney
Galectin 16LGALS16N-acetyl-lactosamine, β-d-galactose and lactose [172]Placenta
a) Only RNA expression data available in The Human Protein Atlas [16,17] and GeneCards [18] databases.

13. X-Type Lectins

Intelectins (Table 12) were classified as X-type lectins because they do not have a typical lectin domain, instead, they contain a fibrinogen-like domain and a unique intelectin-specific region [173].

14. Orphans

Orphan lectins are those that do not belong to known lectin structural families [175]. Proteins that bind to sulfated glycosaminoglycans are usually not considered as lectins [101], however, the specific binding of these proteins to sulfated glycosaminoglycans can provide a valuable tool to develop targeted drug delivery systems. Glycosaminoglycan binding interactions with proteins were described in detail by Vallet, Clerc and Ricard-Blum [176] which information is outside of the scope of this review.

Author Contributions

Conceptualization, C.D.R.; methodology, C.D.R. and A.B.C.; resources, M.T.B.; writing—original draft preparation, C.D.R.; writing—review and editing, A.B.C. and M.T.B.; visualization, C.D.R.; supervision, M.T.B.; funding acquisition, M.T.B. All authors have read and agreed to the published version of the manuscript.

Funding

This work was funded by Fundação para a Ciência e a Tecnologia, grant number PD/BD/109680/2015. This work was also supported by the Associate Laboratory for Green Chemistry, LAQV, which is financed by national funds from FCT/MEC (UID/QUI/50006/2013 and UID/QUI/50006/2019) and co-financed by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007265).

Acknowledgments

The authors acknowledge Christopher D. Maycock for having reviewed this manuscript.

Conflicts of Interest

The authors declare no conflict of interest.

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Biomolecules 11 00188 g001 550
Figure 1. Structures of the carbohydrate building blocks found in Nature.
Figure 1. Structures of the carbohydrate building blocks found in Nature.
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Figure 2. Structures of α- and β-d-glucose.
Figure 2. Structures of α- and β-d-glucose.
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Figure 3. Asialoglycoprotein receptor (Protein Data Bank entry 1DV8, gene symbol ASGR1) binding interactions with N–acetylgalactosamine: (a) ligand conformation inside the binding site; (b) specific interactions are hydrogen bonds (blue dashed lines) and steric interactions (red dashed lines).
Figure 3. Asialoglycoprotein receptor (Protein Data Bank entry 1DV8, gene symbol ASGR1) binding interactions with N–acetylgalactosamine: (a) ligand conformation inside the binding site; (b) specific interactions are hydrogen bonds (blue dashed lines) and steric interactions (red dashed lines).
Biomolecules 11 00188 g003
Table
Table 1. C-type superfamily, their carbohydrate ligands and protein expression in human organs.
Table 1. C-type superfamily, their carbohydrate ligands and protein expression in human organs.
Common Name
(HUGO Name if Different) 		Gene Symbol Carbohydrate Preferential Affinity Protein Expression in the Organs
Proteoglycans or lecticans
AggrecanACANHyaluronic acid [25]Cartilage, soft tissue
BrevicanBCANHyaluronic acid [26,27]Brain
NeurocanNCANHyaluronic acid [28]Brain
VersicanVCANHyaluronic acid [29]Brain
FRAS1 related extracellular matrix 1FREM1b)Adrenal gland, appendix, colon, duodenum, epididymis, kidney, lung, pancreas, placenta, rectum, salivary gland, small intestine, stomach, testis, tonsil, thyroid gland
Type II transmembrane receptors
Blood Dendritic Cell Antigen 2 (C-type lectin domain family 4 member C)CLEC4CGal-β-(1-3 or 1-4)-GlcNAc-β-(1-2)-Man trisaccharides [30,31]Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
DC-SIGN (CD209 molecule)CD209High N-linked d-Mannose- oligosaccharides, and branched l-fucose, both with free OH-3 and OH-4. (N-linked glycans, N-acetyl-d-glucosamine, Lewis a, b, x and y) [32]Bone marrow, lung
DC-SIGN2CLEC4MHigh N-linked d-Mannose- oligosaccharides, branched l-fucose, N-linked glycans, N-acetyl-d-glucosamine, Lewis a, b and yBrain, gastrointestinal tract, lung
Dectin-2 (C-type lectin domain containing 6A)CLEC6Aα-(1-2) or α-(1-4) mannans [33] and other high-α-d-mannose carbohydrates [34]Blood
Dendritic cell immunoreceptor (DCIR) (C-type lectin domain family 4 member A)CLEC4AMannose, fucose and weakly interacts with N-acetylglucosamine [35]Bone marrow, spleen, lung
Fc fragment of IgE receptor IIFCER2Mannose [36], immunoglobulin E, CD21, galactose [37]Lymph node, bone marrow, spleen, appendix, tonsil, skin
Hepatic Asialoglycoprotein Receptor 1ASGR1Terminal β-d-galactose and N-acetylgalactosamine units [38]Stomach, liver, gallbladder
Hepatic Asialoglycoprotein Receptor 2ASGR2Terminal β-d-galactose and N-acetylgalactosamine units [38]Liver
Kupffer Cell receptor (C-type lectin domain family 4 member F)CLEC4FGalactose, fucose, and N-acetylgalactosamine [39]Liver
Langerin (CD207 molecule)CD207High-mannose oligosaccharides, mannose, N-acetylglucosamine, fucose. Note that OH-3 and OH-4 should be free for recognition, and preferentially equatorial. N-acetylmannosamine showed less affinity; thereby axial derivatives should be avoided. Sulfated mannosylated glycans, keratan sulfate and β-glucans [40]Lymph node, tonsil, skin, spleen
Liver sinusoidal epithelial cell lectin (LSECtin) (C-type lectin domain family 4 member G)CLEC4GMannose, N-acetylglucosamine and fucose [41]Lymph node, brain, colon, kidney, liver, testis
Macrophage Asialoglycoprotein ReceptorCLEC10ATerminal galactose and N-acetylgalactosamine residues [42]Bone marrow, brain, lymph node, oral mucosa, skin, spleen, tonsil
Macrophage C-type Lectin (MCL)CLEC4DTrehalose 6,6′-dimycolate, α-d-mannans18 (however it was suggested that MCL is not a carbohydrate-binding lectin) [43]Bone marrow, lung, lymph node, spleen, tonsil
MINCLE (C-type lectin domain family 4 member E)CLEC4Eα-mannose, trehalose-6′6-dimycolate, glucose [19]a)
Collectins
Collectin-K1 (collectin subfamily member 11)COLEC11High mannose oligosaccharides with at least a mannose-α-(1-2)-mannose residue [44]a)
Collectin-L1 (collectin subfamily member 10)COLEC10Galactose, mannose, fucose, N-acetylglucosamine, N-acetylgalactosamine [45]a)
Mannose-binding lectin 2MBL2Mannose, fucose, N-acetylglucosamine [46]Liver
Pulmonary surfactant protein 1 (surfactant protein A1)SFTPA1N-acetylmannosamine, l-fucose, mannose, glucose, poorly to galactose. Preferentially oligosaccharides [47]Lung
Pulmonary surfactant protein 2 (surfactant protein A2)SFTPA2N-acetylmannosamine, l-fucose, mannose, glucose, poorly to galactose. Preferentially oligosaccharides [47]Lung
Pulmonary surfactant protein B (surfactant protein B)SFTPBb)Lung
Pulmonary surfactant protein C (surfactant protein C)SFTPCLipopolysaccharides [47]Lung
Pulmonary surfactant protein D (surfactant protein D)SFTPDMaltose, glucose, mannose, poorly to galactose. Preferentially oligosaccharides [47]Lung
Scavenger receptor with CTLD (SRCL) (collectin subfamily member 12)COLEC12d-galactose, l- and d-fucose, N-acetylgalactosamine (internalizes specifically in nurse-like cells), sialyl Lewis X, or a trisaccharide and asialo-orosomucoid (ASOR). May also play a role in the clearance of amyloid-beta in Alzheimer disease [48]Brain, lung, placenta
Selectins
Selectin ESELESialyl Lewis x, a [49]Bone marrow, colon, nasopharynx
Selectin LSELLSialyl Lewis x [50]Appendix, bone marrow, lymph node, spleen, tonsil
Selectin PSELPSialyl Lewis x [49]Bone marrow, colon
Natural Killer (NK)
C-type lectin domain family 2 member LCLEC2Lb)Brain, skeletal muscle
C-type lectin domain containing 5ACLEC5AFucose, mannose, N-acetylglucosamine, N-acetylmuramic acid-β(1-4)-N-acetylglucosamine [51]Blood
CD72 moleculeCD72b)Appendix, bone marrow, lymph node, spleen, tonsil
Killer cell lectin-like receptor G1KLRG1Mannose [52]Appendix, cervix (uterine), colon, duodenum, small intestine, stomach, tonsil
Killer cell lectin-like receptor G2KLRG2b)Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
CD69 moleculeCD69Fucoidan (weak). N-acetylamine was reported but not supported by a second report. Does not bind glucose, galactose, mannose, fucose or N-acetylglucosamine [53]Appendix, bone marrow, lymph node, spleen, tonsil
Killer cell lectin-like receptor F1KLRF1Predicted to not bind carbohydrates [54]Blood
C-type lectin domain family 2 member BCLEC2Bb)
Known to bind to KLRF1		Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, proximal digestive tract, skin
Oxidized low-density lipoprotein receptor 1OLR1Predicted to not bind to carbohydrates [55]a)
Killer cell lectin-like receptor D1KLRD1α-(2-3)-linked NeuAc on multi-antennary N-glycan, heparin, sulfate-containing polysaccharides [56]a)
C-type lectin domain family 1 member ACLEC1Ab) [57]a)
C-type lectin domain family 1 member BCLEC1BPredicted to not bind to carbohydrates [58]a)
C-type lectin domain family 12 member BCLEC12Bb)a)
C-type lectin-like 1CLECL1Predicted to not bind to carbohydrates [21]a)
C-type lectin domain family 12 member ACLEC12Ab)Bone marrow, lung, spleen
DNGR (C-type lectin domain containing 9A)CLEC9ASpecific interactions were not discovered yet, although it is known that this lectin binds to α-actin filaments and β-spectrin [59]a)
C-type lectin domain family 2 member ACLEC2Ab)Skin
Dectin-1 (C-type lectin domain containing 7A)CLEC7Aβ-(1-3)- and β-(1-6)-d-Glycans (neither mono- or short oligosaccharides/polymers are recognized) [60]Blood, bone marrow
C-type lectin domain family 2 member DCLEC2DHigh molecular weight sulfated glycosaminoglycans [61]Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
Killer cell lectin-like receptor B1KLRB1Terminal Gal-α-(1-3)-Gal, N-acetyllactosamine. [62] Sucrose octasulphate [63]Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
Killer cell lectin-like receptor C1KLRC1b)a)
Killer cell lectin-like receptor C2KLRC2b)a)
Killer cell lectin-like receptor C3KLRC3b)Colon, duodenum, small intestine, stomach, tonsil
Killer cell lectin-like receptor C4KLRC4b)a)
Killer cell lectin-like receptor K1KLRK1α-(2-3)-NeuAc-containing N-glycans [64], heparin, heparan sulfate [56]Appendix, lymph node, spleen, tonsil
Macrophage Mannose Receptor (MMR)
Endo180 (Mannose receptor C type 2)MRC2Mannose, fucose, N-acetylglucosamine [65]Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
Lymphocyte antigen 75LY75Predicted to not bind carbohydrates [65]Appendix, breast, bronchus, cervix (uterine), duodenum, endometrium, fallopian tube, gallbladder, liver, lung, lymph node, nasopharynx, pancreas, placenta, rectum, spleen, stomach, thyroid gland, tonsil, urinary bladder,
Mannose receptor C-type 1 c)MRC1Mannose, fucose, glucose, N-acetylglucosamine [66] (C-type) 4-O-sulphated GalNAc (R-type)Colon, endometrium, kidney, lung, rectum, skin, soft tissue, testis
Phospholipase A2 receptorPLA2R1Predicted to not bind carbohydrates [65] but known to bind collagenKidney
Free C-type Lectin Domains (CTLDs)
C-type lectin domain containing 19ACLEC19Ab)a)
Lithostathine-alpha (Regenerating family member 1 alpha)REG1Ab)Duodenum, pancreas, small intestine, stomach
Lithostathine-beta (Regenerating family member 1 beta)REG1Bb)Duodenum, pancreas, small intestine, stomach
Regenerating family member 3 alphaREG3APeptidoglycan (binding affinity increases with the length of the carbohydrate moiety) [67]Appendix, duodenum, skin, small intestine, stomach
Regenerating family member 3 gammaREG3GPeptidoglycan [67]a)
Regenerating family member 4REG4Mannans, heparin [67]Appendix, colon, duodenum, rectum, small intestine
Type I receptors
ChondrolectinCHODLb) [68]Appendix, colon, duodenum, rectum, small intestine, testis
LayilinLAYNHyaluronan [69]Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
Tetranectin
Cartilage-derived C-type lectin (C-type lectin domain family 3 member A)CLEC3AExpected to bind sulfated polysaccharides such as heparin [70]a)
Stem cell growth factor (SCGF) (C-type lectin domain containing 11A)CLEC11Ab)Bone marrow, soft tissue
Tetranectin (C-type lectin domain family 3 member B)CLEC3BSulfated polysaccharides such as heparin [70]a)
Polycystin
Polycystin 1 like 3, transient receptor potential channel interactingPKD1L3Predicted to not bind carbohydratesa)
Polycystin 1, transient receptor potential channel interactingPKD1Predicted to bind galactosyl and glucosyl residues. Might bind oligosaccharides with mannosyl moieties [71]Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, pancreas, proximal digestive tract, skin
Attractin
AttractinATRNb)Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, pancreas, proximal digestive tract, skin
Attractin-like 1ATRNL1b)a)
CTLD/acidic neck
CD302 moleculeCD302b) [72]a)
Proteoglycan 2, pro eosinophil major basic proteinPRG2Heparin [73]Bone marrow, placenta
Proteoglycan 3, pro eosinophil major basic protein 2PRG3b)Bone marrow
Endosialin
CD93 moleculeCD93b)Bone marrow, brain, colon, kidney, lung, spleen
C-type lectin domain containing 14ACLEC14Ab)Appendix, brain, cervix (uterine), colon, duodenum, esophagus, gallbladder, heart muscle, kidney, lung, pancreas, prostate, rectum, skin, small intestine, stomach, testis
Endosialin (CD248 molecule)CD248b)Adipose and soft tissue, bone marrow and lymphoid tissues, brain, female tissues, gastrointestinal tract, kidney and urinary bladder, muscle tissues, pancreas, skin
ThrombomodulinTHBDb)Cervix (uterine), colon, esophagus, lymph node, oral mucosa, placenta, skin, tonsil, urinary bladder, vagina
Others
C-type lectin domain family 18 member ACLEC18AFucoidan, β-glucans, β-galactans [74]a)
Prolectin (C-type lectin domain containing 17A)CLEC17ATerminal α-d-mannose and fucose residues [75]Appendix, lymph node, spleen, stomach, tonsil
DiGeorge syndrome critical region gene 2DGCR2b)Pancreas
FRAS1 related extracellular matrix 1FREM1b)Adrenal gland, appendix, colon, duodenum, epididymis, kidney, lung, pancreas, placenta, rectum, salivary gland, small intestine, stomach, testis, tonsil, thyroid gland
a) Only RNA expression data available in The Human Protein Atlas [16,17] and GeneCards [18] databases. b) Carbohydrate moieties recognized by this protein have not been discovered yet. c) FDA-approved drug target.
Table
Table 2. Human chitolectins (also called chilectins), their carbohydrate ligands and protein expression in the organs.
Table 2. Human chitolectins (also called chilectins), their carbohydrate ligands and protein expression in the organs.
Common Name
(HUGO Name if Different) 		Gene Symbol Carbohydrate Preferential Affinity Protein Expression in the Organs
Chitinase 3 like 1CHI3L1Chitin [78]a)
Chitinase 3 like 2CHI3L2Chitooligosaccharides ((GlcNAc)5 and (GlcNAc)6 showed the highest affinities) [79]Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, proximal digestive tract
Oviductin (Oviductal glycoprotein 1)OVGP1Chitin [80]Fallopian tube
Stabilin-1 interacting chitinase-like proteinSI-CLPGalNAc, GlcNAc, ribose, mannose. Prefers to bind oligosaccharides with a four-sugar ring core [81]a)
a) Only RNA expression data available in The Human Protein Atlas [16,17] and GeneCards [18] databases.
Table
Table 3. Human f-type lectins, their carbohydrate ligands and protein expression in the organs.
Table 3. Human f-type lectins, their carbohydrate ligands and protein expression in the organs.
Common Name
(HUGO Name if Different) 		Gene Symbol Carbohydrate Preferential Affinity Protein Expression in the Organs
Coagulation factor V a)F5Fucose [83]b)
APC, WNT signalling pathway regulatorAPCc)Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
a) FDA-approved drug target. b) Only RNA expression data available in The Human Protein Atlas [16,17] and GeneCards [18] databases. c) Carbohydrate moieties recognized by this protein have not been discovered yet.
Table
Table 4. Human F-box lectins, their carbohydrate ligands and protein expression in the organs.
Table 4. Human F-box lectins, their carbohydrate ligands and protein expression in the organs.
Common Name
(HUGO Name if Different) 		Gene Symbol Carbohydrate Preferential Affinity Protein Expression in the Organs
Cyclin FCCNFa)Appendix, bone marrow, lung, lymph node, skin, spleen, tonsil
F-box protein 2FBXO2N-acetylglucosamine disaccharide chitobiose [86]Breast, ovary, pancreas
F-box protein 3FBXO3a)b)
F-box protein 4FBXO4a)b)
F-box protein 5FBXO5a)Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
F-box protein 6FBXO6High-mannose glycoproteins [87]Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
F-box protein 7FBXO7a)Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
F-box protein 8FBXO8a)Bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, pancreas, proximal digestive tract, skin
F-box protein 9FBXO9a)b)
F-box protein 10FBXO10a)Cervix (uterine), colon, duodenum, endometrium, fallopian tube, lung, prostate, rectum, seminal vesicle, small intestine, testis
F-box protein 11FBXO11a)b)
F-box protein 15FBXO15a)b)
F-box protein 16FBXO16a)Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
F-box protein 17FBXO17Sulfated and galactose-terminated glycoproteins [88]b)
F-box protein, helicase, 18FBXO18a)Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
LIM domain 7LMO7a)b)
F-box protein 21FBXO21a)Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, proximal digestive tract, skin
F-box protein 22FBXO22a)b)
Tetraspanin 17TSPAN17a)b)
F-box protein 24FBXO24a)b)
F-box protein 25FBXO25a)b)
F-box protein 27FBXO27a)Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, proximal digestive tract, skin
F-box protein 28FBXO28a)b)
F-box protein 30FBXO30a)b)
F-box protein 31FBXO31a)Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, proximal digestive tract, skin
F-box protein 32FBXO32a)b)
F-box protein 33FBXO33a)Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
F-box protein 34FBXO34a)Adrenal gland, bronchus, colon, epididymis, endometrium, gallbladder, placenta, seminal vesicle, skeletal muscle, skin, stomach, testis, thyroid gland
F-box protein 36FBXO36a)b)
F-box protein 38FBXO38a)b)
F-box protein 39FBXO39a)b)
F-box protein 40FBXO40a)b)
F-box protein 41FBXO41a)b)
F-box protein 42FBXO42a)Bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, pancreas
F-box protein 43FBXO43a)b)
F-box protein 44FBXO44a)Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
F-box protein 45FBXO45a)b)
F-box protein 46FBXO46a)b)
F-box protein 47FBXO47a)b)
F-box protein 48FBXO48a)Esophagus, kidney, oral mucosa, parathyroid gland, skin, stomach
a) Carbohydrate moieties recognized by this protein have not been discovered yet. b) Only RNA expression data available in The Human Protein Atlas [16,17] and GeneCards [18] databases.
Table
Table 5. Human ficolins, their carbohydrate ligands and protein expression in the organs.
Table 5. Human ficolins, their carbohydrate ligands and protein expression in the organs.
Common Name
(HUGO Name if Different) 		Gene Symbol Carbohydrate Preferential Affinity Protein Expression in the Organs
Ficolin 1FCN1GlcNAc, GalNAc; sialic acid [89]a)
Ficolin 2FCN2GlcNAc (acetyl group); β-(1-3)-d-glucan [89]a)
Ficolin 3FCN3N-acetylglucose; N-acetylgalactose, fucose, lipopolysaccharides [89]a)
a) Only RNA expression data available in The Human Protein Atlas [16,17] and GeneCards [18] databases.
Table
Table 6. Human I-type lectins, their carbohydrate ligands and protein expression in the organs.
Table 6. Human I-type lectins, their carbohydrate ligands and protein expression in the organs.
Common Name
(HUGO Name if Different) 		Gene Symbol Carbohydrate Preferential Affinity Protein Expression in the Organs
Siglecl1 (Sialic acid binding Ig like lectin 1)SIGLEC1α-(2-3)-Sialic acid, α-(2-6)-Sialic acid, α-(2-8)-Sialic acid [94]Bone marrow, lung
Siglec2 (CD22 molecule) a)CD22α-(2-6)-Sialic acid [95,96]Appendix, lymph node, spleen, tonsil
Siglec3 (CD33 molecule)CD33α-(2-6)-Sialic acid, α-(2-3)-Sialic acid [97]Appendix, bone marrow, lung, lymph node, skin, spleen, tonsil
Siglec4a, MAG (Myelin associated glycoprotein)MAGα-(2-3)-Sialic acid [98]Brain
Siglec5 (Sialic acid binding Ig like lectin 5)SIGLEC5α-(2-3)-Sialic acid, α-(2-6)-Sialic acid, α-(2-8)-Sialic acid [99]Bone marrow, lymph node, placenta, spleen, tonsil
Siglec6 (Sialic acid binding Ig like lectin 6)SIGLEC6Sialic acid-α-(2-6)-N-acetylgalactosamine (Sialyl-Tn) [100] Placenta
Siglec7SIGLEC7α-(2-6)-Sialic acid, α-(2-8)-Sialic acid, α-(2-3)-Sialic acid [101] and disialogangliosides [102,103,104]b)
Siglec8SIGLEC8α-(2-3)-Sialic acid, α-(2-6)-Sialic acid [105]Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
Siglec9 (Sialic acid binding Ig like lectin 9)SIGLEC9α-(2-3)-Sialic acid, Sialyl Lewis x, α-(2-6)-Sialic acid, α-(2-8)-Sialic acid [106]Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
Siglec10 (Sialic acid binding Ig like lectin 10)SIGLEC10α-(2-3)-Sialic acid, α-(2-6)-Sialic acid [107]Appendix, bone marrow, lymph node, soft tissue, spleen, tonsil
Siglec11 (Sialic acid binding Ig like lectin 11)SIGLEC11α-(2-8)-Sialic acid [101]b)
Siglec14 (Sialic acid binding Ig like lectin 14)SIGLEC14Sialic acid- α-(2-6)-N-acetylgalactosamine (Sialyl-Tn), N-acetylneuraminic acid [108]Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
Siglec15 (Sialic acid binding Ig like lectin 15)SIGLEC15Sialyl-Tn [109]b)
CD2 molecule a)CD2N-glycans with fucose [110]Appendix, lymph node, spleen, tonsil
CD83 moleculeCD83Sialic acid [111]Appendix, bone marrow, lung, lymph node, spleen, tonsil
Intercellular adhesion molecule 1ICAM1Hyaluronan [112]Appendix, bone marrow, brain, endometrium, fallopian tube, kidney, lung, lymph node, spleen, testis, tonsil
L1 cell adhesion moleculeL1CAMα-(2-3)-Sialic acid [113]Adipose and soft tissue, bone marrow and lymphoid tissues, brain, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, proximal digestive tract, skin
Myelin protein zeroMPZSO4– –3GlucA-β-(1-3)-Gal-β-(1–4)-GlcNAc (HNK-1 antigen) [101]Bronchus, esophagus, fallopian tube, small intestine, soft tissue, stomach, testis
Neural cell adhesion molecule 1NCAM1High N-linked d-mannose [114]Brain, colon, hearth muscle, pancreas, smooth muscle, soft tissue, thyroid gland
Neural cell adhesion molecule 2NCAM2c)Brain, bronchus, colon, duodenum, gallbladder, ovary, rectum, small intestine, soft tissue, testis
a) FDA-approved drug target. b) Only RNA expression data available in The Human Protein Atlas [16,17] and GeneCards [18] databases. c) Carbohydrate moieties recognized by this protein have not been discovered yet.
Table
Table 7. Human L-type lectins, their carbohydrate ligands and protein expression in the organs.
Table 7. Human L-type lectins, their carbohydrate ligands and protein expression in the organs.
Common Name
(HUGO Name if Different) 		Gene Symbol Carbohydrate Preferential Affinity Protein Expression in the Organs
CalnexinCANXNon-reducing glucose residues in an oligosaccharide (Glc(Man)9(GlcNAc)2) [118]Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
CalreticulinCALRNon-reducing glucose residues in an oligosaccharide (Glc(Man)9(GlcNAc)2) [119]Bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, pancreas, skin
Calreticulin 3CALR3a)Testis
Lectin, mannose-binding 1LMAN1α-(1-2) mannans with free OH-3, OH-4 and OH-6 [120]Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
Lectin, mannose-binding 1 likeLMAN1La)b)
Lectin, mannose-binding 2LMAN2High α-(1-2) mannans, Low affinity for d-glucose and N-acetylglucosamine [121]Bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, pancreas
Lectin, mannose-binding 2 likeLMAN2Lα-(1-2) trimannose [122]Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
Adhesion G protein-coupled receptor D1ADGRD1a)Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
Adhesion G protein-coupled receptor D2ADGRD2a)b)
Amyloid P component, serumAPCSHeparin, dextran sulfate proteoglycans [123]b)
C-reactive proteinCRPGalactose 6-phosphate, Gal-β-(1-3)-GalNAc, Gal-β-(1-4)-GalNAc, Gal-β-(1-4)-Gal-β-(1-4)-GlcNAc, other phosphate-containing ligands [124,125]Liver, gallbladder, soft tissue
Neuronal pentraxin 1NPTX1a)Brain, testis
Neuronal pentraxin 2NPTX2a)Adrenal gland, brain, pancreas, pituitary gland, testis
Neuronal pentraxin receptorNPTXRa)Brain
Pentraxin 3PTX3Heparin [126]b)
Sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1SVEP1a)Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas
a) Carbohydrate moieties recognized by this protein have not been discovered yet. b) Only RNA expression data available in The Human Protein Atlas [16,17] and GeneCards [18] databases.
Table
Table 8. Human M-type lectins, their carbohydrate ligands and protein expression in the organs.
Table 8. Human M-type lectins, their carbohydrate ligands and protein expression in the organs.
Common Name
(HUGO Name if Different) 		Gene Symbol Carbohydrate Preferential Affinity Protein Expression in the Organs
Mannosidase alpha class 1A member 1MAN1A1α-(1-2)-mannans [128,129]Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
Mannosidase alpha class 1A member 2MAN1A2α-(1-2)-mannans [128,129]Bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
Mannosidase alpha class 1B member 1MAN1B1α-(1-2)-mannans [128,129]Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
Mannosidase alpha class 1C member 1MAN1C1α-(1-2)-mannans [128,129]Bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas
Table
Table 9. Human P-type lectins, their carbohydrate ligands and protein expression in the organs.
Table 9. Human P-type lectins, their carbohydrate ligands and protein expression in the organs.
Common Name
(HUGO Name if Different) 		Gene Symbol Carbohydrate Preferential Affinity Protein Expression in the Organs
Mannose-6-phosphate receptor, cation dependent a)M6PRMannose-6-phosphate residues [132,133]Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
Insulin-like growth factor 2 receptorIGF2RMannose-6-phosphate residues (either α or β). Mannose-6-phosphate analogues with carboxylate or malonate groups [134]b)
a) FDA-approved drug target. b) Only RNA expression data available in The Human Protein Atlas [16,17] and GeneCards [18] databases.
Table
Table 10. Human R-type lectins, their carbohydrate ligands and protein expression in the organs.
Table 10. Human R-type lectins, their carbohydrate ligands and protein expression in the organs.
Common Name
(HUGO Name if Different) 		Gene Symbol Carbohydrate Preferential Affinity Protein Expression in the Organs
Polypeptide N-acetylgalactosaminyltransferase 1GALNT1GalNAc [136]Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
Polypeptide N-acetylgalactosaminyltransferase 2GALNT2GalNAc [136,137]Bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
Polypeptide N-acetylgalactosaminyltransferase 3GALNT3GalNAc [136]Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
Polypeptide N-acetylgalactosaminyltransferase 4GALNT4GalNAc, GalNAc-glycosylated substrates [136,138]a)
Polypeptide N-acetylgalactosaminyltransferase 5GALNT5GalNAc [136]Appendix, bronchus, cervix (uterine), colon, duodenum, esophagus, gallbladder, lung, oral mucosa, rectum, salivary gland, small intestine, stomach, tonsil, vagina
Polypeptide N-acetylgalactosaminyltransferase 6GALNT6GalNAc [136]Bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
Polypeptide N-acetylgalactosaminyltransferase 7GALNT7GalNAc, GalNAc-glycosylated substrates [100]Bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract
Polypeptide N-acetylgalactosaminyltransferase 8 b)GALNT8GalNAc [139]Bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, skin
Polypeptide N-acetylgalactosaminyltransferase 9GALNT9GalNAc [140]a)
Polypeptide N-acetylgalactosaminyltransferase 10GALNT10GalNAc [141]Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
Polypeptide N-acetylgalactosaminyltransferase 11GALNT11GalNAc [142]Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
Polypeptide N-acetylgalactosaminyltransferase 12GALNT12GalNAc [143]Appendix, bone marrow, brain, breast, cervix (uterine), endometrium, fallopian tube, prostate, soft tissue, thyroid gland, tonsil, skin
Polypeptide N-acetylgalactosaminyltransferase 13GALNT13GalNAc [144]Adrenal gland, lung, salivary gland
Polypeptide N-acetylgalactosaminyltransferase 14GALNT14GalNAc [145]a)
Polypeptide N-acetylgalactosaminyltransferase 15GALNT15GalNAc [146]a)
Polypeptide N-acetylgalactosaminyltransferase 16GALNT16GalNAc [147]Bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
Polypeptide N-acetylgalactosaminyltransferase 17GALNT17GalNAc [148]Brain
Polypeptide N-acetylgalactosaminyltransferase 18GALNT18GalNAc [149]Adipose and soft tissue, bone marrow and lymphoid tissues, brain, endocrine tissues, female tissues, gastrointestinal tract, kidney and urinary bladder, lung, male tissues, muscle tissues, pancreas, proximal digestive tract, skin
Polypeptide N-acetylgalactosaminyltransferase like 5GALNTL5c) [150]Testis
a) Only RNA expression data available in The Human Protein Atlas [16,17] and GeneCards [18] databases. b) FDA-approved drug target. c) Carbohydrate moieties recognized by this protein have not been discovered yet.
Table
Table 12. Human X-type lectins, their carbohydrate ligands and protein expression in the organs.
Table 12. Human X-type lectins, their carbohydrate ligands and protein expression in the organs.
Common Name
(HUGO Name if Different) 		Gene Symbol Carbohydrate Preferential Affinity Protein Expression in the Organs
Intelectin 1ITLN1Terminal acyclic 1,2-diol-containing structures, including β-d-galactofuranose, d-phosphoglycerol-modified glycans, d-glycero-d-talo-oct-2-ulosonic acid, 3-deoxy-d-manno-oct-2-ulosonic acid [174]Appendix, colon, duodenum, rectum, small intestine
Intelectin 2ITLN2a)Appendix, colon, duodenum, rectum, small intestine
a) Carbohydrate moieties recognized by this protein have not been discovered yet.
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Raposo, C.D.; Canelas, A.B.; Barros, M.T. Human Lectins, Their Carbohydrate Affinities and Where to Find Them. Biomolecules 2021, 11, 188. https://doi.org/10.3390/biom11020188

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Raposo CD, Canelas AB, Barros MT. Human Lectins, Their Carbohydrate Affinities and Where to Find Them. Biomolecules. 2021; 11(2):188. https://doi.org/10.3390/biom11020188

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Raposo, Cláudia D., André B. Canelas, and M. Teresa Barros. 2021. "Human Lectins, Their Carbohydrate Affinities and Where to Find Them" Biomolecules 11, no. 2: 188. https://doi.org/10.3390/biom11020188

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