lipocalin/cytosolic fatty acid-binding protein family; Lipocalins are diverse, mainly low molecular weight extracellular proteins that bind principally small hydrophobic ligands, and form covalent or non-covalent complexes with soluble macromolecules as well as membrane bound-receptors. They have a large beta-barrel ligand-binding cavity. Members include retinol-binding protein, retinoic acid-binding protein, complement protein C8 gamma, Can f 2, apolipoprotein D, extracellular fatty acid-binding protein, beta-lactoglobulin, oderant-binding protein, and bacterial lipocalin Blc. Lipocalins are involved in many important processes such as ligand transport, modulation of cell growth and metabolism, regulation of immune response, smell reception, tissue development and animal behavior. Cytosolic fatty acid-binding proteins also bind hydrophobic ligands in a non-covalent, reversible manner, and are involved in protection and shuttling of fatty acids within the cell, and in acquisition and removal of fatty acids from intracellular sites.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767957411   4 RVFLGKKDHLSMSTRAIRPTEEGGLHVHMEFPGADGCNQVDAEYLKVGSEGHFRVPALGYLDVRIVDTDYSSFAVLYIYK 83
Cdd:cd19422   16 PVFLGMKDHMTSSTTAIRPTPEGDLTMHTEFPLPDGCKQIEAEFQKSGQAGHFRVPELGKRDLRVMDTDYSSYAILYIYK 95

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 767957411  84 ELEGALSTMVQLYSRTQDVSPQALKSFQDFYPTLGLPKDMMVMLPQSD 131
Cdd:cd19422   96 ELEGESSTMVQLYTRNQDVSPQLLQKFKELYPTLGLTEDMMVILPKSD 143

lipocalin 15 and similar proteins, such as chicken CALbeta; This subfamily includes uncharacterized human lipocalin 15, and chicken chondrogenesis-associated lipocalin (CAL) beta which is associated with chondrogenesis and inflammation. It belongs to the lipocalin/cytosolic fatty-acid binding protein family which have a large beta-barrel ligand-binding cavity. Lipocalins are mainly low molecular weight extracellular proteins that bind principally small hydrophobic ligands, and form covalent or non-covalent complexes with soluble macromolecules, as well as membrane bound-receptors. They participate in processes such as ligand transport, modulation of cell growth and metabolism, regulation of immune response, smell reception, tissue development and animal behavior. Cytosolic fatty-acid binding proteins, also bind hydrophobic ligands in a non-covalent, reversible manner, and have been implicated in intracellular uptake, transport and storage of hydrophobic ligands, regulation of lipid metabolism and sequestration of excess toxic fatty acids, as well as in signaling, gene expression, inflammation, cell growth and proliferation, and cancer development.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767957411   4 RVFLGKKDHLSMSTRAIRPTEEGGLHVHMEFPGADGCNQVDAEYLKVGSEGHFRVPALGYLDVRIVDTDYSSFAVLYIYK 83
Cdd:cd19422   16 PVFLGMKDHMTSSTTAIRPTPEGDLTMHTEFPLPDGCKQIEAEFQKSGQAGHFRVPELGKRDLRVMDTDYSSYAILYIYK 95

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 767957411  84 ELEGALSTMVQLYSRTQDVSPQALKSFQDFYPTLGLPKDMMVMLPQSD 131
Cdd:cd19422   96 ELEGESSTMVQLYTRNQDVSPQLLQKFKELYPTLGLTEDMMVILPKSD 143

lipocalin 15 and similar proteins, such as chicken CALbeta; This subfamily includes uncharacterized human lipocalin 15, and chicken chondrogenesis-associated lipocalin (CAL) beta which is associated with chondrogenesis and inflammation. It belongs to the lipocalin/cytosolic fatty-acid binding protein family which have a large beta-barrel ligand-binding cavity. Lipocalins are mainly low molecular weight extracellular proteins that bind principally small hydrophobic ligands, and form covalent or non-covalent complexes with soluble macromolecules, as well as membrane bound-receptors. They participate in processes such as ligand transport, modulation of cell growth and metabolism, regulation of immune response, smell reception, tissue development and animal behavior. Cytosolic fatty-acid binding proteins, also bind hydrophobic ligands in a non-covalent, reversible manner, and have been implicated in intracellular uptake, transport and storage of hydrophobic ligands, regulation of lipid metabolism and sequestration of excess toxic fatty acids, as well as in signaling, gene expression, inflammation, cell growth and proliferation, and cancer development.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767957411   4 RVFLGKKDHLSMSTRAIRPTEEGGLHVHMEFPGADGCNQVDAEYLKVGSEGHFRVPALGYLDVRIVDTDYSSFAVLYIYK 83
Cdd:cd19422   16 PVFLGMKDHMTSSTTAIRPTPEGDLTMHTEFPLPDGCKQIEAEFQKSGQAGHFRVPELGKRDLRVMDTDYSSYAILYIYK 95

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 767957411  84 ELEGALSTMVQLYSRTQDVSPQALKSFQDFYPTLGLPKDMMVMLPQSD 131
Cdd:cd19422   96 ELEGESSTMVQLYTRNQDVSPQLLQKFKELYPTLGLTEDMMVILPKSD 143

Lipocalin / cytosolic fatty-acid binding protein family; Lipocalins are transporters for small hydrophobic molecules, such as lipids, steroid hormones, bilins, and retinoids. The family also encompasses the enzyme prostaglandin D synthase (EC:5.3.99.2). Alignment subsumes both the lipocalin and fatty acid binding protein signatures from PROSITE. This is supported on structural and functional grounds. The structure is an eight-stranded beta barrel.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767957411    6 FLGKKDHLSMSTRAIRPTEEGGLHVHMEFPGADGCNQVDAEYLKVGSEGHFRVPALGYLD---VRIVDTDYSSFAVLYIY 82
Cdd:pfam00061  15 LEEEMKALGVGFATIKVLENGNLPVTEITKEGGKCKTVSVTFKKTEEPGKLGVEFDEYAGgrkVKVLTTDYDNYLIFYQK 94

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 767957411   83 KELEGALSTMVQLYSRTQDVSPQALKSFQDFYPTLGLPKDMMVMLPQSD 131
Cdd:pfam00061  95 GDKDGKTTIVRELYGRDPELSPELLEKFKKFLKELGIDEENIVRLYQKD 143

extracellular fatty acid-binding protein; Ex-FABP (also known as siderocalin, lipocalin Q83 or protein Ch21) displays a dual ligand binding mode as it can bind siderophore and fatty acids simultaneously. ExFABP has a cavity which extends through the protein and has two separate ligand specificities, one for bacterial siderophores at one end, and other specifically binding co-purified lysophosphatidic acid (LPA), a potent cell signaling molecule, at the other end. As well as acting as an LPA "sensor", Ex-FABP is bacteriostatic, and tightly binds the 2,3-catechol-type ferric siderophores enterobactin, bacillibactin, and parabactin, associated with enteric bacteria and Gram-positive bacilli. This group belongs to the lipocalin/cytosolic fatty-acid binding protein family which have a large beta-barrel ligand-binding cavity. Lipocalins are mainly low molecular weight extracellular proteins that bind principally small hydrophobic ligands, and form covalent or non-covalent complexes with soluble macromolecules, as well as membrane bound-receptors. They participate in processes such as ligand transport, modulation of cell growth and metabolism, regulation of immune response, smell reception, tissue development and animal behavior. Cytosolic fatty-acid binding proteins, also bind hydrophobic ligands in a non-covalent, reversible manner, and have been implicated in intracellular uptake, transport and storage of hydrophobic ligands, regulation of lipid metabolism and sequestration of excess toxic fatty acids, as well as in signaling, gene expression, inflammation, cell growth and proliferation, and cancer development.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767957411   6 FLGKKDHLSMSTRAIRPTEEGGLHVHMEFPGADGCNQVDAEYLKVGSEGHFRVPALGYLDVRIVDTDYSSFAVLYIYKEL 85
Cdd:cd19439   20 FLREKGKMKMMMARISFLGEDELLVSYAFPSPGGCRKWETTFKKTSDDGEVYYSEEARKTVEVLDTDYKSYAVIYATRVK 99

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 767957411  86 EGALSTMVQLYSRTQDVSPQALKSFQDFYPTLGLPKDMMVMLP 128
Cdd:cd19439  100 DGRTLHMMRLYSRSQEVSPEAEAIFRKLAEERNYTDEMVAILP 142

lipocalin 2 and similar proteins; Lipocalin-2 (LCN2, also known as siderocalin, uterocalin, oncogene 24p3, and neutrophil gelatinase-associated lipocalin) is expressed in renal, endothelial, liver, smooth muscle cells, cardiomyocytes, in various populations of immune cells and dendritic cells. Roles ascribed to LCN2, include chemotactic and bacteriostatic effects, and iron trafficking. LCN2 can also act as a growth factor. It plays an key role in the pathophysiology of renal and cardiovascular diseases, and is involved in various deleterious processes, such as inflammation and fibrosis. It is used as a renal injury biomarker. This subgroup belongs to the lipocalin/cytosolic fatty-acid binding protein family which have a large beta-barrel ligand-binding cavity. Lipocalins are mainly low molecular weight extracellular proteins that bind principally small hydrophobic ligands, and form covalent or non-covalent complexes with soluble macromolecules, as well as membrane bound-receptors. They participate in processes such as ligand transport, modulation of cell growth and metabolism, regulation of immune response, smell reception, tissue development and animal behavior. Cytosolic fatty-acid binding proteins, also bind hydrophobic ligands in a non-covalent, reversible manner, and have been implicated in intracellular uptake, transport and storage of hydrophobic ligands, regulation of lipid metabolism and sequestration of excess toxic fatty acids, as well as in signaling, gene expression, inflammation, cell growth and proliferation, and cancer development.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767957411  57 RVPALGYLDVRIVDTDYSSFAVLYIYKELEGALSTMVQLYSRTQDVSPQALKSFQDFYPTLGLPKD 122
Cdd:cd19457   96 SYPGLQSYTVRVVATDYNQFAMVFFKKTSENRVYFEITLYGRTKELSPELKERFIKFSKSLGLPDD 161

lipocalin domain of alpha1-microglobulin and similar proteins; Alpha(1)-microglobulin (A1M, also known as protein AMBP, alpha-1 microglycoprotein, and protein HC), has immunosuppressive properties, such as inhibition of antigen induced lymphocyte cell-proliferation, cytokine secretion, and oxidative burst of neutrophils. A1M may participate in the reducing and scavenging of biological pro-oxidants such as heme and heme-proteins. It binds heme strongly, and a C-terminally processed form of the protein degrades the heme. It can reduce cytochrome C, nitroblue tetrazolium, methemoglobin and free iron, using NADH, NADPH or ascorbate as cofactor. Intravenous administration of recombinant A1M in animal models eliminates or significantly reduces the manifestations of preeclampsia. A1M is a useful biomarker in clinical diagnostics for monitoring pre-eclampsia, hepatitis E, renal tubular dysfunction, and renal toxicity. A1M belongs to the lipocalin/cytosolic fatty-acid binding protein family which have a large beta-barrel ligand-binding cavity. Lipocalins are mainly low molecular weight extracellular proteins that bind principally small hydrophobic ligands, and form covalent or non-covalent complexes with soluble macromolecules, as well as membrane bound-receptors. They participate in processes such as ligand transport, modulation of cell growth and metabolism, regulation of immune response, smell reception, tissue development and animal behavior. Cytosolic fatty-acid binding proteins, also bind hydrophobic ligands in a non-covalent, reversible manner, and have been implicated in intracellular uptake, transport and storage of hydrophobic ligands, regulation of lipid metabolism and sequestration of excess toxic fatty acids, as well as in signaling, gene expression, inflammation, cell growth and proliferation, and cancer development.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767957411  40 CNQVDAEYLKVGSEGHFRvpalgY--------LDVRIVDTDYSSFAVLYIYK-ELEGALSTMVQLYSRTQDVSPQALKSF 110
Cdd:cd19418   64 CEEISGEYEKTDTPGKFL-----YhkskwnatVDAYVVHTNYDEYAIFLMKKfKRHGEPTTTLKLYGRTPQLRPTLLQDF 138

                         90       100
                 ....*....|....*....|....*
gi 767957411 111 QDFYPTLGLPKDMMVMLPQSDACNP 135
Cdd:cd19418  139 RTLALEQGIPEDSIIIKADKGECVP 163

Minor allergen Can f 2; The minor dog lipocalin allergen Can f 2 is an important cause of allergic sensitization in humans worldwide. It is one of two major allergens present in dog dander extracts, and is produced by tongue and the parotid gland (a major salivary gland). Can f 2 belongs to the lipocalin/cytosolic fatty-acid binding protein family which have a large beta-barrel ligand-binding cavity. Lipocalins are mainly low molecular weight extracellular proteins that bind principally small hydrophobic ligands, and form covalent or non-covalent complexes with soluble macromolecules, as well as membrane bound-receptors. They participate in processes such as ligand transport, modulation of cell growth and metabolism, regulation of immune response, smell reception, tissue development and animal behavior. Cytosolic fatty-acid binding proteins, also bind hydrophobic ligands in a non-covalent, reversible manner, and have been implicated in intracellular uptake, transport and storage of hydrophobic ligands, regulation of lipid metabolism and sequestration of excess toxic fatty acids, as well as in signaling, gene expression, inflammation, cell growth and proliferation, and cancer development.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767957411  24 EEGGLHVHMEFPGADGCNQVDAEYLKVGSEGHFRVPALGYLDVRIVDTDYSSFAVLYIYKELEGALST----MVQLYSRT 99
Cdd:cd19431   48 KDGNLHGDILIPQDGQCEKVSLTAFKTATSNKFDLEYWGHNDLYLAEVDPKSYLILYMINQYNDDTSLvahlMVRDLSRQ 127

                         90       100       110
                 ....*....|....*....|....*....|....
gi 767957411 100 QDVSPqalkSFQDFYPTLGLPKDMMVMLPQSDAC 133
Cdd:cd19431  128 QDFLP----AFESVCEDIGLHKDQIVVLSDDDRC 157

lipocalin-1, -3, -4, -13 and similar proteins; Lipocalin-1 (LCN1, also known as tear lipocalin, von ebner's gland protein, or tear specific prealbumin), the main lipid carrier in human tears, is critical to functions involving lipids in protection of the ocular surface. Its large ligand pocket accommodates a range of ligands including alkyl alcohols, glycolipids, phospholipids, cholesterol, steroids, and siderophores. Lipocalin-3 (LCN3, also known as vomeronasal secretory protein 1) and lipocalin-4 (LCN4, also known as vomeronasal secretory protein 2) are involved in transport of lipophilic molecules, and are possibly pheromone-carriers. Lipocalin-13 (LCN13, also known as odorant binding protein 2A) may bind and transport small hydrophobic volatile molecules with a higher affinity for aldehydes and large fatty acids. Another member of this family is late lactation protein B (LLPB), a milk protein produced during the late phase of lactation, which may be involved in transporting a small ligand released during the hydrolysis of milk fat. This group belongs to the lipocalin/cytosolic fatty-acid binding protein family which have a large beta-barrel ligand-binding cavity. Lipocalins are mainly low molecular weight extracellular proteins that bind principally small hydrophobic ligands, and form covalent or non-covalent complexes with soluble macromolecules, as well as membrane bound-receptors. They participate in processes such as ligand transport, modulation of cell growth and metabolism, regulation of immune response, smell reception, tissue development and animal behavior. Cytosolic fatty-acid binding proteins, also bind hydrophobic ligands in a non-covalent, reversible manner, and have been implicated in intracellular uptake, transport and storage of hydrophobic ligands, regulation of lipid metabolism and sequestration of excess toxic fatty acids, as well as in signaling, gene expression, inflammation, cell growth and proliferation, and cancer development.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767957411  78 VLYIYKELEGALSTMVQLYSRTQDVSPQALKSFQDFYPTLGLPKDMMVMLPQSDAC 133
Cdd:cd19414   91 ILYCEGELHGMTFRMAKLVGRDPEENPEALEEFKKFVQRKGLNEENIVIPEQSETC 146

lipocalin 9; Lipocalin 9 (LCN9) is specifically expressed in the epididymis. It belongs to the lipocalin/cytosolic fatty-acid binding protein family. Lipocalins are typically small extracellular proteins that bind small hydrophobic molecules, such as lipids, steroid hormones, bilins, and retinoids and form covalent or non-covalent complexes with soluble macromolecules as well as membrane bound-receptors. They are involved in many important functions, like ligand transport, modulation of cell growth and metabolism, regulation of immune response, smell reception, tissue development and animal behavior.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767957411   7 LGKKDHLSMSTRAIRPTEEGGLHVHMEFPGADGCNQVDAEYLKVGSEGHFRVPALGYLDVRIVDTDYSSFAVLYIYKELE 86
Cdd:cd19429   30 IEENGDLRLFIRNIELLNNGSLQFDFHFMLQGECVAVTVVCEKTKKNGEFSIAYEGENKVLLLETDYSMYIIFYLQNIRN 109

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 767957411  87 GALSTMVQLYSRTQDVSPQALKSFQDFYPTLGLPKDMMVMLPQSDAC 133
Cdd:cd19429  110 GTETQVLALYGRSILLDKTHQRRFENICNKYGLGPRNTIDMAKKDFC 156