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 1039762321  71 SGTWYLDSIASDNmTRIEENGDLRLFIRNIKLLNNGSLQFDFHFMLQGECVAVTMVCEKTKNNGEFSV---AYEGKNKVL 147
Cdd:pfam00061   1 SGKWYLIASANFN-ELEEEMKALGVGFATIKVLENGNLPVTEITKEGGKCKTVSVTFKKTEEPGKLGVefdEYAGGRKVK 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1039762321 148 LLETDYSMYIIFYMQNIKNGTKTQVLALYGRSILLDKTHQREFENICNLYGLDSQNIIDMTKKA 211
Cdd:pfam00061  80 VLTTDYDNYLIFYQKGDKDGKTTIVRELYGRDPELSPELLEKFKKFLKELGIDEENIVRLYQKD 143

major urinary proteins (MUPs) and similar proteins; Mouse urine contains major urinary proteins (MUPs) which bind low molecular weight hydrophobic organic compounds such as urinary volatile pheromones such as the male-specific 2-sec-butyl-4,5-dihydrothiazole (SB2HT) which hastens puberty in female mice. The association between MUPs and these volatiles slows the release of the volatiles into the air from urine marks. MUPs may also act as pheromones themselves. MUPs, expressed in the nasal and vomeronasal mucosa, may be important for delivering urinary volatiles to receptors in the vomeronasal organ. This group includes MUPs encoded by central genes in the MUP cluster, as well as those encoded by peripheral genes such as Darcin/Mup20 which binds most of the male pheromone SB2HT in urine and was the first MUP shown to have male pheromonal activity in its own right. This group includes rat MUPs (also called alpha-2U globulins) and other lipocalins such as major horse allergen Equ c 1 and boar salivary lipocalin, a pheromone-binding protein specifically expressed in the submaxillary glands of the boar. 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 1039762321  69 QISGTWYLDSIASDNMTRIEENGDLRLFIRNIKLLNNgSLQFDFHFMLQGECVAVTMVCEKTKNNGEFSVAYEGKNKVLL 148
Cdd:cd19428    10 KINGEWYSILLASDKREKIEENGSMRVFVEHIHVLEN-SLAFKFHTKVNGECTELNLVADKTEKAGEYSVTYDGYNTFTI 88

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1039762321 149 LETDYSMYIIFYMQNIKNGTKTQVLALYGRSILLDKTHQREFENICNLYGLDSQNIIDMTK 209
Cdd:cd19428    89 LETDYDNYIMFHLINFKNGETFQLMELYGREPDVSSDIKERFVKLCEEHGIIKENIIDLTK 149

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 1039762321  69 QISGTWYLDSIASDNmtriEENGDLRLFIRNIKLLNNGSLQFDFHFMLQGECVAVTMVCEKTKNNGEFSVAYE---GKNK 145
Cdd:cd00301     1 KFSGKWYEVASASNA----PEEDEGKCTTAEYTLEGNGNLKVTNSFVRDGVCKSITGTLKKTDGPGKFTVTYPgytGKNE 76

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1039762321 146 VLLLETDYSMYIIFYMQNIKNGTKTQVLALYGR 178
Cdd:cd00301    77 LYVLSTDYDNYAIVYSCKNLDGGHTVVAWLLSR 109

beta-lactoglobulin and similar proteins; Beta-Lactoglobulin (beta-LG) is the major whey protein of ruminant species and present in the milk of many other species, with a notable exception of human. It is the major allergen of bovine milk. Beta-LG has been shown to bind hydrophobic ligands such as curcumin, vitamin E or fatty acids, or hydrophilic such as vitamin B9. This group also includes human glycodelin (also known as placental protein 14, pregnancy-associated endometrial alpha-2 globulin, and progestagen-associated endometrial protein) which is involved in crucial biological processes such as reproduction and immune reaction. Four glycoforms of glycodelin have been identified in reproductive tissue that differ in glycosylation and biological activity. 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 1039762321  69 QISGTWYLDSIASDNMTRIE-ENGDLRLFIRNIKLLNNGSLQFDFHFMLQGECVAVTMVCEKTKNNGEFSVAYEGKNKVL 147
Cdd:cd19416    12 KVAGTWYSLAMAASDISLLDaQSAPLRVYIEELKPTPEGNLEIVLQKWENGRCAEKKLLAEKTKIPAVFKINALNENKVL 91

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1039762321 148 LLETDYSMYIIFYMQNIKNGTKTQVLALYGRSILLDKTHQREFENI 193
Cdd:cd19416    92 VLDTDYDSYLLFCMENSAEPEQSLACQCLVRTLEVDNEAMEKFDKA 137

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039762321  69 QISGTWYLDSIASD-NMTriEENGDLRLFIRNIKLLNNGSLQFDFHFMLQGECVAVTMVCEKTKNNGEFSvAYEGKNKVL 147
Cdd:cd19414     4 DVSGTWYLKAMVVDkEFP--EKRRPRKVSPVTVTALEGGNLEAKFTFMINGRCEEVKIVLEKTDEPGKYT-AFSGKKVVY 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1039762321 148 LLETDYSMYIIFYMQNIKNGTKTQVLALYGRSilldkTHQ-----REFENICNLYGLDSQNII 205
Cdd:cd19414    81 IQETSVKDHYILYCEGELHGMTFRMAKLVGRD-----PEEnpealEEFKKFVQRKGLNEENIV 138

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 1039762321  69 QISGTWYLDSIASDNMTRIEENGDLRLFIRNIKLLNNGSLQFDFHFMLQGECVAVTMVCEKTKNNGEFSVAYEGKNKVLL 148
Cdd:cd19422     1 KFAGLWHVMAMASDCPVFLGMKDHMTSSTTAIRPTPEGDLTMHTEFPLPDGCKQIEAEFQKSGQAGHFRVPELGKRDLRV 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1039762321 149 LETDYSMYIIFYMQNIKNGTKTQVLALYGRS 179
Cdd:cd19422    81 MDTDYSSYAILYIYKELEGESSTMVQLYTRN 111

lipocalin-type prostaglandin D synthase; Lipocalin-type prostaglandin D synthase (L-PGDS; EC:5.3.99.2) is a secreted enzyme and the second most abundant protein in human cerebrospinal fluid. L-PGDS acts as both, an enzyme and as a lipid transporter, converting prostaglandin H2 to prostaglandin D2 and serving as a carrier for hydrophobic ligands including retinoids, hemoglobin metabolites, thyroid hormones, gangliosides, and fatty acids. L-PGDS belongs to the lipocalin/cytosolic fatty-acid binding protein family which has 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 1039762321  68 FQIS---GTWYLDSIASDNMTRIEENGDLRLFIRNIKLLNNGSLQFDFHFMLQGECVAVTMVCEKTKNNGEF---SVAYE 141
Cdd:cd19419     5 FDLDkfaGRWYSVGLASNSNWFVEKKAKLKMCTTVVAPTTDGNLNLTMTFLKKNGCETRTYLYEKTEQPGRFtykSPRWG 84

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1039762321 142 GKNKVLLLETDYSMYIIFYMQNIKNGTKTQVLALYGRSILLDKTHQREFENICNLYGLDSQNIIDMTK 209
Cdd:cd19419    85 SDHDVRVVETNYDEYALVHTIKTKGNEEFTMVTLYSRTQTLRPELKEKFRQFAKAQGFTEENIVTLPQ 152

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 1039762321  69 QISGTWYLDSIASD--NMTRIEEN---GDLRLfirnIKLLNNGSLQFDFHFMLQGECVAVTMVCEKTKNNGEFSVAYEGK 143
Cdd:cd19418    12 RIYGKWYDLAVGSTcpWLKRIKDKmaiGTLVL----QEGATGAELSMTRTRLRRGTCEEISGEYEKTDTPGKFLYHKSKW 87

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1039762321 144 NKVL---LLETDYSMYIIFYMQNIK-NGTKTQVLALYGRSILLDKTHQREFENICNLYGLDSQNIIDMTKK 210
Cdd:cd19418    88 NATVdayVVHTNYDEYAIFLMKKFKrHGEPTTTLKLYGRTPQLRPTLLQDFRTLALEQGIPEDSIIIKADK 158