Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein; other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement; the binding of calcium is required for in vitro formation of the native disulfide isomer and is necessary in establishing and maintaining the modular structure

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 86561097 663 CLPGQFQCHdNHKCLPPGGLCDKVTDCSDSSDEIYC 698
Cdd:cd00112   1 CPPNEFRCA-NGRCIPSSWVCDGEDDCGDGSDEENC 35

Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 86561097 272 CLDVDECESLSSACSQKCVNLPGTFECTCDPRtYKLATDNKT 313
Cdd:cd01475 184 CVVPDLCATLSHVCQQVCISTPGSYLCACTEG-YALLEDNKT 224

Low-density lipoprotein-receptor YWTD domain; Type "B" repeats in low-density lipoprotein (LDL) receptor that plays a central role in mammalian cholesterol metabolism. Also present in a variety of molecules similar to gp300/megalin.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 86561097    343 QLQRAGLQKTAMIDIDVKENRLYYADIGANVIERMNIEGTF 383
Cdd:smart00135   2 TLLSSGLGHPNGLAVDWIEGRLYWTDWGLDVIEVANLDGTN 42

Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein; other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement; the binding of calcium is required for in vitro formation of the native disulfide isomer and is necessary in establishing and maintaining the modular structure

                        10        20        30
                ....*....|....*....|....*....|....*..
gi 86561097 622 CSESQIECGgaDPKCISKIYLCDGLAQCSNQADEEKC 658
Cdd:cd00112   1 CPPNEFRCA--NGRCIPSSWVCDGEDDCGDGSDEENC 35

Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein; other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement; the binding of calcium is required for in vitro formation of the native disulfide isomer and is necessary in establishing and maintaining the modular structure

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 86561097 663 CLPGQFQCHdNHKCLPPGGLCDKVTDCSDSSDEIYC 698
Cdd:cd00112   1 CPPNEFRCA-NGRCIPSSWVCDGEDDCGDGSDEENC 35

Low-density lipoprotein receptor domain class A; Cysteine-rich repeat in the low-density lipoprotein (LDL) receptor that plays a central role in mammalian cholesterol metabolism. The N-terminal type A repeats in LDL receptor bind the lipoproteins. Other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement. Mutations in the LDL receptor gene cause familial hypercholesterolemia.

                           10        20        30
                   ....*....|....*....|....*....|...
gi 86561097    663 CLPGQFQChDNHKCLPPGGLCDKVTDCSDSSDE 695
Cdd:smart00192   2 CPPGEFQC-DNGRCIPSSWVCDGVDDCGDGSDE 33

Low-density lipoprotein-receptor YWTD domain; Type "B" repeats in low-density lipoprotein (LDL) receptor that plays a central role in mammalian cholesterol metabolism. Also present in a variety of molecules similar to gp300/megalin.

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 86561097    513 RVIIADAGSVPHVFGLAIADDYLYWTDWTYRGILRAN 549
Cdd:smart00135   1 RTLLSSGLGHPNGLAVDWIEGRLYWTDWGLDVIEVAN 37

Calcium-binding EGF-like domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 86561097    274 DVDECESlSSACSQ--KCVNLPGTFECTCDPRTyklaTDNKTCE 315
Cdd:smart00179   1 DIDECAS-GNPCQNggTCVNTVGSYRCECPPGY----TDGRNCE 39

Low-density lipoprotein-receptor YWTD domain; Type "B" repeats in low-density lipoprotein (LDL) receptor that plays a central role in mammalian cholesterol metabolism. Also present in a variety of molecules similar to gp300/megalin.

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 86561097    391 DVDGLEGIAVDWIGRNLY--SLRREDILVQSLDGRFR 425
Cdd:smart00135   7 GLGHPNGLAVDWIEGRLYwtDWGLDVIEVANLDGTNR 43

Coagulation Factor Xa inhibitory site; This short domain on coagulation enzyme factor Xa is found to be the target for a potent inhibitor of coagulation, TAK-442.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 86561097   588 GCDQLCLLGENGaATCACGEGFDLLNDGKKC 618
Cdd:pfam14670   7 GCSHLCLNTPGG-YTCSCPEGYELQDDGRTC 36

Low-density lipoprotein receptor domain class A;

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 86561097   663 CLPGQFQCHDNhKCLPPGGLCDKVTDCSDSSDEIYC 698
Cdd:pfam00057   3 CSPNEFQCGSG-ECIPRSWVCDGDPDCGDGSDEENC 37

Uncharacterized NHL-repeat domain in bacterial proteins; The NHL (NCL-1, HT2A and LIN-41) repeat is found in multiple tandem copies, typically as 6 instances. It is about 40 residues long and resembles the WD repeat and other beta-propeller structures.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 86561097 345 QRAGLQKTAMIDIDV-KENRLYYADIGANVIERMNIEGTFPQAV-QRFDVDGLEGIAVDWIGRNLY--SLRREDILVQSL 420
Cdd:cd14962  50 NAGPNRFVSPIGVAIdANGNLYVSDAELGKVFVFDRDGKFLRAIgAGALFKRPTGIAVDPAGKRLYvvDTLAHKVKVFDL 129

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 86561097 421 DGRF----------RQPLYknvmtLPRSITLHPaKGIMFVTDwSANAFIAAASMDGShFRKIITERITW------PNAVA 484
Cdd:cd14962 130 DGRLlfdigkrgsgPGEFN-----LPTDLAVDR-DGNLYVTD-TMNFRVQIFDADGK-FLRSFGERGDGpgsfarPKGIA 201

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 86561097 485 VDIFAeKIYWADAFLDTIESanMDGTGRRVI-IADAGSVPHVF----GLAI-ADDYLYWTD 539
Cdd:cd14962 202 VDSEG-NIYVVDAAFDNVQI--FNPEGELLLtVGGPGSGPGEFylpsGIAIdKDDRIYVVD 259

Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein; other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement; the binding of calcium is required for in vitro formation of the native disulfide isomer and is necessary in establishing and maintaining the modular structure

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 86561097 663 CLPGQFQCHdNHKCLPPGGLCDKVTDCSDSSDEIYC 698
Cdd:cd00112   1 CPPNEFRCA-NGRCIPSSWVCDGEDDCGDGSDEENC 35

Low-density lipoprotein receptor domain class A; Cysteine-rich repeat in the low-density lipoprotein (LDL) receptor that plays a central role in mammalian cholesterol metabolism. The N-terminal type A repeats in LDL receptor bind the lipoproteins. Other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement. Mutations in the LDL receptor gene cause familial hypercholesterolemia.

                           10        20        30
                   ....*....|....*....|....*....|...
gi 86561097    663 CLPGQFQChDNHKCLPPGGLCDKVTDCSDSSDE 695
Cdd:smart00192   2 CPPGEFQC-DNGRCIPSSWVCDGVDDCGDGSDE 33

Low-density lipoprotein-receptor YWTD domain; Type "B" repeats in low-density lipoprotein (LDL) receptor that plays a central role in mammalian cholesterol metabolism. Also present in a variety of molecules similar to gp300/megalin.

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 86561097    513 RVIIADAGSVPHVFGLAIADDYLYWTDWTYRGILRAN 549
Cdd:smart00135   1 RTLLSSGLGHPNGLAVDWIEGRLYWTDWGLDVIEVAN 37

Calcium-binding EGF-like domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 86561097    274 DVDECESlSSACSQ--KCVNLPGTFECTCDPRTyklaTDNKTCE 315
Cdd:smart00179   1 DIDECAS-GNPCQNggTCVNTVGSYRCECPPGY----TDGRNCE 39

Calcium-binding EGF domain;

                          10        20        30
                  ....*....|....*....|....*....|.
gi 86561097   274 DVDECESLSSACSQ--KCVNLPGTFECTCDP 302
Cdd:pfam07645   1 DVDECATGTHNCPAntVCVNTIGSFECRCPD 31

Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein; other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement; the binding of calcium is required for in vitro formation of the native disulfide isomer and is necessary in establishing and maintaining the modular structure

                        10        20        30
                ....*....|....*....|....*....|....*..
gi 86561097 622 CSESQIECGgaDPKCISKIYLCDGLAQCSNQADEEKC 658
Cdd:cd00112   1 CPPNEFRCA--NGRCIPSSWVCDGEDDCGDGSDEENC 35

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                        10        20        30
                ....*....|....*....|....*....|
gi 86561097 274 DVDECESLSS-ACSQKCVNLPGTFECTCDP 302
Cdd:cd00054   1 DIDECASGNPcQNGGTCVNTVGSYRCSCPP 30

Low-density lipoprotein receptor domain class A;

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 86561097   663 CLPGQFQCHDNhKCLPPGGLCDKVTDCSDSSDEIYC 698
Cdd:pfam00057   3 CSPNEFQCGSG-ECIPRSWVCDGDPDCGDGSDEENC 37

Uncharacterized NHL-repeat domain in bacterial proteins; The NHL (NCL-1, HT2A and LIN-41) repeat is found in multiple tandem copies, typically as 6 instances. It is about 40 residues long and resembles the WD repeat and other beta-propeller structures.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 86561097 345 QRAGLQKTAMIDIDV-KENRLYYADIGANVIERMNIEGTFPQAV-QRFDVDGLEGIAVDWIGRNLY--SLRREDILVQSL 420
Cdd:cd14962  50 NAGPNRFVSPIGVAIdANGNLYVSDAELGKVFVFDRDGKFLRAIgAGALFKRPTGIAVDPAGKRLYvvDTLAHKVKVFDL 129

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 86561097 421 DGRF----------RQPLYknvmtLPRSITLHPaKGIMFVTDwSANAFIAAASMDGShFRKIITERITW------PNAVA 484
Cdd:cd14962 130 DGRLlfdigkrgsgPGEFN-----LPTDLAVDR-DGNLYVTD-TMNFRVQIFDADGK-FLRSFGERGDGpgsfarPKGIA 201

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 86561097 485 VDIFAeKIYWADAFLDTIESanMDGTGRRVI-IADAGSVPHVF----GLAI-ADDYLYWTD 539
Cdd:cd14962 202 VDSEG-NIYVVDAAFDNVQI--FNPEGELLLtVGGPGSGPGEFylpsGIAIdKDDRIYVVD 259