first cysteine-rich (Cys-1) domain of Dickkopf-related protein 2; Dickkopf 2 (Dkk2) is a secreted protein which directly binds to LRP5/6 (low-density lipoprotein receptor related protein 5 and 6), and is an inhibitor of Wnt/beta-catenin signaling. Dkk2 expression is modulated by expression of micro RNA-221 (miRNA-221) in esophageal cancer, and inactivation of Dkk2 may increase Wnt activity with accelerating tumor progression. Dkk2 belongs to the Dickkopf (Dkk) family that comprises a discrete class of secreted Wnt inhibitors. The Wnt gene family is a large class of secreted proteins that are expressed in a variety of tissues and organs, and are required for many developmental processes, including segmentation, endoderm development, limb polarity, neural crest differentiation, kidney morphogenesis, sex determination and brain development. Dkks 1-4 each possesses an N-terminal signal peptide and contains two conserved cysteine-rich domains (Cys-1 and Cys-2) separated by a linker region. Each domain possesses 10 conserved cysteine residues. The Cys-2 domain is closely similar to those in the colipase family; it has been suggested that the Cys-2 domain of Dkks may enable interaction with lipids in order to regulate Wnt function. This model corresponds to the Cys-1 domain of Dkk2.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 157816965  74 QAYPCSSDKECEVGRYCHSPHQGSSACMVCRRKKKRCHRDGMCCPGTRCNNGICI 128
Cdd:cd23015    1 QAYPCSSDKECEVGRYCHSPHQAPSRCMTCRRKKKRCHRDGMCCPGNRCSNGICI 55

first cysteine-rich (Cys-1) domain of Dickkopf-related protein 2; Dickkopf 2 (Dkk2) is a secreted protein which directly binds to LRP5/6 (low-density lipoprotein receptor related protein 5 and 6), and is an inhibitor of Wnt/beta-catenin signaling. Dkk2 expression is modulated by expression of micro RNA-221 (miRNA-221) in esophageal cancer, and inactivation of Dkk2 may increase Wnt activity with accelerating tumor progression. Dkk2 belongs to the Dickkopf (Dkk) family that comprises a discrete class of secreted Wnt inhibitors. The Wnt gene family is a large class of secreted proteins that are expressed in a variety of tissues and organs, and are required for many developmental processes, including segmentation, endoderm development, limb polarity, neural crest differentiation, kidney morphogenesis, sex determination and brain development. Dkks 1-4 each possesses an N-terminal signal peptide and contains two conserved cysteine-rich domains (Cys-1 and Cys-2) separated by a linker region. Each domain possesses 10 conserved cysteine residues. The Cys-2 domain is closely similar to those in the colipase family; it has been suggested that the Cys-2 domain of Dkks may enable interaction with lipids in order to regulate Wnt function. This model corresponds to the Cys-1 domain of Dkk2.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 157816965  74 QAYPCSSDKECEVGRYCHSPHQGSSACMVCRRKKKRCHRDGMCCPGTRCNNGICI 128
Cdd:cd23015    1 QAYPCSSDKECEVGRYCHSPHQAPSRCMTCRRKKKRCHRDGMCCPGNRCSNGICI 55

second cysteine-rich (Cys-2) domain of Dickkopf-related protein 1; Dickkopf-1 (Dkk1) is a secreted protein which directly binds to LRP5/6 (low-density lipoprotein receptor related protein 5 and 6), and is an inhibitor of Wnt/beta-catenin signaling. Elevated expression of Dkk-1 may serve as a negative regulator for modulating the wnt/#-catenin signal pathway. Dkk1 is expressed in various human cancers. It has been studied extensively in mouse models of multiple myeloma that results in osteolytic bone lesions. Studies show that Dkk1 levels in bone marrow plasma and serum inhibit the differentiation of osteoblast precursors. Dkk1 belongs to the Dickkopf (Dkk) family that comprises a discrete class of secreted Wnt inhibitors. The Wnt gene family is a large class of secreted proteins that are expressed in a variety of tissues and organs, and are required for many developmental processes, including segmentation, endoderm development, limb polarity, neural crest differentiation, kidney morphogenesis, sex determination and brain development. Dkks 1-4 each possesses an N-terminal signal peptide and contains two conserved cysteine-rich domains (Cys-1 and Cys-2) separated by a linker region. Each domain possesses 10 conserved cysteine residues. The Cys-2 domain is closely similar to those in the colipase family; it has been suggested that the Cys-2 domain of Dkks may enable interaction with lipids in order to regulate Wnt function. This model corresponds to the Cys-2 domain of Dkk1.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157816965 176 KGHEGDPCLRSSDCIDGFCCARHFWTKICKPVLHQGEVCTKQRKKGSHGLEIFQRCDCAKGLSCKVWKDATYSSKAR-LH 254
Cdd:cd23272    1 KGQEGDTCLRSSDCSEGLCCARHFWSKICKPVLKEGQVCTKHRRKGSHGLEIFQRCDCGDGLSCRTQRGDHGASASRrLH 80

                 ...
gi 157816965 255 VCQ 257
Cdd:cd23272   81 TCQ 83

second cysteine-rich (Cys-2) domain of Dickkopf-related protein 4; Dickkopf 4 (Dkk4) is a secreted protein which directly binds to LRP5/6 (low-density lipoprotein receptor related protein 5 and 6), and is an inhibitor of Wnt/beta-catenin signaling. Dkk4, which is upregulated by the activated Wnt pathway, contributes to tumor malignancy in variable tumors, promoting tumor cell invasion and progression. Aberrant accumulation of Dkk4 has been shown to promote tumor progression by forming the immune suppressive microenvironment in gastrointestinal stromal tumor, and thus Dkk4 may be used as a tumor biomarker for prognosis prediction and recurrence monitoring. Dkk4 belongs to the Dickkopf (Dkk) family that comprises a discrete class of secreted Wnt inhibitors. The Wnt gene family is a large class of secreted proteins that are expressed in a variety of tissues and organs, and are required for many developmental processes, including segmentation, endoderm development, limb polarity, neural crest differentiation, kidney morphogenesis, sex determination and brain development. Dkks 1-4 each possesses an N-terminal signal peptide and contains two conserved cysteine-rich domains (Cys-1 and Cys-2) separated by a linker region. Each domain possesses 10 conserved cysteine residues. The Cys-2 domain is closely similar to those in the colipase family; it has been suggested that the Cys-2 domain of Dkks may enable interaction with lipids in order to regulate Wnt function. This model corresponds to the Cys-2 domain of Dkk4.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157816965 171 KMPHIKGHEGDPCLRSSDCIDGFCCARHFWTKICKPVLHQGEVCTKQ-RKKGSHGLEIFQRCDCAKGLSCKVWKDATySS 249
Cdd:cd23275    6 KSQSSKGQEGESCLRTSDCGPGLCCARHFWTKICKPVLLEGQVCSRRgHKDTAQGPEIFQRCDCGPGLSCRSQLTGN-RQ 84

                         90
                 ....*....|
gi 157816965 250 KARLHVCQKI 259
Cdd:cd23275   85 HSRLRVCQRI 94

first cysteine-rich (Cys-1) domain of Dickkopf-related protein 2; Dickkopf 2 (Dkk2) is a secreted protein which directly binds to LRP5/6 (low-density lipoprotein receptor related protein 5 and 6), and is an inhibitor of Wnt/beta-catenin signaling. Dkk2 expression is modulated by expression of micro RNA-221 (miRNA-221) in esophageal cancer, and inactivation of Dkk2 may increase Wnt activity with accelerating tumor progression. Dkk2 belongs to the Dickkopf (Dkk) family that comprises a discrete class of secreted Wnt inhibitors. The Wnt gene family is a large class of secreted proteins that are expressed in a variety of tissues and organs, and are required for many developmental processes, including segmentation, endoderm development, limb polarity, neural crest differentiation, kidney morphogenesis, sex determination and brain development. Dkks 1-4 each possesses an N-terminal signal peptide and contains two conserved cysteine-rich domains (Cys-1 and Cys-2) separated by a linker region. Each domain possesses 10 conserved cysteine residues. The Cys-2 domain is closely similar to those in the colipase family; it has been suggested that the Cys-2 domain of Dkks may enable interaction with lipids in order to regulate Wnt function. This model corresponds to the Cys-1 domain of Dkk2.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 157816965  74 QAYPCSSDKECEVGRYCHSPHQGSSACMVCRRKKKRCHRDGMCCPGTRCNNGICI 128
Cdd:cd23015    1 QAYPCSSDKECEVGRYCHSPHQAPSRCMTCRRKKKRCHRDGMCCPGNRCSNGICI 55

N-terminus of Dickkopf-related protein 1; includes the first cysteine-rich (Cys-1) domain; Dickkopf-1 (Dkk1) is a secreted protein which directly binds to LRP5/6 (low-density lipoprotein receptor related protein 5 and 6), and is an inhibitor of Wnt/beta-catenin signaling. Elevated expression of Dkk-1 may serve as a negative regulator for modulating the wnt/#-catenin signal pathway. Dkk1 is expressed in various human cancers. It has been studied extensively in mouse models of multiple myeloma that results in osteolytic bone lesions. Studies show that Dkk1 levels in bone marrow plasma and serum inhibit the differentiation of osteoblast precursors. Dkk1 belongs to the Dickkopf (Dkk) family that comprises a discrete class of secreted Wnt inhibitors. The Wnt gene family is a large class of secreted proteins that are expressed in a variety of tissues and organs, and are required for many developmental processes, including segmentation, endoderm development, limb polarity, neural crest differentiation, kidney morphogenesis, sex determination and brain development. Dkks 1-4 each possesses an N-terminal signal peptide and contains two conserved cysteine-rich domains (Cys-1 and Cys-2) separated by a linker region. Each domain possesses 10 conserved cysteine residues. The Cys-2 domain is closely similar to those in the colipase family; it has been suggested that the Cys-2 domain of Dkks may enable interaction with lipids in order to regulate Wnt function. This model corresponds to the N-terminal region of Dkk1, including the Cys-1 domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 157816965  74 QAYPCSSDKECEVGRYCHSPHQ--GSSACMVCRRKKKRCHRDGMCCPGTRCNNGICI 128
Cdd:cd23026   66 QPYPCAEDEECGTDEYCASPTGvgGVQICLACRKRRKRCMRHAMCCPGNYCKNGICM 122

first cysteine-rich (Cys-1) domain of Dickkopf-related protein 4; Dickkopf 4 (Dkk4) is a secreted protein which directly binds to LRP5/6 (low-density lipoprotein receptor related protein 5 and 6), and is an inhibitor of Wnt/beta-catenin signaling. Dkk4, which is upregulated by the activated Wnt pathway, contributes to tumor malignancy in variable tumors, promoting tumor cell invasion and progression. Aberrant accumulation of Dkk4 has been shown to promote tumor progression by forming the immune suppressive microenvironment in gastrointestinal stromal tumor, and thus Dkk4 may be used as a tumor biomarker for prognosis prediction and recurrence monitoring. Dkk4 belongs to the Dickkopf (Dkk) family that comprises a discrete class of secreted Wnt inhibitors. The Wnt gene family is a large class of secreted proteins that are expressed in a variety of tissues and organs, and are required for many developmental processes, including segmentation, endoderm development, limb polarity, neural crest differentiation, kidney morphogenesis, sex determination and brain development. Dkks 1-4 each possesses an N-terminal signal peptide and contains two conserved cysteine-rich domains (Cys-1 and Cys-2) separated by a linker region. Each domain possesses 10 conserved cysteine residues. The Cys-2 domain is closely similar to those in the colipase family; it has been suggested that the Cys-2 domain of Dkks may enable interaction with lipids in order to regulate Wnt function. This model corresponds to the Cys-1 domain of Dkk4.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 157816965  74 QAYPCSSDKECEVGRYCHSPHQGSSACMVCRRKKKRCHRDGMCCPGTRCNNGIC 127
Cdd:cd23013    1 KGSQCLSDKDCSTRKFCLAPRDEKPFCATCRGVRRRCQRSAMCCPGTLCVNDVC 54