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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148709761  16 FTMMALCSLPLLGASATLNsVLINSNAIKNLPPPLGGAGGQPGSAVSVAPGVLYEGGNKYQTLDNYQPYPCAEDEECGSD 95
Cdd:cd23026    1 FVALALCSHPLLGVSATLN-MLLNSNAIKNLPPPLGGAAGHPGSAVSAAPGILYDGGNKYQTIDNYQPYPCAEDEECGTD 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 148709761  96 EYCSSPSrgaaGVGGVQICLACRKRRKRCMRHAMCCPGNYCKNGICM 142
Cdd:cd23026   80 EYCASPT----GVGGVQICLACRKRRKRCMRHAMCCPGNYCKNGICM 122

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148709761  16 FTMMALCSLPLLGASATLNsVLINSNAIKNLPPPLGGAGGQPGSAVSVAPGVLYEGGNKYQTLDNYQPYPCAEDEECGSD 95
Cdd:cd23026    1 FVALALCSHPLLGVSATLN-MLLNSNAIKNLPPPLGGAAGHPGSAVSAAPGILYDGGNKYQTIDNYQPYPCAEDEECGTD 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 148709761  96 EYCSSPSrgaaGVGGVQICLACRKRRKRCMRHAMCCPGNYCKNGICM 142
Cdd:cd23026   80 EYCASPT----GVGGVQICLACRKRRKRCMRHAMCCPGNYCKNGICM 122

Dickkopf N-terminal cysteine-rich region; Dickkopf proteins are a class of Wnt antagonists. They possess two conserved cysteine-rich regions. This family represents the N-terminal one. The C-terminal region has been found to share significant sequence similarity to the colipase fold, pfam01114, pfam02740.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 148709761   85 PCAEDEECGSDEYCSSPSRGAagvggvqICLACRKRRKRCMRHAMCCPGNYCKNGICM 142
Cdd:pfam04706   1 ECLSDEDCGKGKYCLSSSGES-------VCLPCRKRRKRCTRDAMCCPGNLCVNGVCV 51

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148709761  16 FTMMALCSLPLLGASATLNsVLINSNAIKNLPPPLGGAGGQPGSAVSVAPGVLYEGGNKYQTLDNYQPYPCAEDEECGSD 95
Cdd:cd23026    1 FVALALCSHPLLGVSATLN-MLLNSNAIKNLPPPLGGAAGHPGSAVSAAPGILYDGGNKYQTIDNYQPYPCAEDEECGTD 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 148709761  96 EYCSSPSrgaaGVGGVQICLACRKRRKRCMRHAMCCPGNYCKNGICM 142
Cdd:cd23026   80 EYCASPT----GVGGVQICLACRKRRKRCMRHAMCCPGNYCKNGICM 122

Colipase and the second cysteine-rich (Cys-2) domain of Dickkopf proteins; Colipase (also called CLPS) is a cysteine-rich protein that adopts a similar fold to a cysteine-rich domain (Cys-2) of the Dickkopf (Dkk) family proteins. Colipase functions to prevent the inhibitory effect of bile salts on lipase-catalyzed intraduodenal hydrolysis of dietary long-chain triglycerides. Dickkopf proteins are a discrete class of secreted Wnt inhibitors that are required for many developmental processes, including segmentation, endoderm development, limb polarity, neural crest differentiation, kidney morphogenesis, sex determination and brain development. They possess an N-terminal signal peptide and contain two conserved cysteine-rich domains (Cys-1 and Cys-2) separated by a linker region. The Dickkopf Cys-2 domain is similar to proteins in the colipase family and it has been suggested that the Cys-2 domain of Dkks may enable interaction with lipids in order to regulate Wnt function.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148709761 188 KGQEGSVCLRSSDCAAGLCCARHFWSKICKPVLKEGQVCTKHKRKGSHGLEIFQRCYCGEGLACRIQKDHHQASNSSRLH 267
Cdd:cd23008    1 KGDEGELCLRSSDCKSGNCCARHFWLKICKPVLREGSVCTKFRLKGSHGLEIFQRCPCERGLSCEGDKDLVGSSTNTRLH 80

                 ..
gi 148709761 268 TC 269
Cdd:cd23008   81 IC 82

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 148709761 188 KGQEGSVCLRSSDCAAGLCCARHFWSKICKPVLKEGQVCTKHKRK-GSHGLEIFQRCYCGEGLACRIQKDhhQASNSSRL 266
Cdd:cd23275   11 KGQEGESCLRTSDCGPGLCCARHFWTKICKPVLLEGQVCSRRGHKdTAQGPEIFQRCDCGPGLSCRSQLT--GNRQHSRL 88

                 ....*.
gi 148709761 267 HTCQRH 272
Cdd:cd23275   89 RVCQRI 94

first cysteine-rich (Cys-1) domain of Dickkopf proteins; The Dickkopf (Dkk) family 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 Dickkopf proteins 1- 4.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 148709761  85 PCAEDEECGSDEYCSSPSRGaagvggVQICLACRKRRKRCMRHAMCCPGNYCKNGIC 141
Cdd:cd23009    1 PCISDEDCGTSMYCQSPSDG------QYTCQPCRGQRKRCTRDAMCCPGTLCVNGIC 51

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 148709761  82 QPYPCAEDEECGSDEYCSSPSRGAAGvggvqiCLACRKRRKRCMRHAMCCPGNYCKNGICM 142
Cdd:cd23015    1 QAYPCSSDKECEVGRYCHSPHQAPSR------CMTCRRKKKRCHRDGMCCPGNRCSNGICI 55