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Conserved domains on  [gi|1331924211|gb|PNJ72115|]
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DKK1 isoform 1 [Pongo abelii]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
Dkk1_N_Cys1 cd23026
N-terminus of Dickkopf-related protein 1; includes the first cysteine-rich (Cys-1) domain; ...
 16-139 4.71e-62

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.


:

Pssm-ID: 438010 [Multi-domain]  Cd Length: 122  Bit Score: 191.26  E-value: 4.71e-62
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331924211  16 LVAAALGGHPLLGVSATLNSVLNSNAIKNLPPPLGGAAGHPGSAVSAAPGILYPGGNKYQTIDNYQPYPCAEDQECGTDE 95
Cdd:cd23026     1 FVALALCSHPLLGVSATLNMLLNSNAIKNLPPPLGGAAGHPGSAVSAAPGILYDGGNKYQTIDNYQPYPCAEDEECGTDE 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1331924211  96 YCASPTRGGDAvvQICLACRKRRKRCMRHAMCCPGNYCKNGICV 139
Cdd:cd23026    81 YCASPTGVGGV--QICLACRKRRKRCMRHAMCCPGNYCKNGICM 122
Dkk1_Cys2 cd23272
second cysteine-rich (Cys-2) domain of Dickkopf-related protein 1; Dickkopf-1 (Dkk1) is a ...
 182-264 6.00e-58

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.


:

Pssm-ID: 437998  Cd Length: 83  Bit Score: 179.50  E-value: 6.00e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331924211 182 KGQEGSVCLRSSDCATGLCCARHFWSKICKPVLKEGQVCTKHRRKGSHGLEIFQRCYCGEGLSCRIQKDHHQASNSSRLH 261
Cdd:cd23272     1 KGQEGDTCLRSSDCSEGLCCARHFWSKICKPVLKEGQVCTKHRRKGSHGLEIFQRCDCGDGLSCRTQRGDHGASASRRLH 80


                  ...
gi 1331924211 262 TCQ 264
Cdd:cd23272    81 TCQ 83
 
Name Accession Description Interval E-value
Dkk1_N_Cys1 cd23026
N-terminus of Dickkopf-related protein 1; includes the first cysteine-rich (Cys-1) domain; ...
 16-139 4.71e-62

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.


Pssm-ID: 438010 [Multi-domain]  Cd Length: 122  Bit Score: 191.26  E-value: 4.71e-62
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331924211  16 LVAAALGGHPLLGVSATLNSVLNSNAIKNLPPPLGGAAGHPGSAVSAAPGILYPGGNKYQTIDNYQPYPCAEDQECGTDE 95
Cdd:cd23026     1 FVALALCSHPLLGVSATLNMLLNSNAIKNLPPPLGGAAGHPGSAVSAAPGILYDGGNKYQTIDNYQPYPCAEDEECGTDE 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1331924211  96 YCASPTRGGDAvvQICLACRKRRKRCMRHAMCCPGNYCKNGICV 139
Cdd:cd23026    81 YCASPTGVGGV--QICLACRKRRKRCMRHAMCCPGNYCKNGICM 122
Dkk1_Cys2 cd23272
second cysteine-rich (Cys-2) domain of Dickkopf-related protein 1; Dickkopf-1 (Dkk1) is a ...
 182-264 6.00e-58

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.


Pssm-ID: 437998  Cd Length: 83  Bit Score: 179.50  E-value: 6.00e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331924211 182 KGQEGSVCLRSSDCATGLCCARHFWSKICKPVLKEGQVCTKHRRKGSHGLEIFQRCYCGEGLSCRIQKDHHQASNSSRLH 261
Cdd:cd23272     1 KGQEGDTCLRSSDCSEGLCCARHFWSKICKPVLKEGQVCTKHRRKGSHGLEIFQRCDCGDGLSCRTQRGDHGASASRRLH 80


                  ...
gi 1331924211 262 TCQ 264
Cdd:cd23272    81 TCQ 83
Dickkopf_N pfam04706
Dickkopf N-terminal cysteine-rich region; Dickkopf proteins are a class of Wnt antagonists. ...
 84-139 1.00e-07

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.


Pssm-ID: 461401  Cd Length: 51  Bit Score: 47.37  E-value: 1.00e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1331924211  84 PCAEDQECGTDEYCASPTRGGdavvqICLACRKRRKRCMRHAMCCPGNYCKNGICV 139
Cdd:pfam04706   1 ECLSDEDCGKGKYCLSSSGES-----VCLPCRKRRKRCTRDAMCCPGNLCVNGVCV 51
 
Name Accession Description Interval E-value
Dkk1_N_Cys1 cd23026
N-terminus of Dickkopf-related protein 1; includes the first cysteine-rich (Cys-1) domain; ...
 16-139 4.71e-62

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.


Pssm-ID: 438010 [Multi-domain]  Cd Length: 122  Bit Score: 191.26  E-value: 4.71e-62
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331924211  16 LVAAALGGHPLLGVSATLNSVLNSNAIKNLPPPLGGAAGHPGSAVSAAPGILYPGGNKYQTIDNYQPYPCAEDQECGTDE 95
Cdd:cd23026     1 FVALALCSHPLLGVSATLNMLLNSNAIKNLPPPLGGAAGHPGSAVSAAPGILYDGGNKYQTIDNYQPYPCAEDEECGTDE 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1331924211  96 YCASPTRGGDAvvQICLACRKRRKRCMRHAMCCPGNYCKNGICV 139
Cdd:cd23026    81 YCASPTGVGGV--QICLACRKRRKRCMRHAMCCPGNYCKNGICM 122
Dkk1_Cys2 cd23272
second cysteine-rich (Cys-2) domain of Dickkopf-related protein 1; Dickkopf-1 (Dkk1) is a ...
 182-264 6.00e-58

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.


Pssm-ID: 437998  Cd Length: 83  Bit Score: 179.50  E-value: 6.00e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331924211 182 KGQEGSVCLRSSDCATGLCCARHFWSKICKPVLKEGQVCTKHRRKGSHGLEIFQRCYCGEGLSCRIQKDHHQASNSSRLH 261
Cdd:cd23272     1 KGQEGDTCLRSSDCSEGLCCARHFWSKICKPVLKEGQVCTKHRRKGSHGLEIFQRCDCGDGLSCRTQRGDHGASASRRLH 80


                  ...
gi 1331924211 262 TCQ 264
Cdd:cd23272    81 TCQ 83
CLPS_Dkk_Cys2 cd23008
Colipase and the second cysteine-rich (Cys-2) domain of Dickkopf proteins; Colipase (also ...
 182-263 3.30e-41

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.


Pssm-ID: 437995  Cd Length: 82  Bit Score: 136.67  E-value: 3.30e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331924211 182 KGQEGSVCLRSSDCATGLCCARHFWSKICKPVLKEGQVCTKHRRKGSHGLEIFQRCYCGEGLSCRIQKDHHQASNSSRLH 261
Cdd:cd23008     1 KGDEGELCLRSSDCKSGNCCARHFWLKICKPVLREGSVCTKFRLKGSHGLEIFQRCPCERGLSCEGDKDLVGSSTNTRLH 80


                  ..
gi 1331924211 262 TC 263
Cdd:cd23008    81 IC 82
Dkk2_Cys2 cd23273
second cysteine-rich (Cys-2) domain of Dickkopf-related protein 2; Dickkopf 2 (Dkk2) is a ...
 181-265 7.35e-40

second cysteine-rich (Cys-2) 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-2 domain of Dkk2.


Pssm-ID: 437999  Cd Length: 84  Bit Score: 133.05  E-value: 7.35e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331924211 181 TKGQEGSVCLRSSDCATGLCCARHFWSKICKPVLKEGQVCTKHRRKGSHGLEIFQRCYCGEGLSCRIQKDhHQASNSSRL 260
Cdd:cd23273     1 IKGHEGDPCLRSSDCAEGFCCARHFWTKICKPVLRQGEVCTKQRRKGSHGLEIFQRCDCAKGLSCKVWKD-ATASSKSRL 79


                  ....*
gi 1331924211 261 HTCQR 265
Cdd:cd23273    80 HVCQK 84
Dkk4_Cys2 cd23275
second cysteine-rich (Cys-2) domain of Dickkopf-related protein 4; Dickkopf 4 (Dkk4) is a ...
 177-266 1.28e-37

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.


Pssm-ID: 438001  Cd Length: 94  Bit Score: 127.79  E-value: 1.28e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331924211 177 KMYHTKGQEGSVCLRSSDCATGLCCARHFWSKICKPVLKEGQVCTKHRRK-GSHGLEIFQRCYCGEGLSCRIQKDhhQAS 255
Cdd:cd23275     6 KSQSSKGQEGESCLRTSDCGPGLCCARHFWTKICKPVLLEGQVCSRRGHKdTAQGPEIFQRCDCGPGLSCRSQLT--GNR 83

                          90
                  ....*....|.
gi 1331924211 256 NSSRLHTCQRH 266
Cdd:cd23275    84 QHSRLRVCQRI 94
Dkk_Cys2 cd23012
second cysteine-rich (Cys-2) domain of Dickkopf proteins; The Dickkopf (Dkk) family comprises ...
 182-264 7.92e-34

second cysteine-rich (Cys-2) 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-2 domain of Dickkopf proteins 1- 4.


Pssm-ID: 437997  Cd Length: 77  Bit Score: 117.46  E-value: 7.92e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331924211 182 KGQEGSVCLRSSDCATGLCCARHFWSKICKPVLKEGQVCTKHRRKGSHGlEIFQRCYCGEGLSCRIQKDHHqasnsSRLH 261
Cdd:cd23012     1 KGREGESCLRSRDCAEGLCCARHLWSKRCKPILLEGDVCTKPRRKKSRG-LIFQRCDCGSGLSCRPQPDSH-----KRLH 74


                  ...
gi 1331924211 262 TCQ 264
Cdd:cd23012    75 VCQ 77
Dkk_Cys1 cd23009
first cysteine-rich (Cys-1) domain of Dickkopf proteins; The Dickkopf (Dkk) family comprises a ...
 84-139 1.79e-11

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.


Pssm-ID: 438006  Cd Length: 52  Bit Score: 57.89  E-value: 1.79e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1331924211  84 PCAEDQECGTDEYCASPTRGgdavVQICLACRKRRKRCMRHAMCCPGNYCKNGICV 139
Cdd:cd23009     1 PCISDEDCGTSMYCQSPSDG----QYTCQPCRGQRKRCTRDAMCCPGTLCVNGICT 52
Dickkopf_N pfam04706
Dickkopf N-terminal cysteine-rich region; Dickkopf proteins are a class of Wnt antagonists. ...
 84-139 1.00e-07

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.


Pssm-ID: 461401  Cd Length: 51  Bit Score: 47.37  E-value: 1.00e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1331924211  84 PCAEDQECGTDEYCASPTRGGdavvqICLACRKRRKRCMRHAMCCPGNYCKNGICV 139
Cdd:pfam04706   1 ECLSDEDCGKGKYCLSSSGES-----VCLPCRKRRKRCTRDAMCCPGNLCVNGVCV 51
Dkk2_Cys1 cd23015
first cysteine-rich (Cys-1) domain of Dickkopf-related protein 2; Dickkopf 2 (Dkk2) is a ...
 81-139 3.00e-07

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.


Pssm-ID: 438009  Cd Length: 55  Bit Score: 46.29  E-value: 3.00e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1331924211  81 QPYPCAEDQECGTDEYCASPTRGGDAvvqiCLACRKRRKRCMRHAMCCPGNYCKNGICV 139
Cdd:cd23015     1 QAYPCSSDKECEVGRYCHSPHQAPSR----CMTCRRKKKRCHRDGMCCPGNRCSNGICI 55
Dkk3_Cys2 cd23274
second cysteine-rich (Cys-2) domain of Dickkopf-related protein 3; Dickkopf 3 (Dkk3) is a ...
 181-246 2.11e-06

second cysteine-rich (Cys-2) domain of Dickkopf-related protein 3; Dickkopf 3 (Dkk3) is a secreted protein which, in contrast to Dkk1, Dkk2, and Dkk4, does not interact with LRP5/6 (low-density lipoprotein receptor related protein 5 and 6), and thus is a divergent family member that is not considered a true Wnt signaling antagonist. The role of Dkk proteins in cancer is considered mainly tumor suppressive since they are usually down-regulated in cancer cells. Dkk3 links heat shock factor 1 (HSF1) and YAP/TAZ signaling to control aggressive behaviors in cancer-associated fibroblasts; it does so via canonical Wnt signaling. It 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 Dkk3.


Pssm-ID: 438000  Cd Length: 86  Bit Score: 44.91  E-value: 2.11e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1331924211 181 TKGQEGSVCLRSSDCATGLCCARH--FWSKICKPVLKEGQVCTKHRrkgSHGLEIF----------QRCYCGEGLSCR 246
Cdd:cd23274     3 TKGEAGTICQYQSDCSPGLCCAFHkaLLFPVCTPLPTEGEPCHDPS---NHLLDLLswdlepegplEHCPCAGGLQCQ 77
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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