KREMEN (kringle containing protein marking the eye and the nose) proteins, including KREMEN1 and KREMEN2, are single pass type I transmembrane proteins that contain extracellular kringle, WSC, and CUB domains. KREMEN proteins cooperate with dickkopf  (Dkk) proteins to antagonize wingless (WNT)/beta-catenin signaling via formation of a KREMEN-Dkk-LRP (LDL-receptor-related protein ternary complex) that triggers the internalization and clearance of the complex from the cell surface. KREMEN1 is a high-affinity Dkk-1 receptor and a component of a ternary membrane complex consisting of Wnt, the 7-transmembrane domain receptor Frizzled, and LRP5/6 co-receptor to block canonical WNT signaling. Dkk-1 and Dkk-4 bind directly to the LRP5/6 co-receptor to antagonize the canonical Wnt signaling pathway, but not the planar cell polarity (PCP) signaling pathway that does not require LRP5/6. In contrast, Dkk-3 has no effect on Wnt signaling and Dkk-2 can function either as an LRP agonist or antagonist, depending on whether the cell expresses Kremen proteins. All three extracellular domains of KREMEN1 are required for binding to the cysteine-rich domain of Dkk-1.

KREMEN (kringle containing protein marking the eye and the nose) proteins, including KREMEN1 and KREMEN2, are single pass type I transmembrane proteins that contain extracellular kringle, WSC, and CUB domains. KREMEN proteins cooperate with dickkopf  (Dkk) proteins to antagonize wingless (WNT)/beta-catenin signaling via formation of a KREMEN-Dkk-LRP (LDL-receptor-related protein ternary complex) that triggers the internalization and clearance of the complex from the cell surface. KREMEN1 is a high-affinity Dkk-1 receptor and a component of a ternary membrane complex consisting of Wnt, the 7-transmembrane domain receptor Frizzled, and LRP5/6 co-receptor to block canonical WNT signaling. Dkk-1 and Dkk-4 bind directly to the LRP5/6 co-receptor to antagonize the canonical Wnt signaling pathway, but not the planar cell polarity (PCP) signaling pathway that does not require LRP5/6. In contrast, Dkk-3 has no effect on Wnt signaling and Dkk-2 can function either as an LRP agonist or antagonist, depending on whether the cell expresses Kremen proteins. All three extracellular domains of KREMEN1 are required for binding to the cysteine-rich domain of Dkk-1.

 

Product Details

 

Gene Symbol: KREMEN1; KRM1; KREMEN; Kremen-1

 

NCBI Gene ID: 83999

 

Uniprot Entry: Q96MU8

 

Construct Details: The recombinant human KREMEN1-Fc fusion is expressed as a 593 amino acid protein consisting of Arg21 -  Gly375 region of KREMEN1 (Uniprot Accession #Q96MU8-3) and a C-terminal Fc from human IgG1, which exists as a dimer under non-reducing conditions.

  

Source:  Human cells stably expressing KREMEN1-Fc growing in chemical-defined media with no animal components or antibiotics 

 

Deduced Amino Acid Sequence:

        10         20         30         40         50         60 

RPAPSPGLGP GPECFTANGA DYRGTQNWTA LQGGKPCLFW NETFQHPYNT LKYPNGEGGL 

        70         80         90        100        110        120 

GEHNYCRNPD GDVSPWCYVA EHEDGVYWKY CEIPACQMPG NLGCYKDHGN PPPLTGTSKT 

       130        140        150        160        170        180 

SNKLTIQTCI SFCRSQRFKF AGMESGYACF CGNNPDYWKY GEAASTECNS VCFGDHTQPC  

       190        200        210        220        230        240 

GGDGRIILFD TLVGACGGNY SAMSSVVYSP DFPDTYATGR VCYWTIRVPG ASHIHFSFPL 

       250        260        270        280        290        300 

FDIRDSADMV ELLDGYTHRV LARFHGRSRP PLSFNVSLDF VILYFFSDRI NQAQGFAVLY 

       310        320        330        340        350        360 

QAVKEELPQE RPAVNQTVAE VITEQANLSV SAARSSKVLY VITTSPSHPP QTVPGSTTEN 

       370        380        390        400        410        420 

LYFQGSTGTH TCPPCPAPEL LGGPSVFLFP PKPKDTLMIS RTPEVTCVVV DVSHEDPEVK 

       430        440        450        460        470        480 

FNWYVDGVEV HNAKTKPREE QYNSTYRVVS VLTVLHQDWL NGKEYKCKVS NKALPAPIEK 

       490        500        510        520        530        540 

TISKAKGQPR EPQVYTLPPS REEMTKNQVS LTCLVKGFYP SDIAVEWESN GQPENNYKTT 

       550        560        570        580        590 

PPVLDSDGSF FLYSKLTVDK SRWQQGNVFS CSVMHEALHN HYTQKSLSLS PGK 

 

M.W.: Calculated molecular mass (kDa): 65.8; Estimated by SDS-PAGE under reducing condition (kDa): 80-90.

 

Calculated PI:  6.12 

 

Calculated Extinction Coefficient (M^-1 cm^-1, at 280nm):  99585

 

Purity: >90% judged by SDS-PAGE under reducing condition (see the gel image above, labeled as DTT "+")

 

Formulation: Supplied at 0.5 mg/ml in sterile PBSpH7.4 (carrier and preservative free). The purified recombinant protein was labeled with Biotin (3-5 Biotin per molecule) using the standard procedure.

 

Endotoxin Level: <0.1 EU per 1 μg of purified recombinant protein determined by the LAL method

 

Biological Activity: Recombinant KREMEN1-Fc binds human Dkk1 with high affinity (apparent K_D < 10 nM)

 

 

 

 

FOR RESEARCH USE ONLY. NOT FOR DIAGNOSTIC OR THERAPEUTIC USE IN HUMAN.

Restriction: This product is not transferable or re-sellable.  Customer obtain no right to transfer, assign, or sublicense its use rights, or to transfer, resell, package, or otherwise distribute the product, or to use the product for the benefit of any third party or for any commercial purpose.  Customer may only use the product in compliance with applicable local, state and federal laws, regulations and rules.  Customer may not directly or indirectly use the product or allow the transfer, transmission, export or re-export of all or any part of the product in violation of any export control law or regulation of the united states or any other relevant jurisdiction.  Your use of this product constitutes acceptance of the terms of this limited use agreement.  Please refer to our “terms & conditions” for details.  If you are not willing to accept the limitation of this agreement, G&P Biosciences will accept return of the product for a full/partial refund.

 

Storage

 

The product is shipped at 4°C. Upon receipt, centrifuge the product briefly before opening the vial. It is recommended to store small aliquots at the temperature below –20°C for long-term storage and the product is stable for 3 months. The undiluted protein can be stored at 4°C for no more than 2 weeks.

 

Use a manual defrost freezer and avoid repeated freeze-thaw cycles.

 

 

 

 

 

FOR RESEARCH USE ONLY. NOT FOR DIAGNOSTIC OR THERAPEUTIC USE IN HUMAN.

 

References

 

1. Biochim Biophys Acta 1518:63 (2001)

2. Development 129:5587 (2002)

3. Nature 417:664 (2002)

4. J Biol Chem. 283:23371 (2008)

5. Mol Cancer. 9:247 (2010)

 

  

 

Additional supporting documents, including PDS, COA and MSDS are available upon request.

 

 

 

FOR RESEARCH USE ONLY. NOT FOR DIAGNOSTIC OR THERAPEUTIC USE IN HUMAN.

Restriction: This product is not transferable or re-sellable.  Customer obtain no right to transfer, assign, or sublicense its use rights, or to transfer, resell, package, or otherwise distribute the product, or to use the product for the benefit of any third party or for any commercial purpose.  Customer may only use the product in compliance with applicable local, state and federal laws, regulations and rules.  Customer may not directly or indirectly use the product or allow the transfer, transmission, export or re-export of all or any part of the product in violation of any export control law or regulation of the united states or any other relevant jurisdiction.  Your use of this product constitutes acceptance of the terms of this limited use agreement.  Please refer to our “terms & conditions” for details.  If you are not willing to accept the limitation of this agreement, G&P Biosciences will accept return of the product for a full/partial refund.