KREM2_MOUSE
ID KREM2_MOUSE Reviewed; 461 AA.
AC Q8K1S7; Q0VBR6;
DT 23-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Kremen protein 2;
DE AltName: Full=Dickkopf receptor 2;
DE AltName: Full=Kringle domain-containing transmembrane protein 2;
DE AltName: Full=Kringle-containing protein marking the eye and the nose;
DE Flags: Precursor;
GN Name=Kremen2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090 {ECO:0000312|EMBL:CAD29805.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND IDENTIFICATION IN A TERNARY
RP COMPLEX WITH DKK1 AND LRP6.
RC STRAIN=C57BL/6J;
RX PubMed=12050670; DOI=10.1038/nature756;
RA Mao B., Wu W., Davidson G., Marhold J., Li M., Mechler B.M., Delius H.,
RA Hoppe D., Stannek P., Walter C., Glinka A., Niehrs C.;
RT "Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin
RT signalling.";
RL Nature 417:664-667(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP INTERACTION WITH ERLEC1.
RX PubMed=16531414; DOI=10.1074/jbc.m511872200;
RA Cruciat C.-M., Hassler C., Niehrs C.;
RT "The MRH protein Erlectin is a member of the endoplasmic reticulum
RT synexpression group and functions in N-glycan recognition.";
RL J. Biol. Chem. 281:12986-12993(2006).
RN [4]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=18505822; DOI=10.1128/mcb.00222-08;
RA Ellwanger K., Saito H., Clement-Lacroix P., Maltry N., Niedermeyer J.,
RA Lee W.K., Baron R., Rawadi G., Westphal H., Niehrs C.;
RT "Targeted disruption of the Wnt regulator Kremen induces limb defects and
RT high bone density.";
RL Mol. Cell. Biol. 28:4875-4882(2008).
RN [5]
RP DEVELOPMENTAL STAGE.
RX PubMed=26206087; DOI=10.1038/cdd.2015.100;
RA Causeret F., Sumia I., Pierani A.;
RT "Kremen1 and Dickkopf1 control cell survival in a Wnt-independent manner.";
RL Cell Death Differ. 23:323-332(2016).
CC -!- FUNCTION: Receptor for Dickkopf proteins. Cooperates with DKK1/2 to
CC inhibit Wnt/beta-catenin signaling by promoting the endocytosis of Wnt
CC receptors LRP5 and LRP6 (PubMed:12050670). Plays a role in limb
CC development; attenuates Wnt signaling in the developing limb to allow
CC normal limb patterning and can also negatively regulate bone formation
CC (PubMed:18505822). {ECO:0000269|PubMed:12050670,
CC ECO:0000269|PubMed:18505822}.
CC -!- SUBUNIT: Interacts with ERLEC1 (PubMed:16531414). Forms a ternary
CC complex with DKK1 and LRP6 (PubMed:12050670).
CC {ECO:0000269|PubMed:12050670, ECO:0000269|PubMed:16531414}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the developing brain and developing
CC limb buds. {ECO:0000269|PubMed:26206087}.
CC -!- DOMAIN: Binding to ERLEC1 is mediated by the oligosaccharides linked to
CC the kringle domain. {ECO:0000269|PubMed:16531414}.
CC -!- DISRUPTION PHENOTYPE: Animals with a double knockout of KREM1 and KREM2
CC exhibit enhanced Wnt signaling accompanied by ectopic postaxial
CC forelimb digits and expanded apical ectodermal ridges. They also
CC exhibit increased bone volume and bone formation rates. Triple knockout
CC mice KREM1/KREM2/DKK1 exhibit enhanced growth of ectopic digits.
CC {ECO:0000269|PubMed:18505822}.
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DR EMBL; AJ457192; CAD29805.1; -; mRNA.
DR EMBL; BC120532; AAI20533.1; -; mRNA.
DR EMBL; BC125438; AAI25439.1; -; mRNA.
DR CCDS; CCDS28462.1; -.
DR RefSeq; NP_082692.1; NM_028416.2.
DR RefSeq; XP_006525047.1; XM_006524984.3.
DR AlphaFoldDB; Q8K1S7; -.
DR SMR; Q8K1S7; -.
DR BioGRID; 215713; 1.
DR CORUM; Q8K1S7; -.
DR STRING; 10090.ENSMUSP00000046369; -.
DR GlyGen; Q8K1S7; 4 sites.
DR PhosphoSitePlus; Q8K1S7; -.
DR PaxDb; Q8K1S7; -.
DR PRIDE; Q8K1S7; -.
DR Antibodypedia; 1159; 118 antibodies from 26 providers.
DR DNASU; 73016; -.
DR Ensembl; ENSMUST00000046525; ENSMUSP00000046369; ENSMUSG00000040680.
DR GeneID; 73016; -.
DR KEGG; mmu:73016; -.
DR UCSC; uc008atd.1; mouse.
DR CTD; 79412; -.
DR MGI; MGI:1920266; Kremen2.
DR VEuPathDB; HostDB:ENSMUSG00000040680; -.
DR eggNOG; KOG4157; Eukaryota.
DR GeneTree; ENSGT00940000162126; -.
DR HOGENOM; CLU_047976_0_0_1; -.
DR InParanoid; Q8K1S7; -.
DR OMA; RNCSWVV; -.
DR OrthoDB; 516719at2759; -.
DR PhylomeDB; Q8K1S7; -.
DR TreeFam; TF331319; -.
DR Reactome; R-MMU-3772470; Negative regulation of TCF-dependent signaling by WNT ligand antagonists.
DR BioGRID-ORCS; 73016; 5 hits in 75 CRISPR screens.
DR PRO; PR:Q8K1S7; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q8K1S7; protein.
DR Bgee; ENSMUSG00000040680; Expressed in skin epidermis and 54 other tissues.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0060173; P:limb development; IMP:UniProtKB.
DR GO; GO:0030279; P:negative regulation of ossification; IMP:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR CDD; cd00041; CUB; 1.
DR CDD; cd00108; KR; 1.
DR Gene3D; 2.40.20.10; -; 1.
DR Gene3D; 2.60.120.290; -; 1.
DR InterPro; IPR000859; CUB_dom.
DR InterPro; IPR017076; Kremen.
DR InterPro; IPR000001; Kringle.
DR InterPro; IPR013806; Kringle-like.
DR InterPro; IPR018056; Kringle_CS.
DR InterPro; IPR038178; Kringle_sf.
DR InterPro; IPR035914; Sperma_CUB_dom_sf.
DR InterPro; IPR002889; WSC_carb-bd.
DR Pfam; PF00431; CUB; 1.
DR Pfam; PF00051; Kringle; 1.
DR Pfam; PF01822; WSC; 1.
DR PIRSF; PIRSF036961; Kremen; 1.
DR SMART; SM00042; CUB; 1.
DR SMART; SM00130; KR; 1.
DR SMART; SM00321; WSC; 1.
DR SUPFAM; SSF49854; SSF49854; 1.
DR SUPFAM; SSF57440; SSF57440; 1.
DR PROSITE; PS01180; CUB; 1.
DR PROSITE; PS00021; KRINGLE_1; 1.
DR PROSITE; PS50070; KRINGLE_2; 1.
DR PROSITE; PS51212; WSC; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Glycoprotein; Kringle; Membrane; Reference proteome;
KW Signal; Transmembrane; Transmembrane helix; Wnt signaling pathway.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..461
FT /note="Kremen protein 2"
FT /id="PRO_0000021569"
FT TOPO_DOM 25..363
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 364..386
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 387..461
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 34..118
FT /note="Kringle"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 120..214
FT /note="WSC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00558,
FT ECO:0000305"
FT DOMAIN 218..325
FT /note="CUB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059,
FT ECO:0000305"
FT REGION 329..357
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 429..452
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 48
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 221
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 243
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 350
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 35..118
FT /evidence="ECO:0000250"
FT DISULFID 59..99
FT /evidence="ECO:0000250"
FT DISULFID 88..113
FT /evidence="ECO:0000250"
FT DISULFID 218..244
FT /evidence="ECO:0000250"
SQ SEQUENCE 461 AA; 49170 MW; 6D58C4A2858E09DA CRC64;
MGTPHLQGFL LLFPLLLRLH GASAGSLHSP GLSECFQVNG ADYRGHQNYT GPRGAGRPCL
FWDQTQQHSY SSASDPQGRW GLGAHNFCRN PDGDVQPWCY VAETEEGIYW RYCDIPTCHM
PGYLGCFVDS GAPPALSGPS GTSTKLTVQV CLRFCRMKGY QLAGVEAGYA CFCGSESDLA
RGRPAPATDC DQICFGHPGQ LCGGDGRLGI YEVSVGSCQG NWSAPQGVIY SPDFPDEYGP
DRNCSWVLGQ LGAVLELTFR LFELADSRDR LELRDVSSGN LLRAFDGAHP PPPGPLRLRT
AALLLTFRSD ARGHAQGFAL TYRGLQDTVE GRASPEDSTE SLAGDPDGAN ASCSPKPGAA
QASIGARVFS TVTAFSVLLL LLLSLLRLLR RRSCLLAPGK GSLAMGPSRG PGRSWAVWYR
RPRGVALPCP PGDSQAEGPA AGYRPLSASS QSSLRSLVSA L
