UniProtKB - Q8NCW0 (KREM2_HUMAN)
Protein
Kremen protein 2
Gene
KREMEN2
Organism
Homo sapiens (Human)
Status
Functioni
Receptor for Dickkopf proteins. Cooperates with DKK1/2 to inhibit Wnt/beta-catenin signaling by promoting the endocytosis of Wnt receptors LRP5 and LRP6. Plays a role in limb development; attenuates Wnt signaling in the developing limb to allow normal limb patterning and can also negatively regulate bone formation.By similarity
GO - Biological processi
- limb development Source: UniProtKB
- negative regulation of canonical Wnt signaling pathway Source: Reactome
- negative regulation of ossification Source: UniProtKB
- Wnt signaling pathway Source: UniProtKB-KW
Keywordsi
Biological process | Wnt signaling pathway |
Enzyme and pathway databases
PathwayCommonsi | Q8NCW0 |
Reactomei | R-HSA-201681, TCF dependent signaling in response to WNT R-HSA-3772470, Negative regulation of TCF-dependent signaling by WNT ligand antagonists R-HSA-5339717, Misspliced LRP5 mutants have enhanced beta-catenin-dependent signaling |
SignaLinki | Q8NCW0 |
SIGNORi | Q8NCW0 |
Names & Taxonomyi
Protein namesi | Recommended name: Kremen protein 2Alternative name(s): Dickkopf receptor 2 Kringle domain-containing transmembrane protein 2 Kringle-containing protein marking the eye and the nose |
Gene namesi | Name:KREMEN2 Synonyms:KRM2 |
Organismi | Homo sapiens (Human)Imported |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000131650.13 |
HGNCi | HGNC:18797, KREMEN2 |
MIMi | 609899, gene |
neXtProti | NX_Q8NCW0 |
Subcellular locationi
Other locations
- Membrane Curated; Single-pass type I membrane protein Curated
Endosome
- early endosome membrane Source: Reactome
Plasma Membrane
- plasma membrane Source: Reactome
Other locations
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 26 – 364 | ExtracellularSequence analysisAdd BLAST | 339 | |
Transmembranei | 365 – 387 | HelicalSequence analysisAdd BLAST | 23 | |
Topological domaini | 388 – 462 | CytoplasmicSequence analysisAdd BLAST | 75 |
Keywords - Cellular componenti
MembranePathology & Biotechi
Organism-specific databases
DisGeNETi | 79412 |
OpenTargetsi | ENSG00000131650 |
PharmGKBi | PA38683 |
Miscellaneous databases
Pharosi | Q8NCW0, Tbio |
Polymorphism and mutation databases
BioMutai | KREMEN2 |
DMDMi | 30173086 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 25 | Sequence analysisAdd BLAST | 25 | |
ChainiPRO_0000021568 | 26 – 462 | Kremen protein 2Add BLAST | 437 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 36 ↔ 119 | By similarity | ||
Glycosylationi | 49 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 60 ↔ 100 | By similarity | ||
Disulfide bondi | 89 ↔ 114 | By similarity | ||
Disulfide bondi | 219 ↔ 245 | By similarity | ||
Glycosylationi | 222 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 244 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 351 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
EPDi | Q8NCW0 |
MassIVEi | Q8NCW0 |
PaxDbi | Q8NCW0 |
PeptideAtlasi | Q8NCW0 |
PRIDEi | Q8NCW0 |
ProteomicsDBi | 47024 5431 72953 [Q8NCW0-1] 72954 [Q8NCW0-2] 72955 [Q8NCW0-3] 72956 [Q8NCW0-4] |
PTM databases
GlyGeni | Q8NCW0, 5 sites |
iPTMneti | Q8NCW0 |
PhosphoSitePlusi | Q8NCW0 |
Expressioni
Gene expression databases
Bgeei | ENSG00000131650, Expressed in ectocervix and 86 other tissues |
Genevisiblei | Q8NCW0, HS |
Organism-specific databases
HPAi | ENSG00000131650, Tissue enhanced (lymphoid tissue, skin) |
Interactioni
Subunit structurei
Interacts with ERLEC1.
Forms a ternary complex with DKK1 and LRP6.
By similarityProtein-protein interaction databases
BioGRIDi | 122662, 2 interactors |
IntActi | Q8NCW0, 1 interactor |
STRINGi | 9606.ENSP00000304422 |
Miscellaneous databases
RNActi | Q8NCW0, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 35 – 119 | KringlePROSITE-ProRule annotationAdd BLAST | 85 | |
Domaini | 121 – 215 | WSCPROSITE-ProRule annotationCuratedAdd BLAST | 95 | |
Domaini | 219 – 326 | CUBPROSITE-ProRule annotationCuratedAdd BLAST | 108 |
Domaini
Binding to ERLEC1 is mediated by the oligosaccharides linked to the kringle domain.By similarity
Keywords - Domaini
Kringle, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG4157, Eukaryota |
GeneTreei | ENSGT00940000162126 |
HOGENOMi | CLU_047976_0_0_1 |
InParanoidi | Q8NCW0 |
OMAi | GRSWAVW |
PhylomeDBi | Q8NCW0 |
TreeFami | TF331319 |
Family and domain databases
CDDi | cd00041, CUB, 1 hit cd00108, KR, 1 hit |
Gene3Di | 2.40.20.10, 1 hit 2.60.120.290, 1 hit |
InterProi | View protein in InterPro IPR000859, CUB_dom IPR017076, Kremen IPR000001, Kringle IPR013806, Kringle-like IPR018056, Kringle_CS IPR038178, Kringle_sf IPR035914, Sperma_CUB_dom_sf IPR002889, WSC_carb-bd |
Pfami | View protein in Pfam PF00431, CUB, 1 hit PF00051, Kringle, 1 hit PF01822, WSC, 1 hit |
PIRSFi | PIRSF036961, Kremen, 1 hit |
SMARTi | View protein in SMART SM00042, CUB, 1 hit SM00130, KR, 1 hit SM00321, WSC, 1 hit |
SUPFAMi | SSF49854, SSF49854, 1 hit SSF57440, SSF57440, 1 hit |
PROSITEi | View protein in PROSITE PS01180, CUB, 1 hit PS00021, KRINGLE_1, 1 hit PS50070, KRINGLE_2, 1 hit PS51212, WSC, 1 hit |
s (6)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 6 produced by isoformsialternative splicing. AlignAdd to basketIsoform 1Curated (identifier: Q8NCW0-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MGTQALQGFL FLLFLPLLQP RGASAGSLHS PGLSECFQVN GADYRGHQNR
60 70 80 90 100
TGPRGAGRPC LFWDQTQQHS YSSASDPHGR WGLGAHNFCR NPDGDVQPWC
110 120 130 140 150
YVAETEEGIY WRYCDIPSCH MPGYLGCFVD SGAPPALSGP SGTSTKLTVQ
160 170 180 190 200
VCLRFCRMKG YQLAGVEAGY ACFCGSESDL ARGRLAPATD CDQICFGHPG
210 220 230 240 250
QLCGGDGRLG VYEVSVGSCQ GNWTAPQGVI YSPDFPDEYG PDRNCSWALG
260 270 280 290 300
PPGAALELTF RLFELADPRD RLELRDAASG SLLRAFDGAR PPPSGPLRLG
310 320 330 340 350
TAALLLTFRS DARGHAQGFA LTYRGLQDAA EDPEAPEGSA QTPAAPLDGA
360 370 380 390 400
NVSCSPRPGA PPAAIGARVF STVTAVSVLL LLLLGLLRPL RRRSCLLAPG
410 420 430 440 450
KGPPALGASR GPRRSWAVWY QQPRGVALPC SPGDPQAEGS AAGYRPLSAS
460
SQSSLRSLIS AL
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 164 – 202 | Missing in BAC11365 (PubMed:14702039).CuratedAdd BLAST | 39 | |
Sequence conflicti | 285 | A → D in BAC11365 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_059691 | 408 | A → P. Corresponds to variant dbSNP:rs11866302Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_046399 | 162 – 200 | Missing in isoform 5 and isoform 6. 1 PublicationAdd BLAST | 39 | |
Alternative sequenceiVSP_047386 | 367 – 462 | ARVFS…LISAL → GAVCWLREKGPRRWGLPGAP GEAGLCGTNSPEGWPCPAPP GTPRLRVLPRATGL in isoform 6. CuratedAdd BLAST | 96 | |
Alternative sequenceiVSP_050511 | 367 – 420 | ARVFS…WAVWY → GAVCWLREKGPRRWGLPGAP GEAGLCGTNSPEGWPCPAPP GTPRLRVLPRATGL in isoform 3. 2 PublicationsAdd BLAST | 54 | |
Alternative sequenceiVSP_050513 | 367 – 399 | ARVFS…CLLAP → GEAGARDGSESGSRPLAPIL TAAVCPQPGSSRR in isoform 4. 2 PublicationsAdd BLAST | 33 | |
Alternative sequenceiVSP_050509 | 394 – 424 | SCLLA…YQQPR → CGALGQGLRADRWWGAGAPE GNRARKELLGS in isoform 2. CuratedAdd BLAST | 31 | |
Alternative sequenceiVSP_050514 | 400 – 462 | Missing in isoform 4. 2 PublicationsAdd BLAST | 63 | |
Alternative sequenceiVSP_050512 | 421 – 462 | Missing in isoform 3. 2 PublicationsAdd BLAST | 42 | |
Alternative sequenceiVSP_050510 | 425 – 462 | Missing in isoform 2. CuratedAdd BLAST | 38 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB086405 mRNA Translation: BAC00872.1 AB086355 mRNA Translation: BAC00823.1 AB086356 mRNA Translation: BAC00824.1 AB086357 mRNA Translation: BAC00825.1 AK027669 mRNA Translation: BAB55281.1 AK075033 mRNA Translation: BAC11365.1 AK301953 mRNA Translation: BAG63368.1 AC004235 Genomic DNA No translation available. CH471112 Genomic DNA Translation: EAW85449.1 BC003533 mRNA Translation: AAH03533.1 BC009383 mRNA Translation: AAH09383.1 |
CCDSi | CCDS10483.1 [Q8NCW0-1] CCDS10484.1 [Q8NCW0-3] CCDS58412.1 [Q8NCW0-5] CCDS58413.1 [Q8NCW0-6] |
RefSeqi | NP_001240654.1, NM_001253725.1 [Q8NCW0-6] NP_001240655.1, NM_001253726.1 [Q8NCW0-5] NP_078783.1, NM_024507.3 [Q8NCW0-3] NP_757384.1, NM_172229.2 [Q8NCW0-1] |
Genome annotation databases
Ensembli | ENST00000303746; ENSP00000304422; ENSG00000131650 [Q8NCW0-1] ENST00000319500; ENSP00000322079; ENSG00000131650 [Q8NCW0-3] ENST00000571007; ENSP00000461860; ENSG00000131650 [Q8NCW0-5] ENST00000572045; ENSP00000460578; ENSG00000131650 [Q8NCW0-4] ENST00000575769; ENSP00000460917; ENSG00000131650 [Q8NCW0-2] ENST00000575885; ENSP00000459878; ENSG00000131650 [Q8NCW0-6] |
GeneIDi | 79412 |
KEGGi | hsa:79412 |
UCSCi | uc002csg.4, human [Q8NCW0-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB086405 mRNA Translation: BAC00872.1 AB086355 mRNA Translation: BAC00823.1 AB086356 mRNA Translation: BAC00824.1 AB086357 mRNA Translation: BAC00825.1 AK027669 mRNA Translation: BAB55281.1 AK075033 mRNA Translation: BAC11365.1 AK301953 mRNA Translation: BAG63368.1 AC004235 Genomic DNA No translation available. CH471112 Genomic DNA Translation: EAW85449.1 BC003533 mRNA Translation: AAH03533.1 BC009383 mRNA Translation: AAH09383.1 |
CCDSi | CCDS10483.1 [Q8NCW0-1] CCDS10484.1 [Q8NCW0-3] CCDS58412.1 [Q8NCW0-5] CCDS58413.1 [Q8NCW0-6] |
RefSeqi | NP_001240654.1, NM_001253725.1 [Q8NCW0-6] NP_001240655.1, NM_001253726.1 [Q8NCW0-5] NP_078783.1, NM_024507.3 [Q8NCW0-3] NP_757384.1, NM_172229.2 [Q8NCW0-1] |
3D structure databases
SMRi | Q8NCW0 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 122662, 2 interactors |
IntActi | Q8NCW0, 1 interactor |
STRINGi | 9606.ENSP00000304422 |
PTM databases
GlyGeni | Q8NCW0, 5 sites |
iPTMneti | Q8NCW0 |
PhosphoSitePlusi | Q8NCW0 |
Polymorphism and mutation databases
BioMutai | KREMEN2 |
DMDMi | 30173086 |
Proteomic databases
EPDi | Q8NCW0 |
MassIVEi | Q8NCW0 |
PaxDbi | Q8NCW0 |
PeptideAtlasi | Q8NCW0 |
PRIDEi | Q8NCW0 |
ProteomicsDBi | 47024 5431 72953 [Q8NCW0-1] 72954 [Q8NCW0-2] 72955 [Q8NCW0-3] 72956 [Q8NCW0-4] |
Protocols and materials databases
Antibodypediai | 1159, 118 antibodies |
DNASUi | 79412 |
Genome annotation databases
Ensembli | ENST00000303746; ENSP00000304422; ENSG00000131650 [Q8NCW0-1] ENST00000319500; ENSP00000322079; ENSG00000131650 [Q8NCW0-3] ENST00000571007; ENSP00000461860; ENSG00000131650 [Q8NCW0-5] ENST00000572045; ENSP00000460578; ENSG00000131650 [Q8NCW0-4] ENST00000575769; ENSP00000460917; ENSG00000131650 [Q8NCW0-2] ENST00000575885; ENSP00000459878; ENSG00000131650 [Q8NCW0-6] |
GeneIDi | 79412 |
KEGGi | hsa:79412 |
UCSCi | uc002csg.4, human [Q8NCW0-1] |
Organism-specific databases
CTDi | 79412 |
DisGeNETi | 79412 |
EuPathDBi | HostDB:ENSG00000131650.13 |
GeneCardsi | KREMEN2 |
HGNCi | HGNC:18797, KREMEN2 |
HPAi | ENSG00000131650, Tissue enhanced (lymphoid tissue, skin) |
MIMi | 609899, gene |
neXtProti | NX_Q8NCW0 |
OpenTargetsi | ENSG00000131650 |
PharmGKBi | PA38683 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4157, Eukaryota |
GeneTreei | ENSGT00940000162126 |
HOGENOMi | CLU_047976_0_0_1 |
InParanoidi | Q8NCW0 |
OMAi | GRSWAVW |
PhylomeDBi | Q8NCW0 |
TreeFami | TF331319 |
Enzyme and pathway databases
PathwayCommonsi | Q8NCW0 |
Reactomei | R-HSA-201681, TCF dependent signaling in response to WNT R-HSA-3772470, Negative regulation of TCF-dependent signaling by WNT ligand antagonists R-HSA-5339717, Misspliced LRP5 mutants have enhanced beta-catenin-dependent signaling |
SignaLinki | Q8NCW0 |
SIGNORi | Q8NCW0 |
Miscellaneous databases
BioGRID-ORCSi | 79412, 6 hits in 842 CRISPR screens |
GenomeRNAii | 79412 |
Pharosi | Q8NCW0, Tbio |
PROi | PR:Q8NCW0 |
RNActi | Q8NCW0, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000131650, Expressed in ectocervix and 86 other tissues |
Genevisiblei | Q8NCW0, HS |
Family and domain databases
CDDi | cd00041, CUB, 1 hit cd00108, KR, 1 hit |
Gene3Di | 2.40.20.10, 1 hit 2.60.120.290, 1 hit |
InterProi | View protein in InterPro IPR000859, CUB_dom IPR017076, Kremen IPR000001, Kringle IPR013806, Kringle-like IPR018056, Kringle_CS IPR038178, Kringle_sf IPR035914, Sperma_CUB_dom_sf IPR002889, WSC_carb-bd |
Pfami | View protein in Pfam PF00431, CUB, 1 hit PF00051, Kringle, 1 hit PF01822, WSC, 1 hit |
PIRSFi | PIRSF036961, Kremen, 1 hit |
SMARTi | View protein in SMART SM00042, CUB, 1 hit SM00130, KR, 1 hit SM00321, WSC, 1 hit |
SUPFAMi | SSF49854, SSF49854, 1 hit SSF57440, SSF57440, 1 hit |
PROSITEi | View protein in PROSITE PS01180, CUB, 1 hit PS00021, KRINGLE_1, 1 hit PS50070, KRINGLE_2, 1 hit PS51212, WSC, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | KREM2_HUMAN | |
Accessioni | Q8NCW0Primary (citable) accession number: Q8NCW0 Secondary accession number(s): B4DXF6 Q9BTP9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 23, 2003 |
Last sequence update: | October 1, 2002 | |
Last modified: | December 2, 2020 | |
This is version 155 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - Human chromosome 16
Human chromosome 16: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations