UniProtKB - Q96MU8 (KREM1_HUMAN)
Protein
Kremen protein 1
Gene
KREMEN1
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. In the absence of DKK1, potentiates Wnt-beta-catenin signaling by maintaining LRP5 or LRP6 at the cell membrane. Can trigger apoptosis in a Wnt-independent manner and this apoptotic activity is inhibited upon binding of the ligand DKK1. 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. Modulates cell fate decisions in the developing cochlea with an inhibitory role in hair cell fate specification.By similarity
GO - Biological processi
- apoptotic process Source: UniProtKB
- cell communication Source: UniProtKB
- limb development Source: UniProtKB
- negative regulation of axon regeneration Source: Ensembl
- negative regulation of canonical Wnt signaling pathway Source: UniProtKB
- negative regulation of ossification Source: Ensembl
- regulation of canonical Wnt signaling pathway Source: BHF-UCL
- Wnt signaling pathway Source: UniProtKB-KW
Keywordsi
Biological process | Wnt signaling pathway |
Enzyme and pathway databases
PathwayCommonsi | Q96MU8 |
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, Signaling by LRP5 mutants |
SignaLinki | Q96MU8 |
SIGNORi | Q96MU8 |
Names & Taxonomyi
Protein namesi | Recommended name: Kremen protein 1Alternative name(s): Dickkopf receptor Kringle domain-containing transmembrane protein 1 Kringle-containing protein marking the eye and the nose |
Gene namesi | Name:KREMEN1 Synonyms:KREMEN, KRM1 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:17550, KREMEN1 |
MIMi | 609898, gene |
neXtProti | NX_Q96MU8 |
VEuPathDBi | HostDB:ENSG00000183762.12 |
Subcellular locationi
Plasma membrane
- Cell membrane By similarity; Single-pass type I membrane protein Curated
Plasma Membrane
- plasma membrane Source: UniProtKB-SubCell
Other locations
- integral component of membrane Source: UniProtKB-KW
- membrane Source: UniProtKB
- neuronal cell body Source: Ensembl
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 21 – 392 | ExtracellularSequence analysisAdd BLAST | 372 | |
Transmembranei | 393 – 413 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 414 – 473 | CytoplasmicSequence analysisAdd BLAST | 60 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Involvement in diseasei
Ectodermal dysplasia 13, hair/tooth type (ECTD13)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA form of ectodermal dysplasia, a disorder due to abnormal development of two or more ectodermal structures. ECTD13 is an autosomal recessive form characterized by severe oligodontia accompanied by anomalies of hair and skin.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_078807 | 207 | F → S in ECTD13. 1 PublicationCorresponds to variant dbSNP:rs1057524917Ensembl. | 1 |
Keywords - Diseasei
Disease variant, Ectodermal dysplasiaOrganism-specific databases
DisGeNETi | 83999 |
MalaCardsi | KREMEN1 |
MIMi | 617392, phenotype |
OpenTargetsi | ENSG00000183762 |
PharmGKBi | PA38241 |
Miscellaneous databases
Pharosi | Q96MU8, Tbio |
Genetic variation databases
BioMutai | KREMEN1 |
DMDMi | 212287927 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 19 | Sequence analysisAdd BLAST | 19 | |
ChainiPRO_0000021564 | 20 – 473 | Kremen protein 1Add BLAST | 454 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 32 ↔ 114 | Combined sources1 Publication | ||
Glycosylationi | 45 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 55 ↔ 95 | Combined sources1 Publication | ||
Glycosylationi | 59 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 84 ↔ 109 | Combined sources1 Publication | ||
Disulfide bondi | 122 ↔ 186 | Combined sources1 Publication | ||
Disulfide bondi | 147 ↔ 167 | Combined sources1 Publication | ||
Disulfide bondi | 151 ↔ 169 | Combined sources1 Publication | ||
Disulfide bondi | 190 ↔ 198 | Combined sources1 Publication | ||
Disulfide bondi | 214 ↔ 240 | Combined sources1 Publication | ||
Glycosylationi | 217 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 293 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 333 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 345 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
jPOSTi | Q96MU8 |
MassIVEi | Q96MU8 |
PaxDbi | Q96MU8 |
PeptideAtlasi | Q96MU8 |
PRIDEi | Q96MU8 |
ProteomicsDBi | 77415 [Q96MU8-1] 77416 [Q96MU8-2] 77417 [Q96MU8-3] |
PTM databases
GlyGeni | Q96MU8, 6 sites |
iPTMneti | Q96MU8 |
PhosphoSitePlusi | Q96MU8 |
Expressioni
Gene expression databases
Bgeei | ENSG00000183762, Expressed in heart left ventricle and 219 other tissues |
ExpressionAtlasi | Q96MU8, baseline and differential |
Genevisiblei | Q96MU8, HS |
Organism-specific databases
HPAi | ENSG00000183762, Low tissue specificity |
Interactioni
Subunit structurei
Protein-protein interaction databases
BioGRIDi | 123844, 1 interactor |
CORUMi | Q96MU8 |
DIPi | DIP-46462N |
IntActi | Q96MU8, 3 interactors |
STRINGi | 9606.ENSP00000331242 |
Miscellaneous databases
RNActi | Q96MU8, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q96MU8 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 31 – 114 | KringlePROSITE-ProRule annotationAdd BLAST | 84 | |
Domaini | 116 – 210 | WSCPROSITE-ProRule annotationAdd BLAST | 95 | |
Domaini | 214 – 321 | CUBPROSITE-ProRule annotationAdd BLAST | 108 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 414 – 473 | Essential for apoptotic activityBy similarityAdd BLAST | 60 |
Keywords - Domaini
Kringle, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG4157, Eukaryota |
GeneTreei | ENSGT00940000158390 |
HOGENOMi | CLU_043485_0_0_1 |
InParanoidi | Q96MU8 |
OMAi | CYIAEHE |
OrthoDBi | 516719at2759 |
PhylomeDBi | Q96MU8 |
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 (3+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
Isoform 1 (identifier: Q96MU8-1) [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
MAPPAARLAL LSAAALTLAA RPAPSPGLGP ECFTANGADY RGTQNWTALQ
60 70 80 90 100
GGKPCLFWNE TFQHPYNTLK YPNGEGGLGE HNYCRNPDGD VSPWCYVAEH
110 120 130 140 150
EDGVYWKYCE IPACQMPGNL GCYKDHGNPP PLTGTSKTSN KLTIQTCISF
160 170 180 190 200
CRSQRFKFAG MESGYACFCG NNPDYWKYGE AASTECNSVC FGDHTQPCGG
210 220 230 240 250
DGRIILFDTL VGACGGNYSA MSSVVYSPDF PDTYATGRVC YWTIRVPGAS
260 270 280 290 300
HIHFSFPLFD IRDSADMVEL LDGYTHRVLA RFHGRSRPPL SFNVSLDFVI
310 320 330 340 350
LYFFSDRINQ AQGFAVLYQA VKEELPQERP AVNQTVAEVI TEQANLSVSA
360 370 380 390 400
ARSSKVLYVI TTSPSHPPQT VPGSNSWAPP MGAGSHRVEG WTVYGLATLL
410 420 430 440 450
ILTVTAIVAK ILLHVTFKSH RVPASGDLRD CHQPGTSGEI WSIFYKPSTS
460 470
ISIFKKKLKG QSQQDDRNPL VSD
Note: Exon 1 splicing donor site is not canonical.
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketH7BZ87 | H7BZ87_HUMAN | Kremen protein 1 | KREMEN1 | 82 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 204 | I → V in BAB71180 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_078807 | 207 | F → S in ECTD13. 1 PublicationCorresponds to variant dbSNP:rs1057524917Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_034914 | 31 | E → GPE in isoform 2 and isoform 3. 2 Publications | 1 | |
Alternative sequenceiVSP_015698 | 373 – 389 | Missing in isoform 3. 1 PublicationAdd BLAST | 17 | |
Alternative sequenceiVSP_003900 | 471 – 473 | VSD → AIQDSEVTSLIWSQGQPRSI in isoform 2. 1 Publication | 3 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB059618 mRNA Translation: BAB40969.1 AK056425 mRNA Translation: BAB71180.1 AL021393 Genomic DNA No translation available. Z95116 Genomic DNA No translation available. CH471095 Genomic DNA Translation: EAW59774.1 BC063787 mRNA Translation: AAH63787.1 |
CCDSi | CCDS13849.1 [Q96MU8-2] CCDS43000.2 [Q96MU8-3] |
RefSeqi | NP_001034659.2, NM_001039570.2 [Q96MU8-3] NP_114434.3, NM_032045.4 [Q96MU8-2] |
Genome annotation databases
Ensembli | ENST00000327813; ENSP00000331242; ENSG00000183762 [Q96MU8-2] ENST00000400335; ENSP00000383189; ENSG00000183762 [Q96MU8-3] ENST00000407188; ENSP00000385431; ENSG00000183762 [Q96MU8-1] |
GeneIDi | 83999 |
KEGGi | hsa:83999 |
UCSCi | uc003ael.3, human [Q96MU8-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB059618 mRNA Translation: BAB40969.1 AK056425 mRNA Translation: BAB71180.1 AL021393 Genomic DNA No translation available. Z95116 Genomic DNA No translation available. CH471095 Genomic DNA Translation: EAW59774.1 BC063787 mRNA Translation: AAH63787.1 |
CCDSi | CCDS13849.1 [Q96MU8-2] CCDS43000.2 [Q96MU8-3] |
RefSeqi | NP_001034659.2, NM_001039570.2 [Q96MU8-3] NP_114434.3, NM_032045.4 [Q96MU8-2] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5FWS | X-ray | 1.90 | A | 29-373 | [»] | |
5FWT | X-ray | 2.10 | A | 29-373 | [»] | |
5FWU | X-ray | 2.80 | A | 29-373 | [»] | |
5FWV | X-ray | 3.20 | A | 29-373 | [»] | |
5FWW | X-ray | 3.50 | B | 30-322 | [»] | |
7BZT | electron microscopy | 3.00 | E | 23-375 | [»] | |
7BZU | electron microscopy | 3.00 | E | 23-375 | [»] | |
SMRi | Q96MU8 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 123844, 1 interactor |
CORUMi | Q96MU8 |
DIPi | DIP-46462N |
IntActi | Q96MU8, 3 interactors |
STRINGi | 9606.ENSP00000331242 |
PTM databases
GlyGeni | Q96MU8, 6 sites |
iPTMneti | Q96MU8 |
PhosphoSitePlusi | Q96MU8 |
Genetic variation databases
BioMutai | KREMEN1 |
DMDMi | 212287927 |
Proteomic databases
jPOSTi | Q96MU8 |
MassIVEi | Q96MU8 |
PaxDbi | Q96MU8 |
PeptideAtlasi | Q96MU8 |
PRIDEi | Q96MU8 |
ProteomicsDBi | 77415 [Q96MU8-1] 77416 [Q96MU8-2] 77417 [Q96MU8-3] |
Protocols and materials databases
Antibodypediai | 24417, 322 antibodies |
Genome annotation databases
Ensembli | ENST00000327813; ENSP00000331242; ENSG00000183762 [Q96MU8-2] ENST00000400335; ENSP00000383189; ENSG00000183762 [Q96MU8-3] ENST00000407188; ENSP00000385431; ENSG00000183762 [Q96MU8-1] |
GeneIDi | 83999 |
KEGGi | hsa:83999 |
UCSCi | uc003ael.3, human [Q96MU8-1] |
Organism-specific databases
CTDi | 83999 |
DisGeNETi | 83999 |
GeneCardsi | KREMEN1 |
HGNCi | HGNC:17550, KREMEN1 |
HPAi | ENSG00000183762, Low tissue specificity |
MalaCardsi | KREMEN1 |
MIMi | 609898, gene 617392, phenotype |
neXtProti | NX_Q96MU8 |
OpenTargetsi | ENSG00000183762 |
PharmGKBi | PA38241 |
VEuPathDBi | HostDB:ENSG00000183762.12 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4157, Eukaryota |
GeneTreei | ENSGT00940000158390 |
HOGENOMi | CLU_043485_0_0_1 |
InParanoidi | Q96MU8 |
OMAi | CYIAEHE |
OrthoDBi | 516719at2759 |
PhylomeDBi | Q96MU8 |
TreeFami | TF331319 |
Enzyme and pathway databases
PathwayCommonsi | Q96MU8 |
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, Signaling by LRP5 mutants |
SignaLinki | Q96MU8 |
SIGNORi | Q96MU8 |
Miscellaneous databases
BioGRID-ORCSi | 83999, 7 hits in 995 CRISPR screens |
ChiTaRSi | KREMEN1, human |
GeneWikii | KREMEN1 |
GenomeRNAii | 83999 |
Pharosi | Q96MU8, Tbio |
PROi | PR:Q96MU8 |
RNActi | Q96MU8, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000183762, Expressed in heart left ventricle and 219 other tissues |
ExpressionAtlasi | Q96MU8, baseline and differential |
Genevisiblei | Q96MU8, 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 | KREM1_HUMAN | |
Accessioni | Q96MU8Primary (citable) accession number: Q96MU8 Secondary accession number(s): B0QY46 Q9UGU1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 15, 2002 |
Last sequence update: | July 22, 2008 | |
Last modified: | April 7, 2021 | |
This is version 174 of the entry and version 3 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
3D-structure, Reference proteomeDocuments
- Human chromosome 22
Human chromosome 22: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references