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Protein

Kremen protein 1

Gene

Kremen1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 (PubMed:12050670). In the absence of DKK1, potentiates Wnt-beta-catenin signaling by maintaining LRP5 or LRP6 at the cell membrane (By similarity). Can trigger apoptosis in a Wnt-independent manner and this apoptotic activity is inhibited upon binding of the ligand DKK1 (PubMed:26206087). 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 (PubMed:18505822). Modulates cell fate decisions in the developing cochlea with an inhibitory role in hair cell fate specification (PubMed:27550540).By similarity4 Publications

GO - Biological processi

  • apoptotic process Source: UniProtKB
  • cell communication Source: GO_Central
  • limb development Source: UniProtKB
  • negative regulation of canonical Wnt signaling pathway Source: UniProtKB
  • negative regulation of ossification Source: UniProtKB
  • Wnt signaling pathway Source: UniProtKB-KW

Keywordsi

Biological processWnt signaling pathway

Names & Taxonomyi

Protein namesi
Recommended name:
Kremen protein 1
Alternative 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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1933988. Kremen1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini21 – 392ExtracellularSequence analysisAdd BLAST372
Transmembranei393 – 413HelicalSequence analysisAdd BLAST21
Topological domaini414 – 473CytoplasmicSequence analysisAdd BLAST60

GO - Cellular componenti

  • integral component of membrane Source: UniProtKB
  • membrane Source: MGI

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Animals with a double knockout of KREM1 and KREM2 exhibit enhanced Wnt signaling accompanied by ectopic postaxial forelimb digits and expanded apical ectodermal ridges. They also exhibit increased bone volume and bone formation rates. Triple knockout mice KREM1/KREM2/DKK1 exhibit enhanced growth of ectopic digits.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi419S → F: Significant reduction of apoptotic activity. 1 Publication1
Mutagenesisi437S → L: Significant reduction of apoptotic activity. 1 Publication1
Mutagenesisi453I → V: Significant reduction of apoptotic activity. 1 Publication1
Mutagenesisi472S → G: Complete loss of apoptotic activity. 1 Publication1
Mutagenesisi473D → N: Complete loss of apoptotic activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
ChainiPRO_000002156520 – 473Kremen protein 1Add BLAST454

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi32 ↔ 114By similarity
Disulfide bondi55 ↔ 95By similarity
Glycosylationi59N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi84 ↔ 109By similarity
Disulfide bondi122 ↔ 186By similarity
Disulfide bondi147 ↔ 167By similarity
Disulfide bondi151 ↔ 169By similarity
Disulfide bondi190 ↔ 198By similarity
Disulfide bondi214 ↔ 240By similarity
Glycosylationi217N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi255N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi293N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi333N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi345N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ99N43.
PeptideAtlasiQ99N43.
PRIDEiQ99N43.

PTM databases

PhosphoSitePlusiQ99N43.

Expressioni

Tissue specificityi

In the adult, widely expressed with high levels in heart, lung, kidney, skeletal muscle and testis.1 Publication

Developmental stagei

Expressed in the developing cochlea. Expressed first in the prosensory domain and the expression is restricted to supporting cells as development proceeds (at protein level). In the embryo, expression is first detected on day 9 and increases up to day 18. Lower levels are found in adult. At 9.5 dpc, expression is localised to the apical ectodermal ridge (AER) of the developing fore- and hindlimb buds, the telencephalon and the first brachial arch. At 10.5 dpc, expression is also observed in the myotome and in sensory tissues such as the nasal pit and optic vesicle. Expressed in the developing brain and developing limb buds.4 Publications

Gene expression databases

BgeeiENSMUSG00000020393.
CleanExiMM_KREMEN1.
ExpressionAtlasiQ99N43. baseline and differential.
GenevisibleiQ99N43. MM.

Interactioni

Subunit structurei

Forms a ternary complex with DKK1 and LRP6 (PubMed:12050670). Interacts with LRP6 in a DKK1-dependent manner. Interacts with DKK1 and RSPO1 (via FU repeats) (By similarity).By similarity1 Publication

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000020662.

Structurei

3D structure databases

ProteinModelPortaliQ99N43.
SMRiQ99N43.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini31 – 114KringlePROSITE-ProRule annotationAdd BLAST84
Domaini116 – 210WSCPROSITE-ProRule annotationAdd BLAST95
Domaini214 – 321CUBPROSITE-ProRule annotationAdd BLAST108

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni414 – 473Essential for apopototic activity1 PublicationAdd BLAST60

Keywords - Domaini

Kringle, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IR07. Eukaryota.
ENOG41112QM. LUCA.
GeneTreeiENSGT00730000110973.
HOGENOMiHOG000070150.
HOVERGENiHBG052290.
InParanoidiQ99N43.
OMAiPECFTAN.
OrthoDBiEOG091G053O.
TreeFamiTF331319.

Family and domain databases

CDDicd00041. CUB. 1 hit.
Gene3Di2.60.120.290. 1 hit.
InterProiView protein in InterPro
IPR000859. CUB_dom.
IPR017076. Kremen.
IPR000001. Kringle.
IPR013806. Kringle-like.
IPR018056. Kringle_CS.
IPR002889. WSC_carb-bd.
PfamiView protein in Pfam
PF00431. CUB. 1 hit.
PF00051. Kringle. 1 hit.
PF01822. WSC. 1 hit.
PIRSFiPIRSF036961. Kremen. 1 hit.
SMARTiView protein in SMART
SM00042. CUB. 1 hit.
SM00130. KR. 1 hit.
SM00321. WSC. 1 hit.
SUPFAMiSSF49854. SSF49854. 1 hit.
SSF57440. SSF57440. 1 hit.
PROSITEiView protein in PROSITE
PS01180. CUB. 1 hit.
PS00021. KRINGLE_1. 1 hit.
PS50070. KRINGLE_2. 1 hit.
PS51212. WSC. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q99N43-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAPPAARLAL LSAAALTLAA RPAPGPRSGP ECFTANGADY RGTQSWTALQ
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 NNPDYWKHGE AASTECNSVC FGDHTQPCGG
210 220 230 240 250
DGRIILFDTL VGACGGNYSA MAAVVYSPDF PDTYATGRVC YWTIRVPGAS
260 270 280 290 300
RIHFNFTLFD IRDSADMVEL LDGYTHRVLV RLSGRSRPPL SFNVSLDFVI
310 320 330 340 350
LYFFSDRINQ AQGFAVLYQA TKEEPPQERP AVNQTLAEVI TEQANLSVSA
360 370 380 390 400
AHSSKVLYVI TPSPSHPPQT APGSHSWAPS VGANSHRVEG WTVYGLATLL
410 420 430 440 450
ILTVTAVVAK ILLHVTFKSH RVPASGDLRD CRQPGASGDI WTIFYEPSTT
460 470
ISIFKKKLKG QSQQDDRNPL VSD
Length:473
Mass (Da):51,673
Last modified:July 27, 2011 - v2
Checksum:i5E7A906662B80F7D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti238R → K in BAB40968 (PubMed:11267660).Curated1
Sequence conflicti248G → E in BAB40968 (PubMed:11267660).Curated1
Sequence conflicti266D → N in BAB40968 (PubMed:11267660).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB059617 mRNA. Translation: BAB40968.1.
AK141321 mRNA. Translation: BAE24649.1.
AL662853 Genomic DNA. Translation: CAI24979.1.
BC082546 mRNA. Translation: AAH82546.1.
BC138465 mRNA. Translation: AAI38466.1.
BC138464 mRNA. Translation: AAI38465.1.
CCDSiCCDS24399.1.
RefSeqiNP_115772.2. NM_032396.3.
UniGeneiMm.209989.

Genome annotation databases

EnsembliENSMUST00000020662; ENSMUSP00000020662; ENSMUSG00000020393.
GeneIDi84035.
KEGGimmu:84035.
UCSCiuc007hwh.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB059617 mRNA. Translation: BAB40968.1.
AK141321 mRNA. Translation: BAE24649.1.
AL662853 Genomic DNA. Translation: CAI24979.1.
BC082546 mRNA. Translation: AAH82546.1.
BC138465 mRNA. Translation: AAI38466.1.
BC138464 mRNA. Translation: AAI38465.1.
CCDSiCCDS24399.1.
RefSeqiNP_115772.2. NM_032396.3.
UniGeneiMm.209989.

3D structure databases

ProteinModelPortaliQ99N43.
SMRiQ99N43.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000020662.

PTM databases

PhosphoSitePlusiQ99N43.

Proteomic databases

PaxDbiQ99N43.
PeptideAtlasiQ99N43.
PRIDEiQ99N43.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000020662; ENSMUSP00000020662; ENSMUSG00000020393.
GeneIDi84035.
KEGGimmu:84035.
UCSCiuc007hwh.1. mouse.

Organism-specific databases

CTDi83999.
MGIiMGI:1933988. Kremen1.

Phylogenomic databases

eggNOGiENOG410IR07. Eukaryota.
ENOG41112QM. LUCA.
GeneTreeiENSGT00730000110973.
HOGENOMiHOG000070150.
HOVERGENiHBG052290.
InParanoidiQ99N43.
OMAiPECFTAN.
OrthoDBiEOG091G053O.
TreeFamiTF331319.

Miscellaneous databases

ChiTaRSiKremen1. mouse.
PROiPR:Q99N43.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000020393.
CleanExiMM_KREMEN1.
ExpressionAtlasiQ99N43. baseline and differential.
GenevisibleiQ99N43. MM.

Family and domain databases

CDDicd00041. CUB. 1 hit.
Gene3Di2.60.120.290. 1 hit.
InterProiView protein in InterPro
IPR000859. CUB_dom.
IPR017076. Kremen.
IPR000001. Kringle.
IPR013806. Kringle-like.
IPR018056. Kringle_CS.
IPR002889. WSC_carb-bd.
PfamiView protein in Pfam
PF00431. CUB. 1 hit.
PF00051. Kringle. 1 hit.
PF01822. WSC. 1 hit.
PIRSFiPIRSF036961. Kremen. 1 hit.
SMARTiView protein in SMART
SM00042. CUB. 1 hit.
SM00130. KR. 1 hit.
SM00321. WSC. 1 hit.
SUPFAMiSSF49854. SSF49854. 1 hit.
SSF57440. SSF57440. 1 hit.
PROSITEiView protein in PROSITE
PS01180. CUB. 1 hit.
PS00021. KRINGLE_1. 1 hit.
PS50070. KRINGLE_2. 1 hit.
PS51212. WSC. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiKREM1_MOUSE
AccessioniPrimary (citable) accession number: Q99N43
Secondary accession number(s): Q640Q6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 15, 2002
Last sequence update: July 27, 2011
Last modified: May 10, 2017
This is version 120 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.