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Protein

Kremen protein 2

Gene

KREMEN2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Receptor for Dickkopf protein. Cooperates with Dickkopf to block Wnt/beta-catenin signaling. Forms a ternary complex with Dkk1 and LRP6 and induces rapid endocytosis and removal of the Wnt receptor LRP6 from the plasma membrane (By similarity).By similarity

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Wnt signaling pathway

Enzyme and pathway databases

ReactomeiR-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.
SignaLinkiQ8NCW0.
SIGNORiQ8NCW0.

Names & Taxonomyi

Protein namesi
Recommended name:
Kremen protein 2
Alternative 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
OrganismiHomo sapiens (Human)Imported
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:18797. KREMEN2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini26 – 364ExtracellularSequence analysisAdd BLAST339
Transmembranei365 – 387HelicalSequence analysisAdd BLAST23
Topological domaini388 – 462CytoplasmicSequence analysisAdd BLAST75

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

OpenTargetsiENSG00000131650.
PharmGKBiPA38683.

Polymorphism and mutation databases

BioMutaiKREMEN2.
DMDMi30173086.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Sequence analysisAdd BLAST25
ChainiPRO_000002156826 – 462Kremen protein 2Add BLAST437

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi36 ↔ 119By similarity
Glycosylationi49N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi60 ↔ 100By similarity
Disulfide bondi89 ↔ 114By similarity
Disulfide bondi219 ↔ 245By similarity
Glycosylationi222N-linked (GlcNAc...)Sequence analysis1
Glycosylationi244N-linked (GlcNAc...)Sequence analysis1
Glycosylationi351N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ8NCW0.
PeptideAtlasiQ8NCW0.
PRIDEiQ8NCW0.

PTM databases

iPTMnetiQ8NCW0.
PhosphoSitePlusiQ8NCW0.

Expressioni

Gene expression databases

BgeeiENSG00000131650.
CleanExiHS_KREMEN2.
ExpressionAtlasiQ8NCW0. baseline and differential.
GenevisibleiQ8NCW0. HS.

Organism-specific databases

HPAiHPA003223.

Interactioni

Subunit structurei

Interacts with ERLEC1.By similarity

Protein-protein interaction databases

STRINGi9606.ENSP00000304422.

Structurei

3D structure databases

ProteinModelPortaliQ8NCW0.
SMRiQ8NCW0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini35 – 119KringlePROSITE-ProRule annotationAdd BLAST85
Domaini121 – 215WSCPROSITE-ProRule annotationCuratedAdd BLAST95
Domaini219 – 326CUBPROSITE-ProRule annotationCuratedAdd BLAST108

Domaini

Binding to ERLEC1 is mediated by the oligosaccharides linked to the kringle domain.By similarity

Sequence similaritiesi

Contains 1 CUB domain.PROSITE-ProRule annotationCurated
Contains 1 kringle domain.PROSITE-ProRule annotationCurated
Contains 1 WSC domain.PROSITE-ProRule annotationCurated

Keywords - Domaini

Kringle, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4157. Eukaryota.
ENOG4111FP9. LUCA.
GeneTreeiENSGT00730000110973.
HOGENOMiHOG000070150.
HOVERGENiHBG052291.
InParanoidiQ8NCW0.
OMAiGRSWAVW.
OrthoDBiEOG091G053O.
PhylomeDBiQ8NCW0.
TreeFamiTF331319.

Family and domain databases

CDDicd00041. CUB. 1 hit.
Gene3Di2.60.120.290. 1 hit.
InterProiIPR000859. CUB_dom.
IPR017076. Kremen.
IPR000001. Kringle.
IPR013806. Kringle-like.
IPR018056. Kringle_CS.
IPR002889. WSC_carb-bd.
[Graphical view]
PfamiPF00431. CUB. 1 hit.
PF00051. Kringle. 1 hit.
PF01822. WSC. 1 hit.
[Graphical view]
PIRSFiPIRSF036961. Kremen. 1 hit.
SMARTiSM00042. CUB. 1 hit.
SM00130. KR. 1 hit.
SM00321. WSC. 1 hit.
[Graphical view]
SUPFAMiSSF49854. SSF49854. 1 hit.
SSF57440. SSF57440. 1 hit.
PROSITEiPS01180. CUB. 1 hit.
PS00021. KRINGLE_1. 1 hit.
PS50070. KRINGLE_2. 1 hit.
PS51212. WSC. 1 hit.
[Graphical view]

Sequences (6)i

Sequence statusi: Complete.

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

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1Curated (identifier: Q8NCW0-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        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
Length:462
Mass (Da):48,849
Last modified:October 1, 2002 - v1
Checksum:iCE33015917A9AA68
GO
Isoform 2Curated (identifier: Q8NCW0-2) [UniParc]FASTAAdd to basket
Also known as: Kremen2a

The sequence of this isoform differs from the canonical sequence as follows:
     394-424: SCLLAPGKGPPALGASRGPRRSWAVWYQQPR → CGALGQGLRADRWWGAGAPEGNRARKELLGS
     425-462: Missing.

Show »
Length:424
Mass (Da):45,055
Checksum:i376B000839A519C4
GO
Isoform 3Curated (identifier: Q8NCW0-3) [UniParc]FASTAAdd to basket
Also known as: Kremen2b

The sequence of this isoform differs from the canonical sequence as follows:
     367-420: ARVFSTVTAV...GPRRSWAVWY → GAVCWLREKG...LRVLPRATGL
     421-462: Missing.

Show »
Length:420
Mass (Da):44,403
Checksum:i75C4479C67BA0D6E
GO
Isoform 4Curated (identifier: Q8NCW0-4) [UniParc]FASTAAdd to basket
Also known as: Kremen2c

The sequence of this isoform differs from the canonical sequence as follows:
     367-399: ARVFSTVTAVSVLLLLLLGLLRPLRRRSCLLAP → GEAGARDGSESGSRPLAPILTAAVCPQPGSSRR
     400-462: Missing.

Show »
Length:399
Mass (Da):42,037
Checksum:i5F677BDEBA72E0D3
GO
Isoform 5 (identifier: Q8NCW0-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     162-200: Missing.

Note: No experimental confirmation available.
Show »
Length:423
Mass (Da):44,880
Checksum:i47DB607DAAB94F9C
GO
Isoform 6 (identifier: Q8NCW0-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     162-200: Missing.
     367-462: ARVFSTVTAV...SSLRSLISAL → GAVCWLREKG...LRVLPRATGL

Note: No experimental confirmation available.
Show »
Length:381
Mass (Da):40,433
Checksum:i454966A1E691F3D0
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti164 – 202Missing in BAC11365 (PubMed:14702039).CuratedAdd BLAST39
Sequence conflicti285A → D in BAC11365 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_059691408A → P.Corresponds to variant rs11866302dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_046399162 – 200Missing in isoform 5 and isoform 6. 1 PublicationAdd BLAST39
Alternative sequenceiVSP_047386367 – 462ARVFS…LISAL → GAVCWLREKGPRRWGLPGAP GEAGLCGTNSPEGWPCPAPP GTPRLRVLPRATGL in isoform 6. CuratedAdd BLAST96
Alternative sequenceiVSP_050511367 – 420ARVFS…WAVWY → GAVCWLREKGPRRWGLPGAP GEAGLCGTNSPEGWPCPAPP GTPRLRVLPRATGL in isoform 3. 2 PublicationsAdd BLAST54
Alternative sequenceiVSP_050513367 – 399ARVFS…CLLAP → GEAGARDGSESGSRPLAPIL TAAVCPQPGSSRR in isoform 4. 2 PublicationsAdd BLAST33
Alternative sequenceiVSP_050509394 – 424SCLLA…YQQPR → CGALGQGLRADRWWGAGAPE GNRARKELLGS in isoform 2. CuratedAdd BLAST31
Alternative sequenceiVSP_050514400 – 462Missing in isoform 4. 2 PublicationsAdd BLAST63
Alternative sequenceiVSP_050512421 – 462Missing in isoform 3. 2 PublicationsAdd BLAST42
Alternative sequenceiVSP_050510425 – 462Missing in isoform 2. CuratedAdd BLAST38

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.
CCDSiCCDS10483.1. [Q8NCW0-1]
CCDS10484.1. [Q8NCW0-3]
CCDS58412.1. [Q8NCW0-5]
CCDS58413.1. [Q8NCW0-6]
RefSeqiNP_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]
UniGeneiHs.661128.

Genome annotation databases

EnsembliENST00000303746; 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]
GeneIDi79412.
KEGGihsa:79412.
UCSCiuc002csg.4. human. [Q8NCW0-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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.
CCDSiCCDS10483.1. [Q8NCW0-1]
CCDS10484.1. [Q8NCW0-3]
CCDS58412.1. [Q8NCW0-5]
CCDS58413.1. [Q8NCW0-6]
RefSeqiNP_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]
UniGeneiHs.661128.

3D structure databases

ProteinModelPortaliQ8NCW0.
SMRiQ8NCW0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000304422.

PTM databases

iPTMnetiQ8NCW0.
PhosphoSitePlusiQ8NCW0.

Polymorphism and mutation databases

BioMutaiKREMEN2.
DMDMi30173086.

Proteomic databases

PaxDbiQ8NCW0.
PeptideAtlasiQ8NCW0.
PRIDEiQ8NCW0.

Protocols and materials databases

DNASUi79412.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000303746; 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]
GeneIDi79412.
KEGGihsa:79412.
UCSCiuc002csg.4. human. [Q8NCW0-1]

Organism-specific databases

CTDi79412.
GeneCardsiKREMEN2.
HGNCiHGNC:18797. KREMEN2.
HPAiHPA003223.
MIMi609899. gene.
neXtProtiNX_Q8NCW0.
OpenTargetsiENSG00000131650.
PharmGKBiPA38683.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4157. Eukaryota.
ENOG4111FP9. LUCA.
GeneTreeiENSGT00730000110973.
HOGENOMiHOG000070150.
HOVERGENiHBG052291.
InParanoidiQ8NCW0.
OMAiGRSWAVW.
OrthoDBiEOG091G053O.
PhylomeDBiQ8NCW0.
TreeFamiTF331319.

Enzyme and pathway databases

ReactomeiR-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.
SignaLinkiQ8NCW0.
SIGNORiQ8NCW0.

Miscellaneous databases

GenomeRNAii79412.
PROiQ8NCW0.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000131650.
CleanExiHS_KREMEN2.
ExpressionAtlasiQ8NCW0. baseline and differential.
GenevisibleiQ8NCW0. HS.

Family and domain databases

CDDicd00041. CUB. 1 hit.
Gene3Di2.60.120.290. 1 hit.
InterProiIPR000859. CUB_dom.
IPR017076. Kremen.
IPR000001. Kringle.
IPR013806. Kringle-like.
IPR018056. Kringle_CS.
IPR002889. WSC_carb-bd.
[Graphical view]
PfamiPF00431. CUB. 1 hit.
PF00051. Kringle. 1 hit.
PF01822. WSC. 1 hit.
[Graphical view]
PIRSFiPIRSF036961. Kremen. 1 hit.
SMARTiSM00042. CUB. 1 hit.
SM00130. KR. 1 hit.
SM00321. WSC. 1 hit.
[Graphical view]
SUPFAMiSSF49854. SSF49854. 1 hit.
SSF57440. SSF57440. 1 hit.
PROSITEiPS01180. CUB. 1 hit.
PS00021. KRINGLE_1. 1 hit.
PS50070. KRINGLE_2. 1 hit.
PS51212. WSC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKREM2_HUMAN
AccessioniPrimary (citable) accession number: Q8NCW0
Secondary accession number(s): B4DXF6
, I3L2S2, Q8N2J4, Q8NCW1, Q96GL8, Q9BTP9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 23, 2003
Last sequence update: October 1, 2002
Last modified: November 30, 2016
This is version 128 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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.