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Protein

Kremen protein 2

Gene

KREMEN2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at transcript 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. 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

Keywordsi

Biological processWnt 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

EuPathDBiHostDB:ENSG00000131650.13
HGNCiHGNC:18797 KREMEN2
MIMi609899 gene
neXtProtiNX_Q8NCW0

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi79412
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...) asparagineSequence analysis1
Disulfide bondi60 ↔ 100By similarity
Disulfide bondi89 ↔ 114By similarity
Disulfide bondi219 ↔ 245By similarity
Glycosylationi222N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi244N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi351N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ8NCW0
PaxDbiQ8NCW0
PeptideAtlasiQ8NCW0
PRIDEiQ8NCW0
ProteomicsDBi72953
72954 [Q8NCW0-2]
72955 [Q8NCW0-3]
72956 [Q8NCW0-4]

PTM databases

iPTMnetiQ8NCW0
PhosphoSitePlusiQ8NCW0

Expressioni

Gene expression databases

BgeeiENSG00000131650 Expressed in 68 organ(s), highest expression level in ectocervix
CleanExiHS_KREMEN2
GenevisibleiQ8NCW0 HS

Organism-specific databases

HPAiHPA003223

Interactioni

Subunit structurei

Interacts with ERLEC1. Forms a ternary complex with DKK1 and LRP6.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

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
cd00108 KR, 1 hit
Gene3Di2.40.20.10, 1 hit
2.60.120.290, 1 hit
InterProiView 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
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

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 dbSNP:rs11866302Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiKREM2_HUMAN
AccessioniPrimary (citable) accession number: Q8NCW0
Secondary accession number(s): B4DXF6
, I3L2S2, Q8N2J4, Q8NCW1, Q96GL8, Q9BTP9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 23, 2003
Last sequence update: October 1, 2002
Last modified: September 12, 2018
This is version 139 of the entry and version 1 of the sequence. See 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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