Q9UBT3 (DKK4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Dickkopf-related protein 4
Short name=Dickkopf-4
Short name=Dkk-4
Short name=hDkk-4

Cleaved into the following chain:

1. Dickkopf-related protein 4 short form

Gene names

Name:

DKK4

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	224 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6. DKKs play an important role in vertebrate development, where they locally inhibit Wnt regulated processes such as antero-posterior axial patterning, limb development, somitogenesis and eye formation. In the adult, Dkks are implicated in bone formation and bone disease, cancer and Alzheimer disease By similarity.
Subunit structure	Interacts with LRP5 and LRP6 By similarity.
Subcellular location	Secreted.
Tissue specificity	Expressed in cerebellum, T-cells, esophagus and lung.
Domain	The C-terminal cysteine-rich domain mediates interaction with LRP5 and LRP6 By similarity.
Post-translational modification	Appears to be not glycosylated. Can be proteolytically processed by a furin-like protease.
Sequence similarities	Belongs to the dickkopf family.

Ontologies

Keywords
Biological process	Wnt signaling pathway
Cellular component	Secreted
Domain	Signal
Molecular function	Developmental protein
PTM	Cleavage on pair of basic residues Disulfide bond
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of Wnt receptor signaling pathway Non-traceable author statement Ref.1. Source: UniProtKB
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Ref.1 Ref.4
	Chain	19 – 224	206	Dickkopf-related protein 4		PRO_0000007225
	Chain	134 – 224	91	Dickkopf-related protein 4 short form		PRO_0000007226
Regions
	Region	41 – 90	50	DKK-type Cys-1
	Region	145 – 218	74	DKK-type Cys-2
Amino acid modifications
	Disulfide bond	145 ↔ 157		By similarity
	Disulfide bond	151 ↔ 166		By similarity
	Disulfide bond	156 ↔ 194		By similarity
	Disulfide bond	176 ↔ 202		By similarity
	Disulfide bond	196 ↔ 218		By similarity
Experimental info
	Sequence conflict	93	1	M → L in BAA33438. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9UBT3 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 45F8EBC476961357	FASTA	224	24,876
	10 20 30 40 50 60 MVAAVLLGLS WLCSPLGALV LDFNNIRSSA DLHGARKGSQ CLSDTDCNTR KFCLQPRDEK 70 80 90 100 110 120 PFCATCRGLR RRCQRDAMCC PGTLCVNDVC TTMEDATPIL ERQLDEQDGT HAEGTTGHPV 130 140 150 160 170 180 QENQPKRKPS IKKSQGRKGQ EGESCLRTFD CGPGLCCARH FWTKICKPVL LEGQVCSRRG 190 200 210 220 HKDTAQAPEI FQRCDCGPGL LCRSQLTSNR QHARLRVCQK IEKL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Functional and structural diversity of the human Dickkopf gene family." Krupnik V.E., Sharp J.D., Jiang C., Robison K., Chickering T.W., Amaravadi L., Brown D.E., Guyot D., Mays G., Leiby K., Chang B., Duong T., Goodearl A.D.J., Gearing D.P., Sokol S.Y., McCarthy S.A. Gene 238:301-313(1999) [PubMed: 10570958] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 19-28 AND 134-144, PROTEOLYTIC PROCESSING.
[2]	"Human Dickkopf as well as DAN family members, Cerberus and Gremlin, are preferentially expressed in the epithelial malignant cell lines." Tate G., Mitsuya T. J. Biochem. Mol. Biol. Biophys. 3:239-242(1999) Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed: 15340161] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-33.
[5]	"Function and biological roles of the Dickkopf family of Wnt modulators." Niehrs C. Oncogene 25:7469-7481(2006) [PubMed: 17143291] [Abstract] Cited for: REVIEW OF THE DKK FAMILY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF177397 mRNA. Translation: AAF02677.1. AB018005 Genomic DNA. Translation: BAA33475.1. AB017788 mRNA. Translation: BAA33438.1. BC107046 mRNA. Translation: AAI07047.1. BC107047 mRNA. Translation: AAI07048.1.
IPI	IPI00002771.
RefSeq	NP_055235.1. NM_014420.2.
UniGene	Hs.159311.
3D structure databases
ProteinModelPortal	Q9UBT3.
SMR	Q9UBT3. Positions 134-221.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9UBT3.
Polymorphism databases
DMDM	13124092.
Proteomic databases
PRIDE	Q9UBT3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000220812; ENSP00000220812; ENSG00000104371.
GeneID	27121.
KEGG	hsa:27121.
UCSC	uc003xpb.1. human.
Organism-specific databases
CTD	27121.
GeneCards	GC08M042248.
H-InvDB	HIX0034234.
HGNC	HGNC:2894. DKK4.
MIM	605417. gene.
neXtProt	NX_Q9UBT3.
PharmGKB	PA27348.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG04206.
GeneTree	ENSGT00390000007000.
HOGENOM	HBG445081.
HOVERGEN	HBG081443.
InParanoid	Q9UBT3.
OMA	GSQCLSD.
OrthoDB	EOG40GCRN.
PhylomeDB	Q9UBT3.
Gene expression databases
ArrayExpress	Q9UBT3.
Bgee	Q9UBT3.
CleanEx	HS_DKK4.
Genevestigator	Q9UBT3.
GermOnline	ENSG00000104371. Homo sapiens.
Family and domain databases
InterPro	IPR006796. Dickkopf_N. IPR023569. Prokineticin_domain. [Graphical view]
KO	K02165.
Pfam	PF04706. Dickkopf_N. 1 hit. PF06607. Prokineticin. 1 hit. [Graphical view]
ProDom	PD059788. Prokineticin. 1 hit. [Graphical view] [Entries sharing at least one domain]
ProtoNet	Search...
Other
NextBio	49808.
SOURCE	Search...

Entry information

Entry name

DKK4_HUMAN

Accession

Primary (citable) accession number: Q9UBT3
Secondary accession number(s): Q3KNX0, Q9Y4C3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	May 1, 2000
Last modified:	January 25, 2012
This is version 88 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.