The protein encoded by this gene is a cysteine-rich, extracellular protein with protease inhibitor-like domains whose expression is suppressed strongly in many tumors and cells transformed by various kinds of oncogenes. In normal cells, this membrane-anchored glycoprotein may serve as a negative regulator for matrix metalloproteinase-9, a key enzyme involved in tumor invasion a... See more...

Aliases for RECK Gene

Aliases for RECK Gene

  • Reversion Inducing Cysteine Rich Protein With Kazal Motifs 2 3 5
  • Reversion-Inducing Cysteine-Rich Protein With Kazal Motifs 3 4
  • Suppressor Of Tumorigenicity 15 Protein 3 4
  • ST15 3 4
  • Suppression Of Tumorigenicity 15 (Reversion-Inducing-Cysteine-Rich Protein With Kazal Motifs) 3
  • Suppression Of Tumorigenicity 5 (Reversion-Inducing-Cysteine-Rich Protein With Kazal Motifs) 3
  • Membrane-Anchored Glycoprotein (Metastasis And Invasion) 3
  • HRECK 4

External Ids for RECK Gene

Previous HGNC Symbols for RECK Gene

  • ST15

Previous GeneCards Identifiers for RECK Gene

  • GC09P036349
  • GC09P036206
  • GC09P036026
  • GC09P035990

Summaries for RECK Gene

Entrez Gene Summary for RECK Gene

  • The protein encoded by this gene is a cysteine-rich, extracellular protein with protease inhibitor-like domains whose expression is suppressed strongly in many tumors and cells transformed by various kinds of oncogenes. In normal cells, this membrane-anchored glycoprotein may serve as a negative regulator for matrix metalloproteinase-9, a key enzyme involved in tumor invasion and metastasis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

GeneCards Summary for RECK Gene

RECK (Reversion Inducing Cysteine Rich Protein With Kazal Motifs) is a Protein Coding gene. Diseases associated with RECK include Ovarian Cancer and Middle Ear Squamous Cell Carcinoma. Among its related pathways are Metabolism of proteins and Matrix Metalloproteinases. Gene Ontology (GO) annotations related to this gene include serine-type endopeptidase inhibitor activity and peptidase inhibitor activity.

UniProtKB/Swiss-Prot Summary for RECK Gene

  • Functions together with ADGRA2 to enable brain endothelial cells to selectively respond to Wnt7 signals (WNT7A or WNT7B) (PubMed:28289266, PubMed:30026314). Plays a key role in Wnt7-specific responses: required for central nervous system (CNS) angiogenesis and blood-brain barrier regulation (By similarity). Acts as a Wnt7-specific coactivator of canonical Wnt signaling by decoding Wnt ligands: acts by interacting specifically with the disordered linker region of Wnt7, thereby conferring ligand selectivity for Wnt7 (PubMed:30026314). ADGRA2 is then required to deliver RECK-bound Wnt7 to frizzled by assembling a higher-order RECK-ADGRA2-Fzd-LRP5-LRP6 complex (PubMed:30026314). Also acts as a serine protease inhibitor: negatively regulates matrix metalloproteinase-9 (MMP9) by suppressing MMP9 secretion and by direct inhibition of its enzymatic activity (PubMed:9789069, PubMed:18194466). Also inhibits metalloproteinase activity of MMP2 and MMP14 (MT1-MMP) (PubMed:9789069).

Gene Wiki entry for RECK Gene

Additional gene information for RECK Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for RECK Gene

Genomics for RECK Gene

GeneHancer (GH) Regulatory Elements for RECK Gene

Promoters and enhancers for RECK Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH09J036035 Promoter/Enhancer 2.2 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 510.6 +1.3 1336 4.6 NRF1 PHF8 ZBTB10 ZBTB26 SAP30 CTBP1 ZBTB7A POLR2A MXI1 KMT2B RECK GLIPR2 ATP8B5P OR2S2 ENSG00000276730
GH09J035656 Promoter/Enhancer 2.4 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 11.5 -375.9 -375897 10 RXRA EP300 ZBTB40 ZNF217 CTCF ZSCAN5C SIN3A NRF1 TCF12 MYC ARHGEF39 CCDC107 lnc-SIT1-1 PIGO NPR2 RECK CCL21 VCP FANCG ENSG00000230074
GH09J035913 Promoter/Enhancer 1.5 Ensembl ENCODE dbSUPER 11.6 -119.3 -119299 6.9 NRF1 NCOR1 BCLAF1 PHB2 ZBTB5 ZBTB11 REST TSC22D4 TOE1 MYC TLN1 GBA2 SPAAR ARHGEF39 RECK PIGO NDUFA5P4 OR13J1 FAM221B TMEM8B
GH09J036147 Promoter/Enhancer 1.3 Ensembl ENCODE dbSUPER 9.8 +111.7 111704 2.5 ZNF300 SP1 JUND FOS REST EP300 MXI1 BCL11A NR2F2 TCF12 CCIN CLTA ZCCHC7 RECK GLIPR2 GNE
GH09J036283 Enhancer 0.7 ENCODE 10.4 +247.5 247530 1 RBAK ZNF266 ZBTB11 ZNF426 ZNF213 ZFP64 ZNF34 ZC3H11A ZNF781 ZNF518A ZCCHC7 ARHGEF39 SPAG8 TMEM8B RUSC2 HMGB3P24 ENSG00000231393 RECK RNF38 RGP1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around RECK on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for RECK

Top Transcription factor binding sites by QIAGEN in the RECK gene promoter:
  • ATF6
  • c-Myc
  • C/EBPalpha
  • E47
  • FOXO4
  • ITF-2
  • Max
  • MyoD
  • Tal-1beta

Genomic Locations for RECK Gene

Genomic Locations for RECK Gene
chr9:36,036,913-36,124,455
(GRCh38/hg38)
Size:
87,543 bases
Orientation:
Plus strand
chr9:36,036,430-36,124,452
(GRCh37/hg19)
Size:
88,023 bases
Orientation:
Plus strand

Genomic View for RECK Gene

Genes around RECK on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RECK Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RECK Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RECK Gene

Proteins for RECK Gene

  • Protein details for RECK Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O95980-RECK_HUMAN
    Recommended name:
    Reversion-inducing cysteine-rich protein with Kazal motifs
    Protein Accession:
    O95980
    Secondary Accessions:
    • B2RNS1
    • Q5W0K6
    • Q8WX37

    Protein attributes for RECK Gene

    Size:
    971 amino acids
    Molecular mass:
    106457 Da
    Quaternary structure:
    • Interacts (via knot repeats) with WNT7A (via disordered linker region); the interaction is direct (PubMed:30026314). Interacts (via knot repeats) with WNT7B (via disordered linker region); the interaction is direct (PubMed:30026314). Interacts with ADGRA2; the interaction is direct (PubMed:30026314). Interacts with MMP9 (PubMed:9789069).

neXtProt entry for RECK Gene

Post-translational modifications for RECK Gene

  • N-glycosylated.
  • Glycosylation at Asn39, Asn86, Asn200, Asn297, and Asn352
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for RECK Gene

Domains & Families for RECK Gene

Gene Families for RECK Gene

Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted membrane proteins

Protein Domains for RECK Gene

Blocks:
  • Protease inhibitor, Kazal-type
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for RECK Gene

GenScript: Design optimal peptide antigens:
  • RECK protein (Q6P9E2_HUMAN)
  • Suppressor of tumorigenicity 15 protein (RECK_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O95980

UniProtKB/Swiss-Prot:

RECK_HUMAN :
  • The Kazal-like domains mediate the serine protease inhibitor activity.
  • Belongs to the RECK family.
Domain:
  • The Kazal-like domains mediate the serine protease inhibitor activity.
Family:
  • Belongs to the RECK family.
genes like me logo Genes that share domains with RECK: view

Function for RECK Gene

Molecular function for RECK Gene

UniProtKB/Swiss-Prot Function:
Functions together with ADGRA2 to enable brain endothelial cells to selectively respond to Wnt7 signals (WNT7A or WNT7B) (PubMed:28289266, PubMed:30026314). Plays a key role in Wnt7-specific responses: required for central nervous system (CNS) angiogenesis and blood-brain barrier regulation (By similarity). Acts as a Wnt7-specific coactivator of canonical Wnt signaling by decoding Wnt ligands: acts by interacting specifically with the disordered linker region of Wnt7, thereby conferring ligand selectivity for Wnt7 (PubMed:30026314). ADGRA2 is then required to deliver RECK-bound Wnt7 to frizzled by assembling a higher-order RECK-ADGRA2-Fzd-LRP5-LRP6 complex (PubMed:30026314). Also acts as a serine protease inhibitor: negatively regulates matrix metalloproteinase-9 (MMP9) by suppressing MMP9 secretion and by direct inhibition of its enzymatic activity (PubMed:9789069, PubMed:18194466). Also inhibits metalloproteinase activity of MMP2 and MMP14 (MT1-MMP) (PubMed:9789069).

Phenotypes From GWAS Catalog for RECK Gene

Gene Ontology (GO) - Molecular Function for RECK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004866 endopeptidase inhibitor activity IDA 9789069
GO:0004867 serine-type endopeptidase inhibitor activity IEA --
GO:0005515 protein binding IPI,IEA 21255571
GO:0008191 metalloendopeptidase inhibitor activity IDA,TAS 18194466
GO:0017147 Wnt-protein binding IEA --
genes like me logo Genes that share ontologies with RECK: view
genes like me logo Genes that share phenotypes with RECK: view

Animal Models for RECK Gene

MGI Knock Outs for RECK:
  • Reck Reck<tm1Ito>
  • Reck Reck<tm2.2Noda>

Animal Model Products

miRNA for RECK Gene

miRTarBase miRNAs that target RECK

Clone Products

  • Addgene plasmids for RECK

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for RECK Gene

Localization for RECK Gene

Subcellular locations from UniProtKB/Swiss-Prot for RECK Gene

Cell membrane; Lipid-anchor, GPI-anchor.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for RECK gene
Compartment Confidence
plasma membrane 5
extracellular 5
cytoskeleton 2
nucleus 2
mitochondrion 1
endoplasmic reticulum 1
endosome 1
cytosol 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Plasma membrane (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for RECK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005886 plasma membrane IBA,TAS --
GO:0016020 membrane TAS 9789069
GO:0031225 anchored component of membrane IEA --
GO:1990909 Wnt signalosome IEA --
genes like me logo Genes that share ontologies with RECK: view

Pathways & Interactions for RECK Gene

genes like me logo Genes that share pathways with RECK: view

Pathways by source for RECK Gene

1 Qiagen pathway for RECK Gene
  • Inhibition of Matrix Metalloproteinases
1 Cell Signaling Technology pathway for RECK Gene

Gene Ontology (GO) - Biological Process for RECK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001944 vasculature development IBA 21873635
GO:0001955 blood vessel maturation IBA 21873635
GO:0002040 sprouting angiogenesis IBA 21873635
GO:0007566 embryo implantation IEA --
GO:0010466 negative regulation of peptidase activity IEA --
genes like me logo Genes that share ontologies with RECK: view

No data available for SIGNOR curated interactions for RECK Gene

Drugs & Compounds for RECK Gene

(39) Drugs for RECK Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(30) Additional Compounds for RECK Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with RECK: view

Transcripts for RECK Gene

mRNA/cDNA for RECK Gene

5 REFSEQ mRNAs :
14 NCBI additional mRNA sequence :
3 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Clone Products

  • Addgene plasmids for RECK

Alternative Splicing Database (ASD) splice patterns (SP) for RECK Gene

No ASD Table

Relevant External Links for RECK Gene

GeneLoc Exon Structure for
RECK

Expression for RECK Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for RECK Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for RECK Gene

This gene is overexpressed in Plasma (11.0), Skin (9.7), Cerebral cortex (8.6), and Serum (8.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for RECK Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for RECK

SOURCE GeneReport for Unigene cluster for RECK Gene:

Hs.388918

mRNA Expression by UniProt/SwissProt for RECK Gene:

O95980-RECK_HUMAN
Tissue specificity: Expressed in various tissues and untransformed cells (PubMed:9789069). It is undetectable in tumor-derived cell lines and oncogenically transformed cells (PubMed:9789069).

Evidence on tissue expression from TISSUES for RECK Gene

  • Lung(4.4)
  • Intestine(2)
genes like me logo Genes that share expression patterns with RECK: view

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for RECK Gene

Orthologs for RECK Gene

This gene was present in the common ancestor of animals.

Orthologs for RECK Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia RECK 31 30
  • 99.9 (n)
OneToOne
dog
(Canis familiaris)
Mammalia RECK 31 30
  • 92.34 (n)
OneToOne
cow
(Bos Taurus)
Mammalia RECK 31 30
  • 91.59 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia RECK 31
  • 89 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia RECK 31
  • 88 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Reck 17 31 30
  • 87.96 (n)
rat
(Rattus norvegicus)
Mammalia Reck 30
  • 87.35 (n)
chicken
(Gallus gallus)
Aves RECK 31 30
  • 80.36 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia RECK 31
  • 79 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia reck 30
  • 72.66 (n)
zebrafish
(Danio rerio)
Actinopterygii RECK 31
  • 55 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta Reck 31 30
  • 47.08 (n)
OneToOne
CG5392 32
  • 33 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP010646 30
  • 46.12 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 38 (a)
OneToOne
Species where no ortholog for RECK was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for RECK Gene

ENSEMBL:
Gene Tree for RECK (if available)
TreeFam:
Gene Tree for RECK (if available)
Aminode:
Evolutionary constrained regions (ECRs) for RECK: view image

Paralogs for RECK Gene

No data available for Paralogs for RECK Gene

Variants for RECK Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for RECK Gene

SNP ID Clinical significance and condition Chr 09 pos Variation AA Info Type
707848 Benign: not provided 36,102,091(+) A/C INTRON_VARIANT
729613 Likely Benign: not provided 36,102,099(+) A/G MISSENSE_VARIANT
768292 Benign: not provided 36,122,958(+) C/T SYNONYMOUS_VARIANT
770385 Benign: not provided 36,058,819(+) T/G INTRON_VARIANT
rs16932912 - p.Val275Ile

Additional dbSNP identifiers (rs#s) for RECK Gene

Structural Variations from Database of Genomic Variants (DGV) for RECK Gene

Variant ID Type Subtype PubMed ID
esv34080 CNV loss 18971310
nsv1017711 CNV gain 25217958
nsv1125318 OTHER inversion 24896259
nsv478248 CNV novel sequence insertion 20440878
nsv831546 CNV loss 17160897
nsv831547 CNV loss 17160897

Variation tolerance for RECK Gene

Residual Variation Intolerance Score: 23.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.99; 80.01% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for RECK Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
RECK

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for RECK Gene

Disorders for RECK Gene

MalaCards: The human disease database

(23) MalaCards diseases for RECK Gene - From: LncRNADisease, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
ovarian cancer
  • ovarian cancer, somatic
middle ear squamous cell carcinoma
  • epidermoid carcinoma of the middle ear
middle ear carcinoma
  • carcinoma of middle ear
lactose intolerance
  • lm - lactose malabsorption
ocular albinism
  • albinism, ocular
- elite association - COSMIC cancer census association via MalaCards
Search RECK in MalaCards View complete list of genes associated with diseases

Additional Disease Information for RECK

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with RECK: view

No data available for UniProtKB/Swiss-Prot and Genatlas for RECK Gene

Publications for RECK Gene

  1. Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion by the membrane-anchored glycoprotein RECK. (PMID: 9789069) Takahashi C … Noda M (Proceedings of the National Academy of Sciences of the United States of America 1998) 2 3 4 23 54
  2. Promoter polymorphisms in matrix metalloproteinases and their inhibitors: few associations with breast cancer susceptibility and progression. (PMID: 17033924) Lei H … Försti A (Breast cancer research and treatment 2007) 3 23 41 54
  3. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41 54
  4. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 41 54
  5. The ß1-integrin-dependent function of RECK in physiologic and tumor angiogenesis. (PMID: 20407016) Miki T … Takahashi C (Molecular cancer research : MCR 2010) 3 23 54

Products for RECK Gene

Sources for RECK Gene