UniProtKB - O95980 (RECK_HUMAN)
Protein
Reversion-inducing cysteine-rich protein with Kazal motifs
Gene
RECK
Organism
Homo sapiens (Human)
Status
Functioni
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).By similarity4 Publications
GO - Molecular functioni
- coreceptor activity involved in canonical Wnt signaling pathway Source: Ensembl
- endopeptidase inhibitor activity Source: MGI
- metalloendopeptidase inhibitor activity Source: UniProtKB
- serine-type endopeptidase inhibitor activity Source: UniProtKB-KW
- Wnt-protein binding Source: Ensembl
GO - Biological processi
- blood vessel maturation Source: GO_Central
- embryo implantation Source: Ensembl
- embryonic forelimb morphogenesis Source: Ensembl
- extracellular matrix organization Source: GO_Central
- negative regulation of cell migration Source: BHF-UCL
- negative regulation of endopeptidase activity Source: GO_Central
- negative regulation of metalloendopeptidase activity Source: UniProtKB
- positive regulation of canonical Wnt signaling pathway Source: Ensembl
- regulation of angiogenesis Source: Ensembl
- regulation of establishment of blood-brain barrier Source: Ensembl
- sprouting angiogenesis Source: GO_Central
- vasculature development Source: GO_Central
Keywordsi
Molecular function | Protease inhibitor, Serine protease inhibitor |
Biological process | Wnt signaling pathway |
Enzyme and pathway databases
PathwayCommonsi | O95980 |
Reactomei | R-HSA-163125, Post-translational modification: synthesis of GPI-anchored proteins |
Protein family/group databases
MEROPSi | I01.037 |
Names & Taxonomyi
Protein namesi | Recommended name: Reversion-inducing cysteine-rich protein with Kazal motifs1 PublicationShort name: hRECK1 Publication Alternative name(s): Suppressor of tumorigenicity 15 proteinImported |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:11345, RECK |
MIMi | 605227, gene |
neXtProti | NX_O95980 |
VEuPathDBi | HostDB:ENSG00000122707.11 |
Subcellular locationi
Plasma membrane
- Cell membrane 2 Publications; GPI-anchor 1 Publication
Extracellular region or secreted
- extracellular region Source: Reactome
Plasma Membrane
- plasma membrane Source: HPA
Other locations
- anchored component of membrane Source: UniProtKB-KW
- membrane Source: GO_Central
- Wnt signalosome Source: Ensembl
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 225 – 272 | Missing : Abolished interaction with WNT7A. 1 PublicationAdd BLAST | 48 |
Keywords - Diseasei
Tumor suppressorOrganism-specific databases
DisGeNETi | 8434 |
OpenTargetsi | ENSG00000122707 |
PharmGKBi | PA34314 |
Miscellaneous databases
Pharosi | O95980, Tbio |
Genetic variation databases
BioMutai | RECK |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 22 | Sequence analysisAdd BLAST | 22 | |
ChainiPRO_0000016583 | 23 – 942 | Reversion-inducing cysteine-rich protein with Kazal motifsAdd BLAST | 920 | |
PropeptideiPRO_0000016584 | 943 – 971 | Removed in mature formSequence analysisAdd BLAST | 29 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 39 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 86 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 200 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 297 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 352 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 633 ↔ 658 | PROSITE-ProRule annotation | ||
Disulfide bondi | 635 ↔ 654 | PROSITE-ProRule annotation | ||
Disulfide bondi | 643 ↔ 671 | PROSITE-ProRule annotation | ||
Disulfide bondi | 716 ↔ 735 | PROSITE-ProRule annotation | ||
Disulfide bondi | 724 ↔ 750 | PROSITE-ProRule annotation | ||
Disulfide bondi | 761 ↔ 787 | PROSITE-ProRule annotation | ||
Lipidationi | 942 | GPI-anchor amidated serineSequence analysis | 1 |
Post-translational modificationi
N-glycosylated.1 Publication
Keywords - PTMi
Disulfide bond, Glycoprotein, GPI-anchor, LipoproteinProteomic databases
jPOSTi | O95980 |
MassIVEi | O95980 |
MaxQBi | O95980 |
PaxDbi | O95980 |
PeptideAtlasi | O95980 |
PRIDEi | O95980 |
ProteomicsDBi | 51158 |
PTM databases
GlyGeni | O95980, 6 sites, 1 O-linked glycan (1 site) |
iPTMneti | O95980 |
PhosphoSitePlusi | O95980 |
Expressioni
Tissue specificityi
Expressed in various tissues and untransformed cells (PubMed:9789069). It is undetectable in tumor-derived cell lines and oncogenically transformed cells (PubMed:9789069).1 Publication
Gene expression databases
Bgeei | ENSG00000122707, Expressed in parietal pleura and 235 other tissues |
Genevisiblei | O95980, HS |
Organism-specific databases
HPAi | ENSG00000122707, Low tissue specificity |
Interactioni
Subunit structurei
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).
2 PublicationsBinary interactionsi
O95980
With | #Exp. | IntAct |
---|---|---|
ERBB2 [P04626] | 4 | EBI-2823742,EBI-641062 |
GO - Molecular functioni
- Wnt-protein binding Source: Ensembl
Protein-protein interaction databases
BioGRIDi | 114014, 45 interactors |
IntActi | O95980, 8 interactors |
MINTi | O95980 |
STRINGi | 9606.ENSP00000367202 |
Miscellaneous databases
RNActi | O95980, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 37 – 84 | Knot 1Add BLAST | 48 | |
Repeati | 104 – 141 | Knot 2Add BLAST | 38 | |
Repeati | 151 – 197 | Knot 3Add BLAST | 47 | |
Repeati | 216 – 263 | Knot 4Add BLAST | 48 | |
Repeati | 292 – 338 | Knot 5Add BLAST | 47 | |
Domaini | 627 – 673 | Kazal-like 1PROSITE-ProRule annotationAdd BLAST | 47 | |
Domaini | 698 – 752 | Kazal-like 2PROSITE-ProRule annotationAdd BLAST | 55 | |
Domaini | 753 – 789 | Kazal-like 3PROSITE-ProRule annotationAdd BLAST | 37 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 37 – 338 | 5 X Knot repeatsAdd BLAST | 302 |
Domaini
The Kazal-like domains mediate the serine protease inhibitor activity.1 Publication
Sequence similaritiesi
Belongs to the RECK family.Curated
Keywords - Domaini
Repeat, SignalPhylogenomic databases
eggNOGi | KOG3649, Eukaryota |
GeneTreei | ENSGT00390000018540 |
HOGENOMi | CLU_013883_0_0_1 |
InParanoidi | O95980 |
OMAi | NTYPSAC |
OrthoDBi | 620790at2759 |
PhylomeDBi | O95980 |
TreeFami | TF324424 |
Family and domain databases
InterProi | View protein in InterPro IPR002350, Kazal_dom IPR036058, Kazal_dom_sf IPR039016, RECK |
PANTHERi | PTHR13487, PTHR13487, 1 hit |
Pfami | View protein in Pfam PF07648, Kazal_2, 3 hits |
SMARTi | View protein in SMART SM00280, KAZAL, 3 hits |
SUPFAMi | SSF100895, SSF100895, 3 hits |
PROSITEi | View protein in PROSITE PS00282, KAZAL_1, 1 hit PS51465, KAZAL_2, 3 hits |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
O95980-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MATVRASLRG ALLLLLAVAG VAEVAGGLAP GSAGALCCNH SKDNQMCRDV
60 70 80 90 100
CEQIFSSKSE SRLKHLLQRA PDYCPETMVE IWNCMNSSLP GVFKKSDGWV
110 120 130 140 150
GLGCCELAIA LECRQACKQA SSKNDISKVC RKEYENALFS CISRNEMGSV
160 170 180 190 200
CCSYAGHHTN CREYCQAIFR TDSSPGPSQI KAVENYCASI SPQLIHCVNN
210 220 230 240 250
YTQSYPMRNP TDSLYCCDRA EDHACQNACK RILMSKKTEM EIVDGLIEGC
260 270 280 290 300
KTQPLPQDPL WQCFLESSQS VHPGVTVHPP PSTGLDGAKL HCCSKANTST
310 320 330 340 350
CRELCTKLYS MSWGNTQSWQ EFDRFCEYNP VEVSMLTCLA DVREPCQLGC
360 370 380 390 400
RNLTYCTNFN NRPTELFRSC NAQSDQGAMN DMKLWEKGSI KMPFINIPVL
410 420 430 440 450
DIKKCQPEMW KAIACSLQIK PCHSKSRGSI ICKSDCVEIL KKCGDQNKFP
460 470 480 490 500
EDHTAESICE LLSPTDDLKN CIPLDTYLRP STLGNIVEEV THPCNPNPCP
510 520 530 540 550
ANELCEVNRK GCPSGDPCLP YFCVQGCKLG EASDFIVRQG TLIQVPSSAG
560 570 580 590 600
EVGCYKICSC GQSGLLENCM EMHCIDLQKS CIVGGKRKSH GTSFSIDCNV
610 620 630 640 650
CSCFAGNLVC STRLCLSEHS SEDDRRTFTG LPCNCADQFV PVCGQNGRTY
660 670 680 690 700
PSACIARCVG LQDHQFEFGS CMSKDPCNPN PCQKNQRCIP KPQVCLTTFD
710 720 730 740 750
KFGCSQYECV PRQLACDQVQ DPVCDTDHME HNNLCTLYQR GKSLSYKGPC
760 770 780 790 800
QPFCRATEPV CGHNGETYSS VCAAYSDRVA VDYYGDCQAV GVLSEHSSVA
810 820 830 840 850
ECASVKCPSL LAAGCKPIIP PGACCPLCAG MLRVLFDKEK LDTIAKVTNK
860 870 880 890 900
KPITVLEILQ KIRMHVSVPQ CDVFGYFSIE SEIVILIIPV DHYPKALQIE
910 920 930 940 950
ACNKEAEKIE SLINSDSPTL ASHVPLSALI ISQVQVSSSV PSAGVRARPS
960 970
CHSLLLPLSL GLALHLLWTY N
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_034021 | 275 | V → I. Corresponds to variant dbSNP:rs16932912Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D50406 mRNA Translation: BAA34060.1 AL158830 Genomic DNA No translation available. AL138834 Genomic DNA No translation available. CH471071 Genomic DNA Translation: EAW58318.1 BC137093 mRNA Translation: AAI37094.1 |
CCDSi | CCDS6597.1 |
RefSeqi | NP_066934.1, NM_021111.2 |
Genome annotation databases
Ensembli | ENST00000377966; ENSP00000367202; ENSG00000122707 |
GeneIDi | 8434 |
KEGGi | hsa:8434 |
UCSCi | uc003zyv.4, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D50406 mRNA Translation: BAA34060.1 AL158830 Genomic DNA No translation available. AL138834 Genomic DNA No translation available. CH471071 Genomic DNA Translation: EAW58318.1 BC137093 mRNA Translation: AAI37094.1 |
CCDSi | CCDS6597.1 |
RefSeqi | NP_066934.1, NM_021111.2 |
3D structure databases
SMRi | O95980 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 114014, 45 interactors |
IntActi | O95980, 8 interactors |
MINTi | O95980 |
STRINGi | 9606.ENSP00000367202 |
Protein family/group databases
MEROPSi | I01.037 |
PTM databases
GlyGeni | O95980, 6 sites, 1 O-linked glycan (1 site) |
iPTMneti | O95980 |
PhosphoSitePlusi | O95980 |
Genetic variation databases
BioMutai | RECK |
Proteomic databases
jPOSTi | O95980 |
MassIVEi | O95980 |
MaxQBi | O95980 |
PaxDbi | O95980 |
PeptideAtlasi | O95980 |
PRIDEi | O95980 |
ProteomicsDBi | 51158 |
Protocols and materials databases
Antibodypediai | 26128, 287 antibodies |
Genome annotation databases
Ensembli | ENST00000377966; ENSP00000367202; ENSG00000122707 |
GeneIDi | 8434 |
KEGGi | hsa:8434 |
UCSCi | uc003zyv.4, human |
Organism-specific databases
CTDi | 8434 |
DisGeNETi | 8434 |
GeneCardsi | RECK |
HGNCi | HGNC:11345, RECK |
HPAi | ENSG00000122707, Low tissue specificity |
MIMi | 605227, gene |
neXtProti | NX_O95980 |
OpenTargetsi | ENSG00000122707 |
PharmGKBi | PA34314 |
VEuPathDBi | HostDB:ENSG00000122707.11 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3649, Eukaryota |
GeneTreei | ENSGT00390000018540 |
HOGENOMi | CLU_013883_0_0_1 |
InParanoidi | O95980 |
OMAi | NTYPSAC |
OrthoDBi | 620790at2759 |
PhylomeDBi | O95980 |
TreeFami | TF324424 |
Enzyme and pathway databases
PathwayCommonsi | O95980 |
Reactomei | R-HSA-163125, Post-translational modification: synthesis of GPI-anchored proteins |
Miscellaneous databases
BioGRID-ORCSi | 8434, 3 hits in 874 CRISPR screens |
ChiTaRSi | RECK, human |
GeneWikii | RECK |
GenomeRNAii | 8434 |
Pharosi | O95980, Tbio |
PROi | PR:O95980 |
RNActi | O95980, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000122707, Expressed in parietal pleura and 235 other tissues |
Genevisiblei | O95980, HS |
Family and domain databases
InterProi | View protein in InterPro IPR002350, Kazal_dom IPR036058, Kazal_dom_sf IPR039016, RECK |
PANTHERi | PTHR13487, PTHR13487, 1 hit |
Pfami | View protein in Pfam PF07648, Kazal_2, 3 hits |
SMARTi | View protein in SMART SM00280, KAZAL, 3 hits |
SUPFAMi | SSF100895, SSF100895, 3 hits |
PROSITEi | View protein in PROSITE PS00282, KAZAL_1, 1 hit PS51465, KAZAL_2, 3 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | RECK_HUMAN | |
Accessioni | O95980Primary (citable) accession number: O95980 Secondary accession number(s): B2RNS1, Q5W0K6, Q8WX37 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 16, 2002 |
Last sequence update: | May 1, 1999 | |
Last modified: | February 10, 2021 | |
This is version 162 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 9
Human chromosome 9: entries, gene names and cross-references to MIM - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Human entries with genetic variants
List of human entries with genetic variants