ID RECK_HUMAN Reviewed; 971 AA. AC O95980; B2RNS1; Q5W0K6; Q8WX37; DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1999, sequence version 1. DT 13-FEB-2019, entry version 151. DE RecName: Full=Reversion-inducing cysteine-rich protein with Kazal motifs {ECO:0000303|PubMed:9789069}; DE Short=hRECK {ECO:0000303|PubMed:9789069}; DE AltName: Full=Suppressor of tumorigenicity 15 protein {ECO:0000312|EMBL:BAA34060.1}; DE Flags: Precursor; GN Name=RECK {ECO:0000303|PubMed:9789069, ECO:0000312|HGNC:HGNC:11345}; GN Synonyms=ST15 {ECO:0000312|EMBL:BAA34060.1}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, RP GLYCOSYLATION, AND TISSUE SPECIFICITY. RC TISSUE=Fibroblast; RX PubMed=9789069; DOI=10.1073/pnas.95.22.13221; RA Takahashi C., Sheng Z., Horan T.P., Kitayama H., Maki M., Hitomi K., RA Kitaura Y., Takai S., Sasahara R.M., Horimoto A., Ikawa Y., RA Ratzkin B.J., Arakawa T., Noda M.; RT "Regulation of matrix metalloproteinase-9 and inhibition of tumor RT invasion by the membrane-anchored glycoprotein RECK."; RL Proc. Natl. Acad. Sci. U.S.A. 95:13221-13226(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R., RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., RA Rogers J., Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP FUNCTION, AND DOMAIN. RX PubMed=18194466; DOI=10.1111/j.1582-4934.2008.00215.x; RA Chang C.K., Hung W.C., Chang H.C.; RT "The Kazal motifs of RECK protein inhibit MMP-9 secretion and activity RT and reduce metastasis of lung cancer cells in vitro and in vivo."; RL J. Cell. Mol. Med. 12:2781-2789(2008). RN [6] RP FUNCTION. RX PubMed=28289266; DOI=10.1242/jcs.198093; RA Alok A., Lei Z., Jagannathan N.S., Kaur S., Harmston N., Rozen S.G., RA Tucker-Kellogg L., Virshup D.M.; RT "Wnt proteins synergize to activate beta-catenin signaling."; RL J. Cell Sci. 130:1532-1544(2017). RN [7] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ADGRA2; WNT7A AND RP WNT7B, AND MUTAGENESIS OF 225-CYS--HIS-272. RX PubMed=30026314; DOI=10.1126/science.aat1178; RA Eubelen M., Bostaille N., Cabochette P., Gauquier A., Tebabi P., RA Dumitru A.C., Koehler M., Gut P., Alsteens D., Stainier D.Y.R., RA Garcia-Pino A., Vanhollebeke B.; RT "A molecular mechanism for Wnt ligand-specific signaling."; RL Science 361:0-0(2018). CC -!- FUNCTION: Functions together with ADGRA2 to enable brain CC endothelial cells to selectively respond to Wnt7 signals (WNT7A or CC WNT7B) (PubMed:28289266, PubMed:30026314). Plays a key role in CC Wnt7-specific responses: required for central nervous system (CNS) CC angiogenesis and blood-brain barrier regulation (By similarity). CC Acts as a Wnt7-specific coactivator of canonical Wnt signaling by CC decoding Wnt ligands: acts by interacting specifically with the CC disordered linker region of Wnt7, thereby conferring ligand CC selectivity for Wnt7 (PubMed:30026314). ADGRA2 is then required to CC deliver RECK-bound Wnt7 to frizzled by assembling a higher-order CC RECK-ADGRA2-Fzd-LRP5-LRP6 complex (PubMed:30026314). Also acts as CC a serine protease inhibitor: negatively regulates matrix CC metalloproteinase-9 (MMP9) by suppressing MMP9 secretion and by CC direct inhibition of its enzymatic activity (PubMed:9789069, CC PubMed:18194466). Also inhibits metalloproteinase activity of MMP2 CC and MMP14 (MT1-MMP) (PubMed:9789069). CC {ECO:0000250|UniProtKB:Q9Z0J1, ECO:0000269|PubMed:18194466, CC ECO:0000269|PubMed:28289266, ECO:0000269|PubMed:30026314, CC ECO:0000269|PubMed:9789069}. CC -!- SUBUNIT: Interacts (via knot repeats) with WNT7A (via disordered CC linker region); the interaction is direct (PubMed:30026314). CC Interacts (via knot repeats) with WNT7B (via disordered linker CC region); the interaction is direct (PubMed:30026314). Interacts CC with ADGRA2; the interaction is direct (PubMed:30026314). CC Interacts with MMP9 (PubMed:9789069). CC {ECO:0000269|PubMed:30026314, ECO:0000269|PubMed:9789069}. CC -!- INTERACTION: CC P04626:ERBB2; NbExp=4; IntAct=EBI-2823742, EBI-641062; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:30026314, CC ECO:0000269|PubMed:9789069}; Lipid-anchor, GPI-anchor CC {ECO:0000269|PubMed:9789069}. CC -!- TISSUE SPECIFICITY: Expressed in various tissues and untransformed CC cells (PubMed:9789069). It is undetectable in tumor-derived cell CC lines and oncogenically transformed cells (PubMed:9789069). CC {ECO:0000269|PubMed:9789069}. CC -!- DOMAIN: The Kazal-like domains mediate the serine protease CC inhibitor activity. {ECO:0000269|PubMed:18194466}. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:9789069}. CC -!- SIMILARITY: Belongs to the RECK family. {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; D50406; BAA34060.1; -; mRNA. DR EMBL; AL158830; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL138834; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471071; EAW58318.1; -; Genomic_DNA. DR EMBL; BC137093; AAI37094.1; -; mRNA. DR CCDS; CCDS6597.1; -. DR RefSeq; NP_066934.1; NM_021111.2. DR UniGene; Hs.388918; -. DR ProteinModelPortal; O95980; -. DR SMR; O95980; -. DR BioGrid; 114014; 17. DR IntAct; O95980; 4. DR MINT; O95980; -. DR STRING; 9606.ENSP00000367202; -. DR MEROPS; I01.037; -. DR iPTMnet; O95980; -. DR PhosphoSitePlus; O95980; -. DR BioMuta; RECK; -. DR jPOST; O95980; -. DR MaxQB; O95980; -. DR PaxDb; O95980; -. DR PeptideAtlas; O95980; -. DR PRIDE; O95980; -. DR ProteomicsDB; 51158; -. DR Ensembl; ENST00000377966; ENSP00000367202; ENSG00000122707. DR GeneID; 8434; -. DR KEGG; hsa:8434; -. DR UCSC; uc003zyv.4; human. DR CTD; 8434; -. DR DisGeNET; 8434; -. DR EuPathDB; HostDB:ENSG00000122707.11; -. DR GeneCards; RECK; -. DR HGNC; HGNC:11345; RECK. DR HPA; CAB025109; -. DR HPA; HPA071729; -. DR MIM; 605227; gene. DR neXtProt; NX_O95980; -. DR OpenTargets; ENSG00000122707; -. DR PharmGKB; PA34314; -. DR eggNOG; KOG3649; Eukaryota. DR eggNOG; ENOG410YC3T; LUCA. DR GeneTree; ENSGT00390000018540; -. DR HOGENOM; HOG000007167; -. DR HOVERGEN; HBG036100; -. DR InParanoid; O95980; -. DR KO; K17461; -. DR OMA; ISKDPCN; -. DR OrthoDB; 620790at2759; -. DR PhylomeDB; O95980; -. DR TreeFam; TF324424; -. DR Reactome; R-HSA-163125; Post-translational modification: synthesis of GPI-anchored proteins. DR ChiTaRS; RECK; human. DR GeneWiki; RECK; -. DR GenomeRNAi; 8434; -. DR PRO; PR:O95980; -. DR Proteomes; UP000005640; Chromosome 9. DR Bgee; ENSG00000122707; Expressed in 223 organ(s), highest expression level in parietal pleura. DR Genevisible; O95980; HS. DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0016020; C:membrane; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:1990909; C:Wnt signalosome; IEA:Ensembl. DR GO; GO:1904928; F:coreceptor activity involved in canonical Wnt signaling pathway; IEA:Ensembl. DR GO; GO:0004866; F:endopeptidase inhibitor activity; IDA:MGI. DR GO; GO:0008191; F:metalloendopeptidase inhibitor activity; IDA:UniProtKB. DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW. DR GO; GO:0017147; F:Wnt-protein binding; IEA:Ensembl. DR GO; GO:0001955; P:blood vessel maturation; IBA:GO_Central. DR GO; GO:0007566; P:embryo implantation; IEA:Ensembl. DR GO; GO:0035115; P:embryonic forelimb morphogenesis; IEA:Ensembl. DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central. DR GO; GO:0030336; P:negative regulation of cell migration; IMP:BHF-UCL. DR GO; GO:1904684; P:negative regulation of metalloendopeptidase activity; IDA:UniProtKB. DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IEA:Ensembl. DR GO; GO:0045765; P:regulation of angiogenesis; IEA:Ensembl. DR GO; GO:0090210; P:regulation of establishment of blood-brain barrier; IEA:Ensembl. DR InterPro; IPR002350; Kazal_dom. DR InterPro; IPR036058; Kazal_dom_sf. DR InterPro; IPR039016; RECK. DR PANTHER; PTHR13487; PTHR13487; 1. DR Pfam; PF07648; Kazal_2; 3. DR SMART; SM00280; KAZAL; 3. DR SUPFAM; SSF100895; SSF100895; 3. DR PROSITE; PS00282; KAZAL_1; 1. DR PROSITE; PS51465; KAZAL_2; 3. PE 1: Evidence at protein level; KW Cell membrane; Complete proteome; Disulfide bond; Glycoprotein; KW GPI-anchor; Lipoprotein; Membrane; Polymorphism; Protease inhibitor; KW Reference proteome; Repeat; Serine protease inhibitor; Signal; KW Tumor suppressor; Wnt signaling pathway. FT SIGNAL 1 22 {ECO:0000255}. FT CHAIN 23 942 Reversion-inducing cysteine-rich protein FT with Kazal motifs. FT /FTId=PRO_0000016583. FT PROPEP 943 971 Removed in mature form. {ECO:0000255}. FT /FTId=PRO_0000016584. FT REPEAT 37 84 Knot 1. FT REPEAT 104 141 Knot 2. FT REPEAT 151 197 Knot 3. FT REPEAT 216 263 Knot 4. FT REPEAT 292 338 Knot 5. FT DOMAIN 627 673 Kazal-like 1. {ECO:0000255|PROSITE- FT ProRule:PRU00798}. FT DOMAIN 698 752 Kazal-like 2. {ECO:0000255|PROSITE- FT ProRule:PRU00798}. FT DOMAIN 753 789 Kazal-like 3. {ECO:0000255|PROSITE- FT ProRule:PRU00798}. FT REGION 37 338 5 X Knot repeats. FT LIPID 942 942 GPI-anchor amidated serine. FT {ECO:0000255}. FT CARBOHYD 39 39 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 86 86 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 200 200 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 297 297 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 352 352 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 633 658 {ECO:0000255|PROSITE-ProRule:PRU00798}. FT DISULFID 635 654 {ECO:0000255|PROSITE-ProRule:PRU00798}. FT DISULFID 643 671 {ECO:0000255|PROSITE-ProRule:PRU00798}. FT DISULFID 716 735 {ECO:0000255|PROSITE-ProRule:PRU00798}. FT DISULFID 724 750 {ECO:0000255|PROSITE-ProRule:PRU00798}. FT DISULFID 761 787 {ECO:0000255|PROSITE-ProRule:PRU00798}. FT VARIANT 275 275 V -> I (in dbSNP:rs16932912). FT /FTId=VAR_034021. FT MUTAGEN 225 272 Missing: Abolished interaction with FT WNT7A. {ECO:0000269|PubMed:30026314}. SQ SEQUENCE 971 AA; 106457 MW; 173D47D6AEE6F834 CRC64; MATVRASLRG ALLLLLAVAG VAEVAGGLAP GSAGALCCNH SKDNQMCRDV CEQIFSSKSE SRLKHLLQRA PDYCPETMVE IWNCMNSSLP GVFKKSDGWV GLGCCELAIA LECRQACKQA SSKNDISKVC RKEYENALFS CISRNEMGSV CCSYAGHHTN CREYCQAIFR TDSSPGPSQI KAVENYCASI SPQLIHCVNN YTQSYPMRNP TDSLYCCDRA EDHACQNACK RILMSKKTEM EIVDGLIEGC KTQPLPQDPL WQCFLESSQS VHPGVTVHPP PSTGLDGAKL HCCSKANTST CRELCTKLYS MSWGNTQSWQ EFDRFCEYNP VEVSMLTCLA DVREPCQLGC RNLTYCTNFN NRPTELFRSC NAQSDQGAMN DMKLWEKGSI KMPFINIPVL DIKKCQPEMW KAIACSLQIK PCHSKSRGSI ICKSDCVEIL KKCGDQNKFP EDHTAESICE LLSPTDDLKN CIPLDTYLRP STLGNIVEEV THPCNPNPCP ANELCEVNRK GCPSGDPCLP YFCVQGCKLG EASDFIVRQG TLIQVPSSAG EVGCYKICSC GQSGLLENCM EMHCIDLQKS CIVGGKRKSH GTSFSIDCNV CSCFAGNLVC STRLCLSEHS SEDDRRTFTG LPCNCADQFV PVCGQNGRTY PSACIARCVG LQDHQFEFGS CMSKDPCNPN PCQKNQRCIP KPQVCLTTFD KFGCSQYECV PRQLACDQVQ DPVCDTDHME HNNLCTLYQR GKSLSYKGPC QPFCRATEPV CGHNGETYSS VCAAYSDRVA VDYYGDCQAV GVLSEHSSVA ECASVKCPSL LAAGCKPIIP PGACCPLCAG MLRVLFDKEK LDTIAKVTNK KPITVLEILQ KIRMHVSVPQ CDVFGYFSIE SEIVILIIPV DHYPKALQIE ACNKEAEKIE SLINSDSPTL ASHVPLSALI ISQVQVSSSV PSAGVRARPS CHSLLLPLSL GLALHLLWTY N //