RECK_HUMAN
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 03-AUG-2022, entry version 168.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, GLYCOSYLATION,
RP 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., Ratzkin B.J.,
RA Arakawa T., Noda M.;
RT "Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion
RT 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., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., 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., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., 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., Rogers J.,
RA 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 project:
RT 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 and
RT 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 WNT7B,
RP 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 endothelial
CC cells to selectively respond to Wnt7 signals (WNT7A or WNT7B)
CC (PubMed:28289266, PubMed:30026314). Plays a key role in Wnt7-specific
CC responses: required for central nervous system (CNS) angiogenesis and
CC blood-brain barrier regulation (By similarity). Acts as a Wnt7-specific
CC coactivator of canonical Wnt signaling by decoding Wnt ligands: acts by
CC interacting specifically with the disordered linker region of Wnt7,
CC thereby conferring ligand selectivity for Wnt7 (PubMed:30026314).
CC ADGRA2 is then required to deliver RECK-bound Wnt7 to frizzled by
CC assembling a higher-order RECK-ADGRA2-Fzd-LRP5-LRP6 complex
CC (PubMed:30026314). Also acts as a serine protease inhibitor: negatively
CC regulates matrix metalloproteinase-9 (MMP9) by suppressing MMP9
CC secretion and by direct inhibition of its enzymatic activity
CC (PubMed:9789069, PubMed:18194466). Also inhibits metalloproteinase
CC activity of MMP2 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 linker
CC region); the interaction is direct (PubMed:30026314). Interacts (via
CC knot repeats) with WNT7B (via disordered linker region); the
CC interaction is direct (PubMed:30026314). Interacts with ADGRA2; the
CC interaction is direct (PubMed:30026314). Interacts with MMP9
CC (PubMed:9789069). {ECO:0000269|PubMed:30026314,
CC ECO:0000269|PubMed:9789069}.
CC -!- INTERACTION:
CC O95980; 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 lines
CC and oncogenically transformed cells (PubMed:9789069).
CC {ECO:0000269|PubMed:9789069}.
CC -!- DOMAIN: The Kazal-like domains mediate the serine protease inhibitor
CC activity. {ECO:0000269|PubMed:18194466}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:9789069}.
CC -!- SIMILARITY: Belongs to the RECK family. {ECO:0000305}.
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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 AlphaFoldDB; O95980; -.
DR SMR; O95980; -.
DR BioGRID; 114014; 50.
DR IntAct; O95980; 8.
DR MINT; O95980; -.
DR STRING; 9606.ENSP00000367202; -.
DR MEROPS; I01.037; -.
DR GlyGen; O95980; 6 sites, 1 O-linked glycan (1 site).
DR iPTMnet; O95980; -.
DR PhosphoSitePlus; O95980; -.
DR BioMuta; RECK; -.
DR jPOST; O95980; -.
DR MassIVE; O95980; -.
DR MaxQB; O95980; -.
DR PaxDb; O95980; -.
DR PeptideAtlas; O95980; -.
DR PRIDE; O95980; -.
DR ProteomicsDB; 51158; -.
DR Antibodypedia; 26128; 307 antibodies from 34 providers.
DR DNASU; 8434; -.
DR Ensembl; ENST00000377966.4; ENSP00000367202.3; ENSG00000122707.12.
DR GeneID; 8434; -.
DR KEGG; hsa:8434; -.
DR MANE-Select; ENST00000377966.4; ENSP00000367202.3; NM_021111.3; NP_066934.1.
DR UCSC; uc003zyv.4; human.
DR CTD; 8434; -.
DR DisGeNET; 8434; -.
DR GeneCards; RECK; -.
DR HGNC; HGNC:11345; RECK.
DR HPA; ENSG00000122707; Low tissue specificity.
DR MIM; 605227; gene.
DR neXtProt; NX_O95980; -.
DR OpenTargets; ENSG00000122707; -.
DR PharmGKB; PA34314; -.
DR VEuPathDB; HostDB:ENSG00000122707; -.
DR eggNOG; KOG3649; Eukaryota.
DR GeneTree; ENSGT00390000018540; -.
DR HOGENOM; CLU_013883_0_0_1; -.
DR InParanoid; O95980; -.
DR OMA; IPCCEYS; -.
DR OrthoDB; 620790at2759; -.
DR PhylomeDB; O95980; -.
DR TreeFam; TF324424; -.
DR PathwayCommons; O95980; -.
DR Reactome; R-HSA-163125; Post-translational modification: synthesis of GPI-anchored proteins.
DR SignaLink; O95980; -.
DR BioGRID-ORCS; 8434; 10 hits in 1069 CRISPR screens.
DR ChiTaRS; RECK; human.
DR GeneWiki; RECK; -.
DR GenomeRNAi; 8434; -.
DR Pharos; O95980; Tbio.
DR PRO; PR:O95980; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; O95980; protein.
DR Bgee; ENSG00000122707; Expressed in skin of hip and 196 other tissues.
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 GO; GO:0002040; P:sprouting angiogenesis; IBA:GO_Central.
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; Disulfide bond; Glycoprotein; GPI-anchor; Lipoprotein;
KW Membrane; Protease inhibitor; Reference proteome; Repeat;
KW Serine protease inhibitor; Signal; Tumor suppressor; Wnt signaling pathway.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..942
FT /note="Reversion-inducing cysteine-rich protein with Kazal
FT motifs"
FT /id="PRO_0000016583"
FT PROPEP 943..971
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000016584"
FT REPEAT 37..84
FT /note="Knot 1"
FT REPEAT 104..141
FT /note="Knot 2"
FT REPEAT 151..197
FT /note="Knot 3"
FT REPEAT 216..263
FT /note="Knot 4"
FT REPEAT 292..338
FT /note="Knot 5"
FT DOMAIN 627..673
FT /note="Kazal-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 698..752
FT /note="Kazal-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 753..789
FT /note="Kazal-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT REGION 37..338
FT /note="5 X Knot repeats"
FT LIPID 942
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 39
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 86
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 200
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 297
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 352
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 633..658
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 635..654
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 643..671
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 716..735
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 724..750
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 761..787
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT VARIANT 275
FT /note="V -> I (in dbSNP:rs16932912)"
FT /id="VAR_034021"
FT MUTAGEN 225..272
FT /note="Missing: Abolished interaction with WNT7A."
FT /evidence="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
