RECK_MOUSE
ID RECK_MOUSE Reviewed; 971 AA.
AC Q9Z0J1; B1AWM3;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Reversion-inducing cysteine-rich protein with Kazal motifs {ECO:0000303|PubMed:9789069};
DE Short=mRECK {ECO:0000303|PubMed:9789069};
DE Flags: Precursor;
GN Name=Reck {ECO:0000303|PubMed:9789069, ECO:0000312|MGI:MGI:1855698};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
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].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11747814; DOI=10.1016/s0092-8674(01)00597-9;
RA Oh J., Takahashi R., Kondo S., Mizoguchi A., Adachi E., Sasahara R.M.,
RA Nishimura S., Imamura Y., Kitayama H., Alexander D.B., Ide C., Horan T.P.,
RA Arakawa T., Yoshida H., Nishikawa S., Itoh Y., Seiki M., Itohara S.,
RA Takahashi C., Noda M.;
RT "The membrane-anchored MMP inhibitor RECK is a key regulator of
RT extracellular matrix integrity and angiogenesis.";
RL Cell 107:789-800(2001).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=26658478; DOI=10.1038/srep17860;
RA de Almeida G.M., Yamamoto M., Morioka Y., Ogawa S., Matsuzaki T., Noda M.;
RT "Critical roles for murine Reck in the regulation of vascular patterning
RT and stabilization.";
RL Sci. Rep. 5:17860-17860(2015).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ADGRA2, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF GLN-68; ARG-69; PRO-71; ASP-72 AND TYR-73.
RX PubMed=28803732; DOI=10.1016/j.neuron.2017.07.031;
RA Cho C., Smallwood P.M., Nathans J.;
RT "Reck and Gpr124 Are Essential Receptor Cofactors for Wnt7a/Wnt7b-specific
RT signaling in mammalian CNS angiogenesis and blood-brain barrier
RT regulation.";
RL Neuron 95:1056-1073(2017).
CC -!- FUNCTION: Functions together with ADGRA2 to enable brain endothelial
CC cells to selectively respond to Wnt7 signals (WNT7A or WNT7B)
CC (PubMed:28803732). Plays a key role in Wnt7-specific responses:
CC required for central nervous system (CNS) angiogenesis and blood-brain
CC barrier regulation (PubMed:26658478, PubMed:28803732). Acts as a Wnt7-
CC specific coactivator of canonical Wnt signaling by decoding Wnt
CC ligands: acts by interacting specifically with the disordered linker
CC region of Wnt7, thereby conferring ligand selectivity for Wnt7 (By
CC similarity). ADGRA2 is then required to deliver RECK-bound Wnt7 to
CC frizzled by assembling a higher-order RECK-ADGRA2-Fzd-LRP5-LRP6 complex
CC (By similarity). 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:11747814). Also inhibits metalloproteinase activity of MMP2 and
CC MMP14 (MT1-MMP) (PubMed:11747814). {ECO:0000250|UniProtKB:O95980,
CC ECO:0000269|PubMed:11747814, ECO:0000269|PubMed:26658478,
CC ECO:0000269|PubMed:28803732}.
CC -!- SUBUNIT: Interacts (via knot repeats) with WNT7A (via disordered linker
CC region); the interaction is direct (By similarity). Interacts (via knot
CC repeats) with WNT7B (via disordered linker region); the interaction is
CC direct (By similarity). Interacts with ADGRA2; the interaction is
CC direct (PubMed:28803732). Interacts with MMP9 (By similarity).
CC {ECO:0000250|UniProtKB:O95980, ECO:0000269|PubMed:28803732}.
CC -!- INTERACTION:
CC Q9Z0J1; O00755: WNT7A; Xeno; NbExp=4; IntAct=EBI-20720091, EBI-727198;
CC Q9Z0J1; P56706: WNT7B; Xeno; NbExp=4; IntAct=EBI-20720091, EBI-3913589;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:28803732};
CC Lipid-anchor, GPI-anchor {ECO:0000250|UniProtKB:O95980}.
CC -!- DEVELOPMENTAL STAGE: In 10.5 dpc embryos, widely expressed in
CC mesenchymal tissues and is relatively abundant in the marginal zone of
CC the neural tube and large blood vessels such as the aorta.
CC {ECO:0000269|PubMed:9789069}.
CC -!- DOMAIN: The Kazal-like domains mediate the serine protease inhibitor
CC activity. {ECO:0000250|UniProtKB:O95980}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethality around 10.5 dpc, caused by
CC reduced tissue integrity, arrested vasculogenesis and precocious
CC neuronal differentiation (PubMed:11747814). Conditional knockout mice
CC lacking Reck in endothelial cells show central nervous system (CNS)
CC angiogenesis defects, characterized by moderate hemorrhages in the
CC forebrain and vascular malformations in the cortex (PubMed:26658478,
CC PubMed:28803732). Conditional deletion in endothelial cells also cause
CC blood-brain barrier defects in neonates (PubMed:28803732). Phenotypes
CC are caused by impaired beta-catenin-dependent signaling
CC (PubMed:28803732). {ECO:0000269|PubMed:11747814,
CC ECO:0000269|PubMed:26658478, ECO:0000269|PubMed:28803732}.
CC -!- SIMILARITY: Belongs to the RECK family. {ECO:0000305}.
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DR EMBL; AB006960; BAA34061.1; -; mRNA.
DR EMBL; AL772204; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL773539; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS18116.1; -.
DR PIR; PC7035; PC7035.
DR RefSeq; NP_057887.2; NM_016678.2.
DR PDB; 6WBH; X-ray; 2.46 A; A=206-270.
DR PDB; 6WBJ; X-ray; 1.65 A; A=206-270.
DR PDBsum; 6WBH; -.
DR PDBsum; 6WBJ; -.
DR AlphaFoldDB; Q9Z0J1; -.
DR SMR; Q9Z0J1; -.
DR BioGRID; 207333; 1.
DR IntAct; Q9Z0J1; 2.
DR STRING; 10090.ENSMUSP00000030198; -.
DR GlyGen; Q9Z0J1; 5 sites.
DR iPTMnet; Q9Z0J1; -.
DR PhosphoSitePlus; Q9Z0J1; -.
DR MaxQB; Q9Z0J1; -.
DR PaxDb; Q9Z0J1; -.
DR PRIDE; Q9Z0J1; -.
DR ProteomicsDB; 255059; -.
DR Antibodypedia; 26128; 307 antibodies from 34 providers.
DR DNASU; 53614; -.
DR Ensembl; ENSMUST00000030198; ENSMUSP00000030198; ENSMUSG00000028476.
DR GeneID; 53614; -.
DR KEGG; mmu:53614; -.
DR UCSC; uc012ddg.1; mouse.
DR CTD; 8434; -.
DR MGI; MGI:1855698; Reck.
DR VEuPathDB; HostDB:ENSMUSG00000028476; -.
DR eggNOG; KOG3649; Eukaryota.
DR GeneTree; ENSGT00390000018540; -.
DR HOGENOM; CLU_013883_0_0_1; -.
DR InParanoid; Q9Z0J1; -.
DR OMA; IPCCEYS; -.
DR OrthoDB; 620790at2759; -.
DR PhylomeDB; Q9Z0J1; -.
DR TreeFam; TF324424; -.
DR Reactome; R-MMU-163125; Post-translational modification: synthesis of GPI-anchored proteins.
DR BioGRID-ORCS; 53614; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Reck; mouse.
DR PRO; PR:Q9Z0J1; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q9Z0J1; protein.
DR Bgee; ENSMUSG00000028476; Expressed in iris and 254 other tissues.
DR Genevisible; Q9Z0J1; MM.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:1990909; C:Wnt signalosome; IDA:UniProtKB.
DR GO; GO:1904928; F:coreceptor activity involved in canonical Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IDA:MGI.
DR GO; GO:0008191; F:metalloendopeptidase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0017147; F:Wnt-protein binding; IPI:UniProtKB.
DR GO; GO:0001955; P:blood vessel maturation; IMP:MGI.
DR GO; GO:0007566; P:embryo implantation; IDA:MGI.
DR GO; GO:0035115; P:embryonic forelimb morphogenesis; IMP:MGI.
DR GO; GO:0030198; P:extracellular matrix organization; IMP:MGI.
DR GO; GO:0030336; P:negative regulation of cell migration; ISO:MGI.
DR GO; GO:1904684; P:negative regulation of metalloendopeptidase activity; IMP:BHF-UCL.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0045765; P:regulation of angiogenesis; IMP:UniProtKB.
DR GO; GO:0090210; P:regulation of establishment of blood-brain barrier; IMP:UniProtKB.
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 3D-structure; Cell membrane; Disulfide bond; Glycoprotein; GPI-anchor;
KW Lipoprotein; 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_0000016585"
FT PROPEP 943..971
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000016586"
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 704..750
FT /note="Kazal-like 2; degenerate"
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 MUTAGEN 68
FT /note="Q->A: Does not affect interaction with ADGRA2."
FT /evidence="ECO:0000269|PubMed:28803732"
FT MUTAGEN 69
FT /note="R->A: Decreased interaction with ADGRA2."
FT /evidence="ECO:0000269|PubMed:28803732"
FT MUTAGEN 71
FT /note="P->A: Decreased interaction with ADGRA2."
FT /evidence="ECO:0000269|PubMed:28803732"
FT MUTAGEN 72
FT /note="D->A: Does not affect interaction with ADGRA2."
FT /evidence="ECO:0000269|PubMed:28803732"
FT MUTAGEN 73
FT /note="Y->A: Decreased interaction with ADGRA2."
FT /evidence="ECO:0000269|PubMed:28803732"
FT CONFLICT 447..449
FT /note="NKF -> PKG (in Ref. 1; BAA34061)"
FT /evidence="ECO:0000305"
FT CONFLICT 539
FT /note="Q -> P (in Ref. 1; BAA34061)"
FT /evidence="ECO:0000305"
FT CONFLICT 662..663
FT /note="QD -> HH (in Ref. 1; BAA34061)"
FT /evidence="ECO:0000305"
FT CONFLICT 757
FT /note="K -> T (in Ref. 1; BAA34061)"
FT /evidence="ECO:0000305"
FT CONFLICT 804
FT /note="A -> S (in Ref. 1; BAA34061)"
FT /evidence="ECO:0000305"
FT CONFLICT 921
FT /note="A -> E (in Ref. 1; BAA34061)"
FT /evidence="ECO:0000305"
FT CONFLICT 925
FT /note="P -> H (in Ref. 1; BAA34061)"
FT /evidence="ECO:0000305"
FT CONFLICT 960
FT /note="L -> W (in Ref. 1; BAA34061)"
FT /evidence="ECO:0000305"
FT HELIX 210..213
FT /evidence="ECO:0007829|PDB:6WBJ"
FT HELIX 214..217
FT /evidence="ECO:0007829|PDB:6WBJ"
FT HELIX 223..233
FT /evidence="ECO:0007829|PDB:6WBJ"
FT TURN 234..236
FT /evidence="ECO:0007829|PDB:6WBJ"
FT HELIX 239..250
FT /evidence="ECO:0007829|PDB:6WBJ"
FT HELIX 255..257
FT /evidence="ECO:0007829|PDB:6WBJ"
FT HELIX 259..267
FT /evidence="ECO:0007829|PDB:6WBJ"
SQ SEQUENCE 971 AA; 106082 MW; CD5C462EA08A6866 CRC64;
MASVRASPRS ALLLLLAAAG VAEVTGGLAP GSAGAVCCNH SKDNQMCRDV CEQIFSSKSE
SRLKHLLQRA PDYCPETMVE IWSCMNSSLP GVFKKSDGWV GLGCCELAIG LECRQACKQA
SSKNDISKVC RKEYENALFS CISRNEMGSV CCSYAGHHTN CREFCQAIFR TDSSPGPSQI
KAVENYCASI SPQLIHCVNN YTQSYPMRNP TDSLYCCDRA EDHACQNACK RILMSKKTEM
EIVDGLIEGC KTQPLPQDPL WQCFLESSQS VHPGVTVHPP PSTGLDGAKL HCCSKANTST
CRELCTKLYS MSWGNTQSWQ EFDRICEYNP VEVSMLTCLA DVREPCQLGC TNLTYCTNFN
NRPTELFRSC TAQSDQGAMS DMKLWEKGSI KMPFISIPVL DIKTCQPEMW KAVACSLQIK
PCHSKSRGSI ICKSDCVEIL KKCGDQNKFP EEHTAESICE FLSPADDLES CIPLDTYLRP
SALGNIIEEV THPCNPNPCP ANELCEVNRK GCPSADPCLP YSCVQGCKLG EASDFIVRQG
TLIQVPSSAG EVGCYKICSC GQSGLLENCM EMHCIDLQKS CIVGGKRKSH GTSFTIDCNV
CSCFAGNLVC STRLCLSEHS SDDDRRTFTG LPCNCADQFV PVCAQNGRTY PSACIARCVG
LQDHQFEFGP CISKNPCNPN LCPKSQRCVP KPQVCLTTFD KFGCSQYECV PRQLTCDQAR
DPVCDTDHME HSNLCTLYQR GKSLSYRGPC QPFCRAKEPV CGHNGETYSS VCAAYSDRVA
VDYYGPCQAV GVLSEYSAVA ECAAVKCPSL SAIGCKPIIP PGACCPLCAG MLRVLFDKEK
LDTIAKVTSK KPITVVEILQ KVRMHVSVPQ CDVFGYLSIE SEIVILIIPV DHYPKALQIE
ACNKEAEKIE SLINSDSPTL ASHVPLSALI ISQVQVSSSL PSSAVVGRPL FHSLLLLLSL
GLTVHLLWTR P
