RECK_DANRE
ID RECK_DANRE Reviewed; 955 AA.
AC A0A0R4IKU3; A0A2R8QDM9; F1QWT7;
DT 07-NOV-2018, integrated into UniProtKB/Swiss-Prot.
DT 07-NOV-2018, sequence version 3.
DT 03-AUG-2022, entry version 33.
DE RecName: Full=Reversion-inducing cysteine-rich protein with Kazal motifs {ECO:0000303|PubMed:26051822};
DE Flags: Precursor;
GN Name=reck {ECO:0000303|PubMed:26051822,
GN ECO:0000312|ZFIN:ZDB-GENE-070117-37};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH ADGRA2.
RX PubMed=26051822; DOI=10.7554/elife.06489;
RA Vanhollebeke B., Stone O.A., Bostaille N., Cho C., Zhou Y., Maquet E.,
RA Gauquier A., Cabochette P., Fukuhara S., Mochizuki N., Nathans J.,
RA Stainier D.Y.;
RT "Tip cell-specific requirement for an atypical Gpr124- and Reck-dependent
RT Wnt/beta-catenin pathway during brain angiogenesis.";
RL Elife 4:0-0(2015).
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=27979830; DOI=10.1242/bio.021287;
RA Bostaille N., Gauquier A., Twyffels L., Vanhollebeke B.;
RT "Molecular insights into Adgra2/Gpr124 and Reck intracellular
RT trafficking.";
RL Biol. Open 5:1874-1881(2016).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, AND MUTAGENESIS OF CYS-254.
RX PubMed=26657775; DOI=10.1242/dev.123059;
RA Ulrich F., Carretero-Ortega J., Menendez J., Narvaez C., Sun B.,
RA Lancaster E., Pershad V., Trzaska S., Veliz E., Kamei M., Prendergast A.,
RA Kidd K.R., Shaw K.M., Castranova D.A., Pham V.N., Lo B.D., Martin B.L.,
RA Raible D.W., Weinstein B.M., Torres-Vazquez J.;
RT "Reck enables cerebrovascular development by promoting canonical Wnt
RT signaling.";
RL Development 143:147-159(2016).
CC -!- FUNCTION: Functions together with adgra2 to enable brain endothelial
CC cells to selectively respond to Wnt7 signals (wnt7a or wnt7b)
CC (PubMed:26051822, PubMed:26657775). Plays a key role in Wnt7-specific
CC responses: required for central nervous system (CNS) angiogenesis and
CC blood-brain barrier regulation (PubMed:26051822, PubMed:26657775). Acts
CC as a Wnt7-specific coactivator of canonical Wnt signaling by decoding
CC Wnt ligands: acts by interacting specifically with the disordered
CC linker region of Wnt7, thereby conferring ligand selectivity for Wnt7.
CC Adgra2 is then required to deliver reck-bound Wnt7 to frizzled by
CC assembling a higher-order RECK-ADGRA2-Fzd-LRP5-LRP6 complex. Also acts
CC as a serine protease inhibitor (By similarity).
CC {ECO:0000250|UniProtKB:O95980, ECO:0000269|PubMed:26051822,
CC ECO:0000269|PubMed:26657775}.
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:26051822). {ECO:0000250|UniProtKB:O95980,
CC ECO:0000269|PubMed:26051822}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26051822,
CC ECO:0000269|PubMed:27979830}; Lipid-anchor, GPI-anchor
CC {ECO:0000250|UniProtKB:A0A1D5PUP4}. Note=Colocalizes with adgra2 at the
CC plasma membrane. {ECO:0000269|PubMed:26051822}.
CC -!- TISSUE SPECIFICITY: Expressed in the cerebral endothelium.
CC {ECO:0000269|PubMed:26657775}.
CC -!- DOMAIN: The Kazal-like domains mediate the serine protease inhibitor
CC activity. {ECO:0000250|UniProtKB:O95980}.
CC -!- SIMILARITY: Belongs to the RECK family. {ECO:0000305}.
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DR EMBL; CU467964; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; FP016176; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; FP565452; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; FP565456; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; FP565458; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_009295477.1; XM_009297202.2.
DR AlphaFoldDB; A0A0R4IKU3; -.
DR SMR; A0A0R4IKU3; -.
DR STRING; 7955.ENSDARP00000108231; -.
DR GeneID; 100334698; -.
DR KEGG; dre:100334698; -.
DR CTD; 8434; -.
DR ZFIN; ZDB-GENE-070117-37; reck.
DR eggNOG; KOG3649; Eukaryota.
DR HOGENOM; CLU_013883_0_0_1; -.
DR OMA; IPCCEYS; -.
DR OrthoDB; 620790at2759; -.
DR PRO; PR:A0A0R4IKU3; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
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; ISS:UniProtKB.
DR GO; GO:1904928; F:coreceptor activity involved in canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IBA:GO_Central.
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:0001955; P:blood vessel maturation; IBA:GO_Central.
DR GO; GO:1990791; P:dorsal root ganglion development; IMP:ZFIN.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:1904684; P:negative regulation of metalloendopeptidase activity; ISS:UniProtKB.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0045765; P:regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:0060828; P:regulation of canonical Wnt signaling pathway; IMP:ZFIN.
DR GO; GO:0051726; P:regulation of cell cycle; IGI:ZFIN.
DR GO; GO:0090049; P:regulation of cell migration involved in sprouting angiogenesis; IMP:ZFIN.
DR GO; GO:0090210; P:regulation of establishment of blood-brain barrier; ISS:UniProtKB.
DR GO; GO:0002040; P:sprouting angiogenesis; IMP:ZFIN.
DR GO; GO:0001944; P:vasculature development; IMP:ZFIN.
DR GO; GO:0016055; P:Wnt signaling pathway; IMP:ZFIN.
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; 2.
DR SMART; SM00280; KAZAL; 3.
DR SUPFAM; SSF100895; SSF100895; 2.
DR PROSITE; PS00282; KAZAL_1; 1.
DR PROSITE; PS51465; KAZAL_2; 2.
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; Wnt signaling pathway.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..931
FT /note="Reversion-inducing cysteine-rich protein with Kazal
FT motifs"
FT /evidence="ECO:0000255"
FT /id="PRO_5015302792"
FT PROPEP 932..955
FT /evidence="ECO:0000255"
FT /id="PRO_0000445620"
FT REPEAT 28..75
FT /note="Knot 1"
FT /evidence="ECO:0000250|UniProtKB:O95980"
FT REPEAT 95..132
FT /note="Knot 2"
FT /evidence="ECO:0000250|UniProtKB:O95980"
FT REPEAT 142..188
FT /note="Knot 3"
FT /evidence="ECO:0000250|UniProtKB:O95980"
FT REPEAT 207..254
FT /note="Knot 4"
FT /evidence="ECO:0000250|UniProtKB:O95980"
FT REPEAT 282..326
FT /note="Knot 5"
FT /evidence="ECO:0000250|UniProtKB:O95980"
FT DOMAIN 615..661
FT /note="Kazal-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 686..741
FT /note="Kazal-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 742..778
FT /note="Kazal-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT REGION 28..326
FT /note="5 X Knot repeats"
FT /evidence="ECO:0000250|UniProtKB:O95980"
FT SITE 625..626
FT /note="Reactive bond"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT SITE 706..707
FT /note="Reactive bond"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT LIPID 931
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 77
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 191
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 287
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 375
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 621..646
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 623..642
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 631..659
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 704..724
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 713..739
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT MUTAGEN 254
FT /note="C->Y: In no food for thought mutant (nft); lethality
FT caused by the absence of most of the intracerebral central
FT arteries. Defects are caused by impaired Wnt signaling."
FT /evidence="ECO:0000269|PubMed:26657775"
SQ SEQUENCE 955 AA; 105521 MW; A7B5B5DD5CA810BD CRC64;
MSGCLQILTV LLCCRFWALV FSQDQSCCVH HAADIPRCRD ACEQLASIRS ESRLRHLLHR
LPSYCPETLS ELWICINNSL PGASRKSDGW VGLGCCELAI SAECRRDCKQ ASSKNDISKV
CKKDTENPLY SCITKNEMGS VCCSYAGRHT TCREYCQAIF RTDSSPTVSQ ISAVKEYCQS
VSPPLILCVE NYTRLHPTHR PIDSLHCCDR AEEAHCQLAC KRILRTLSTE QEIMDGLISE
CGSQPLPQDP LWQCFLGSAH PPANTDPESP PIAKMDSAKL HCCFKANTSI CRNMCVEIST
SWGTQSWQEF DQHCEYNPVE MDLITCLADV REPCQLGCKE LSYCTNFNNR PTELFRSCNV
QSDQGALNDF KLWSNGSIRM PLMNIPVLDI RRCRPEMWKT VACALQIKPC YSRSRGSVIC
RSDCVEILRQ CGDRRRFAEA QTPERICDLL SPTDDPERCI PLNRYLTASE LESSVEEVIH
PCNPNPCPSS HLCHVNRKGC HVGHDCLPYY CVPGCKLGEA SEFLVPADAR LQVPVHSAQP
GCYEVCVCGQ SGRLENCAEM PCFDTSKSCQ IAGQRRSHGS SFRVDCNPCS CFAGDAVCSS
RQCVRSDSSE EDRRLFTGLP CGCADHFVPV CAGNGRTYPS ACVARCVGFT DSQFVFGSCR
SFDPCSPNPC QRNQRCVPRR QVCLTDLSEF PCPQYECVSR PSSCDQKLLD PVCDTDNMEH
ANLCVLNLRG KTLAYSGHCQ DACRRPREVC AHNGESYSTV CEAFSERVAV DYQGRCHAVG
LESEFGSDSG CNAVPCPPLA SDACQPVTPP GACCPVCAGM LRILWNKAQM NIFAKLNRDQ
PVSLHDILKI LRLHVSVPQC DIFGYLSINS EIIILIAPVD QQPTPLQIEA CSKEAEKIDS
LINSGSPTLV SHVPLSAFLS SELQLSSVRS SSCVSISVCV LLLLCSLILT LTSDL
