ID RELN_MOUSE STANDARD; PRT; 3461 AA. AC Q60841; Q9CUA6; DT 01-MAR-2002 (Rel. 41, Created) DT 01-MAR-2002 (Rel. 41, Last sequence update) DT 01-MAR-2002 (Rel. 41, Last annotation update) DE Reelin precursor (EC 3.4.21.-) (Reeler protein). GN RELN OR RL. OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Rodentia; Sciurognathi; Muridae; Murinae; Mus. OX NCBI_TaxID=10090; RN [1] RP SEQUENCE FROM N.A. (ISOFORM 1). RC TISSUE=Cerebellum; RX MEDLINE=95231649; PubMed=7715726; RA D'Arcangelo G., Miao G.G., Chen S.-C., Soares H.D., Morgan J.I., RA Curran T.; RT "A protein related to extracellular matrix proteins deleted in the RT mouse mutant reeler."; RL Nature 374:719-723(1995). RN [2] RP SEQUENCE FROM N.A., AND ALTERNATIVE SPLICING. RX MEDLINE=98086481; PubMed=9417911; RA Royaux I., Lambert de Rouvroit C., D'Arcangelo G., Demirov D., RA Goffinet A.M.; RT "Genomic organization of the mouse reelin gene."; RL Genomics 46:240-250(1997). RN [3] RP SEQUENCE OF 2152-3461 FROM N.A. (ISOFORM 1). RC STRAIN=BALB/c; TISSUE=Brain; RX MEDLINE=95375789; PubMed=7647795; RA Hirotsune S., Takahara T., Sasaki N., Hirose K., Yoshiki A., RA Ohashi T., Kusakabe M., Murakami Y., Muramatsu M., Watanabe S., RA Nakao K., Katsuki M., Hayashizaki Y.; RT "The reeler gene encodes a protein with an EGF-like motif expressed by RT pioneer neurons."; RL Nat. Genet. 10:77-83(1995). RN [4] RP SEQUENCE OF 3044-3461 FROM N.A. (ISOFORM 2). RC STRAIN=C57BL/6J; TISSUE=Testis; RX MEDLINE=21085660; PubMed=11217851; RA Kawai J., Shinagawa A., Shibata K., Yoshino M., Itoh M., Ishii Y., RA Arakawa T., Hara A., Fukunishi Y., Konno H., Adachi J., Fukuda S., RA Aizawa K., Izawa M., Nishi K., Kiyosawa H., Kondo S., Yamanaka I., RA Saito T., Okazaki Y., Gojobori T., Bono H., Kasukawa T., Saito R., RA Kadota K., Matsuda H.A., Ashburner M., Batalov S., Casavant T., RA Fleischmann W., Gaasterland T., Gissi C., King B., Kochiwa H., RA Kuehl P., Lewis S., Matsuo Y., Nikaido I., Pesole G., Quackenbush J., RA Schriml L.M., Staubli F., Suzuki R., Tomita M., Wagner L., Washio T., RA Sakai K., Okido T., Furuno M., Aono H., Baldarelli R., Barsh G., RA Blake J., Boffelli D., Bojunga N., Carninci P., de Bonaldo M.F., RA Brownstein M.J., Bult C., Fletcher C., Fujita M., Gariboldi M., RA Gustincich S., Hill D., Hofmann M., Hume D.A., Kamiya M., Lee N.H., RA Lyons P., Marchionni L., Mashima J., Mazzarelli J., Mombaerts P., RA Nordone P., Ring B., Ringwald M., Rodriguez I., Sakamoto N., RA Sasaki H., Sato K., Schoenbach C., Seya T., Shibata Y., Storch K.-F., RA Suzuki H., Toyo-oka K., Wang K.H., Weitz C., Whittaker C., Wilming L., RA Wynshaw-Boris A., Yoshida K., Hasegawa Y., Kawaji H., Kohtsuki S., RA Hayashizaki Y.; RT "Functional annotation of a full-length mouse cDNA collection."; RL Nature 409:685-690(2001). RN [5] RP CHARACTERIZATION. RX MEDLINE=97141547; PubMed=8987733; RA D'Arcangelo G., Nakajima K., Miyata T., Ogawa M., Mikoshiba K., RA Curran T.; RT "Reelin is a secreted glycoprotein recognized by the CR-50 monoclonal RT antibody."; RL J. Neurosci. 17:23-31(1997). RN [6] RP CHARACTERIZATION. RX MEDLINE=21634904; PubMed=11689558; RA Quattrocchi C.C., Wannenes F., Persico A.M., Ciafre S.A., RA D'Arcangelo G., Farace M.G., Keller F.; RT "Reelin is a serine protease of the extracellular matrix."; RL J. Biol. Chem. 277:303-309(2002). RN [7] RP TISSUE SPECIFICITY. RX MEDLINE=97325946; PubMed=9182958; RA Schiffmann S.N., Bernier B., Goffinet A.M.; RT "Reelin mRNA expression during mouse brain development."; RL Eur. J. Neurosci. 9:1055-1071(1997). RN [8] RP ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY. RX MEDLINE=99263436; PubMed=10328932; RA Lambert de Rouvroit C., Bernier B., Royaux I., de Bergeyck V., RA Goffinet A.M.; RT "Evolutionarily conserved, alternative splicing of reelin during brain RT development."; RL Exp. Neurol. 156:229-238(1999). RN [9] RP BINDING TO VLDLR AND APOER2. RX MEDLINE=20036019; PubMed=10571241; RA Hiesberger T., Trommsdorff M., Howell B.W., Goffinet A.M., Mumby M.C., RA Cooper J.A., Herz J.; RT "Direct binding of Reelin to VLDL receptor and ApoE receptor 2 induces RT tyrosine phosphorylation of disabled-1 and modulates tau RT phosphorylation."; RL Neuron 24:481-489(1999). RN [10] RP FUNCTION. RX MEDLINE=20359755; PubMed=10880573; RA Yip J.W., Yip Y.P.L., Nakajima K., Capriotti C.; RT "Reelin controls position of autonomic neurons in the spinal cord."; RL Proc. Natl. Acad. Sci. U.S.A. 97:8612-8616(2000). CC -!- FUNCTION: Extracellular matrix serine protease that plays a role CC in layering of neurons in the cerebral cortex and cerebellum. CC Regulates microtubule function in neurons and neuronal migration. CC Affects migration of sympathetic preganglionic neurons in the CC spinal cord, where it seems to act as a barrier to neuronal CC migration. Enzymatic activity is important for the modulation of CC cell adhesion. Binding to the extracellular domains of lipoprotein CC receptors VLDLR and ApoER2 induces tyrosine phosphorylation of CC Dab1 and modulation of Tau phosphorylation. CC -!- SUBUNIT: Binds to the ectodomains of VLDLR and ApoER2. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- ALTERNATIVE PRODUCTS: 3 isoforms; 1 (shown here), 2 and 3; are CC produced by alternative splicing. CC -!- TISSUE SPECIFICITY: The major isoform 1 is neuron-specific. It is CC abundantly produced during brain ontogenesis by the Cajal-Retzius CC cells and other pioneer neurons located in the telencephalic CC marginal zone and by granule cells of the external granular layer CC of the cerebellum. Expression is located in deeper layers in the CC developing hippocampus and olfactory bulb, low levels of CC expression are also detected in the immature striatum. At early CC developmental stages, expressed also in hypothalamic CC differentiation fields, tectum and spinal cord. A moderate to low CC level of expression occurs in the septal area, striatal fields, CC habenular nuclei, some thalamic nuclei, particularly the lateral CC geniculate, the retina and some nuclei of the reticular formation CC in the central field of the medulla. Very low levels found in CC liver and kidney. No expression in radial glial cells, cortical CC plate, Purkinje cells and inferior olivary neurons. The minor CC isoform 2 is only expressed in non neuronal cells. The minor CC isoform 3 is found in the same cells as isoform 1, but is almost CC undetectable in retina and brain stem. CC -!- DEVELOPMENTAL STAGE: First detected at embryonic day 11.5. CC Expression increases up to birth and remains high from post-natal CC day 2 to 11 in both cerebellum and fore/midbrain. Expression CC declines thereafter and is largely brain specific in the adult. CC -!- DOMAIN: The basic C-terminal region is essential for secretion. CC -!- PTM: N-glycosylated and to a lesser extent also O-glycosylated. CC -!- DISEASE: Defects in reln are the cause of the autosomal CC recessive reeler (rl) phenotype which is characterized by impaired CC motor coordination, tremors and ataxia. Neurons in affected mice CC fail to reach their correct locations in the developing brain, CC disrupting the organization of the cerebellar and cerebral CC cortices and other laminated regions. CC -!- SIMILARITY: BELONGS TO THE REELIN FAMILY. CC -!- SIMILARITY: CONTAINS 8 EGF-LIKE DOMAINS. CC -!- SIMILARITY: CONTAINS 15 BNR REPEATS. 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; U24703; AAB91599.1; -. DR EMBL; D63520; BAA09788.1; ALT_INIT. DR EMBL; AK017094; BAB30592.1; -. DR MGD; MGI:103022; Reln. DR InterPro; IPR000561; EGF-like. DR InterPro; IPR002860; GH_BNR. DR InterPro; IPR002861; Reeler. DR Pfam; PF00008; EGF; 5. DR Pfam; PF02012; BNR; 15. DR Pfam; PF02014; Reeler; 1. DR SMART; SM00181; EGF; 5. DR SMART; SM00001; EGF_like; 2. DR PROSITE; PS00022; EGF_1; 7. DR PROSITE; PS01186; EGF_2; 6. KW Hydrolase; Serine protease; Developmental protein; Matrix protein; KW Cell adhesion; EGF-like domain; Glycoprotein; Repeat; Signal; KW Alternative splicing. FT SIGNAL 1 26 POTENTIAL. FT CHAIN 27 3461 REELIN. FT DOMAIN 40 172 REELER. FT DOMAIN 671 702 EGF-LIKE 1. FT DOMAIN 1030 1061 EGF-LIKE 2. FT DOMAIN 1409 1442 EGF-LIKE 3. FT DOMAIN 1765 1796 EGF-LIKE 4. FT DOMAIN 2129 2161 EGF-LIKE 5. FT DOMAIN 2478 2509 EGF-LIKE 6. FT DOMAIN 2853 2884 EGF-LIKE 7. FT DOMAIN 3228 3260 EGF-LIKE 8. FT REPEAT 593 604 BNR 1. FT REPEAT 799 810 BNR 2. FT REPEAT 952 963 BNR 3. FT REPEAT 1157 1168 BNR 4. FT REPEAT 1323 1334 BNR 5. FT REPEAT 1535 1546 BNR 6. FT REPEAT 1686 1697 BNR 7. FT REPEAT 1884 1895 BNR 8. FT REPEAT 2043 2054 BNR 9. FT REPEAT 2250 2261 BNR 10. FT REPEAT 2399 2410 BNR 11. FT REPEAT 2598 2609 BNR 12. FT REPEAT 2778 2789 BNR 13. FT REPEAT 2979 2990 BNR 14. FT REPEAT 3363 3374 BNR 15. FT DOMAIN 3432 3461 ARG-RICH (BASIC). FT CARBOHYD 141 141 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 258 258 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 290 290 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 306 306 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 629 629 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 1267 1267 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 1447 1447 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 1503 1503 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 1600 1600 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 1750 1750 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 1921 1921 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 2145 2145 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 2269 2269 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 2317 2317 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 2569 2569 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 2962 2962 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 3016 3016 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 3073 3073 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 3185 3185 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 3412 3412 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 3439 3439 N-LINKED (GLCNAC...) (POTENTIAL). FT VARSPLIC 3429 3430 MISSING (IN ISOFORM 2). FT VARSPLIC 3429 3461 MISSING (IN ISOFORM 3). FT CONFLICT 3066 3066 MISSING (IN REF. 4). SQ SEQUENCE 3461 AA; 387510 MW; 4131F3E84A9D4AE2 CRC64; MERGCWAPRA LVLAVLLLLA TLRARAATGY YPRFSPFFFL CTHHGELEGD GEQGEVLISL HIAGNPTYYV PGQEYHVTIS TSTFFDGLLV TGLYTSTSIQ SSQSIGGSSA FGFGIMSDHQ FGNQFMCSVV ASHVSHLPTT NLSFVWIAPP AGTGCVNFMA TATHRGQVIF KDALAQQLCE QGAPTEATAY SHLAEIHSDS VILRDDFDSY QQLELNPNIW VECSNCEMGE QCGTIMHGNA VTFCEPYGPR ELTTTCLNTT TASVLQFSIG SGSCRFSYSD PSITVSYAKN NTADWIQLEK IRAPSNVSTV IHILYLPEEA KGESVQFQWK QDSLRVGEVY EACWALDNIL VINSAHREVV LEDNLDPVDT GNWLFFPGAT VKHSCQSDGN SIYFHGNEGS EFNFATTRDV DLSTEDIQEQ WSEEFESQPT GWDILGAVVG ADCGTVESGL SLVFLKDGER KLCTPYMDTT GYGNLRFYFV MGGICDPGVS HENDIILYAK IEGRKEHIAL DTLTYSSYKV PSLVSVVINP ELQTPATKFC LRQKSHQGYN RNVWAVDFFH VLPVLPSTMS HMIQFSINLG CGTHQPGNSV SLEFSTNHGR SWSLLHTECL PEICAGPHLP HSTVYSSENY SGWNRITIPL PNAALTRDTR IRWRQTGPIL GNMWAIDNVY IGPSCLKFCS GRGQCTRHGC KCDPGFSGPA CEMASQTFPM FISESFGSAR LSSYHNFYSI RGAEVSFGCG VLASGKALVF NKDGRRQLIT SFLDSSQSRF LQFTLRLGSK SVLSTCRAPD QPGEGVLLHY SYDNGITWKL LEHYSYVNYH EPRIISVELP DDARQFGIQF RWWQPYHSSQ GEDVWAIDEI VMTSVLFNSI SLDFTNLVEV TQSLGFYLGN VQPYCGHDWT LCFTGDSKLA SSMRYVETQS MQIGASYMIQ FSLVMGCGQK YTPHMDNQVK LEYSANHGLT WHLVQEECLP SMPSCQEFTS ASIYHASEFT QWRRVTVVLP QKTWSGATRF RWSQSYYTAQ DEWALDNIYI GQQCPNMCSG HGSCDHGVCR CDQGYQGTEC HPEAALPSTI MSDFENPSSW ESDWQEVIGG EVVKPEQGCG VVSSGSSLYF SKAGKRQLVS WDLDTSWVDF VQFYIQIGGE SAACNKPDSR EEGILLQYSN NGGIQWHLLA EMYFSDFSKP RFVYLELPAA GKTPCTRFRW WKPVFSGEDY DQWAVDDIII LSEKQKQVIP VVNPTLPQNF YEKPAFDYPM NQMSVWLMLA NEGMAKNDSF CATTPSAMVF GKSDGDRFAV TRDLTLKPGY VLQFKLNIGC TSQFSSTAPV LLQYSHDAGM SWFLLKEGCF PASAAKGCEG NSRELSEPTV YYTGDFEEWT RITIAIPRSL ASSKTRFRWI QESSSQKNVP PFGLDGVYIS EPCPSYCSGH GDCISGVCFC DLGYTAAQGT CVSNTPNHSE MFDRFEGKLS PLWYKITGGQ VGTGCGTLND GRSLYFNGLG KREARTVPLD TRNISLVQFY IQIGSKTSGI TYITPRARYE GLVVQYSNDN GILWHLLREL DFMSFLEPQI ISIDLPREAK TPATAFRWWQ PQHGKHSAQW ALGDVLIGVN DSSQTGFQDK LDGSIDLQAN WYRIQGGQVD IDCLSMDTAL IFTENIGNPR YAETWDFHVS ESSFLQWEMN MGCSKPFSGA HGIQLQYSLN NGKDWQLVTE ECVPPTIGCV HYTESSTYTS ERFQNWRRVT VYLPLATNSP RTRFRWIQTN YTVGADSWAI DNVILASGCP WMCSGRGICD SGRCVCDRGF GGPFCVPVVP LPSILKDDFN GNLHPDLWPE VYGAERGNLN GETIKSGTCL IFKGEGLRML ISRDLDCTNT MYVQFSLRFI AKGTPERSHS ILLQFSVSGG VTWHLMDEFY FPQTTSILFI NVPLPYGAQT NATRFRLWQP YNNGKKEEIW IIDDFIIDGN NLNNPVLLLD TFDFGPREDN WFFYPGGNIG LYCPYSSKGA PEEDSAMVFV SNEVGEHSIT TRDLSVNENT IIQFEINVGC STDSSSADPV RLEFSRDFGA TWHLLLPLCY HSSSLVSSLC STEHHPSSTY YAGTTQGWRR EVVHFGKLHL CGSVRFRWYQ GFYPAGSQPV TWAIDNVYIG PQCEEMCYGH GSCINGTKCI CDPGYSGPTC KISTKNPDFL KDDFEGQLES DRFLLMSGGK PSRKCGILSS GNNLFFNEDG LRMLVTRDLD LSHARFVQFF MRLGCGKGVP DPRSQPVLLQ YSLNGGLSWS LLQEFLFSNS SNVGRYIALE MPLKARSGST RLRWWQPSEN GHFYSPWVID QILIGGNISG NTVLEDDFST LDSRKWLLHP GGTKMPVCGS TGDALVFIEK ASTRYVVTTD IAVNEDSFLQ IDFAASCSVT DSCYAIELEY SVDLGLSWHP LVRDCLPTNV ECSRYHLQRI LVSDTFNKWT RITLPLPSYT RSQATRFRWH QPAPFDKQQT WAIDNVYIGD GCLDMCSGHG RCVQGSCVCD EQWGGLYCDE PETSLPTQLK DNFNRAPSNQ NWLTVSGGKL STVCGAVASG LALHFSGGCS RLLVTVDLNL TNAEFIQFYF MYGCLITPSN RNQGVLLEYS VNGGITWNLL MEIFYDQYSK PGFVNILLPP DAKEIATRFR WWQPRHDGLD QNDWAIDNVL ISGSADQRTV MLDTFSSAPV PQHERSPADA GPVGRIAFEM FLEDKTSVNE NWLFHDDCTV ERFCDSPDGV MLCGSHDGRE VYAVTHDLTP TENWIMQFKI SVGCKVPEKI AQNQIHVQFS TDFGVSWSYL VPQCLPADPK CSGSVSQPSV FFPTEGWKRI TYPLPESLTG NPVRFRFYQK YSDVQWAIDN FYLGPGCLDN CGGHGDCLKE QCICDPGYSG PNCYLTHSLK TFLKERFDSE EIKPDLWMSL EGGSTCTECG VLAENTALYF GGSTVRQAIT QDLDLRGAKF LQYWGRIGSE NNMTSCHRPV CRKEGVLLDF STDGGITWTL LHEMDFQKYI SVRHDYILLP EGALTNTTRL RWWQPFVISN GLVVSGVERA QWALDNILIG GAEINPSQLV DTFDDEGSSH EENWSFYPNA VRTAGFCGNP SFHLYWPNKK KDKTHNALSS RELIIQPGYM MQFKIVVGCE ATSCGDLHSV MLEYTKDARS DSWQLVQTQC LPSSSNSIGC SPFQFHEATI YNAVNSSSWK RITIQLPDHV SSSATQFRWI QKGEETEKQS WAIDHVYIGE ACPKLCSGHG YCTTGAVCIC DESFQGDDCS VFSHELPSYI KDNFESARVT EANWETIQGG VIGSGCGQLA PYAHGDSLYF NGCQIRQAAT KPLDLTRASK IMFVLQIGSP AQTDSCNSDL SGPHTVDKAV LLQYSVNNGI TWHVIAQHQP KDFTQAQRVS YNVPLEARMK GVLLRWWQPR HNGTGHDQWA LDHVEVVLVS TRKQNYMMNF SRQHGLRHFY NRRRRSLRRY P //