ID LNX1_MOUSE STANDARD; PRT; 728 AA. AC O70263; O70264; Q8BRI8; Q8CFR3; DT 28-FEB-2003 (Rel. 41, Created) DT 28-FEB-2003 (Rel. 41, Last sequence update) DT 10-MAY-2005 (Rel. 47, Last annotation update) DE Ubiquitin ligase LNX (EC 6.3.2.-) (Numb-binding protein 1) (Ligand of DE Numb-binding protein 1) (Ligand of Numb-protein X 1). GN Name=Lnx; Synonyms=Lnx1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muridae; Murinae; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, TISSUE RP SPECIFICITY, AND MUTAGENESIS OF PRO-181; GLY-182; LEU-183; ASP-184; RP ASN-185; PRO-186 AND TYR-188. RC TISSUE=Brain, and Embryo; RX MEDLINE=98204916; PubMed=9535908; DOI=10.1074/jbc.273.15.9179; RA Dho S.E., Jacob S., Wolting C.D., French M.B., Rohrschneider L.R., RA McGlade C.J.; RT "The mammalian numb phosphotyrosine-binding domain. Characterization RT of binding specificity and identification of a novel PDZ domain- RT containing numb binding protein, LNX."; RL J. Biol. Chem. 273:9179-9187(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC STRAIN=C57BL/6J; TISSUE=Brain cortex; RX MEDLINE=22354683; PubMed=12466851; DOI=10.1038/nature01266; RA Okazaki Y., Furuno M., Kasukawa T., Adachi J., Bono H., Kondo S., RA Nikaido I., Osato N., Saito R., Suzuki H., Yamanaka I., Kiyosawa H., RA Yagi K., Tomaru Y., Hasegawa Y., Nogami A., Schonbach C., Gojobori T., RA Baldarelli R., Hill D.P., Bult C., Hume D.A., Quackenbush J., RA Schriml L.M., Kanapin A., Matsuda H., Batalov S., Beisel K.W., RA Blake J.A., Bradt D., Brusic V., Chothia C., Corbani L.E., Cousins S., RA Dalla E., Dragani T.A., Fletcher C.F., Forrest A., Frazer K.S., RA Gaasterland T., Gariboldi M., Gissi C., Godzik A., Gough J., RA Grimmond S., Gustincich S., Hirokawa N., Jackson I.J., Jarvis E.D., RA Kanai A., Kawaji H., Kawasawa Y., Kedzierski R.M., King B.L., RA Konagaya A., Kurochkin I.V., Lee Y., Lenhard B., Lyons P.A., RA Maglott D.R., Maltais L., Marchionni L., McKenzie L., Miki H., RA Nagashima T., Numata K., Okido T., Pavan W.J., Pertea G., Pesole G., RA Petrovsky N., Pillai R., Pontius J.U., Qi D., Ramachandran S., RA Ravasi T., Reed J.C., Reed D.J., Reid J., Ring B.Z., Ringwald M., RA Sandelin A., Schneider C., Semple C.A., Setou M., Shimada K., RA Sultana R., Takenaka Y., Taylor M.S., Teasdale R.D., Tomita M., RA Verardo R., Wagner L., Wahlestedt C., Wang Y., Watanabe Y., Wells C., RA Wilming L.G., Wynshaw-Boris A., Yanagisawa M., Yang I., Yang L., RA Yuan Z., Zavolan M., Zhu Y., Zimmer A., Carninci P., Hayatsu N., RA Hirozane-Kishikawa T., Konno H., Nakamura M., Sakazume N., Sato K., RA Shiraki T., Waki K., Kawai J., Aizawa K., Arakawa T., Fukuda S., RA Hara A., Hashizume W., Imotani K., Ishii Y., Itoh M., Kagawa I., RA Miyazaki A., Sakai K., Sasaki D., Shibata K., Shinagawa A., RA Yasunishi A., Yoshino M., Waterston R., Lander E.S., Rogers J., RA Birney E., Hayashizaki Y.; RT "Analysis of the mouse transcriptome based on functional annotation of RT 60,770 full-length cDNAs."; RL Nature 420:563-573(2002). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Eye; RX MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length human RT and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [4] RP FUNCTION, NPXY DOMAIN, AND MUTAGENESIS OF CYS-48. RX PubMed=11782429; DOI=10.1093/emboj/21.1.93; RA Nie J., McGill M.A., Dermer M., Dho S.E., Wolting C.D., McGlade C.J.; RT "LNX functions as a RING type E3 ubiquitin ligase that targets the RT cell fate determinant Numb for ubiquitin-dependent degradation."; RL EMBO J. 21:93-102(2002). RN [5] RP FUNCTION, PDZ DOMAIN, AND INTERACTION WITH NUMB. RX PubMed=14990566; DOI=10.1074/jbc.M311396200; RA Nie J., Li S.S.-C., McGlade C.J.; RT "A novel PTB-PDZ domain interaction mediates isoform-specific RT ubiquitylation of mammalian Numb."; RL J. Biol. Chem. 279:20807-20815(2004). CC -!- FUNCTION: E3 Ubiquitin ligase protein that mediates ubiquitination CC and subsequent proteasomal degradation of NUMB. E3 ubiquitin CC ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme CC in the form of a thioester and then directly transfers the CC ubiquitin to targeted substrates. Mediates ubiquitination of CC isoform p66 and isoform p72 of NUMB, but not that of isoform p71 CC or isoform p65. CC -!- PATHWAY: Ubiquitin conjugation; third step. CC -!- SUBUNIT: Interacts with CXADR (By similarity). Interacts with the CC phosphotyrosine interaction domain of all isoforms of NUMB. CC -!- SUBCELLULAR LOCATION: Cytoplasmic. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=LNX, LNXp80; CC IsoId=O70263-1; Sequence=Displayed; CC Name=2; Synonyms=LNX-B, LNXp70; CC IsoId=O70263-2; Sequence=VSP_005734; CC Name=3; CC IsoId=O70263-3; Sequence=VSP_005734, VSP_012588, VSP_012589; CC Note=No experimental conformation available; CC -!- TISSUE SPECIFICITY: Isoform 1 and isoform 2 are expressed in the CC heart. Isoform 1 is also expressed in kidney, lung and skeletal CC muscle while isoform 2 is also expressed in brain. CC -!- DOMAIN: The NPXY motif is required for the interaction with the CC PID domain of NUMB. It is however not sufficient. CC -!- DOMAIN: The PDZ 1 domain participates in the interaction with the CC PID domain of NUMB, and participates in the isoform-specific CC ubiquitination of NUMB. CC -!- SIMILARITY: Contains 4 PDZ (DHR) domains. CC -!- SIMILARITY: Contains 1 RING-type zinc finger. 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; AF034745; AAC40075.1; -; mRNA. DR EMBL; AF034746; AAC40076.1; -; mRNA. DR EMBL; AK044127; BAC31789.1; -; mRNA. DR EMBL; BC040367; AAH40367.1; -; mRNA. DR PIR; T09457; T09457. DR PIR; T09458; T09458. DR HSSP; Q64512; 1GM1. DR MGI; MGI:1278335; Lnx1. DR GO; GO:0005737; C:cytoplasm; IDA. DR GO; GO:0005615; C:extracellular space; TAS. DR GO; GO:0030165; F:PDZ domain binding; IDA. DR GO; GO:0005515; F:protein binding; IPI. DR GO; GO:0004842; F:ubiquitin-protein ligase activity; IDA. DR GO; GO:0051260; P:protein homooligomerization; IDA. DR GO; GO:0042787; P:protein ubiquitination during ubiquitin-dep...; IDA. DR InterPro; IPR001478; PDZ. DR InterPro; IPR001841; Znf_ring. DR Pfam; PF00595; PDZ; 4. DR Pfam; PF00097; zf-C3HC4; 1. DR SMART; SM00228; PDZ; 4. DR SMART; SM00184; RING; 1. DR PROSITE; PS50106; PDZ; 4. DR PROSITE; PS00518; ZF_RING_1; 1. DR PROSITE; PS50089; ZF_RING_2; 1. KW Alternative splicing; Ligase; Metal-binding; Repeat; KW Ubl conjugation pathway; Zinc; Zinc-finger. FT DOMAIN 278 362 PDZ 1. FT DOMAIN 385 467 PDZ 2. FT DOMAIN 508 593 PDZ 3. FT DOMAIN 638 723 PDZ 4. FT ZN_FING 45 83 RING-type. FT MOTIF 185 188 NPXY motif. FT VARSPLIC 1 131 MNQPDLADDPDPSPEPLCIVCGQNHSPEENHFYTYTEDVDD FT DLICHICLQALLDPLDTPCGHTYCTLCLTNFLVEKDFCPVD FT RKPVVLQHCKKSSILVNKLLNKLLVTCPFTEHCTEVLQRCD FT LQHHFQTS -> MKALLLLVLPWLSPANYIDNVGNLHFLYS FT EL (in isoform 2 and isoform 3). FT /FTId=VSP_005734. FT VARSPLIC 332 357 NGMDISNVPHNYAVRLLRQPCQVLRL -> PMRRELVTIGY FT KIVSCRLCVAHNLSP (in isoform 3). FT /FTId=VSP_012588. FT VARSPLIC 358 728 Missing (in isoform 3). FT /FTId=VSP_012589. FT MUTAGEN 48 48 C->A: Loss of function. FT MUTAGEN 181 181 P->A: No effect on binding to NUMB FT protein. FT MUTAGEN 182 182 G->A: Slightly affects binding to NUMB FT protein. FT MUTAGEN 183 183 L->A: Abolishes binding to NUMB protein. FT MUTAGEN 184 184 D->A: Slightly affects binding to NUMB FT protein. FT MUTAGEN 185 185 N->A: Abolishes binding to NUMB protein. FT MUTAGEN 186 186 P->A: Slightly affects binding to NUMB FT protein. FT MUTAGEN 188 188 Y->A: Abolishes binding to NUMB protein. FT MUTAGEN 188 188 Y->F: No effect on binding to NUMB FT protein. FT CONFLICT 258 258 T -> N (in Ref. 2). SQ SEQUENCE 728 AA; 80157 MW; E2914BD364C0CEC4 CRC64; MNQPDLADDP DPSPEPLCIV CGQNHSPEEN HFYTYTEDVD DDLICHICLQ ALLDPLDTPC GHTYCTLCLT NFLVEKDFCP VDRKPVVLQH CKKSSILVNK LLNKLLVTCP FTEHCTEVLQ RCDLQHHFQT SCKGASHYGL TKDRKRRSQD GCPDGCASLM ATTLSPEVSA AATISLMTDE PGLDNPAYVS SVEDGEPVAN SSDSGRSNRT RARPFERSTM RSRSFKKINR ALSALRRTKS GSVVANHVDQ GRDNSENTTV PEVFPRLFHL IPDGEITSIK INRADPSESL SIRLVGGSET PLVHIIIQHI YRDGVIARDG RLLPGDIILK VNGMDISNVP HNYAVRLLRQ PCQVLRLTVL REQKFRSRSN AHVPDSYGPR DDSFHVILNK SSPEEQLGIK LVRRVDEPGV FIFNVLNGGV ADRHGQLEEN DRVLAINGHD LRFGSPESAA HLIQASERRV HLVVSRQVRQ SSPDIFQEAG WISNGQQSPG PGERNTASKP AATCHEKVVS VWKDPSESLG MTVGGGASHR EWDLPIYVIS VEPGGVISRD GRIKTGDILL NVNGIELTEV SRTEAVAILK SAPSSVVLKA LEVKEQEAQE DCSPAALDSN HNVTPPGDWS PSWVMWLELP QYLCNCKDVI LRRNTAGSLG FCIVGGYEEY SGNKPFFIKS IVEGTPAYND GRIRCGDILL AVNGRSTSGM IHACLARMLK ELKGRITLTI ASWPGTFL //