ID LNX1_MOUSE Reviewed; 728 AA. AC O70263; O70264; Q8BRI8; Q8CFR3; DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1998, sequence version 1. DT 07-JAN-2015, entry version 128. DE RecName: Full=E3 ubiquitin-protein ligase LNX; DE EC=6.3.2.-; DE AltName: Full=Ligand of Numb protein X 1; DE AltName: Full=Ligand of Numb-binding protein 1; DE AltName: Full=Numb-binding protein 1; GN Name=Lnx1; Synonyms=Lnx; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus; 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 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 PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., RA Davis M.J., Wilming L.G., Aidinis V., Allen J.E., RA Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., RA Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., RA Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., RA Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., RA di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., RA Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., RA Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., RA Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., RA Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., RA Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., RA Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., RA Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., RA Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., RA Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., RA Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., RA Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., RA Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., RA Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., RA Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., RA Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., RA Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., RA Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., RA Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., RA Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., RA Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., RA Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., RA Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., RA Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., RA Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., RA Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Eye; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP FUNCTION, DOMAIN NPXY MOTIF, 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, DOMAINS PDZ, 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). RN [6] RP INTERACTION WITH IGSF5. RX PubMed=16832352; DOI=10.1038/sj.onc.1209468; RA Kansaku A., Hirabayashi S., Mori H., Fujiwara N., Kawata A., Ikeda M., RA Rokukawa C., Kurihara H., Hata Y.; RT "Ligand-of-Numb protein X is an endocytic scaffold for junctional RT adhesion molecule 4."; RL Oncogene 25:5071-5084(2006). CC -!- FUNCTION: E3 ubiquitin-protein ligase 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 -!- FUNCTION: Isoform 2 provides an endocytic scaffold for IGSF5/JAM4. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Interacts with CXADR. Interacts with MAGEB18 and MAGEF1 CC (By similarity). Interacts with the phosphotyrosine interaction CC domain of all isoforms of NUMB. IGSF5/JAM4 interacts with isoform CC 2 through the second PDZ domain, other isoforms may also interact CC with IGSF5/JAM4. {ECO:0000250, ECO:0000269|PubMed:14990566, CC ECO:0000269|PubMed:16832352}. CC -!- SUBCELLULAR LOCATION: Cytoplasm. 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 {ECO:0000269|PubMed:9535908}. 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. The PDZ 2 domain of isoform 2 participates CC in the interaction with IGSF5/JAM4, other isoforms containing this CC domain may also interact with IGSF5/JAM4. CC -!- SIMILARITY: Contains 4 PDZ (DHR) domains. {ECO:0000255|PROSITE- CC ProRule:PRU00143}. CC -!- SIMILARITY: Contains 1 RING-type zinc finger. CC {ECO:0000255|PROSITE-ProRule:PRU00175}. 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 CCDS; CCDS19347.1; -. [O70263-2] DR CCDS; CCDS51524.1; -. [O70263-1] DR PIR; T09457; T09457. DR PIR; T09458; T09458. DR RefSeq; NP_001153049.1; NM_001159577.1. [O70263-1] DR RefSeq; NP_001153050.1; NM_001159578.1. DR RefSeq; NP_001153051.1; NM_001159579.1. [O70263-2] DR RefSeq; NP_001153052.1; NM_001159580.1. DR RefSeq; NP_034857.3; NM_010727.4. [O70263-2] DR RefSeq; XP_006504317.1; XM_006504254.1. [O70263-1] DR UniGene; Mm.440403; -. DR PDB; 3VQF; X-ray; 1.20 A; A=381-467. DR PDB; 3VQG; X-ray; 1.35 A; A=381-467. DR PDBsum; 3VQF; -. DR PDBsum; 3VQG; -. DR ProteinModelPortal; O70263; -. DR SMR; O70263; 45-130, 277-722. DR BioGrid; 201187; 8. DR IntAct; O70263; 3. DR MINT; MINT-253029; -. DR PhosphoSite; O70263; -. DR PaxDb; O70263; -. DR PRIDE; O70263; -. DR Ensembl; ENSMUST00000039744; ENSMUSP00000040098; ENSMUSG00000029228. [O70263-2] DR Ensembl; ENSMUST00000087161; ENSMUSP00000084405; ENSMUSG00000029228. [O70263-1] DR Ensembl; ENSMUST00000117388; ENSMUSP00000113035; ENSMUSG00000029228. [O70263-1] DR Ensembl; ENSMUST00000117525; ENSMUSP00000113837; ENSMUSG00000029228. [O70263-2] DR GeneID; 16924; -. DR KEGG; mmu:16924; -. DR UCSC; uc008xtr.2; mouse. [O70263-1] DR UCSC; uc008xtu.2; mouse. [O70263-3] DR CTD; 84708; -. DR MGI; MGI:1278335; Lnx1. DR eggNOG; NOG236845; -. DR GeneTree; ENSGT00760000119017; -. DR HOGENOM; HOG000261605; -. DR HOVERGEN; HBG039539; -. DR InParanoid; O70263; -. DR KO; K10692; -. DR OMA; PDIFQEA; -. DR OrthoDB; EOG75F4CJ; -. DR PhylomeDB; O70263; -. DR TreeFam; TF330709; -. DR UniPathway; UPA00143; -. DR ChiTaRS; Lnx1; mouse. DR NextBio; 290980; -. DR PRO; PR:O70263; -. DR Proteomes; UP000000589; Chromosome 5. DR Bgee; O70263; -. DR CleanEx; MM_LNX1; -. DR ExpressionAtlas; O70263; baseline and differential. DR Genevestigator; O70263; -. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW. DR GO; GO:0030165; F:PDZ domain binding; IDA:MGI. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:MGI. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0051260; P:protein homooligomerization; IDA:MGI. DR GO; GO:0042787; P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process; IDA:MGI. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:MGI. DR Gene3D; 2.30.42.10; -; 4. DR Gene3D; 3.30.40.10; -; 1. DR InterPro; IPR001478; PDZ. DR InterPro; IPR018957; Znf_C3HC4_RING-type. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR InterPro; IPR017907; Znf_RING_CS. DR Pfam; PF00595; PDZ; 4. DR Pfam; PF00097; zf-C3HC4; 1. DR SMART; SM00228; PDZ; 4. DR SMART; SM00184; RING; 1. DR SUPFAM; SSF50156; SSF50156; 4. DR PROSITE; PS50106; PDZ; 4. DR PROSITE; PS00518; ZF_RING_1; 1. DR PROSITE; PS50089; ZF_RING_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Complete proteome; Cytoplasm; KW Ligase; Metal-binding; Reference proteome; Repeat; KW Ubl conjugation pathway; Zinc; Zinc-finger. FT CHAIN 1 728 E3 ubiquitin-protein ligase LNX. FT /FTId=PRO_0000055914. FT DOMAIN 278 362 PDZ 1. {ECO:0000255|PROSITE- FT ProRule:PRU00143}. FT DOMAIN 385 467 PDZ 2. {ECO:0000255|PROSITE- FT ProRule:PRU00143}. FT DOMAIN 508 593 PDZ 3. {ECO:0000255|PROSITE- FT ProRule:PRU00143}. FT DOMAIN 638 723 PDZ 4. {ECO:0000255|PROSITE- FT ProRule:PRU00143}. FT ZN_FING 45 83 RING-type. {ECO:0000255|PROSITE- FT ProRule:PRU00175}. FT REGION 186 244 Interaction with MAGEB18. {ECO:0000250}. FT MOTIF 185 188 NPXY motif. FT VAR_SEQ 1 131 MNQPDLADDPDPSPEPLCIVCGQNHSPEENHFYTYTEDVDD FT DLICHICLQALLDPLDTPCGHTYCTLCLTNFLVEKDFCPVD FT RKPVVLQHCKKSSILVNKLLNKLLVTCPFTEHCTEVLQRCD FT LQHHFQTS -> MKALLLLVLPWLSPANYIDNVGNLHFLYS FT EL (in isoform 2 and isoform 3). FT {ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:16141072, FT ECO:0000303|PubMed:9535908}. FT /FTId=VSP_005734. FT VAR_SEQ 332 357 NGMDISNVPHNYAVRLLRQPCQVLRL -> PMRRELVTIGY FT KIVSCRLCVAHNLSP (in isoform 3). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_012588. FT VAR_SEQ 358 728 Missing (in isoform 3). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_012589. FT MUTAGEN 48 48 C->A: Loss of function. FT {ECO:0000269|PubMed:11782429}. FT MUTAGEN 181 181 P->A: No effect on binding to NUMB FT protein. {ECO:0000269|PubMed:9535908}. FT MUTAGEN 182 182 G->A: Slightly affects binding to NUMB FT protein. {ECO:0000269|PubMed:9535908}. FT MUTAGEN 183 183 L->A: Abolishes binding to NUMB protein. FT {ECO:0000269|PubMed:9535908}. FT MUTAGEN 184 184 D->A: Slightly affects binding to NUMB FT protein. {ECO:0000269|PubMed:9535908}. FT MUTAGEN 185 185 N->A: Abolishes binding to NUMB protein. FT {ECO:0000269|PubMed:9535908}. FT MUTAGEN 186 186 P->A: Slightly affects binding to NUMB FT protein. {ECO:0000269|PubMed:9535908}. FT MUTAGEN 188 188 Y->A: Abolishes binding to NUMB protein. FT {ECO:0000269|PubMed:9535908}. FT MUTAGEN 188 188 Y->F: No effect on binding to NUMB FT protein. {ECO:0000269|PubMed:9535908}. FT CONFLICT 258 258 T -> N (in Ref. 2; BAC31789). FT {ECO:0000305}. FT STRAND 384 389 {ECO:0000244|PDB:3VQF}. FT STRAND 398 402 {ECO:0000244|PDB:3VQF}. FT STRAND 405 407 {ECO:0000244|PDB:3VQF}. FT STRAND 409 415 {ECO:0000244|PDB:3VQF}. FT HELIX 420 424 {ECO:0000244|PDB:3VQF}. FT STRAND 432 436 {ECO:0000244|PDB:3VQF}. FT HELIX 446 455 {ECO:0000244|PDB:3VQF}. FT STRAND 456 465 {ECO:0000244|PDB:3VQF}. 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 //