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 24-JAN-2024, entry version 186. DE RecName: Full=E3 ubiquitin-protein ligase LNX; DE EC=2.3.2.27; 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; DE AltName: Full=RING-type E3 ubiquitin transferase LNX {ECO:0000305}; GN Name=Lnx1; Synonyms=Lnx; 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] (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 of RT binding specificity and identification of a novel PDZ domain-containing RT 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., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., 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., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., 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 project: RT 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 cell RT 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 adhesion RT molecule 4."; RL Oncogene 25:5071-5084(2006). CC -!- FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination and CC subsequent proteasomal degradation of NUMB. E3 ubiquitin ligases accept CC ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a CC thioester and then directly transfers the ubiquitin to targeted CC substrates. Mediates ubiquitination of isoform p66 and isoform p72 of CC NUMB, but not that of isoform p71 or isoform p65. CC {ECO:0000269|PubMed:11782429, ECO:0000269|PubMed:14990566, CC ECO:0000269|PubMed:9535908}. CC -!- FUNCTION: Isoform 2 provides an endocytic scaffold for IGSF5/JAM4. CC {ECO:0000269|PubMed:9535908}. CC -!- CATALYTIC ACTIVITY: CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; CC EC=2.3.2.27; CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Interacts with CXADR. Interacts with MAGEB18 and MAGEF1 (By CC similarity). Interacts with the phosphotyrosine interaction domain of CC all isoforms of NUMB. IGSF5/JAM4 interacts with isoform 2 through the CC second PDZ domain, other isoforms may also interact with IGSF5/JAM4. CC {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 -!- TISSUE SPECIFICITY: Isoform 1 and isoform 2 are expressed in the heart. CC Isoform 1 is also expressed in kidney, lung and skeletal muscle while CC isoform 2 is also expressed in brain. {ECO:0000269|PubMed:9535908}. CC -!- DOMAIN: The NPXY motif is required for the interaction with the PID CC domain of NUMB. It is however not sufficient. CC -!- DOMAIN: The PDZ 1 domain participates in the interaction with the PID CC domain of NUMB, and participates in the isoform-specific ubiquitination CC of NUMB. The PDZ 2 domain of isoform 2 participates in the interaction CC with IGSF5/JAM4, other isoforms containing this domain may also CC interact with IGSF5/JAM4. 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_006504254.3. [O70263-1] 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 AlphaFoldDB; O70263; -. DR SMR; O70263; -. DR BioGRID; 201187; 87. DR CORUM; O70263; -. DR IntAct; O70263; 3. DR MINT; O70263; -. DR STRING; 10090.ENSMUSP00000084405; -. DR GlyGen; O70263; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; O70263; -. DR PhosphoSitePlus; O70263; -. DR PaxDb; 10090-ENSMUSP00000113035; -. DR ProteomicsDB; 290136; -. [O70263-1] DR ProteomicsDB; 290137; -. [O70263-2] DR ProteomicsDB; 290138; -. [O70263-3] DR Antibodypedia; 1114; 259 antibodies from 29 providers. DR DNASU; 16924; -. DR Ensembl; ENSMUST00000039744.13; ENSMUSP00000040098.7; ENSMUSG00000029228.16. [O70263-2] DR Ensembl; ENSMUST00000087161.10; ENSMUSP00000084405.4; ENSMUSG00000029228.16. [O70263-1] DR Ensembl; ENSMUST00000117388.8; ENSMUSP00000113035.2; ENSMUSG00000029228.16. [O70263-1] DR Ensembl; ENSMUST00000117525.8; ENSMUSP00000113837.2; ENSMUSG00000029228.16. [O70263-2] DR GeneID; 16924; -. DR UCSC; uc008xtr.2; mouse. [O70263-1] DR UCSC; uc008xtu.2; mouse. [O70263-3] DR AGR; MGI:1278335; -. DR CTD; 84708; -. DR MGI; MGI:1278335; Lnx1. DR VEuPathDB; HostDB:ENSMUSG00000029228; -. DR eggNOG; KOG0297; Eukaryota. DR eggNOG; KOG3528; Eukaryota. DR GeneTree; ENSGT00940000158757; -. DR HOGENOM; CLU_021213_0_0_1; -. DR InParanoid; O70263; -. DR OMA; NHNMAPA; -. DR OrthoDB; 3028121at2759; -. DR PhylomeDB; O70263; -. DR TreeFam; TF330709; -. DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 16924; 2 hits in 78 CRISPR screens. DR ChiTaRS; Lnx1; mouse. DR PRO; PR:O70263; -. DR Proteomes; UP000000589; Chromosome 5. DR RNAct; O70263; Protein. DR Bgee; ENSMUSG00000029228; Expressed in motor neuron and 227 other cell types or tissues. DR ExpressionAtlas; O70263; baseline and differential. DR Genevisible; O70263; MM. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0042802; F:identical protein binding; IPI:MGI. DR GO; GO:0046872; F:metal ion binding; 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:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:MGI. DR CDD; cd16779; mRING-HC-C3HC3D_LNX1; 1. DR CDD; cd00992; PDZ_signaling; 4. DR Gene3D; 2.30.42.10; -; 4. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR001478; PDZ. DR InterPro; IPR036034; PDZ_sf. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR InterPro; IPR017907; Znf_RING_CS. DR PANTHER; PTHR19964:SF14; E3 UBIQUITIN-PROTEIN LIGASE LNX; 1. DR PANTHER; PTHR19964; MULTIPLE PDZ DOMAIN PROTEIN; 1. DR Pfam; PF00595; PDZ; 4. DR Pfam; PF13920; zf-C3HC4_3; 1. DR SMART; SM00228; PDZ; 4. DR SMART; SM00184; RING; 1. DR SUPFAM; SSF50156; PDZ domain-like; 4. DR SUPFAM; SSF57850; RING/U-box; 1. 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; Cytoplasm; Metal-binding; KW Phosphoprotein; Reference proteome; Repeat; Transferase; KW Ubl conjugation pathway; Zinc; Zinc-finger. FT CHAIN 1..728 FT /note="E3 ubiquitin-protein ligase LNX" FT /id="PRO_0000055914" FT DOMAIN 278..362 FT /note="PDZ 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143" FT DOMAIN 385..467 FT /note="PDZ 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143" FT DOMAIN 508..593 FT /note="PDZ 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143" FT DOMAIN 638..723 FT /note="PDZ 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143" FT ZN_FING 45..83 FT /note="RING-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175" FT REGION 185..220 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 186..244 FT /note="Interaction with MAGEB18" FT /evidence="ECO:0000250" FT REGION 481..500 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 185..188 FT /note="NPXY motif" FT MOD_RES 445 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8TBB1" FT VAR_SEQ 1..131 FT /note="MNQPDLADDPDPSPEPLCIVCGQNHSPEENHFYTYTEDVDDDLICHICLQAL FT LDPLDTPCGHTYCTLCLTNFLVEKDFCPVDRKPVVLQHCKKSSILVNKLLNKLLVTCPF FT TEHCTEVLQRCDLQHHFQTS -> MKALLLLVLPWLSPANYIDNVGNLHFLYSEL (in FT isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:16141072, ECO:0000303|PubMed:9535908" FT /id="VSP_005734" FT VAR_SEQ 332..357 FT /note="NGMDISNVPHNYAVRLLRQPCQVLRL -> PMRRELVTIGYKIVSCRLCVAH FT NLSP (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_012588" FT VAR_SEQ 358..728 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_012589" FT MUTAGEN 48 FT /note="C->A: Loss of function." FT /evidence="ECO:0000269|PubMed:11782429" FT MUTAGEN 181 FT /note="P->A: No effect on binding to NUMB protein." FT /evidence="ECO:0000269|PubMed:9535908" FT MUTAGEN 182 FT /note="G->A: Slightly affects binding to NUMB protein." FT /evidence="ECO:0000269|PubMed:9535908" FT MUTAGEN 183 FT /note="L->A: Abolishes binding to NUMB protein." FT /evidence="ECO:0000269|PubMed:9535908" FT MUTAGEN 184 FT /note="D->A: Slightly affects binding to NUMB protein." FT /evidence="ECO:0000269|PubMed:9535908" FT MUTAGEN 185 FT /note="N->A: Abolishes binding to NUMB protein." FT /evidence="ECO:0000269|PubMed:9535908" FT MUTAGEN 186 FT /note="P->A: Slightly affects binding to NUMB protein." FT /evidence="ECO:0000269|PubMed:9535908" FT MUTAGEN 188 FT /note="Y->A: Abolishes binding to NUMB protein." FT /evidence="ECO:0000269|PubMed:9535908" FT MUTAGEN 188 FT /note="Y->F: No effect on binding to NUMB protein." FT /evidence="ECO:0000269|PubMed:9535908" FT CONFLICT 258 FT /note="T -> N (in Ref. 2; BAC31789)" FT /evidence="ECO:0000305" FT STRAND 384..389 FT /evidence="ECO:0007829|PDB:3VQF" FT STRAND 398..402 FT /evidence="ECO:0007829|PDB:3VQF" FT STRAND 405..407 FT /evidence="ECO:0007829|PDB:3VQF" FT STRAND 409..415 FT /evidence="ECO:0007829|PDB:3VQF" FT HELIX 420..424 FT /evidence="ECO:0007829|PDB:3VQF" FT STRAND 432..436 FT /evidence="ECO:0007829|PDB:3VQF" FT HELIX 446..455 FT /evidence="ECO:0007829|PDB:3VQF" FT STRAND 456..465 FT /evidence="ECO:0007829|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 //