LNX1_MOUSE
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 03-AUG-2022, entry version 178.
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.ENSMUSP00000113035; -.
DR iPTMnet; O70263; -.
DR PhosphoSitePlus; O70263; -.
DR PaxDb; O70263; -.
DR PRIDE; O70263; -.
DR ProteomicsDB; 290136; -. [O70263-1]
DR ProteomicsDB; 290137; -. [O70263-2]
DR ProteomicsDB; 290138; -. [O70263-3]
DR Antibodypedia; 1114; 237 antibodies from 29 providers.
DR DNASU; 16924; -.
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 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; AYGPRDD; -.
DR OrthoDB; 615205at2759; -.
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 73 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 225 other 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: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; IPR036034; PDZ_sf.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR Pfam; PF00595; PDZ; 4.
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; 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
