Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

O70263 (LNX1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
E3 ubiquitin-protein ligase LNX

EC=6.3.2.-
Alternative name(s):
Ligand of Numb protein X 1
Ligand of Numb-binding protein 1
Numb-binding protein 1
Gene names
Name:Lnx1
Synonyms:Lnx
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length728 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of NUMB. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates ubiquitination of isoform p66and isoform p72of NUMB, but not that of isoform p71or isoform p65 Ref.1 Ref.4 Ref.5

Isoform 2 provides an endocytic scaffold for IGSF5/JAM4. Ref.1 Ref.4 Ref.5

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Interacts with CXADR. Interacts with MAGEB18 and MAGEF1 By similarity. Interacts with the phosphotyrosine interaction domain of all isoforms of NUMB. IGSF5/JAM4 interacts with isoform 2 through the second PDZ domain, other isoforms may also interact with IGSF5/JAM4. Ref.5 Ref.6

Subcellular location

Cytoplasm.

Tissue specificity

Isoform 1 and isoform 2 are expressed in the heart. Isoform 1 is also expressed in kidney, lung and skeletal muscle while isoform 2 is also expressed in brain. Ref.1

Domain

The NPXY motif is required for the interaction with the PID domain of NUMB. It is however not sufficient. Ref.4 Ref.5

The PDZ 1 domain participates in the interaction with the PID domain of NUMB, and participates in the isoform-specific ubiquitination of NUMB. The PDZ 2 domain of isoform 2 participates in the interaction with IGSF5/JAM4, other isoforms containing this domain may also interact with IGSF5/JAM4. Ref.4 Ref.5

Sequence similarities

Contains 4 PDZ (DHR) domains.

Contains 1 RING-type zinc finger.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O70263-1)

Also known as: LNX; LNXp80;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O70263-2)

Also known as: LNX-B; LNXp70;

The sequence of this isoform differs from the canonical sequence as follows:
     1-131: MNQPDLADDP...CDLQHHFQTS → MKALLLLVLPWLSPANYIDNVGNLHFLYSEL
Isoform 3 (identifier: O70263-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-131: MNQPDLADDP...CDLQHHFQTS → MKALLLLVLPWLSPANYIDNVGNLHFLYSEL
     332-357: NGMDISNVPHNYAVRLLRQPCQVLRL → PMRRELVTIGYKIVSCRLCVAHNLSP
     358-728: Missing.
Note: No experimental conformation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 728728E3 ubiquitin-protein ligase LNX
PRO_0000055914

Regions

Domain278 – 36285PDZ 1
Domain385 – 46783PDZ 2
Domain508 – 59386PDZ 3
Domain638 – 72386PDZ 4
Zinc finger45 – 8339RING-type
Region186 – 24459Interaction with MAGEB18 By similarity
Motif185 – 1884NPXY motif

Natural variations

Alternative sequence1 – 131131MNQPD…HFQTS → MKALLLLVLPWLSPANYIDN VGNLHFLYSEL in isoform 2 and isoform 3.
VSP_005734
Alternative sequence332 – 35726NGMDI…QVLRL → PMRRELVTIGYKIVSCRLCV AHNLSP in isoform 3.
VSP_012588
Alternative sequence358 – 728371Missing in isoform 3.
VSP_012589

Experimental info

Mutagenesis481C → A: Loss of function. Ref.4
Mutagenesis1811P → A: No effect on binding to NUMB protein. Ref.1
Mutagenesis1821G → A: Slightly affects binding to NUMB protein. Ref.1
Mutagenesis1831L → A: Abolishes binding to NUMB protein. Ref.1
Mutagenesis1841D → A: Slightly affects binding to NUMB protein. Ref.1
Mutagenesis1851N → A: Abolishes binding to NUMB protein. Ref.1
Mutagenesis1861P → A: Slightly affects binding to NUMB protein. Ref.1
Mutagenesis1881Y → A: Abolishes binding to NUMB protein. Ref.1
Mutagenesis1881Y → F: No effect on binding to NUMB protein. Ref.1
Sequence conflict2581T → N in BAC31789. Ref.2

Secondary structure

................ 728
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (LNX) (LNXp80) [UniParc].

Last modified August 1, 1998. Version 1.
Checksum: E2914BD364C0CEC4

FASTA72880,157
        10         20         30         40         50         60 
MNQPDLADDP DPSPEPLCIV CGQNHSPEEN HFYTYTEDVD DDLICHICLQ ALLDPLDTPC 

        70         80         90        100        110        120 
GHTYCTLCLT NFLVEKDFCP VDRKPVVLQH CKKSSILVNK LLNKLLVTCP FTEHCTEVLQ 

       130        140        150        160        170        180 
RCDLQHHFQT SCKGASHYGL TKDRKRRSQD GCPDGCASLM ATTLSPEVSA AATISLMTDE 

       190        200        210        220        230        240 
PGLDNPAYVS SVEDGEPVAN SSDSGRSNRT RARPFERSTM RSRSFKKINR ALSALRRTKS 

       250        260        270        280        290        300 
GSVVANHVDQ GRDNSENTTV PEVFPRLFHL IPDGEITSIK INRADPSESL SIRLVGGSET 

       310        320        330        340        350        360 
PLVHIIIQHI YRDGVIARDG RLLPGDIILK VNGMDISNVP HNYAVRLLRQ PCQVLRLTVL 

       370        380        390        400        410        420 
REQKFRSRSN AHVPDSYGPR DDSFHVILNK SSPEEQLGIK LVRRVDEPGV FIFNVLNGGV 

       430        440        450        460        470        480 
ADRHGQLEEN DRVLAINGHD LRFGSPESAA HLIQASERRV HLVVSRQVRQ SSPDIFQEAG 

       490        500        510        520        530        540 
WISNGQQSPG PGERNTASKP AATCHEKVVS VWKDPSESLG MTVGGGASHR EWDLPIYVIS 

       550        560        570        580        590        600 
VEPGGVISRD GRIKTGDILL NVNGIELTEV SRTEAVAILK SAPSSVVLKA LEVKEQEAQE 

       610        620        630        640        650        660 
DCSPAALDSN HNVTPPGDWS PSWVMWLELP QYLCNCKDVI LRRNTAGSLG FCIVGGYEEY 

       670        680        690        700        710        720 
SGNKPFFIKS IVEGTPAYND GRIRCGDILL AVNGRSTSGM IHACLARMLK ELKGRITLTI 


ASWPGTFL 

« Hide

Isoform 2 (LNX-B) (LNXp70) [UniParc].

Checksum: F4CC529ED9D33D55
Show »

FASTA62868,790
Isoform 3 [UniParc].

Checksum: ADCE0552F3BAA28D
Show »

FASTA25728,202

References

« Hide 'large scale' references
[1]"The mammalian numb phosphotyrosine-binding domain. Characterization of binding specificity and identification of a novel PDZ domain-containing numb binding protein, LNX."
Dho S.E., Jacob S., Wolting C.D., French M.B., Rohrschneider L.R., McGlade C.J.
J. Biol. Chem. 273:9179-9187(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF PRO-181; GLY-182; LEU-183; ASP-184; ASN-185; PRO-186 AND TYR-188.
Tissue: Brain and Embryo.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Strain: C57BL/6J.
Tissue: Brain cortex.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Eye.
[4]"LNX functions as a RING type E3 ubiquitin ligase that targets the cell fate determinant Numb for ubiquitin-dependent degradation."
Nie J., McGill M.A., Dermer M., Dho S.E., Wolting C.D., McGlade C.J.
EMBO J. 21:93-102(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DOMAIN NPXY MOTIF, MUTAGENESIS OF CYS-48.
[5]"A novel PTB-PDZ domain interaction mediates isoform-specific ubiquitylation of mammalian Numb."
Nie J., Li S.S.-C., McGlade C.J.
J. Biol. Chem. 279:20807-20815(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DOMAINS PDZ, INTERACTION WITH NUMB.
[6]"Ligand-of-Numb protein X is an endocytic scaffold for junctional adhesion molecule 4."
Kansaku A., Hirabayashi S., Mori H., Fujiwara N., Kawata A., Ikeda M., Rokukawa C., Kurihara H., Hata Y.
Oncogene 25:5071-5084(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IGSF5.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF034745 mRNA. Translation: AAC40075.1.
AF034746 mRNA. Translation: AAC40076.1.
AK044127 mRNA. Translation: BAC31789.1.
BC040367 mRNA. Translation: AAH40367.1.
CCDSCCDS19347.1. [O70263-2]
CCDS51524.1. [O70263-1]
PIRT09457.
T09458.
RefSeqNP_001153049.1. NM_001159577.1. [O70263-1]
NP_001153050.1. NM_001159578.1.
NP_001153051.1. NM_001159579.1. [O70263-2]
NP_001153052.1. NM_001159580.1.
NP_034857.3. NM_010727.4. [O70263-2]
XP_006504317.1. XM_006504254.1. [O70263-1]
UniGeneMm.440403.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3VQFX-ray1.20A381-467[»]
3VQGX-ray1.35A381-467[»]
ProteinModelPortalO70263.
SMRO70263. Positions 45-130, 277-722.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201187. 8 interactions.
IntActO70263. 3 interactions.
MINTMINT-253029.

PTM databases

PhosphoSiteO70263.

Proteomic databases

PaxDbO70263.
PRIDEO70263.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000039744; ENSMUSP00000040098; ENSMUSG00000029228. [O70263-2]
ENSMUST00000087161; ENSMUSP00000084405; ENSMUSG00000029228. [O70263-1]
ENSMUST00000117388; ENSMUSP00000113035; ENSMUSG00000029228. [O70263-1]
ENSMUST00000117525; ENSMUSP00000113837; ENSMUSG00000029228. [O70263-2]
GeneID16924.
KEGGmmu:16924.
UCSCuc008xtr.2. mouse. [O70263-1]
uc008xtu.2. mouse. [O70263-3]

Organism-specific databases

CTD84708.
MGIMGI:1278335. Lnx1.

Phylogenomic databases

eggNOGNOG236845.
GeneTreeENSGT00740000115038.
HOGENOMHOG000261605.
HOVERGENHBG039539.
InParanoidO70263.
KOK10692.
OMAVFPRLYH.
OrthoDBEOG75F4CJ.
PhylomeDBO70263.
TreeFamTF330709.

Enzyme and pathway databases

UniPathwayUPA00143.

Gene expression databases

ArrayExpressO70263.
BgeeO70263.
CleanExMM_LNX1.
GenevestigatorO70263.

Family and domain databases

Gene3D2.30.42.10. 4 hits.
3.30.40.10. 1 hit.
InterProIPR001478. PDZ.
IPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamPF00595. PDZ. 4 hits.
PF00097. zf-C3HC4. 1 hit.
[Graphical view]
SMARTSM00228. PDZ. 4 hits.
SM00184. RING. 1 hit.
[Graphical view]
SUPFAMSSF50156. SSF50156. 4 hits.
PROSITEPS50106. PDZ. 4 hits.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSLNX1. mouse.
NextBio290980.
PROO70263.
SOURCESearch...

Entry information

Entry nameLNX1_MOUSE
AccessionPrimary (citable) accession number: O70263
Secondary accession number(s): O70264, Q8BRI8, Q8CFR3
Entry history
Integrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: August 1, 1998
Last modified: July 9, 2014
This is version 123 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot