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Protein

E3 ubiquitin-protein ligase LNX

Gene

LNX1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 p66 and isoform p72 of NUMB, but not that of isoform p71 or isoform p65.By similarity
Isoform 2 provides an endocytic scaffold for IGSF5/JAM4.By similarity

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri41 – 79RING-typePROSITE-ProRule annotationAdd BLAST39

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processUbl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SIGNORiQ8TBB1.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase LNX (EC:2.3.2.27)
Alternative name(s):
Ligand of Numb-protein X 1
Numb-binding protein 1
PDZ domain-containing RING finger protein 2
RING-type E3 ubiquitin transferase LNXCurated
Gene namesi
Name:LNX1
Synonyms:LNX, PDZRN2
ORF Names:UNQ574/PRO1136
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000072201.13.
HGNCiHGNC:6657. LNX1.

Subcellular locationi

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi84708.
OpenTargetsiENSG00000072201.
PharmGKBiPA30419.

Polymorphism and mutation databases

BioMutaiLNX1.
DMDMi29840786.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000559131 – 728E3 ubiquitin-protein ligase LNXAdd BLAST728

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei441PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ8TBB1.
PeptideAtlasiQ8TBB1.
PRIDEiQ8TBB1.

PTM databases

iPTMnetiQ8TBB1.
PhosphoSitePlusiQ8TBB1.

Expressioni

Tissue specificityi

Expressed in heart, placenta, kidney, pancreas and brain.1 Publication

Gene expression databases

BgeeiENSG00000072201.
CleanExiHS_LNX1.
ExpressionAtlasiQ8TBB1. baseline and differential.
GenevisibleiQ8TBB1. HS.

Organism-specific databases

HPAiHPA002235.
HPA071091.

Interactioni

Subunit structurei

Interacts with the phosphotyrosine interaction domain of all isoforms of NUMB (By similarity). Interacts with MAGEB18 and MAGEF1. Interacts with the Coxsackievirus and adenovirus receptor CXADR. Interacts with endogenous retrovirus K protein Np9. IGSF5/JAM4 interacts with isoform 2 through the second PDZ domain, other isoforms may also interact with IGSF5/JAM4 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
ACAT2Q9BWD13EBI-739832,EBI-1047273
ACY3Q96HD93EBI-739832,EBI-3916242
AGTRAPQ6RW133EBI-739832,EBI-741181
AIDAQ96BJ33EBI-739832,EBI-4401674
AIMP2Q131556EBI-739832,EBI-745226
ALDOCP099727EBI-739832,EBI-2952751
ALKBH3Q96Q833EBI-739832,EBI-6658697
APIPQ96GX910EBI-739832,EBI-359248
APOL4Q9BRG63EBI-739832,EBI-10296818
ATPAF2Q8N5M18EBI-739832,EBI-1166928
ATRIPQ8WXE13EBI-739832,EBI-747353
BLVRAP530043EBI-739832,EBI-7410441
C1QTNF1Q9BXJ13EBI-739832,EBI-750200
CA8P352196EBI-739832,EBI-718700
CATSPERDQ86XM03EBI-739832,EBI-10260328
CBX1P839164EBI-739832,EBI-78129
CCDC102BQ68D863EBI-739832,EBI-10171570
CCDC114Q96M633EBI-739832,EBI-10173858
CCDC36Q8IYA84EBI-739832,EBI-8638439
CDAP323208EBI-739832,EBI-9250559
CEP72Q9P2093EBI-739832,EBI-739498
CIB3Q96Q773EBI-739832,EBI-10292696
CIRBPQ140113EBI-739832,EBI-538850
CLK1P49759-34EBI-739832,EBI-11981867
CLK2P497607EBI-739832,EBI-750020
COILP384322EBI-739832,EBI-945751
CPNE2Q96FN43EBI-739832,EBI-7097057
DAB1O755533EBI-739832,EBI-7875264
DCTDP323213EBI-739832,EBI-739870
DCUN1D5Q9BTE73EBI-739832,EBI-3924013
DDIT3P356384EBI-739832,EBI-742651
DDX17Q928413EBI-739832,EBI-746012
DIB1Q068193EBI-739832,EBI-166From Saccharomyces cerevisiae (strain ATCC 204508 / S288c).
DNPEPQ9ULA05EBI-739832,EBI-748356
DPF2Q927853EBI-739832,EBI-359932
EIF4HQ150563EBI-739832,EBI-748492
ENOX1Q8TC923EBI-739832,EBI-713221
EXOSC8Q96B268EBI-739832,EBI-371922
FAM118AQ9NWS63EBI-739832,EBI-8638992
FAM124AQ86V423EBI-739832,EBI-744506
FAM9BQ8IZU03EBI-739832,EBI-10175124
FBXL12Q9NXK83EBI-739832,EBI-719790
GDI1P311506EBI-739832,EBI-946999
GOLPH3LQ9H4A53EBI-739832,EBI-4403434
GRAP2O757914EBI-739832,EBI-740418
GRB2P629933EBI-739832,EBI-401755
GRIPAP1Q4V3284EBI-739832,EBI-717919
HEL-S-108V9HW563EBI-739832,EBI-10330141
HEL-S-30V9HWB83EBI-739832,EBI-10215395
HEL-S-69pV9HWF53EBI-739832,EBI-10330249
HEL-S-70V9HW803EBI-739832,EBI-10175326
HMBOX1Q6NT763EBI-739832,EBI-2549423
HMG20AQ9NP664EBI-739832,EBI-740641
HOMER3Q9NSC56EBI-739832,EBI-748420
HOMEZQ8IX15-33EBI-739832,EBI-10172004
HSBP1O755067EBI-739832,EBI-748664
INPP5KQ9BT403EBI-739832,EBI-749162
ISCUQ9H1K13EBI-739832,EBI-1047335
KCTD1Q719H95EBI-739832,EBI-9027502
KCTD13Q8WZ193EBI-739832,EBI-742916
KCTD6Q8NC693EBI-739832,EBI-2511344
KCTD9Q7L2734EBI-739832,EBI-4397613
KIF24Q5T7B8-24EBI-739832,EBI-10213781
KIFC3Q9BVG8-54EBI-739832,EBI-14069005
KLHL12Q53G593EBI-739832,EBI-740929
KRT15P190123EBI-739832,EBI-739566
KRTAP4-2Q9BYR55EBI-739832,EBI-10172511
KRTAP9-2Q9BYQ43EBI-739832,EBI-1044640
KXD1Q9BQD33EBI-739832,EBI-739657
LCLAT1Q6UWP73EBI-739832,EBI-10254507
LCP2Q130944EBI-739832,EBI-346946
LDB2O436794EBI-739832,EBI-2865580
LGALS14Q8TCE93EBI-739832,EBI-10274069
LSM2Q9Y3333EBI-739832,EBI-347416
MAGEB18Q96M6113EBI-739832,EBI-741835
MAPK9P459845EBI-739832,EBI-713568
MEMO1Q9Y3165EBI-739832,EBI-1104564
METTL21AQ8WXB13EBI-739832,EBI-8652459
MID2Q9UJV3-24EBI-739832,EBI-10172526
MRFAP1L1Q96HT85EBI-739832,EBI-748896
MTMR9Q96QG73EBI-739832,EBI-744593
MTUS2Q5JR593EBI-739832,EBI-742948
MVB12BQ9H7P63EBI-739832,EBI-6149062
NADKO955443EBI-739832,EBI-743949
NAGKQ9UJ702EBI-739832,EBI-372578
NCK2O436393EBI-739832,EBI-713635
NECAB1Q8N9874EBI-739832,EBI-11956853
NECAB2Q7Z6G33EBI-739832,EBI-950070
NECAB2Q7Z6G3-23EBI-739832,EBI-10172876
NEK6Q9HC983EBI-739832,EBI-740364
NME7Q9Y5B85EBI-739832,EBI-744782
NOTCH2NLQ7Z3S95EBI-739832,EBI-945833
NUDT14O958487EBI-739832,EBI-536866
NXT2Q9NPJ83EBI-739832,EBI-752122
OSBP2Q969R23EBI-739832,EBI-7405817
OSBPL3Q9H4L54EBI-739832,EBI-1051317
OSGIN1Q9UJX03EBI-739832,EBI-9057006
PAFAH1B3Q151026EBI-739832,EBI-711522
PAICSP222343EBI-739832,EBI-712261
PBLDP300393EBI-739832,EBI-750589
PCBD1P614576EBI-739832,EBI-740475
PNMA1Q8ND906EBI-739832,EBI-302345
PNMA5Q96PV44EBI-739832,EBI-10171633
POMGNT1Q8WZA13EBI-739832,EBI-3912424
PPIAP629373EBI-739832,EBI-437708
PRKAR1BP313214EBI-739832,EBI-2805516
PRR13Q9NZ814EBI-739832,EBI-740924
PTSQ033933EBI-739832,EBI-712344
RAD51DO757716EBI-739832,EBI-1055693
RAD54BQ9Y6203EBI-739832,EBI-740830
RBMXP381593EBI-739832,EBI-743526
RBMY1A1P0DJD33EBI-739832,EBI-8638511
RBMY1JQ154154EBI-739832,EBI-8642021
RFPL3O756793EBI-739832,EBI-10188956
ROBO3Q96HH03EBI-739832,EBI-10288358
ROPN1Q9HAT03EBI-739832,EBI-1378139
RPIAP492473EBI-739832,EBI-744831
RUFY4Q6ZNE95EBI-739832,EBI-10181525
RUVBL2Q9Y2305EBI-739832,EBI-352939
SAT1P216738EBI-739832,EBI-711613
SEPT1Q8WYJ64EBI-739832,EBI-693002
SGF29Q96ES73EBI-739832,EBI-743117
SNRNP25Q9BV903EBI-739832,EBI-9675976
SNRPFP623063EBI-739832,EBI-356900
SPERTQ8NA61-26EBI-739832,EBI-11524851
SRCP129316EBI-739832,EBI-621482
SSNA1O438055EBI-739832,EBI-2515299
STAC2Q6ZMT13EBI-739832,EBI-948802
TBC1D1Q86TI04EBI-739832,EBI-1644036
TBCELQ5QJ743EBI-739832,EBI-10244795
THAP7Q9BT493EBI-739832,EBI-741350
TIFAQ96CG33EBI-739832,EBI-740711
TRAF1Q130776EBI-739832,EBI-359224
TRAF2Q129335EBI-739832,EBI-355744
TRIM39Q9HCM93EBI-739832,EBI-739510
TRIM54Q9BYV25EBI-739832,EBI-2130429
TRIP13Q156456EBI-739832,EBI-358993
TRMT12Q53H543EBI-739832,EBI-10242598
TRX2P228033EBI-739832,EBI-19598From Saccharomyces cerevisiae (strain ATCC 204508 / S288c).
TSG101Q998164EBI-739832,EBI-346882
TSSK3Q96PN85EBI-739832,EBI-3918381
WASHC3Q9Y3C04EBI-739832,EBI-712969
YCR051WP256313EBI-739832,EBI-2347265From Saccharomyces cerevisiae (strain ATCC 204508 / S288c).
ZBTB24O431674EBI-739832,EBI-744471
ZBTB43O432983EBI-739832,EBI-740718
ZCCHC10Q8TBK63EBI-739832,EBI-597063
ZFP64Q9NTW73EBI-739832,EBI-745730
ZNF212Q9UDV64EBI-739832,EBI-1640204
ZNF581Q9P0T45EBI-739832,EBI-745520
ZNF593O004883EBI-739832,EBI-726769

GO - Molecular functioni

Protein-protein interaction databases

BioGridi124219. 238 interactors.
ELMiQ8TBB1.
IntActiQ8TBB1. 408 interactors.
MINTiMINT-1441889.
STRINGi9606.ENSP00000263925.

Structurei

Secondary structure

1728
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi504 – 511Combined sources8
Beta strandi520 – 524Combined sources5
Beta strandi535 – 540Combined sources6
Helixi545 – 549Combined sources5
Beta strandi557 – 561Combined sources5
Helixi566 – 568Combined sources3
Helixi571 – 579Combined sources9
Beta strandi583 – 594Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3B76X-ray1.75A/B504-594[»]
ProteinModelPortaliQ8TBB1.
SMRiQ8TBB1.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8TBB1.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini274 – 359PDZ 1PROSITE-ProRule annotationAdd BLAST86
Domaini381 – 464PDZ 2PROSITE-ProRule annotationAdd BLAST84
Domaini507 – 593PDZ 3PROSITE-ProRule annotationAdd BLAST87
Domaini638 – 724PDZ 4PROSITE-ProRule annotationAdd BLAST87

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni186 – 244Interaction with MAGEB181 PublicationAdd BLAST59

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi181 – 184NPXY motif4

Domaini

The NPXY motif is required for the interaction with the PID domain of NUMB. It is however not sufficient.
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 (By similarity).By similarity

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri41 – 79RING-typePROSITE-ProRule annotationAdd BLAST39

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG3528. Eukaryota.
ENOG4110362. LUCA.
GeneTreeiENSGT00760000119017.
HOGENOMiHOG000261605.
HOVERGENiHBG039539.
InParanoidiQ8TBB1.
KOiK10692.
OMAiHSPEENH.
OrthoDBiEOG091G0CBZ.
PhylomeDBiQ8TBB1.
TreeFamiTF330709.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiView protein in InterPro
IPR001478. PDZ.
IPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
PfamiView protein in Pfam
PF00595. PDZ. 4 hits.
PF00097. zf-C3HC4. 1 hit.
SMARTiView protein in SMART
SM00228. PDZ. 4 hits.
SM00184. RING. 1 hit.
SUPFAMiSSF50156. SSF50156. 4 hits.
PROSITEiView protein in PROSITE
PS50106. PDZ. 4 hits.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8TBB1-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MNQPESANDP EPLCAVCGQA HSLEENHFYS YPEEVDDDLI CHICLQALLD
60 70 80 90 100
PLDTPCGHTY CTLCLTNFLV EKDFCPMDRK PLVLQHCKKS SILVNKLLNK
110 120 130 140 150
LLVTCPFREH CTQVLQRCDL EHHFQTSCKG ASHYGLTKDR KRRSQDGCPD
160 170 180 190 200
GCASLTATAP SPEVSAAATI SLMTDEPGLD NPAYVSSAED GQPAISPVDS
210 220 230 240 250
GRSNRTRARP FERSTIRSRS FKKINRALSV LRRTKSGSAV ANHADQGREN
260 270 280 290 300
SENTTAPEVF PRLYHLIPDG EITSIKINRV DPSESLSIRL VGGSETPLVH
310 320 330 340 350
IIIQHIYRDG VIARDGRLLP GDIILKVNGM DISNVPHNYA VRLLRQPCQV
360 370 380 390 400
LWLTVMREQK FRSRNNGQAP DAYRPRDDSF HVILNKSSPE EQLGIKLVRK
410 420 430 440 450
VDEPGVFIFN VLDGGVAYRH GQLEENDRVL AINGHDLRYG SPESAAHLIQ
460 470 480 490 500
ASERRVHLVV SRQVRQRSPD IFQEAGWNSN GSWSPGPGER SNTPKPLHPT
510 520 530 540 550
ITCHEKVVNI QKDPGESLGM TVAGGASHRE WDLPIYVISV EPGGVISRDG
560 570 580 590 600
RIKTGDILLN VDGVELTEVS RSEAVALLKR TSSSIVLKAL EVKEYEPQED
610 620 630 640 650
CSSPAALDSN HNMAPPSDWS PSWVMWLELP RCLYNCKDIV LRRNTAGSLG
660 670 680 690 700
FCIVGGYEEY NGNKPFFIKS IVEGTPAYND GRIRCGDILL AVNGRSTSGM
710 720
IHACLARLLK ELKGRITLTI VSWPGTFL
Length:728
Mass (Da):80,629
Last modified:June 1, 2002 - v1
Checksum:i5590E8D8976AE093
GO
Isoform 2 (identifier: Q8TBB1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-127: MNQPESANDP...CDLEHHFQTS → MKALLLLVLPWLSPANYIDNVGNLHFLYSEL

Show »
Length:632
Mass (Da):69,643
Checksum:i1B343BEF469CB005
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti132S → F in AAK15039 (PubMed:11521506).Curated1
Sequence conflicti321G → R in BAB71291 (PubMed:14702039).Curated1
Sequence conflicti366N → T in BAB71291 (PubMed:14702039).Curated1
Sequence conflicti411V → A in BAB71291 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0057331 – 127MNQPE…HFQTS → MKALLLLVLPWLSPANYIDN VGNLHFLYSEL in isoform 2. 3 PublicationsAdd BLAST127

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF237782 mRNA. Translation: AAK15039.1.
AY358326 mRNA. Translation: AAQ88692.1.
AK056823 mRNA. Translation: BAB71291.1.
AC058822 Genomic DNA. No translation available.
AC095040 Genomic DNA. Translation: AAY41000.1.
BC022983 mRNA. Translation: AAH22983.1.
BC034737 mRNA. Translation: AAH34737.1.
CCDSiCCDS3492.1. [Q8TBB1-2]
CCDS47057.1. [Q8TBB1-1]
RefSeqiNP_001119800.1. NM_001126328.2. [Q8TBB1-1]
NP_116011.2. NM_032622.2. [Q8TBB1-2]
XP_005265842.1. XM_005265785.4. [Q8TBB1-1]
XP_016864265.1. XM_017008776.1. [Q8TBB1-1]
UniGeneiHs.518760.

Genome annotation databases

EnsembliENST00000263925; ENSP00000263925; ENSG00000072201. [Q8TBB1-1]
ENST00000306888; ENSP00000302879; ENSG00000072201. [Q8TBB1-2]
GeneIDi84708.
KEGGihsa:84708.
UCSCiuc003haf.5. human. [Q8TBB1-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiLNX1_HUMAN
AccessioniPrimary (citable) accession number: Q8TBB1
Secondary accession number(s): Q4W5K7
, Q8N4C2, Q96MJ7, Q9BY20
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: June 1, 2002
Last modified: September 27, 2017
This is version 151 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references