Q8TBB1 (LNX1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase LNX
EC=6.3.2.-

Alternative name(s):
Ligand of Numb-protein X 1
Numb-binding protein 1
PDZ domain-containing RING finger protein 2

Gene names

Name:	LNX1
Synonyms:	LNX, PDZRN2
ORF Names:	UNQ574/PRO1136

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	728 AA.
Sequence status	Complete.
Protein existence	Evidence 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 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.
Pathway	Protein modification; protein ubiquitination.
Subunit structure	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. Ref.6 Ref.7 Ref.8
Subcellular location	Cytoplasm By similarity.
Tissue specificity	Expressed in heart, placenta, kidney, pancreas and brain. Ref.1
Domain	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.
Sequence similarities	Contains 4 PDZ (DHR) domains. Contains 1 RING-type zinc finger.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Domain	Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	protein homooligomerization Inferred from electronic annotation. Source: Compara protein ubiquitination involved in ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ubiquitin-protein ligase activity Inferred from electronic annotation. Source: Compara zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
COIL	P38432	2	EBI-739832,EBI-945751
INPP5K	Q9BT40	3	EBI-739832,EBI-749162
MAGEB18	Q96M61	6	EBI-739832,EBI-741835
NAGK	Q9UJ70	2	EBI-739832,EBI-372578
PAFAH1B3	Q15102	2	EBI-739832,EBI-711522

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8TBB1-1)

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: Q8TBB1-2)

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 728

728

E3 ubiquitin-protein ligase LNX

PRO_0000055913

Regions

Domain

274 – 359

86

PDZ 1

Domain

381 – 464

84

PDZ 2

Domain

507 – 593

87

PDZ 3

Domain

638 – 724

87

PDZ 4

Zinc finger

41 – 79

39

RING-type

Region

186 – 244

59

Interaction with MAGEB18

Motif

181 – 184

4

NPXY motif

Natural variations

Alternative sequence

1 – 127

127

MNQPE…HFQTS → MKALLLLVLPWLSPANYIDN VGNLHFLYSEL in isoform 2.

VSP_005733

Experimental info

Sequence conflict

132

1

S → F in AAK15039. Ref.1

Sequence conflict

321

1

G → R in BAB71291. Ref.3

Sequence conflict

366

1

N → T in BAB71291. Ref.3

Sequence conflict

411

1

V → A in BAB71291. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

728

Helix Strand Turn

Details...

Beta strand

504 – 511

8

Beta strand

520 – 524

5

Beta strand

535 – 540

6

Helix

545 – 549

5

Beta strand

557 – 561

5

Helix

566 – 568

3

Helix

571 – 579

9

Beta strand

583 – 594

12

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2002. Version 1. Checksum: 5590E8D8976AE093	FASTA	728	80,629
	10 20 30 40 50 60 MNQPESANDP EPLCAVCGQA HSLEENHFYS YPEEVDDDLI CHICLQALLD PLDTPCGHTY 70 80 90 100 110 120 CTLCLTNFLV EKDFCPMDRK PLVLQHCKKS SILVNKLLNK LLVTCPFREH CTQVLQRCDL 130 140 150 160 170 180 EHHFQTSCKG ASHYGLTKDR KRRSQDGCPD GCASLTATAP SPEVSAAATI SLMTDEPGLD 190 200 210 220 230 240 NPAYVSSAED GQPAISPVDS GRSNRTRARP FERSTIRSRS FKKINRALSV LRRTKSGSAV 250 260 270 280 290 300 ANHADQGREN SENTTAPEVF PRLYHLIPDG EITSIKINRV DPSESLSIRL VGGSETPLVH 310 320 330 340 350 360 IIIQHIYRDG VIARDGRLLP GDIILKVNGM DISNVPHNYA VRLLRQPCQV LWLTVMREQK 370 380 390 400 410 420 FRSRNNGQAP DAYRPRDDSF HVILNKSSPE EQLGIKLVRK VDEPGVFIFN VLDGGVAYRH 430 440 450 460 470 480 GQLEENDRVL AINGHDLRYG SPESAAHLIQ ASERRVHLVV SRQVRQRSPD IFQEAGWNSN 490 500 510 520 530 540 GSWSPGPGER SNTPKPLHPT ITCHEKVVNI QKDPGESLGM TVAGGASHRE WDLPIYVISV 550 560 570 580 590 600 EPGGVISRDG RIKTGDILLN VDGVELTEVS RSEAVALLKR TSSSIVLKAL EVKEYEPQED 610 620 630 640 650 660 CSSPAALDSN HNMAPPSDWS PSWVMWLELP RCLYNCKDIV LRRNTAGSLG FCIVGGYEEY 670 680 690 700 710 720 NGNKPFFIKS IVEGTPAYND GRIRCGDILL AVNGRSTSGM IHACLARLLK ELKGRITLTI VSWPGTFL
	Isoform 2 [UniParc]. Checksum: 1B343BEF469CB005	FASTA	632	69,643
	10 20 30 40 50 60 MKALLLLVLP WLSPANYIDN VGNLHFLYSE LCKGASHYGL TKDRKRRSQD GCPDGCASLT 70 80 90 100 110 120 ATAPSPEVSA AATISLMTDE PGLDNPAYVS SAEDGQPAIS PVDSGRSNRT RARPFERSTI 130 140 150 160 170 180 RSRSFKKINR ALSVLRRTKS GSAVANHADQ GRENSENTTA PEVFPRLYHL IPDGEITSIK 190 200 210 220 230 240 INRVDPSESL SIRLVGGSET PLVHIIIQHI YRDGVIARDG RLLPGDIILK VNGMDISNVP 250 260 270 280 290 300 HNYAVRLLRQ PCQVLWLTVM REQKFRSRNN GQAPDAYRPR DDSFHVILNK SSPEEQLGIK 310 320 330 340 350 360 LVRKVDEPGV FIFNVLDGGV AYRHGQLEEN DRVLAINGHD LRYGSPESAA HLIQASERRV 370 380 390 400 410 420 HLVVSRQVRQ RSPDIFQEAG WNSNGSWSPG PGERSNTPKP LHPTITCHEK VVNIQKDPGE 430 440 450 460 470 480 SLGMTVAGGA SHREWDLPIY VISVEPGGVI SRDGRIKTGD ILLNVDGVEL TEVSRSEAVA 490 500 510 520 530 540 LLKRTSSSIV LKALEVKEYE PQEDCSSPAA LDSNHNMAPP SDWSPSWVMW LELPRCLYNC 550 560 570 580 590 600 KDIVLRRNTA GSLGFCIVGG YEEYNGNKPF FIKSIVEGTP AYNDGRIRCG DILLAVNGRS 610 620 630 TSGMIHACLA RLLKELKGRI TLTIVSWPGT FL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of a human LNX protein containing multiple PDZ domains." Xie Y., Zhao W., Wang W., Zhao S., Tang R., Ying K., Zhou Z., Mao Y. Biochem. Genet. 39:117-126(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY. Tissue: Fetal brain.
[2]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Prostate.
[4]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] (ISOFORMS 1 AND 2). Tissue: Brain and Placenta.
[6]	"The Coxsackievirus and adenovirus receptor (CAR) forms a complex with the PDZ domain-containing protein ligand-of-numb protein-X (LNX)." Sollerbrant K., Raschperger E., Mirza M., Engstroem U., Philipson L., Ljungdahl P.O., Pettersson R.F. J. Biol. Chem. 278:7439-7444(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CXADR.
[7]	"Np9 protein of human endogenous retrovirus K interacts with ligand of numb protein X." Armbruester V., Sauter M., Roemer K., Best B., Hahn S., Nty A., Schmid A., Philipp S., Mueller A., Mueller-Lantzsch N. J. Virol. 78:10310-10319(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NP9.
[8]	"MAGE-RING protein complexes comprise a family of E3 ubiquitin ligases." Doyle J.M., Gao J., Wang J., Yang M., Potts P.R. Mol. Cell 39:963-974(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MAGEB18 AND MAGEF1.
[9]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00152181.
IPI00305598.

RefSeq

NP_001119800.1. NM_001126328.2.
NP_116011.2. NM_032622.2.

UniGene

Hs.518760.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3B76	X-ray	1.75	A/B	504-594	[»]

ProteinModelPortal

Q8TBB1.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q8TBB1. 48 interactions.

MINT

MINT-1441889.

STRING

9606.ENSP00000263925.

PTM databases

PhosphoSite

Q8TBB1.

Polymorphism databases

DMDM

29840786.

Proteomic databases

PaxDb

Q8TBB1.

PRIDE

Q8TBB1.

Protocols and materials databases

DNASU

84708.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000263925; ENSP00000263925; ENSG00000072201.
ENST00000306888; ENSP00000302879; ENSG00000072201.
ENST00000513421; ENSP00000426445; ENSG00000072201.

GeneID

84708.

KEGG

hsa:84708.

UCSC

uc003haf.4. human.
uc003hag.4. human.

Organism-specific databases

CTD

84708.

GeneCards

GC04M054325.

HGNC

HGNC:6657. LNX1.

HPA

HPA002235.

MIM

609732. gene.

neXtProt

NX_Q8TBB1.

PharmGKB

PA30419.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG236845.

HOGENOM

HOG000261605.

HOVERGEN

HBG039539.

InParanoid

Q8TBB1.

KO

K10692.

OMA

LQHCKKS.

PhylomeDB

Q8TBB1.

Enzyme and pathway databases

UniPathway

UPA00143.

Gene expression databases

ArrayExpress

Q8TBB1.

Bgee

Q8TBB1.

CleanEx

HS_LNX1.

Genevestigator

Q8TBB1.

GermOnline

ENSG00000072201. Homo sapiens.

Family and domain databases

Gene3D

3.30.40.10. 1 hit.

InterPro

IPR001478. PDZ.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]

Pfam

PF00595. PDZ. 4 hits.
[Graphical view]

SMART

SM00228. PDZ. 4 hits.
SM00184. RING. 1 hit.
[Graphical view]

SUPFAM

SSF50156. PDZ. 4 hits.

PROSITE

PS50106. PDZ. 4 hits.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q8TBB1.

GenomeRNAi

84708.

NextBio

74806.

SOURCE

Search...

Entry information

Entry name

LNX1_HUMAN

Accession

Primary (citable) accession number: Q8TBB1
Secondary accession number(s): Q4W5K7 , Q8N4C2, Q96MJ7, Q9BY20

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 28, 2003
Last sequence update:	June 1, 2002
Last modified:	May 1, 2013
This is version 109 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.