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Protein

Leucine-rich repeats and immunoglobulin-like domains protein 1

Gene

LRIG1

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

Functioni

Acts as a feedback negative regulator of signaling by receptor tyrosine kinases, through a mechanism that involves enhancement of receptor ubiquitination and accelerated intracellular degradation.1 Publication

GO - Biological processi

Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-HSA-177929. Signaling by EGFR.
R-HSA-6807004. Negative regulation of MET activity.
SignaLinkiQ96JA1.
SIGNORiQ96JA1.

Names & Taxonomyi

Protein namesi
Recommended name:
Leucine-rich repeats and immunoglobulin-like domains protein 1
Short name:
LIG-1
Gene namesi
Name:LRIG1
Synonyms:LIG1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:17360. LRIG1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini35 – 794ExtracellularSequence analysisAdd BLAST760
Transmembranei795 – 815HelicalSequence analysisAdd BLAST21
Topological domaini816 – 1093CytoplasmicSequence analysisAdd BLAST278

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi26018.
OpenTargetsiENSG00000144749.
ENSG00000282243.
PharmGKBiPA38450.

Polymorphism and mutation databases

BioMutaiLRIG1.
DMDMi143811415.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 34Sequence analysisAdd BLAST34
ChainiPRO_000001482735 – 1093Leucine-rich repeats and immunoglobulin-like domains protein 1Add BLAST1059

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi74N-linked (GlcNAc...)Sequence analysis1
Glycosylationi150N-linked (GlcNAc...)Sequence analysis1
Glycosylationi246N-linked (GlcNAc...)Sequence analysis1
Glycosylationi292N-linked (GlcNAc...)Sequence analysis1
Glycosylationi318N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi516 ↔ 577PROSITE-ProRule annotation
Disulfide bondi620 ↔ 672PROSITE-ProRule annotation
Glycosylationi684N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi714 ↔ 763PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ96JA1.
MaxQBiQ96JA1.
PaxDbiQ96JA1.
PeptideAtlasiQ96JA1.
PRIDEiQ96JA1.

PTM databases

iPTMnetiQ96JA1.
PhosphoSitePlusiQ96JA1.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Inductioni

By EGF.1 Publication

Gene expression databases

BgeeiENSG00000144749.
CleanExiHS_LIG1.
HS_LRIG1.
GenevisibleiQ96JA1. HS.

Organism-specific databases

HPAiHPA011846.

Interactioni

Subunit structurei

Interacts with EGFR/ERBB1, ERBB2, ERBB3 and ERBB4.1 Publication

Protein-protein interaction databases

BioGridi117489. 27 interactors.
IntActiQ96JA1. 1 interactor.
STRINGi9606.ENSP00000273261.

Structurei

Secondary structure

11093
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi43 – 48Combined sources6
Beta strandi51 – 53Combined sources3
Beta strandi72 – 74Combined sources3
Helixi85 – 87Combined sources3
Beta strandi96 – 98Combined sources3
Helixi111 – 116Combined sources6
Beta strandi119 – 121Combined sources3
Helixi132 – 135Combined sources4
Beta strandi143 – 145Combined sources3
Helixi156 – 158Combined sources3
Beta strandi161 – 163Combined sources3
Beta strandi166 – 169Combined sources4
Turni180 – 183Combined sources4
Helixi184 – 186Combined sources3
Turni187 – 189Combined sources3
Beta strandi192 – 194Combined sources3
Beta strandi215 – 217Combined sources3
Turni228 – 233Combined sources6
Beta strandi239 – 241Combined sources3
Turni252 – 257Combined sources6
Beta strandi263 – 265Combined sources3
Helixi276 – 279Combined sources4
Beta strandi287 – 289Combined sources3
Helixi301 – 305Combined sources5
Beta strandi311 – 313Combined sources3
Turni324 – 329Combined sources6
Beta strandi335 – 337Combined sources3
Turni348 – 353Combined sources6
Beta strandi359 – 361Combined sources3
Helixi369 – 372Combined sources4
Turni377 – 380Combined sources4
Beta strandi386 – 388Combined sources3
Helixi399 – 402Combined sources4
Beta strandi410 – 412Combined sources3
Turni423 – 428Combined sources6
Beta strandi434 – 443Combined sources10
Turni446 – 450Combined sources5
Helixi451 – 457Combined sources7
Beta strandi464 – 471Combined sources8
Turni479 – 481Combined sources3
Helixi484 – 486Combined sources3
Beta strandi495 – 499Combined sources5
Beta strandi504 – 507Combined sources4
Beta strandi512 – 524Combined sources13
Beta strandi527 – 532Combined sources6
Beta strandi541 – 548Combined sources8
Beta strandi556 – 564Combined sources9
Helixi569 – 571Combined sources3
Beta strandi573 – 580Combined sources8
Beta strandi585 – 587Combined sources3
Beta strandi591 – 603Combined sources13
Beta strandi608 – 611Combined sources4
Beta strandi616 – 619Combined sources4
Beta strandi621 – 626Combined sources6
Beta strandi629 – 634Combined sources6
Helixi641 – 644Combined sources4
Beta strandi648 – 650Combined sources3
Turni652 – 654Combined sources3
Beta strandi656 – 661Combined sources6
Helixi664 – 666Combined sources3
Beta strandi668 – 675Combined sources8
Beta strandi680 – 697Combined sources18
Beta strandi702 – 705Combined sources4
Beta strandi710 – 713Combined sources4
Beta strandi716 – 720Combined sources5
Beta strandi723 – 728Combined sources6
Beta strandi739 – 741Combined sources3
Beta strandi747 – 750Combined sources4
Helixi755 – 757Combined sources3
Beta strandi759 – 767Combined sources9
Beta strandi770 – 781Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4U7LX-ray2.30A42-494[»]
4U7MX-ray2.76A494-781[»]
ProteinModelPortaliQ96JA1.
SMRiQ96JA1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini35 – 68LRRNTAdd BLAST34
Repeati69 – 90LRR 1Add BLAST22
Repeati93 – 114LRR 2Add BLAST22
Repeati116 – 137LRR 3Add BLAST22
Repeati140 – 161LRR 4Add BLAST22
Repeati164 – 185LRR 5Add BLAST22
Repeati189 – 210LRR 6Add BLAST22
Repeati212 – 233LRR 7Add BLAST22
Repeati236 – 257LRR 8Add BLAST22
Repeati260 – 281LRR 9Add BLAST22
Repeati284 – 305LRR 10Add BLAST22
Repeati308 – 329LRR 11Add BLAST22
Repeati332 – 353LRR 12Add BLAST22
Repeati356 – 378LRR 13Add BLAST23
Repeati383 – 404LRR 14Add BLAST22
Repeati407 – 428LRR 15Add BLAST22
Domaini440 – 491LRRCTAdd BLAST52
Domaini495 – 594Ig-like C2-type 1Add BLAST100
Domaini599 – 688Ig-like C2-type 2Add BLAST90
Domaini693 – 779Ig-like C2-type 3Add BLAST87

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi520 – 524Poly-Ser5

Domaini

The LRRs and the Ig-domains are each sufficient for EGFR/ERBB1 binding. This interaction is abolished only when these two domains are deleted.

Sequence similaritiesi

Contains 15 LRR (leucine-rich) repeats.Curated
Contains 1 LRRCT domain.Curated
Contains 1 LRRNT domain.Curated

Keywords - Domaini

Immunoglobulin domain, Leucine-rich repeat, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4194. Eukaryota.
COG4886. LUCA.
GeneTreeiENSGT00760000118777.
HOGENOMiHOG000113380.
HOVERGENiHBG052353.
InParanoidiQ96JA1.
OMAiPTPGCRK.
OrthoDBiEOG091G04H0.
PhylomeDBiQ96JA1.
TreeFamiTF325380.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
3.80.10.10. 3 hits.
InterProiIPR000483. Cys-rich_flank_reg_C.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000372. LRRNT.
[Graphical view]
PfamiPF07679. I-set. 2 hits.
PF13855. LRR_8. 5 hits.
PF01463. LRRCT. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 3 hits.
SM00408. IGc2. 3 hits.
SM00369. LRR_TYP. 14 hits.
SM00082. LRRCT. 1 hit.
SM00013. LRRNT. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 3 hits.
SSF52058. SSF52058. 2 hits.
PROSITEiPS50835. IG_LIKE. 3 hits.
PS51450. LRR. 14 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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

Isoform 1 (identifier: Q96JA1-1) [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
MARPVRGGLG APRRSPCLLL LWLLLLRLEP VTAAAGPRAP CAAACTCAGD
60 70 80 90 100
SLDCGGRGLA ALPGDLPSWT RSLNLSYNKL SEIDPAGFED LPNLQEVYLN
110 120 130 140 150
NNELTAVPSL GAASSHVVSL FLQHNKIRSV EGSQLKAYLS LEVLDLSLNN
160 170 180 190 200
ITEVRNTCFP HGPPIKELNL AGNRIGTLEL GAFDGLSRSL LTLRLSKNRI
210 220 230 240 250
TQLPVRAFKL PRLTQLDLNR NRIRLIEGLT FQGLNSLEVL KLQRNNISKL
260 270 280 290 300
TDGAFWGLSK MHVLHLEYNS LVEVNSGSLY GLTALHQLHL SNNSIARIHR
310 320 330 340 350
KGWSFCQKLH ELVLSFNNLT RLDEESLAEL SSLSVLRLSH NSISHIAEGA
360 370 380 390 400
FKGLRSLRVL DLDHNEISGT IEDTSGAFSG LDSLSKLTLF GNKIKSVAKR
410 420 430 440 450
AFSGLEGLEH LNLGGNAIRS VQFDAFVKMK NLKELHISSD SFLCDCQLKW
460 470 480 490 500
LPPWLIGRML QAFVTATCAH PESLKGQSIF SVPPESFVCD DFLKPQIITQ
510 520 530 540 550
PETTMAMVGK DIRFTCSAAS SSSSPMTFAW KKDNEVLTNA DMENFVHVHA
560 570 580 590 600
QDGEVMEYTT ILHLRQVTFG HEGRYQCVIT NHFGSTYSHK ARLTVNVLPS
610 620 630 640 650
FTKTPHDITI RTTTMARLEC AATGHPNPQI AWQKDGGTDF PAARERRMHV
660 670 680 690 700
MPDDDVFFIT DVKIDDAGVY SCTAQNSAGS ISANATLTVL ETPSLVVPLE
710 720 730 740 750
DRVVSVGETV ALQCKATGNP PPRITWFKGD RPLSLTERHH LTPDNQLLVV
760 770 780 790 800
QNVVAEDAGR YTCEMSNTLG TERAHSQLSV LPAAGCRKDG TTVGIFTIAV
810 820 830 840 850
VSSIVLTSLV WVCIIYQTRK KSEEYSVTNT DETVVPPDVP SYLSSQGTLS
860 870 880 890 900
DRQETVVRTE GGPQANGHIE SNGVCPRDAS HFPEPDTHSV ACRQPKLCAG
910 920 930 940 950
SAYHKEPWKA MEKAEGTPGP HKMEHGGRVV CSDCNTEVDC YSRGQAFHPQ
960 970 980 990 1000
PVSRDSAQPS APNGPEPGGS DQEHSPHHQC SRTAAGSCPE CQGSLYPSNH
1010 1020 1030 1040 1050
DRMLTAVKKK PMASLDGKGD SSWTLARLYH PDSTELQPAS SLTSGSPERA
1060 1070 1080 1090
EAQYLLVSNG HLPKACDASP ESTPLTGQLP GKQRVPLLLA PKS
Length:1,093
Mass (Da):119,113
Last modified:April 3, 2007 - v2
Checksum:i7B4F13CA343AF943
GO
Isoform 2 (identifier: Q96JA1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     387-387: L → LLLLEPSQSAGCSSPSQPHMSAGGR
     644-691: RERRMHVMPDDDVFFITDVKIDDAGVYSCTAQNSAGSISANATLTVLE → Q

Show »
Length:1,070
Mass (Da):116,378
Checksum:i3EDFDDF0C1319D67
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti24 – 26LLL → VLV in AAK62357 (PubMed:11414704).Curated3
Sequence conflicti24 – 26LLL → VLV in AAH71561 (PubMed:15489334).Curated3
Sequence conflicti80L → F in AAH71561 (PubMed:15489334).Curated1
Sequence conflicti612 – 613TT → VR in CAB56036 (PubMed:17974005).Curated2
Sequence conflicti861G → GA in BAB40659 (Ref. 2) Curated1
Sequence conflicti911M → I in BAB40659 (Ref. 2) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04988924L → V.Corresponds to variant rs1403626dbSNPEnsembl.1
Natural variantiVAR_031581615M → V.2 PublicationsCorresponds to variant rs2306272dbSNPEnsembl.1
Natural variantiVAR_031582926G → S.Corresponds to variant rs9877201dbSNPEnsembl.1
Natural variantiVAR_031583957A → T.Corresponds to variant rs332373dbSNPEnsembl.1
Natural variantiVAR_049890993G → A.Corresponds to variant rs2279289dbSNPEnsembl.1
Natural variantiVAR_0315841031P → R.Corresponds to variant rs332374dbSNPEnsembl.1
Natural variantiVAR_0315851053Q → P.Corresponds to variant rs2279290dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_011730387L → LLLLEPSQSAGCSSPSQPHM SAGGR in isoform 2. 1 Publication1
Alternative sequenceiVSP_011731644 – 691RERRM…LTVLE → Q in isoform 2. 1 PublicationAdd BLAST48

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF381545 mRNA. Translation: AAK62357.1.
AB050468 mRNA. Translation: BAB40659.1.
BC071561 mRNA. Translation: AAH71561.1.
BC014276 mRNA. Translation: AAH14276.2.
AL117666 mRNA. Translation: CAB56036.1.
CCDSiCCDS33783.1. [Q96JA1-1]
PIRiT17346.
RefSeqiNP_056356.2. NM_015541.2. [Q96JA1-1]
UniGeneiHs.518055.

Genome annotation databases

EnsembliENST00000273261; ENSP00000273261; ENSG00000144749. [Q96JA1-1]
ENST00000383703; ENSP00000373208; ENSG00000144749. [Q96JA1-2]
ENST00000631853; ENSP00000488729; ENSG00000282243. [Q96JA1-1]
ENST00000633161; ENSP00000488182; ENSG00000282243. [Q96JA1-2]
GeneIDi26018.
KEGGihsa:26018.
UCSCiuc003dmx.4. human. [Q96JA1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF381545 mRNA. Translation: AAK62357.1.
AB050468 mRNA. Translation: BAB40659.1.
BC071561 mRNA. Translation: AAH71561.1.
BC014276 mRNA. Translation: AAH14276.2.
AL117666 mRNA. Translation: CAB56036.1.
CCDSiCCDS33783.1. [Q96JA1-1]
PIRiT17346.
RefSeqiNP_056356.2. NM_015541.2. [Q96JA1-1]
UniGeneiHs.518055.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4U7LX-ray2.30A42-494[»]
4U7MX-ray2.76A494-781[»]
ProteinModelPortaliQ96JA1.
SMRiQ96JA1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117489. 27 interactors.
IntActiQ96JA1. 1 interactor.
STRINGi9606.ENSP00000273261.

PTM databases

iPTMnetiQ96JA1.
PhosphoSitePlusiQ96JA1.

Polymorphism and mutation databases

BioMutaiLRIG1.
DMDMi143811415.

Proteomic databases

EPDiQ96JA1.
MaxQBiQ96JA1.
PaxDbiQ96JA1.
PeptideAtlasiQ96JA1.
PRIDEiQ96JA1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000273261; ENSP00000273261; ENSG00000144749. [Q96JA1-1]
ENST00000383703; ENSP00000373208; ENSG00000144749. [Q96JA1-2]
ENST00000631853; ENSP00000488729; ENSG00000282243. [Q96JA1-1]
ENST00000633161; ENSP00000488182; ENSG00000282243. [Q96JA1-2]
GeneIDi26018.
KEGGihsa:26018.
UCSCiuc003dmx.4. human. [Q96JA1-1]

Organism-specific databases

CTDi26018.
DisGeNETi26018.
GeneCardsiLRIG1.
H-InvDBHIX0003431.
HGNCiHGNC:17360. LRIG1.
HPAiHPA011846.
MIMi608868. gene.
neXtProtiNX_Q96JA1.
OpenTargetsiENSG00000144749.
ENSG00000282243.
PharmGKBiPA38450.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4194. Eukaryota.
COG4886. LUCA.
GeneTreeiENSGT00760000118777.
HOGENOMiHOG000113380.
HOVERGENiHBG052353.
InParanoidiQ96JA1.
OMAiPTPGCRK.
OrthoDBiEOG091G04H0.
PhylomeDBiQ96JA1.
TreeFamiTF325380.

Enzyme and pathway databases

ReactomeiR-HSA-177929. Signaling by EGFR.
R-HSA-6807004. Negative regulation of MET activity.
SignaLinkiQ96JA1.
SIGNORiQ96JA1.

Miscellaneous databases

GeneWikiiLRIG1.
GenomeRNAii26018.
PROiQ96JA1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000144749.
CleanExiHS_LIG1.
HS_LRIG1.
GenevisibleiQ96JA1. HS.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
3.80.10.10. 3 hits.
InterProiIPR000483. Cys-rich_flank_reg_C.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000372. LRRNT.
[Graphical view]
PfamiPF07679. I-set. 2 hits.
PF13855. LRR_8. 5 hits.
PF01463. LRRCT. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 3 hits.
SM00408. IGc2. 3 hits.
SM00369. LRR_TYP. 14 hits.
SM00082. LRRCT. 1 hit.
SM00013. LRRNT. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 3 hits.
SSF52058. SSF52058. 2 hits.
PROSITEiPS50835. IG_LIKE. 3 hits.
PS51450. LRR. 14 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLRIG1_HUMAN
AccessioniPrimary (citable) accession number: Q96JA1
Secondary accession number(s): Q6IQ51
, Q96CF9, Q9BYB8, Q9UFI4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: April 3, 2007
Last modified: November 30, 2016
This is version 129 of the entry and version 2 of the sequence. [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 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.