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Protein

Leucine-rich repeats and immunoglobulin-like domains protein 1

Gene

LRIG1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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-11 Publication
Gene namesi
Name:LRIG11 Publication
Synonyms:LIG1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000144749.13
HGNCiHGNC:17360 LRIG1
MIMi608868 gene
neXtProtiNX_Q96JA1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi26018
OpenTargetsiENSG00000144749
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
Disulfide bondi45 ↔ 54Combined sources1 Publication
Glycosylationi74N-linked (GlcNAc...) asparagineSequence analysisCombined sources1 Publication1
Glycosylationi150N-linked (GlcNAc...) asparagineSequence analysisCombined sources1 Publication1
Glycosylationi246N-linked (GlcNAc...) asparagineSequence analysisCombined sources1 Publication1
Glycosylationi292N-linked (GlcNAc...) asparagineSequence analysisCombined sources1 Publication1
Glycosylationi318N-linked (GlcNAc...) asparagineSequence analysisCombined sources1 Publication1
Disulfide bondi444 ↔ 468Combined sources1 Publication
Disulfide bondi446 ↔ 489Combined sources1 Publication
Disulfide bondi516 ↔ 577PROSITE-ProRule annotationCombined sources1 Publication
Disulfide bondi620 ↔ 672PROSITE-ProRule annotationCombined sources1 Publication
Glycosylationi684N-linked (GlcNAc...) asparagineSequence analysisCombined sources1 Publication1
Disulfide bondi714 ↔ 763PROSITE-ProRule annotationCombined sources1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ96JA1
MaxQBiQ96JA1
PaxDbiQ96JA1
PeptideAtlasiQ96JA1
PRIDEiQ96JA1
ProteomicsDBi76916
76917 [Q96JA1-2]

PTM databases

iPTMnetiQ96JA1
PhosphoSitePlusiQ96JA1

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Inductioni

By EGF.1 Publication

Gene expression databases

BgeeiENSG00000144749 Expressed in 232 organ(s), highest expression level in secondary oocyte
CleanExiHS_LIG1
HS_LRIG1
GenevisibleiQ96JA1 HS

Organism-specific databases

HPAiHPA011846

Interactioni

Subunit structurei

Interacts (via extracellular LRR and Ig-like domains) with EGFR/ERBB1, ERBB2, ERBB3 and ERBB4 (via extracellular domain) (PubMed:15282549). The physiological relevance of the interaction is controversial; LRIG1 may have low affinity for EGFR, and interaction may occur only when high levels of both proteins are present (PubMed:25765764).2 Publications

Protein-protein interaction databases

BioGridi117489, 37 interactors
IntActiQ96JA1, 2 interactors
STRINGi9606.ENSP00000273261

Structurei

Secondary structure

11093
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Contains LRR and Ig-domains that can mediate low-affinity interaction with EGFR (PubMed:25765764). The LRRs and the Ig-domains are each sufficient for EGFR/ERBB1 binding. This interaction is abolished only when both the LRRs and the Ig-domains are deleted (PubMed:15282549).2 Publications

Keywords - Domaini

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

Phylogenomic databases

eggNOGiKOG4194 Eukaryota
COG4886 LUCA
GeneTreeiENSGT00920000148957
HOGENOMiHOG000113380
HOVERGENiHBG052353
InParanoidiQ96JA1
OMAiIEDTNGA
OrthoDBiEOG091G04H0
PhylomeDBiQ96JA1
TreeFamiTF325380

Family and domain databases

Gene3Di2.60.40.10, 3 hits
3.80.10.10, 2 hits
InterProiView protein in InterPro
IPR000483 Cys-rich_flank_reg_C
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR013098 Ig_I-set
IPR003599 Ig_sub
IPR003598 Ig_sub2
IPR001611 Leu-rich_rpt
IPR003591 Leu-rich_rpt_typical-subtyp
IPR032675 LRR_dom_sf
IPR000372 LRRNT
PfamiView protein in Pfam
PF07679 I-set, 2 hits
PF13855 LRR_8, 5 hits
PF01463 LRRCT, 1 hit
SMARTiView protein in SMART
SM00409 IG, 3 hits
SM00408 IGc2, 3 hits
SM00369 LRR_TYP, 14 hits
SM00082 LRRCT, 1 hit
SM00013 LRRNT, 1 hit
SUPFAMiSSF48726 SSF48726, 3 hits
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 3 hits
PS51450 LRR, 14 hits

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 dbSNP:rs1403626EnsemblClinVar.1
Natural variantiVAR_031581615M → V2 PublicationsCorresponds to variant dbSNP:rs2306272EnsemblClinVar.1
Natural variantiVAR_031582926G → S. Corresponds to variant dbSNP:rs9877201Ensembl.1
Natural variantiVAR_031583957A → T. Corresponds to variant dbSNP:rs332373Ensembl.1
Natural variantiVAR_049890993G → A. Corresponds to variant dbSNP:rs2279289Ensembl.1
Natural variantiVAR_0315841031P → R. Corresponds to variant dbSNP:rs332374Ensembl.1
Natural variantiVAR_0315851053Q → P. Corresponds to variant dbSNP:rs2279290EnsemblClinVar.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

Similar proteinsi

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, 37 interactors
IntActiQ96JA1, 2 interactors
STRINGi9606.ENSP00000273261

PTM databases

iPTMnetiQ96JA1
PhosphoSitePlusiQ96JA1

Polymorphism and mutation databases

BioMutaiLRIG1
DMDMi143811415

Proteomic databases

EPDiQ96JA1
MaxQBiQ96JA1
PaxDbiQ96JA1
PeptideAtlasiQ96JA1
PRIDEiQ96JA1
ProteomicsDBi76916
76917 [Q96JA1-2]

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
EuPathDBiHostDB:ENSG00000144749.13
GeneCardsiLRIG1
H-InvDBiHIX0003431
HGNCiHGNC:17360 LRIG1
HPAiHPA011846
MIMi608868 gene
neXtProtiNX_Q96JA1
OpenTargetsiENSG00000144749
PharmGKBiPA38450
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4194 Eukaryota
COG4886 LUCA
GeneTreeiENSGT00920000148957
HOGENOMiHOG000113380
HOVERGENiHBG052353
InParanoidiQ96JA1
OMAiIEDTNGA
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

ChiTaRSiLRIG1 human
GeneWikiiLRIG1
GenomeRNAii26018
PROiPR:Q96JA1
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000144749 Expressed in 232 organ(s), highest expression level in secondary oocyte
CleanExiHS_LIG1
HS_LRIG1
GenevisibleiQ96JA1 HS

Family and domain databases

Gene3Di2.60.40.10, 3 hits
3.80.10.10, 2 hits
InterProiView protein in InterPro
IPR000483 Cys-rich_flank_reg_C
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR013098 Ig_I-set
IPR003599 Ig_sub
IPR003598 Ig_sub2
IPR001611 Leu-rich_rpt
IPR003591 Leu-rich_rpt_typical-subtyp
IPR032675 LRR_dom_sf
IPR000372 LRRNT
PfamiView protein in Pfam
PF07679 I-set, 2 hits
PF13855 LRR_8, 5 hits
PF01463 LRRCT, 1 hit
SMARTiView protein in SMART
SM00409 IG, 3 hits
SM00408 IGc2, 3 hits
SM00369 LRR_TYP, 14 hits
SM00082 LRRCT, 1 hit
SM00013 LRRNT, 1 hit
SUPFAMiSSF48726 SSF48726, 3 hits
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 3 hits
PS51450 LRR, 14 hits
ProtoNetiSearch...

Entry informationi

Entry nameiLRIG1_HUMAN
AccessioniPrimary (citable) accession number: Q96JA1
Secondary accession number(s): Q6IQ51
, Q96CF9, Q9BYB8, Q9UFI4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: April 3, 2007
Last modified: November 7, 2018
This is version 144 of the entry and version 2 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 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
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