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Protein

Leucine-rich repeat flightless-interacting protein 2

Gene

LRRFIP2

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

Functioni

May function as activator of the canonical Wnt signaling pathway, in association with DVL3, upstream of CTNNB1/beta-catenin. Positively regulates Toll-like receptor (TLR) signaling in response to agonist probably by competing with the negative FLII regulator for MYD88-binding.2 Publications

GO - Molecular functioni

  • LRR domain binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Wnt signaling pathway

Enzyme and pathway databases

SignaLinkiQ9Y608.
SIGNORiQ9Y608.

Names & Taxonomyi

Protein namesi
Recommended name:
Leucine-rich repeat flightless-interacting protein 2
Short name:
LRR FLII-interacting protein 2
Gene namesi
Name:LRRFIP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:6703. LRRFIP2.

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi190S → A: No change in LPS-induced NFKB activity. 1 Publication1
Mutagenesisi200S → A: No change in LPS-induced NFKB activity. 1 Publication1
Mutagenesisi202S → A: Reduction in LPS-induced NFKB activity. 1 Publication1
Mutagenesisi202S → E: No change in LPS-induced NFKB activity. Interacts with MYD88 in an LPS-inducible manner. 1 Publication1

Organism-specific databases

DisGeNETi9209.
OpenTargetsiENSG00000093167.
Orphaneti144. Hereditary nonpolyposis colon cancer.
PharmGKBiPA30466.

Polymorphism and mutation databases

BioMutaiLRRFIP2.
DMDMi74721508.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002452461 – 721Leucine-rich repeat flightless-interacting protein 2Add BLAST721

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei18PhosphoserineCombined sources1
Modified residuei190Phosphoserine1 Publication1
Modified residuei202Phosphoserine1 Publication1
Modified residuei309PhosphoserineCombined sources1
Modified residuei312PhosphoserineCombined sources1
Modified residuei320PhosphoserineCombined sources1
Modified residuei324PhosphoserineCombined sources1
Modified residuei328PhosphoserineCombined sources1
Modified residuei331PhosphothreonineBy similarity1
Modified residuei332PhosphoserineBy similarity1
Modified residuei333PhosphoserineBy similarity1
Isoform 2 (identifier: Q9Y608-2)
Modified residuei96PhosphoserineCombined sources1
Modified residuei101PhosphoserineCombined sources1
Isoform 5 (identifier: Q9Y608-5)
Modified residuei168PhosphoserineCombined sources1
Modified residuei173PhosphoserineCombined sources1

Post-translational modificationi

Ser-190 and Ser-202 are phosphorylated in response to LPS stimulation. Ser-202 phosphorylation regulates the LPS-induced interaction with MYD88.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9Y608.
PaxDbiQ9Y608.
PeptideAtlasiQ9Y608.
PRIDEiQ9Y608.

PTM databases

iPTMnetiQ9Y608.
PhosphoSitePlusiQ9Y608.

Expressioni

Tissue specificityi

Widely expressed, with highest levels in heart and skeletal muscle.1 Publication

Gene expression databases

BgeeiENSG00000093167.
CleanExiHS_LRRFIP2.
ExpressionAtlasiQ9Y608. baseline and differential.
GenevisibleiQ9Y608. HS.

Organism-specific databases

HPAiHPA035956.
HPA042023.

Interactioni

Subunit structurei

Interacts (via N-terminus) with DVL3. Interacts with FLII. Weakly interacts with MYD88 in resting cells. Following LPS-stimulation, the interaction with MYD88 is rapidly enhanced; the complex gradually dissociates to basal levels after 6 hours of stimulation. Interaction with MYD88 is regulated by LPS-induced phosphorylation at Ser-202. In the presence of LPS, competes with FLII for MYD88-binding.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ATPAF2Q8N5M13EBI-1023718,EBI-1166928
DVL3Q929972EBI-1023718,EBI-739789

GO - Molecular functioni

  • LRR domain binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114643. 43 interactors.
IntActiQ9Y608. 39 interactors.
MINTiMINT-2824015.
STRINGi9606.ENSP00000338727.

Structurei

3D structure databases

ProteinModelPortaliQ9Y608.
SMRiQ9Y608.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 370DVL3-bindingAdd BLAST370

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili22 – 49Sequence analysisAdd BLAST28
Coiled coili349 – 524Sequence analysisAdd BLAST176
Coiled coili566 – 714Sequence analysisAdd BLAST149

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi118 – 342Ser-richAdd BLAST225

Sequence similaritiesi

Belongs to the LRRFIP family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG2010. Eukaryota.
ENOG4111H1S. LUCA.
GeneTreeiENSGT00530000063564.
HOGENOMiHOG000294125.
HOVERGENiHBG061558.
InParanoidiQ9Y608.
OMAiDRKWGQI.
OrthoDBiEOG091G0C5Y.
PhylomeDBiQ9Y608.
TreeFamiTF314109.

Family and domain databases

InterProiIPR019139. LRRFIP1/2.
[Graphical view]
PANTHERiPTHR19212. PTHR19212. 3 hits.
PfamiPF09738. LRRFIP. 3 hits.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9Y608-1) [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
MGTPASGRKR TPVKDRFSAE DEALSNIARE AEARLAAKRA ARAEARDIRM
60 70 80 90 100
RELERQQKEY SLHSFDRKWG QIQKWLEDSE RARYSHRSSH HRPYLGVEDA
110 120 130 140 150
LSIRSVGSHR YDMFKDRSSR LSSLNHSYSH SHGMKKRSSD SHKDLLSGLY
160 170 180 190 200
FDQRNYSSLR HSKPTSAYYT RQSSSLYSDP LATYKSDRAS PTANSGLLRS
210 220 230 240 250
ASLASLYNGG LYNPYGPRTP SECSYYSSRI SSARSSPGFT NDDTASIVSS
260 270 280 290 300
DRASRGRRES VVSAADYFSR SNRRGSVVSE VDDISIPDLS SLDEKSDKQY
310 320 330 340 350
AENYTRPSSR NSASATTPLS GNSSRRGSGD TSSLIDPDTS LSELRDIYDL
360 370 380 390 400
KDQIQDVEGR YMQGLKELKE SLSEVEEKYK KAMVSNAQLD NEKNNLIYQV
410 420 430 440 450
DTLKDVIEEQ EEQMAEFYRE NEEKSKELER QKHMCSVLQH KMEELKEGLR
460 470 480 490 500
QRDELIEEKQ RMQQKIDTMT KEVFDLQETL LWKDKKIGAL EKQKEYIACL
510 520 530 540 550
RNERDMLREE LADLQETVKT GEKHGLVIIP DGTPNGDVSH EPVAGAITVV
560 570 580 590 600
SQEAAQVLES AGEGPLDVRL RKLAGEKEEL LSQIRKLKLQ LEEERQKCSR
610 620 630 640 650
NDGTVGDLAG LQNGSDLQFI EMQRDANRQI SEYKFKLSKA EQDITTLEQS
660 670 680 690 700
ISRLEGQVLR YKTAAENAEK VEDELKAEKR KLQRELRTAL DKIEEMEMTN
710 720
SHLAKRLEKM KANRTALLAQ Q
Length:721
Mass (Da):82,171
Last modified:November 1, 1999 - v1
Checksum:i94B18B274656CB0B
GO
Isoform 2 (identifier: Q9Y608-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     60-291: Missing.
     346-369: Missing.
     457-521: Missing.

Show »
Length:400
Mass (Da):45,414
Checksum:iAD687735EAFE04F6
GO
Isoform 3 (identifier: Q9Y608-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-621: Missing.

Show »
Length:100
Mass (Da):11,736
Checksum:iEFCDC5B6AC68785F
GO
Isoform 4 (identifier: Q9Y608-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     60-291: Missing.
     457-521: Missing.

Show »
Length:424
Mass (Da):48,294
Checksum:iA5BFF9F6869503DE
GO
Isoform 5 (identifier: Q9Y608-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     60-76: Missing.
     111-124: Missing.
     146-202: Missing.
     220-291: Missing.
     346-369: Missing.
     489-522: Missing.

Note: No experimental confirmation available.Combined sources
Show »
Length:503
Mass (Da):57,394
Checksum:i965FF6DABB76907F
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_050001143K → E.Corresponds to variant rs34902788dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0196741 – 621Missing in isoform 3. 1 PublicationAdd BLAST621
Alternative sequenceiVSP_01967560 – 291Missing in isoform 2 and isoform 4. 2 PublicationsAdd BLAST232
Alternative sequenceiVSP_05696960 – 76Missing in isoform 5. 1 PublicationAdd BLAST17
Alternative sequenceiVSP_056970111 – 124Missing in isoform 5. 1 PublicationAdd BLAST14
Alternative sequenceiVSP_056971146 – 202Missing in isoform 5. 1 PublicationAdd BLAST57
Alternative sequenceiVSP_056972220 – 291Missing in isoform 5. 1 PublicationAdd BLAST72
Alternative sequenceiVSP_019676346 – 369Missing in isoform 2 and isoform 5. 2 PublicationsAdd BLAST24
Alternative sequenceiVSP_019677457 – 521Missing in isoform 2 and isoform 4. 2 PublicationsAdd BLAST65
Alternative sequenceiVSP_056973489 – 522Missing in isoform 5. 1 PublicationAdd BLAST34

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF115509 mRNA. Translation: AAD41257.1.
AK000255 mRNA. Translation: BAA91035.1.
AK291514 mRNA. Translation: BAF84203.1.
AK302282 mRNA. Translation: BAG63625.1.
CR749705 mRNA. Translation: CAH18481.1.
AC006583 Genomic DNA. No translation available.
AC126118 Genomic DNA. No translation available.
BC053668 mRNA. Translation: AAH53668.1.
CCDSiCCDS2664.1. [Q9Y608-1]
CCDS2665.1. [Q9Y608-2]
CCDS46791.1. [Q9Y608-4]
CCDS63592.1. [Q9Y608-5]
PIRiT50611.
RefSeqiNP_001127841.1. NM_001134369.2. [Q9Y608-4]
NP_001269620.1. NM_001282691.1. [Q9Y608-5]
NP_006300.1. NM_006309.3. [Q9Y608-1]
NP_060194.1. NM_017724.2. [Q9Y608-2]
XP_005265596.1. XM_005265539.2. [Q9Y608-1]
XP_005265597.1. XM_005265540.1. [Q9Y608-1]
XP_011532519.1. XM_011534217.1. [Q9Y608-1]
XP_011532520.1. XM_011534218.1. [Q9Y608-1]
XP_011532521.1. XM_011534219.1. [Q9Y608-1]
XP_016862972.1. XM_017007483.1. [Q9Y608-4]
XP_016862973.1. XM_017007484.1. [Q9Y608-4]
UniGeneiHs.740522.

Genome annotation databases

EnsembliENST00000336686; ENSP00000338727; ENSG00000093167. [Q9Y608-1]
ENST00000354379; ENSP00000346349; ENSG00000093167. [Q9Y608-2]
ENST00000396428; ENSP00000379705; ENSG00000093167. [Q9Y608-5]
ENST00000421276; ENSP00000416364; ENSG00000093167. [Q9Y608-4]
ENST00000440230; ENSP00000405480; ENSG00000093167. [Q9Y608-4]
GeneIDi9209.
KEGGihsa:9209.
UCSCiuc003cgs.4. human. [Q9Y608-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF115509 mRNA. Translation: AAD41257.1.
AK000255 mRNA. Translation: BAA91035.1.
AK291514 mRNA. Translation: BAF84203.1.
AK302282 mRNA. Translation: BAG63625.1.
CR749705 mRNA. Translation: CAH18481.1.
AC006583 Genomic DNA. No translation available.
AC126118 Genomic DNA. No translation available.
BC053668 mRNA. Translation: AAH53668.1.
CCDSiCCDS2664.1. [Q9Y608-1]
CCDS2665.1. [Q9Y608-2]
CCDS46791.1. [Q9Y608-4]
CCDS63592.1. [Q9Y608-5]
PIRiT50611.
RefSeqiNP_001127841.1. NM_001134369.2. [Q9Y608-4]
NP_001269620.1. NM_001282691.1. [Q9Y608-5]
NP_006300.1. NM_006309.3. [Q9Y608-1]
NP_060194.1. NM_017724.2. [Q9Y608-2]
XP_005265596.1. XM_005265539.2. [Q9Y608-1]
XP_005265597.1. XM_005265540.1. [Q9Y608-1]
XP_011532519.1. XM_011534217.1. [Q9Y608-1]
XP_011532520.1. XM_011534218.1. [Q9Y608-1]
XP_011532521.1. XM_011534219.1. [Q9Y608-1]
XP_016862972.1. XM_017007483.1. [Q9Y608-4]
XP_016862973.1. XM_017007484.1. [Q9Y608-4]
UniGeneiHs.740522.

3D structure databases

ProteinModelPortaliQ9Y608.
SMRiQ9Y608.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114643. 43 interactors.
IntActiQ9Y608. 39 interactors.
MINTiMINT-2824015.
STRINGi9606.ENSP00000338727.

PTM databases

iPTMnetiQ9Y608.
PhosphoSitePlusiQ9Y608.

Polymorphism and mutation databases

BioMutaiLRRFIP2.
DMDMi74721508.

Proteomic databases

EPDiQ9Y608.
PaxDbiQ9Y608.
PeptideAtlasiQ9Y608.
PRIDEiQ9Y608.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000336686; ENSP00000338727; ENSG00000093167. [Q9Y608-1]
ENST00000354379; ENSP00000346349; ENSG00000093167. [Q9Y608-2]
ENST00000396428; ENSP00000379705; ENSG00000093167. [Q9Y608-5]
ENST00000421276; ENSP00000416364; ENSG00000093167. [Q9Y608-4]
ENST00000440230; ENSP00000405480; ENSG00000093167. [Q9Y608-4]
GeneIDi9209.
KEGGihsa:9209.
UCSCiuc003cgs.4. human. [Q9Y608-1]

Organism-specific databases

CTDi9209.
DisGeNETi9209.
GeneCardsiLRRFIP2.
HGNCiHGNC:6703. LRRFIP2.
HPAiHPA035956.
HPA042023.
MIMi614043. gene.
neXtProtiNX_Q9Y608.
OpenTargetsiENSG00000093167.
Orphaneti144. Hereditary nonpolyposis colon cancer.
PharmGKBiPA30466.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2010. Eukaryota.
ENOG4111H1S. LUCA.
GeneTreeiENSGT00530000063564.
HOGENOMiHOG000294125.
HOVERGENiHBG061558.
InParanoidiQ9Y608.
OMAiDRKWGQI.
OrthoDBiEOG091G0C5Y.
PhylomeDBiQ9Y608.
TreeFamiTF314109.

Enzyme and pathway databases

SignaLinkiQ9Y608.
SIGNORiQ9Y608.

Miscellaneous databases

ChiTaRSiLRRFIP2. human.
GenomeRNAii9209.
PROiQ9Y608.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000093167.
CleanExiHS_LRRFIP2.
ExpressionAtlasiQ9Y608. baseline and differential.
GenevisibleiQ9Y608. HS.

Family and domain databases

InterProiIPR019139. LRRFIP1/2.
[Graphical view]
PANTHERiPTHR19212. PTHR19212. 3 hits.
PfamiPF09738. LRRFIP. 3 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLRRF2_HUMAN
AccessioniPrimary (citable) accession number: Q9Y608
Secondary accession number(s): A8K649
, A8MXR0, B4DY63, Q68CV3, Q9NXH5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 11, 2006
Last sequence update: November 1, 1999
Last modified: November 2, 2016
This is version 123 of the entry and version 1 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

Complete proteome, Direct protein sequencing, 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. 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.