Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Innate immunity activator protein

Gene

INAVA

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

Functioni

Expressed in peripheral macrophages and intestinal myeloid-derived cells, is required for optimal PRR (pattern recognition receptor)-induced signaling, cytokine secretion, and bacterial clearance. Upon stimulation of a broad range of PRRs (pattern recognition receptor) such as NOD2 or TLR2, TLR3, TLR4, TLR5, TLR7 and TLR9, associates with YWHAQ/14-3-3T, which in turn leads to the recruitment and activation of MAP kinases and NF-kappa-B signaling complexes that amplifies PRR-induced downstream signals and cytokine secretion (PubMed:28436939). In the intestine, regulates adherens junction stability by regulating the degradation of CYTH1 and CYTH2, probably acting as substrate cofactor for SCF E3 ubiquitin-protein ligase complexes. Stabilizes adherens junctions by limiting CYTH1-dependent ARF6 activation (PubMed:29420262).2 Publications

GO - Biological processi

  • activation of MAPK activity Source: UniProtKB
  • adherens junction maintenance Source: UniProtKB
  • cytokine production involved in immune response Source: UniProtKB
  • innate immune response Source: UniProtKB
  • intestinal epithelial structure maintenance Source: UniProtKB
  • nucleotide-binding oligomerization domain containing 2 signaling pathway Source: UniProtKB
  • pattern recognition receptor signaling pathway Source: UniProtKB
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • positive regulation of interleukin-10 production Source: UniProtKB
  • positive regulation of interleukin-1 beta production Source: UniProtKB
  • positive regulation of interleukin-6 production Source: UniProtKB
  • positive regulation of protein ubiquitination Source: UniProtKB
  • positive regulation of stress-activated MAPK cascade Source: UniProtKB
  • reactive oxygen species biosynthetic process Source: UniProtKB
  • response to muramyl dipeptide Source: UniProtKB
  • response to peptidoglycan Source: UniProtKB

Keywordsi

Biological processImmunity, Innate immunity

Names & Taxonomyi

Protein namesi
Recommended name:
Innate immunity activator proteinImported
Gene namesi
Name:INAVAImported
Synonyms:C1orf106
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000163362.10
HGNCiHGNC:25599 INAVA
neXtProtiNX_Q3KP66

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

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Genetic variations in INAVA are associated with an increased risk of inflammatory bowel disease. A chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology which is subdivided into Crohn disease and ulcerative colitis phenotypes.3 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi164 – 170PKVRRRI → AAAAAAA: No effect on nuclear translocation upon induction by MDP. Abolishes nuclear translocation upon induction by MDP and slightly decreases NOD2-induced AP-1 and NF-kappaB activation and IL6 secretion; when associated with 335-A--A-338 and 423-A--A-426. 1 Publication7
Mutagenesisi246S → A: Decreases interaction with YWHAQ, cellular signaling pathway activation and cytokine secretion. 1 Publication1
Mutagenesisi335 – 338KPRK → AAAA: No effect on nuclear translocation upon induction by MDP. Abolishes nuclear translocation upon induction by MDP and slightly decreases NOD2-induced AP-1 and NF-kappaB activation and IL6 secretion; when associated with 164-A--A-170 and 423-A--A-426. 1 Publication4
Mutagenesisi340S → A: Decreases interaction with YWHAQ, cellular signaling pathway activation and cytokine secretion. 1 Publication1
Mutagenesisi423 – 426RRRP → AAAA: No effect on nuclear translocation upon induction by MDP. Abolishes nuclear translocation upon induction by MDP and slightly decreases NOD2-induced AP-1 and NF-kappaB activation and IL6 secretion; when associated with 164-A--A-170 and 335-A--A-338. 1 Publication4
Mutagenesisi616S → A: Decreases interaction with YWHAQ, cellular signaling pathway activation and cytokine secretion. 1 Publication1

Organism-specific databases

DisGeNETi55765
OpenTargetsiENSG00000163362
PharmGKBiPA142672490

Polymorphism and mutation databases

BioMutaiC1orf106
DMDMi317373328

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002517291 – 663Innate immunity activator proteinAdd BLAST663

Proteomic databases

EPDiQ3KP66
MaxQBiQ3KP66
PaxDbiQ3KP66
PeptideAtlasiQ3KP66
PRIDEiQ3KP66
ProteomicsDBi61715

PTM databases

iPTMnetiQ3KP66
PhosphoSitePlusiQ3KP66

Expressioni

Tissue specificityi

Highly expressed in intestinal myeloid-derived cells and expressed in monocyte-derived macrophages upon induction by PRR activation.2 Publications

Inductioni

Expression is induced by the component of peptidoglycan muramyl dipeptide (PubMed:28436939). Negatively regulated by microRNA-24 (miR-24) (PubMed:28436939).1 Publication

Gene expression databases

BgeeiENSG00000163362
CleanExiHS_C1orf106
ExpressionAtlasiQ3KP66 baseline and differential
GenevisibleiQ3KP66 HS

Organism-specific databases

HPAiHPA027499
HPA027511

Interactioni

Subunit structurei

Interacts with IRAK1, NOD2 and RIPK2; the interaction takes place upon PRR stimulation (PubMed:28436939). Interacts with YWHAQ/14-3-3T; the interaction increases upon PRR stimulation and is required for cellular signaling pathway activation and cytokine secretion (PubMed:28436939). Interacts (via N-terminal domain) with CYTH1 and CYTH2 (via their N-terminal domains) (PubMed:29420262). Interacts with FBXW11 and BTRC; associates with SCF E3 ubiquitin-protein ligase complexes (PubMed:29420262).2 Publications

Protein-protein interaction databases

BioGridi120883, 24 interactors
IntActiQ3KP66, 1 interactor
MINTiQ3KP66
STRINGi9606.ENSP00000356311

Structurei

3D structure databases

ProteinModelPortaliQ3KP66
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili118 – 147Sequence analysisAdd BLAST30

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi164 – 170Nuclear localization signal (NLS) 11 Publication7
Motifi332 – 338Nuclear localization signal (NLS) 21 Publication7
Motifi422 – 428Nuclear localization signal (NLS) 31 Publication7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi282 – 357Pro-richAdd BLAST76

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG3529 Eukaryota
ENOG410XQFP LUCA
GeneTreeiENSGT00920000149019
HOGENOMiHOG000233699
HOVERGENiHBG080963
InParanoidiQ3KP66
OMAiHREDPLS
OrthoDBiEOG091G0784
PhylomeDBiQ3KP66
TreeFamiTF328984

Family and domain databases

InterProiView protein in InterPro
IPR021774 DUF3338
PfamiView protein in Pfam
PF11819 DUF3338, 1 hit

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q3KP66-1) [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
MLQMPKLNEI PPGRAGRREA RGEGRWPGQT GPEAARLEWR AQGQAGGARA
60 70 80 90 100
PWDSWGSSRL PTQPGPGWSR CPPSLLCALS FQKSTMESKD EVSDTDSGII
110 120 130 140 150
LQSGPDSPVS PMKELTHAVH KQQRALEARL EACLEELRRL CLREAELTGT
160 170 180 190 200
LPAEYPLKPG EKAPKVRRRI GAAYKLDDWA LHREDPLSSL ERQLALQLQI
210 220 230 240 250
TEAARRLCLE ENLSRQARRQ RKHSMLQEEK KLQELQRCLV ERRRNSEPPP
260 270 280 290 300
AAALPLGREL SASDDSSLSD GLLLEEEESQ VPKPPPESPA PPSRPLPPQT
310 320 330 340 350
LEGLQPTGPE AGSPERAPVQ NSPWKETSLD HPYEKPRKSS EPWSESSSPA
360 370 380 390 400
TTPQDGPSAS SLWLLEPASY HVVPIRGVPG QWQGRTSAPA TPEIQGRRGQ
410 420 430 440 450
SQSLRVDSFR AGPEGRGRSA FPRRRPTHYT VTVPDSCFPA TKPPLPHAAC
460 470 480 490 500
HSCSEDSGSD VSSISHPTSP GSSSPDISFL QPLSPPKTHR HRGAWVPAGS
510 520 530 540 550
RELVAHHPKL LLPPGYFPAG RYVVVAESPL PPGEWELRRA APGPAYEEEG
560 570 580 590 600
TPLRYQRLVP SRSRIVRTPS LKDSPAGRGL SKAAVSEELK WWHERARLRS
610 620 630 640 650
TRPHSLDRQG AFRVRSLPLG REGFGRALGP RAQVPTVCVL RRSPDGAPVQ
660
VFVPEKGEII SQV
Length:663
Mass (Da):72,914
Last modified:January 11, 2011 - v2
Checksum:i77EB3D76DC55EF8A
GO
Isoform 2 (identifier: Q3KP66-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-85: Missing.

Show »
Length:578
Mass (Da):63,695
Checksum:i92B58F00B878C9B5
GO

Sequence cautioni

The sequence BAA91771 differs from that shown. Unlikely isoform. Aberrant splice sites.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti641R → W in BAA91892 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_080249333Y → F Found in patients with inflammatory bowel disease; unknown pathological significance; decreases protein stability. 2 PublicationsCorresponds to variant dbSNP:rs41313912Ensembl.1
Natural variantiVAR_030835538R → C2 PublicationsCorresponds to variant dbSNP:rs296520Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0460481 – 85Missing in isoform 2. 1 PublicationAdd BLAST85

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK001583 mRNA Translation: BAA91771.1 Sequence problems.
AK001763 mRNA Translation: BAA91892.1
AK303885 mRNA Translation: BAG64821.1
AK316510 mRNA Translation: BAH14881.1
AC099756 Genomic DNA No translation available.
BC106877 mRNA Translation: AAI06878.1
CCDSiCCDS44292.1 [Q3KP66-3]
RefSeqiNP_001136041.1, NM_001142569.2 [Q3KP66-3]
NP_060735.3, NM_018265.3
XP_011508056.1, XM_011509754.2 [Q3KP66-3]
XP_011508057.1, XM_011509755.1 [Q3KP66-3]
UniGeneiHs.518997

Genome annotation databases

EnsembliENST00000367342; ENSP00000356311; ENSG00000163362 [Q3KP66-1]
ENST00000413687; ENSP00000392105; ENSG00000163362 [Q3KP66-3]
GeneIDi55765
KEGGihsa:55765
UCSCiuc010ppm.3 human [Q3KP66-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiINAVA_HUMAN
AccessioniPrimary (citable) accession number: Q3KP66
Secondary accession number(s): B4E1K9
, E9PFY0, Q9NV65, Q9NVI0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 3, 2006
Last sequence update: January 11, 2011
Last modified: June 20, 2018
This is version 100 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

Complete proteome, Reference proteome

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health