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Protein

Inversin

Gene

Invs

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Required for normal renal development and establishment of left-right axis. Probably acts as a molecular switch between different Wnt signaling pathways. Inhibits the canonical Wnt pathway by targeting cytoplasmic disheveled (DVL1) for degradation by the ubiquitin-proteasome. This suggests that it is required in renal development to oppose the repression of terminal differentiation of tubular epithelial cells by Wnt signaling (By similarity). Involved in the organization of apical junctions in kidney cells together with NPHP1, NPHP4 and RPGRIP1L/NPHP8. Does not seem to be strictly required for ciliogenesis.By similarity3 Publications

GO - Biological processi

  • animal organ development Source: MGI
  • embryonic heart tube left/right pattern formation Source: MGI
  • kidney development Source: MGI
  • negative regulation of canonical Wnt signaling pathway Source: UniProtKB
  • pancreas development Source: MGI
  • post-embryonic development Source: MGI
  • Wnt signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Wnt signaling pathway

Keywords - Ligandi

Calmodulin-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Inversin
Alternative name(s):
Inversion of embryo turning protein
Nephrocystin-2
Gene namesi
Name:Invs
Synonyms:Inv, Nphp2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1335082. Invs.

Subcellular locationi

GO - Cellular componenti

  • ciliary base Source: MGI
  • ciliary inversin compartment Source: MGI
  • membrane Source: UniProtKB-SubCell
  • microtubule Source: UniProtKB-KW
  • nucleus Source: UniProtKB-SubCell
  • perinuclear region of cytoplasm Source: UniProtKB-SubCell
  • spindle Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Membrane, Microtubule, Nucleus

Pathology & Biotechi

Disruption phenotypei

Constant reversal of left/right polarity (situs inversus) and cyst formation in the kidneys.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi498N → A: Abolishes interaction with APC2. 1 Publication1
Mutagenesisi915N → A: Does not affect interaction with APC2. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000670171 – 1062InversinAdd BLAST1062

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei753-hydroxyasparagineBy similarity1

Post-translational modificationi

May be ubiquitinated via its interaction with APC2.
Hydroxylated at Asn-75, most probably by HIF1AN.By similarity

Keywords - PTMi

Hydroxylation, Ubl conjugation

Proteomic databases

PaxDbiO89019.
PRIDEiO89019.

PTM databases

iPTMnetiO89019.
PhosphoSitePlusiO89019.

Expressioni

Tissue specificityi

Strongly expressed in the primary cilia of renal cells, especially in the varicosities, swellings observed in the cilia. Localizes in the node monocilia and in other 9+0 monocilia, including those of kidney epithelial cells and the pituitary gland, but it does not localize to 9+2 cilia (at protein level). In adult, it is expressed at high level in liver and kidney. Weakly or not expressed in other tissues.2 Publications

Developmental stagei

Expressed from E7. Expressed in presomite-stage embryos, before asymmetrical expression of Nodal and Lefty.1 Publication

Gene expression databases

CleanExiMM_INVS.

Interactioni

Subunit structurei

Interacts with microtubules. Interacts with NPHP1. Interacts with DVL1, PRICKLE (PRICKLE1 or PRICKLE2) and Strabismus (VANGL1 or VANGL2) (By similarity). Binds calmodulin via its IQ domains. Interacts with APC2. Interacts with alpha-, beta-, and gamma-catenin. Interacts with N-cadherin (CDH2). Interacts with NPHP3 (By similarity). Interacts with IQCB1; the interaction likely requires additional interactors (By similarity). Component of a complex containing at least ANKS6, INVS, NEK8 and NPHP3. ANKS6 may organize complex assembly by linking INVS and NPHP3 to NEK8 and INVS may target the complex to the proximal ciliary axoneme (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Iqcb1Q8BP002EBI-4281337,EBI-4282243
Nek8Q91ZR42EBI-4281337,EBI-4282339

Protein-protein interaction databases

IntActiO89019. 7 interactors.
STRINGi10090.ENSMUSP00000030029.

Structurei

3D structure databases

ProteinModelPortaliO89019.
SMRiO89019.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati13 – 42ANK 1Add BLAST30
Repeati47 – 76ANK 2Add BLAST30
Repeati80 – 110ANK 3Add BLAST31
Repeati113 – 144ANK 4Add BLAST32
Repeati148 – 177ANK 5Add BLAST30
Repeati181 – 213ANK 6Add BLAST33
Repeati220 – 250ANK 7Add BLAST31
Repeati254 – 283ANK 8Add BLAST30
Repeati288 – 317ANK 9Add BLAST30
Repeati321 – 350ANK 10Add BLAST30
Repeati356 – 385ANK 11Add BLAST30
Repeati389 – 418ANK 12Add BLAST30
Repeati422 – 451ANK 13Add BLAST30
Repeati455 – 484ANK 14Add BLAST30
Repeati488 – 517ANK 15Add BLAST30
Repeati523 – 553ANK 16Add BLAST31
Domaini555 – 584IQ 1PROSITE-ProRule annotationAdd BLAST30
Domaini914 – 943IQ 2PROSITE-ProRule annotationAdd BLAST30

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi490 – 498D-box 19
Motifi907 – 915D-box 29

Domaini

The D-box 1 (destruction box 1) mediates the interaction with APC2, and may act as a recognition signal for degradation via the ubiquitin-proteasome pathway.

Sequence similaritiesi

Contains 16 ANK repeats.PROSITE-ProRule annotation
Contains 2 IQ domains.PROSITE-ProRule annotation

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiKOG0504. Eukaryota.
COG0666. LUCA.
HOGENOMiHOG000234066.
HOVERGENiHBG083788.
InParanoidiO89019.
PhylomeDBiO89019.

Family and domain databases

Gene3Di1.25.40.20. 5 hits.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR000048. IQ_motif_EF-hand-BS.
[Graphical view]
PfamiPF00023. Ank. 2 hits.
PF12796. Ank_2. 5 hits.
PF00612. IQ. 2 hits.
[Graphical view]
SMARTiSM00248. ANK. 15 hits.
SM00015. IQ. 2 hits.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 2 hits.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 11 hits.
PS50096. IQ. 2 hits.
[Graphical view]

Sequences (7)i

Sequence statusi: Complete.

This entry describes 7 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O89019-1) [UniParc]FASTAAdd to basket
Also known as: F

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
MNISEDVLST GSSLASQVHA AAVNGDKGAL QRLIVGNSAL RDKEDRFGRT
60 70 80 90 100
PLMYCVLADR VDCADALLKA GADVNKTDHS RRTALHLAAQ KGNYRFMKLL
110 120 130 140 150
LTRRANWMQK DLEEMTPLHL STRHRSPKCL ALLLKFMAPG EVDTQDKNKQ
160 170 180 190 200
TALHWSAYYN NPEHAKLLIK HDSNIGIPDV EGKIPLHWAA NHKDPSAVHT
210 220 230 240 250
VRCILDAAPT ESLLNWQDYE GRTPLHFAVA DGNLTVVDVL TSYESCNITS
260 270 280 290 300
YDNLFRTPLH WAALLGHAQI VHLLLERNKS GTIPSDSQGA TPLHYAAQSN
310 320 330 340 350
FAETVKVFLQ HPSVKDDSDL EGRTSFMWAA GKGNDDVLRT MLSLKSDIDI
360 370 380 390 400
NMSDKYGGTA LHAAALSGHV STVKLLLDND AQVDATDVMK HTPLFRACEM
410 420 430 440 450
GHRDVIQTLI KGGARVDLVD QDGHSLLHWA ALGGNADVCQ ILIENKINPN
460 470 480 490 500
VQDYAGRTPL QCAAYGGYIN CMAVLMENNA DPNIQDKEGR TALHWSCNNG
510 520 530 540 550
YLDAIKLLLD FAAFPNQMEN NEERYTPLDY ALLGERHEVI QFMLEHGALS
560 570 580 590 600
IAAIQDIAAF KIQAVYKGYK VRKAFRDRKN LLMKHEQLRK DAAAKKREEE
610 620 630 640 650
NKRKEAEQQK GQLDTDPPRS HCSSSAPVLP CPPSPQNEGS KQDATPSKQP
660 670 680 690 700
PASHTVQSPD PEHSRLPGRC PGRASQGDSS IDLQGTASRK PSETPIEHCR
710 720 730 740 750
GPSACVHPRS WEGGNSSKNQ GTSSVEKRRG ETNGKHRRCE EGPSSARQPL
760 770 780 790 800
CTGSGRPAEK GEDSSPAVAS ASQQDHPRKP NKRQDRAARP RGASQKRRTH
810 820 830 840 850
QLRDRCSPAG SSRPGSAKGE VACADQSSLH RHTPRSKVTQ DKLIGGVSSG
860 870 880 890 900
LPLSTEASRS GCKQLYEDIC ASPETGVAHG PPPGQCMNIH LLPVEQRLLI
910 920 930 940 950
IQRERSRKEL FRRKNKAAAV IQRAWRSYQL RKHLSRLLHL KQLGAREVLR
960 970 980 990 1000
CTQVCTALLL QVWRKELELK FPKSISVSRT SKSPSKGSSA TKYARHSVLR
1010 1020 1030 1040 1050
QIYGCSQEGK GHHPIKSSKA PAVLHLSSVN SLQSIHLDNS GRSKKFSYNL
1060
QPSSQSKNKP KL
Length:1,062
Mass (Da):117,129
Last modified:July 5, 2005 - v2
Checksum:i048DF1D94F23C033
GO
Isoform 2 (identifier: O89019-2) [UniParc]FASTAAdd to basket
Also known as: S2

The sequence of this isoform differs from the canonical sequence as follows:
     730-894: Missing.

Note: Exon 14b skipped.
Show »
Length:897
Mass (Da):99,673
Checksum:iB2ABCE372FE3615A
GO
Isoform 3 (identifier: O89019-3) [UniParc]FASTAAdd to basket
Also known as: S1

The sequence of this isoform differs from the canonical sequence as follows:
     730-849: Missing.

Note: Exon 14a skipped.
Show »
Length:942
Mass (Da):104,330
Checksum:iD3C68E55C8359F1F
GO
Isoform 4 (identifier: O89019-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     150-205: Missing.

Note: Exon 5 skipped.
Show »
Length:1,006
Mass (Da):110,825
Checksum:i50B8D8D6DF5319DA
GO
Isoform 5 (identifier: O89019-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     489-492: GRTA → VHTP
     493-1062: Missing.

Note: Exon 13 skipped.
Show »
Length:492
Mass (Da):54,108
Checksum:iF9DD542789B638CE
GO
Isoform 6 (identifier: O89019-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     596-632: KREEENKRKEAEQQKGQLDTDPPRSHCSSSAPVLPCP → NTHRALQRPFCLCAPQILGRWQQLQEPGNILCGEAQR
     633-1062: Missing.

Show »
Length:632
Mass (Da):70,222
Checksum:i29E5903A10FA45C9
GO
Isoform 7 (identifier: O89019-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     596-755: KREEENKRKE...ARQPLCTGSG → NTHRALQRPF...RERTSSHQIF
     756-1062: Missing.

Note: Exon 13 skipped with exon 14b.
Show »
Length:755
Mass (Da):83,455
Checksum:iCAD02CD113EBAB23
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti23V → I in CAA09388 (PubMed:9771707).Curated1
Sequence conflicti32R → K in CAA09388 (PubMed:9771707).Curated1
Sequence conflicti320L → Q in CAA09388 (PubMed:9771707).Curated1
Sequence conflicti460 – 462LQC → IQS in CAA09388 (PubMed:9771707).Curated3
Sequence conflicti468Y → N in CAA09388 (PubMed:9771707).Curated1
Sequence conflicti639G → A in CAA09388 (PubMed:9771707).Curated1
Sequence conflicti666L → P in CAA09388 (PubMed:9771707).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_014498150 – 205Missing in isoform 4. CuratedAdd BLAST56
Alternative sequenceiVSP_014499489 – 492GRTA → VHTP in isoform 5. Curated4
Alternative sequenceiVSP_014500493 – 1062Missing in isoform 5. CuratedAdd BLAST570
Alternative sequenceiVSP_014501596 – 755KREEE…CTGSG → NTHRALQRPFCLCAPQILGR WQQLQEPGNILCGEAQRAAP ADNPEGTKQERAVSTEKQGS GGHPASLAKLPAQEAPVSAS AFEAAWSQRSAQMYPSVHSP APPGLEERTGTQIPKVHLSK QDIEESIQRLVGHKVCQALS AQADLRLFSRRERTSSHQIF in isoform 7. CuratedAdd BLAST160
Alternative sequenceiVSP_014503596 – 632KREEE…VLPCP → NTHRALQRPFCLCAPQILGR WQQLQEPGNILCGEAQR in isoform 6. CuratedAdd BLAST37
Alternative sequenceiVSP_014504633 – 1062Missing in isoform 6. CuratedAdd BLAST430
Alternative sequenceiVSP_014505730 – 894Missing in isoform 2. 1 PublicationAdd BLAST165
Alternative sequenceiVSP_014506730 – 849Missing in isoform 3. 1 PublicationAdd BLAST120
Alternative sequenceiVSP_014502756 – 1062Missing in isoform 7. CuratedAdd BLAST307

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF034860 mRNA. Translation: AAC34976.3.
AJ004828 Genomic DNA. No translation available.
AJ010902 mRNA. Translation: CAA09388.1.
CCDSiCCDS18166.1. [O89019-1]
PIRiT14151.
T30255.
UniGeneiMm.317706.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF034860 mRNA. Translation: AAC34976.3.
AJ004828 Genomic DNA. No translation available.
AJ010902 mRNA. Translation: CAA09388.1.
CCDSiCCDS18166.1. [O89019-1]
PIRiT14151.
T30255.
UniGeneiMm.317706.

3D structure databases

ProteinModelPortaliO89019.
SMRiO89019.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO89019. 7 interactors.
STRINGi10090.ENSMUSP00000030029.

PTM databases

iPTMnetiO89019.
PhosphoSitePlusiO89019.

Proteomic databases

PaxDbiO89019.
PRIDEiO89019.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:1335082. Invs.

Phylogenomic databases

eggNOGiKOG0504. Eukaryota.
COG0666. LUCA.
HOGENOMiHOG000234066.
HOVERGENiHBG083788.
InParanoidiO89019.
PhylomeDBiO89019.

Miscellaneous databases

PROiO89019.
SOURCEiSearch...

Gene expression databases

CleanExiMM_INVS.

Family and domain databases

Gene3Di1.25.40.20. 5 hits.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR000048. IQ_motif_EF-hand-BS.
[Graphical view]
PfamiPF00023. Ank. 2 hits.
PF12796. Ank_2. 5 hits.
PF00612. IQ. 2 hits.
[Graphical view]
SMARTiSM00248. ANK. 15 hits.
SM00015. IQ. 2 hits.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 2 hits.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 11 hits.
PS50096. IQ. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiINVS_MOUSE
AccessioniPrimary (citable) accession number: O89019
Secondary accession number(s): O88849
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: July 5, 2005
Last modified: November 2, 2016
This is version 123 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.