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Protein

Inversin

Gene

INVS

Organism
Homo sapiens (Human)
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. Involved in the organization of apical junctions in kidney cells together with NPHP1, NPHP4 and RPGRIP1L/NPHP8 (By similarity). Does not seem to be strictly required for ciliogenesis (By similarity).By similarity2 Publications

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Wnt signaling pathway

Keywords - Ligandi

Calmodulin-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000119509-MONOMER.
SignaLinkiQ9Y283.
SIGNORiQ9Y283.

Names & Taxonomyi

Protein namesi
Recommended name:
Inversin
Alternative name(s):
Inversion of embryo turning homolog
Nephrocystin-2
Gene namesi
Name:INVS
Synonyms:INV, NPHP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:17870. INVS.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cilium, Cytoplasm, Cytoskeleton, Membrane, Microtubule, Nucleus

Pathology & Biotechi

Involvement in diseasei

Nephronophthisis 2 (NPHP2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive disorder resulting in end-stage renal disease. It is characterized by early onset and rapid progression. Phenotypic manifestations include enlarged kidneys, chronic tubulo-interstitial nephritis, anemia, hyperkalemic metabolic acidosis. Some patients also display situs inversus. Pathologically, it differs from later-onset nephronophthisis by the absence of medullary cysts and thickened tubular basement membranes, and by the presence of cortical microcysts.
See also OMIM:602088
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_022822482P → R in NPHP2. 1 Publication1
Natural variantiVAR_022823493L → S in NPHP2; impairs ability to target DVL1 for degradation. 1 PublicationCorresponds to variant rs121964995dbSNPEnsembl.1

Keywords - Diseasei

Ciliopathy, Disease mutation, Nephronophthisis

Organism-specific databases

DisGeNETi27130.
MalaCardsiINVS.
MIMi602088. phenotype.
OpenTargetsiENSG00000119509.
Orphaneti93591. Infantile nephronophthisis.
3156. Senior-Loken syndrome.
PharmGKBiPA38472.

Polymorphism and mutation databases

BioMutaiINVS.
DMDMi68565551.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000670161 – 1065InversinAdd BLAST1065

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei753-hydroxyasparagine1 Publication1
Modified residuei661PhosphoserineCombined sources1

Post-translational modificationi

May be ubiquitinated via its interaction with APC2.By similarity
Hydroxylated at Asn-75, most probably by HIF1AN.1 Publication

Keywords - PTMi

Hydroxylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9Y283.
PaxDbiQ9Y283.
PeptideAtlasiQ9Y283.
PRIDEiQ9Y283.

PTM databases

iPTMnetiQ9Y283.
PhosphoSitePlusiQ9Y283.

Expressioni

Tissue specificityi

Widely expressed. Strongly expressed in the primary cilia of renal tubular cells.2 Publications

Gene expression databases

BgeeiENSG00000119509.
CleanExiHS_INVS.
ExpressionAtlasiQ9Y283. baseline and differential.
GenevisibleiQ9Y283. HS.

Organism-specific databases

HPAiHPA049994.

Interactioni

Subunit structurei

Binds calmodulin via its IQ domains. Interacts with APC2. Interacts with alpha-, beta-, and gamma-catenin. Interacts with N-cadherin (CDH2). Interacts with microtubules (By similarity). Interacts with NPHP1. Interacts with DVL1, PRICKLE (PRICKLE1 or PRICKLE2) and Strabismus (VANGL1 or VANGL2). Interacts with IQCB1; the interaction likely requires additional interactors. 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 similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
B9D2Q9BPU94EBI-751472,EBI-6958971

Protein-protein interaction databases

BioGridi118021. 9 interactors.
IntActiQ9Y283. 10 interactors.
MINTiMINT-1196568.
STRINGi9606.ENSP00000262457.

Structurei

3D structure databases

ProteinModelPortaliQ9Y283.
SMRiQ9Y283.
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
Domaini916 – 945IQ 2PROSITE-ProRule annotationAdd BLAST30

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi490 – 498D-box 19
Motifi909 – 917D-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.By similarity

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.
GeneTreeiENSGT00840000129677.
HOVERGENiHBG083788.
InParanoidiQ9Y283.
KOiK19626.
OMAiNLQCIHL.
OrthoDBiEOG091G01EB.
PhylomeDBiQ9Y283.
TreeFamiTF312824.

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]
PRINTSiPR01415. ANKYRIN.
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 (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9Y283-1) [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
MNKSENLLFA GSSLASQVHA AAVNGDKGAL QRLIVGNSAL KDKEDQFGRT
60 70 80 90 100
PLMYCVLADR LDCADALLKA GADVNKTDHS QRTALHLAAQ KGNYRFMKLL
110 120 130 140 150
LTRRANWMQK DLEEMTPLHL TTRHRSPKCL ALLLKFMAPG EVDTQDKNKQ
160 170 180 190 200
TALHWSAYYN NPEHVKLLIK HDSNIGIPDV EGKIPLHWAA NHKDPSAVHT
210 220 230 240 250
VRCILDAAPT ESLLNWQDYE GRTPLHFAVA DGNVTVVDVL TSYESCNITS
260 270 280 290 300
YDNLFRTPLH WAALLGHAQI VHLLLERNKS GTIPSDSQGA TPLHYAAQSN
310 320 330 340 350
FAETVKVFLK HPSVKDDSDL EGRTSFMWAA GKGSDDVLRT MLSLKSDIDI
360 370 380 390 400
NMADKYGGTA LHAAALSGHV STVKLLLENN AQVDATDVMK HTPLFRACEM
410 420 430 440 450
GHKDVIQTLI 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 GRRSPDSCRP QALPCLPSTQ DVPSRQSRAP SKQPPAGNVA
660 670 680 690 700
QGPEPRDSRG SPGGSLGGAL QKEQHVSSDL QGTNSRRPNE TAREHSKGQS
710 720 730 740 750
ACVHFRPNEG SDGSRHPGVP SVEKSRGETA GDERCAKGKG FVKQPSCIRV
760 770 780 790 800
AGPDEKGEDS RRAAASLPPH DSHWKPSRRH DTEPKAKCAP QKRRTQELRG
810 820 830 840 850
GRCSPAGSSR PGSARGEAVH AGQNPPHHRT PRNKVTQAKL TGGLYSHLPQ
860 870 880 890 900
STEELRSGAR RLETSTLSED FQVSKETDPA PGPLSGQSVN IDLLPVELRL
910 920 930 940 950
QIIQRERRRK ELFRKKNKAA AVIQRAWRSY QLRKHLSHLR HMKQLGAGDV
960 970 980 990 1000
DRWRQESTAL LLQVWRKELE LKFPQTTAVS KAPKSPSKGT SGTKSTKHSV
1010 1020 1030 1040 1050
LKQIYGCSHE GKIHHPTRSV KASSVLRLNS VSNLQCIHLL ENSGRSKNFS
1060
YNLQSATQPK NKTKP
Length:1,065
Mass (Da):117,826
Last modified:July 5, 2005 - v2
Checksum:iDACDF33C1B8573AC
GO
Isoform 2 (identifier: Q9Y283-2) [UniParc]FASTAAdd to basket
Also known as: S2

The sequence of this isoform differs from the canonical sequence as follows:
     727-896: Missing.

Show »
Length:895
Mass (Da):99,564
Checksum:i4604C8A1C03E40C6
GO
Isoform 3 (identifier: Q9Y283-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     92-101: GNYRFMKLLL → ALRTISTGRI
     102-1065: Missing.

Note: No experimental confirmation available.
Show »
Length:101
Mass (Da):10,748
Checksum:iC98F2838A19DFD5D
GO

Sequence cautioni

The sequence AAD02131 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAH41665 differs from that shown. Contaminating sequence. Potential poly-A sequence.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti487K → Q in AAI11762 (PubMed:15489334).Curated1
Sequence conflicti764A → G in AAC79436 (PubMed:11941489).Curated1
Sequence conflicti764A → G in AAC79456 (PubMed:11941489).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_044119242S → L.Corresponds to variant rs2491097dbSNPEnsembl.1
Natural variantiVAR_022822482P → R in NPHP2. 1 Publication1
Natural variantiVAR_022823493L → S in NPHP2; impairs ability to target DVL1 for degradation. 1 PublicationCorresponds to variant rs121964995dbSNPEnsembl.1
Natural variantiVAR_044120888S → R.Corresponds to variant rs1052867dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01449592 – 101GNYRFMKLLL → ALRTISTGRI in isoform 3. 1 Publication10
Alternative sequenceiVSP_014496102 – 1065Missing in isoform 3. 1 PublicationAdd BLAST964
Alternative sequenceiVSP_014497727 – 896Missing in isoform 2. 1 PublicationAdd BLAST170

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF039217 mRNA. Translation: AAD02131.2. Different initiation.
AF084367 mRNA. Translation: AAC79436.1.
AF084382
, AF084373, AF084374, AF084375, AF084377, AF084379, AF084381, AF084371, AF084369, AF084368, AF084370, AF084372, AF084380, AF084378, AF084376 Genomic DNA. Translation: AAC79456.1.
AF084382
, AF084368, AF084369, AF084370, AF084371, AF084372, AF084373, AF084374, AF084375, AF084376, AF084377, AF084378, AF084379, AF084380, AF084381 Genomic DNA. Translation: AAC79457.1.
AL137072, AL356798, AL445214 Genomic DNA. Translation: CAH72173.1.
AL137072 Genomic DNA. Translation: CAH72174.1.
AL445214, AL137072, AL356798 Genomic DNA. Translation: CAI39744.1.
AL445214, AL137072, AL356798 Genomic DNA. Translation: CAI39745.2.
AL356798, AL137072, AL445214 Genomic DNA. Translation: CAI40807.1.
AL356798, AL137072, AL445214 Genomic DNA. Translation: CAI40808.2.
AL137072, AL356798, AL445214 Genomic DNA. Translation: CAM16212.1.
CH471105 Genomic DNA. Translation: EAW58926.1.
BC006370 mRNA. Translation: AAH06370.1.
BC041665 mRNA. Translation: AAH41665.1. Sequence problems.
BC111761 mRNA. Translation: AAI11762.1.
CCDSiCCDS6746.1. [Q9Y283-1]
RefSeqiNP_055240.2. NM_014425.4. [Q9Y283-1]
UniGeneiHs.558477.
Hs.655024.
Hs.742075.

Genome annotation databases

EnsembliENST00000262456; ENSP00000262456; ENSG00000119509. [Q9Y283-2]
ENST00000262457; ENSP00000262457; ENSG00000119509. [Q9Y283-1]
ENST00000374921; ENSP00000364056; ENSG00000119509. [Q9Y283-3]
GeneIDi27130.
KEGGihsa:27130.
UCSCiuc004bao.3. human. [Q9Y283-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF039217 mRNA. Translation: AAD02131.2. Different initiation.
AF084367 mRNA. Translation: AAC79436.1.
AF084382
, AF084373, AF084374, AF084375, AF084377, AF084379, AF084381, AF084371, AF084369, AF084368, AF084370, AF084372, AF084380, AF084378, AF084376 Genomic DNA. Translation: AAC79456.1.
AF084382
, AF084368, AF084369, AF084370, AF084371, AF084372, AF084373, AF084374, AF084375, AF084376, AF084377, AF084378, AF084379, AF084380, AF084381 Genomic DNA. Translation: AAC79457.1.
AL137072, AL356798, AL445214 Genomic DNA. Translation: CAH72173.1.
AL137072 Genomic DNA. Translation: CAH72174.1.
AL445214, AL137072, AL356798 Genomic DNA. Translation: CAI39744.1.
AL445214, AL137072, AL356798 Genomic DNA. Translation: CAI39745.2.
AL356798, AL137072, AL445214 Genomic DNA. Translation: CAI40807.1.
AL356798, AL137072, AL445214 Genomic DNA. Translation: CAI40808.2.
AL137072, AL356798, AL445214 Genomic DNA. Translation: CAM16212.1.
CH471105 Genomic DNA. Translation: EAW58926.1.
BC006370 mRNA. Translation: AAH06370.1.
BC041665 mRNA. Translation: AAH41665.1. Sequence problems.
BC111761 mRNA. Translation: AAI11762.1.
CCDSiCCDS6746.1. [Q9Y283-1]
RefSeqiNP_055240.2. NM_014425.4. [Q9Y283-1]
UniGeneiHs.558477.
Hs.655024.
Hs.742075.

3D structure databases

ProteinModelPortaliQ9Y283.
SMRiQ9Y283.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118021. 9 interactors.
IntActiQ9Y283. 10 interactors.
MINTiMINT-1196568.
STRINGi9606.ENSP00000262457.

PTM databases

iPTMnetiQ9Y283.
PhosphoSitePlusiQ9Y283.

Polymorphism and mutation databases

BioMutaiINVS.
DMDMi68565551.

Proteomic databases

EPDiQ9Y283.
PaxDbiQ9Y283.
PeptideAtlasiQ9Y283.
PRIDEiQ9Y283.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262456; ENSP00000262456; ENSG00000119509. [Q9Y283-2]
ENST00000262457; ENSP00000262457; ENSG00000119509. [Q9Y283-1]
ENST00000374921; ENSP00000364056; ENSG00000119509. [Q9Y283-3]
GeneIDi27130.
KEGGihsa:27130.
UCSCiuc004bao.3. human. [Q9Y283-1]

Organism-specific databases

CTDi27130.
DisGeNETi27130.
GeneCardsiINVS.
HGNCiHGNC:17870. INVS.
HPAiHPA049994.
MalaCardsiINVS.
MIMi243305. gene.
602088. phenotype.
neXtProtiNX_Q9Y283.
OpenTargetsiENSG00000119509.
Orphaneti93591. Infantile nephronophthisis.
3156. Senior-Loken syndrome.
PharmGKBiPA38472.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0504. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00840000129677.
HOVERGENiHBG083788.
InParanoidiQ9Y283.
KOiK19626.
OMAiNLQCIHL.
OrthoDBiEOG091G01EB.
PhylomeDBiQ9Y283.
TreeFamiTF312824.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000119509-MONOMER.
SignaLinkiQ9Y283.
SIGNORiQ9Y283.

Miscellaneous databases

ChiTaRSiINVS. human.
GeneWikiiINVS.
GenomeRNAii27130.
PROiQ9Y283.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000119509.
CleanExiHS_INVS.
ExpressionAtlasiQ9Y283. baseline and differential.
GenevisibleiQ9Y283. HS.

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]
PRINTSiPR01415. ANKYRIN.
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_HUMAN
AccessioniPrimary (citable) accession number: Q9Y283
Secondary accession number(s): A2A2Y2
, Q2NKL0, Q5W0T6, Q8IVX8, Q9BRB9, Q9Y488, Q9Y498
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: July 5, 2005
Last modified: November 30, 2016
This is version 146 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: 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.