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Protein

Inversin

Gene

INVS

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

GO - Biological processi

Keywordsi

Molecular functionCalmodulin-binding, Developmental protein
Biological processWnt signaling pathway

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000119509.12
HGNCiHGNC:17870 INVS
MIMi243305 gene
neXtProtiNX_Q9Y283

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

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 dbSNP:rs121964995Ensembl.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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi118021, 11 interactors
CORUMiQ9Y283
IntActiQ9Y283, 11 interactors
MINTiQ9Y283
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

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiKOG0504 Eukaryota
COG0666 LUCA
GeneTreeiENSGT00910000143997
HOVERGENiHBG083788
InParanoidiQ9Y283
KOiK19626
OMAiNFSYNLQ
OrthoDBiEOG091G01EB
PhylomeDBiQ9Y283
TreeFamiTF312824

Family and domain databases

CDDicd00204 ANK, 4 hits
Gene3Di1.25.40.20, 4 hits
InterProiView protein in InterPro
IPR002110 Ankyrin_rpt
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
IPR000048 IQ_motif_EF-hand-BS
PfamiView protein in Pfam
PF00023 Ank, 1 hit
PF12796 Ank_2, 6 hits
PF00612 IQ, 2 hits
PRINTSiPR01415 ANKYRIN
SMARTiView protein in SMART
SM00248 ANK, 15 hits
SM00015 IQ, 2 hits
SUPFAMiSSF48403 SSF48403, 2 hits
PROSITEiView protein in PROSITE
PS50297 ANK_REP_REGION, 1 hit
PS50088 ANK_REPEAT, 11 hits
PS50096 IQ, 2 hits

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 dbSNP:rs2491097Ensembl.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 dbSNP:rs121964995Ensembl.1
Natural variantiVAR_044120888S → R. Corresponds to variant dbSNP:rs1052867Ensembl.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 Genomic DNA No translation available.
AL445214 Genomic DNA No translation available.
AL356798 Genomic DNA No translation available.
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

Similar proteinsi

Entry informationi

Entry nameiINVS_HUMAN
AccessioniPrimary (citable) accession number: Q9Y283
Secondary accession number(s): A2A2Y2
, Q2NKL0, Q5W0T6, Q8IVX8, Q9BRB9, Q9Y488, Q9Y498
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: July 5, 2005
Last modified: March 28, 2018
This is version 156 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
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Main funding by: National Institutes of Health