ID INVS_HUMAN Reviewed; 1065 AA.
AC Q9Y283; A2A2Y2; Q2NKL0; Q5W0T6; Q8IVX8; Q9BRB9; Q9Y488; Q9Y498;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 2.
DT 27-MAR-2024, entry version 191.
DE RecName: Full=Inversin;
DE AltName: Full=Inversion of embryo turning homolog;
DE AltName: Full=Nephrocystin-2;
GN Name=INVS; Synonyms=INV, NPHP2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=11935322; DOI=10.1007/s00439-001-0655-5;
RA Schoen P., Tsuchiya K., Lenoir D., Mochizuki T., Guichard C., Takai S.,
RA Maiti A.K., Nihei H., Weil J., Yokoyama T., Bouvagnet P.;
RT "Identification, genomic organization, chromosomal mapping and mutation
RT analysis of the human INV gene, the ortholog of a murine gene implicated in
RT left-right axis development and biliary atresia.";
RL Hum. Genet. 110:157-165(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2).
RX PubMed=11941489; DOI=10.1007/s00439-002-0696-4;
RA Morgan D., Goodship J., Essner J.J., Vogan K.J., Turnpenny L., Yost H.J.,
RA Tabin C.J., Strachan T.;
RT "The left-right determinant inversin has highly conserved ankyrin repeat
RT and IQ domains and interacts with calmodulin.";
RL Hum. Genet. 110:377-384(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Lymph, and Muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH NPHP1, AND
RP VARIANTS NPHP2 ARG-482 AND SER-493.
RX PubMed=12872123; DOI=10.1038/ng1217;
RA Otto E.A., Schermer B., Obara T., O'Toole J.F., Hiller K.S., Mueller A.M.,
RA Ruf R.G., Hoefele J., Beekmann F., Landau D., Foreman J.W., Goodship J.A.,
RA Strachan T., Kispert A., Wolf M.T., Gagnadoux M.F., Nivet H., Antignac C.,
RA Walz G., Drummond I.A., Benzing T., Hildebrandt F.;
RT "Mutations in INVS encoding inversin cause nephronophthisis type 2, linking
RT renal cystic disease to the function of primary cilia and left-right axis
RT determination.";
RL Nat. Genet. 34:413-420(2003).
RN [7]
RP FUNCTION, AND INTERACTION WITH DVL1; PRICKLE AND VANGL.
RX PubMed=15852005; DOI=10.1038/ng1552;
RA Simons M., Gloy J., Ganner A., Bullerkotte A., Bashkurov M., Kroenig C.,
RA Schermer B., Benzing T., Cabello O.A., Jenny A., Mlodzik M., Polok B.,
RA Driever W., Obara T., Walz G.;
RT "Inversin, the gene product mutated in nephronophthisis type II, functions
RT as a molecular switch between Wnt signaling pathways.";
RL Nat. Genet. 37:537-543(2005).
RN [8]
RP FUNCTION, AND INTERACTION WITH NPHP3.
RX PubMed=18371931; DOI=10.1016/j.ajhg.2008.02.017;
RA Bergmann C., Fliegauf M., Bruechle N.O., Frank V., Olbrich H.,
RA Kirschner J., Schermer B., Schmedding I., Kispert A., Kraenzlin B.,
RA Nuernberg G., Becker C., Grimm T., Girschick G., Lynch S.A., Kelehan P.,
RA Senderek J., Neuhaus T.J., Stallmach T., Zentgraf H., Nuernberg P.,
RA Gretz N., Lo C., Lienkamp S., Schaefer T., Walz G., Benzing T., Zerres K.,
RA Omran H.;
RT "Loss of nephrocystin-3 function can cause embryonic lethality, Meckel-
RT Gruber-like syndrome, situs inversus, and renal-hepatic-pancreatic
RT dysplasia.";
RL Am. J. Hum. Genet. 82:959-970(2008).
RN [9]
RP INTERACTION WITH NPHP1 AND IQCB1.
RX PubMed=21565611; DOI=10.1016/j.cell.2011.04.019;
RA Sang L., Miller J.J., Corbit K.C., Giles R.H., Brauer M.J., Otto E.A.,
RA Baye L.M., Wen X., Scales S.J., Kwong M., Huntzicker E.G., Sfakianos M.K.,
RA Sandoval W., Bazan J.F., Kulkarni P., Garcia-Gonzalo F.R., Seol A.D.,
RA O'Toole J.F., Held S., Reutter H.M., Lane W.S., Rafiq M.A., Noor A.,
RA Ansar M., Devi A.R., Sheffield V.C., Slusarski D.C., Vincent J.B.,
RA Doherty D.A., Hildebrandt F., Reiter J.F., Jackson P.K.;
RT "Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes
RT and pathways.";
RL Cell 145:513-528(2011).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-661, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [11]
RP INTERACTION WITH ANKS6; NEK8 AND NPHP3, AND HYDROXYLATION AT ASN-75.
RX PubMed=23793029; DOI=10.1038/ng.2681;
RA Hoff S., Halbritter J., Epting D., Frank V., Nguyen T.M., van Reeuwijk J.,
RA Boehlke C., Schell C., Yasunaga T., Helmstadter M., Mergen M., Filhol E.,
RA Boldt K., Horn N., Ueffing M., Otto E.A., Eisenberger T., Elting M.W.,
RA van Wijk J.A., Bockenhauer D., Sebire N.J., Rittig S., Vyberg M., Ring T.,
RA Pohl M., Pape L., Neuhaus T.J., Elshakhs N.A., Koon S.J., Harris P.C.,
RA Grahammer F., Huber T.B., Kuehn E.W., Kramer-Zucker A., Bolz H.J.,
RA Roepman R., Saunier S., Walz G., Hildebrandt F., Bergmann C.,
RA Lienkamp S.S.;
RT "ANKS6 is a central component of a nephronophthisis module linking NEK8 to
RT INVS and NPHP3.";
RL Nat. Genet. 45:951-956(2013).
CC -!- FUNCTION: Required for normal renal development and establishment of
CC left-right axis. Probably acts as a molecular switch between different
CC Wnt signaling pathways. Inhibits the canonical Wnt pathway by targeting
CC cytoplasmic disheveled (DVL1) for degradation by the ubiquitin-
CC proteasome. This suggests that it is required in renal development to
CC oppose the repression of terminal differentiation of tubular epithelial
CC cells by Wnt signaling. Involved in the organization of apical
CC junctions in kidney cells together with NPHP1, NPHP4 and RPGRIP1L/NPHP8
CC (By similarity). Does not seem to be strictly required for ciliogenesis
CC (By similarity). {ECO:0000250, ECO:0000269|PubMed:15852005,
CC ECO:0000269|PubMed:18371931}.
CC -!- SUBUNIT: Binds calmodulin via its IQ domains. Interacts with APC2.
CC Interacts with alpha-, beta-, and gamma-catenin. Interacts with N-
CC cadherin (CDH2). Interacts with microtubules (By similarity). Interacts
CC with NPHP1. Interacts with DVL1, PRICKLE (PRICKLE1 or PRICKLE2) and
CC Strabismus (VANGL1 or VANGL2). Interacts with IQCB1; the interaction
CC likely requires additional interactors. Component of a complex
CC containing at least ANKS6, INVS, NEK8 and NPHP3. ANKS6 may organize
CC complex assembly by linking INVS and NPHP3 to NEK8 and INVS may target
CC the complex to the proximal ciliary axoneme. {ECO:0000250,
CC ECO:0000269|PubMed:12872123, ECO:0000269|PubMed:15852005,
CC ECO:0000269|PubMed:18371931, ECO:0000269|PubMed:21565611,
CC ECO:0000269|PubMed:23793029}.
CC -!- INTERACTION:
CC Q9Y283; Q9BPU9: B9D2; NbExp=4; IntAct=EBI-751472, EBI-6958971;
CC Q9Y283; Q9Y265: RUVBL1; NbExp=2; IntAct=EBI-751472, EBI-353675;
CC Q9Y283-3; Q92876: KLK6; NbExp=3; IntAct=EBI-11944909, EBI-2432309;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cytoplasm, cytoskeleton
CC {ECO:0000250}. Cytoplasm, cytoskeleton, spindle {ECO:0000250}. Membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Nucleus
CC {ECO:0000250}. Cell projection, cilium {ECO:0000269|PubMed:12872123}.
CC Note=Associates with several components of the cytoskeleton including
CC ciliary, random and polarized microtubules. During mitosis, it is
CC recruited to mitotic spindle. Frequently membrane-associated, membrane
CC localization is dependent upon cell-cell contacts and is redistributed
CC when cell adhesion is disrupted after incubation of the cell monolayer
CC with low-calcium/EGTA medium.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9Y283-1; Sequence=Displayed;
CC Name=2; Synonyms=S2;
CC IsoId=Q9Y283-2; Sequence=VSP_014497;
CC Name=3;
CC IsoId=Q9Y283-3; Sequence=VSP_014495, VSP_014496;
CC -!- TISSUE SPECIFICITY: Widely expressed. Strongly expressed in the primary
CC cilia of renal tubular cells. {ECO:0000269|PubMed:11935322,
CC ECO:0000269|PubMed:12872123}.
CC -!- DOMAIN: The D-box 1 (destruction box 1) mediates the interaction with
CC APC2, and may act as a recognition signal for degradation via the
CC ubiquitin-proteasome pathway. {ECO:0000250}.
CC -!- PTM: May be ubiquitinated via its interaction with APC2. {ECO:0000250}.
CC -!- PTM: Hydroxylated at Asn-75, most probably by HIF1AN.
CC {ECO:0000269|PubMed:23793029}.
CC -!- DISEASE: Nephronophthisis 2 (NPHP2) [MIM:602088]: An autosomal
CC recessive disorder resulting in end-stage renal disease. It is
CC characterized by early onset and rapid progression. Phenotypic
CC manifestations include enlarged kidneys, chronic tubulo-interstitial
CC nephritis, anemia, hyperkalemic metabolic acidosis. Some patients also
CC display situs inversus. Pathologically, it differs from later-onset
CC nephronophthisis by the absence of medullary cysts and thickened
CC tubular basement membranes, and by the presence of cortical microcysts.
CC {ECO:0000269|PubMed:12872123}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD02131.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH41665.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
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DR EMBL; AF039217; AAD02131.2; ALT_INIT; mRNA.
DR EMBL; AF084367; AAC79436.1; -; mRNA.
DR EMBL; AF084382; AAC79456.1; -; Genomic_DNA.
DR EMBL; AF084373; AAC79456.1; JOINED; Genomic_DNA.
DR EMBL; AF084374; AAC79456.1; JOINED; Genomic_DNA.
DR EMBL; AF084375; AAC79456.1; JOINED; Genomic_DNA.
DR EMBL; AF084377; AAC79456.1; JOINED; Genomic_DNA.
DR EMBL; AF084379; AAC79456.1; JOINED; Genomic_DNA.
DR EMBL; AF084381; AAC79456.1; JOINED; Genomic_DNA.
DR EMBL; AF084371; AAC79456.1; JOINED; Genomic_DNA.
DR EMBL; AF084369; AAC79456.1; JOINED; Genomic_DNA.
DR EMBL; AF084368; AAC79456.1; JOINED; Genomic_DNA.
DR EMBL; AF084370; AAC79456.1; JOINED; Genomic_DNA.
DR EMBL; AF084372; AAC79456.1; JOINED; Genomic_DNA.
DR EMBL; AF084380; AAC79456.1; JOINED; Genomic_DNA.
DR EMBL; AF084378; AAC79456.1; JOINED; Genomic_DNA.
DR EMBL; AF084376; AAC79456.1; JOINED; Genomic_DNA.
DR EMBL; AF084382; AAC79457.1; -; Genomic_DNA.
DR EMBL; AF084368; AAC79457.1; JOINED; Genomic_DNA.
DR EMBL; AF084369; AAC79457.1; JOINED; Genomic_DNA.
DR EMBL; AF084370; AAC79457.1; JOINED; Genomic_DNA.
DR EMBL; AF084371; AAC79457.1; JOINED; Genomic_DNA.
DR EMBL; AF084372; AAC79457.1; JOINED; Genomic_DNA.
DR EMBL; AF084373; AAC79457.1; JOINED; Genomic_DNA.
DR EMBL; AF084374; AAC79457.1; JOINED; Genomic_DNA.
DR EMBL; AF084375; AAC79457.1; JOINED; Genomic_DNA.
DR EMBL; AF084376; AAC79457.1; JOINED; Genomic_DNA.
DR EMBL; AF084377; AAC79457.1; JOINED; Genomic_DNA.
DR EMBL; AF084378; AAC79457.1; JOINED; Genomic_DNA.
DR EMBL; AF084379; AAC79457.1; JOINED; Genomic_DNA.
DR EMBL; AF084380; AAC79457.1; JOINED; Genomic_DNA.
DR EMBL; AF084381; AAC79457.1; JOINED; Genomic_DNA.
DR EMBL; AL137072; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL445214; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL356798; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471105; EAW58926.1; -; Genomic_DNA.
DR EMBL; BC006370; AAH06370.1; -; mRNA.
DR EMBL; BC041665; AAH41665.1; ALT_SEQ; mRNA.
DR EMBL; BC111761; AAI11762.1; -; mRNA.
DR CCDS; CCDS6746.1; -. [Q9Y283-1]
DR RefSeq; NP_055240.2; NM_014425.4. [Q9Y283-1]
DR AlphaFoldDB; Q9Y283; -.
DR SMR; Q9Y283; -.
DR BioGRID; 118021; 17.
DR CORUM; Q9Y283; -.
DR IntAct; Q9Y283; 15.
DR MINT; Q9Y283; -.
DR STRING; 9606.ENSP00000262457; -.
DR GlyGen; Q9Y283; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q9Y283; -.
DR PhosphoSitePlus; Q9Y283; -.
DR BioMuta; INVS; -.
DR DMDM; 68565551; -.
DR EPD; Q9Y283; -.
DR jPOST; Q9Y283; -.
DR MassIVE; Q9Y283; -.
DR MaxQB; Q9Y283; -.
DR PaxDb; 9606-ENSP00000262457; -.
DR PeptideAtlas; Q9Y283; -.
DR ProteomicsDB; 85690; -. [Q9Y283-1]
DR ProteomicsDB; 85691; -. [Q9Y283-2]
DR Pumba; Q9Y283; -.
DR Antibodypedia; 29080; 128 antibodies from 19 providers.
DR DNASU; 27130; -.
DR Ensembl; ENST00000262456.6; ENSP00000262456.2; ENSG00000119509.13. [Q9Y283-2]
DR Ensembl; ENST00000262457.7; ENSP00000262457.2; ENSG00000119509.13. [Q9Y283-1]
DR Ensembl; ENST00000374921.3; ENSP00000364056.3; ENSG00000119509.13. [Q9Y283-3]
DR GeneID; 27130; -.
DR KEGG; hsa:27130; -.
DR MANE-Select; ENST00000262457.7; ENSP00000262457.2; NM_014425.5; NP_055240.2.
DR UCSC; uc004bao.3; human. [Q9Y283-1]
DR AGR; HGNC:17870; -.
DR CTD; 27130; -.
DR DisGeNET; 27130; -.
DR GeneCards; INVS; -.
DR GeneReviews; INVS; -.
DR HGNC; HGNC:17870; INVS.
DR HPA; ENSG00000119509; Low tissue specificity.
DR MalaCards; INVS; -.
DR MIM; 243305; gene.
DR MIM; 602088; phenotype.
DR neXtProt; NX_Q9Y283; -.
DR OpenTargets; ENSG00000119509; -.
DR Orphanet; 93591; Infantile nephronophthisis.
DR Orphanet; 3156; Senior-Loken syndrome.
DR PharmGKB; PA38472; -.
DR VEuPathDB; HostDB:ENSG00000119509; -.
DR eggNOG; KOG0504; Eukaryota.
DR GeneTree; ENSGT00940000157688; -.
DR HOGENOM; CLU_010082_0_0_1; -.
DR InParanoid; Q9Y283; -.
DR OMA; DGHWKPS; -.
DR OrthoDB; 5474520at2759; -.
DR PhylomeDB; Q9Y283; -.
DR TreeFam; TF312824; -.
DR PathwayCommons; Q9Y283; -.
DR SignaLink; Q9Y283; -.
DR SIGNOR; Q9Y283; -.
DR BioGRID-ORCS; 27130; 13 hits in 1161 CRISPR screens.
DR ChiTaRS; INVS; human.
DR GeneWiki; INVS; -.
DR GenomeRNAi; 27130; -.
DR Pharos; Q9Y283; Tbio.
DR PRO; PR:Q9Y283; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q9Y283; Protein.
DR Bgee; ENSG00000119509; Expressed in calcaneal tendon and 137 other cell types or tissues.
DR ExpressionAtlas; Q9Y283; baseline and differential.
DR Genevisible; Q9Y283; HS.
DR GO; GO:0097543; C:ciliary inversin compartment; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:1904108; P:protein localization to ciliary inversin compartment; IBA:GO_Central.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 4.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR000048; IQ_motif_EF-hand-BS.
DR PANTHER; PTHR24178:SF2; INVERSIN; 1.
DR PANTHER; PTHR24178; MOLTING PROTEIN MLT-4; 1.
DR Pfam; PF00023; Ank; 3.
DR Pfam; PF12796; Ank_2; 4.
DR Pfam; PF00612; IQ; 2.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 15.
DR SMART; SM00015; IQ; 2.
DR SUPFAM; SSF48403; Ankyrin repeat; 2.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 11.
DR PROSITE; PS50096; IQ; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; ANK repeat; Calmodulin-binding; Cell projection;
KW Ciliopathy; Cilium; Cytoplasm; Cytoskeleton; Developmental protein;
KW Disease variant; Hydroxylation; Membrane; Microtubule; Nephronophthisis;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Ubl conjugation;
KW Wnt signaling pathway.
FT CHAIN 1..1065
FT /note="Inversin"
FT /id="PRO_0000067016"
FT REPEAT 13..42
FT /note="ANK 1"
FT REPEAT 47..76
FT /note="ANK 2"
FT REPEAT 80..110
FT /note="ANK 3"
FT REPEAT 113..144
FT /note="ANK 4"
FT REPEAT 148..177
FT /note="ANK 5"
FT REPEAT 181..213
FT /note="ANK 6"
FT REPEAT 220..250
FT /note="ANK 7"
FT REPEAT 254..283
FT /note="ANK 8"
FT REPEAT 288..317
FT /note="ANK 9"
FT REPEAT 321..350
FT /note="ANK 10"
FT REPEAT 356..385
FT /note="ANK 11"
FT REPEAT 389..418
FT /note="ANK 12"
FT REPEAT 422..451
FT /note="ANK 13"
FT REPEAT 455..484
FT /note="ANK 14"
FT REPEAT 488..517
FT /note="ANK 15"
FT REPEAT 523..553
FT /note="ANK 16"
FT DOMAIN 555..584
FT /note="IQ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT DOMAIN 916..945
FT /note="IQ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT REGION 589..833
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 847..886
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 976..999
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 490..498
FT /note="D-box 1"
FT MOTIF 909..917
FT /note="D-box 2"
FT COMPBIAS 589..614
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 623..644
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 671..687
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 719..739
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 752..799
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 978..999
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 75
FT /note="3-hydroxyasparagine"
FT /evidence="ECO:0000269|PubMed:23793029"
FT MOD_RES 661
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 92..101
FT /note="GNYRFMKLLL -> ALRTISTGRI (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_014495"
FT VAR_SEQ 102..1065
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_014496"
FT VAR_SEQ 727..896
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11941489"
FT /id="VSP_014497"
FT VARIANT 242
FT /note="S -> L (in dbSNP:rs2491097)"
FT /id="VAR_044119"
FT VARIANT 482
FT /note="P -> R (in NPHP2)"
FT /evidence="ECO:0000269|PubMed:12872123"
FT /id="VAR_022822"
FT VARIANT 493
FT /note="L -> S (in NPHP2; impairs ability to target DVL1 for
FT degradation; dbSNP:rs121964995)"
FT /evidence="ECO:0000269|PubMed:12872123"
FT /id="VAR_022823"
FT VARIANT 888
FT /note="S -> R (in dbSNP:rs1052867)"
FT /id="VAR_044120"
FT CONFLICT 487
FT /note="K -> Q (in Ref. 5; AAI11762)"
FT /evidence="ECO:0000305"
FT CONFLICT 764
FT /note="A -> G (in Ref. 2; AAC79436/AAC79456)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1065 AA; 117826 MW; DACDF33C1B8573AC CRC64;
MNKSENLLFA GSSLASQVHA AAVNGDKGAL QRLIVGNSAL KDKEDQFGRT PLMYCVLADR
LDCADALLKA GADVNKTDHS QRTALHLAAQ KGNYRFMKLL LTRRANWMQK DLEEMTPLHL
TTRHRSPKCL ALLLKFMAPG EVDTQDKNKQ TALHWSAYYN NPEHVKLLIK HDSNIGIPDV
EGKIPLHWAA NHKDPSAVHT VRCILDAAPT ESLLNWQDYE GRTPLHFAVA DGNVTVVDVL
TSYESCNITS YDNLFRTPLH WAALLGHAQI VHLLLERNKS GTIPSDSQGA TPLHYAAQSN
FAETVKVFLK HPSVKDDSDL EGRTSFMWAA GKGSDDVLRT MLSLKSDIDI NMADKYGGTA
LHAAALSGHV STVKLLLENN AQVDATDVMK HTPLFRACEM GHKDVIQTLI KGGARVDLVD
QDGHSLLHWA ALGGNADVCQ ILIENKINPN VQDYAGRTPL QCAAYGGYIN CMAVLMENNA
DPNIQDKEGR TALHWSCNNG YLDAIKLLLD FAAFPNQMEN NEERYTPLDY ALLGERHEVI
QFMLEHGALS IAAIQDIAAF KIQAVYKGYK VRKAFRDRKN LLMKHEQLRK DAAAKKREEE
NKRKEAEQQK GRRSPDSCRP QALPCLPSTQ DVPSRQSRAP SKQPPAGNVA QGPEPRDSRG
SPGGSLGGAL QKEQHVSSDL QGTNSRRPNE TAREHSKGQS ACVHFRPNEG SDGSRHPGVP
SVEKSRGETA GDERCAKGKG FVKQPSCIRV AGPDEKGEDS RRAAASLPPH DSHWKPSRRH
DTEPKAKCAP QKRRTQELRG GRCSPAGSSR PGSARGEAVH AGQNPPHHRT PRNKVTQAKL
TGGLYSHLPQ STEELRSGAR RLETSTLSED FQVSKETDPA PGPLSGQSVN IDLLPVELRL
QIIQRERRRK ELFRKKNKAA AVIQRAWRSY QLRKHLSHLR HMKQLGAGDV DRWRQESTAL
LLQVWRKELE LKFPQTTAVS KAPKSPSKGT SGTKSTKHSV LKQIYGCSHE GKIHHPTRSV
KASSVLRLNS VSNLQCIHLL ENSGRSKNFS YNLQSATQPK NKTKP
//
