ID   INVSA_XENLA             Reviewed;        1007 AA.
AC   Q71S22; Q8UVC0;
DT   05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   03-AUG-2022, entry version 87.
DE   RecName: Full=Inversin-A;
GN   Name=invs-a; Synonyms=inv1, invs-1;
OS   Xenopus laevis (African clawed frog).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX   NCBI_TaxID=8355;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH CALMODULIN.
RA   Yasuhiko Y., Shiokawa K., Yokoyama T.;
RT   "The inv RNA randomizes left-right asymmetry in Xenopus embryos through
RT   binding to calmodulin.";
RL   Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-653.
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   FUNCTION.
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).
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 for degradation by the ubiquitin-proteasome.
CC       This suggests that it is required in renal development to oppose the
CC       repression of terminal differentiation of tubular epithelial cells by
CC       Wnt signaling (By similarity). Plays a central role in convergent
CC       extension movements in gastrulating embryos, a processus regulated by
CC       Wnt signaling. {ECO:0000250, ECO:0000269|PubMed:15852005}.
CC   -!- SUBUNIT: Interacts with apc2 (By similarity). Binds calmodulin.
CC       {ECO:0000250, ECO:0000269|Ref.1}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cytoplasm, cytoskeleton
CC       {ECO:0000250}. Note=Associates with the cytoskeleton. {ECO:0000250}.
CC   -!- DOMAIN: The D-box (destruction box) mediate the interaction with APC
CC       proteins, and may act as a recognition signal for degradation via the
CC       ubiquitin-proteasome pathway. {ECO:0000250}.
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DR   EMBL; AF321228; AAQ14847.1; -; mRNA.
DR   EMBL; AF465262; AAL69978.1; -; mRNA.
DR   RefSeq; NP_001079230.1; NM_001085761.1.
DR   AlphaFoldDB; Q71S22; -.
DR   SMR; Q71S22; -.
DR   GeneID; 378491; -.
DR   KEGG; xla:378491; -.
DR   CTD; 378491; -.
DR   Xenbase; XB-GENE-1221139; invs.S.
DR   OrthoDB; 316949at2759; -.
DR   Proteomes; UP000186698; Chromosome 8S.
DR   Bgee; 378491; Expressed in blastula and 17 other tissues.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR   GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR   GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR   Gene3D; 1.25.40.20; -; 4.
DR   InterPro; IPR002110; Ankyrin_rpt.
DR   InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR   InterPro; IPR000048; IQ_motif_EF-hand-BS.
DR   Pfam; PF12796; Ank_2; 5.
DR   Pfam; PF13637; Ank_4; 1.
DR   Pfam; PF00612; IQ; 2.
DR   SMART; SM00248; ANK; 16.
DR   SMART; SM00015; IQ; 2.
DR   SUPFAM; SSF48403; SSF48403; 2.
DR   PROSITE; PS50297; ANK_REP_REGION; 1.
DR   PROSITE; PS50088; ANK_REPEAT; 12.
DR   PROSITE; PS50096; IQ; 2.
PE   1: Evidence at protein level;
KW   ANK repeat; Calmodulin-binding; Cytoplasm; Cytoskeleton;
KW   Developmental protein; Reference proteome; Repeat; Wnt signaling pathway.
FT   CHAIN           1..1007
FT                   /note="Inversin-A"
FT                   /id="PRO_0000067020"
FT   REPEAT          9..39
FT                   /note="ANK 1"
FT   REPEAT          43..72
FT                   /note="ANK 2"
FT   REPEAT          76..105
FT                   /note="ANK 3"
FT   REPEAT          109..140
FT                   /note="ANK 4"
FT   REPEAT          144..173
FT                   /note="ANK 5"
FT   REPEAT          177..209
FT                   /note="ANK 6"
FT   REPEAT          216..246
FT                   /note="ANK 7"
FT   REPEAT          250..279
FT                   /note="ANK 8"
FT   REPEAT          284..313
FT                   /note="ANK 9"
FT   REPEAT          317..346
FT                   /note="ANK 10"
FT   REPEAT          352..381
FT                   /note="ANK 11"
FT   REPEAT          385..414
FT                   /note="ANK 12"
FT   REPEAT          418..447
FT                   /note="ANK 13"
FT   REPEAT          451..480
FT                   /note="ANK 14"
FT   REPEAT          484..513
FT                   /note="ANK 15"
FT   REPEAT          519..549
FT                   /note="ANK 16"
FT   DOMAIN          551..580
FT                   /note="IQ 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT   DOMAIN          971..1000
FT                   /note="IQ 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT   REGION          585..837
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          868..893
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           486..494
FT                   /note="D-box 1"
FT   MOTIF           964..972
FT                   /note="D-box 2"
FT   COMPBIAS        585..673
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        674..745
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        753..813
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        872..893
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CONFLICT        129
FT                   /note="I -> L (in Ref. 2; AAL69978)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1007 AA;  112558 MW;  AAA66B0A4E5A7588 CRC64;
     MSSPPQGSSL ASPVQAAAVT GDKTTLLKLI ASSPEVIDQE DQLGRTPLMY SVLGDRRSCA
     EALLKHGAQV NHPDRSGRTA LHLAAQTGNH RLLKLLLSRK ADCTHRDLRD ITAVHLSTRH
     QDTRCLALIL KYTPPGQVDA QDQRKQTALH WSAYYNRPRH VRLLVRHGSN IGIPDTEGKI
     PLHWAAGHKD PEAALTVRCL LEAAPTESLL NWQDYEGRTP LHLAVGDGNQ EVVRLLTSYR
     GCNVAPYDNL FRTPLHWAAL LGYTPIAHLL LETNNSPNIP SDSQGATPLH YAAQGNCPDT
     VRVLLSHISV RDEADLEGRT AFMWAAGKGS DEVVRTMLEL DPELEVNRTD KYGGTALHAA
     SLSGQITTVR ILLENRVQVD AVDVMKHTAL FRACEMGHRE VISTLIKGGA KVHLVDKDGR
     SPLHWAALGG NANVCQILIE NNINPDAQDY EGRTPLQCAA YGGYIGCMEV LMENKADPNI
     QDKNGRTALH WSCNNGYLDA VKLLLGYSAF PNQMENTEER YTPLDYALLG GHQEVIQFML
     EHGALSIAAI QDIAASKIQA VYKGHKVRRA FQERKNLLMK HEQLRKGAAA KKREGENRQK
     GKVGQTEGKQ KDENHVMRQD KSNEHIQNEV MREWYGEETG RAEDRKEEHQ EENQNIEPKQ
     LKHSKHMEQN SKSIAKNQKR AGHIQSSPIE HVHTNSIQTR MSPSRTSISH SSPLGNETPK
     NMYWDDNPTQ NNTQPRRTSR PQIESPNIIV HRIEDLVQKE SRRKSHREER KGSHRQRASS
     HHRLQASERE TAGSVIHGEV EFKKKETKKG RRTAAGTSKI RASGEAGRLS QSEKEFSSTG
     IQGRVDCITS PESCETPSRV CRERKMISAK SGQRPLTETQ SPEKACQGSS ALKPSLTSHT
     KQTAIASKCL DSTPSYIGFG EAIKPLTPMG ILREGSFSSK WQNIDIELIP LEARLQLVEK
     EKARKQLFQR KKHAATVIQK AWRTYCIRKS SRKTRHSHLR NNPRAMV