INVS_CANLF
ID INVS_CANLF Reviewed; 1081 AA.
AC Q6JAN1;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Inversin;
DE AltName: Full=Inversion of embryo turning protein;
DE AltName: Full=Nephrocystin-2;
GN Name=INVS; Synonyms=INV, NPHP2;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX PubMed=15533716; DOI=10.1016/j.ygeno.2004.08.002;
RA Ward H.H., Wang J., Phillips C.;
RT "Analysis of multiple Invs transcripts in mouse and MDCK cells.";
RL Genomics 84:991-1001(2004).
RN [2]
RP DEVELOPMENTAL STAGE.
RX PubMed=12471060; DOI=10.1093/hmg/11.26.3345;
RA Morgan D., Eley L., Sayer J., Strachan T., Yates L.M., Craighead A.S.,
RA Goodship J.A.;
RT "Expression analyses and interaction with the anaphase promoting complex
RT protein Apc2 suggest a role for inversin in primary cilia and involvement
RT in the cell cycle.";
RL Hum. Mol. Genet. 11:3345-3350(2002).
RN [3]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH MICROTUBULES.
RX PubMed=15213257; DOI=10.1097/01.asn.0000128291.30249.d0;
RA Nuernberger J., Kribben A., Opazo Saez A., Heusch G., Philipp T.,
RA Phillips C.L.;
RT "The Invs gene encodes a microtubule-associated protein.";
RL J. Am. Soc. Nephrol. 15:1700-1710(2004).
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 (By similarity). Involved in the organization of
CC apical junctions in kidney cells together with NPHP1, NPHP4 and
CC RPGRIP1L/NPHP8 (By similarity). Does not seem to be strictly required
CC for ciliogenesis (By similarity). {ECO:0000250}.
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 NPHP1. Interacts with DVL1, PRICKLE
CC (PRICKLE1 or PRICKLE2) and Strabismus (VANGL1 or VANGL2). Component of
CC a complex containing at least ANKS6, INVS, NEK8 and NPHP3. ANKS6 may
CC organize complex assembly by linking INVS and NPHP3 to NEK8 and INVS
CC may target the complex to the proximal ciliary axoneme. Interacts with
CC IQCB1; the interaction likely requires additional interactors (By
CC similarity). Interacts with microtubules. {ECO:0000250,
CC ECO:0000269|PubMed:15213257}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:15213257}. Membrane {ECO:0000269|PubMed:15213257};
CC Peripheral membrane protein {ECO:0000269|PubMed:15213257}. Cytoplasm,
CC cytoskeleton, spindle {ECO:0000269|PubMed:15213257}. Nucleus
CC {ECO:0000269|PubMed:15213257}. Note=Frequently membrane-associated.
CC Membrane localization is dependent upon cell-cell contacts and is
CC redistributed when cell adhesion is disrupted after incubation of the
CC cell monolayer with low-calcium/EGTA medium (By similarity). Associates
CC with several components of the cytoskeleton including ciliary, random
CC and polarized microtubules. During mitosis, it is recruited to mitotic
CC spindle. Also nuclear. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6JAN1-1; Sequence=Displayed;
CC Name=2; Synonyms=Exon 12 skipped;
CC IsoId=Q6JAN1-2; Sequence=VSP_014494;
CC -!- DEVELOPMENTAL STAGE: Nuclear prior to nuclear envelope breakdown.
CC Localizes at the centrosomes in early prophase but in metaphase and
CC anaphase, it localizes to the spindle poles In cells at late telophase
CC undergoing cytokinesis it is detected at the midbody, a region of
CC microtubule overlap (at protein level). {ECO:0000269|PubMed:12471060}.
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. {ECO:0000250}.
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DR EMBL; AY539827; AAT07450.1; -; mRNA.
DR RefSeq; NP_001003361.1; NM_001003361.1. [Q6JAN1-1]
DR RefSeq; XP_005626448.1; XM_005626391.2. [Q6JAN1-1]
DR RefSeq; XP_005626449.1; XM_005626392.2. [Q6JAN1-1]
DR RefSeq; XP_005626450.1; XM_005626393.2. [Q6JAN1-1]
DR AlphaFoldDB; Q6JAN1; -.
DR SMR; Q6JAN1; -.
DR STRING; 9615.ENSCAFP00000050118; -.
DR PaxDb; Q6JAN1; -.
DR Ensembl; ENSCAFT00040038103; ENSCAFP00040033215; ENSCAFG00040020482. [Q6JAN1-1]
DR Ensembl; ENSCAFT00040038398; ENSCAFP00040033486; ENSCAFG00040020482. [Q6JAN1-2]
DR Ensembl; ENSCAFT00845014700; ENSCAFP00845011388; ENSCAFG00845008291. [Q6JAN1-1]
DR Ensembl; ENSCAFT00845014964; ENSCAFP00845011603; ENSCAFG00845008291. [Q6JAN1-2]
DR GeneID; 442950; -.
DR KEGG; cfa:442950; -.
DR CTD; 27130; -.
DR VEuPathDB; HostDB:ENSCAFG00845008291; -.
DR eggNOG; KOG0504; Eukaryota.
DR GeneTree; ENSGT00940000157688; -.
DR HOGENOM; CLU_010082_0_0_1; -.
DR InParanoid; Q6JAN1; -.
DR OMA; GKVHHPT; -.
DR OrthoDB; 316949at2759; -.
DR TreeFam; TF312824; -.
DR Proteomes; UP000002254; Chromosome 11.
DR Bgee; ENSCAFG00000002552; Expressed in metanephros cortex and 51 other tissues.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
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; ISS:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 1.25.40.20; -; 5.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR000048; IQ_motif_EF-hand-BS.
DR Pfam; PF00023; Ank; 2.
DR Pfam; PF12796; Ank_2; 5.
DR Pfam; PF00612; IQ; 2.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 15.
DR SMART; SM00015; IQ; 2.
DR SUPFAM; SSF48403; SSF48403; 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; Cytoplasm;
KW Cytoskeleton; Developmental protein; Hydroxylation; Membrane; Microtubule;
KW Nucleus; Reference proteome; Repeat; Ubl conjugation;
KW Wnt signaling pathway.
FT CHAIN 1..1081
FT /note="Inversin"
FT /id="PRO_0000067015"
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 917..946
FT /note="IQ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT REPEAT 1022..1050
FT /note="ANK 17"
FT REGION 589..889
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1051..1081
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 490..498
FT /note="D-box 1"
FT MOTIF 910..918
FT /note="D-box 2"
FT COMPBIAS 589..612
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 623..648
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 717..740
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 773..801
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 851..874
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 75
FT /note="3-hydroxyasparagine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 525..595
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15533716"
FT /id="VSP_014494"
SQ SEQUENCE 1081 AA; 119540 MW; FB43DCCBF77B5244 CRC64;
MNRSENLFFS GSSLASQVHA AAINGDKGAL HRLIIGNSAL KDKEDQFGRT PLMYCVLADR
LDCADALLKA GADVNKTDHS QRTALHLAAQ KGNYRFMKLL LTRRANWMQK DLEEMTPLHL
ATRHKSPKCL 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
NKRREAEQQK GRLSPDSCRP QALPCLPNTQ TDSHKQSRAP SKQPPSSEAA QDPDKRACRG
GPGRVSPSRA PQKEQHLSPD VQGTVPRKPN ESPREQCKGR SACVHFSPSE GSDGKRHPGV
SSVEKSRSET GGEQRCDKGK GFLKQPSCLR VAGPGDEGED PGWAAASLPQ QDGHRKPSRR
QDTASKAKCT SQKRRVQELR GGRHSPAGSS RPGSAKGEVV HAGPNALQHR TPRNKTTQDK
LAGGIYSDLP QNTEVLRSGV RKSGTSTLSE DAQVSKETDP APGPLSGQSV NIDLLPVELR
LQIIQKERSR KELFRKKNKA AAVIQRAWRS YQLRKHLSHL LHMKELGARD VDRWNRECLA
LLLQVWRKDL ELTPPKTTAV TRTTKSLSKG SSGAKSTRHS VLKQIYGCSQ EGKVPHSTRS
SRTHSVLHLN SVSNLQCIHL LENSGRSKNF SYNLQSATPP KTKTKLRPSL EEECVRGSWN
S
