KANK2_DANRE
ID KANK2_DANRE Reviewed; 1085 AA.
AC X1WE18;
DT 07-NOV-2018, integrated into UniProtKB/Swiss-Prot.
DT 14-MAY-2014, sequence version 1.
DT 03-AUG-2022, entry version 51.
DE RecName: Full=KN motif and ankyrin repeat domain-containing protein 2;
GN Name=kank2;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25961457; DOI=10.1172/jci79504;
RA Gee H.Y., Zhang F., Ashraf S., Kohl S., Sadowski C.E., Vega-Warner V.,
RA Zhou W., Lovric S., Fang H., Nettleton M., Zhu J.Y., Hoefele J.,
RA Weber L.T., Podracka L., Boor A., Fehrenbach H., Innis J.W., Washburn J.,
RA Levy S., Lifton R.P., Otto E.A., Han Z., Hildebrandt F.;
RT "KANK deficiency leads to podocyte dysfunction and nephrotic syndrome.";
RL J. Clin. Invest. 125:2375-2384(2015).
CC -!- FUNCTION: May be involved in different biological processes including
CC transcription and apoptosis by sequestering specific proteins outside
CC of the nucleus (By similarity). Involved in actin stress fibers
CC formation probably through its interaction with ARHGDIA and the
CC regulation of the Rho signaling pathway (By similarity). May thereby
CC play a role in cell adhesion and migration, regulating for instance
CC podocytes migration during development of the kidney (PubMed:25961457).
CC {ECO:0000250|UniProtKB:Q63ZY3, ECO:0000269|PubMed:25961457}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q63ZY3}.
CC Mitochondrion {ECO:0000250|UniProtKB:Q63ZY3}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown of the protein results in an
CC edematous phenotype and proteinuria (PubMed:25961457). Podocyte foot
CC process effacement and disorganization, rarefaction of slit membranes,
CC and disorganization of the glomerular basement membrane in glomeruli
CC which are characteritic of nephrosis are observed (PubMed:25961457).
CC {ECO:0000269|PubMed:25961457}.
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DR EMBL; CT583658; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CU464181; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001292549.1; NM_001305620.1.
DR RefSeq; XP_005164396.1; XM_005164339.3.
DR AlphaFoldDB; X1WE18; -.
DR SMR; X1WE18; -.
DR STRING; 7955.ENSDARP00000128469; -.
DR Ensembl; ENSDART00000154031; ENSDARP00000128469; ENSDARG00000018393.
DR Ensembl; ENSDART00000179903; ENSDARP00000146055; ENSDARG00000018393.
DR GeneID; 571549; -.
DR KEGG; dre:571549; -.
DR CTD; 25959; -.
DR ZFIN; ZDB-GENE-040724-121; kank2.
DR eggNOG; KOG0514; Eukaryota.
DR GeneTree; ENSGT00940000161012; -.
DR HOGENOM; CLU_004269_1_1_1; -.
DR OMA; HQRSLQF; -.
DR OrthoDB; 98668at2759; -.
DR PRO; PR:X1WE18; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 3.
DR Bgee; ENSDARG00000018393; Expressed in swim bladder and 20 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0032836; P:glomerular basement membrane development; IMP:ZFIN.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0033147; P:negative regulation of intracellular estrogen receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0070563; P:negative regulation of vitamin D receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0072015; P:podocyte development; IMP:ZFIN.
DR GO; GO:0035023; P:regulation of Rho protein signal transduction; ISS:UniProtKB.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR021939; KN_motif.
DR Pfam; PF13637; Ank_4; 1.
DR Pfam; PF13857; Ank_5; 1.
DR Pfam; PF12075; KN_motif; 1.
DR SMART; SM00248; ANK; 5.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 3.
PE 3: Inferred from homology;
KW ANK repeat; Apoptosis; Coiled coil; Cytoplasm; Methylation; Mitochondrion;
KW Phosphoprotein; Reference proteome; Repeat; Transcription;
KW Transcription regulation.
FT CHAIN 1..1085
FT /note="KN motif and ankyrin repeat domain-containing
FT protein 2"
FT /id="PRO_0000445622"
FT REPEAT 895..925
FT /note="ANK 1"
FT /evidence="ECO:0000255"
FT REPEAT 929..962
FT /note="ANK 2"
FT /evidence="ECO:0000255"
FT REPEAT 967..996
FT /note="ANK 3"
FT /evidence="ECO:0000255"
FT REPEAT 1000..1030
FT /note="ANK 4"
FT /evidence="ECO:0000255"
FT REPEAT 1034..1063
FT /note="ANK 5"
FT /evidence="ECO:0000255"
FT REGION 136..192
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 273..295
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 557..736
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 752..791
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 798..817
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1064..1085
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 196..216
FT /evidence="ECO:0000255"
FT COILED 356..383
FT /evidence="ECO:0000255"
FT COMPBIAS 148..192
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 279..295
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 611..696
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 703..736
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 1085 AA; 116153 MW; 002E572016B9A51E CRC64;
MTIMAQVLHM DSSFPGKINP PVPPSLHAKD QEAPYSVETP YGYRLDLDFL KYVNDIEKGN
TIKKVPVQRR PRYGSLPRGY GYTGSWWTST ESLCSNASMD SRHSSYSYCA PGFHTSQRPN
FSTARVEKTL MDARRKLEEE KDGRRFSNLG SMHSSMAGSN TSLSSAHSFN RAQGGGSYTP
MSSGLSTPVS PTPAHLQHVR EQMAVALRKI RELEEQVKTI PVLQVKISVL QEEKRQLSVQ
LKSQKFLGHT LGFNRSRPRG ELYIDIPEEE AGNGAGAANK ATGSLSPTTP GSLQDSGCEI
EETVIVAGAR PGAKREVRTV GVGPEAEERG YRQVGVGVRE QDLGLLPETE ALKTKVGLLE
VQLRKTMQEL QSAQQQVEAA QKERQTVCPQ VDHAVRATSL GWQDQQGQAG AGLHTVVSFT
KQPHQQRTVG IQVYTLEQPT VVGVGTLLRA QGCTHPAQLE ASHRRYGESP AAGDSPHEFP
IAISSKQVRE VLRSEVSKSV PVTNQATPME TKCNQVTAVC QRLKEGEINQ QPAEEAIQVD
PANPASPQSN LRSIMKRKAD GEPGSPYTKK NLQFLGVNGG YESTSSEESS SESSEDESDA
SEYHEATEKL PESATPQSLV SSCIPQLASE TPATQTAQHS TAQIPTNHTP AAQTTSQSHT
TDATTQQHVT QSPAAEADVQ HCVSQSSVTT TPPPEGDVQC VFQGCNPPST ATSLEQNSVQ
LSSATQQSKA TDSNVQPDLA QTDVSDFAAQ QTTTQTQFTS AKPQQEASQS KTADLTAQKG
ATHSTDGSAK QDIAISSTTK PAADTATPPT NKQTDSLELS GGLMSALHIL QKALSEPNAF
SHQDARTAYT SVLQEWLRVS CHKAADTAVV KAHMDAFASI SPQLLEFVIN MADGNGNTAL
HYTVSHSNFP VVKLLLDTGL CNADKQNKAG YTAIMLTALA AFSSDSDLQT VLQLLRTGDV
NAKASQAGQT ALMLAVSHGR GDMVKALLAC GAQVNLRDDD GSTALMCACE HGHVDIVRQL
LSVPGCDATL TDNDGSTALS IALEASQNDI AVLLYAHLNF AKPPSPVSPK SPILGSSPPS
SSELK
