KANK2_RAT
ID KANK2_RAT Reviewed; 847 AA.
AC D3ZD05;
DT 07-NOV-2018, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2015, sequence version 2.
DT 03-AUG-2022, entry version 74.
DE RecName: Full=KN motif and ankyrin repeat domain-containing protein 2;
GN Name=Kank2 {ECO:0000312|RGD:2320289};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [3]
RP INTERACTION WITH ARHGDIA, AND TISSUE SPECIFICITY.
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: Involved in transcription regulation by sequestering in the
CC cytoplasm nuclear receptor coactivators such as NCOA1, NCOA2 and NCOA3
CC (By similarity). Involved in regulation of caspase-independent
CC apoptosis by sequestering the proapoptotic factor AIFM1 in mitochondria
CC (By similarity). Pro-apoptotic stimuli can induce its proteasomal
CC degradation allowing the translocation of AIFM1 to the nucleus to
CC induce apoptosis (By similarity). Involved in the negative control of
CC vitamin D receptor signaling pathway (By similarity). Involved in actin
CC stress fibers formation 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 (By similarity).
CC Through the Rho signaling pathway may also regulate cell proliferation
CC (By similarity). {ECO:0000250|UniProtKB:Q63ZY3,
CC ECO:0000250|UniProtKB:Q8BX02}.
CC -!- SUBUNIT: Interacts (non-phosphorylated form) with NCOA1; NCOA2 AND
CC NCOA3 (By similarity). Interacts with AIFM1 (By similarity). Interacts
CC with ARHGDIA; the interaction is direct and may regulate the
CC interaction of ARHGDIA with RHOA, RAC1 and CDC42 (PubMed:25961457).
CC Interacts (via ANK repeats 1-5) with KIF21A (By similarity).
CC {ECO:0000250|UniProtKB:Q63ZY3, ECO:0000269|PubMed:25961457}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q63ZY3}.
CC Mitochondrion {ECO:0000250|UniProtKB:Q63ZY3}.
CC -!- TISSUE SPECIFICITY: Expressed by podocytes in kidney glomeruli (at
CC protein level). {ECO:0000269|PubMed:25961457}.
CC -!- PTM: Phosphorylated by casein kinase II upon estrogen stimulation (By
CC similarity). Phosphorylation induces the release by KANK2 of NCOA1 and
CC its translocation to the nucleus where NCOA1 can activate gene
CC transcription (By similarity). {ECO:0000250|UniProtKB:Q63ZY3}.
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DR EMBL; AC119556; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_006242651.1; XM_006242589.3.
DR RefSeq; XP_006242652.1; XM_006242590.3.
DR AlphaFoldDB; D3ZD05; -.
DR SMR; D3ZD05; -.
DR IntAct; D3ZD05; 2.
DR MINT; D3ZD05; -.
DR STRING; 10116.ENSRNOP00000014135; -.
DR jPOST; D3ZD05; -.
DR PeptideAtlas; D3ZD05; -.
DR Ensembl; ENSRNOT00000014135; ENSRNOP00000014135; ENSRNOG00000010643.
DR GeneID; 100361376; -.
DR CTD; 25959; -.
DR RGD; 2320289; Kank2.
DR OMA; HQRSLQF; -.
DR OrthoDB; 98668at2759; -.
DR PRO; PR:D3ZD05; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Bgee; ENSRNOG00000010643; Expressed in heart and 18 other tissues.
DR ExpressionAtlas; D3ZD05; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0072073; P:kidney epithelium development; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; ISO:RGD.
DR GO; GO:0033147; P:negative regulation of intracellular estrogen receptor signaling pathway; ISO:RGD.
DR GO; GO:0043069; P:negative regulation of programmed cell death; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0070563; P:negative regulation of vitamin D receptor signaling pathway; ISO:RGD.
DR GO; GO:0090521; P:podocyte cell migration; ISS:UniProtKB.
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; PF12796; Ank_2; 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; 2.
PE 1: Evidence at protein level;
KW ANK repeat; Apoptosis; Coiled coil; Cytoplasm; Methylation; Mitochondrion;
KW Phosphoprotein; Reference proteome; Repeat; Transcription;
KW Transcription regulation.
FT CHAIN 1..847
FT /note="KN motif and ankyrin repeat domain-containing
FT protein 2"
FT /id="PRO_0000445621"
FT REPEAT 610..647
FT /note="ANK 0; degenerate"
FT /evidence="ECO:0000250|UniProtKB:Q63ZY3"
FT REPEAT 662..692
FT /note="ANK 1"
FT /evidence="ECO:0000255"
FT REPEAT 696..729
FT /note="ANK 2"
FT /evidence="ECO:0000255"
FT REPEAT 734..763
FT /note="ANK 3"
FT /evidence="ECO:0000255"
FT REPEAT 767..797
FT /note="ANK 4"
FT /evidence="ECO:0000255"
FT REPEAT 801..831
FT /note="ANK 5"
FT /evidence="ECO:0000255"
FT REGION 1..72
FT /note="Interaction with AIFM1"
FT /evidence="ECO:0000250|UniProtKB:Q63ZY3"
FT REGION 1..32
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 161..182
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 414..473
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 502..581
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 665..831
FT /note="Interaction with NCOA1"
FT /evidence="ECO:0000250|UniProtKB:Q63ZY3"
FT COILED 187..207
FT /evidence="ECO:0000255"
FT COILED 284..311
FT /evidence="ECO:0000255"
FT COMPBIAS 421..440
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 513..527
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 19
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63ZY3"
FT MOD_RES 83
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BX02"
FT MOD_RES 86
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BX02"
FT MOD_RES 89
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BX02"
FT MOD_RES 92
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63ZY3"
FT MOD_RES 105
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q63ZY3"
FT MOD_RES 170
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8BX02"
FT MOD_RES 331
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q63ZY3"
FT MOD_RES 358
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63ZY3"
FT MOD_RES 536
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63ZY3"
SQ SEQUENCE 847 AA; 90884 MW; F2EA38E155AC5ECC CRC64;
MAQVLHVPAP FPGTPGQASS AAFPNKEPDP PYSVETPYGY RLDLDFLKYV DDIEKGHTLR
RVPVQRRPRL GSLPRGPGSW WTSTESLCSD ASGDSRHSAY SYCGRGFYPQ YGALETRSGT
NPRVERTLLD ARRRLEDQAA APSSGGLGSL TPSAAGSTSS LAGVGLLPPT PRSSGLSTPV
APSAGHLAHV REQMAGALRK LRQLEEQVKL IPVLQVKLSV LQEEKRQLTV QLKSQKFLGH
PSGTRSRSEL CLDLPEAPDD PAVLETRSVG TWVRERDLGI PDGEAALVAK VAVLETQLKK
ALQELRAAQT QQVDLQPQAW PPPDTQVRVD TVRVVEGPRE VEVAASTAAG APAQRAQSLE
PYGAGLKALA TSAENTLVFR SHEVVETMCP LPTASTSNMH TAKKISITER NCTGAARMAD
PPPSPAEPSP SSPYPAAEPE NPAPAAQDTT DRELTRPVAS QDSQAAEGAG GASLGVQSAL
KRKEVPADPD VHQRNLQFVG INGGYESSSE DSSTAENSEH ESTENEAPEP PVRVLSTAEG
PQLRPLGPAV GKTSQDERQL SQESQRVPEA KVAPGPDPEE EIRMDLSPDL ISACLALEKY
LENPNALTER ELKVAYTTVL QEWLRLACRS DAHPELVRRH LVTFRAMSAR LLDYVVNIAD
SNGNTALHYS VSHANFPVVR QLLDSGVCQV DKLNRAGYSP IMLTALATLK TQDDIDTILQ
LFRLGNVNAK ASQAGQTALM LAVSHGRVDV VKALLACEVD VNMQDEDGST ALMCACEHGH
KEITGLLLAV PSCDISLTDR DGSTALMVAL DAGQSEIASM LYSRMNIKCS FAPMSDYESP
ASSSAEE
