KANK2_MOUSE
ID KANK2_MOUSE Reviewed; 843 AA.
AC Q8BX02; Q8BLD5; Q91Z35;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=KN motif and ankyrin repeat domain-containing protein 2;
DE AltName: Full=Ankyrin repeat domain-containing protein 25;
GN Name=Kank2; Synonyms=Ankrd25;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Corpora quadrigemina;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 [3]
RP POSSIBLE FUNCTION.
RX PubMed=16024821; DOI=10.1101/gr.3889305;
RA Harada J.N., Bower K.E., Orth A.P., Callaway S., Nelson C.G., Laris C.,
RA Hogenesch J.B., Vogt P.K., Chanda S.K.;
RT "Identification of novel mammalian growth regulatory factors by genome-
RT scale quantitative image analysis.";
RL Genome Res. 15:1136-1144(2005).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83; SER-86; SER-89; SER-92
RP AND THR-170, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=20720434; DOI=10.1159/000320049;
RA Xu X., Patrakka J., Sistani L., Uhlen M., Jalanko H., Betsholtz C.,
RA Tryggvason K.;
RT "Expression of novel podocyte-associated proteins sult1b1 and ankrd25.";
RL Nephron Exp. Nephrol. 117:E39-E46(2011).
RN [7]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-105, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [8]
RP FUNCTION.
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 (PubMed:25961457). 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 Through the Rho signaling pathway may also regulate cell proliferation
CC (PubMed:16024821). {ECO:0000250|UniProtKB:Q63ZY3,
CC ECO:0000269|PubMed:16024821, ECO:0000269|PubMed:25961457}.
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 (By similarity).
CC Interacts (via ANK repeats 1-5) with KIF21A (via residues 1148-1169)
CC (By similarity). {ECO:0000250|UniProtKB:Q63ZY3}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q63ZY3}.
CC Mitochondrion {ECO:0000250|UniProtKB:Q63ZY3}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8BX02-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BX02-2; Sequence=VSP_019430, VSP_019431;
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels in liver and
CC skeletal muscle. {ECO:0000269|PubMed:20720434}.
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; AK045492; BAC32392.1; -; mRNA.
DR EMBL; AK049288; BAC33660.1; -; mRNA.
DR EMBL; BC010245; AAH10245.1; -; mRNA.
DR CCDS; CCDS22911.1; -. [Q8BX02-1]
DR RefSeq; NP_663586.3; NM_145611.4. [Q8BX02-1]
DR AlphaFoldDB; Q8BX02; -.
DR SMR; Q8BX02; -.
DR BioGRID; 231612; 7.
DR IntAct; Q8BX02; 3.
DR STRING; 10090.ENSMUSP00000034717; -.
DR iPTMnet; Q8BX02; -.
DR PhosphoSitePlus; Q8BX02; -.
DR SwissPalm; Q8BX02; -.
DR jPOST; Q8BX02; -.
DR MaxQB; Q8BX02; -.
DR PaxDb; Q8BX02; -.
DR PeptideAtlas; Q8BX02; -.
DR PRIDE; Q8BX02; -.
DR ProteomicsDB; 269058; -. [Q8BX02-1]
DR ProteomicsDB; 269059; -. [Q8BX02-2]
DR Antibodypedia; 2885; 199 antibodies from 28 providers.
DR DNASU; 235041; -.
DR Ensembl; ENSMUST00000034717; ENSMUSP00000034717; ENSMUSG00000032194. [Q8BX02-1]
DR Ensembl; ENSMUST00000216008; ENSMUSP00000151181; ENSMUSG00000032194. [Q8BX02-2]
DR GeneID; 235041; -.
DR KEGG; mmu:235041; -.
DR UCSC; uc009omm.2; mouse. [Q8BX02-1]
DR CTD; 25959; -.
DR MGI; MGI:2384568; Kank2.
DR VEuPathDB; HostDB:ENSMUSG00000032194; -.
DR eggNOG; KOG0514; Eukaryota.
DR GeneTree; ENSGT00940000161012; -.
DR HOGENOM; CLU_004269_2_0_1; -.
DR InParanoid; Q8BX02; -.
DR OMA; HQRSLQF; -.
DR OrthoDB; 98668at2759; -.
DR PhylomeDB; Q8BX02; -.
DR TreeFam; TF324499; -.
DR BioGRID-ORCS; 235041; 0 hits in 72 CRISPR screens.
DR ChiTaRS; Kank2; mouse.
DR PRO; PR:Q8BX02; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q8BX02; protein.
DR Bgee; ENSMUSG00000032194; Expressed in ascending aorta and 216 other tissues.
DR ExpressionAtlas; Q8BX02; baseline and differential.
DR Genevisible; Q8BX02; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0033147; P:negative regulation of intracellular estrogen receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0043069; P:negative regulation of programmed cell death; ISS:UniProtKB.
DR GO; GO:0051497; P:negative regulation of stress fiber assembly; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0070563; P:negative regulation of vitamin D receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0090521; P:podocyte cell migration; IMP:UniProtKB.
DR GO; GO:0035023; P:regulation of Rho protein signal transduction; IMP: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 Alternative splicing; ANK repeat; Apoptosis; Coiled coil; Cytoplasm;
KW Methylation; Mitochondrion; Phosphoprotein; Reference proteome; Repeat;
KW Transcription; Transcription regulation.
FT CHAIN 1..843
FT /note="KN motif and ankyrin repeat domain-containing
FT protein 2"
FT /id="PRO_0000240841"
FT REPEAT 606..643
FT /note="ANK 0; degenerate"
FT /evidence="ECO:0000250|UniProtKB:Q63ZY3"
FT REPEAT 673..703
FT /note="ANK 1"
FT /evidence="ECO:0000255"
FT REPEAT 707..740
FT /note="ANK 2"
FT /evidence="ECO:0000255"
FT REPEAT 745..774
FT /note="ANK 3"
FT /evidence="ECO:0000255"
FT REPEAT 778..808
FT /note="ANK 4"
FT /evidence="ECO:0000255"
FT REPEAT 812..842
FT /note="ANK 5"
FT /evidence="ECO:0000255"
FT REGION 1..72
FT /note="Interaction with AIFM1"
FT /evidence="ECO:0000250"
FT REGION 1..31
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 410..577
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 661..827
FT /note="Interaction with NCOA1"
FT /evidence="ECO:0000250"
FT COILED 183..234
FT /evidence="ECO:0000255"
FT COILED 282..313
FT /evidence="ECO:0000255"
FT COMPBIAS 410..431
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 491..508
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 509..523
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 550..564
FT /note="Polar 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:0007744|PubMed:21183079"
FT MOD_RES 86
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 89
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 92
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 105
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 170
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
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 532
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63ZY3"
FT VAR_SEQ 580..607
FT /note="MDLSPDLISACLALEKYLENPNALTERE -> KWPIPQCFRSGCAWPAAVTH
FT TLSLCGDI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_019430"
FT VAR_SEQ 608..843
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_019431"
FT CONFLICT 135
FT /note="L -> V (in Ref. 1; BAC32392)"
FT /evidence="ECO:0000305"
FT CONFLICT 139
FT /note="A -> V (in Ref. 2; AAH10245)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 843 AA; 90245 MW; CEC694861A228DE1 CRC64;
MAQVLHVPAP FPGTPGQASP AAFPSKEPDP PYSVETPYGY RLDLDFLKYV DDIEKGHTLR
RVAVQRRPRL GSLPRGPGSW WTSTESLCSD ASGDSRHSAY SYCGRGFYPQ YGALETRIGS
NPRVERTLLD ARRRLEDQAA APSSGGLGSL TPSAAGSTSS LAGVGLLPPT PRSSGLSTPV
APSAGHLAHV REQMAGALRK LRQLEEQVKL IPVLQVKLSV LQEEKRQLTV QLKSQKFLGH
PSGTRSRSEL CLDLPEAPDD PAALETRSVG TWVRERDLGI PDGEAALVAK VAVLETQLKK
ALQELRAAQT QQVDLQPQAW PPPDTQVRVD TVRVVEGPRE VEVAASTAAG ALAQRAQSLE
PYGTGLKALT TSGGPENTLV FRSHEVVETM CPLPTATTGN VHTAKKISIT ERSCTGAPRM
TEPSSVNPRP AAASVVQPEN PVPAAQDTTD KKPTRPAAAS QDSQAADGAG RASLATKRKE
DPADPEVNQR NLQFVGVNGG YESPSEDSST AENSEHESTE NEGPEPPARV LSPAECPQLR
PPGAAVATTS LEGPQLSQES QRVPAPEVAS GPDPEEEIRM DLSPDLISAC LALEKYLENP
NALTERELKV AYTTVLQEWL RLACRSDAHP ELVRRHLVTF RAMSARLLDY VVNIADSNGN
TALHYSVSHA NFPVVRQLLD SGVCHVDKLN RAGYSPIMLT ALATLKTQDD IETILQLFRL
GNVNAKASQA GQTALMLAVS HGRVDVVRAL LACEADVNIQ DEDGSTALMC ACEHGHKEIT
GLLLAVPSCD ISLTDRDGST ALMVALDAGQ SEIASMLYSR MNIKCSFAPM SDYESPASSS
AEE
