KANK1_HUMAN
ID KANK1_HUMAN Reviewed; 1352 AA.
AC Q14678; A2A2W8; D3DRH3; Q5W0W0; Q8IY65; Q8WX74;
DT 29-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2005, sequence version 3.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=KN motif and ankyrin repeat domain-containing protein 1;
DE AltName: Full=Ankyrin repeat domain-containing protein 15;
DE AltName: Full=Kidney ankyrin repeat-containing protein;
GN Name=KANK1; Synonyms=ANKRD15, KANK, KIAA0172;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ALA-464.
RC TISSUE=Bone marrow;
RX PubMed=8724849; DOI=10.1093/dnares/3.1.17;
RA Nagase T., Seki N., Ishikawa K., Tanaka A., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. V. The
RT coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 3:17-24(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLN-432.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS LYS-206
RP AND GLN-432.
RC TISSUE=Testis;
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 [5]
RP PUTATIVE FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=12133830; DOI=10.1074/jbc.m204244200;
RA Sarkar S., Roy B.C., Hatano N., Aoyagi T., Gohji K., Kiyama R.;
RT "A novel ankyrin repeat-containing gene (Kank) located at 9p24 is a growth
RT suppressor of renal cell carcinoma.";
RL J. Biol. Chem. 277:36585-36591(2002).
RN [6]
RP ALTERNATIVE PROMOTER USAGE (ISOFORM 2), AND TISSUE SPECIFICITY.
RX PubMed=15823577; DOI=10.1016/j.bbrc.2005.03.106;
RA Wang Y., Onishi Y., Kakinuma N., Roy B.C., Aoyagi T., Kiyama R.;
RT "Alternative splicing of the human Kank gene produces two types of Kank
RT protein.";
RL Biochem. Biophys. Res. Commun. 330:1247-1253(2005).
RN [7]
RP INVOLVEMENT IN CPSQ2.
RX PubMed=16301218; DOI=10.1093/hmg/ddi415;
RA Lerer I., Sagi M., Meiner V., Cohen T., Zlotogora J., Abeliovich D.;
RT "Deletion of the ANKRD15 gene at 9p24.3 causes parent-of-origin-dependent
RT inheritance of familial cerebral palsy.";
RL Hum. Mol. Genet. 14:3911-3920(2005).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CTNNB1, AND MUTAGENESIS OF
RP LEU-43; ILE-52; 65-LYS--LYS-68; LEU-125; LEU-129; ILE-134; LEU-613;
RP LEU-616; LEU-620; LEU-622; 979-LYS--LYS-981 AND 991-LYS-LYS-992.
RX PubMed=16968744; DOI=10.1242/jcs.03169;
RA Wang Y., Kakinuma N., Zhu Y., Kiyama R.;
RT "Nucleo-cytoplasmic shuttling of human Kank protein accompanies
RT intracellular translocation of beta-catenin.";
RL J. Cell Sci. 119:4002-4010(2006).
RN [9]
RP FUNCTION, PHOSPHORYLATION AT SER-325, INTERACTION WITH YWHAB; YWHAG; YWHAE;
RP YWHAH; YWHAQ; YWHAZ AND SFN, AND MUTAGENESIS OF SER-325.
RX PubMed=18458160; DOI=10.1083/jcb.200707022;
RA Kakinuma N., Roy B.C., Zhu Y., Wang Y., Kiyama R.;
RT "Kank regulates RhoA-dependent formation of actin stress fibers and cell
RT migration via 14-3-3 in PI3K-Akt signaling.";
RL J. Cell Biol. 181:537-549(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP INTERACTION WITH KIF21A, AND SUBCELLULAR LOCATION.
RX PubMed=19559006; DOI=10.1016/j.bbrc.2009.06.109;
RA Kakinuma N., Kiyama R.;
RT "A major mutation of KIF21A associated with congenital fibrosis of the
RT extraocular muscles type 1 (CFEOM1) enhances translocation of Kank1 to the
RT membrane.";
RL Biochem. Biophys. Res. Commun. 386:639-644(2009).
RN [12]
RP FUNCTION, AND INTERACTION WITH BAIAP2.
RX PubMed=19171758; DOI=10.1083/jcb.200805147;
RA Roy B.C., Kakinuma N., Kiyama R.;
RT "Kank attenuates actin remodeling by preventing interaction between IRSp53
RT and Rac1.";
RL J. Cell Biol. 184:253-267(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-325, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
RP FUNCTION, AND INTERACTION WITH ARFGEF1.
RX PubMed=22084092; DOI=10.1073/pnas.1117011108;
RA Li C.C., Kuo J.C., Waterman C.M., Kiyama R., Moss J., Vaughan M.;
RT "Effects of brefeldin A-inhibited guanine nucleotide-exchange (BIG) 1 and
RT KANK1 proteins on cell polarity and directed migration during wound
RT healing.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:19228-19233(2011).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-325, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-325, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [19]
RP FUNCTION, SUBCELLULAR LOCATION, VARIANT LYS-454, AND CHARACTERIZATION OF
RP VARIANT LYS-454.
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).
RN [20] {ECO:0007744|PDB:5YBJ, ECO:0007744|PDB:5YBU}
RP X-RAY CRYSTALLOGRAPHY (1.89 ANGSTROMS) OF 1080-1329 IN COMPLEX WITH KIF21A
RP PEPTIDE, INTERACTION WITH KIF21A, AND MUTAGENESIS OF TYR-1197; GLU-1276;
RP ASP-1298 AND ASP-1300.
RX PubMed=29183992; DOI=10.1074/jbc.m117.817494;
RA Guo Q., Liao S., Zhu Z., Li Y., Li F., Xu C.;
RT "Structural basis for the recognition of kinesin family member 21A (KIF21A)
RT by the ankyrin domains of KANK1 and KANK2 proteins.";
RL J. Biol. Chem. 293:557-566(2018).
CC -!- FUNCTION: Involved in the control of cytoskeleton formation by
CC regulating actin polymerization. Inhibits actin fiber formation and
CC cell migration (PubMed:25961457). Inhibits RhoA activity; the function
CC involves phosphorylation through PI3K/Akt signaling and may depend on
CC the competitive interaction with 14-3-3 adapter proteins to sequester
CC them from active complexes (PubMed:25961457). Inhibits the formation of
CC lamellipodia but not of filopodia; the function may depend on the
CC competitive interaction with BAIAP2 to block its association with
CC activated RAC1 (PubMed:25961457). Inhibits fibronectin-mediated cell
CC spreading; the function is partially mediated by BAIAP2. Inhibits
CC neurite outgrowth. Involved in the establishment and persistence of
CC cell polarity during directed cell movement in wound healing. In the
CC nucleus, is involved in beta-catenin-dependent activation of
CC transcription. Potential tumor suppressor for renal cell carcinoma.
CC Regulates Rac signaling pathways (PubMed:25961457).
CC {ECO:0000269|PubMed:16968744, ECO:0000269|PubMed:18458160,
CC ECO:0000269|PubMed:19171758, ECO:0000269|PubMed:22084092,
CC ECO:0000269|PubMed:25961457}.
CC -!- SUBUNIT: Interacts with YWHAQ; the interaction requires KANK1
CC phosphorylation at Ser-325 and is enhanced by growth factor stimulation
CC (PubMed:18458160). Interacts with YWHAB, YWHAG, YWHAE, YWHAH, YWHAZ and
CC SFN; the interaction requires KANK1 phosphorylation at Ser-325
CC (PubMed:18458160). Interacts with ARFGEF1; however, colocalization
CC cannot be experimentally confirmed (PubMed:22084092). Interacts with
CC BAIAP2 (PubMed:19171758). Interacts (via ANK repeats 1-5) with KIF21A
CC (via residues 1146-1167); KIF21A enhances translocation of KANK1 to the
CC plasma membrane (PubMed:19559006, PubMed:29183992). Interacts with
CC CTNNB1 (PubMed:16968744). {ECO:0000269|PubMed:16968744,
CC ECO:0000269|PubMed:18458160, ECO:0000269|PubMed:19171758,
CC ECO:0000269|PubMed:19559006, ECO:0000269|PubMed:22084092,
CC ECO:0000269|PubMed:29183992}.
CC -!- INTERACTION:
CC Q14678; Q9Y6D6: ARFGEF1; NbExp=8; IntAct=EBI-2556221, EBI-1044254;
CC Q14678; Q9UQB8: BAIAP2; NbExp=6; IntAct=EBI-2556221, EBI-525456;
CC Q14678; P35222: CTNNB1; NbExp=2; IntAct=EBI-2556221, EBI-491549;
CC Q14678; Q7Z4S6: KIF21A; NbExp=5; IntAct=EBI-2556221, EBI-2691397;
CC Q14678; P27348: YWHAQ; NbExp=2; IntAct=EBI-2556221, EBI-359854;
CC Q14678-2; Q9UQB8-4: BAIAP2; NbExp=4; IntAct=EBI-6173812, EBI-6174091;
CC Q14678-2; Q7Z4S6: KIF21A; NbExp=3; IntAct=EBI-6173812, EBI-2691397;
CC Q14678-2; P62258: YWHAE; NbExp=3; IntAct=EBI-6173812, EBI-356498;
CC Q14678-2; P61981: YWHAG; NbExp=3; IntAct=EBI-6173812, EBI-359832;
CC Q14678-2; Q04917: YWHAH; NbExp=3; IntAct=EBI-6173812, EBI-306940;
CC Q14678-2; P27348: YWHAQ; NbExp=3; IntAct=EBI-6173812, EBI-359854;
CC -!- SUBCELLULAR LOCATION: Cell projection, ruffle membrane
CC {ECO:0000269|PubMed:19559006}. Cytoplasm {ECO:0000269|PubMed:12133830,
CC ECO:0000269|PubMed:16968744}. Nucleus {ECO:0000269|PubMed:16968744}.
CC Note=Colocalizes with KIF21A in membrane ruffles (PubMed:19559006).
CC Shuttles between the cytoplasm and nucleus (PubMed:16968744).
CC {ECO:0000269|PubMed:16968744, ECO:0000269|PubMed:19559006}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm
CC {ECO:0000269|PubMed:16968744, ECO:0000269|PubMed:25961457}. Nucleus
CC {ECO:0000269|PubMed:16968744, ECO:0000269|PubMed:25961457}.
CC Note=Shuttles between the cytoplasm and nucleus.
CC {ECO:0000269|PubMed:16968744}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000269|PubMed:16968744}. Nucleus {ECO:0000269|PubMed:16968744}.
CC Note=Shuttles between the cytoplasm and nucleus.
CC {ECO:0000269|PubMed:16968744}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage; Named isoforms=2;
CC Name=1; Synonyms=Kank-L;
CC IsoId=Q14678-1; Sequence=Displayed;
CC Name=2; Synonyms=Kank-S;
CC IsoId=Q14678-2; Sequence=VSP_043958;
CC -!- TISSUE SPECIFICITY: Widely expressed. Isoform 1 is predominantly
CC expressed in heart and kidney. Isoform 2 probably is widely expressed
CC at basic levels. {ECO:0000269|PubMed:15823577}.
CC -!- DISEASE: Cerebral palsy, spastic quadriplegic 2 (CPSQ2) [MIM:612900]: A
CC non-progressive disorder of movement and/or posture resulting from
CC defects in the developing central nervous system. Affected individuals
CC manifest congenital hypotonia evolving over the first year to spastic
CC quadriplegia with accompanying transient nystagmus and varying degrees
CC of intellectual disability. Neuroimaging shows brain atrophy and
CC ventriculomegaly. {ECO:0000269|PubMed:16301218}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA11489.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; D79994; BAA11489.2; ALT_INIT; mRNA.
DR EMBL; AL136979; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471071; EAW58821.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58822.1; -; Genomic_DNA.
DR EMBL; BC037495; AAH37495.1; -; mRNA.
DR CCDS; CCDS34976.1; -. [Q14678-1]
DR CCDS; CCDS6441.1; -. [Q14678-2]
DR RefSeq; NP_001243805.1; NM_001256876.1. [Q14678-1]
DR RefSeq; NP_001243806.1; NM_001256877.1. [Q14678-1]
DR RefSeq; NP_055973.2; NM_015158.3. [Q14678-1]
DR RefSeq; NP_694856.1; NM_153186.4. [Q14678-2]
DR RefSeq; XP_016870003.1; XM_017014514.1.
DR RefSeq; XP_016870004.1; XM_017014515.1.
DR RefSeq; XP_016870016.1; XM_017014527.1.
DR RefSeq; XP_016870017.1; XM_017014528.1.
DR RefSeq; XP_016870018.1; XM_017014529.1.
DR RefSeq; XP_016870019.1; XM_017014530.1.
DR PDB; 5YBJ; X-ray; 2.34 A; A=1080-1329.
DR PDB; 5YBU; X-ray; 1.89 A; A=1080-1329.
DR PDBsum; 5YBJ; -.
DR PDBsum; 5YBU; -.
DR AlphaFoldDB; Q14678; -.
DR SMR; Q14678; -.
DR BioGRID; 116798; 45.
DR DIP; DIP-56491N; -.
DR IntAct; Q14678; 20.
DR STRING; 9606.ENSP00000477725; -.
DR iPTMnet; Q14678; -.
DR PhosphoSitePlus; Q14678; -.
DR SwissPalm; Q14678; -.
DR BioMuta; KANK1; -.
DR DMDM; 73920184; -.
DR EPD; Q14678; -.
DR jPOST; Q14678; -.
DR MassIVE; Q14678; -.
DR MaxQB; Q14678; -.
DR PaxDb; Q14678; -.
DR PeptideAtlas; Q14678; -.
DR PRIDE; Q14678; -.
DR ProteomicsDB; 60112; -. [Q14678-1]
DR ProteomicsDB; 60113; -. [Q14678-2]
DR Antibodypedia; 1018; 102 antibodies from 24 providers.
DR DNASU; 23189; -.
DR Ensembl; ENST00000382293.7; ENSP00000371730.3; ENSG00000107104.21. [Q14678-2]
DR Ensembl; ENST00000382297.7; ENSP00000371734.2; ENSG00000107104.21. [Q14678-1]
DR Ensembl; ENST00000382303.5; ENSP00000371740.1; ENSG00000107104.21. [Q14678-1]
DR Ensembl; ENST00000674102.1; ENSP00000501167.1; ENSG00000107104.21. [Q14678-1]
DR Ensembl; ENST00000685947.1; ENSP00000508833.1; ENSG00000107104.21. [Q14678-1]
DR Ensembl; ENST00000687796.1; ENSP00000510058.1; ENSG00000107104.21. [Q14678-2]
DR Ensembl; ENST00000689779.1; ENSP00000508451.1; ENSG00000107104.21. [Q14678-1]
DR Ensembl; ENST00000690372.1; ENSP00000509433.1; ENSG00000107104.21. [Q14678-2]
DR GeneID; 23189; -.
DR KEGG; hsa:23189; -.
DR MANE-Select; ENST00000382297.7; ENSP00000371734.2; NM_015158.5; NP_055973.2.
DR UCSC; uc003zgl.3; human. [Q14678-1]
DR CTD; 23189; -.
DR DisGeNET; 23189; -.
DR GeneCards; KANK1; -.
DR HGNC; HGNC:19309; KANK1.
DR HPA; ENSG00000107104; Low tissue specificity.
DR MalaCards; KANK1; -.
DR MIM; 607704; gene.
DR MIM; 612900; phenotype.
DR neXtProt; NX_Q14678; -.
DR OpenTargets; ENSG00000107104; -.
DR Orphanet; 210141; Inherited congenital spastic tetraplegia.
DR PharmGKB; PA162392554; -.
DR VEuPathDB; HostDB:ENSG00000107104; -.
DR eggNOG; KOG0514; Eukaryota.
DR GeneTree; ENSGT00940000154886; -.
DR HOGENOM; CLU_004269_1_1_1; -.
DR InParanoid; Q14678; -.
DR OMA; FNPYLCS; -.
DR PhylomeDB; Q14678; -.
DR TreeFam; TF324499; -.
DR PathwayCommons; Q14678; -.
DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression.
DR Reactome; R-HSA-9673768; Signaling by membrane-tethered fusions of PDGFRA or PDGFRB.
DR SignaLink; Q14678; -.
DR SIGNOR; Q14678; -.
DR BioGRID-ORCS; 23189; 14 hits in 1075 CRISPR screens.
DR ChiTaRS; KANK1; human.
DR GeneWiki; ANKRD15; -.
DR GenomeRNAi; 23189; -.
DR Pharos; Q14678; Tbio.
DR PRO; PR:Q14678; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q14678; protein.
DR Bgee; ENSG00000107104; Expressed in blood vessel layer and 204 other tissues.
DR ExpressionAtlas; Q14678; baseline and differential.
DR Genevisible; Q14678; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0032587; C:ruffle membrane; IDA:UniProtKB.
DR GO; GO:0008013; F:beta-catenin binding; IDA:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; IMP:UniProtKB.
DR GO; GO:0030837; P:negative regulation of actin filament polymerization; IDA:UniProtKB.
DR GO; GO:0030336; P:negative regulation of cell migration; IMP:UniProtKB.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:2000393; P:negative regulation of lamellipodium morphogenesis; IDA:UniProtKB.
DR GO; GO:0010977; P:negative regulation of neuron projection development; IDA:UniProtKB.
DR GO; GO:0035024; P:negative regulation of Rho protein signal transduction; IMP:UniProtKB.
DR GO; GO:1900028; P:negative regulation of ruffle assembly; IDA:UniProtKB.
DR GO; GO:1900025; P:negative regulation of substrate adhesion-dependent cell spreading; IDA:UniProtKB.
DR GO; GO:0090521; P:podocyte cell migration; IMP:UniProtKB.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0090303; P:positive regulation of wound healing; IMP:UniProtKB.
DR GO; GO:2000114; P:regulation of establishment of cell polarity; 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; 2.
DR Pfam; PF12075; KN_motif; 1.
DR SMART; SM00248; ANK; 6.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative promoter usage; ANK repeat; Cell membrane;
KW Cell projection; Coiled coil; Cytoplasm; Membrane; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Transcription; Transcription regulation;
KW Tumor suppressor.
FT CHAIN 1..1352
FT /note="KN motif and ankyrin repeat domain-containing
FT protein 1"
FT /id="PRO_0000066911"
FT REPEAT 1109..1146
FT /note="ANK 0; degenerate"
FT /evidence="ECO:0000269|PubMed:29183992"
FT REPEAT 1161..1191
FT /note="ANK 1"
FT /evidence="ECO:0000255"
FT REPEAT 1195..1228
FT /note="ANK 2"
FT /evidence="ECO:0000255"
FT REPEAT 1233..1262
FT /note="ANK 3"
FT /evidence="ECO:0000255"
FT REPEAT 1266..1298
FT /note="ANK 4"
FT /evidence="ECO:0000255"
FT REPEAT 1300..1329
FT /note="ANK 5"
FT /evidence="ECO:0000255"
FT REGION 1..31
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 63..103
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 291..467
FT /note="Interaction with KIF21A"
FT /evidence="ECO:0000269|PubMed:19559006"
FT REGION 914..951
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 979..1026
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1156..1308
FT /note="Interaction with KIF21A"
FT /evidence="ECO:0000269|PubMed:19559006"
FT REGION 1331..1352
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 258..316
FT /evidence="ECO:0000255"
FT COILED 361..395
FT /evidence="ECO:0000255"
FT COILED 446..500
FT /evidence="ECO:0000255"
FT MOTIF 43..52
FT /note="Nuclear export signal 1 (NES 1)"
FT MOTIF 65..68
FT /note="Nuclear localization signal 1 (NLS 1)"
FT MOTIF 125..134
FT /note="Nuclear export signal 2 (NES 2)"
FT MOTIF 613..622
FT /note="Nuclear export signal 3 (NES 3)"
FT MOTIF 979..992
FT /note="Nuclear localization signal 2 (NLS 2)"
FT COMPBIAS 75..103
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 989..1014
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 186
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 325
FT /note="Phosphoserine; by PKB"
FT /evidence="ECO:0000269|PubMed:18458160,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..158
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_043958"
FT VARIANT 206
FT /note="N -> K (in dbSNP:rs17857145)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_026212"
FT VARIANT 210
FT /note="H -> Q (in dbSNP:rs28374506)"
FT /id="VAR_048298"
FT VARIANT 321
FT /note="K -> R (in dbSNP:rs17857159)"
FT /id="VAR_048299"
FT VARIANT 432
FT /note="E -> Q (in dbSNP:rs4465020)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.3"
FT /id="VAR_026213"
FT VARIANT 454
FT /note="E -> K (found in a patient with nephrotic syndrome;
FT unknown pathological significance; no effect on protein
FT localization; dbSNP:rs1554698949)"
FT /evidence="ECO:0000269|PubMed:25961457"
FT /id="VAR_080958"
FT VARIANT 464
FT /note="S -> A (in dbSNP:rs912174)"
FT /evidence="ECO:0000269|PubMed:8724849"
FT /id="VAR_016697"
FT VARIANT 664
FT /note="A -> V (in dbSNP:rs3824421)"
FT /id="VAR_048300"
FT VARIANT 667
FT /note="R -> H (in dbSNP:rs3824420)"
FT /id="VAR_048301"
FT VARIANT 901
FT /note="N -> S (in dbSNP:rs12352313)"
FT /id="VAR_048302"
FT VARIANT 1055
FT /note="I -> T (in dbSNP:rs34832656)"
FT /id="VAR_048303"
FT MUTAGEN 43
FT /note="L->A: Nuclear localization; when associated A-52; A-
FT 125; A-129; A-134; A-613; A-616; A-620 and A-622."
FT /evidence="ECO:0000269|PubMed:16968744"
FT MUTAGEN 52
FT /note="I->A: Nuclear localization; when associated A-43; A-
FT 125; A-129; A-134; A-613; A-616; A-620 and A-622."
FT /evidence="ECO:0000269|PubMed:16968744"
FT MUTAGEN 65..68
FT /note="KRRK->AAAA: Enhanced cytoplasmic localization; when
FT associated with 979-A--A-981 and 991-A-A-992."
FT /evidence="ECO:0000269|PubMed:16968744"
FT MUTAGEN 125
FT /note="L->A: Nuclear localization; when associated A-43; A-
FT 52; A-129; A-134; A-613; A-616; A-620 and A-622."
FT /evidence="ECO:0000269|PubMed:16968744"
FT MUTAGEN 129
FT /note="L->A: Nuclear localization; when associated A-43; A-
FT 52; A-125; A-134; A-613; A-616; A-620 and A-622."
FT /evidence="ECO:0000269|PubMed:16968744"
FT MUTAGEN 134
FT /note="I->A: Nuclear localization; when associated A-43; A-
FT 52; A-125; A-129; A-613; A-616; A-620 and A-622."
FT /evidence="ECO:0000269|PubMed:16968744"
FT MUTAGEN 325
FT /note="S->A: Abolishes phosphorylation by PKB. Abolishes
FT interaction with YWHAB; YWHAG; YWHAE; YWHAH; YWHAQ; YWHAZ
FT and SFN."
FT /evidence="ECO:0000269|PubMed:18458160"
FT MUTAGEN 613
FT /note="L->A: Nuclear localization; when associated A-43; A-
FT 52; A-125; A-129; A-134; A-616; A-620 and A-622."
FT /evidence="ECO:0000269|PubMed:16968744"
FT MUTAGEN 616
FT /note="L->A: Nuclear localization; when associated A-43; A-
FT 52; A-125; A-129; A-134; A-613; A-620 and A-622."
FT /evidence="ECO:0000269|PubMed:16968744"
FT MUTAGEN 620
FT /note="L->A: Nuclear localization; when associated A-43; A-
FT 52; A-125; A-129; A-134; A-613; A-616 and A-622."
FT /evidence="ECO:0000269|PubMed:16968744"
FT MUTAGEN 622
FT /note="L->A: Nuclear localization; when associated A-43; A-
FT 52; A-125; A-129; A-134; A-613; A-616 and A-620."
FT /evidence="ECO:0000269|PubMed:16968744"
FT MUTAGEN 979..981
FT /note="KKK->AAA: Enhanced cytoplasmic localization; when
FT associated with 65-A--A-68 and 991-A-A-992."
FT /evidence="ECO:0000269|PubMed:16968744"
FT MUTAGEN 991..992
FT /note="KK->AA: Enhanced cytoplasmic localization; when
FT associated with 65-A--68 and 979-A--A-981."
FT /evidence="ECO:0000269|PubMed:16968744"
FT MUTAGEN 1197
FT /note="Y->A: 4.5-fold decrease in binding to KIF21A."
FT /evidence="ECO:0000269|PubMed:29183992"
FT MUTAGEN 1197
FT /note="Y->L: Very weak binding affinity for KIF21A."
FT /evidence="ECO:0000269|PubMed:29183992"
FT MUTAGEN 1276
FT /note="E->H: Abolishes binding to KIF21A."
FT /evidence="ECO:0000269|PubMed:29183992"
FT MUTAGEN 1298
FT /note="D->A: 15-fold decrease in binding to KIF21A."
FT /evidence="ECO:0000269|PubMed:29183992"
FT MUTAGEN 1300
FT /note="D->A: 10-fold decrease in binding to KIF21A."
FT /evidence="ECO:0000269|PubMed:29183992"
FT HELIX 1087..1099
FT /evidence="ECO:0007829|PDB:5YBU"
FT HELIX 1103..1106
FT /evidence="ECO:0007829|PDB:5YBU"
FT HELIX 1109..1126
FT /evidence="ECO:0007829|PDB:5YBU"
FT HELIX 1133..1146
FT /evidence="ECO:0007829|PDB:5YBU"
FT HELIX 1148..1155
FT /evidence="ECO:0007829|PDB:5YBU"
FT HELIX 1165..1171
FT /evidence="ECO:0007829|PDB:5YBU"
FT HELIX 1175..1183
FT /evidence="ECO:0007829|PDB:5YBU"
FT HELIX 1199..1205
FT /evidence="ECO:0007829|PDB:5YBU"
FT HELIX 1211..1223
FT /evidence="ECO:0007829|PDB:5YBU"
FT TURN 1231..1234
FT /evidence="ECO:0007829|PDB:5YBU"
FT HELIX 1237..1243
FT /evidence="ECO:0007829|PDB:5YBU"
FT HELIX 1247..1255
FT /evidence="ECO:0007829|PDB:5YBU"
FT HELIX 1270..1277
FT /evidence="ECO:0007829|PDB:5YBU"
FT HELIX 1280..1287
FT /evidence="ECO:0007829|PDB:5YBU"
FT HELIX 1304..1310
FT /evidence="ECO:0007829|PDB:5YBU"
FT HELIX 1314..1324
FT /evidence="ECO:0007829|PDB:5YBU"
SQ SEQUENCE 1352 AA; 147289 MW; 0C3993143391363B CRC64;
MAHTTKVNGS ASGKAGDILS GDQDKEQKDP YFVETPYGYQ LDLDFLKYVD DIQKGNTIKR
LNIQKRRKPS VPCPEPRTTS GQQGIWTSTE SLSSSNSDDN KQCPNFLIAR SQVTSTPISK
PPPPLETSLP FLTIPENRQL PPPSPQLPKH NLHVTKTLME TRRRLEQERA TMQMTPGEFR
RPRLASFGGM GTTSSLPSFV GSGNHNPAKH QLQNGYQGNG DYGSYAPAAP TTSSMGSSIR
HSPLSSGIST PVTNVSPMHL QHIREQMAIA LKRLKELEEQ VRTIPVLQVK ISVLQEEKRQ
LVSQLKNQRA ASQINVCGVR KRSYSAGNAS QLEQLSRARR SGGELYIDYE EEEMETVEQS
TQRIKEFRQL TADMQALEQK IQDSSCEASS ELRENGECRS VAVGAEENMN DIVVYHRGSR
SCKDAAVGTL VEMRNCGVSV TEAMLGVMTE ADKEIELQQQ TIESLKEKIY RLEVQLRETT
HDREMTKLKQ ELQAAGSRKK VDKATMAQPL VFSKVVEAVV QTRDQMVGSH MDLVDTCVGT
SVETNSVGIS CQPECKNKVV GPELPMNWWI VKERVEMHDR CAGRSVEMCD KSVSVEVSVC
ETGSNTEESV NDLTLLKTNL NLKEVRSIGC GDCSVDVTVC SPKECASRGV NTEAVSQVEA
AVMAVPRTAD QDTSTDLEQV HQFTNTETAT LIESCTNTCL STLDKQTSTQ TVETRTVAVG
EGRVKDINSS TKTRSIGVGT LLSGHSGFDR PSAVKTKESG VGQININDNY LVGLKMRTIA
CGPPQLTVGL TASRRSVGVG DDPVGESLEN PQPQAPLGMM TGLDHYIERI QKLLAEQQTL
LAENYSELAE AFGEPHSQMG SLNSQLISTL SSINSVMKSA STEELRNPDF QKTSLGKITG
NYLGYTCKCG GLQSGSPLSS QTSQPEQEVG TSEGKPISSL DAFPTQEGTL SPVNLTDDQI
AAGLYACTNN ESTLKSIMKK KDGNKDSNGA KKNLQFVGIN GGYETTSSDD SSSDESSSSE
SDDECDVIEY PLEEEEEEED EDTRGMAEGH HAVNIEGLKS ARVEDEMQVQ ECEPEKVEIR
ERYELSEKML SACNLLKNTI NDPKALTSKD MRFCLNTLQH EWFRVSSQKS AIPAMVGDYI
AAFEAISPDV LRYVINLADG NGNTALHYSV SHSNFEIVKL LLDADVCNVD HQNKAGYTPI
MLAALAAVEA EKDMRIVEEL FGCGDVNAKA SQAGQTALML AVSHGRIDMV KGLLACGADV
NIQDDEGSTA LMCASEHGHV EIVKLLLAQP GCNGHLEDND GSTALSIALE AGHKDIAVLL
YAHVNFAKAQ SPGTPRLGRK TSPGPTHRGS FD
