PKHO1_MOUSE
ID PKHO1_MOUSE Reviewed; 408 AA.
AC Q9JIY0; Q9CXH2;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Pleckstrin homology domain-containing family O member 1;
DE Short=PH domain-containing family O member 1;
GN Name=Plekho1;
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 [MRNA].
RA Kohchi C., Shige K.;
RT "Identification of a protein that associates with TNF intracellular
RT domain.";
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Head;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [4]
RP FUNCTION.
RX PubMed=17942896; DOI=10.1158/0008-5472.can-07-1050;
RA Tokuda E., Fujita N., Oh-hara T., Sato S., Kurata A., Katayama R., Itoh T.,
RA Takenawa T., Miyazono K., Tsuruo T.;
RT "Casein kinase 2-interacting protein-1, a novel Akt pleckstrin homology
RT domain-interacting protein, down-regulates PI3K/Akt signaling and
RT suppresses tumor growth in vivo.";
RL Cancer Res. 67:9666-9676(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226 AND SER-270, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
CC -!- FUNCTION: Plays a role in the regulation of the actin cytoskeleton
CC through its interactions with actin capping protein (CP). May function
CC to target CK2 to the plasma membrane thereby serving as an adapter to
CC facilitate the phosphorylation of CP by protein kinase 2 (CK2). Appears
CC to target ATM to the plasma membrane. Appears to also inhibit tumor
CC cell growth by inhibiting AKT-mediated cell-survival. Also implicated
CC in PI3K-regulated muscle differentiation, the regulation of AP-1
CC activity (plasma membrane bound AP-1 regulator that translocates to the
CC nucleus) and the promotion of apoptosis induced by tumor necrosis
CC factor TNF. When bound to PKB, it inhibits it probably by decreasing
CC PKB level of phosphorylation (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:17942896}.
CC -!- SUBUNIT: Heterodimer or homodimer. Interacts with CK2 and actin capping
CC subunits (capping protein CP-alpha and CP-beta). CKIP1 and CK2 together
CC inhibit the activity of actin capping protein at the barbed ends of
CC actin filaments. Interacts with ATM, IFP35, JUN, JUND, NMI and PI3K.
CC Interacts with AKT1, AKT2 and AKT3 (each isozyme of PKB),
CC PtdIns(3,5)P2, PtdIns(4,5)P2 and PtdIns(3,4,5)P2 (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q53GL0};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:Q53GL0}. Nucleus
CC {ECO:0000250|UniProtKB:Q53GL0}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q53GL0}. Note=Predominantly localized to the
CC plasma membrane through the binding to phosphatidylinositol 3-
CC phosphate. In C2C12 cells, with the absence of growth factor, it is
CC found in the nucleus. It rapidly translocates to the plasma membrane
CC after insulin stimulation. In response to TNF, it translocates from the
CC plasma membrane to the cytoplasm and then to the nucleus accompanied by
CC cleavage by caspase-3. However, the subcellular location is highly
CC dependent of the cell type, and this explains why it is found
CC exclusively at the plasma membrane, in some type of cells.
CC {ECO:0000250|UniProtKB:Q53GL0}.
CC -!- PTM: C-terminal fragments could be released during apoptosis via
CC caspase-3-dependent cleavage. {ECO:0000250}.
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DR EMBL; AF168675; AAF89643.1; -; mRNA.
DR EMBL; AK014374; BAB29306.1; -; mRNA.
DR EMBL; AK170025; BAE41517.1; -; mRNA.
DR EMBL; AK170922; BAE42115.1; -; mRNA.
DR EMBL; BC117003; AAI17004.1; -; mRNA.
DR EMBL; BC125441; AAI25442.1; -; mRNA.
DR CCDS; CCDS17627.1; -.
DR RefSeq; NP_075809.1; NM_023320.2.
DR AlphaFoldDB; Q9JIY0; -.
DR SMR; Q9JIY0; -.
DR BioGRID; 212026; 5.
DR STRING; 10090.ENSMUSP00000015889; -.
DR iPTMnet; Q9JIY0; -.
DR PhosphoSitePlus; Q9JIY0; -.
DR jPOST; Q9JIY0; -.
DR MaxQB; Q9JIY0; -.
DR PaxDb; Q9JIY0; -.
DR PRIDE; Q9JIY0; -.
DR ProteomicsDB; 289663; -.
DR Antibodypedia; 35196; 195 antibodies from 30 providers.
DR DNASU; 67220; -.
DR Ensembl; ENSMUST00000015889; ENSMUSP00000015889; ENSMUSG00000015745.
DR GeneID; 67220; -.
DR KEGG; mmu:67220; -.
DR UCSC; uc008qlx.2; mouse.
DR CTD; 51177; -.
DR MGI; MGI:1914470; Plekho1.
DR VEuPathDB; HostDB:ENSMUSG00000015745; -.
DR eggNOG; ENOG502QSPU; Eukaryota.
DR GeneTree; ENSGT00530000063760; -.
DR HOGENOM; CLU_052292_0_0_1; -.
DR InParanoid; Q9JIY0; -.
DR OMA; KPDRGAT; -.
DR OrthoDB; 929437at2759; -.
DR PhylomeDB; Q9JIY0; -.
DR TreeFam; TF333115; -.
DR BioGRID-ORCS; 67220; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Plekho1; mouse.
DR PRO; PR:Q9JIY0; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q9JIY0; protein.
DR Bgee; ENSMUSG00000015745; Expressed in undifferentiated genital tubercle and 224 other tissues.
DR ExpressionAtlas; Q9JIY0; baseline and differential.
DR Genevisible; Q9JIY0; MM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0036195; C:muscle cell projection membrane; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0032587; C:ruffle membrane; IDA:MGI.
DR GO; GO:0072673; P:lamellipodium morphogenesis; IDA:MGI.
DR GO; GO:0007520; P:myoblast fusion; IDA:MGI.
DR GO; GO:0051451; P:myoblast migration; IMP:MGI.
DR GO; GO:0008360; P:regulation of cell shape; IDA:MGI.
DR GO; GO:1901739; P:regulation of myoblast fusion; IBA:GO_Central.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR028452; CKIP-1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR043448; PKHO1/2.
DR PANTHER; PTHR15871; PTHR15871; 1.
DR PANTHER; PTHR15871:SF1; PTHR15871:SF1; 1.
DR Pfam; PF00169; PH; 1.
DR SMART; SM00233; PH; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasm; Membrane; Nucleus; Phosphoprotein;
KW Reference proteome; Tumor suppressor.
FT CHAIN 1..408
FT /note="Pleckstrin homology domain-containing family O
FT member 1"
FT /id="PRO_0000310424"
FT DOMAIN 20..131
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 132..192
FT /note="Interaction with capping proteins (CPs)"
FT /evidence="ECO:0000250"
FT REGION 135..307
FT /note="Interaction with ATM, CKIP, IFP35 and NMI"
FT /evidence="ECO:0000250"
FT REGION 217..264
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 307..408
FT /note="Negative regulator of AP-1 activity"
FT /evidence="ECO:0000250"
FT REGION 325..348
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 389..408
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 327..341
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 154
FT /note="Interacts with capping protein"
FT /evidence="ECO:0000250"
FT SITE 156
FT /note="Interacts with capping protein"
FT /evidence="ECO:0000250"
FT SITE 309..310
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000255"
FT SITE 344..345
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000255"
FT MOD_RES 226
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 270
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 341
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5BJM5"
FT CONFLICT 116
FT /note="P -> S (in Ref. 2; BAB29306)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 408 AA; 45997 MW; 33C36EC5DC8D4A72 CRC64;
MKKSGSGKRG PPDGNHQSAA PEKVGWVRKF CGKGIFREIW KNRYVVLKGD QLYVSEKEVK
DEKNSQEVFD LSDYEKCEEL RKSKSRSKKN HSKFTLARCR QPGTTAPNLI FLAVSPEEKE
SWINALSSAI TRAKNRILDE VTVEEDSYLA HPTRDRAKIQ HSRRPPTRGH LMAVASTSTS
DGMLTLDLIQ EEDPSPEEPA SCAESFRVDL DKSVAQLAGS RRRADSDRIQ PSSQRASSLS
RPWEKPDKGA PYTPQALKKF PSTEKSRCAS LEEILSQRDT APARPLHLQA EESLPPVPAQ
PGQLSRIQDL VARKLEKTQE LLAEVQGLGD GKRKAKDPPQ SPPDSESEQL LLETERLLGE
ASSNWSQAKR VLQEVRELRD LYRQMDLQTP DSHLRQTSQH SQYRKSLM
