NYAP2_MOUSE
ID NYAP2_MOUSE Reviewed; 682 AA.
AC Q8BM65; D3Z7K6; Q641L6; Q6ZPP8; Q8BWV8;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 25-MAY-2022, entry version 109.
DE RecName: Full=Neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adapter 2;
GN Name=Nyap2; Synonyms=Kiaa1486;
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] (ISOFORM 5), FUNCTION, INTERACTION WITH ACOT9;
RP ARHGAP26; CYFIP1; NCKAP1 AND PIK3R2, SUBUNIT, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, PHOSPHORYLATION, AND MUTAGENESIS
RP OF TYR-277 AND TYR-300.
RC TISSUE=Brain;
RX PubMed=21946561; DOI=10.1038/emboj.2011.348;
RA Yokoyama K., Tezuka T., Kotani M., Nakazawa T., Hoshina N., Shimoda Y.,
RA Kakuta S., Sudo K., Watanabe K., Iwakura Y., Yamamoto T.;
RT "NYAP: a phosphoprotein family that links PI3K to WAVE1 signalling in
RT neurons.";
RL EMBO J. 30:4739-4754(2011).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Embryonic breast, and Spinal cord;
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 GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC STRAIN=C57BL/6J; 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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 257-682 (ISOFORM 4).
RC TISSUE=Brain;
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-300, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-120 AND SER-238, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
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 [8]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-81, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
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).
CC -!- FUNCTION: Activates PI3K and concomitantly recruits the WAVE1 complex
CC to the close vicinity of PI3K and regulates neuronal morphogenesis.
CC {ECO:0000269|PubMed:21946561}.
CC -!- SUBUNIT: Interacts with ACOT9, ARHGAP26 and PIK3R2. Interacts with
CC components of the WAVE1 complex, CYFIP1 and NCKAP1; this interaction
CC mediates PI3K-WAVE1 association and actin cytoskeleton remodeling.
CC {ECO:0000269|PubMed:21946561}.
CC -!- INTERACTION:
CC Q8BM65-4; P27986: PIK3R1; Xeno; NbExp=3; IntAct=EBI-7447598, EBI-79464;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q8BM65-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BM65-2; Sequence=VSP_032436;
CC Name=3;
CC IsoId=Q8BM65-3; Sequence=VSP_032437;
CC Name=4;
CC IsoId=Q8BM65-4; Sequence=VSP_032438;
CC Name=5;
CC IsoId=Q8BM65-5; Sequence=VSP_032436, VSP_032438;
CC -!- TISSUE SPECIFICITY: Expressed predominantly in brain where it is
CC present in the neurons, but not in astrocytes or oligodendrites.
CC {ECO:0000269|PubMed:21946561}.
CC -!- DEVELOPMENTAL STAGE: Expression first detected in the lower neocortex
CC at 18 dpc and decreases thereafter. At postnatal day 1, also expressed
CC in the striatum and the olfactory bulb. {ECO:0000269|PubMed:21946561}.
CC -!- PTM: Phosphorylated on tyrosine residues by FYN upon stimulation with
CC CNTN5. Phosphorylation begins at 16 dpc and persists in adult brain.
CC {ECO:0000269|PubMed:21946561}.
CC -!- DISRUPTION PHENOTYPE: Triple knockout mice NYAP1/NYAP2/MYO16 are
CC fertile and appear healthy. However, compared to wild-type mice they
CC show a clear reduction in brain size, exhibiting a reduction in the
CC size of the cortex and striatum, but not the olfactory bulb or corpus
CC callosum. The total neurite length of neurons in these mice is also
CC significantly shorter. {ECO:0000269|PubMed:21946561}.
CC -!- SIMILARITY: Belongs to the NYAP family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB429290; BAJ19139.1; -; mRNA.
DR EMBL; AK034747; BAC28819.1; -; mRNA.
DR EMBL; AK049778; BAC33918.1; -; mRNA.
DR EMBL; AK137094; BAE23236.1; -; mRNA.
DR EMBL; AC116105; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC131336; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC163450; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC082310; AAH82310.1; -; mRNA.
DR EMBL; AK129372; BAC98182.1; -; mRNA.
DR CCDS; CCDS87851.1; -. [Q8BM65-5]
DR CCDS; CCDS87852.1; -. [Q8BM65-2]
DR CCDS; CCDS87853.1; -. [Q8BM65-1]
DR RefSeq; NP_766437.2; NM_172849.3.
DR RefSeq; XP_006496550.1; XM_006496487.3.
DR RefSeq; XP_006496553.1; XM_006496490.3.
DR AlphaFoldDB; Q8BM65; -.
DR BioGRID; 232283; 11.
DR IntAct; Q8BM65; 11.
DR MINT; Q8BM65; -.
DR STRING; 10090.ENSMUSP00000065468; -.
DR iPTMnet; Q8BM65; -.
DR PhosphoSitePlus; Q8BM65; -.
DR MaxQB; Q8BM65; -.
DR PaxDb; Q8BM65; -.
DR PRIDE; Q8BM65; -.
DR ProteomicsDB; 293796; -. [Q8BM65-1]
DR ProteomicsDB; 293797; -. [Q8BM65-2]
DR ProteomicsDB; 293798; -. [Q8BM65-3]
DR ProteomicsDB; 293799; -. [Q8BM65-4]
DR ProteomicsDB; 293800; -. [Q8BM65-5]
DR UCSC; uc007brj.1; mouse. [Q8BM65-2]
DR UCSC; uc007brl.1; mouse. [Q8BM65-3]
DR UCSC; uc007brn.1; mouse. [Q8BM65-5]
DR MGI; MGI:2443135; Nyap2.
DR eggNOG; ENOG502QTY4; Eukaryota.
DR InParanoid; Q8BM65; -.
DR OrthoDB; 295010at2759; -.
DR PhylomeDB; Q8BM65; -.
DR BioGRID-ORCS; 241134; 0 hits in 71 CRISPR screens.
DR ChiTaRS; Nyap2; mouse.
DR PRO; PR:Q8BM65; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q8BM65; protein.
DR GO; GO:0048812; P:neuron projection morphogenesis; IDA:UniProtKB.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IDA:UniProtKB.
DR InterPro; IPR026722; NYAP1/NYAP2.
DR InterPro; IPR026723; NYAP2.
DR InterPro; IPR029353; NYAP_C.
DR InterPro; IPR039482; NYAP_N.
DR PANTHER; PTHR22633; PTHR22633; 1.
DR PANTHER; PTHR22633:SF1; PTHR22633:SF1; 1.
DR Pfam; PF15452; NYAP_C; 1.
DR Pfam; PF15439; NYAP_N; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Methylation; Phosphoprotein; Reference proteome.
FT CHAIN 1..682
FT /note="Neuronal tyrosine-phosphorylated phosphoinositide-3-
FT kinase adapter 2"
FT /id="PRO_0000325831"
FT REGION 98..271
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 150..161
FT /note="Involved in CYFIP1- and NCKAP1-binding"
FT REGION 407..682
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 112..134
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 147..167
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 183..204
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 207..224
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 442..474
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 491..507
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 516..556
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 558..598
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 623..682
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 81
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 120
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 238
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 300
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18034455"
FT MOD_RES 463
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P242"
FT VAR_SEQ 175..206
FT /note="Missing (in isoform 2 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:16141072,
FT ECO:0000303|PubMed:21946561"
FT /id="VSP_032436"
FT VAR_SEQ 639..682
FT /note="EPKVSCKLGRSASTSGVPPPSVTPLRQASDLQQSQVPSSLANRD -> GKHD
FT PVLPNGSKSLEAAHMQISLRKPSPQLSLLPPRLAPQTHTLRSRHMKNATVPLFIAMARE
FT TMLLEALLCSSLQLGKTLYQMSSKMTTGLNSSHCNL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_032437"
FT VAR_SEQ 675..682
FT /note="PSSLANRD -> ACMQWFHGDHTMLEMIEKKRCLCKEIKARQKTEKGLCKQD
FT SMPILPSWKKNAGAKKYSPPPYSKQQTVFWDTAI (in isoform 4 and
FT isoform 5)"
FT /evidence="ECO:0000303|PubMed:14621295,
FT ECO:0000303|PubMed:21946561"
FT /id="VSP_032438"
FT MUTAGEN 277
FT /note="Y->F: Abolishes binding to PIK3R2. Slight reduction
FT of phosphorylation in HEK293T cells. Abolishes
FT phosphorylation in HEK293T cells and in neurons; when
FT associated with F-300."
FT /evidence="ECO:0000269|PubMed:21946561"
FT MUTAGEN 300
FT /note="Y->F: Reduced binding to PIK3R2. Slight reduction of
FT phosphorylation in HEK293T cells. Abolishes phosphorylation
FT in HEK293T cells and neurons; when associated with F-277."
FT /evidence="ECO:0000269|PubMed:21946561"
FT CONFLICT 54
FT /note="K -> N (in Ref. 1; BAJ19139, 2; BAC33918/BAE23236
FT and 4; AAH82310)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 682 AA; 73897 MW; 76FDE6609FFDAC8F CRC64;
MIPSKMMSAN PEEDPLDTFF QYIEDMGMKA YDGLVIQNAS DIARENDRLR NETKLAYLKE
KNEKRRRQEE TIKRIGGEVG RGQDASYAGK HFRMGFMTMP APQDRLPHPC SSGFTVRSQS
LHSVGGTEDD SSCGSRRQPP PKPKRDPSTK LSTSSETVNS TAASKSGRSL ERAEGKFTVP
ASHSPPRAST SGHLFPSPGS QERNIKVSAK PRPHSDEYSK KIPPPKPKRN PNTQLSTSFD
ETYIKKHVPR RTSLPRDSSL SQVCSPAADP EEEEPVYIEM VGNILRDFRK EEDDQSEAVY
EEMKYPIFDD LGHDSKCDFD HHSCSSQCAT PTVPDLDFVK SSGPCTPKGL LCDIPPPFPN
LLSHRPPLLV FPPAPVHCSP NSDESPLTPL EVTKLPVLEN VSYMKQPPGA CPSSLPSHGS
SHAKDQTGAL GPAPGASILS SSPPPPSTLY RTQSPHGYPK SHSTSPSPVS MGRSLTPLSL
KRPPPYDAVH SGSLSRSSSS VPHTTPRPVS QDGAKMVNAA VNTYSAAQSG SRSRTPTSPL
EELTSLFTSG RSLLRKSSSG RRSKEPAEKS TEELKVRSHS TEPLPKLDSK ERGHYGSSSS
REPVKAQEWD GTPGPPVVTS RMGRCSVSPT LLAGNHSSEP KVSCKLGRSA STSGVPPPSV
TPLRQASDLQ QSQVPSSLAN RD
