NCKP1_MOUSE
ID NCKP1_MOUSE Reviewed; 1128 AA.
AC P28660; Q3UPY6; Q80TX0; Q8CG49; Q99KY0;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 22-NOV-2005, sequence version 2.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Nck-associated protein 1;
DE Short=NAP 1;
DE AltName: Full=Brain protein H19;
DE AltName: Full=MH19;
DE AltName: Full=Membrane-associated protein HEM-2;
DE AltName: Full=p125Nap1;
GN Name=Nckap1; Synonyms=Hem2, Kiaa0587, Nap1;
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 1), FUNCTION, SUBCELLULAR LOCATION, AND
RP COMPONENT OF WAVE2 COMPLEX.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=14765121; DOI=10.1038/sj.emboj.7600084;
RA Steffen A., Rottner K., Ehinger J., Innocenti M., Scita G., Wehland J.,
RA Stradal T.E.B.;
RT "Sra-1 and Nap1 link Rac to actin assembly driving lamellipodia
RT formation.";
RL EMBO J. 23:749-759(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=12693553; DOI=10.1093/dnares/10.1.35;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S.,
RA Nakajima D., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: II.
RT The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:35-48(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 288-935 (ISOFORMS 1/2).
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=12106288; DOI=10.1111/j.1460-9568.1990.tb00460.x;
RA Kato K.;
RT "A collection of cDNA clones with specific expression patterns in mouse
RT brain.";
RL Eur. J. Neurosci. 2:704-711(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 755-1128 (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 876-1128 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Eye;
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, 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 [7]
RP INTERACTION WITH NYAP1; NYAP2 AND MYO16.
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 [8]
RP FUNCTION OF WAVE1 COMPLEX.
RX PubMed=27605705; DOI=10.1091/mbc.e16-05-0326;
RA Xu C., Fu X., Zhu S., Liu J.J.;
RT "Retrolinkin recruits the WAVE1 protein complex to facilitate BDNF-induced
RT TrkB endocytosis and dendrite outgrowth.";
RL Mol. Biol. Cell 27:3342-3356(2016).
CC -!- FUNCTION: Part of the WAVE complex that regulates lamellipodia
CC formation. The WAVE complex regulates actin filament reorganization via
CC its interaction with the Arp2/3 complex. Actin remodeling activity is
CC regulated by RAC1. As component of the WAVE1 complex, required for
CC BDNF-NTRK2 endocytic trafficking and signaling from early endosomes
CC (PubMed:27605705). {ECO:0000269|PubMed:14765121,
CC ECO:0000269|PubMed:27605705}.
CC -!- SUBUNIT: Associates preferentially with the first SH3 domain of NCK (By
CC similarity). Component of the WAVE1 complex composed of ABI2, CYFIP1 or
CC CYFIP2, BRK1, NCKAP1 and WASF1/WAVE1. Within the complex, a heterodimer
CC containing NCKAP1 and CYFIP1 interacts with a heterotrimer formed by
CC WAVE1, ABI2 and BRK1. Component of the WAVE2 complex composed of ABI1,
CC CYFIP1/SRA1, NCKAP1/NAP1 and WASF2/WAVE2. CYFIP2 binds to activated
CC RAC1 which causes the complex to dissociate, releasing activated WASF1.
CC The complex can also be activated by NCK1. Interacts with NYAP1, NYAP2
CC and MYO16. {ECO:0000250|UniProtKB:Q9Y2A7, ECO:0000269|PubMed:21946561}.
CC -!- INTERACTION:
CC P28660; Q5DU14: Myo16; NbExp=2; IntAct=EBI-771576, EBI-7448308;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14765121};
CC Single-pass membrane protein {ECO:0000269|PubMed:14765121}; Cytoplasmic
CC side {ECO:0000269|PubMed:14765121}. Cell projection, lamellipodium
CC membrane {ECO:0000269|PubMed:14765121}; Single-pass membrane protein
CC {ECO:0000269|PubMed:14765121}; Cytoplasmic side
CC {ECO:0000269|PubMed:14765121}. Cytoplasm {ECO:0000269|PubMed:14765121}.
CC Note=At the interface between the lamellipodial actin meshwork and the
CC membrane.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P28660-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P28660-2; Sequence=VSP_016261, VSP_016262;
CC -!- TISSUE SPECIFICITY: High expression in cerebral cortex, not in
CC cerebellar cortex.
CC -!- SIMILARITY: Belongs to the HEM-1/HEM-2 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC65600.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AJ534525; CAD58932.1; -; mRNA.
DR EMBL; AK122318; BAC65600.1; ALT_INIT; Transcribed_RNA.
DR EMBL; X61453; CAA43693.1; -; mRNA.
DR EMBL; BC003962; AAH03962.1; -; mRNA.
DR EMBL; AK143049; BAE25258.1; -; mRNA.
DR CCDS; CCDS16177.1; -. [P28660-1]
DR PIR; S16866; S16866.
DR RefSeq; NP_058661.1; NM_016965.3. [P28660-1]
DR AlphaFoldDB; P28660; -.
DR SMR; P28660; -.
DR BioGRID; 206144; 58.
DR CORUM; P28660; -.
DR IntAct; P28660; 37.
DR MINT; P28660; -.
DR STRING; 10090.ENSMUSP00000028386; -.
DR iPTMnet; P28660; -.
DR PhosphoSitePlus; P28660; -.
DR EPD; P28660; -.
DR jPOST; P28660; -.
DR MaxQB; P28660; -.
DR PaxDb; P28660; -.
DR PeptideAtlas; P28660; -.
DR PRIDE; P28660; -.
DR ProteomicsDB; 252923; -. [P28660-1]
DR ProteomicsDB; 252924; -. [P28660-2]
DR Antibodypedia; 19761; 212 antibodies from 32 providers.
DR DNASU; 50884; -.
DR Ensembl; ENSMUST00000028386; ENSMUSP00000028386; ENSMUSG00000027002. [P28660-1]
DR GeneID; 50884; -.
DR KEGG; mmu:50884; -.
DR UCSC; uc008khm.2; mouse. [P28660-1]
DR CTD; 10787; -.
DR MGI; MGI:1355333; Nckap1.
DR VEuPathDB; HostDB:ENSMUSG00000027002; -.
DR eggNOG; KOG1917; Eukaryota.
DR GeneTree; ENSGT00390000016619; -.
DR HOGENOM; CLU_004450_0_0_1; -.
DR InParanoid; P28660; -.
DR OMA; XSIVGMT; -.
DR TreeFam; TF313683; -.
DR Reactome; R-MMU-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-MMU-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-MMU-5663213; RHO GTPases Activate WASPs and WAVEs.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR Reactome; R-MMU-9013404; RAC2 GTPase cycle.
DR Reactome; R-MMU-9013423; RAC3 GTPase cycle.
DR BioGRID-ORCS; 50884; 12 hits in 75 CRISPR screens.
DR ChiTaRS; Nckap1; mouse.
DR PRO; PR:P28660; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P28660; protein.
DR Bgee; ENSMUSG00000027002; Expressed in CA3 field of hippocampus and 268 other tissues.
DR ExpressionAtlas; P28660; baseline and differential.
DR Genevisible; P28660; MM.
DR GO; GO:0031941; C:filamentous actin; IDA:BHF-UCL.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0030027; C:lamellipodium; IDA:BHF-UCL.
DR GO; GO:0031258; C:lamellipodium membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0098794; C:postsynapse; IDA:SynGO.
DR GO; GO:0001726; C:ruffle; IDA:BHF-UCL.
DR GO; GO:0031209; C:SCAR complex; ISO:MGI.
DR GO; GO:0031267; F:small GTPase binding; ISO:MGI.
DR GO; GO:0045176; P:apical protein localization; IDA:MGI.
DR GO; GO:0045175; P:basal protein localization; IDA:MGI.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0042074; P:cell migration involved in gastrulation; IMP:MGI.
DR GO; GO:0000902; P:cell morphogenesis; IBA:GO_Central.
DR GO; GO:0030031; P:cell projection assembly; IBA:GO_Central.
DR GO; GO:0030866; P:cortical actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0010172; P:embryonic body morphogenesis; IMP:MGI.
DR GO; GO:0048617; P:embryonic foregut morphogenesis; IMP:MGI.
DR GO; GO:0035050; P:embryonic heart tube development; IMP:MGI.
DR GO; GO:0007492; P:endoderm development; IMP:MGI.
DR GO; GO:0030950; P:establishment or maintenance of actin cytoskeleton polarity; IMP:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0030032; P:lamellipodium assembly; IDA:MGI.
DR GO; GO:0008078; P:mesodermal cell migration; IMP:MGI.
DR GO; GO:0001843; P:neural tube closure; IMP:MGI.
DR GO; GO:0048812; P:neuron projection morphogenesis; IBA:GO_Central.
DR GO; GO:0030903; P:notochord development; IMP:MGI.
DR GO; GO:0048570; P:notochord morphogenesis; IMP:MGI.
DR GO; GO:0048339; P:paraxial mesoderm development; IMP:MGI.
DR GO; GO:0048340; P:paraxial mesoderm morphogenesis; IMP:MGI.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IDA:BHF-UCL.
DR GO; GO:2000601; P:positive regulation of Arp2/3 complex-mediated actin nucleation; ISO:MGI.
DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; IDA:BHF-UCL.
DR GO; GO:0050821; P:protein stabilization; IMP:MGI.
DR GO; GO:0016601; P:Rac protein signal transduction; ISO:MGI.
DR GO; GO:0032880; P:regulation of protein localization; IMP:MGI.
DR GO; GO:0001756; P:somitogenesis; IMP:MGI.
DR GO; GO:0007354; P:zygotic determination of anterior/posterior axis, embryo; IMP:MGI.
DR InterPro; IPR019137; Nck-associated_protein-1.
DR PANTHER; PTHR12093; PTHR12093; 1.
DR Pfam; PF09735; Nckap1; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cell membrane; Cell projection;
KW Cytoplasm; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2A7"
FT CHAIN 2..1128
FT /note="Nck-associated protein 1"
FT /id="PRO_0000216173"
FT TRANSMEM 995..1015
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 640..665
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 647..665
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2A7"
FT VAR_SEQ 242..263
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12693553"
FT /id="VSP_016261"
FT VAR_SEQ 1060..1128
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12693553"
FT /id="VSP_016262"
FT CONFLICT 745
FT /note="A -> E (in Ref. 3; CAA43693)"
FT /evidence="ECO:0000305"
FT CONFLICT 876
FT /note="V -> F (in Ref. 5; BAE25258)"
FT /evidence="ECO:0000305"
FT CONFLICT 934..935
FT /note="FL -> SS (in Ref. 3; CAA43693)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1128 AA; 128784 MW; 279246384B0F4B77 CRC64;
MSRSVLQPSQ QKLAEKLTIL NDRGVGMLTR LYNIKKACGD PKAKPSYLID KNLESAVKFI
VRKFPAVETR NNNQQLAQLQ KEKSEILKNL ALYYFTFVDV MEFKDHVCDL LNTIDVCQVF
FDITVNFDLT KNYLDLTVTY TTLMILLSRI EERKAIIGLY NYAHEMTHGA SDREYPRLGQ
MIVDYENPLK KMMEEFVPHS KSLSDALISL QMVYPRRNLS ADQWRNAQLL SLISAPSTML
NPAQSDTMPC EYLSLDAMEK WIIFGFILCH GMLNTEATAL NLWKLALQSS SCLSLFRDEV
FHIHKAAEDL FVNIRGYNKR INDIRECKEA AVSHAGSMHR ERRKFLRSAL KELATVLSDQ
PGLLGPKALF VFMALSFARD EIIWLLRHAD NMPKKSADDF IDKHIAELIF YMEELRAHVR
KYGPVMQRYY VQYLSGFDAV VLNELVQNLS VCPEDESIIM SSFVNTMTSL SVKQVEDGEV
FDFRGMRLDW FRLQAYTSVS KASLSLADHR ELGKMMNTII FHTKMVDSLV EMLVETSDLS
IFCFYSRAFE KMFQQCLELP SQSRYSIAFP LLCTHFMSCT HELCPEERHH IGDRSLSLCN
MFLDEMAKQA RNLITDICTE QCTLSDQLLP KHCAKTISQA VNKKSKKQTG KKGEPEREKP
GVESMRKNRL VVTNLDKLHT ALSELCFSIN YVPNMAVWEH TFTPREYLTS HLEIRFTKSI
VGMTMYNQAT QEIAKPSELL TSVRAYMTVL QSIENYVQID ITRVFNNVLL QQTQHLDSHG
EPTITSLYTN WYLETLLRQV SNGHIAYFPA MKAFVNLPTE NELTFNAEEY SDISEMRSLS
ELLGPYGMKF LSESLMWHIS SQVAELKKLV VENVDVLTQM RTSFDKPDQM AALFKRLSSV
DSVLKRMTII GVILSFRSLA QEALRDVLSY HIPFLVSSIE DFKDHIPRET DMKVAMNVYE
LSSAAGLPCE IDPALVVALS SQKSENISPE EEYKIACLLM VFVAVSLPTL ASNVMSQYSP
AIEGHCNNIH CLAKAINQIA AALFTIHKGS IEDRLKEFLA LASSSLLKIG QETDKTTTRN
RESVYLLLDM IVQESPFLTM DLLESCFPYV LLRNAYHAVY KQSVTSSA
