WASL_HUMAN
ID WASL_HUMAN Reviewed; 505 AA.
AC O00401; A1JUI9; Q7Z746;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 2.
DT 03-AUG-2022, entry version 213.
DE RecName: Full=Actin nucleation-promoting factor WASL {ECO:0000305};
DE AltName: Full=Neural Wiskott-Aldrich syndrome protein {ECO:0000303|PubMed:16767080};
DE Short=N-WASP {ECO:0000303|PubMed:16767080};
GN Name=WASL;
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 [MRNA].
RC TISSUE=Brain;
RX PubMed=9322739; DOI=10.1016/s0378-1119(97)00184-4;
RA Fukuoka M., Miki H., Takenawa T.;
RT "Identification of N-WASP homologs in human and rat brain.";
RL Gene 196:43-48(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Melanoma;
RA Lennerz V., Fatho M., Eberts D., Woelfel C., Schreiber S., Huber C.,
RA van der Bruggen P., Schmidt C.W., Woelfel T.;
RT "Analysis of the anti-tumor T cell repertoire of melanoma patients
RT vaccinated with a mixed tumor cell/DC vaccine.";
RL Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [4]
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 [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CDC42.
RX PubMed=9422512; DOI=10.1038/34208;
RA Miki H., Sasaki T., Takai Y., Takenawa T.;
RT "Induction of filopodium formation by a WASP-related actin-depolymerizing
RT protein N-WASP.";
RL Nature 391:93-96(1998).
RN [6]
RP INTERACTION WITH SHIGELLA FLEXNERI ICSA (MICROBIAL INFECTION).
RX PubMed=9582270; DOI=10.1093/emboj/17.10.2767;
RA Suzuki T., Miki H., Takenawa T., Sasakawa C.;
RT "Neural Wiskott-Aldrich syndrome protein is implicated in the actin-based
RT motility of Shigella flexneri.";
RL EMBO J. 17:2767-2776(1998).
RN [7]
RP INTERACTION WITH SHIGELLA FLEXNERI ICSA (MICROBIAL INFECTION).
RX PubMed=10491394; DOI=10.1083/jcb.146.6.1319;
RA Egile C., Loisel T.P., Laurent V., Li R., Pantaloni D., Sansonetti P.J.,
RA Carlier M.-F.;
RT "Activation of the CDC42 effector N-WASP by the Shigella flexneri IcsA
RT protein promotes actin nucleation by Arp2/3 complex and bacterial actin-
RT based motility.";
RL J. Cell Biol. 146:1319-1332(1999).
RN [8]
RP PHOSPHORYLATION AT SER-242 AND TYR-256 BY TNK2, AND INTERACTION WITH TNK2.
RX PubMed=16257963; DOI=10.1074/jbc.m506996200;
RA Yokoyama N., Lougheed J., Miller W.T.;
RT "Phosphorylation of WASP by the Cdc42-associated kinase ACK1: dual
RT hydroxyamino acid specificity in a tyrosine kinase.";
RL J. Biol. Chem. 280:42219-42226(2005).
RN [9]
RP INTERACTION WITH NOSTRIN.
RX PubMed=16234328; DOI=10.1242/jcs.02620;
RA Icking A., Matt S., Opitz N., Wiesenthal A., Mueller-Esterl W.,
RA Schilling K.;
RT "NOSTRIN functions as a homotrimeric adaptor protein facilitating
RT internalization of eNOS.";
RL J. Cell Sci. 118:5059-5069(2005).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN A COMPLEX WITH NONO AND
RP SFPQ, AND INTERACTION WITH NONO.
RX PubMed=16767080; DOI=10.1038/ncb1433;
RA Wu X., Yoo Y., Okuhama N.N., Tucker P.W., Liu G., Guan J.L.;
RT "Regulation of RNA-polymerase-II-dependent transcription by N-WASP and its
RT nuclear-binding partners.";
RL Nat. Cell Biol. 8:756-763(2006).
RN [11]
RP INTERACTION WITH DNMBP.
RX PubMed=17015620; DOI=10.1083/jcb.200605012;
RA Otani T., Ichii T., Aono S., Takeichi M.;
RT "Cdc42 GEF Tuba regulates the junctional configuration of simple epithelial
RT cells.";
RL J. Cell Biol. 175:135-146(2006).
RN [12]
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 [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP FUNCTION, AND INTERACTION WITH SNX33.
RX PubMed=19487689; DOI=10.1074/jbc.m109.007278;
RA Zhang J., Zhang X., Guo Y., Xu L., Pei D.;
RT "Sorting nexin 33 induces mammalian cell micronucleated phenotype and actin
RT polymerization by interacting with Wiskott-Aldrich syndrome protein.";
RL J. Biol. Chem. 284:21659-21669(2009).
RN [15]
RP FUNCTION, AND INTERACTION WITH DNMBP.
RX PubMed=19767742; DOI=10.1038/ncb1964;
RA Rajabian T., Gavicherla B., Heisig M., Mueller-Altrock S., Goebel W.,
RA Gray-Owen S.D., Ireton K.;
RT "The bacterial virulence factor InlC perturbs apical cell junctions and
RT promotes cell-to-cell spread of Listeria.";
RL Nat. Cell Biol. 11:1212-1218(2009).
RN [16]
RP FUNCTION, INTERACTION WITH E.COLI EFFECTOR PROTEIN ESPF(U) (MICROBIAL
RP INFECTION), AND IDENTIFICATION IN A COMPLEX WITH BAIAP2L1 AND E.COLI
RP EFFECTOR PROTEIN ESPF(U).
RX PubMed=19366662; DOI=10.1073/pnas.0809131106;
RA Vingadassalom D., Kazlauskas A., Skehan B., Cheng H.C., Magoun L.,
RA Robbins D., Rosen M.K., Saksela K., Leong J.M.;
RT "Insulin receptor tyrosine kinase substrate links the E. coli O157:H7 actin
RT assembly effectors Tir and EspF(U) during pedestal formation.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:6754-6759(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-256; SER-484 AND SER-485, AND
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 [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-484 AND SER-485, AND
RP IDENTIFICATION BY 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 [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [22]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-307, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
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 [23]
RP INTERACTION WITH FCHSD2.
RX PubMed=29887380; DOI=10.1016/j.cell.2018.05.020;
RA Almeida-Souza L., Frank R.A.W., Garcia-Nafria J., Colussi A.,
RA Gunawardana N., Johnson C.M., Yu M., Howard G., Andrews B., Vallis Y.,
RA McMahon H.T.;
RT "A Flat BAR Protein Promotes Actin Polymerization at the Base of Clathrin-
RT Coated Pits.";
RL Cell 174:325-337(2018).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 451-465.
RX PubMed=16531231; DOI=10.1016/j.str.2005.12.011;
RA Aguda A.H., Xue B., Irobi E., Preat T., Robinson R.C.;
RT "The structural basis of actin interaction with multiple WH2/beta-thymosin
RT motif-containing proteins.";
RL Structure 14:469-476(2006).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 392-484 IN COMPLEX WITH ACTIN,
RP FUNCTION, SUBUNIT, INTERACTION WITH THE ARP2/3 COMPLEX, AND ACTIN-BINDING.
RX PubMed=22847007; DOI=10.1074/jbc.m112.394361;
RA Gaucher J.F., Mauge C., Didry D., Guichard B., Renault L., Carlier M.F.;
RT "Interactions of isolated C-terminal fragments of neural Wiskott-Aldrich
RT syndrome protein (N-WASP) with actin and Arp2/3 complex.";
RL J. Biol. Chem. 287:34646-34659(2012).
RN [26]
RP STRUCTURE BY NMR OF 207-270 IN COMPLEX WITH BAIAP2L1 AND THE E.COLI
RP SECRETED EFFECTOR PROTEIN ESPF(U) (MICROBIAL INFECTION), IDENTIFICATION IN
RP A COMPLEX WITH BAIAP2L1 AND E.COLI EFFECTOR PROTEIN ESPF(U), AND FUNCTION.
RX PubMed=22921828; DOI=10.1016/j.str.2012.07.015;
RA Aitio O., Hellman M., Skehan B., Kesti T., Leong J.M., Saksela K.,
RA Permi P.;
RT "Enterohaemorrhagic Escherichia coli exploits a tryptophan switch to hijack
RT host f-actin assembly.";
RL Structure 20:1692-1703(2012).
RN [27] {ECO:0007744|PDB:4CC2, ECO:0007744|PDB:4CC7}
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 346-357 IN COMPLEX WITH DNMBP,
RP AND SUBUNIT.
RX PubMed=24332715; DOI=10.1016/j.str.2013.10.017;
RA Polle L., Rigano L.A., Julian R., Ireton K., Schubert W.D.;
RT "Structural details of human tuba recruitment by InlC of Listeria
RT monocytogenes elucidate bacterial cell-cell spreading.";
RL Structure 22:304-314(2014).
CC -!- FUNCTION: Regulates actin polymerization by stimulating the actin-
CC nucleating activity of the Arp2/3 complex (PubMed:9422512,
CC PubMed:16767080, PubMed:19366662, PubMed:19487689, PubMed:22847007,
CC PubMed:22921828). Involved in various processes, such as mitosis and
CC cytokinesis, via its role in the regulation of actin polymerization
CC (PubMed:9422512, PubMed:19366662, PubMed:19487689, PubMed:22847007,
CC PubMed:22921828). Together with CDC42, involved in the extension and
CC maintenance of the formation of thin, actin-rich surface projections
CC called filopodia (PubMed:9422512). In addition to its role in the
CC cytoplasm, also plays a role in the nucleus by regulating gene
CC transcription, probably by promoting nuclear actin polymerization
CC (PubMed:16767080). Binds to HSF1/HSTF1 and forms a complex on heat
CC shock promoter elements (HSE) that negatively regulates HSP90
CC expression (By similarity). Plays a role in dendrite spine
CC morphogenesis (By similarity). Decreasing levels of DNMBP (using
CC antisense RNA) alters apical junction morphology in cultured
CC enterocytes, junctions curve instead of being nearly linear
CC (PubMed:19767742). {ECO:0000250|UniProtKB:Q91YD9,
CC ECO:0000269|PubMed:16767080, ECO:0000269|PubMed:19366662,
CC ECO:0000269|PubMed:19487689, ECO:0000269|PubMed:19767742,
CC ECO:0000269|PubMed:22847007, ECO:0000269|PubMed:22921828,
CC ECO:0000269|PubMed:9422512}.
CC -!- SUBUNIT: Binds actin and the Arp2/3 complex (PubMed:22847007).
CC Interacts with CDC42 (PubMed:9422512). Interacts with FCHSD1 (By
CC similarity). Interacts with FCHSD2 (PubMed:29887380). Binds to SH3
CC domains of GRB2. Interacts with the C-terminal SH3 domain of DNMBP
CC (PubMed:19767742, PubMed:24332715, PubMed:17015620). Interacts with
CC SNX9 (By similarity). Interacts with the WW domains of PRPF40A/FBP11
CC (By similarity). Interacts with PTK2/FAK1 (By similarity). Interacts
CC with PACSIN1, PACSIN2 and PACSIN3 (By similarity). Interacts with
CC NOSTRIN (PubMed:16234328). Binds to TNK2 (PubMed:16257963). Interacts
CC with SNX33 (PubMed:19487689). Interacts with NONO (via second RRM
CC domain); the interaction is direct (PubMed:16767080). Component of a
CC multiprotein complex with NONO and SFPQ; associates with the complex
CC via direct interaction with NONO (PubMed:16767080).
CC {ECO:0000250|UniProtKB:Q91YD9, ECO:0000250|UniProtKB:Q95107,
CC ECO:0000269|PubMed:16234328, ECO:0000269|PubMed:16257963,
CC ECO:0000269|PubMed:16767080, ECO:0000269|PubMed:17015620,
CC ECO:0000269|PubMed:19487689, ECO:0000269|PubMed:19767742,
CC ECO:0000269|PubMed:22847007, ECO:0000269|PubMed:24332715,
CC ECO:0000269|PubMed:29887380, ECO:0000269|PubMed:9422512}.
CC -!- SUBUNIT: (Microbial infection) Interacts with E.coli effector protein
CC EspF(U) (PubMed:19366662, PubMed:22921828). Identified in a complex
CC containing at least WASL, BAIAP2L1 and E.coli EspF(U)
CC (PubMed:22921828). {ECO:0000269|PubMed:19366662,
CC ECO:0000269|PubMed:22921828}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Shigella flexneri protein
CC IcsA (PubMed:9582270, PubMed:10491394). The interaction with IcsA
CC enhances the affinity of WASL for Arp2/3, thus assembling a tight
CC complex which has maximal activity in actin assembly (PubMed:9582270,
CC PubMed:10491394). {ECO:0000269|PubMed:10491394,
CC ECO:0000269|PubMed:9582270}.
CC -!- INTERACTION:
CC O00401; Q9NYB9-2: ABI2; NbExp=5; IntAct=EBI-957615, EBI-11096309;
CC O00401; Q8IWW6-4: ARHGAP12; NbExp=3; IntAct=EBI-957615, EBI-11959591;
CC O00401; O15145: ARPC3; NbExp=6; IntAct=EBI-957615, EBI-351829;
CC O00401; P59998: ARPC4; NbExp=3; IntAct=EBI-957615, EBI-351872;
CC O00401; P60953: CDC42; NbExp=3; IntAct=EBI-957615, EBI-81752;
CC O00401; Q99828: CIB1; NbExp=7; IntAct=EBI-957615, EBI-372594;
CC O00401; Q6XZF7-1: DNMBP; NbExp=2; IntAct=EBI-957615, EBI-16085546;
CC O00401; P62993: GRB2; NbExp=11; IntAct=EBI-957615, EBI-401755;
CC O00401; A0A0S2Z4D7: NCK1; NbExp=3; IntAct=EBI-957615, EBI-16429340;
CC O00401; P16333: NCK1; NbExp=2; IntAct=EBI-957615, EBI-389883;
CC O00401; P16333-1: NCK1; NbExp=2; IntAct=EBI-957615, EBI-15578122;
CC O00401; E7ERP6: NCK2; NbExp=3; IntAct=EBI-957615, EBI-16429362;
CC O00401; O43639: NCK2; NbExp=7; IntAct=EBI-957615, EBI-713635;
CC O00401; Q9UNF0: PACSIN2; NbExp=3; IntAct=EBI-957615, EBI-742503;
CC O00401; Q9UKS6: PACSIN3; NbExp=3; IntAct=EBI-957615, EBI-77926;
CC O00401; O96013: PAK4; NbExp=8; IntAct=EBI-957615, EBI-713738;
CC O00401; Q13882: PTK6; NbExp=3; IntAct=EBI-957615, EBI-1383632;
CC O00401; Q9H4E5: RHOJ; NbExp=6; IntAct=EBI-957615, EBI-6285694;
CC O00401; O76064: RNF8; NbExp=8; IntAct=EBI-957615, EBI-373337;
CC O00401; O00560: SDCBP; NbExp=6; IntAct=EBI-957615, EBI-727004;
CC O00401; Q9Y5X1: SNX9; NbExp=2; IntAct=EBI-957615, EBI-77848;
CC O00401; O94875-10: SORBS2; NbExp=3; IntAct=EBI-957615, EBI-12037893;
CC O00401; O60504-2: SORBS3; NbExp=3; IntAct=EBI-957615, EBI-1222956;
CC O00401; Q15642-2: TRIP10; NbExp=5; IntAct=EBI-957615, EBI-6550597;
CC O00401; P57075-2: UBASH3A; NbExp=3; IntAct=EBI-957615, EBI-7353612;
CC O00401; Q8TF42: UBASH3B; NbExp=3; IntAct=EBI-957615, EBI-1380492;
CC O00401; O43516: WIPF1; NbExp=8; IntAct=EBI-957615, EBI-346356;
CC O00401; Q8TF74: WIPF2; NbExp=5; IntAct=EBI-957615, EBI-2850112;
CC O00401; P68135: ACTA1; Xeno; NbExp=2; IntAct=EBI-957615, EBI-367540;
CC O00401; P61157: ACTR3; Xeno; NbExp=3; IntAct=EBI-957615, EBI-351419;
CC O00401; P0DJ88: espF(U); Xeno; NbExp=2; IntAct=EBI-957615, EBI-10039462;
CC O00401; Q8X482: espF(U); Xeno; NbExp=5; IntAct=EBI-957615, EBI-22229752;
CC O00401; Q8R511: Fnbp1; Xeno; NbExp=2; IntAct=EBI-957615, EBI-1111424;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:9422512}. Nucleus {ECO:0000269|PubMed:16767080}.
CC Cytoplasm {ECO:0000250|UniProtKB:Q91YD9}. Note=Preferentially localized
CC in the cytoplasm when phosphorylated and in the nucleus when
CC unphosphorylated (By similarity). Exported from the nucleus by an
CC nuclear export signal (NES)-dependent mechanism to the cytoplasm (By
CC similarity). {ECO:0000250|UniProtKB:Q91YD9}.
CC -!- PTM: Phosphorylation at Ser-242, Tyr-256, Ser-484 and Ser-485 enhances
CC actin polymerization activity. {ECO:0000269|PubMed:16257963}.
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DR EMBL; D88460; BAA20128.1; -; mRNA.
DR EMBL; AM295156; CAL26602.1; -; mRNA.
DR EMBL; AC006333; AAQ96857.1; -; Genomic_DNA.
DR EMBL; BC052955; AAH52955.1; -; mRNA.
DR CCDS; CCDS34743.1; -.
DR RefSeq; NP_003932.3; NM_003941.3.
DR PDB; 2FF3; X-ray; 2.00 A; C=451-465.
DR PDB; 2LNH; NMR; -; A=207-270.
DR PDB; 2VCP; X-ray; 3.20 A; D/E=392-484.
DR PDB; 4CC2; X-ray; 1.55 A; B/D=346-357.
DR PDB; 4CC7; X-ray; 1.97 A; B/D/F/H/J/L/N=346-357.
DR PDBsum; 2FF3; -.
DR PDBsum; 2LNH; -.
DR PDBsum; 2VCP; -.
DR PDBsum; 4CC2; -.
DR PDBsum; 4CC7; -.
DR AlphaFoldDB; O00401; -.
DR BMRB; O00401; -.
DR SMR; O00401; -.
DR BioGRID; 114466; 104.
DR CORUM; O00401; -.
DR DIP; DIP-29042N; -.
DR ELM; O00401; -.
DR IntAct; O00401; 69.
DR MINT; O00401; -.
DR STRING; 9606.ENSP00000223023; -.
DR GlyGen; O00401; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O00401; -.
DR PhosphoSitePlus; O00401; -.
DR BioMuta; WASL; -.
DR EPD; O00401; -.
DR jPOST; O00401; -.
DR MassIVE; O00401; -.
DR MaxQB; O00401; -.
DR PaxDb; O00401; -.
DR PeptideAtlas; O00401; -.
DR PRIDE; O00401; -.
DR ProteomicsDB; 47867; -.
DR Antibodypedia; 1487; 243 antibodies from 37 providers.
DR DNASU; 8976; -.
DR Ensembl; ENST00000223023.5; ENSP00000223023.4; ENSG00000106299.8.
DR GeneID; 8976; -.
DR KEGG; hsa:8976; -.
DR MANE-Select; ENST00000223023.5; ENSP00000223023.4; NM_003941.4; NP_003932.3.
DR UCSC; uc003vkz.5; human.
DR CTD; 8976; -.
DR DisGeNET; 8976; -.
DR GeneCards; WASL; -.
DR HGNC; HGNC:12735; WASL.
DR HPA; ENSG00000106299; Low tissue specificity.
DR MIM; 605056; gene.
DR neXtProt; NX_O00401; -.
DR OpenTargets; ENSG00000106299; -.
DR PharmGKB; PA37346; -.
DR VEuPathDB; HostDB:ENSG00000106299; -.
DR eggNOG; KOG3671; Eukaryota.
DR GeneTree; ENSGT00730000110895; -.
DR HOGENOM; CLU_015385_3_1_1; -.
DR InParanoid; O00401; -.
DR OMA; LGRKCQT; -.
DR OrthoDB; 1407277at2759; -.
DR PhylomeDB; O00401; -.
DR TreeFam; TF316736; -.
DR PathwayCommons; O00401; -.
DR Reactome; R-HSA-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-HSA-203641; NOSTRIN mediated eNOS trafficking.
DR Reactome; R-HSA-373753; Nephrin family interactions.
DR Reactome; R-HSA-3928662; EPHB-mediated forward signaling.
DR Reactome; R-HSA-418885; DCC mediated attractive signaling.
DR Reactome; R-HSA-5663213; RHO GTPases Activate WASPs and WAVEs.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013406; RHOQ GTPase cycle.
DR Reactome; R-HSA-9013409; RHOJ GTPase cycle.
DR Reactome; R-HSA-9013424; RHOV GTPase cycle.
DR Reactome; R-HSA-9664422; FCGR3A-mediated phagocytosis.
DR SignaLink; O00401; -.
DR SIGNOR; O00401; -.
DR BioGRID-ORCS; 8976; 33 hits in 1092 CRISPR screens.
DR ChiTaRS; WASL; human.
DR EvolutionaryTrace; O00401; -.
DR GeneWiki; WASL_(gene); -.
DR GenomeRNAi; 8976; -.
DR Pharos; O00401; Tbio.
DR PRO; PR:O00401; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; O00401; protein.
DR Bgee; ENSG00000106299; Expressed in middle temporal gyrus and 203 other tissues.
DR Genevisible; O00401; HS.
DR GO; GO:0030478; C:actin cap; IEA:Ensembl.
DR GO; GO:0015629; C:actin cytoskeleton; TAS:ProtInc.
DR GO; GO:0005884; C:actin filament; IBA:GO_Central.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0030666; C:endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR GO; GO:0030695; F:GTPase regulator activity; TAS:ProtInc.
DR GO; GO:0030041; P:actin filament polymerization; IDA:UniProtKB.
DR GO; GO:0030048; P:actin filament-based movement; IBA:GO_Central.
DR GO; GO:0008154; P:actin polymerization or depolymerization; TAS:ProtInc.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0060997; P:dendritic spine morphogenesis; ISS:UniProtKB.
DR GO; GO:2000402; P:negative regulation of lymphocyte migration; IMP:CACAO.
DR GO; GO:1903526; P:negative regulation of membrane tubulation; IDA:UniProtKB.
DR GO; GO:2000601; P:positive regulation of Arp2/3 complex-mediated actin nucleation; IEA:InterPro.
DR GO; GO:2000370; P:positive regulation of clathrin-dependent endocytosis; ISS:BHF-UCL.
DR GO; GO:0051491; P:positive regulation of filopodium assembly; ISS:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; TAS:ProtInc.
DR GO; GO:0031503; P:protein-containing complex localization; IEA:Ensembl.
DR GO; GO:0032880; P:regulation of protein localization; IEA:Ensembl.
DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
DR GO; GO:0051653; P:spindle localization; IEA:Ensembl.
DR GO; GO:0006900; P:vesicle budding from membrane; ISS:BHF-UCL.
DR GO; GO:0016050; P:vesicle organization; ISS:BHF-UCL.
DR GO; GO:0030050; P:vesicle transport along actin filament; ISS:BHF-UCL.
DR CDD; cd01205; EVH1_WASP-like; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.90.810.10; -; 2.
DR IDEAL; IID00256; -.
DR InterPro; IPR000095; CRIB_dom.
DR InterPro; IPR036936; CRIB_dom_sf.
DR InterPro; IPR030214; N-WASP.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR011026; WASP_C.
DR InterPro; IPR033927; WASPfam_EVH1.
DR InterPro; IPR000697; WH1/EVH1_dom.
DR InterPro; IPR003124; WH2_dom.
DR PANTHER; PTHR23202:SF39; PTHR23202:SF39; 1.
DR Pfam; PF00786; PBD; 1.
DR Pfam; PF00568; WH1; 1.
DR Pfam; PF02205; WH2; 2.
DR SMART; SM00285; PBD; 1.
DR SMART; SM00461; WH1; 1.
DR SMART; SM00246; WH2; 2.
DR SUPFAM; SSF47912; SSF47912; 2.
DR PROSITE; PS50108; CRIB; 1.
DR PROSITE; PS50229; WH1; 1.
DR PROSITE; PS51082; WH2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Actin-binding; Cell cycle; Cell division;
KW Cytoplasm; Cytoskeleton; Methylation; Mitosis; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Transcription; Transcription regulation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT CHAIN 2..505
FT /note="Actin nucleation-promoting factor WASL"
FT /id="PRO_0000189000"
FT DOMAIN 34..141
FT /note="WH1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00410"
FT DOMAIN 203..216
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT DOMAIN 405..422
FT /note="WH2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00406"
FT DOMAIN 433..450
FT /note="WH2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00406"
FT REGION 138..163
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 184..205
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 266..406
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 476..505
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 274..394
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 486..505
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT MOD_RES 242
FT /note="Phosphoserine; by TNK2"
FT /evidence="ECO:0000269|PubMed:16257963"
FT MOD_RES 256
FT /note="Phosphotyrosine; by FAK1 and TNK2"
FT /evidence="ECO:0000269|PubMed:16257963,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 307
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 484
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 485
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT CONFLICT 76
FT /note="Y -> H (in Ref. 1; BAA20128)"
FT /evidence="ECO:0000305"
FT CONFLICT 201
FT /note="A -> G (in Ref. 1; BAA20128)"
FT /evidence="ECO:0000305"
FT CONFLICT 223
FT /note="F -> S (in Ref. 1; BAA20128)"
FT /evidence="ECO:0000305"
FT CONFLICT 242
FT /note="S -> L (in Ref. 1; BAA20128)"
FT /evidence="ECO:0000305"
FT CONFLICT 248
FT /note="D -> E (in Ref. 1; BAA20128)"
FT /evidence="ECO:0000305"
FT CONFLICT 252
FT /note="S -> L (in Ref. 1; BAA20128)"
FT /evidence="ECO:0000305"
FT CONFLICT 296
FT /note="N -> S (in Ref. 1; BAA20128)"
FT /evidence="ECO:0000305"
FT CONFLICT 333
FT /note="A -> E (in Ref. 1; BAA20128)"
FT /evidence="ECO:0000305"
FT CONFLICT 351
FT /note="P -> L (in Ref. 2; CAL26602)"
FT /evidence="ECO:0000305"
FT TURN 219..221
FT /evidence="ECO:0007829|PDB:2LNH"
FT HELIX 225..227
FT /evidence="ECO:0007829|PDB:2LNH"
FT HELIX 232..239
FT /evidence="ECO:0007829|PDB:2LNH"
FT HELIX 243..246
FT /evidence="ECO:0007829|PDB:2LNH"
FT TURN 249..251
FT /evidence="ECO:0007829|PDB:2LNH"
FT HELIX 252..262
FT /evidence="ECO:0007829|PDB:2LNH"
FT HELIX 265..269
FT /evidence="ECO:0007829|PDB:2LNH"
FT HELIX 435..443
FT /evidence="ECO:0007829|PDB:2VCP"
SQ SEQUENCE 505 AA; 54827 MW; B5895C6055E23049 CRC64;
MSSVQQQPPP PRRVTNVGSL LLTPQENESL FTFLGKKCVT MSSAVVQLYA ADRNCMWSKK
CSGVACLVKD NPQRSYFLRI FDIKDGKLLW EQELYNNFVY NSPRGYFHTF AGDTCQVALN
FANEEEAKKF RKAVTDLLGR RQRKSEKRRD PPNGPNLPMA TVDIKNPEIT TNRFYGPQVN
NISHTKEKKK GKAKKKRLTK ADIGTPSNFQ HIGHVGWDPN TGFDLNNLDP ELKNLFDMCG
ISEAQLKDRE TSKVIYDFIE KTGGVEAVKN ELRRQAPPPP PPSRGGPPPP PPPPHNSGPP
PPPARGRGAP PPPPSRAPTA APPPPPPSRP SVAVPPPPPN RMYPPPPPAL PSSAPSGPPP
PPPSVLGVGP VAPPPPPPPP PPPGPPPPPG LPSDGDHQVP TTAGNKAALL DQIREGAQLK
KVEQNSRPVS CSGRDALLDQ IRQGIQLKSV ADGQESTPPT PAPTSGIVGA LMEVMQKRSK
AIHSSDEDED EDDEEDFEDD DEWED
