WAC_HUMAN
ID WAC_HUMAN Reviewed; 647 AA.
AC Q9BTA9; A8K2A9; C9JBT9; D3DRW5; D3DRW6; D3DRW7; Q53EN9; Q5JU75; Q5JU77;
AC Q5VXK0; Q5VXK2; Q8TCK1; Q96DP3; Q96FW6; Q96JI3;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=WW domain-containing adapter protein with coiled-coil;
GN Name=WAC; Synonyms=KIAA1844;
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] (ISOFORMS 1 AND 2).
RC TISSUE=Kidney, and Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 157-647 (ISOFORM 4).
RC TISSUE=Kidney, and Urinary bladder;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 69-647 (ISOFORMS 1/2).
RC TISSUE=Brain;
RX PubMed=11347906; DOI=10.1093/dnares/8.2.85;
RA Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 8:85-95(2001).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-511, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-53, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-293, AND IDENTIFICATION BY
RP 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 IDENTIFICATION BY MASS SPECTROMETRY [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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-471; SER-523 AND SER-525, AND
RP IDENTIFICATION BY 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 [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-302, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-53, AND IDENTIFICATION BY
RP 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 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 [16]
RP FUNCTION.
RX PubMed=22354037; DOI=10.1038/emboj.2012.36;
RA McKnight N.C., Jefferies H.B., Alemu E.A., Saunders R.E., Howell M.,
RA Johansen T., Tooze S.A.;
RT "Genome-wide siRNA screen reveals amino acid starvation-induced autophagy
RT requires SCOC and WAC.";
RL EMBO J. 31:1931-1946(2012).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-53; SER-131; SER-142;
RP SER-225; THR-293; SER-511; SER-523 AND SER-525, AND IDENTIFICATION BY MASS
RP 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 THR-293; SER-446; SER-523 AND
RP SER-525, AND IDENTIFICATION BY 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 INVOLVEMENT IN DESSH.
RX PubMed=25356899; DOI=10.1371/journal.pgen.1004772;
RA Hamdan F.F., Srour M., Capo-Chichi J.M., Daoud H., Nassif C., Patry L.,
RA Massicotte C., Ambalavanan A., Spiegelman D., Diallo O., Henrion E.,
RA Dionne-Laporte A., Fougerat A., Pshezhetsky A.V., Venkateswaran S.,
RA Rouleau G.A., Michaud J.L.;
RT "De novo mutations in moderate or severe intellectual disability.";
RL PLoS Genet. 10:E1004772-E1004772(2014).
RN [20]
RP INVOLVEMENT IN DESSH.
RX PubMed=26264232; DOI=10.1136/jmedgenet-2015-103069;
RG DDD Study;
RA DeSanto C., D'Aco K., Araujo G.C., Shannon N., Vernon H., Rahrig A.,
RA Monaghan K.G., Niu Z., Vitazka P., Dodd J., Tang S., Manwaring L.,
RA Martir-Negron A., Schnur R.E., Juusola J., Schroeder A., Pan V.,
RA Helbig K.L., Friedman B., Shinawi M.;
RT "WAC loss-of-function mutations cause a recognisable syndrome characterised
RT by dysmorphic features, developmental delay and hypotonia and recapitulate
RT 10p11.23 microdeletion syndrome.";
RL J. Med. Genet. 52:754-761(2015).
RN [21]
RP FUNCTION, AND INTERACTION WITH MTOR; RPTOR; RUVBL1; RUVBL2; TTI1 AND TTI2.
RX PubMed=26812014; DOI=10.1016/j.devcel.2015.12.019;
RA David-Morrison G., Xu Z., Rui Y.N., Charng W.L., Jaiswal M., Yamamoto S.,
RA Xiong B., Zhang K., Sandoval H., Duraine L., Zuo Z., Zhang S., Bellen H.J.;
RT "WAC regulates mTOR activity by acting as an adaptor for the TTT and
RT Pontin/Reptin complexes.";
RL Dev. Cell 36:139-151(2016).
RN [22]
RP INVOLVEMENT IN INTELLECTUAL DISABILITY.
RX PubMed=26757981; DOI=10.1038/ejhg.2015.282;
RA Lugtenberg D., Reijnders M.R., Fenckova M., Bijlsma E.K., Bernier R.,
RA van Bon B.W., Smeets E., Vulto-van Silfhout A.T., Bosch D., Eichler E.E.,
RA Mefford H.C., Carvill G.L., Bongers E.M., Schuurs-Hoeijmakers J.H.,
RA Ruivenkamp C.A., Santen G.W., van den Maagdenberg A.M.,
RA Peeters-Scholte C.M., Kuenen S., Verstreken P., Pfundt R., Yntema H.G.,
RA de Vries P.F., Veltman J.A., Hoischen A., Gilissen C., de Vries B.B.,
RA Schenck A., Kleefstra T., Vissers L.E.;
RT "De novo loss-of-function mutations in WAC cause a recognizable
RT intellectual disability syndrome and learning deficits in Drosophila.";
RL Eur. J. Hum. Genet. 24:1145-1153(2016).
RN [23]
RP VARIANT [LARGE SCALE ANALYSIS] LEU-475.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [24]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH RNA POLYMERASE II;
RP RNF20; RNF40 AND UBE2A.
RX PubMed=21329877; DOI=10.1016/j.molcel.2011.01.024;
RA Zhang F., Yu X.;
RT "WAC, a functional partner of RNF20/40, regulates histone H2B
RT ubiquitination and gene transcription.";
RL Mol. Cell 41:384-397(2011).
RN [25]
RP VARIANT 47-ARG--VAL-647 DEL.
RX PubMed=23033978; DOI=10.1056/nejmoa1206524;
RA de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G.,
RA Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P., Gilissen C.,
RA del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G.,
RA Veltman J.A., Vissers L.E.;
RT "Diagnostic exome sequencing in persons with severe intellectual
RT disability.";
RL N. Engl. J. Med. 367:1921-1929(2012).
CC -!- FUNCTION: Acts as a linker between gene transcription and histone H2B
CC monoubiquitination at 'Lys-120' (H2BK120ub1) (PubMed:21329877).
CC Interacts with the RNA polymerase II transcriptional machinery via its
CC WW domain and with RNF20-RNF40 via its coiled coil region, thereby
CC linking and regulating H2BK120ub1 and gene transcription
CC (PubMed:21329877). Regulates the cell-cycle checkpoint activation in
CC response to DNA damage (PubMed:21329877). Positive regulator of amino
CC acid starvation-induced autophagy (PubMed:22354037). Also acts as a
CC negative regulator of basal autophagy (PubMed:26812014). Positively
CC regulates MTOR activity by promoting, in an energy-dependent manner,
CC the assembly of the TTT complex composed of TELO2, TTI1 and TTI2 and
CC the RUVBL complex composed of RUVBL1 and RUVBL2 into the TTT-RUVBL
CC complex. This leads to the dimerization of the mTORC1 complex and its
CC subsequent activation (PubMed:26812014). May negatively regulate the
CC ubiquitin proteasome pathway (PubMed:21329877).
CC {ECO:0000269|PubMed:21329877, ECO:0000269|PubMed:22354037,
CC ECO:0000269|PubMed:26812014}.
CC -!- SUBUNIT: Interacts (via coiled coil domain) with RNF20, RNF40 and UBE2A
CC (PubMed:21329877). Interacts (via WW domain) with RNA polymerase II
CC (PubMed:21329877). Interacts with MTOR and other components of the MTOR
CC pathway including RPTOR, RUVBL1, RUVBL2, TTI1 and TTI2
CC (PubMed:26812014). {ECO:0000269|PubMed:21329877,
CC ECO:0000269|PubMed:26812014}.
CC -!- INTERACTION:
CC Q9BTA9; Q99996-2: AKAP9; NbExp=3; IntAct=EBI-749118, EBI-9641546;
CC Q9BTA9; Q8WWB3: DYDC1; NbExp=3; IntAct=EBI-749118, EBI-740680;
CC Q9BTA9; P42858: HTT; NbExp=5; IntAct=EBI-749118, EBI-466029;
CC Q9BTA9; Q6P597: KLC3; NbExp=3; IntAct=EBI-749118, EBI-1643885;
CC Q9BTA9; P19012: KRT15; NbExp=4; IntAct=EBI-749118, EBI-739566;
CC Q9BTA9; Q5JR59: MTUS2; NbExp=3; IntAct=EBI-749118, EBI-742948;
CC Q9BTA9; Q16236: NFE2L2; NbExp=3; IntAct=EBI-749118, EBI-2007911;
CC Q9BTA9; Q8TDW5: SYTL5; NbExp=3; IntAct=EBI-749118, EBI-2939487;
CC Q9BTA9; Q13077: TRAF1; NbExp=3; IntAct=EBI-749118, EBI-359224;
CC Q9BTA9; Q9Y228: TRAF3IP3; NbExp=3; IntAct=EBI-749118, EBI-765817;
CC Q9BTA9-2; P19012: KRT15; NbExp=3; IntAct=EBI-10298216, EBI-739566;
CC Q9BTA9-2; Q5JR59: MTUS2; NbExp=3; IntAct=EBI-10298216, EBI-742948;
CC Q9BTA9-5; P42858: HTT; NbExp=3; IntAct=EBI-25956668, EBI-466029;
CC -!- SUBCELLULAR LOCATION: Nucleus speckle {ECO:0000250|UniProtKB:Q924H7}.
CC Nucleus {ECO:0000269|PubMed:21329877}. Note=In distinct nuclear
CC speckles. Colocalizes with pre-mRNA processing complexes.
CC {ECO:0000250|UniProtKB:Q924H7}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9BTA9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BTA9-2; Sequence=VSP_021230;
CC Name=3;
CC IsoId=Q9BTA9-3; Sequence=VSP_021230, VSP_021233, VSP_021236;
CC Name=4;
CC IsoId=Q9BTA9-5; Sequence=VSP_021231;
CC -!- PTM: Phosphorylated on tyrosine residues.
CC {ECO:0000250|UniProtKB:Q924H7}.
CC -!- DISEASE: DeSanto-Shinawi syndrome (DESSH) [MIM:616708]: An autosomal
CC dominant syndrome characterized by developmental delay, hypotonia,
CC behavioral problems, eye abnormalities, constipation, feeding
CC difficulties, seizures and sleep problems. Patients exhibit dysmorphic
CC features, including broad/prominent forehead, synophrys and/or bushy
CC eyebrows, depressed nasal bridge and bulbous nasal tip. Additional
CC variable features are posteriorly rotated ears, hirsutism, deep-set
CC eyes, thin upper lip, inverted nipples, hearing loss and branchial
CC cleft anomalies. {ECO:0000269|PubMed:25356899,
CC ECO:0000269|PubMed:26264232}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Note=Defects in WAC are the cause of a form of intellectual
CC disability characterized by hypotonia, behavioral problems and
CC distinctive facial dysmorphisms including a square-shaped face, deep
CC set eyes, long palpebral fissures, and a broad mouth and chin.
CC {ECO:0000269|PubMed:26757981}.
CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH04258.2; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAH10356.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB47473.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
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DR EMBL; AK055852; BAB71029.1; -; mRNA.
DR EMBL; AK223600; BAD97320.1; -; mRNA.
DR EMBL; AK290174; BAF82863.1; -; mRNA.
DR EMBL; AL713727; CAD28517.1; -; mRNA.
DR EMBL; AL161936; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL358234; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471072; EAW86032.1; -; Genomic_DNA.
DR EMBL; CH471072; EAW86035.1; -; Genomic_DNA.
DR EMBL; CH471072; EAW86037.1; -; Genomic_DNA.
DR EMBL; CH471072; EAW86039.1; -; Genomic_DNA.
DR EMBL; CH471072; EAW86040.1; -; Genomic_DNA.
DR EMBL; CH471072; EAW86042.1; -; Genomic_DNA.
DR EMBL; BC004258; AAH04258.2; ALT_FRAME; mRNA.
DR EMBL; BC010356; AAH10356.1; ALT_INIT; mRNA.
DR EMBL; AB058747; BAB47473.1; ALT_SEQ; mRNA.
DR CCDS; CCDS7159.1; -. [Q9BTA9-1]
DR CCDS; CCDS7160.1; -. [Q9BTA9-5]
DR CCDS; CCDS7161.1; -. [Q9BTA9-2]
DR RefSeq; NP_057712.2; NM_016628.4. [Q9BTA9-1]
DR RefSeq; NP_567822.1; NM_100264.2. [Q9BTA9-2]
DR RefSeq; NP_567823.1; NM_100486.3. [Q9BTA9-5]
DR RefSeq; XP_011517793.1; XM_011519491.2.
DR AlphaFoldDB; Q9BTA9; -.
DR SMR; Q9BTA9; -.
DR BioGRID; 119473; 66.
DR IntAct; Q9BTA9; 39.
DR MINT; Q9BTA9; -.
DR STRING; 9606.ENSP00000346986; -.
DR GlyGen; Q9BTA9; 4 sites, 1 O-linked glycan (4 sites).
DR iPTMnet; Q9BTA9; -.
DR PhosphoSitePlus; Q9BTA9; -.
DR BioMuta; WAC; -.
DR DMDM; 117949358; -.
DR EPD; Q9BTA9; -.
DR jPOST; Q9BTA9; -.
DR MassIVE; Q9BTA9; -.
DR MaxQB; Q9BTA9; -.
DR PaxDb; Q9BTA9; -.
DR PeptideAtlas; Q9BTA9; -.
DR PRIDE; Q9BTA9; -.
DR ProteomicsDB; 78963; -. [Q9BTA9-1]
DR ProteomicsDB; 78964; -. [Q9BTA9-2]
DR ProteomicsDB; 78965; -. [Q9BTA9-3]
DR ProteomicsDB; 78966; -. [Q9BTA9-5]
DR Antibodypedia; 50013; 131 antibodies from 25 providers.
DR DNASU; 51322; -.
DR Ensembl; ENST00000347934.8; ENSP00000311106.4; ENSG00000095787.24. [Q9BTA9-5]
DR Ensembl; ENST00000354911.9; ENSP00000346986.4; ENSG00000095787.24. [Q9BTA9-1]
DR Ensembl; ENST00000375664.8; ENSP00000364816.3; ENSG00000095787.24. [Q9BTA9-2]
DR Ensembl; ENST00000439676.5; ENSP00000415727.1; ENSG00000095787.24. [Q9BTA9-3]
DR Ensembl; ENST00000442148.6; ENSP00000400848.2; ENSG00000095787.24. [Q9BTA9-2]
DR Ensembl; ENST00000679398.1; ENSP00000506624.1; ENSG00000095787.24. [Q9BTA9-2]
DR Ensembl; ENST00000679428.1; ENSP00000506445.1; ENSG00000095787.24. [Q9BTA9-2]
DR GeneID; 51322; -.
DR KEGG; hsa:51322; -.
DR MANE-Select; ENST00000354911.9; ENSP00000346986.4; NM_016628.5; NP_057712.2.
DR UCSC; uc001iud.3; human. [Q9BTA9-1]
DR CTD; 51322; -.
DR DisGeNET; 51322; -.
DR GeneCards; WAC; -.
DR GeneReviews; WAC; -.
DR HGNC; HGNC:17327; WAC.
DR HPA; ENSG00000095787; Low tissue specificity.
DR MalaCards; WAC; -.
DR MIM; 615049; gene.
DR MIM; 616708; phenotype.
DR neXtProt; NX_Q9BTA9; -.
DR OpenTargets; ENSG00000095787; -.
DR Orphanet; 284169; Facial dysmorphism-developmental delay-behavioral abnormalities syndrome due to 10p11.21p12.31 microdeletion.
DR Orphanet; 466950; Facial dysmorphism-developmental delay-behavioral abnormalities syndrome due to WAC point mutation.
DR PharmGKB; PA134978936; -.
DR VEuPathDB; HostDB:ENSG00000095787; -.
DR eggNOG; KOG0152; Eukaryota.
DR GeneTree; ENSGT00440000037780; -.
DR HOGENOM; CLU_024845_2_1_1; -.
DR InParanoid; Q9BTA9; -.
DR OMA; ICLSENC; -.
DR OrthoDB; 1111788at2759; -.
DR PhylomeDB; Q9BTA9; -.
DR TreeFam; TF328635; -.
DR PathwayCommons; Q9BTA9; -.
DR Reactome; R-HSA-8866654; E3 ubiquitin ligases ubiquitinate target proteins.
DR SignaLink; Q9BTA9; -.
DR SIGNOR; Q9BTA9; -.
DR BioGRID-ORCS; 51322; 325 hits in 1082 CRISPR screens.
DR ChiTaRS; WAC; human.
DR GeneWiki; WAC_(gene); -.
DR GenomeRNAi; 51322; -.
DR Pharos; Q9BTA9; Tbio.
DR PRO; PR:Q9BTA9; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9BTA9; protein.
DR Bgee; ENSG00000095787; Expressed in endothelial cell and 204 other tissues.
DR ExpressionAtlas; Q9BTA9; baseline and differential.
DR Genevisible; Q9BTA9; HS.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005681; C:spliceosomal complex; IEA:Ensembl.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0000993; F:RNA polymerase II complex binding; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0071894; P:histone H2B conserved C-terminal lysine ubiquitination; IMP:UniProtKB.
DR GO; GO:0010390; P:histone monoubiquitination; IMP:UniProtKB.
DR GO; GO:0031571; P:mitotic G1 DNA damage checkpoint signaling; IMP:UniProtKB.
DR GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:BHF-UCL.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IMP:BHF-UCL.
DR GO; GO:1904263; P:positive regulation of TORC1 signaling; IBA:GO_Central.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; IBA:GO_Central.
DR CDD; cd00201; WW; 1.
DR InterPro; IPR038867; WAC.
DR InterPro; IPR001202; WW_dom.
DR InterPro; IPR036020; WW_dom_sf.
DR PANTHER; PTHR15911; PTHR15911; 1.
DR Pfam; PF00397; WW; 1.
DR SMART; SM00456; WW; 1.
DR SUPFAM; SSF51045; SSF51045; 1.
DR PROSITE; PS01159; WW_DOMAIN_1; 1.
DR PROSITE; PS50020; WW_DOMAIN_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Chromatin regulator; Coiled coil;
KW Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..647
FT /note="WW domain-containing adapter protein with coiled-
FT coil"
FT /id="PRO_0000254558"
FT DOMAIN 129..162
FT /note="WW"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT REGION 1..138
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 168..353
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 428..549
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 618..644
FT /evidence="ECO:0000255"
FT COMPBIAS 35..51
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 61..92
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 93..129
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 168..191
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 195..225
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 258..304
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 313..346
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 53
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 131
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 142
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 225
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 293
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 302
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 446
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 471
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 511
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 523
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 525
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..45
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_021230"
FT VAR_SEQ 204..307
FT /note="MEDKHSSDASSLLPQNILSQTSRHNDRDYRLPRAETHSSSTPVQHPIKPVVH
FT PTATPSTVPSSPFTLQSDHQPKKSFDANGASTLSKLPTPTSSVPAQKTERKE -> K
FT (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_021231"
FT VAR_SEQ 430..481
FT /note="AQPSNQSPMSLTSDASSPRSYVSPRISTPQTNTVPIKPLISTPPVSSQPKVS
FT -> DIPLHEGIQMERDTHRSKWEVKGSLCQKADKQQECLVWNGSIMVQRLLQPSG (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_021233"
FT VAR_SEQ 482..647
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_021236"
FT VARIANT 47..647
FT /note="Missing (probable disease-associated variant found
FT in a patient severe intellectual disability)"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_078694"
FT VARIANT 242
FT /note="S -> R (in dbSNP:rs11595926)"
FT /id="VAR_028838"
FT VARIANT 309
FT /note="T -> A (in dbSNP:rs2232791)"
FT /id="VAR_053448"
FT VARIANT 475
FT /note="S -> L (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036351"
FT VARIANT 531
FT /note="T -> S (in dbSNP:rs7127)"
FT /id="VAR_028839"
FT CONFLICT 426
FT /note="L -> F (in Ref. 1; BAB71029)"
FT /evidence="ECO:0000305"
FT CONFLICT 581
FT /note="K -> R (in Ref. 6; AAH10356)"
FT /evidence="ECO:0000305"
FT CONFLICT 599
FT /note="S -> P (in Ref. 2; BAD97320)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 647 AA; 70724 MW; 15C32DAAA3A94129 CRC64;
MVMYARKQQR LSDGCHDRRG DSQPYQALKY SSKSHPSSGD HRHEKMRDAG DPSPPNKMLR
RSDSPENKYS DSTGHSKAKN VHTHRVRERD GGTSYSPQEN SHNHSALHSS NSHSSNPSNN
PSKTSDAPYD SADDWSEHIS SSGKKYYYNC RTEVSQWEKP KEWLEREQRQ KEANKMAVNS
FPKDRDYRRE VMQATATSGF ASGMEDKHSS DASSLLPQNI LSQTSRHNDR DYRLPRAETH
SSSTPVQHPI KPVVHPTATP STVPSSPFTL QSDHQPKKSF DANGASTLSK LPTPTSSVPA
QKTERKESTS GDKPVSHSCT TPSTSSASGL NPTSAPPTSA SAVPVSPVPQ SPIPPLLQDP
NLLRQLLPAL QATLQLNNSN VDISKINEVL TAAVTQASLQ SIIHKFLTAG PSAFNITSLI
SQAAQLSTQA QPSNQSPMSL TSDASSPRSY VSPRISTPQT NTVPIKPLIS TPPVSSQPKV
STPVVKQGPV SQSATQQPVT ADKQQGHEPV SPRSLQRSSS QRSPSPGPNH TSNSSNASNA
TVVPQNSSAR STCSLTPALA AHFSENLIKH VQGWPADHAE KQASRLREEA HNMGTIHMSE
ICTELKNLRS LVRVCEIQAT LREQRILFLR QQIKELEKLK NQNSFMV
