PHIP_HUMAN
ID PHIP_HUMAN Reviewed; 1821 AA.
AC Q8WWQ0; A7J992; B2RPK4; Q05CQ9; Q5VVH4; Q66I29; Q69YV1; Q8NBZ5; Q96H52;
AC Q96ME2; Q9H261;
DT 21-AUG-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 2.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=PH-interacting protein;
DE Short=PHIP;
DE AltName: Full=DDB1- and CUL4-associated factor 14;
DE AltName: Full=IRS-1 PH domain-binding protein;
DE AltName: Full=WD repeat-containing protein 11;
GN Name=PHIP; Synonyms=DCAF14, WDR11;
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], AND VARIANT GLY-663.
RX PubMed=17636024; DOI=10.1128/mcb.02409-06;
RA Podcheko A., Northcott P., Bikopoulos G., Lee A., Bommareddi S.R.,
RA Kushner J.A., Farhang-Fallah J., Rozakis-Adcock M.;
RT "Identification of a WD40 repeat-containing isoform of PHIP as a novel
RT regulator of beta-cell growth and survival.";
RL Mol. Cell. Biol. 27:6484-6496(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLY-663.
RA Antonarakis S.E.;
RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLY-663.
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS GLY-663; ILE-874 AND
RP PRO-1093.
RC TISSUE=Brain, Lymph, and Skin;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-912, NUCLEOTIDE SEQUENCE [LARGE
RP SCALE MRNA] OF 1230-1821, AND VARIANT GLY-663.
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 905-1821, AND VARIANT PRO-1093.
RC TISSUE=Amygdala;
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 [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 960-1821, AND TISSUE SPECIFICITY.
RX PubMed=11018022; DOI=10.1074/jbc.c000611200;
RA Farhang-Fallah J., Yin X., Trentin G., Cheng A.M., Rozakis-Adcock M.;
RT "Cloning and characterization of PHIP, a novel insulin receptor substrate-1
RT pleckstrin homology domain interacting protein.";
RL J. Biol. Chem. 275:40492-40497(2000).
RN [9]
RP FUNCTION.
RX PubMed=12242307; DOI=10.1128/mcb.22.20.7325-7336.2002;
RA Farhang-Fallah J., Randhawa V.K., Nimnual A., Klip A., Bar-Sagi D.,
RA Rozakis-Adcock M.;
RT "The pleckstrin homology (PH) domain-interacting protein couples the
RT insulin receptor substrate 1 PH domain to insulin signaling pathways
RT leading to mitogenesis and GLUT4 translocation.";
RL Mol. Cell. Biol. 22:7325-7336(2002).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-911, 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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-683, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-136; SER-1281; SER-1283;
RP SER-1296; SER-1405; SER-1479 AND SER-1783, AND IDENTIFICATION BY MASS
RP 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 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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1281; SER-1283; SER-1315 AND
RP SER-1783, AND 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 [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-1497 AND LYS-1533, AND
RP IDENTIFICATION BY MASS 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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-641; SER-659; SER-692;
RP SER-911; SER-1315; THR-1359; SER-1405; SER-1525; SER-1651; SER-1762 AND
RP SER-1783, VARIANT [LARGE SCALE ANALYSIS] GLY-663, 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 [17]
RP FUNCTION.
RX PubMed=21834987; DOI=10.1186/1741-7007-9-54;
RA Bai S.W., Herrera-Abreu M.T., Rohn J.L., Racine V., Tajadura V.,
RA Suryavanshi N., Bechtel S., Wiemann S., Baum B., Ridley A.J.;
RT "Identification and characterization of a set of conserved and new
RT regulators of cytoskeletal organisation, cell morphology and migration.";
RL BMC Biol. 9:54-54(2011).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-683; SER-692; SER-879;
RP SER-880; SER-881; SER-911; SER-1315 AND SER-1783, AND IDENTIFICATION BY
RP 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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-674; SER-677; SER-683;
RP SER-911; SER-1281; SER-1283; SER-1315; SER-1525; SER-1560; SER-1762 AND
RP SER-1783, AND IDENTIFICATION BY MASS 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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1315, AND IDENTIFICATION BY
RP 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 [21]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1470, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [22]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-421 AND LYS-1470, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [23]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-421; LYS-1470; LYS-1644 AND
RP LYS-1670, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 1302-1434, AND SUBUNIT.
RX PubMed=22464331; DOI=10.1016/j.cell.2012.02.013;
RA Filippakopoulos P., Picaud S., Mangos M., Keates T., Lambert J.P.,
RA Barsyte-Lovejoy D., Felletar I., Volkmer R., Muller S., Pawson T.,
RA Gingras A.C., Arrowsmith C.H., Knapp S.;
RT "Histone recognition and large-scale structural analysis of the human
RT bromodomain family.";
RL Cell 149:214-231(2012).
RN [25]
RP VARIANTS [LARGE SCALE ANALYSIS] ILE-469 AND ILE-1767.
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 [26]
RP INVOLVEMENT IN CHUJANS, AND VARIANT CHUJANS 1149-TYR--TRP-1821 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).
RN [27]
RP INVOLVEMENT IN CHUJANS, AND VARIANT CHUJANS SER-17.
RX PubMed=27900362; DOI=10.1101/mcs.a001172;
RA Webster E., Cho M.T., Alexander N., Desai S., Naidu S., Bekheirnia M.R.,
RA Lewis A., Retterer K., Juusola J., Chung W.K.;
RT "De novo PHIP-predicted deleterious variants are associated with
RT developmental delay, intellectual disability, obesity, and dysmorphic
RT features.";
RL Cold Spring Harb. Mol. Case Stud. 2:A001172-A001172(2016).
RN [28]
RP INVOLVEMENT IN CHUJANS, AND VARIANTS CHUJANS CYS-110; SER-110;
RP 274-GLN--TRP-1821 DEL; 555-GLN--TRP-1821 DEL; 634-GLN--TRP-1821 DEL;
RP 968-ARG--TRP-1821 DEL; 1149-TYR--TRP-1821 DEL; 1191-GLN--TRP-1821 DEL;
RP GLU-1263; 1298-ARG--TRP-1821 DEL AND 1354-ARG--TRP-1821 DEL.
RX PubMed=29209020; DOI=10.1038/s41431-017-0039-5;
RA Jansen S., Hoischen A., Coe B.P., Carvill G.L., Van Esch H., Bosch D.G.M.,
RA Andersen U.A., Baker C., Bauters M., Bernier R.A., van Bon B.W.,
RA Claahsen-van der Grinten H.L., Gecz J., Gilissen C., Grillo L., Hackett A.,
RA Kleefstra T., Koolen D., Kvarnung M., Larsen M.J., Marcelis C.,
RA McKenzie F., Monin M.L., Nava C., Schuurs-Hoeijmakers J.H., Pfundt R.,
RA Steehouwer M., Stevens S.J.C., Stumpel C.T., Vansenne F., Vinci M.,
RA van de Vorst M., Vries P., Witherspoon K., Veltman J.A., Brunner H.G.,
RA Mefford H.C., Romano C., Vissers L.E.L.M., Eichler E.E., de Vries B.B.A.;
RT "A genotype-first approach identifies an intellectual disability-overweight
RT syndrome caused by PHIP haploinsufficiency.";
RL Eur. J. Hum. Genet. 26:54-63(2018).
CC -!- FUNCTION: Probable regulator of the insulin and insulin-like growth
CC factor signaling pathways. Stimulates cell proliferation through
CC regulation of cyclin transcription and has an anti-apoptotic activity
CC through AKT1 phosphorylation and activation. Plays a role in the
CC regulation of cell morphology and cytoskeletal organization.
CC {ECO:0000269|PubMed:12242307, ECO:0000269|PubMed:21834987}.
CC -!- SUBUNIT: Interacts with IRS1 and IRS2 (By similarity). Interacts (via
CC bromo domain) with acetylated lysine residues on histone H1.4, histone
CC H3 and H4 (in vitro). {ECO:0000250, ECO:0000269|PubMed:22464331}.
CC -!- INTERACTION:
CC Q8WWQ0; P40337-2: VHL; NbExp=3; IntAct=EBI-722984, EBI-12157263;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in myeloma and epidermoid carcinoma cell
CC lines. {ECO:0000269|PubMed:11018022}.
CC -!- DISEASE: Chung-Jansen syndrome (CHUJANS) [MIM:617991]: An autosomal
CC dominant disorder characterized by developmental delay, intellectual
CC disability, autistic features, anxiety, hypotonia, obesity, and
CC dysmorphic features. {ECO:0000269|PubMed:23033978,
CC ECO:0000269|PubMed:27900362, ECO:0000269|PubMed:29209020}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH21905.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=BAC11417.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; DQ924532; ABK76299.1; -; mRNA.
DR EMBL; AJ303102; CAC83118.1; -; mRNA.
DR EMBL; AL450327; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL356776; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW48718.1; -; Genomic_DNA.
DR EMBL; BC008909; AAH08909.2; -; mRNA.
DR EMBL; BC021905; AAH21905.1; ALT_SEQ; mRNA.
DR EMBL; BC081569; AAH81569.1; -; mRNA.
DR EMBL; BC137488; AAI37489.1; -; mRNA.
DR EMBL; AK057039; BAB71353.1; -; mRNA.
DR EMBL; AK075124; BAC11417.1; ALT_FRAME; mRNA.
DR EMBL; AL161957; CAH10776.1; -; mRNA.
DR EMBL; AF310250; AAG45145.1; -; mRNA.
DR CCDS; CCDS4987.1; -.
DR RefSeq; NP_060404.4; NM_017934.6.
DR PDB; 3MB3; X-ray; 2.25 A; A=1302-1434.
DR PDB; 5ENB; X-ray; 1.73 A; A=1315-1440.
DR PDB; 5ENC; X-ray; 1.59 A; A=1315-1440.
DR PDB; 5ENE; X-ray; 1.49 A; A=1315-1440.
DR PDB; 5ENF; X-ray; 1.37 A; A=1315-1440.
DR PDB; 5ENH; X-ray; 1.95 A; A=1315-1440.
DR PDB; 5ENI; X-ray; 1.69 A; A=1315-1440.
DR PDB; 5ENJ; X-ray; 1.63 A; A=1315-1440.
DR PDB; 5RJI; X-ray; 1.24 A; A=1315-1440.
DR PDB; 5RJJ; X-ray; 1.15 A; A=1315-1440.
DR PDB; 5RJK; X-ray; 1.21 A; A=1315-1440.
DR PDB; 5RJL; X-ray; 1.31 A; A=1315-1440.
DR PDB; 5RJM; X-ray; 1.41 A; A=1315-1440.
DR PDB; 5RJN; X-ray; 1.44 A; A=1315-1440.
DR PDB; 5RJO; X-ray; 1.22 A; A=1315-1440.
DR PDB; 5RJP; X-ray; 1.24 A; A=1315-1440.
DR PDB; 5RJQ; X-ray; 1.35 A; A=1315-1440.
DR PDB; 5RJR; X-ray; 1.27 A; A=1315-1440.
DR PDB; 5RJS; X-ray; 1.37 A; A=1315-1440.
DR PDB; 5RJT; X-ray; 1.17 A; A=1315-1440.
DR PDB; 5RJU; X-ray; 1.32 A; A=1315-1440.
DR PDB; 5RJV; X-ray; 1.45 A; A=1315-1440.
DR PDB; 5RJW; X-ray; 1.51 A; A=1315-1440.
DR PDB; 5RJX; X-ray; 1.29 A; A=1315-1440.
DR PDB; 5RJY; X-ray; 1.25 A; A=1315-1440.
DR PDB; 5RJZ; X-ray; 1.27 A; A=1315-1440.
DR PDB; 5RK0; X-ray; 1.24 A; A=1315-1440.
DR PDB; 5RK1; X-ray; 1.27 A; A=1315-1440.
DR PDB; 5RK2; X-ray; 1.24 A; A=1315-1440.
DR PDB; 5RK3; X-ray; 1.31 A; A=1315-1440.
DR PDB; 5RK4; X-ray; 1.28 A; A=1315-1440.
DR PDB; 5RK5; X-ray; 1.24 A; A=1315-1440.
DR PDB; 5RK6; X-ray; 1.24 A; A=1315-1440.
DR PDB; 5RK7; X-ray; 1.30 A; A=1315-1440.
DR PDB; 5RK8; X-ray; 1.27 A; A=1315-1440.
DR PDB; 5RK9; X-ray; 1.48 A; A=1315-1440.
DR PDB; 5RKA; X-ray; 1.33 A; A=1315-1440.
DR PDB; 5RKB; X-ray; 1.28 A; A=1315-1440.
DR PDB; 5RKC; X-ray; 1.24 A; A=1315-1440.
DR PDB; 5RKD; X-ray; 1.24 A; A=1315-1440.
DR PDB; 5RKE; X-ray; 1.29 A; A=1315-1440.
DR PDB; 5RKF; X-ray; 1.26 A; A=1315-1440.
DR PDB; 5RKG; X-ray; 1.28 A; A=1315-1440.
DR PDB; 5RKH; X-ray; 1.25 A; A=1315-1440.
DR PDB; 5RKI; X-ray; 1.27 A; A=1315-1440.
DR PDB; 5RKJ; X-ray; 1.46 A; A=1315-1440.
DR PDB; 5RKK; X-ray; 1.43 A; A=1315-1440.
DR PDB; 5RKL; X-ray; 1.36 A; A=1315-1440.
DR PDB; 5RKM; X-ray; 1.28 A; A=1315-1440.
DR PDB; 5RKN; X-ray; 1.23 A; A=1315-1440.
DR PDB; 5RKO; X-ray; 1.42 A; A=1315-1440.
DR PDB; 5RKP; X-ray; 1.35 A; A=1315-1440.
DR PDB; 5RKQ; X-ray; 1.30 A; A=1315-1440.
DR PDB; 5RKR; X-ray; 1.37 A; A=1315-1440.
DR PDB; 5RKS; X-ray; 1.24 A; A=1315-1440.
DR PDB; 5RKT; X-ray; 1.24 A; A=1315-1440.
DR PDB; 5RKU; X-ray; 1.40 A; A=1315-1440.
DR PDB; 5RKV; X-ray; 1.28 A; A=1315-1440.
DR PDB; 5RKW; X-ray; 1.24 A; A=1315-1440.
DR PDB; 5RKX; X-ray; 1.24 A; A=1315-1440.
DR PDB; 5RKY; X-ray; 1.38 A; A=1315-1440.
DR PDB; 5S8C; X-ray; 1.25 A; A=1315-1440.
DR PDB; 5S8D; X-ray; 1.26 A; A=1315-1440.
DR PDB; 5S8E; X-ray; 1.24 A; A=1315-1440.
DR PDB; 5S8F; X-ray; 1.18 A; A=1315-1440.
DR PDB; 5S8G; X-ray; 1.19 A; A=1315-1440.
DR PDB; 5S8H; X-ray; 1.29 A; A=1315-1440.
DR PDB; 5S8I; X-ray; 1.30 A; A=1315-1440.
DR PDB; 5S8J; X-ray; 1.21 A; A=1315-1440.
DR PDB; 5S8K; X-ray; 1.24 A; A=1315-1440.
DR PDB; 5S8L; X-ray; 1.23 A; A=1315-1440.
DR PDB; 5S8M; X-ray; 1.20 A; A=1315-1440.
DR PDB; 5S8N; X-ray; 1.23 A; A=1315-1440.
DR PDB; 5S8O; X-ray; 1.67 A; A/B=1315-1440.
DR PDB; 5S8P; X-ray; 1.41 A; A/B=1315-1440.
DR PDB; 5S8Q; X-ray; 1.50 A; A/B=1315-1440.
DR PDB; 5S8R; X-ray; 1.22 A; A=1315-1440.
DR PDB; 5S8S; X-ray; 1.22 A; A=1315-1440.
DR PDB; 5S8T; X-ray; 1.22 A; A=1315-1440.
DR PDB; 5S8U; X-ray; 1.33 A; A=1315-1440.
DR PDB; 5S8V; X-ray; 1.18 A; A=1315-1440.
DR PDB; 5S8W; X-ray; 1.20 A; A=1315-1440.
DR PDB; 5S8X; X-ray; 1.15 A; A=1315-1440.
DR PDB; 5S8Y; X-ray; 1.24 A; A=1315-1440.
DR PDB; 5S8Z; X-ray; 1.25 A; A=1315-1440.
DR PDB; 5S90; X-ray; 1.10 A; A=1315-1440.
DR PDB; 5S91; X-ray; 1.29 A; A=1315-1440.
DR PDB; 5S92; X-ray; 1.19 A; A=1315-1440.
DR PDB; 5S93; X-ray; 1.19 A; A=1315-1440.
DR PDB; 5S94; X-ray; 1.20 A; A=1315-1440.
DR PDB; 5S95; X-ray; 1.21 A; A=1315-1440.
DR PDB; 5S96; X-ray; 1.17 A; A=1315-1440.
DR PDB; 5S97; X-ray; 1.15 A; A=1315-1440.
DR PDB; 5S98; X-ray; 1.10 A; A=1315-1440.
DR PDB; 5S99; X-ray; 1.18 A; A=1315-1440.
DR PDB; 5S9A; X-ray; 1.36 A; A=1315-1440.
DR PDB; 5S9B; X-ray; 1.15 A; A=1315-1440.
DR PDB; 5S9C; X-ray; 1.14 A; A=1315-1440.
DR PDB; 5S9D; X-ray; 1.19 A; A=1315-1440.
DR PDB; 5S9E; X-ray; 1.18 A; A=1315-1440.
DR PDB; 5S9F; X-ray; 1.35 A; A=1315-1440.
DR PDB; 5S9G; X-ray; 1.09 A; A=1315-1440.
DR PDB; 5S9H; X-ray; 1.32 A; A=1315-1440.
DR PDB; 5S9I; X-ray; 1.41 A; A=1315-1440.
DR PDB; 5S9J; X-ray; 1.15 A; A=1315-1440.
DR PDB; 7AV8; X-ray; 1.63 A; AAA=1315-1440.
DR PDB; 7AV9; X-ray; 1.23 A; AAA=1315-1440.
DR PDB; 7BBO; X-ray; 1.32 A; AAA/BBB=1315-1440.
DR PDB; 7BBP; X-ray; 1.99 A; AAA/BBB/CCC/DDD=1315-1440.
DR PDBsum; 3MB3; -.
DR PDBsum; 5ENB; -.
DR PDBsum; 5ENC; -.
DR PDBsum; 5ENE; -.
DR PDBsum; 5ENF; -.
DR PDBsum; 5ENH; -.
DR PDBsum; 5ENI; -.
DR PDBsum; 5ENJ; -.
DR PDBsum; 5RJI; -.
DR PDBsum; 5RJJ; -.
DR PDBsum; 5RJK; -.
DR PDBsum; 5RJL; -.
DR PDBsum; 5RJM; -.
DR PDBsum; 5RJN; -.
DR PDBsum; 5RJO; -.
DR PDBsum; 5RJP; -.
DR PDBsum; 5RJQ; -.
DR PDBsum; 5RJR; -.
DR PDBsum; 5RJS; -.
DR PDBsum; 5RJT; -.
DR PDBsum; 5RJU; -.
DR PDBsum; 5RJV; -.
DR PDBsum; 5RJW; -.
DR PDBsum; 5RJX; -.
DR PDBsum; 5RJY; -.
DR PDBsum; 5RJZ; -.
DR PDBsum; 5RK0; -.
DR PDBsum; 5RK1; -.
DR PDBsum; 5RK2; -.
DR PDBsum; 5RK3; -.
DR PDBsum; 5RK4; -.
DR PDBsum; 5RK5; -.
DR PDBsum; 5RK6; -.
DR PDBsum; 5RK7; -.
DR PDBsum; 5RK8; -.
DR PDBsum; 5RK9; -.
DR PDBsum; 5RKA; -.
DR PDBsum; 5RKB; -.
DR PDBsum; 5RKC; -.
DR PDBsum; 5RKD; -.
DR PDBsum; 5RKE; -.
DR PDBsum; 5RKF; -.
DR PDBsum; 5RKG; -.
DR PDBsum; 5RKH; -.
DR PDBsum; 5RKI; -.
DR PDBsum; 5RKJ; -.
DR PDBsum; 5RKK; -.
DR PDBsum; 5RKL; -.
DR PDBsum; 5RKM; -.
DR PDBsum; 5RKN; -.
DR PDBsum; 5RKO; -.
DR PDBsum; 5RKP; -.
DR PDBsum; 5RKQ; -.
DR PDBsum; 5RKR; -.
DR PDBsum; 5RKS; -.
DR PDBsum; 5RKT; -.
DR PDBsum; 5RKU; -.
DR PDBsum; 5RKV; -.
DR PDBsum; 5RKW; -.
DR PDBsum; 5RKX; -.
DR PDBsum; 5RKY; -.
DR PDBsum; 5S8C; -.
DR PDBsum; 5S8D; -.
DR PDBsum; 5S8E; -.
DR PDBsum; 5S8F; -.
DR PDBsum; 5S8G; -.
DR PDBsum; 5S8H; -.
DR PDBsum; 5S8I; -.
DR PDBsum; 5S8J; -.
DR PDBsum; 5S8K; -.
DR PDBsum; 5S8L; -.
DR PDBsum; 5S8M; -.
DR PDBsum; 5S8N; -.
DR PDBsum; 5S8O; -.
DR PDBsum; 5S8P; -.
DR PDBsum; 5S8Q; -.
DR PDBsum; 5S8R; -.
DR PDBsum; 5S8S; -.
DR PDBsum; 5S8T; -.
DR PDBsum; 5S8U; -.
DR PDBsum; 5S8V; -.
DR PDBsum; 5S8W; -.
DR PDBsum; 5S8X; -.
DR PDBsum; 5S8Y; -.
DR PDBsum; 5S8Z; -.
DR PDBsum; 5S90; -.
DR PDBsum; 5S91; -.
DR PDBsum; 5S92; -.
DR PDBsum; 5S93; -.
DR PDBsum; 5S94; -.
DR PDBsum; 5S95; -.
DR PDBsum; 5S96; -.
DR PDBsum; 5S97; -.
DR PDBsum; 5S98; -.
DR PDBsum; 5S99; -.
DR PDBsum; 5S9A; -.
DR PDBsum; 5S9B; -.
DR PDBsum; 5S9C; -.
DR PDBsum; 5S9D; -.
DR PDBsum; 5S9E; -.
DR PDBsum; 5S9F; -.
DR PDBsum; 5S9G; -.
DR PDBsum; 5S9H; -.
DR PDBsum; 5S9I; -.
DR PDBsum; 5S9J; -.
DR PDBsum; 7AV8; -.
DR PDBsum; 7AV9; -.
DR PDBsum; 7BBO; -.
DR PDBsum; 7BBP; -.
DR AlphaFoldDB; Q8WWQ0; -.
DR SMR; Q8WWQ0; -.
DR BioGRID; 120353; 184.
DR IntAct; Q8WWQ0; 29.
DR MINT; Q8WWQ0; -.
DR STRING; 9606.ENSP00000275034; -.
DR ChEMBL; CHEMBL2176773; -.
DR GlyGen; Q8WWQ0; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8WWQ0; -.
DR PhosphoSitePlus; Q8WWQ0; -.
DR SwissPalm; Q8WWQ0; -.
DR BioMuta; PHIP; -.
DR DMDM; 308153472; -.
DR CPTAC; CPTAC-1363; -.
DR EPD; Q8WWQ0; -.
DR jPOST; Q8WWQ0; -.
DR MassIVE; Q8WWQ0; -.
DR MaxQB; Q8WWQ0; -.
DR PaxDb; Q8WWQ0; -.
DR PeptideAtlas; Q8WWQ0; -.
DR PRIDE; Q8WWQ0; -.
DR ProteomicsDB; 74919; -.
DR ABCD; Q8WWQ0; 1 sequenced antibody.
DR Antibodypedia; 31574; 117 antibodies from 21 providers.
DR DNASU; 55023; -.
DR Ensembl; ENST00000275034.5; ENSP00000275034.3; ENSG00000146247.14.
DR GeneID; 55023; -.
DR KEGG; hsa:55023; -.
DR MANE-Select; ENST00000275034.5; ENSP00000275034.3; NM_017934.7; NP_060404.4.
DR UCSC; uc003pir.4; human.
DR CTD; 55023; -.
DR DisGeNET; 55023; -.
DR GeneCards; PHIP; -.
DR HGNC; HGNC:15673; PHIP.
DR HPA; ENSG00000146247; Low tissue specificity.
DR MalaCards; PHIP; -.
DR MIM; 612870; gene.
DR MIM; 617991; phenotype.
DR neXtProt; NX_Q8WWQ0; -.
DR OpenTargets; ENSG00000146247; -.
DR Orphanet; 589905; PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome.
DR PharmGKB; PA33265; -.
DR VEuPathDB; HostDB:ENSG00000146247; -.
DR eggNOG; KOG0644; Eukaryota.
DR GeneTree; ENSGT00950000183107; -.
DR HOGENOM; CLU_001108_0_0_1; -.
DR InParanoid; Q8WWQ0; -.
DR OMA; EQADCKN; -.
DR OrthoDB; 240778at2759; -.
DR PhylomeDB; Q8WWQ0; -.
DR TreeFam; TF324197; -.
DR PathwayCommons; Q8WWQ0; -.
DR Reactome; R-HSA-9013418; RHOBTB2 GTPase cycle.
DR SignaLink; Q8WWQ0; -.
DR SIGNOR; Q8WWQ0; -.
DR BioGRID-ORCS; 55023; 64 hits in 1141 CRISPR screens.
DR ChiTaRS; PHIP; human.
DR EvolutionaryTrace; Q8WWQ0; -.
DR GenomeRNAi; 55023; -.
DR Pharos; Q8WWQ0; Tbio.
DR PRO; PR:Q8WWQ0; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q8WWQ0; protein.
DR Bgee; ENSG00000146247; Expressed in bronchial epithelial cell and 210 other tissues.
DR Genevisible; Q8WWQ0; HS.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005158; F:insulin receptor binding; NAS:UniProtKB.
DR GO; GO:0070577; F:lysine-acetylated histone binding; IDA:UniProtKB.
DR GO; GO:0007010; P:cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0008286; P:insulin receptor signaling pathway; NAS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IDA:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0043568; P:positive regulation of insulin-like growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0022604; P:regulation of cell morphogenesis; IMP:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; IBA:GO_Central.
DR GO; GO:0001932; P:regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 1.20.920.10; -; 2.
DR Gene3D; 2.130.10.10; -; 2.
DR InterPro; IPR001487; Bromodomain.
DR InterPro; IPR036427; Bromodomain-like_sf.
DR InterPro; IPR018359; Bromodomain_CS.
DR InterPro; IPR028738; PHIP.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR16266:SF4; PTHR16266:SF4; 1.
DR Pfam; PF00439; Bromodomain; 2.
DR Pfam; PF00400; WD40; 5.
DR PRINTS; PR00503; BROMODOMAIN.
DR SMART; SM00297; BROMO; 2.
DR SMART; SM00320; WD40; 8.
DR SUPFAM; SSF47370; SSF47370; 2.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS00633; BROMODOMAIN_1; 1.
DR PROSITE; PS50014; BROMODOMAIN_2; 2.
DR PROSITE; PS00678; WD_REPEATS_1; 2.
DR PROSITE; PS50082; WD_REPEATS_2; 5.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Bromodomain; Disease variant;
KW Intellectual disability; Isopeptide bond; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Ubl conjugation; WD repeat.
FT CHAIN 1..1821
FT /note="PH-interacting protein"
FT /id="PRO_0000297757"
FT REPEAT 181..222
FT /note="WD 1"
FT REPEAT 224..262
FT /note="WD 2"
FT REPEAT 265..310
FT /note="WD 3"
FT REPEAT 319..360
FT /note="WD 4"
FT REPEAT 363..402
FT /note="WD 5"
FT REPEAT 422..461
FT /note="WD 6"
FT REPEAT 464..504
FT /note="WD 7"
FT REPEAT 512..551
FT /note="WD 8"
FT DOMAIN 1176..1246
FT /note="Bromo 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00035"
FT DOMAIN 1333..1403
FT /note="Bromo 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00035"
FT REGION 658..689
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 751..927
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 924..1129
FT /note="Mediates interaction with IRS1"
FT /evidence="ECO:0000250"
FT REGION 1280..1310
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1435..1507
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1555..1597
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1623..1646
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1751..1784
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 658..685
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 751..785
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 811..825
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 843..857
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 871..914
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1280..1299
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1469..1507
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1555..1573
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1574..1589
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1759..1784
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 136
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 641
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 659
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 674
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 677
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 683
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 692
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 879
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 880
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 881
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 911
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1281
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 1283
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 1296
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1315
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 1359
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 1405
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 1479
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1497
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 1525
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1533
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 1560
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1651
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 1762
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1783
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT CROSSLNK 421
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 1470
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CROSSLNK 1470
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25114211,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:28112733"
FT CROSSLNK 1644
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1670
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 17
FT /note="F -> S (in CHUJANS; unknown pathological
FT significance; dbSNP:rs878854420)"
FT /evidence="ECO:0000269|PubMed:27900362"
FT /id="VAR_080981"
FT VARIANT 110
FT /note="R -> C (in CHUJANS; unknown pathological
FT significance; dbSNP:rs768324201)"
FT /evidence="ECO:0000269|PubMed:29209020"
FT /id="VAR_080982"
FT VARIANT 110
FT /note="R -> S (in CHUJANS; unknown pathological
FT significance; dbSNP:rs768324201)"
FT /evidence="ECO:0000269|PubMed:29209020"
FT /id="VAR_080983"
FT VARIANT 274..1821
FT /note="Missing (in CHUJANS)"
FT /evidence="ECO:0000269|PubMed:29209020"
FT /id="VAR_080984"
FT VARIANT 469
FT /note="V -> I (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036238"
FT VARIANT 555..1821
FT /note="Missing (in CHUJANS)"
FT /evidence="ECO:0000269|PubMed:29209020"
FT /id="VAR_080985"
FT VARIANT 634..1821
FT /note="Missing (in CHUJANS)"
FT /evidence="ECO:0000269|PubMed:29209020"
FT /id="VAR_080986"
FT VARIANT 663
FT /note="V -> G (in dbSNP:rs7747479)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17636024,
FT ECO:0000269|Ref.2, ECO:0000269|Ref.4,
FT ECO:0007744|PubMed:20068231"
FT /id="VAR_034683"
FT VARIANT 874
FT /note="T -> I (in dbSNP:rs11547228)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_034684"
FT VARIANT 968..1821
FT /note="Missing (in CHUJANS)"
FT /evidence="ECO:0000269|PubMed:29209020"
FT /id="VAR_080987"
FT VARIANT 1093
FT /note="L -> P (in dbSNP:rs9350797)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17974005"
FT /id="VAR_034685"
FT VARIANT 1135
FT /note="T -> P (in dbSNP:rs34841569)"
FT /id="VAR_034686"
FT VARIANT 1149..1821
FT /note="Missing (in CHUJANS)"
FT /evidence="ECO:0000269|PubMed:23033978,
FT ECO:0000269|PubMed:29209020"
FT /id="VAR_078691"
FT VARIANT 1191..1821
FT /note="Missing (in CHUJANS)"
FT /evidence="ECO:0000269|PubMed:29209020"
FT /id="VAR_080988"
FT VARIANT 1263
FT /note="Q -> E (in CHUJANS; unknown pathological
FT significance; found in a patient who also carries a de novo
FT missense variant in TBC1D8B)"
FT /evidence="ECO:0000269|PubMed:29209020"
FT /id="VAR_080989"
FT VARIANT 1298..1821
FT /note="Missing (in CHUJANS)"
FT /evidence="ECO:0000269|PubMed:29209020"
FT /id="VAR_080990"
FT VARIANT 1354..1821
FT /note="Missing (in CHUJANS)"
FT /evidence="ECO:0000269|PubMed:29209020"
FT /id="VAR_080991"
FT VARIANT 1445
FT /note="N -> T (in dbSNP:rs36048894)"
FT /id="VAR_034687"
FT VARIANT 1767
FT /note="R -> I (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036239"
FT CONFLICT 2
FT /note="S -> P (in Ref. 6; BAB71353)"
FT /evidence="ECO:0000305"
FT CONFLICT 770
FT /note="T -> I (in Ref. 6; BAB71353)"
FT /evidence="ECO:0000305"
FT CONFLICT 1648
FT /note="N -> I (in Ref. 6; BAC11417)"
FT /evidence="ECO:0000305"
FT TURN 1318..1320
FT /evidence="ECO:0007829|PDB:5S9G"
FT HELIX 1321..1334
FT /evidence="ECO:0007829|PDB:5S9G"
FT HELIX 1336..1341
FT /evidence="ECO:0007829|PDB:5S9G"
FT TURN 1347..1349
FT /evidence="ECO:0007829|PDB:5S9G"
FT HELIX 1353..1356
FT /evidence="ECO:0007829|PDB:5S9G"
FT HELIX 1363..1371
FT /evidence="ECO:0007829|PDB:5S9G"
FT HELIX 1378..1395
FT /evidence="ECO:0007829|PDB:5S9G"
FT STRAND 1397..1399
FT /evidence="ECO:0007829|PDB:5RJO"
FT HELIX 1402..1432
FT /evidence="ECO:0007829|PDB:5S9G"
SQ SEQUENCE 1821 AA; 206689 MW; 88688EF8743C980F CRC64;
MSCERKGLSE LRSELYFLIA RFLEDGPCQQ AAQVLIREVA EKELLPRRTD WTGKEHPRTY
QNLVKYYRHL APDHLLQICH RLGPLLEQEI PQSVPGVQTL LGAGRQSLLR TNKSCKHVVW
KGSALAALHC GRPPESPVNY GSPPSIADTL FSRKLNGKYR LERLVPTAVY QHMKMHKRIL
GHLSSVYCVT FDRTGRRIFT GSDDCLVKIW ATDDGRLLAT LRGHAAEISD MAVNYENTMI
AAGSCDKMIR VWCLRTCAPL AVLQGHSASI TSLQFSPLCS GSKRYLSSTG ADGTICFWLW
DAGTLKINPR PAKFTERPRP GVQMICSSFS AGGMFLATGS TDHIIRVYFF GSGQPEKISE
LEFHTDKVDS IQFSNTSNRF VSGSRDGTAR IWQFKRREWK SILLDMATRP AGQNLQGIED
KITKMKVTMV AWDRHDNTVI TAVNNMTLKV WNSYTGQLIH VLMGHEDEVF VLEPHPFDPR
VLFSAGHDGN VIVWDLARGV KIRSYFNMIE GQGHGAVFDC KCSPDGQHFA CTDSHGHLLI
FGFGSSSKYD KIADQMFFHS DYRPLIRDAN NFVLDEQTQQ APHLMPPPFL VDVDGNPHPS
RYQRLVPGRE NCREEQLIPQ MGVTSSGLNQ VLSQQANQEI SPLDSMIQRL QQEQDLRRSG
EAVISNTSRL SRGSISSTSE VHSPPNVGLR RSGQIEGVRQ MHSNAPRSEI ATERDLVAWS
RRVVVPELSA GVASRQEEWR TAKGEEEIKT YRSEEKRKHL TVPKENKIPT VSKNHAHEHF
LDLGESKKQQ TNQHNYRTRS ALEETPRPSE EIENGSSSSD EGEVVAVSGG TSEEEERAWH
SDGSSSDYSS DYSDWTADAG INLQPPKKVP KNKTKKAESS SDEEEESEKQ KQKQIKKEKK
KVNEEKDGPI SPKKKKPKER KQKRLAVGEL TENGLTLEEW LPSTWITDTI PRRCPFVPQM
GDEVYYFRQG HEAYVEMARK NKIYSINPKK QPWHKMELRE QELMKIVGIK YEVGLPTLCC
LKLAFLDPDT GKLTGGSFTM KYHDMPDVID FLVLRQQFDD AKYRRWNIGD RFRSVIDDAW
WFGTIESQEP LQLEYPDSLF QCYNVCWDNG DTEKMSPWDM ELIPNNAVFP EELGTSVPLT
DGECRSLIYK PLDGEWGTNP RDEECERIVA GINQLMTLDI ASAFVAPVDL QAYPMYCTVV
AYPTDLSTIK QRLENRFYRR VSSLMWEVRY IEHNTRTFNE PGSPIVKSAK FVTDLLLHFI
KDQTCYNIIP LYNSMKKKVL SDSEDEEKDA DVPGTSTRKR KDHQPRRRLR NRAQSYDIQA
WKKQCEELLN LIFQCEDSEP FRQPVDLLEY PDYRDIIDTP MDFATVRETL EAGNYESPME
LCKDVRLIFS NSKAYTPSKR SRIYSMSLRL SAFFEEHISS VLSDYKSALR FHKRNTITKR
RKKRNRSSSV SSSAASSPER KKRILKPQLK SESSTSAFST PTRSIPPRHN AAQINGKTES
SSVVRTRSNR VVVDPVVTEQ PSTSSAAKTF ITKANASAIP GKTILENSVK HSKALNTLSS
PGQSSFSHGT RNNSAKENME KEKPVKRKMK SSVLPKASTL SKSSAVIEQG DCKNNALVPG
TIQVNGHGGQ PSKLVKRGPG RKPKVEVNTN SGEIIHKKRG RKPKKLQYAK PEDLEQNNVH
PIRDEVLPSS TCNFLSETNN VKEDLLQKKN RGGRKPKRKM KTQKLDADLL VPASVKVLRR
SNRKKIDDPI DEEEEFEELK GSEPHMRTRN QGRRTAFYNE DDSEEEQRQL LFEDTSLTFG
TSSRGRVRKL TEKAKANLIG W
