CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-011224
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Neurogenic locus notch homolog protein 2 
Protein Synonyms/Alias
 Notch 2; hN2; Notch 2 extracellular truncation; Notch 2 intracellular domain 
Gene Name
 NOTCH2 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
1705IMAKRKRKHGSLWLPubiquitination[1, 2, 3]
1738GQDAVGLKNLSVQVSubiquitination[4]
Reference
 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [3] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [4] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094] 
Functional Description
 Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs (By similarity). Involved in bone remodeling and homeostasis. In collaboration with RELA/p65 enhances NFATc1 promoter activity and positively regulates RANKL-induced osteoclast differentiation. 
Sequence Annotation
 DOMAIN 26 63 EGF-like 1.
 DOMAIN 64 102 EGF-like 2.
 DOMAIN 105 143 EGF-like 3.
 DOMAIN 144 180 EGF-like 4.
 DOMAIN 182 219 EGF-like 5; calcium-binding (Potential).
 DOMAIN 221 258 EGF-like 6.
 DOMAIN 260 296 EGF-like 7; calcium-binding (Potential).
 DOMAIN 298 336 EGF-like 8; calcium-binding (Potential).
 DOMAIN 338 374 EGF-like 9; calcium-binding (Potential).
 DOMAIN 375 413 EGF-like 10.
 DOMAIN 415 454 EGF-like 11; calcium-binding (Potential).
 DOMAIN 456 492 EGF-like 12; calcium-binding (Potential).
 DOMAIN 494 530 EGF-like 13; calcium-binding (Potential).
 DOMAIN 532 568 EGF-like 14; calcium-binding (Potential).
 DOMAIN 570 605 EGF-like 15; calcium-binding (Potential).
 DOMAIN 607 643 EGF-like 16; calcium-binding (Potential).
 DOMAIN 645 680 EGF-like 17; calcium-binding (Potential).
 DOMAIN 682 718 EGF-like 18; calcium-binding (Potential).
 DOMAIN 720 755 EGF-like 19.
 DOMAIN 757 793 EGF-like 20; calcium-binding (Potential).
 DOMAIN 795 831 EGF-like 21; calcium-binding (Potential).
 DOMAIN 833 871 EGF-like 22.
 DOMAIN 873 909 EGF-like 23; calcium-binding (Potential).
 DOMAIN 911 947 EGF-like 24; calcium-binding (Potential).
 DOMAIN 949 985 EGF-like 25; calcium-binding (Potential).
 DOMAIN 987 1023 EGF-like 26; calcium-binding (Potential).
 DOMAIN 1025 1061 EGF-like 27; calcium-binding (Potential).
 DOMAIN 1063 1099 EGF-like 28.
 DOMAIN 1101 1147 EGF-like 29.
 DOMAIN 1149 1185 EGF-like 30; calcium-binding (Potential).
 DOMAIN 1187 1223 EGF-like 31; calcium-binding (Potential).
 DOMAIN 1225 1262 EGF-like 32; calcium-binding (Potential).
 DOMAIN 1264 1302 EGF-like 33.
 DOMAIN 1304 1343 EGF-like 34.
 DOMAIN 1374 1412 EGF-like 35.
 REPEAT 1425 1465 LNR 1.
 REPEAT 1466 1502 LNR 2.
 REPEAT 1503 1544 LNR 3.
 REPEAT 1827 1871 ANK 1.
 REPEAT 1876 1905 ANK 2.
 REPEAT 1909 1939 ANK 3.
 REPEAT 1943 1972 ANK 4.
 REPEAT 1976 2005 ANK 5.
 REPEAT 2009 2038 ANK 6.
 REGION 1425 1677 Negative regulatory region (NRR).
 MOD_RES 1716 1716 Phosphothreonine.
 MOD_RES 1778 1778 Phosphoserine.
 MOD_RES 1802 1802 Phosphothreonine.
 MOD_RES 1804 1804 Phosphoserine.
 MOD_RES 1808 1808 Phosphothreonine.
 MOD_RES 1845 1845 Phosphoserine.
 MOD_RES 2070 2070 Phosphoserine.
 MOD_RES 2078 2078 Phosphoserine (By similarity).
 MOD_RES 2081 2081 Phosphoserine.
 MOD_RES 2097 2097 Phosphothreonine.
 CARBOHYD 46 46 N-linked (GlcNAc...) (Potential).
 CARBOHYD 155 155 N-linked (GlcNAc...) (Potential).
 CARBOHYD 733 733 N-linked (GlcNAc...) (Potential).
 CARBOHYD 1102 1102 N-linked (GlcNAc...) (Potential).
 CARBOHYD 1465 1465 N-linked (GlcNAc...) (Potential).
 DISULFID 28 41 By similarity.
 DISULFID 35 51 By similarity.
 DISULFID 53 62 By similarity.
 DISULFID 68 79 By similarity.
 DISULFID 73 90 By similarity.
 DISULFID 92 101 By similarity.
 DISULFID 109 121 By similarity.
 DISULFID 115 131 By similarity.
 DISULFID 133 142 By similarity.
 DISULFID 148 159 By similarity.
 DISULFID 153 168 By similarity.
 DISULFID 170 179 By similarity.
 DISULFID 186 198 By similarity.
 DISULFID 192 207 By similarity.
 DISULFID 209 218 By similarity.
 DISULFID 225 236 By similarity.
 DISULFID 230 246 By similarity.
 DISULFID 248 257 By similarity.
 DISULFID 264 275 By similarity.
 DISULFID 269 284 By similarity.
 DISULFID 286 295 By similarity.
 DISULFID 302 315 By similarity.
 DISULFID 309 324 By similarity.
 DISULFID 326 335 By similarity.
 DISULFID 342 353 By similarity.
 DISULFID 347 362 By similarity.
 DISULFID 364 373 By similarity.
 DISULFID 379 390 By similarity.
 DISULFID 384 401 By similarity.
 DISULFID 403 412 By similarity.
 DISULFID 419 433 By similarity.
 DISULFID 427 442 By similarity.
 DISULFID 444 453 By similarity.
 DISULFID 460 471 By similarity.
 DISULFID 465 480 By similarity.
 DISULFID 482 491 By similarity.
 DISULFID 498 509 By similarity.
 DISULFID 503 518 By similarity.
 DISULFID 520 529 By similarity.
 DISULFID 536 547 By similarity.
 DISULFID 541 556 By similarity.
 DISULFID 558 567 By similarity.
 DISULFID 574 584 By similarity.
 DISULFID 579 593 By similarity.
 DISULFID 595 604 By similarity.
 DISULFID 611 622 By similarity.
 DISULFID 616 631 By similarity.
 DISULFID 633 642 By similarity.
 DISULFID 649 659 By similarity.
 DISULFID 654 668 By similarity.
 DISULFID 670 679 By similarity.
 DISULFID 686 697 By similarity.
 DISULFID 691 706 By similarity.
 DISULFID 708 717 By similarity.
 DISULFID 724 734 By similarity.
 DISULFID 729 743 By similarity.
 DISULFID 745 754 By similarity.
 DISULFID 761 772 By similarity.
 DISULFID 766 781 By similarity.
 DISULFID 783 792 By similarity.
 DISULFID 799 810 By similarity.
 DISULFID 804 819 By similarity.
 DISULFID 821 830 By similarity.
 DISULFID 837 848 By similarity.
 DISULFID 842 859 By similarity.
 DISULFID 861 870 By similarity.
 DISULFID 877 888 By similarity.
 DISULFID 882 897 By similarity.
 DISULFID 899 908 By similarity.
 DISULFID 915 926 By similarity.
 DISULFID 920 935 By similarity.
 DISULFID 937 946 By similarity.
 DISULFID 953 964 By similarity.
 DISULFID 958 973 By similarity.
 DISULFID 975 984 By similarity.
 DISULFID 991 1002 By similarity.
 DISULFID 996 1011 By similarity.
 DISULFID 1013 1022 By similarity.
 DISULFID 1029 1040 By similarity.
 DISULFID 1034 1049 By similarity.
 DISULFID 1051 1060 By similarity.
 DISULFID 1067 1078 By similarity.
 DISULFID 1072 1087 By similarity.
 DISULFID 1089 1098 By similarity.
 DISULFID 1105 1126 By similarity.
 DISULFID 1120 1135 By similarity.
 DISULFID 1137 1146 By similarity.
 DISULFID 1153 1164 By similarity.
 DISULFID 1158 1173 By similarity.
 DISULFID 1175 1184 By similarity.
 DISULFID 1191 1202 By similarity.
 DISULFID 1196 1211 By similarity.
 DISULFID 1213 1222 By similarity.
 DISULFID 1229 1241 By similarity.
 DISULFID 1235 1250 By similarity.
 DISULFID 1252 1261 By similarity.
 DISULFID 1268 1281 By similarity.
 DISULFID 1273 1290 By similarity.
 DISULFID 1292 1301 By similarity.
 DISULFID 1308 1319 By similarity.
 DISULFID 1313 1331 By similarity.
 DISULFID 1333 1342 By similarity.
 DISULFID 1378 1389 By similarity.
 DISULFID 1383 1400 By similarity.
 DISULFID 1402 1411 By similarity.
 DISULFID 1425 1448
 DISULFID 1430 1443
 DISULFID 1439 1455
 DISULFID 1466 1489
 DISULFID 1472 1484
 DISULFID 1480 1496
 DISULFID 1503 1527
 DISULFID 1509 1522
 DISULFID 1518 1534
 DISULFID 1632 1639  
Keyword
 3D-structure; Activator; ANK repeat; Cell membrane; Complete proteome; Developmental protein; Differentiation; Disease mutation; Disulfide bond; EGF-like domain; Glycoprotein; Membrane; Notch signaling pathway; Nucleus; Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Transcription; Transcription regulation; Transmembrane; Transmembrane helix. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 2471 AA 
Protein Sequence
MPALRPALLW ALLALWLCCA APAHALQCRD GYEPCVNEGM CVTYHNGTGY CKCPEGFLGE 60
YCQHRDPCEK NRCQNGGTCV AQAMLGKATC RCASGFTGED CQYSTSHPCF VSRPCLNGGT 120
CHMLSRDTYE CTCQVGFTGK ECQWTDACLS HPCANGSTCT TVANQFSCKC LTGFTGQKCE 180
TDVNECDIPG HCQHGGTCLN LPGSYQCQCP QGFTGQYCDS LYVPCAPSPC VNGGTCRQTG 240
DFTFECNCLP GFEGSTCERN IDDCPNHRCQ NGGVCVDGVN TYNCRCPPQW TGQFCTEDVD 300
ECLLQPNACQ NGGTCANRNG GYGCVCVNGW SGDDCSENID DCAFASCTPG STCIDRVASF 360
SCMCPEGKAG LLCHLDDACI SNPCHKGALC DTNPLNGQYI CTCPQGYKGA DCTEDVDECA 420
MANSNPCEHA GKCVNTDGAF HCECLKGYAG PRCEMDINEC HSDPCQNDAT CLDKIGGFTC 480
LCMPGFKGVH CELEINECQS NPCVNNGQCV DKVNRFQCLC PPGFTGPVCQ IDIDDCSSTP 540
CLNGAKCIDH PNGYECQCAT GFTGVLCEEN IDNCDPDPCH HGQCQDGIDS YTCICNPGYM 600
GAICSDQIDE CYSSPCLNDG RCIDLVNGYQ CNCQPGTSGV NCEINFDDCA SNPCIHGICM 660
DGINRYSCVC SPGFTGQRCN IDIDECASNP CRKGATCING VNGFRCICPE GPHHPSCYSQ 720
VNECLSNPCI HGNCTGGLSG YKCLCDAGWV GINCEVDKNE CLSNPCQNGG TCDNLVNGYR 780
CTCKKGFKGY NCQVNIDECA SNPCLNQGTC FDDISGYTCH CVLPYTGKNC QTVLAPCSPN 840
PCENAAVCKE SPNFESYTCL CAPGWQGQRC TIDIDECISK PCMNHGLCHN TQGSYMCECP 900
PGFSGMDCEE DIDDCLANPC QNGGSCMDGV NTFSCLCLPG FTGDKCQTDM NECLSEPCKN 960
GGTCSDYVNS YTCKCQAGFD GVHCENNINE CTESSCFNGG TCVDGINSFS CLCPVGFTGS 1020
FCLHEINECS SHPCLNEGTC VDGLGTYRCS CPLGYTGKNC QTLVNLCSRS PCKNKGTCVQ 1080
KKAESQCLCP SGWAGAYCDV PNVSCDIAAS RRGVLVEHLC QHSGVCINAG NTHYCQCPLG 1140
YTGSYCEEQL DECASNPCQH GATCSDFIGG YRCECVPGYQ GVNCEYEVDE CQNQPCQNGG 1200
TCIDLVNHFK CSCPPGTRGL LCEENIDDCA RGPHCLNGGQ CMDRIGGYSC RCLPGFAGER 1260
CEGDINECLS NPCSSEGSLD CIQLTNDYLC VCRSAFTGRH CETFVDVCPQ MPCLNGGTCA 1320
VASNMPDGFI CRCPPGFSGA RCQSSCGQVK CRKGEQCVHT ASGPRCFCPS PRDCESGCAS 1380
SPCQHGGSCH PQRQPPYYSC QCAPPFSGSR CELYTAPPST PPATCLSQYC ADKARDGVCD 1440
EACNSHACQW DGGDCSLTME NPWANCSSPL PCWDYINNQC DELCNTVECL FDNFECQGNS 1500
KTCKYDKYCA DHFKDNHCDQ GCNSEECGWD GLDCAADQPE NLAEGTLVIV VLMPPEQLLQ 1560
DARSFLRALG TLLHTNLRIK RDSQGELMVY PYYGEKSAAM KKQRMTRRSL PGEQEQEVAG 1620
SKVFLEIDNR QCVQDSDHCF KNTDAAAALL ASHAIQGTLS YPLVSVVSES LTPERTQLLY 1680
LLAVAVVIIL FIILLGVIMA KRKRKHGSLW LPEGFTLRRD ASNHKRREPV GQDAVGLKNL 1740
SVQVSEANLI GTGTSEHWVD DEGPQPKKVK AEDEALLSEE DDPIDRRPWT QQHLEAADIR 1800
RTPSLALTPP QAEQEVDVLD VNVRGPDGCT PLMLASLRGG SSDLSDEDED AEDSSANIIT 1860
DLVYQGASLQ AQTDRTGEMA LHLAARYSRA DAAKRLLDAG ADANAQDNMG RCPLHAAVAA 1920
DAQGVFQILI RNRVTDLDAR MNDGTTPLIL AARLAVEGMV AELINCQADV NAVDDHGKSA 1980
LHWAAAVNNV EATLLLLKNG ANRDMQDNKE ETPLFLAARE GSYEAAKILL DHFANRDITD 2040
HMDRLPRDVA RDRMHHDIVR LLDEYNVTPS PPGTVLTSAL SPVICGPNRS FLSLKHTPMG 2100
KKSRRPSAKS TMPTSLPNLA KEAKDAKGSR RKKSLSEKVQ LSESSVTLSP VDSLESPHTY 2160
VSDTTSSPMI TSPGILQASP NPMLATAAPP APVHAQHALS FSNLHEMQPL AHGASTVLPS 2220
VSQLLSHHHI VSPGSGSAGS LSRLHPVPVP ADWMNRMEVN ETQYNEMFGM VLAPAEGTHP 2280
GIAPQSRPPE GKHITTPREP LPPIVTFQLI PKGSIAQPAG APQPQSTCPP AVAGPLPTMY 2340
QIPEMARLPS VAFPTAMMPQ QDGQVAQTIL PAYHPFPASV GKYPTPPSQH SYASSNAAER 2400
TPSHSGHLQG EHPYLTPSPE SPDQWSSSSP HSASDWSDVT TSPTPGGAGG GQRGPGTHMS 2460
EPPHNNMQVY A 2471 
Gene Ontology
 GO:0009986; C:cell surface; IDA:UniProtKB.
 GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
 GO:0005576; C:extracellular region; TAS:Reactome.
 GO:0000139; C:Golgi membrane; TAS:Reactome.
 GO:0005887; C:integral to plasma membrane; IDA:UniProtKB.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0005509; F:calcium ion binding; IEA:InterPro.
 GO:0004872; F:receptor activity; NAS:UniProtKB.
 GO:0060413; P:atrial septum morphogenesis; IMP:BHF-UCL.
 GO:0046849; P:bone remodeling; IMP:UniProtKB.
 GO:0007050; P:cell cycle arrest; IDA:UniProtKB.
 GO:0001709; P:cell fate determination; TAS:UniProtKB.
 GO:0016049; P:cell growth; IDA:UniProtKB.
 GO:0007368; P:determination of left/right symmetry; IEA:Compara.
 GO:0030326; P:embryonic limb morphogenesis; IEA:Compara.
 GO:0030097; P:hemopoiesis; TAS:UniProtKB.
 GO:0006959; P:humoral immune response; IEA:Compara.
 GO:0001701; P:in utero embryonic development; IEA:Compara.
 GO:0006917; P:induction of apoptosis; TAS:UniProtKB.
 GO:0002437; P:inflammatory response to antigenic stimulus; IEA:Compara.
 GO:0072602; P:interleukin-4 secretion; IEA:Compara.
 GO:0002011; P:morphogenesis of an epithelial sheet; IEA:Compara.
 GO:0043066; P:negative regulation of apoptotic process; TAS:UniProtKB.
 GO:0008285; P:negative regulation of cell proliferation; IDA:UniProtKB.
 GO:0007399; P:nervous system development; NAS:UniProtKB.
 GO:0007220; P:Notch receptor processing; TAS:Reactome.
 GO:0061314; P:Notch signaling involved in heart development; IC:BHF-UCL.
 GO:0060674; P:placenta blood vessel development; IEA:Compara.
 GO:0046579; P:positive regulation of Ras protein signal transduction; IDA:UniProtKB.
 GO:0003184; P:pulmonary valve morphogenesis; IMP:BHF-UCL.
 GO:0006355; P:regulation of transcription, DNA-dependent; TAS:UniProtKB.
 GO:0019827; P:stem cell maintenance; TAS:UniProtKB.
 GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome. 
Interpro
 IPR002110; Ankyrin_rpt.
 IPR020683; Ankyrin_rpt-contain_dom.
 IPR024600; DUF3454_notch.
 IPR000742; EG-like_dom.
 IPR001881; EGF-like_Ca-bd.
 IPR013032; EGF-like_CS.
 IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
 IPR018097; EGF_Ca-bd_CS.
 IPR008297; Notch.
 IPR022336; Notch_2.
 IPR000800; Notch_dom.
 IPR010660; Notch_NOD_dom.
 IPR011656; Notch_NODP_dom. 
Pfam
 PF00023; Ank
 PF12796; Ank_2
 PF11936; DUF3454
 PF00008; EGF
 PF07645; EGF_CA
 PF06816; NOD
 PF07684; NODP
 PF00066; Notch 
SMART
 SM00248; ANK
 SM00181; EGF
 SM00179; EGF_CA
 SM00004; NL 
PROSITE
 PS50297; ANK_REP_REGION
 PS50088; ANK_REPEAT
 PS00010; ASX_HYDROXYL
 PS00022; EGF_1
 PS01186; EGF_2
 PS50026; EGF_3
 PS01187; EGF_CA
 PS50258; LNR 
PRINTS
 PR01452; LNOTCHREPEAT.
 PR01985; NOTCH2.