| UniProt ID | MERL_HUMAN | |
|---|---|---|
| UniProt AC | P35240 | |
| Protein Name | Merlin | |
| Gene Name | NF2 | |
| Organism | Homo sapiens (Human). | |
| Sequence Length | 595 | |
| Subcellular Localization |
Isoform 1: Cell projection, filopodium membrane Peripheral membrane protein Cytoplasmic side. Cell projection, ruffle membrane Peripheral membrane protein Cytoplasmic side. Nucleus. In a fibroblastic cell line, isoform 1 is found homogeneously di |
|
| Protein Description | Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis. Along with WWC1 can synergistically induce the phosphorylation of LATS1 and LATS2 and can probably function in the regulation of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway. May act as a membrane stabilizing protein. May inhibit PI3 kinase by binding to AGAP2 and impairing its stimulating activity. Suppresses cell proliferation and tumorigenesis by inhibiting the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex.. | |
| Protein Sequence | MAGAIASRMSFSSLKRKQPKTFTVRIVTMDAEMEFNCEMKWKGKDLFDLVCRTLGLRETWFFGLQYTIKDTVAWLKMDKKVLDHDVSKEEPVTFHFLAKFYPENAEEELVQEITQHLFFLQVKKQILDEKIYCPPEASVLLASYAVQAKYGDYDPSVHKRGFLAQEELLPKRVINLYQMTPEMWEERITAWYAEHRGRARDEAEMEYLKIAQDLEMYGVNYFAIRNKKGTELLLGVDALGLHIYDPENRLTPKISFPWNEIRNISYSDKEFTIKPLDKKIDVFKFNSSKLRVNKLILQLCIGNHDLFMRRRKADSLEVQQMKAQAREEKARKQMERQRLAREKQMREEAERTRDELERRLLQMKEEATMANEALMRSEETADLLAEKAQITEEEAKLLAQKAAEAEQEMQRIKATAIRTEEEKRLMEQKVLEAEVLALKMAEESERRAKEADQLKQDLQEAREAERRAKQKLLEIATKPTYPPMNPIPAPLPPDIPSFNLIGDSLSFDFKDTDMKRLSMEIEKEKVEYMEKSKHLQEQLNELKTEIEALKLKERETALDILHNENSDRGGSSKHNTIKKLTLQSAKSRVAFFEEL | |
| Overview of Protein Modification Sites with Functional and Structural Information | ||
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* ASA = Accessible Surface Area
| Locations | Modification | Substrate Peptides & Secondary Structure |
ASA (%) | Reference | Orthologous Protein Cluster |
|---|---|---|---|---|---|
| 7 | Phosphorylation | -MAGAIASRMSFSSL -CCHHHHHCCCHHHH | 23.54 | 29514088 | |
| 10 | Phosphorylation | GAIASRMSFSSLKRK HHHHHCCCHHHHCCC | 22.37 | 25159151 | |
| 12 | Phosphorylation | IASRMSFSSLKRKQP HHHCCCHHHHCCCCC | 27.70 | 22617229 | |
| 13 | Phosphorylation | ASRMSFSSLKRKQPK HHCCCHHHHCCCCCC | 35.58 | 23401153 | |
| 15 | Sumoylation | RMSFSSLKRKQPKTF CCCHHHHCCCCCCCE | 60.54 | - | |
| 15 | Sumoylation | RMSFSSLKRKQPKTF CCCHHHHCCCCCCCE | 60.54 | - | |
| 67 | Phosphorylation | WFFGLQYTIKDTVAW EEEEEEEEEHHHHHH | 14.48 | 22985185 | |
| 76 | Sumoylation | KDTVAWLKMDKKVLD HHHHHHHHCCHHHHC | 34.06 | - | |
| 76 | Sumoylation | KDTVAWLKMDKKVLD HHHHHHHHCCHHHHC | 34.06 | - | |
| 76 (in isoform 4) | Ubiquitination | - | 34.06 | 21890473 | |
| 80 | Ubiquitination | AWLKMDKKVLDHDVS HHHHCCHHHHCCCCC | 43.71 | - | |
| 87 | Phosphorylation | KVLDHDVSKEEPVTF HHHCCCCCCCCCCCH | 40.17 | 20068231 | |
| 88 | Ubiquitination | VLDHDVSKEEPVTFH HHCCCCCCCCCCCHH | 66.98 | - | |
| 110 (in isoform 10) | Ubiquitination | - | 5.62 | 21890473 | |
| 117 (in isoform 6) | Ubiquitination | - | 2.03 | 21890473 | |
| 118 (in isoform 5) | Ubiquitination | - | 5.57 | 21890473 | |
| 159 | Ubiquitination | DYDPSVHKRGFLAQE CCCCCHHHCCCCCCH | 52.65 | 21906983 | |
| 159 (in isoform 2) | Ubiquitination | - | 52.65 | 21890473 | |
| 159 (in isoform 1) | Ubiquitination | - | 52.65 | 21890473 | |
| 159 (in isoform 3) | Ubiquitination | - | 52.65 | 21890473 | |
| 159 (in isoform 7) | Ubiquitination | - | 52.65 | 21906983 | |
| 159 (in isoform 8) | Ubiquitination | - | 52.65 | 21890473 | |
| 171 | Ubiquitination | AQEELLPKRVINLYQ CCHHHCCHHHHHHHH | 60.30 | - | |
| 177 | Phosphorylation | PKRVINLYQMTPEMW CHHHHHHHHCCHHHH | 7.55 | 25262027 | |
| 180 | Phosphorylation | VINLYQMTPEMWEER HHHHHHCCHHHHHHH | 10.69 | 25262027 | |
| 186 (in isoform 4) | Ubiquitination | - | 33.59 | 21890473 | |
| 189 | Phosphorylation | EMWEERITAWYAEHR HHHHHHHHHHHHHHC | 19.84 | 25262027 | |
| 192 | Phosphorylation | EERITAWYAEHRGRA HHHHHHHHHHHCCCC | 10.31 | 25262027 | |
| 227 (in isoform 6) | Ubiquitination | - | 42.61 | 21890473 | |
| 228 (in isoform 5) | Ubiquitination | - | 74.70 | 21890473 | |
| 230 | Phosphorylation | AIRNKKGTELLLGVD EEECCCCCCEEEEEC | 32.13 | 17891137 | |
| 251 | Phosphorylation | YDPENRLTPKISFPW ECCCCCCCCCEECCH | 21.21 | 26074081 | |
| 253 | Ubiquitination | PENRLTPKISFPWNE CCCCCCCCEECCHHH | 45.83 | - | |
| 255 | Phosphorylation | NRLTPKISFPWNEIR CCCCCCEECCHHHHC | 31.23 | 26074081 | |
| 265 | Phosphorylation | WNEIRNISYSDKEFT HHHHCCCCCCCCEEE | 23.33 | 26074081 | |
| 266 | Phosphorylation | NEIRNISYSDKEFTI HHHCCCCCCCCEEEE | 19.66 | 26074081 | |
| 267 | Phosphorylation | EIRNISYSDKEFTIK HHCCCCCCCCEEEEC | 35.10 | 26074081 | |
| 269 | Ubiquitination | RNISYSDKEFTIKPL CCCCCCCCEEEECCC | 49.11 | 21890473 | |
| 269 (in isoform 2) | Ubiquitination | - | 49.11 | 21890473 | |
| 269 (in isoform 1) | Ubiquitination | - | 49.11 | 21890473 | |
| 269 (in isoform 3) | Ubiquitination | - | 49.11 | 21890473 | |
| 269 (in isoform 8) | Ubiquitination | - | 49.11 | 21890473 | |
| 279 | Acetylation | TIKPLDKKIDVFKFN EECCCCCCCCEEEEC | 43.75 | 20167786 | |
| 289 | Ubiquitination | VFKFNSSKLRVNKLI EEEECCCHHHHHHHH | 39.88 | - | |
| 304 (in isoform 4) | Ubiquitination | - | 28.12 | 21890473 | |
| 313 (in isoform 4) | Ubiquitination | - | 15.15 | 21890473 | |
| 315 | Phosphorylation | MRRRKADSLEVQQMK HHHHHCHHHHHHHHH | 31.15 | 29255136 | |
| 318 (in isoform 4) | Ubiquitination | - | 6.09 | 21890473 | |
| 322 | Ubiquitination | SLEVQQMKAQAREEK HHHHHHHHHHHHHHH | 32.77 | - | |
| 345 (in isoform 6) | Ubiquitination | - | 9.61 | 21890473 | |
| 346 (in isoform 5) | Ubiquitination | - | 35.79 | 21890473 | |
| 351 | Dimethylation | QMREEAERTRDELER HHHHHHHHHHHHHHH | 41.95 | - | |
| 351 | Methylation | QMREEAERTRDELER HHHHHHHHHHHHHHH | 41.95 | 24154205 | |
| 353 | Dimethylation | REEAERTRDELERRL HHHHHHHHHHHHHHH | 41.44 | - | |
| 353 | Methylation | REEAERTRDELERRL HHHHHHHHHHHHHHH | 41.44 | 24154215 | |
| 354 (in isoform 6) | Ubiquitination | - | 65.31 | 21890473 | |
| 355 (in isoform 5) | Ubiquitination | - | 49.60 | 21890473 | |
| 358 (in isoform 8) | Ubiquitination | - | 47.36 | 21890473 | |
| 359 (in isoform 6) | Ubiquitination | - | 30.30 | 21890473 | |
| 360 (in isoform 5) | Ubiquitination | - | 4.95 | 21890473 | |
| 364 | Ubiquitination | ERRLLQMKEEATMAN HHHHHHHHHHHHHHH | 39.17 | 22053931 | |
| 364 (in isoform 2) | Ubiquitination | - | 39.17 | 21890473 | |
| 367 (in isoform 8) | Ubiquitination | - | 12.08 | 21890473 | |
| 372 (in isoform 8) | Ubiquitination | - | 33.37 | 21890473 | |
| 387 | Ubiquitination | TADLLAEKAQITEEE HHHHHHHHHCCCHHH | 39.73 | 21906983 | |
| 387 (in isoform 2) | Ubiquitination | - | 39.73 | 21890473 | |
| 387 (in isoform 1) | Ubiquitination | - | 39.73 | 21890473 | |
| 387 (in isoform 3) | Ubiquitination | - | 39.73 | 21890473 | |
| 396 | Ubiquitination | QITEEEAKLLAQKAA CCCHHHHHHHHHHHH | 47.52 | 22053931 | |
| 396 (in isoform 2) | Ubiquitination | - | 47.52 | 21890473 | |
| 396 (in isoform 1) | Ubiquitination | - | 47.52 | 21890473 | |
| 396 (in isoform 3) | Ubiquitination | - | 47.52 | 21890473 | |
| 401 | Ubiquitination | EAKLLAQKAAEAEQE HHHHHHHHHHHHHHH | 43.91 | 2190698 | |
| 401 (in isoform 1) | Ubiquitination | - | 43.91 | 21890473 | |
| 401 (in isoform 2) | Ubiquitination | - | 43.91 | 21890473 | |
| 401 (in isoform 3) | Ubiquitination | - | 43.91 | 21890473 | |
| 415 | Phosphorylation | EMQRIKATAIRTEEE HHHHHHHHHCCCHHH | 20.02 | 20860994 | |
| 419 | Phosphorylation | IKATAIRTEEEKRLM HHHHHCCCHHHHHHH | 41.45 | 20860994 | |
| 439 | Ubiquitination | EAEVLALKMAEESER HHHHHHHHHHHHHHH | 30.38 | - | |
| 449 | Ubiquitination | EESERRAKEADQLKQ HHHHHHHHHHHHHHH | 52.18 | - | |
| 455 | Ubiquitination | AKEADQLKQDLQEAR HHHHHHHHHHHHHHH | 35.81 | - | |
| 477 | Phosphorylation | QKLLEIATKPTYPPM HHHHHHHCCCCCCCC | 43.12 | 20068231 | |
| 480 | Phosphorylation | LEIATKPTYPPMNPI HHHHCCCCCCCCCCC | 50.66 | 22210691 | |
| 489 (in isoform 4) | Phosphorylation | - | 20.98 | 25056879 | |
| 518 | Phosphorylation | DTDMKRLSMEIEKEK CCCHHHHHHHHHHHH | 20.57 | 29255136 | |
| 530 (in isoform 6) | Phosphorylation | - | 53.96 | 25056879 | |
| 531 (in isoform 5) | Phosphorylation | - | 48.55 | 25056879 | |
| 533 | Ubiquitination | VEYMEKSKHLQEQLN HHHHHHHHHHHHHHH | 60.44 | 22053931 | |
| 533 (in isoform 2) | Ubiquitination | - | 60.44 | 21890473 | |
| 543 (in isoform 8) | Phosphorylation | - | 37.62 | 25056879 | |
| 550 | Sumoylation | KTEIEALKLKERETA HHHHHHHHHHHHHHH | 65.64 | - | |
| 550 | Sumoylation | KTEIEALKLKERETA HHHHHHHHHHHHHHH | 65.64 | - | |
| 550 | Ubiquitination | KTEIEALKLKERETA HHHHHHHHHHHHHHH | 65.64 | - | |
| 568 | Methylation | LHNENSDRGGSSKHN HCCCCCCCCCCCCCC | 51.71 | 58858529 | |
| 571 | Phosphorylation | ENSDRGGSSKHNTIK CCCCCCCCCCCCHHH | 38.75 | 28555341 | |
| 572 | Phosphorylation | NSDRGGSSKHNTIKK CCCCCCCCCCCHHHH | 41.00 | 30576142 | |
| 572 (in isoform 3) | Phosphorylation | - | 41.00 | 25056879 | |
| 573 (in isoform 2) | Ubiquitination | - | 42.44 | 21890473 | |
| 573 | Ubiquitination | SDRGGSSKHNTIKKL CCCCCCCCCCHHHHH | 42.44 | 22053931 | |
| 576 (in isoform 2) | Phosphorylation | - | 33.61 | 20068231 | |
| 579 | Ubiquitination | SKHNTIKKLTLQSAK CCCCHHHHHHHHCHH | 42.74 | - | |
| 580 (in isoform 2) | Phosphorylation | - | 4.99 | 20068231 | |
| 581 | Phosphorylation | HNTIKKLTLQSAKSR CCHHHHHHHHCHHHH | 31.47 | 25159151 | |
| 581 (in isoform 2) | Phosphorylation | - | 31.47 | 20068231 | |
| 584 | Phosphorylation | IKKLTLQSAKSRVAF HHHHHHHCHHHHHHH | 40.55 | 28060719 | |
| 586 | Ubiquitination | KLTLQSAKSRVAFFE HHHHHCHHHHHHHHH | 44.00 | - | |
| 586 (in isoform 2) | Phosphorylation | - | 44.00 | 20068231 | |
| 587 | Phosphorylation | LTLQSAKSRVAFFEE HHHHCHHHHHHHHHC | 31.53 | 20363803 | |
| 587 (in isoform 2) | Phosphorylation | - | 31.53 | 20068231 | |
| 591 (in isoform 2) | Phosphorylation | - | 7.87 | 20068231 | |
| 594 (in isoform 2) | Phosphorylation | - | 55.40 | 20068231 | |
| 600 (in isoform 2) | Phosphorylation | - | 24043423 | ||
| 602 (in isoform 2) | Phosphorylation | - | 24043423 | ||
| 607 (in isoform 2) | Phosphorylation | - | 24043423 | ||
| 614 (in isoform 2) | Phosphorylation | - | 24043423 | ||
| 618 (in isoform 2) | Phosphorylation | - | 24043423 |
| Modified Location | Modified Residue | Modification | Type of Upstream Proteins | Gene Name of Upstream Proteins | UniProt AC of Upstream Proteins | Sources |
|---|---|---|---|---|---|---|
| 10 | S | Phosphorylation | Kinase | AKT1 | P31749 | PSP |
| 10 | S | Phosphorylation | Kinase | AKT2 | P31751 | PSP |
| 10 | S | Phosphorylation | Kinase | AKT3 | Q9Y243 | PSP |
| 10 | S | Phosphorylation | Kinase | PRKACA | P17612 | GPS |
| 230 | T | Phosphorylation | Kinase | AKT1 | P31749 | PSP |
| 230 | T | Phosphorylation | Kinase | AKT1 | P47196 | PSP |
| 315 | S | Phosphorylation | Kinase | AKT1 | P47196 | PSP |
| 315 | S | Phosphorylation | Kinase | AKT1 | P31749 | PSP |
| 518 | S | Phosphorylation | Kinase | PAK_GROUP | - | PhosphoELM |
| 518 | S | Phosphorylation | Kinase | PKA_GROUP | - | PhosphoELM |
| 518 | S | Phosphorylation | Kinase | PAK | - | Uniprot |
| 518 | S | Phosphorylation | Kinase | PKA-FAMILY | - | GPS |
| 518 | S | Phosphorylation | Kinase | PAK-SUBFAMILY | - | GPS |
| 518 | S | Phosphorylation | Kinase | PAK2 | Q13177 | PSP |
| 518 | S | Phosphorylation | Kinase | PAK1 | Q13153 | PSP |
| 518 | S | Phosphorylation | Kinase | PKACA | P17612 | PSP |
| 518 | S | Phosphorylation | Kinase | PRKACA | P00517 | GPS |
| - | K | Ubiquitination | E3 ubiquitin ligase | DCAF1 | Q9Y4B6 | PMID:18332868 |
* Distance = the distance between SAP position and PTM sites.
| Modified Location | Modification | Variant Position (Distance <= 10) |
Residue Change | SAP | Related Disease | Reference |
|---|---|---|---|---|---|---|
Oops, there are no SNP-PTM records of MERL_HUMAN !! | ||||||
| Kegg Disease | ||||||
|---|---|---|---|---|---|---|
| H00015 | Malignant pleural mesothelioma | |||||
| H00523 | Noonan syndrome and related disorders, including: Noonan syndrome (NS); Leopard syndrome (LS); Noona | |||||
| OMIM Disease | ||||||
| 101000 | Neurofibromatosis 2 (NF2) | |||||
| 162091 | Schwannomatosis 1 (SWNTS1) | |||||
| 156240 | Mesothelioma, malignant (MESOM) | |||||
| Kegg Drug | ||||||
| There are no disease associations of PTM sites. | ||||||
| DrugBank | ||||||
| There are no disease associations of PTM sites. | ||||||
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| Phosphorylation | |
| Reference | PubMed |
| "A quantitative atlas of mitotic phosphorylation."; Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-518, AND MASSSPECTROMETRY. | |
| "Global, in vivo, and site-specific phosphorylation dynamics insignaling networks."; Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,Mann M.; Cell 127:635-648(2006). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-518, AND MASSSPECTROMETRY. | |
