| UniProt ID | ITCH_HUMAN | |
|---|---|---|
| UniProt AC | Q96J02 | |
| Protein Name | E3 ubiquitin-protein ligase Itchy homolog | |
| Gene Name | ITCH | |
| Organism | Homo sapiens (Human). | |
| Sequence Length | 903 | |
| Subcellular Localization |
Cell membrane Peripheral membrane protein Cytoplasmic side . Cytoplasm . Nucleus . Early endosome membrane Peripheral membrane protein Cytoplasmic side . Endosome membrane Peripheral membrane protein Cytoplasmic side . May be recruited to |
|
| Protein Description | Acts as an E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. [PubMed: 14602072] | |
| Protein Sequence | MSDSGSQLGSMGSLTMKSQLQITVISAKLKENKKNWFGPSPYVEVTVDGQSKKTEKCNNTNSPKWKQPLTVIVTPVSKLHFRVWSHQTLKSDVLLGTAALDIYETLKSNNMKLEEVVVTLQLGGDKEPTETIGDLSICLDGLQLESEVVTNGETTCSENGVSLCLPRLECNSAISAHCNLCLPGLSDSPISASRVAGFTGASQNDDGSRSKDETRVSTNGSDDPEDAGAGENRRVSGNNSPSLSNGGFKPSRPPRPSRPPPPTPRRPASVNGSPSATSESDGSSTGSLPPTNTNTNTSEGATSGLIIPLTISGGSGPRPLNPVTQAPLPPGWEQRVDQHGRVYYVDHVEKRTTWDRPEPLPPGWERRVDNMGRIYYVDHFTRTTTWQRPTLESVRNYEQWQLQRSQLQGAMQQFNQRFIYGNQDLFATSQSKEFDPLGPLPPGWEKRTDSNGRVYFVNHNTRITQWEDPRSQGQLNEKPLPEGWEMRFTVDGIPYFVDHNRRTTTYIDPRTGKSALDNGPQIAYVRDFKAKVQYFRFWCQQLAMPQHIKITVTRKTLFEDSFQQIMSFSPQDLRRRLWVIFPGEEGLDYGGVAREWFFLLSHEVLNPMYCLFEYAGKDNYCLQINPASYINPDHLKYFRFIGRFIAMALFHGKFIDTGFSLPFYKRILNKPVGLKDLESIDPEFYNSLIWVKENNIEECDLEMYFSVDKEILGEIKSHDLKPNGGNILVTEENKEEYIRMVAEWRLSRGVEEQTQAFFEGFNEILPQQYLQYFDAKELEVLLCGMQEIDLNDWQRHAIYRHYARTSKQIMWFWQFVKEIDNEKRMRLLQFVTGTCRLPVGGFADLMGSNGPQKFCIEKVGKENWLPRSHTCFNRLDLPPYKSYEQLKEKLLFAIEETEGFGQE | |
| 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 |
|---|---|---|---|---|---|
| 2 (in isoform 2) | Phosphorylation | - | 40.25 | 24719451 | |
| 2 | Phosphorylation | ------MSDSGSQLG ------CCCCCCCCC | 40.25 | 25159151 | |
| 2 | Acetylation | ------MSDSGSQLG ------CCCCCCCCC | 40.25 | 19413330 | |
| 4 | Phosphorylation | ----MSDSGSQLGSM ----CCCCCCCCCCC | 32.79 | 30108239 | |
| 6 | Phosphorylation | --MSDSGSQLGSMGS --CCCCCCCCCCCCC | 26.61 | 20068231 | |
| 10 | Phosphorylation | DSGSQLGSMGSLTMK CCCCCCCCCCCEEHH | 28.67 | 20068231 | |
| 13 | Phosphorylation | SQLGSMGSLTMKSQL CCCCCCCCEEHHHCE | 16.42 | 20068231 | |
| 15 | Phosphorylation | LGSMGSLTMKSQLQI CCCCCCEEHHHCEEE | 25.01 | 20068231 | |
| 18 | Phosphorylation | MGSLTMKSQLQITVI CCCEEHHHCEEEEEE | 25.87 | 24043423 | |
| 23 | Phosphorylation | MKSQLQITVISAKLK HHHCEEEEEEEHHHH | 9.99 | 24043423 | |
| 26 | Phosphorylation | QLQITVISAKLKENK CEEEEEEEHHHHHCC | 18.27 | 29759185 | |
| 34 | Ubiquitination | AKLKENKKNWFGPSP HHHHHCCCCCCCCCC | 71.62 | 21890473 | |
| 34 (in isoform 1) | Ubiquitination | - | 71.62 | 21890473 | |
| 34 (in isoform 2) | Ubiquitination | - | 71.62 | 21890473 | |
| 34 | Ubiquitination | AKLKENKKNWFGPSP HHHHHCCCCCCCCCC | 71.62 | 21890473 | |
| 51 (in isoform 3) | Phosphorylation | - | 41.47 | - | |
| 53 | Methylation | TVDGQSKKTEKCNNT EECCCCCCCCCCCCC | 68.13 | - | |
| 56 | Ubiquitination | GQSKKTEKCNNTNSP CCCCCCCCCCCCCCC | 47.71 | - | |
| 60 | Phosphorylation | KTEKCNNTNSPKWKQ CCCCCCCCCCCCCCC | 24.07 | 23312004 | |
| 62 | Phosphorylation | EKCNNTNSPKWKQPL CCCCCCCCCCCCCCE | 26.31 | 23312004 | |
| 64 | Ubiquitination | CNNTNSPKWKQPLTV CCCCCCCCCCCCEEE | 67.83 | - | |
| 66 | Ubiquitination | NTNSPKWKQPLTVIV CCCCCCCCCCEEEEE | 48.43 | 21890473 | |
| 66 | Ubiquitination | NTNSPKWKQPLTVIV CCCCCCCCCCEEEEE | 48.43 | 21890473 | |
| 66 (in isoform 1) | Ubiquitination | - | 48.43 | 21890473 | |
| 66 (in isoform 2) | Ubiquitination | - | 48.43 | 21890473 | |
| 70 | Phosphorylation | PKWKQPLTVIVTPVS CCCCCCEEEEEEECC | 18.18 | 23312004 | |
| 74 | Phosphorylation | QPLTVIVTPVSKLHF CCEEEEEEECCCCCC | 13.57 | 20068231 | |
| 90 | Ubiquitination | VWSHQTLKSDVLLGT ECCCCCHHCCEEHHH | 48.25 | - | |
| 107 | Ubiquitination | LDIYETLKSNNMKLE HHHHHHHHHCCCEEE | 59.56 | - | |
| 161 (in isoform 2) | Phosphorylation | - | 6.27 | - | |
| 180 (in isoform 2) | Phosphorylation | - | 3.75 | 24719451 | |
| 199 (in isoform 2) | Phosphorylation | - | 30.81 | 24719451 | |
| 214 | Phosphorylation | GSRSKDETRVSTNGS CCCCCCCCCCCCCCC | 46.64 | 28555341 | |
| 217 | Phosphorylation | SKDETRVSTNGSDDP CCCCCCCCCCCCCCH | 16.92 | 28450419 | |
| 218 | Phosphorylation | KDETRVSTNGSDDPE CCCCCCCCCCCCCHH | 40.52 | 28450419 | |
| 221 | Phosphorylation | TRVSTNGSDDPEDAG CCCCCCCCCCHHHCC | 40.69 | 25159151 | |
| 222 (in isoform 2) | Phosphorylation | - | 76.51 | - | |
| 236 | Phosphorylation | AGENRRVSGNNSPSL CCCCCCCCCCCCCCC | 33.71 | 25159151 | |
| 240 | Phosphorylation | RRVSGNNSPSLSNGG CCCCCCCCCCCCCCC | 21.62 | 25159151 | |
| 242 | Phosphorylation | VSGNNSPSLSNGGFK CCCCCCCCCCCCCCC | 44.22 | 22199227 | |
| 244 | Phosphorylation | GNNSPSLSNGGFKPS CCCCCCCCCCCCCCC | 37.45 | 22496350 | |
| 251 | Phosphorylation | SNGGFKPSRPPRPSR CCCCCCCCCCCCCCC | 58.99 | 21082442 | |
| 257 | Phosphorylation | PSRPPRPSRPPPPTP CCCCCCCCCCCCCCC | 59.71 | - | |
| 263 | Phosphorylation | PSRPPPPTPRRPASV CCCCCCCCCCCCCCC | 34.89 | - | |
| 273 | Phosphorylation | RPASVNGSPSATSES CCCCCCCCCCCCCCC | 15.52 | - | |
| 343 | Phosphorylation | VDQHGRVYYVDHVEK CCCCCCEEEEECCCC | 9.08 | 19534553 | |
| 344 | Phosphorylation | DQHGRVYYVDHVEKR CCCCCEEEEECCCCC | 9.13 | 27642862 | |
| 350 (in isoform 1) | Ubiquitination | - | 54.69 | 21890473 | |
| 350 | Ubiquitination | YYVDHVEKRTTWDRP EEEECCCCCCCCCCC | 54.69 | 22053931 | |
| 375 | Phosphorylation | VDNMGRIYYVDHFTR CCCCCEEEEEECCCC | 8.97 | 28152594 | |
| 376 | Phosphorylation | DNMGRIYYVDHFTRT CCCCEEEEEECCCCC | 9.31 | 28152594 | |
| 385 | Phosphorylation | DHFTRTTTWQRPTLE ECCCCCCCCCCCCHH | 20.98 | 16888620 | |
| 391 | Ubiquitination | TTWQRPTLESVRNYE CCCCCCCHHHHHCHH | 5.24 | 21890473 | |
| 391 (in isoform 2) | Ubiquitination | - | 5.24 | 21890473 | |
| 391 | Ubiquitination | TTWQRPTLESVRNYE CCCCCCCHHHHHCHH | 5.24 | 20972266 | |
| 393 | Phosphorylation | WQRPTLESVRNYEQW CCCCCHHHHHCHHHH | 29.50 | - | |
| 397 | Phosphorylation | TLESVRNYEQWQLQR CHHHHHCHHHHHHHH | 10.03 | 21945579 | |
| 405 (in isoform 2) | Ubiquitination | - | 23.45 | 21890473 | |
| 405 | Ubiquitination | EQWQLQRSQLQGAMQ HHHHHHHHHHHHHHH | 23.45 | 21890473 | |
| 420 | Phosphorylation | QFNQRFIYGNQDLFA HHHHHHHHCCCCCEE | 13.81 | 21945579 | |
| 431 | Phosphorylation | DLFATSQSKEFDPLG CCEECCCCCCCCCCC | 33.64 | 28555341 | |
| 432 | Ubiquitination | LFATSQSKEFDPLGP CEECCCCCCCCCCCC | 55.55 | 22053931 | |
| 432 (in isoform 1) | Ubiquitination | - | 55.55 | 21890473 | |
| 437 (in isoform 2) | Ubiquitination | - | 13.69 | 21890473 | |
| 437 | Ubiquitination | QSKEFDPLGPLPPGW CCCCCCCCCCCCCCC | 13.69 | 21890473 | |
| 437 | Ubiquitination | QSKEFDPLGPLPPGW CCCCCCCCCCCCCCC | 13.69 | 20972266 | |
| 446 (in isoform 1) | Ubiquitination | - | 54.83 | 21890473 | |
| 446 | Ubiquitination | PLPPGWEKRTDSNGR CCCCCCEECCCCCCC | 54.83 | 21890473 | |
| 450 | Phosphorylation | GWEKRTDSNGRVYFV CCEECCCCCCCEEEE | 40.34 | 14602072 | |
| 472 (in isoform 2) | Ubiquitination | - | 44.95 | 21890473 | |
| 472 | Ubiquitination | QWEDPRSQGQLNEKP ECCCCCCCCCCCCCC | 44.95 | 21890473 | |
| 478 | Ubiquitination | SQGQLNEKPLPEGWE CCCCCCCCCCCCCCE | 51.27 | 21890473 | |
| 478 (in isoform 1) | Ubiquitination | - | 51.27 | 21890473 | |
| 495 | Phosphorylation | FTVDGIPYFVDHNRR EEECCEEEEEECCCC | 17.83 | - | |
| 503 | Phosphorylation | FVDHNRRTTTYIDPR EEECCCCCCEEECCC | 21.91 | - | |
| 504 | Phosphorylation | VDHNRRTTTYIDPRT EECCCCCCEEECCCC | 18.78 | - | |
| 505 | Phosphorylation | DHNRRTTTYIDPRTG ECCCCCCEEECCCCC | 20.19 | - | |
| 506 | Phosphorylation | HNRRTTTYIDPRTGK CCCCCCEEECCCCCC | 10.96 | - | |
| 513 (in isoform 1) | Ubiquitination | - | 31.76 | 21890473 | |
| 513 | Ubiquitination | YIDPRTGKSALDNGP EECCCCCCCCCCCCC | 31.76 | 21890473 | |
| 589 | Phosphorylation | PGEEGLDYGGVAREW ECCCCCCCCHHHHHH | 22.33 | - | |
| 665 | Ubiquitination | GFSLPFYKRILNKPV CCCHHHHHHHHCCCC | 33.08 | - | |
| 670 | Ubiquitination | FYKRILNKPVGLKDL HHHHHHCCCCCCCCH | 37.32 | - | |
| 687 | Phosphorylation | IDPEFYNSLIWVKEN CCHHHHHCEEEEECC | 15.17 | - | |
| 820 | Ubiquitination | WQFVKEIDNEKRMRL HHHHHHCCHHHHHHH | 59.32 | 21890473 | |
| 820 (in isoform 2) | Ubiquitination | - | 59.32 | 21890473 | |
| 820 | Ubiquitination | WQFVKEIDNEKRMRL HHHHHHCCHHHHHHH | 59.32 | 20972266 | |
| 840 | Ubiquitination | GTCRLPVGGFADLMG CCCCCCCCCHHHHCC | 24.46 | 21890473 | |
| 840 (in isoform 2) | Ubiquitination | - | 24.46 | 21890473 | |
| 858 | Ubiquitination | PQKFCIEKVGKENWL CCEEEEEECCCCCCC | 36.05 | - | |
| 858 | Malonylation | PQKFCIEKVGKENWL CCEEEEEECCCCCCC | 36.05 | 26320211 | |
| 861 | Ubiquitination | FCIEKVGKENWLPRS EEEEECCCCCCCCCC | 51.35 | 21890473 | |
| 861 (in isoform 1) | Ubiquitination | - | 51.35 | 21890473 | |
| 881 (in isoform 1) | Ubiquitination | - | 52.95 | 21890473 | |
| 881 | Ubiquitination | RLDLPPYKSYEQLKE CCCCCCCCCHHHHHH | 52.95 | 21890473 |
| Modified Location | Modified Residue | Modification | Type of Upstream Proteins | Gene Name of Upstream Proteins | UniProt AC of Upstream Proteins | Sources |
|---|---|---|---|---|---|---|
| 161 | S | Phosphorylation | Kinase | ATM | Q13315 | PSP |
| 240 | S | Phosphorylation | Kinase | MAPK8 | P45983 | Uniprot |
| 257 | S | Phosphorylation | Kinase | AKT1 | P31749 | PSP |
| 263 | T | Phosphorylation | Kinase | MAPK8 | P45983 | Uniprot |
| 273 | S | Phosphorylation | Kinase | MAPK8 | P45983 | Uniprot |
| 385 | T | Phosphorylation | Kinase | SGK3 | Q96BR1 | Uniprot |
| 420 | Y | Phosphorylation | Kinase | FYN | P06241 | Uniprot |
| 450 | S | Phosphorylation | Kinase | SGK3 | Q96BR1 | Uniprot |
| - | K | Ubiquitination | E3 ubiquitin ligase | ITCH | Q96J02 | PMID:17592138 |
| Modified Location | Modified Residue | Modification | Function | Reference |
|---|---|---|---|---|
| 63 | K | ubiquitylation |
| 18718449 |
* 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 ITCH_HUMAN !! | ||||||
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| Phosphorylation | |
| Reference | PubMed |
| "CISK attenuates degradation of the chemokine receptor CXCR4 via theubiquitin ligase AIP4."; Slagsvold T., Marchese A., Brech A., Stenmark H.; EMBO J. 25:3738-3749(2006). Cited for: PHOSPHORYLATION AT THR-385 AND SER-450, AND INTERACTION WITH SGK3. | |
| "Negative regulation of the E3 ubiquitin ligase itch via Fyn-mediatedtyrosine phosphorylation."; Yang C., Zhou W., Jeon M.S., Demydenko D., Harada Y., Zhou H.,Liu Y.C.; Mol. Cell 21:135-141(2006). Cited for: PHOSPHORYLATION AT TYR-420, INTERACTION WITH JUNB AND FYN, FUNCTION,MASS SPECTROMETRY, AND MUTAGENESIS OF TYR-343; TYR-420 AND TYR-455. | |
| "Tyrosine phosphorylated Par3 regulates epithelial tight junctionassembly promoted by EGFR signaling."; Wang Y., Du D., Fang L., Yang G., Zhang C., Zeng R., Ullrich A.,Lottspeich F., Chen Z.; EMBO J. 25:5058-5070(2006). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-420, AND MASSSPECTROMETRY. | |
