Descriptions

E3 ubiquitin-protein ligase Itchy (Itch) is a HECT domain E3 ubiquitin ligase that provides substrate specificity to the ubiquitylation cascade and mediates the transfer of ubiquitin to substrates. In Itch, the WW domains proceeding the catalytic HECT domain play an inhibitory role by binding directly to HECT. Binding of the Ndfip1 adaptor or JNK1-mediated phosphorylation relieves the autoinhibition of Itch.

Autoinhibitory domains (AIDs)

Target domain

594-949 (HECT domain)

Relief mechanism

PTM, Partner binding

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

3 structures for Q9Y0H4

Entry ID Method Resolution Chain Position Source
1TK7 NMR - A 474-554 PDB
2JMF NMR - A 515-557 PDB
AF-Q9Y0H4-F1 Predicted AlphaFoldDB

No variants for Q9Y0H4

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q9Y0H4

No associated diseases with Q9Y0H4

3 regional properties for Q9Y0H4

Type Name Position InterPro Accession
domain Kinesin motor domain 7 - 344 IPR001752
conserved_site Kinesin motor domain, conserved site 234 - 245 IPR019821
domain Tesmin/TSO1-like CXC domain 1083 - 1125 IPR033467

Functions

Description
EC Number 2.3.2.26 Aminoacyltransferases
Subcellular Localization
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

2 GO annotations of cellular component

Name Definition
cell cortex The region of a cell that lies just beneath the plasma membrane and often, but not always, contains a network of actin filaments and associated proteins.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.

3 GO annotations of molecular function

Name Definition
Notch binding Binding to a Notch (N) protein, a surface receptor.
ubiquitin protein ligase activity Catalysis of the transfer of ubiquitin to a substrate protein via the reaction X-ubiquitin + S -> X + S-ubiquitin, where X is either an E2 or E3 enzyme, the X-ubiquitin linkage is a thioester bond, and the S-ubiquitin linkage is an amide bond
ubiquitin-protein transferase activity Catalysis of the transfer of ubiquitin from one protein to another via the reaction X-Ub + Y --> Y-Ub + X, where both X-Ub and Y-Ub are covalent linkages.

18 GO annotations of biological process

Name Definition
imaginal disc-derived leg joint morphogenesis The process in which the anatomical structures of an imaginal disc-derived leg joint are generated and organized. The leg joint is a flexible region that separates the rigid sections of a leg to allow movement in a controlled manner. An example of this is found in Drosophila melanogaster.
imaginal disc-derived wing margin morphogenesis The process in which the anatomical structures of the imaginal disc-derived wing margin are generated and organized. The wing margin is a strip of cells in the third instar disc at the boundary between the presumptive dorsal and ventral surfaces of the wing blade.
imaginal disc-derived wing vein morphogenesis The process in which anatomical structures of the veins on an imaginal disc-derived wing are generated and organized.
lipid storage The accumulation and maintenance in cells or tissues of lipids, compounds soluble in organic solvents but insoluble or sparingly soluble in aqueous solvents. Lipid reserves can be accumulated during early developmental stages for mobilization and utilization at later stages of development.
negative regulation of hippo signaling Any process that stops, prevents, or reduces the frequency, rate or extent of hippo signaling.
negative regulation of Notch signaling pathway Any process that stops, prevents, or reduces the frequency, rate or extent of the Notch signaling pathway.
negative regulation of smoothened signaling pathway Any process that stops, prevents, or reduces the frequency, rate or extent of smoothened signaling.
Notch signaling pathway The series of molecular signals initiated by an extracellular ligand binding to the receptor Notch on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
positive regulation of endocytosis Any process that activates or increases the frequency, rate or extent of endocytosis.
proteasome-mediated ubiquitin-dependent protein catabolic process The chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of ubiquitin, and mediated by the proteasome.
protein polyubiquitination Addition of multiple ubiquitin groups to a protein, forming a ubiquitin chain.
protein targeting to lysosome The process of directing proteins towards the lysosome using signals contained within the protein.
protein ubiquitination The process in which one or more ubiquitin groups are added to a protein.
pupal development The process whose specific outcome is the progression of the pupa over time, from its formation to the mature structure. The pupa is a dormant life stage interposed between the larval and the adult stages in insects that undergo a complete metamorphosis.
R8 cell development The process whose specific outcome is the progression of the R8 photoreceptor over time, from its formation to the mature structure. The R8 photoreceptor is the founding receptor of each ommatidium.
receptor internalization A receptor-mediated endocytosis process that results in the movement of receptors from the plasma membrane to the inside of the cell. The process begins when cell surface receptors are monoubiquitinated following ligand-induced activation. Receptors are subsequently taken up into endocytic vesicles from where they are either targeted to the lysosome or vacuole for degradation or recycled back to the plasma membrane.
regulation of protein localization Any process that modulates the frequency, rate or extent of any process in which a protein is transported to, or maintained in, a specific location.
wing disc dorsal/ventral pattern formation The establishment, maintenance and elaboration of the dorsal/ventral axis of the wing disc, a precursor to the adult wing.

22 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
P39940 RSP5 E3 ubiquitin-protein ligase RSP5 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) PR
Q9V853 Smurf E3 ubiquitin-protein ligase Smurf1 Drosophila melanogaster (Fruit fly) SS
Q9HAU4 SMURF2 E3 ubiquitin-protein ligase SMURF2 Homo sapiens (Human) EV
Q9HCE7 SMURF1 E3 ubiquitin-protein ligase SMURF1 Homo sapiens (Human) PR
O95817 BAG3 BAG family molecular chaperone regulator 3 Homo sapiens (Human) PR
Q96PU5 NEDD4L E3 ubiquitin-protein ligase NEDD4-like Homo sapiens (Human) PR
O60861 GAS7 Growth arrest-specific protein 7 Homo sapiens (Human) PR
P46934 NEDD4 E3 ubiquitin-protein ligase NEDD4 Homo sapiens (Human) EV
Q9H0M0 WWP1 NEDD4-like E3 ubiquitin-protein ligase WWP1 Homo sapiens (Human) EV
Q96J02 ITCH E3 ubiquitin-protein ligase Itchy homolog Homo sapiens (Human) EV
O00308 WWP2 NEDD4-like E3 ubiquitin-protein ligase WWP2 Homo sapiens (Human) EV
P46935 Nedd4 E3 ubiquitin-protein ligase NEDD4 Mus musculus (Mouse) PR
Q9CUN6 Smurf1 E3 ubiquitin-protein ligase SMURF1 Mus musculus (Mouse) PR
A2A5Z6 Smurf2 E3 ubiquitin-protein ligase SMURF2 Mus musculus (Mouse) SS
Q60780 Gas7 Growth arrest-specific protein 7 Mus musculus (Mouse) PR
Q8CFI0 Nedd4l E3 ubiquitin-protein ligase NEDD4-like Mus musculus (Mouse) PR
Q8BZZ3 Wwp1 NEDD4-like E3 ubiquitin-protein ligase WWP1 Mus musculus (Mouse) SS
Q9DBH0 Wwp2 NEDD4-like E3 ubiquitin-protein ligase WWP2 Mus musculus (Mouse) SS
Q8C863 Itch E3 ubiquitin-protein ligase Itchy Mus musculus (Mouse) EV
Q62940 Nedd4 E3 ubiquitin-protein ligase NEDD4 Rattus norvegicus (Rat) PR
Q9N2Z7 wwp-1 E3 ubiquitin-protein ligase wwp-1 Caenorhabditis elegans SS
A9JRZ0 smurf2 E3 ubiquitin-protein ligase SMURF2 Danio rerio (Zebrafish) (Brachydanio rerio) SS
10 20 30 40 50 60
MADGNGLPAG AASGGMEAGQ TVNGAGSASP TPTSSSGAGA SGSANQGYHQ LSVTIEEASL
70 80 90 100 110 120
RNNGFLKPNP YVELLIDSKS KRKTDLVKNS YLPKWNEEFT VLITPNSTLH FKVLDHSSFR
130 140 150 160 170 180
KDAMLGERII NLAHILQHYN GRCEFLELTI DLFVTSKSDN RQTKSGELVA ILNGLKLDMS
190 200 210 220 230 240
KLQIQPVAGQ QNGNPPVQAV NPSVVSDAAA GRSCMIYGGV RARMRLRSSS GNSNGGETRS
250 260 270 280 290 300
PLPNGGGDHR RSTQAPPVWE QQQQQSQNQQ QPLRMVNGSG AAVPQTAPYP QQPPAPALAR
310 320 330 340 350 360
PLTQVYGALP ENTQPAAVYL PAGGGAAVGP PGVAGPPIEQ PGVGLPVSQS TDPQLQTQPA
370 380 390 400 410 420
DDEPLPAGWE IRLDQYGRRY YVDHNTRSTY WEKPTPLPPG WEIRKDGRGR VYYVDHNTRK
430 440 450 460 470 480
TTWQRPNSER LMHFQHWQGQ RAHVVSQGNQ RYLYSQQQQQ PTAVTAQVTQ DDEDALGPLP
490 500 510 520 530 540
DGWEKKIQSD NRVYFVNHKN RTTQWEDPRT QGQEVSLINE GPLPPGWEIR YTAAGERFFV
550 560 570 580 590 600
DHNTRRTTFE DPRPGAPKGA KGVYGVPRAY ERSFRWKLSQ FRYLCQSNAL PSHIKITVTR
610 620 630 640 650 660
QTLFEDSYHQ IMRLPAYELR RRLYIIFRGE EGLDYGGVSR EWFFLLSHEV LNPMYCLFEY
670 680 690 700 710 720
ANKNNYSLQI NPASYVNPDH LQYFKFIGRF IAMALYHGRF IYSGFTMPFY KRMLNKKLTI
730 740 750 760 770 780
KDIETIDPEF YNSLIWVKDN NIDECGLELW FSVDFEVLGQ IIHHELKENG EKERVTEENK
790 800 810 820 830 840
EEYITLMTEW RMTRGIEQQT KTFLEGFNEV VPLEWLKYFD ERELELILCG MQDVDVEDWQ
850 860 870 880 890 900
RNTIYRHYNR NSKQVVWFWQ FVRETDNEKR ARLLQFVTGT CRVPVGGFAE LMGSNGPQRF
910 920 930 940
CIEKVGKETW LPRSHTCFNR LDLPPYKSYD QLVEKLTFAI EETEGFCQE