5SXP

STRUCTURAL BASIS FOR THE INTERACTION BETWEEN ITCH PRR AND BETA-PIX

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d5sxpa_	All beta proteins	SH3-like barrel	SH3-domain	SH3-domain	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d5sxpb_	All beta proteins	SH3-like barrel	SH3-domain	SH3-domain	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d5sxpc_	All beta proteins	SH3-like barrel	SH3-domain	SH3-domain	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d5sxpd_	All beta proteins	SH3-like barrel	SH3-domain	SH3-domain	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	SH3-domain	8057905	3000153	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	SH3-domain	8057905	3000153	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	SH3-domain	8057905	3000153	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	SH3-domain	8057905	3000153	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	SH3_1	e5sxpA1	A: beta barrels	X: SH3	H: SH3	T: SH3	F: SH3_1	ECOD (1.6)
B	SH3_1	e5sxpB1	A: beta barrels	X: SH3	H: SH3	T: SH3	F: SH3_1	ECOD (1.6)
C	SH3_1	e5sxpC1	A: beta barrels	X: SH3	H: SH3	T: SH3	F: SH3_1	ECOD (1.6)
D	SH3_1	e5sxpD1	A: beta barrels	X: SH3	H: SH3	T: SH3	F: SH3_1	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	2.30.30.40	Mainly Beta	Roll	SH3 type barrels.	SH3 Domains	CATH (4.3.0)
B	2.30.30.40	Mainly Beta	Roll	SH3 type barrels.	SH3 Domains	CATH (4.3.0)
C	2.30.30.40	Mainly Beta	Roll	SH3 type barrels.	SH3 Domains	CATH (4.3.0)
D	2.30.30.40	Mainly Beta	Roll	SH3 type barrels.	SH3 Domains	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C, D	PF07653	Variant SH3 domain (SH3_2)	Variant SH3 domain	SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organisation. First described in the Src cytoplasmic tyrosine kinase Swiss:P12931. The structure is a partly opened beta barrel.	Domain
A, B, C, D	PF16615	Unstructured region one on RhoGEF 6 and 7 (RhoGEF67_u1)	Unstructured region one on RhoGEF 6 and 7	-	Disordered

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D	Rho guanine nucleotide exchange factor 7	cytoskeletal protein binding protein binding binding gamma-tubulin binding tubulin binding kinase binding enzyme binding protein kinase binding GTPase regulator activity enzyme regulator activity guanyl-nucleotide exchange factor activity nucleoside-triphosphatase regulator activity molecular function regulator activity	lamellipodium assembly plasma membrane bounded cell projection organization cell projection organization plasma membrane bounded cell projection assembly cellular component organization cellular component biogenesis cellular component assembly lamellipodium organization cellular process cellular component organization or biogenesis cell projection assembly cellular response to stimulus regulation of biological process regulation of cellular process lamellipodium assembly plasma membrane bounded cell projection organization cell projection organization plasma membrane bounded cell projection assembly cellular component organization cellular component biogenesis cellular component assembly lamellipodium organization cellular process cellular component organization or biogenesis cell projection assembly cellular response to stimulus regulation of biological process regulation of cellular process cell surface receptor signaling pathway response to stimulus signaling biological regulation cell surface receptor protein tyrosine kinase signaling pathway cell communication signal transduction enzyme-linked receptor protein signaling pathway ephrin receptor signaling pathway positive regulation of molecular function regulation of molecular function positive regulation of hydrolase activity regulation of catalytic activity regulation of hydrolase activity positive regulation of catalytic activity regulation of GTPase activity positive regulation of GTPase activity positive regulation of locomotion regulation of cell motility regulation of fibroblast migration positive regulation of fibroblast migration positive regulation of biological process fibroblast migration positive regulation of cell migration regulation of locomotion ameboidal-type cell migration positive regulation of cell motility regulation of cell migration cell migration cell motility locomotion positive regulation of cellular process positive regulation of programmed cell death regulation of apoptotic process regulation of programmed cell death cell death positive regulation of apoptotic process apoptotic process programmed cell death positive regulation of substrate adhesion-dependent cell spreading regulation of cell-substrate adhesion positive regulation of cell adhesion regulation of substrate adhesion-dependent cell spreading regulation of cell adhesion cell-substrate adhesion cell adhesion positive regulation of cell-substrate adhesion substrate adhesion-dependent cell spreading regulation of cytoskeleton organization regulation of microtubule polymerization or depolymerization regulation of cellular component organization microtubule cytoskeleton organization negative regulation of biological process regulation of protein-containing complex assembly microtubule polymerization or depolymerization protein-containing complex assembly negative regulation of cellular process negative regulation of microtubule nucleation negative regulation of protein polymerization negative regulation of supramolecular fiber organization protein polymerization negative regulation of cellular component organization negative regulation of microtubule polymerization or depolymerization protein-containing complex organization negative regulation of cytoskeleton organization regulation of microtubule-based process negative regulation of microtubule polymerization microtubule polymerization regulation of cellular component biogenesis regulation of microtubule nucleation regulation of organelle organization negative regulation of protein-containing complex assembly organelle organization microtubule nucleation negative regulation of organelle organization regulation of microtubule polymerization regulation of protein polymerization regulation of supramolecular fiber organization microtubule-based process supramolecular fiber organization cytoskeleton organization regulation of microtubule cytoskeleton organization developmental process multicellular organism development multicellular organismal process anatomical structure development nervous system development system development positive regulation of cellular component organization regulation of developmental process plasma membrane bounded cell projection morphogenesis cell morphogenesis regulation of cell morphogenesis positive regulation of developmental process cell projection morphogenesis regulation of lamellipodium organization regulation of lamellipodium morphogenesis positive regulation of cell projection organization regulation of anatomical structure morphogenesis positive regulation of lamellipodium morphogenesis regulation of cell projection organization positive regulation of lamellipodium organization anatomical structure morphogenesis lamellipodium morphogenesis regulation of plasma membrane bounded cell projection organization focal adhesion assembly cell-substrate junction assembly cell junction organization cell-matrix adhesion cell junction assembly cell-substrate junction organization small GTPase-mediated signal transduction Rho protein signal transduction intracellular signal transduction intracellular signaling cassette Golgi organization endomembrane system organization	anchoring junction cell junction cellular anatomical entity focal adhesion cell-substrate junction cell projection cell leading edge plasma membrane bounded cell projection lamellipodium cell periphery cell cortex intracellular anatomical structure cytoplasm intracellular organelle anchoring junction cell junction cellular anatomical entity focal adhesion cell-substrate junction cell projection cell leading edge plasma membrane bounded cell projection lamellipodium cell periphery cell cortex intracellular anatomical structure cytoplasm intracellular organelle centrosome microtubule organizing center cytoskeleton organelle intracellular non-membrane-bounded organelle microtubule cytoskeleton non-membrane-bounded organelle cytosol protein-containing complex neuron projection ruffle somatodendritic compartment cell body neuronal cell body mitotic spindle spindle mitotic spindle pole spindle pole postsynapse synapse
E [auth F], F [auth G]	E3 ubiquitin-protein ligase Itchy homolog	protein binding binding arrestin family protein binding aminoacyltransferase activity ubiquitin-like protein transferase activity catalytic activity, acting on a protein acyltransferase activity ubiquitin-like protein ligase activity ubiquitin protein ligase activity transferase activity catalytic activity ubiquitin-protein transferase activity ligase activity ribonucleoprotein complex binding protein binding binding arrestin family protein binding aminoacyltransferase activity ubiquitin-like protein transferase activity catalytic activity, acting on a protein acyltransferase activity ubiquitin-like protein ligase activity ubiquitin protein ligase activity transferase activity catalytic activity ubiquitin-protein transferase activity ligase activity ribonucleoprotein complex binding protein-containing complex binding signaling receptor binding cytokine receptor binding CXCR chemokine receptor binding G protein-coupled receptor binding chemokine receptor binding ubiquitin-like protein ligase binding enzyme binding	multicellular organismal process regulation of cellular process cellular biosynthetic process negative regulation of biological process negative regulation of cellular metabolic process negative regulation of type I interferon production organic substance metabolic process cytokine production organic substance biosynthetic process negative regulation of cellular process regulation of cytokine production regulation of multicellular organismal process negative regulation of macromolecule metabolic process regulation of biosynthetic process multicellular organismal process regulation of cellular process cellular biosynthetic process negative regulation of biological process negative regulation of cellular metabolic process negative regulation of type I interferon production organic substance metabolic process cytokine production organic substance biosynthetic process negative regulation of cellular process regulation of cytokine production regulation of multicellular organismal process negative regulation of macromolecule metabolic process regulation of biosynthetic process regulation of biological process type I interferon production cellular metabolic process negative regulation of metabolic process biological regulation negative regulation of cytokine production regulation of cellular metabolic process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process negative regulation of cellular biosynthetic process regulation of cellular biosynthetic process regulation of gene expression negative regulation of gene expression biosynthetic process negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process metabolic process cellular process regulation of macromolecule biosynthetic process macromolecule metabolic process negative regulation of multicellular organismal process regulation of metabolic process regulation of type I interferon production localization import into cell receptor internalization transport receptor-mediated endocytosis endocytosis establishment of localization vesicle-mediated transport apoptotic process cell death programmed cell death biological process involved in interspecies interaction between organisms response to stimulus immune response response to other organism defense response defense response to symbiont response to external stimulus response to biotic stimulus immune system process defense response to other organism response to stress innate immune response response to external biotic stimulus organonitrogen compound metabolic process protein autoubiquitination primary metabolic process protein ubiquitination macromolecule modification protein metabolic process post-translational protein modification protein modification process protein modification by small protein conjugation protein modification by small protein conjugation or removal regulation of defense response regulation of response to biotic stimulus negative regulation of response to biotic stimulus regulation of response to external stimulus regulation of defense response to virus regulation of response to stress response to virus negative regulation of response to stimulus defense response to virus regulation of response to stimulus negative regulation of response to external stimulus negative regulation of defense response negative regulation of defense response to virus regulation of growth regulation of cellular component organization growth regulation of cell growth cell growth cellular component organization cellular component organization or biogenesis receptor catabolic process catabolic process positive regulation of biological process positive regulation of cellular metabolic process macromolecule catabolic process cellular catabolic process positive regulation of metabolic process receptor metabolic process positive regulation of macromolecule metabolic process positive regulation of receptor catabolic process positive regulation of cellular process regulation of catabolic process positive regulation of catabolic process regulation of receptor catabolic process regulation of cellular catabolic process positive regulation of cellular catabolic process organic substance catabolic process immune system development regulation of T cell anergy lymphocyte anergy regulation of lymphocyte anergy positive regulation of lymphocyte anergy positive regulation of T cell tolerance induction multicellular organism development positive regulation of T cell anergy anatomical structure development regulation of immune system process regulation of T cell tolerance induction positive regulation of immune system process T cell anergy system development developmental process T cell tolerance induction positive regulation of multicellular organismal process regulation of tolerance induction positive regulation of tolerance induction tolerance induction organonitrogen compound catabolic process proteolysis involved in protein catabolic process protein catabolic process modification-dependent macromolecule catabolic process modification-dependent protein catabolic process proteolysis ubiquitin-dependent protein catabolic process protein polyubiquitination protein K48-linked ubiquitination necroptotic process programmed necrotic cell death regulation of programmed cell death regulation of necroptotic process regulation of programmed necrotic cell death cellular response to stimulus positive regulation of response to biotic stimulus pattern recognition receptor signaling pathway regulation of signal transduction cell communication immune response-activating signaling pathway positive regulation of immune response signal transduction innate immune response-activating signaling pathway regulation of innate immune response regulation of pattern recognition receptor signaling pathway positive regulation of defense response activation of innate immune response regulation of immune response activation of immune response cytoplasmic pattern recognition receptor signaling pathway intracellular receptor signaling pathway signaling negative regulation of signaling negative regulation of cytoplasmic pattern recognition receptor signaling pathway regulation of cytoplasmic pattern recognition receptor signaling pathway negative regulation of cell communication positive regulation of response to stimulus positive regulation of response to external stimulus immune response-regulating signaling pathway regulation of signaling positive regulation of innate immune response negative regulation of signal transduction negative regulation of immune system process regulation of cell communication protein deubiquitination regulation of protein modification process regulation of post-translational protein modification regulation of protein metabolic process regulation of primary metabolic process protein modification by small protein removal regulation of protein deubiquitination regulation of protein modification by small protein conjugation or removal symbiont entry into host cell viral process symbiont entry into host viral life cycle biological process involved in interaction with host biological process involved in symbiotic interaction protein monoubiquitination regulation of developmental process cellular developmental process hemopoiesis cell development regulation of cell differentiation regulation of hematopoietic stem cell differentiation stem cell differentiation cell differentiation regulation of stem cell differentiation hematopoietic stem cell differentiation regulation of hematopoietic progenitor cell differentiation hematopoietic progenitor cell differentiation negative regulation of programmed cell death regulation of apoptotic process negative regulation of apoptotic process protein K29-linked ubiquitination positive regulation of protein metabolic process positive regulation of protein catabolic process regulation of protein catabolic process proteasomal protein catabolic process proteasome-mediated ubiquitin-dependent protein catabolic process negative regulation of intracellular signal transduction intracellular signal transduction negative regulation of JNK cascade regulation of intracellular signal transduction JNK cascade intracellular signaling cassette regulation of JNK cascade regulation of MAPK cascade MAPK cascade negative regulation of MAPK cascade negative regulation of DNA-binding transcription factor activity RNA metabolic process nucleobase-containing compound metabolic process RNA biosynthetic process negative regulation of NF-kappaB transcription factor activity nucleic acid biosynthetic process DNA-templated transcription regulation of RNA metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process negative regulation of molecular function nucleobase-containing compound biosynthetic process nucleic acid metabolic process regulation of molecular function organic cyclic compound metabolic process regulation of DNA-binding transcription factor activity organic cyclic compound biosynthetic process regulation of DNA-templated transcription protein K63-linked ubiquitination inflammatory response negative regulation of lymphocyte proliferation regulation of alpha-beta T cell activation regulation of leukocyte activation regulation of cell activation negative regulation of T cell proliferation negative regulation of cell adhesion negative regulation of leukocyte proliferation alpha-beta T cell proliferation T cell activation lymphocyte proliferation alpha-beta T cell activation regulation of leukocyte proliferation cell population proliferation regulation of CD4-positive, alpha-beta T cell proliferation negative regulation of CD4-positive, alpha-beta T cell activation negative regulation of T cell activation negative regulation of leukocyte cell-cell adhesion mononuclear cell proliferation regulation of cell population proliferation negative regulation of cell-cell adhesion regulation of leukocyte cell-cell adhesion negative regulation of leukocyte activation lymphocyte activation negative regulation of lymphocyte activation leukocyte proliferation leukocyte cell-cell adhesion leukocyte activation negative regulation of mononuclear cell proliferation regulation of alpha-beta T cell proliferation cell adhesion cell-cell adhesion CD4-positive, alpha-beta T cell activation regulation of cell-cell adhesion T cell proliferation regulation of lymphocyte proliferation CD4-positive, alpha-beta T cell proliferation negative regulation of cell population proliferation regulation of cell adhesion cell activation regulation of T cell activation negative regulation of cell activation regulation of T cell proliferation negative regulation of alpha-beta T cell proliferation regulation of CD4-positive, alpha-beta T cell activation negative regulation of CD4-positive, alpha-beta T cell proliferation regulation of mononuclear cell proliferation negative regulation of alpha-beta T cell activation regulation of lymphocyte activation	membrane cellular anatomical entity extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle intracellular anatomical structure cytoplasm cytosol membrane cellular anatomical entity extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle intracellular anatomical structure cytoplasm cytosol intracellular organelle mitochondrion intracellular membrane-bounded organelle cell periphery cell cortex plasma membrane nucleus membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen protein-containing complex cytoplasmic vesicle intracellular vesicle endosome membrane early endosome endosome early endosome membrane endomembrane system cytoplasmic vesicle membrane bounding membrane of organelle vesicle membrane organelle membrane

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D	IPR001849	Pleckstrin homology domain	Domain
A, B, C, D	IPR000219	Dbl homology (DH) domain	Domain
A, B, C, D	IPR035789	Rho guanine nucleotide exchange factor 7, SH3 domain	Domain
A, B, C, D	IPR001715	Calponin homology domain	Domain
A, B, C, D	IPR036028	SH3-like domain superfamily	Homologous Superfamily
A, B, C, D	IPR011993	PH-like domain superfamily	Homologous Superfamily
A, B, C, D	IPR001331	Guanine-nucleotide dissociation stimulator, CDC24, conserved site	Conserved Site
A, B, C, D	IPR001452	SH3 domain	Domain
A, B, C, D	IPR036872	CH domain superfamily	Homologous Superfamily
A, B, C, D	IPR035899	Dbl homology (DH) domain superfamily	Homologous Superfamily
A, B, C, D	IPR046376	RhoGEF 6/7, PH domain	Domain
E [auth F], F [auth G]	IPR035983	HECT, E3 ligase catalytic domain	Homologous Superfamily
E [auth F], F [auth G]	IPR036020	WW domain superfamily	Homologous Superfamily
E [auth F], F [auth G]	IPR000008	C2 domain	Domain
E [auth F], F [auth G]	IPR000569	HECT domain	Domain
E [auth F], F [auth G]	IPR024928	E3 ubiquitin-protein ligase, SMURF1 type	Family
E [auth F], F [auth G]	IPR035892	C2 domain superfamily	Homologous Superfamily
E [auth F], F [auth G]	IPR001202	WW domain	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C, D	Pharos: Q14155	astrocytic tumor large cell medulloblastoma medulloblastoma ovarian cancer Pick disease progressive supranuclear palsy tuberculosis atypical teratoid rhabdoid tumor malignant ependymoma oligodendroglioma pancreatic intraductal papillary-mucinous carcinoma pilocytic astrocytoma psoriasis glioblastoma malignant glioma astrocytic tumor large cell medulloblastoma medulloblastoma ovarian cancer Pick disease progressive supranuclear palsy tuberculosis atypical teratoid rhabdoid tumor malignant ependymoma oligodendroglioma pancreatic intraductal papillary-mucinous carcinoma pilocytic astrocytoma psoriasis glioblastoma malignant glioma osteosarcoma pancreatic intraductal papillary-mucinous neoplasm primitive neuroectodermal tumor subependymal giant cell astrocytoma
E [auth F], F [auth G]	Pharos: Q96J02	syndromic multisystem autoimmune disease due to ITCH deficiency astrocytic tumor glioblastoma large cell medulloblastoma melanoma osteosarcoma primitive neuroectodermal tumor spina bifida atypical teratoid rhabdoid tumor IgA glomerulonephritis malignant ependymoma non-small cell lung carcinoma ovarian cancer psoriasis esophageal adenocarcinoma syndromic multisystem autoimmune disease due to ITCH deficiency astrocytic tumor glioblastoma large cell medulloblastoma melanoma osteosarcoma primitive neuroectodermal tumor spina bifida atypical teratoid rhabdoid tumor IgA glomerulonephritis malignant ependymoma non-small cell lung carcinoma ovarian cancer psoriasis esophageal adenocarcinoma intellectual disability medulloblastoma oligodendroglioma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia sarcoidosis

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.