Annotations: 4XZ1

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	SH2 domain	8043591	3000197	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	SH2 domain	8043589	3000197	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	PF00017	e4xz1A2	A: a+b two layers	X: SH2 (From Topology)	H: SH2 (From Topology)	T: SH2	F: PF00017	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.30.505.10	Alpha Beta	2-Layer Sandwich	SHC Adaptor Protein	SH2 domain	CATH (4.3.0)
A	1.10.930.10	Mainly Alpha	Orthogonal Bundle	Syk Kinase	Chain A, domain 2	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF00017	SH2 domain (SH2)	SH2 domain	-	Domain
B	PF02189	Immunoreceptor tyrosine-based activation motif (ITAM)	Immunoreceptor tyrosine-based activation motif	-	Motif

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Tyrosine-protein kinase ZAP-70	protein binding binding signaling receptor binding phosphoprotein binding phosphotyrosine residue binding protein phosphorylated amino acid binding protein tyrosine kinase activity catalytic activity, acting on a protein kinase activity protein kinase activity transferase activity catalytic activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups protein binding binding signaling receptor binding phosphoprotein binding phosphotyrosine residue binding protein phosphorylated amino acid binding protein tyrosine kinase activity catalytic activity, acting on a protein kinase activity protein kinase activity transferase activity catalytic activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding non-membrane spanning protein tyrosine kinase activity	cellular response to stimulus positive regulation of cell communication regulation of cellular process positive regulation of signal transduction response to stimulus signaling positive regulation of biological process regulation of signal transduction intracellular signal transduction cell communication positive regulation of response to stimulus regulation of intracellular signal transduction intracellular signaling cassette regulation of calcium-mediated signaling cellular response to stimulus positive regulation of cell communication regulation of cellular process positive regulation of signal transduction response to stimulus signaling positive regulation of biological process regulation of signal transduction intracellular signal transduction cell communication positive regulation of response to stimulus regulation of intracellular signal transduction intracellular signaling cassette regulation of calcium-mediated signaling positive regulation of calcium-mediated signaling signal transduction positive regulation of cellular process regulation of biological process regulation of signaling biological regulation positive regulation of intracellular signal transduction regulation of response to stimulus calcium-mediated signaling regulation of cell communication cellular process positive regulation of signaling developmental process cellular developmental process cell differentiation thymic T cell selection multicellular organismal process hemopoiesis cell activation cell development mononuclear cell differentiation lymphocyte activation lymphocyte differentiation leukocyte activation T cell differentiation in thymus T cell activation immune system process negative thymic T cell selection anatomical structure development T cell differentiation negative T cell selection T cell selection leukocyte differentiation immune response-regulating cell surface receptor signaling pathway immune response-activating signaling pathway immune response-regulating signaling pathway positive regulation of immune response regulation of immune system process positive regulation of immune system process cell surface receptor signaling pathway immune response-activating cell surface receptor signaling pathway immune response T cell receptor signaling pathway regulation of immune response antigen receptor-mediated signaling pathway activation of immune response adaptive immune response beta selection alpha-beta T cell differentiation alpha-beta T cell activation positive regulation of cell population proliferation regulation of leukocyte activation regulation of alpha-beta T cell activation positive regulation of alpha-beta T cell proliferation regulation of cell activation positive regulation of cell activation alpha-beta T cell proliferation lymphocyte proliferation positive regulation of leukocyte activation regulation of leukocyte proliferation cell population proliferation positive regulation of T cell activation positive regulation of lymphocyte proliferation positive regulation of T cell proliferation positive regulation of alpha-beta T cell activation regulation of cell population proliferation mononuclear cell proliferation regulation of leukocyte cell-cell adhesion positive regulation of leukocyte proliferation positive regulation of multicellular organismal process positive regulation of leukocyte cell-cell adhesion leukocyte proliferation leukocyte cell-cell adhesion positive regulation of cell-cell adhesion regulation of alpha-beta T cell proliferation positive regulation of lymphocyte activation cell adhesion cell-cell adhesion positive regulation of mononuclear cell proliferation regulation of multicellular organismal process regulation of cell-cell adhesion T cell proliferation regulation of lymphocyte proliferation positive regulation of cell adhesion regulation of cell adhesion regulation of T cell activation regulation of T cell proliferation regulation of mononuclear cell proliferation regulation of lymphocyte activation positive thymic T cell selection positive T cell selection leukocyte migration mononuclear cell migration lymphocyte migration cell migration T cell migration cell motility B cell activation biological process involved in interspecies interaction between organisms response to other organism defense response defense response to symbiont response to external stimulus response to biotic stimulus defense response to other organism response to stress innate immune response response to external biotic stimulus organonitrogen compound metabolic process protein phosphorylation phosphorylation cellular metabolic process primary metabolic process peptidyl-tyrosine modification organic substance metabolic process macromolecule modification peptidyl-amino acid modification phosphate-containing compound metabolic process metabolic process protein metabolic process macromolecule metabolic process peptidyl-tyrosine phosphorylation protein modification process phosphorus metabolic process T cell aggregation lymphocyte aggregation leukocyte aggregation regulation of leukocyte differentiation regulation of cell differentiation positive regulation of T cell differentiation regulation of cell development positive regulation of developmental process multicellular organism development positive regulation of cell development positive regulation of alpha-beta T cell differentiation regulation of developmental process regulation of alpha-beta T cell differentiation regulation of T cell differentiation positive regulation of hemopoiesis positive regulation of cell differentiation regulation of lymphocyte differentiation regulation of multicellular organismal development regulation of hemopoiesis positive regulation of leukocyte differentiation positive regulation of lymphocyte differentiation cell surface receptor protein tyrosine kinase signaling pathway enzyme-linked receptor protein signaling pathway	cell-cell junction anchoring junction cell junction cellular anatomical entity cell periphery protein-containing complex plasma membrane protein complex membrane plasma membrane plasma membrane signaling receptor complex membrane protein complex T cell receptor complex receptor complex intracellular anatomical structure cell-cell junction anchoring junction cell junction cellular anatomical entity cell periphery protein-containing complex plasma membrane protein complex membrane plasma membrane plasma membrane signaling receptor complex membrane protein complex T cell receptor complex receptor complex intracellular anatomical structure cytoplasm cytosol immunological synapse extrinsic component of plasma membrane cytoplasmic side of plasma membrane cytoplasmic side of membrane extrinsic component of membrane extrinsic component of cytoplasmic side of plasma membrane side of membrane
B	doubly phosphorylated ITAM peptide	identical protein binding protein binding binding protein homodimerization activity protein dimerization activity protein heterodimerization activity protein tyrosine kinase binding kinase binding enzyme binding protein kinase binding molecular transducer activity transmembrane signaling receptor activity signaling receptor activity	cellular component organization cellular component biogenesis cellular component assembly protein-containing complex organization protein complex oligomerization protein-containing complex assembly cellular process cellular component organization or biogenesis cellular response to stimulus regulation of biological process regulation of cellular process cell surface receptor signaling pathway response to stimulus signaling cellular component organization cellular component biogenesis cellular component assembly protein-containing complex organization protein complex oligomerization protein-containing complex assembly cellular process cellular component organization or biogenesis cellular response to stimulus regulation of biological process regulation of cellular process cell surface receptor signaling pathway response to stimulus signaling biological regulation signal transduction cell communication immune response-regulating cell surface receptor signaling pathway positive regulation of biological process positive regulation of response to stimulus immune response-activating signaling pathway immune response-regulating signaling pathway positive regulation of immune response regulation of immune system process positive regulation of immune system process immune response-activating cell surface receptor signaling pathway immune response T cell receptor signaling pathway regulation of response to stimulus immune system process regulation of immune response antigen receptor-mediated signaling pathway activation of immune response adaptive immune response Fc receptor signaling pathway Fc-gamma receptor signaling pathway protein localization regulation of localization cellular localization regulation of protein localization positive regulation of protein localization to cell surface localization protein localization to cell surface regulation of cellular localization cellular macromolecule localization macromolecule localization positive regulation of protein localization regulation of protein localization to cell surface positive regulation of cellular process multicellular organismal process gamma-delta T cell activation T cell activation cell activation lymphocyte activation leukocyte activation alpha-beta T cell activation	protein-containing complex plasma membrane protein complex membrane plasma membrane membrane protein complex gamma-delta T cell receptor complex cellular anatomical entity receptor complex cell periphery plasma membrane signaling receptor complex T cell receptor complex Fc-gamma receptor III complex Fc receptor complex membrane-bounded organelle protein-containing complex plasma membrane protein complex membrane plasma membrane membrane protein complex gamma-delta T cell receptor complex cellular anatomical entity receptor complex cell periphery plasma membrane signaling receptor complex T cell receptor complex Fc-gamma receptor III complex Fc receptor complex membrane-bounded organelle intracellular organelle intracellular anatomical structure Golgi apparatus organelle cytoplasm intracellular membrane-bounded organelle endomembrane system alpha-beta T cell receptor complex

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR017441	Protein kinase, ATP binding site	Binding Site
A	IPR036860	SH2 domain superfamily	Homologous Superfamily
A	IPR008266	Tyrosine-protein kinase, active site	Active Site
A	IPR023420	Tyrosine-protein kinase SYK/ZAP-70, inter-SH2 domain superfamily	Homologous Superfamily
A	IPR020635	Tyrosine-protein kinase, catalytic domain	Domain
A	IPR000980	SH2 domain	Domain
A	IPR000719	Protein kinase domain	Domain
A	IPR001245	Serine-threonine/tyrosine-protein kinase, catalytic domain	Domain
A	IPR012234	Tyrosine-protein kinase, non-receptor SYK/ZAP-70	Family
A	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
A	IPR035838	SYK/ZAP-70, N-terminal SH2 domain	Domain
B	IPR024128	T-cell surface glycoprotein CD3 zeta subunit	Family
B	IPR003110	Phosphorylated immunoreceptor signalling ITAM	Repeat
B	IPR021663	T-cell surface glycoprotein CD3 zeta subunit/High affinity IgE receptor gamma subunit	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P43403	severe combined immunodeficiency autoimmune disease, multisystem, infantile-onset, 2 combined immunodeficiency due to ZAP70 deficiency primary immunodeficiency disease T cell immunodeficiency primary cancer cutaneous lupus erythematosus interstitial cystitis Omenn syndrome colorectal cancer hematologic disease lymphatic system disease osteosarcoma thrombocytopenia due to immune destruction MHC class II deficiency severe combined immunodeficiency autoimmune disease, multisystem, infantile-onset, 2 combined immunodeficiency due to ZAP70 deficiency primary immunodeficiency disease T cell immunodeficiency primary cancer cutaneous lupus erythematosus interstitial cystitis Omenn syndrome colorectal cancer hematologic disease lymphatic system disease osteosarcoma thrombocytopenia due to immune destruction MHC class II deficiency ovarian cancer susceptibility to respiratory infections associated with CD8alpha chain mutation
B	Pharos: P20963	systemic sclerosis immunodeficiency 25 oligoarticular juvenile idiopathic arthritis allergic rhinitis cutaneous lupus erythematosus hematologic disease interstitial cystitis lung carcinoma osteosarcoma Systemic Scleroderma asthma diffuse scleroderma hypothyroidism juvenile idiopathic arthritis lymphatic system disease systemic sclerosis immunodeficiency 25 oligoarticular juvenile idiopathic arthritis allergic rhinitis cutaneous lupus erythematosus hematologic disease interstitial cystitis lung carcinoma osteosarcoma Systemic Scleroderma asthma diffuse scleroderma hypothyroidism juvenile idiopathic arthritis lymphatic system disease psoriasis cancer Hashimoto thyroiditis lung cancer rheumatoid factor-negative juvenile idiopathic arthritis

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
B	PTR	Parent Component: TYR RESID: AA0039 PSI-MOD : O4'-phospho-L-tyrosine MOD:00048

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), 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.