Annotations: 7UMG

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
C	SCOP2B Superfamily	Immunoglobulin (Ig) domain-like	8054487	3000071	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Immunoglobulin (Ig) domain-like	8054487	3000071	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Immunoglobulin (Ig) domain-like	8003766	3000071	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)
C	V-set_7	e7umgC1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set_7	ECOD (1.6)
D	V-set_7	e7umgD1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set_7	ECOD (1.6)
A	C1-set_2	e7umgA2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set_2	ECOD (1.6)
A	MHC_I	e7umgA1	A: a+b two layers	X: MHC antigen-recognition domain (From Topology)	H: MHC antigen-recognition domain (From Topology)	T: MHC antigen-recognition domain	F: MHC_I	ECOD (1.6)
B	C1-set_2	e7umgB1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set_2	ECOD (1.6)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
C, D	PF07686	Immunoglobulin V-set domain (V-set)	Immunoglobulin V-set domain	This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.	Domain
A	PF00129	Class I Histocompatibility antigen, domains alpha 1 and 2 (MHC_I)	Class I Histocompatibility antigen, domains alpha 1 and 2	-	Domain
A	PF07654	Immunoglobulin C1-set domain (C1-set)	Immunoglobulin C1-set domain	-	Domain
B	PF07654	Immunoglobulin C1-set domain (C1-set)	Immunoglobulin C1-set domain	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
C, D	T-cell surface glycoprotein CD8 alpha chain	molecular transducer activity coreceptor activity signaling receptor activity protein-containing complex binding binding MHC protein complex binding MHC class I protein complex binding protein binding MHC class I protein binding signaling receptor binding MHC protein binding	multicellular organismal process T cell activation immune system process cell activation cellular process lymphocyte activation leukocyte activation adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains lymphocyte mediated immunity T cell mediated immunity response to stimulus immune response leukocyte mediated immunity adaptive immune response multicellular organismal process T cell activation immune system process cell activation cellular process lymphocyte activation leukocyte activation adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains lymphocyte mediated immunity T cell mediated immunity response to stimulus immune response leukocyte mediated immunity adaptive immune response immune effector process cellular response to stimulus regulation of biological process regulation of cellular process cell surface receptor signaling pathway 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 T cell receptor signaling pathway regulation of response to stimulus regulation of immune response antigen receptor-mediated signaling pathway activation of immune response cell surface receptor protein tyrosine kinase signaling pathway enzyme-linked receptor protein signaling pathway developmental process cytotoxic T cell differentiation cellular developmental process hemopoiesis cell development mononuclear cell differentiation lymphocyte differentiation cell differentiation anatomical structure development T cell differentiation leukocyte differentiation antigen processing and presentation	protein-containing complex receptor complex cell periphery cellular anatomical structure cell surface membrane plasma membrane external side of plasma membrane side of membrane plasma membrane protein complex plasma membrane signaling receptor complex membrane protein complex T cell receptor complex extracellular region protein-containing complex receptor complex cell periphery cellular anatomical structure cell surface membrane plasma membrane external side of plasma membrane side of membrane plasma membrane protein complex plasma membrane signaling receptor complex membrane protein complex T cell receptor complex extracellular region membrane microdomain membrane raft plasma membrane raft plasma membrane region
A	Major histocompatibility complex class I-related gene protein	MHC class I receptor activity molecular transducer activity transmembrane signaling receptor activity signaling receptor activity immune receptor activity beta-2-microglobulin binding protein binding binding protein-containing complex binding signaling receptor binding T cell receptor binding	response to stimulus immune response immune system process 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 developmental process response to stimulus immune response immune system process 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 developmental process multicellular organismal process cellular developmental process hemopoiesis cell activation cell development mononuclear cell differentiation lymphocyte activation lymphocyte differentiation leukocyte activation T cell differentiation in thymus T cell activation cell differentiation anatomical structure development T cell differentiation cellular process leukocyte differentiation antigen processing and presentation antigen processing and presentation of exogenous antigen defense response to Gram-negative bacterium defense response to bacterium response to bacterium antigen processing and presentation of peptide antigen via MHC class I antigen processing and presentation of peptide antigen adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains lymphocyte mediated immunity regulation of immune effector process T cell mediated immunity positive regulation of leukocyte mediated immunity positive regulation of response to biotic stimulus regulation of cellular process immune response to tumor cell regulation of T cell mediated cytotoxicity directed against tumor cell target regulation of T cell mediated immune response to tumor cell positive regulation of immune response positive regulation of leukocyte mediated cytotoxicity leukocyte mediated immunity regulation of immune system process positive regulation of adaptive immune response positive regulation of immune system process regulation of T cell mediated immunity regulation of biological process positive regulation of immune response to tumor cell regulation of adaptive immune response leukocyte mediated cytotoxicity immune effector process regulation of leukocyte mediated immunity regulation of T cell mediated cytotoxicity regulation of response to stimulus regulation of immune response regulation of cell killing positive regulation of cell killing positive regulation of response to tumor cell regulation of response to biotic stimulus T cell mediated cytotoxicity directed against tumor cell target positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains positive regulation of lymphocyte mediated immunity positive regulation of biological process regulation of response to tumor cell positive regulation of response to stimulus T cell mediated immune response to tumor cell regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains positive regulation of immune effector process positive regulation of cellular process T cell mediated cytotoxicity response to tumor cell positive regulation of T cell mediated cytotoxicity biological regulation regulation of leukocyte mediated cytotoxicity regulation of immune response to tumor cell adaptive immune response positive regulation of T cell mediated immune response to tumor cell regulation of lymphocyte mediated immunity positive regulation of T cell mediated immunity positive regulation of T cell mediated cytotoxicity directed against tumor cell target cell killing defense response to Gram-positive bacterium	cell periphery cellular anatomical structure cell surface membrane plasma membrane external side of plasma membrane side of membrane MHC class I protein complex MHC protein complex protein-containing complex plasma membrane protein complex membrane protein complex membrane-bounded organelle endosome membrane cell periphery cellular anatomical structure cell surface membrane plasma membrane external side of plasma membrane side of membrane MHC class I protein complex MHC protein complex protein-containing complex plasma membrane protein complex membrane protein complex membrane-bounded organelle endosome membrane intracellular anatomical structure endosome intracellular vesicle late endosome membrane intracellular membrane-bounded organelle endomembrane system intracellular organelle cytoplasmic vesicle membrane bounding membrane of organelle cytoplasmic vesicle vesicle membrane organelle late endosome cytoplasm vesicle organelle membrane organelle subcompartment endoplasmic reticulum subcompartment nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum endoplasmic reticulum membrane Golgi membrane Golgi apparatus early endosome early endosome membrane extracellular region extracellular space
B	Beta-2-microglobulin	binding antigen binding peptide antigen binding peptide binding protein-containing complex binding MHC protein complex binding MHC class II protein complex binding identical protein binding protein binding protein homodimerization activity protein dimerization activity structural molecule activity	intracellular iron ion homeostasis inorganic ion homeostasis cellular homeostasis chemical homeostasis homeostatic process intracellular monoatomic cation homeostasis monoatomic ion homeostasis intracellular chemical homeostasis monoatomic cation homeostasis intracellular monoatomic ion homeostasis protein refolding primary metabolic process gene expression macromolecule biosynthetic process intracellular iron ion homeostasis inorganic ion homeostasis cellular homeostasis chemical homeostasis homeostatic process intracellular monoatomic cation homeostasis monoatomic ion homeostasis intracellular chemical homeostasis monoatomic cation homeostasis intracellular monoatomic ion homeostasis protein refolding primary metabolic process gene expression macromolecule biosynthetic process protein maturation protein folding biosynthetic process metabolic process cellular process protein metabolic process macromolecule metabolic process adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains multicellular organismal process regulation of immune effector process lymphocyte mediated immunity T cell mediated immunity positive regulation of leukocyte mediated immunity regulation of cellular process response to stimulus T cell cytokine production positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of immune response cytokine production leukocyte mediated immunity regulation of immune system process positive regulation of macromolecule metabolic process positive regulation of adaptive immune response positive regulation of T cell cytokine production positive regulation of immune system process regulation of T cell mediated immunity regulation of biological process regulation of cytokine production involved in immune response immune response regulation of adaptive immune response immune effector process regulation of gene expression regulation of leukocyte mediated immunity regulation of response to stimulus positive regulation of production of molecular mediator of immune response positive regulation of multicellular organismal process regulation of immune response regulation of macromolecule biosynthetic process regulation of production of molecular mediator of immune response positive regulation of cytokine production regulation of metabolic process positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains positive regulation of lymphocyte mediated immunity positive regulation of biological process positive regulation of response to stimulus regulation of T cell cytokine production regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains positive regulation of biosynthetic process regulation of cytokine production positive regulation of immune effector process regulation of multicellular organismal process cytokine production involved in immune response positive regulation of cellular process production of molecular mediator of immune response regulation of biosynthetic process biological regulation regulation of macromolecule metabolic process adaptive immune response regulation of lymphocyte mediated immunity positive regulation of gene expression immune system process positive regulation of T cell mediated immunity positive regulation of cytokine production involved in immune response cellular response to stimulus cellular response to iron ion cellular response to metal ion cellular response to chemical stimulus response to metal ion response to chemical response to iron ion cellular response to iron(III) ion response to iron(III) ion multicellular organismal-level iron ion homeostasis multicellular organismal-level homeostasis multicellular organismal-level chemical homeostasis regulation of neuron projection development regulation of cellular component organization cellular developmental process cell projection organization negative regulation of biological process cell development neuron projection development cellular component organization neurogenesis multicellular organism development neuron differentiation cell differentiation anatomical structure development negative regulation of cellular process cellular component organization or biogenesis negative regulation of cell projection organization system development developmental process plasma membrane bounded cell projection organization negative regulation of cellular component organization regulation of cell projection organization nervous system development negative regulation of neuron projection development generation of neurons neuron development regulation of plasma membrane bounded cell projection organization positive regulation of protein binding regulation of binding positive regulation of binding regulation of protein binding positive regulation of molecular function regulation of molecular function regulation of receptor binding regulation of transferrin receptor binding positive regulation of receptor binding positive regulation of transferrin receptor binding regulation of developmental process regulation of cell differentiation regulation of cell development myeloid cell homeostasis erythrocyte homeostasis regulation of multicellular organismal development hemopoiesis regulation of myeloid cell differentiation erythrocyte differentiation regulation of erythrocyte differentiation myeloid cell differentiation regulation of hemopoiesis homeostasis of number of cells antigen processing and presentation antigen processing and presentation of peptide antigen via MHC class Ib antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent antigen processing and presentation via MHC class Ib antigen processing and presentation of exogenous peptide antigen via MHC class Ib antigen processing and presentation of exogenous peptide antigen antigen processing and presentation of peptide antigen antigen processing and presentation of exogenous antigen cell activation mononuclear cell differentiation lymphocyte activation lymphocyte differentiation leukocyte activation T cell differentiation in thymus T cell activation T cell differentiation leukocyte differentiation regulation of localization import into cell positive regulation of cellular component organization transport vesicle-mediated transport localization positive regulation of endocytosis positive regulation of receptor-mediated endocytosis regulation of endocytosis regulation of transport regulation of receptor-mediated endocytosis regulation of vesicle-mediated transport establishment of localization positive regulation of transport endocytosis receptor-mediated endocytosis peptide antigen assembly with MHC class I protein complex protein-containing complex organization peptide antigen assembly with MHC protein complex MHC class I protein complex assembly cellular component biogenesis cellular component assembly protein-containing complex assembly antigen processing and presentation of peptide antigen via MHC class I MHC protein complex assembly regulation of neurogenesis regulation of nervous system development negative regulation of neurogenesis negative regulation of nervous system development negative regulation of cell differentiation negative regulation of developmental process negative regulation of cell development negative regulation of multicellular organismal process positive regulation of ferrous iron binding regulation of ferrous iron binding negative regulation of cell population proliferation cell population proliferation regulation of cell population proliferation regulation of epithelial cell proliferation epithelial cell proliferation negative regulation of epithelial cell proliferation positive regulation of leukocyte mediated cytotoxicity T cell mediated cytotoxicity positive regulation of T cell mediated cytotoxicity regulation of leukocyte mediated cytotoxicity leukocyte mediated cytotoxicity regulation of T cell mediated cytotoxicity regulation of cell killing positive regulation of cell killing cell killing iron ion transport transition metal ion transport monoatomic ion transport monoatomic cation transport metal ion transport system process sensory perception of chemical stimulus sensory perception nervous system process sensory perception of smell supramolecular fiber organization amyloid fibril formation protein homotetramerization protein complex oligomerization protein tetramerization protein homooligomerization antigen processing and presentation of exogenous peptide antigen via MHC class II antigen processing and presentation of peptide or polysaccharide antigen via MHC class II antigen processing and presentation of peptide antigen via MHC class II negative regulation of receptor binding negative regulation of protein binding negative regulation of binding negative regulation of molecular function peptide antigen assembly with MHC class II protein complex MHC class II protein complex assembly cellular response to nicotine response to nicotine regulation of cellular senescence cellular senescence positive regulation of cellular senescence cellular response to stress response to stress antigen processing and presentation of endogenous peptide antigen antigen processing and presentation of endogenous antigen antigen processing and presentation of endogenous peptide antigen via MHC class I behavior learning or memory cognition regulation of leukocyte activation regulation of cell activation positive regulation of leukocyte cell-cell adhesion leukocyte cell-cell adhesion positive regulation of cell-cell adhesion positive regulation of lymphocyte activation positive regulation of cell activation cell adhesion cell-cell adhesion positive regulation of leukocyte activation regulation of cell-cell adhesion positive regulation of T cell activation positive regulation of cell adhesion regulation of cell adhesion regulation of T cell activation regulation of leukocyte cell-cell adhesion regulation of lymphocyte activation negative regulation of forebrain neuron differentiation forebrain development regulation of forebrain neuron differentiation central nervous system neuron differentiation head development forebrain generation of neurons animal organ development brain development central nervous system development forebrain neuron differentiation negative regulation of neuron differentiation regulation of neuron differentiation regulation of monoatomic ion transport regulation of iron ion transport regulation of metal ion transport biological process involved in interspecies interaction between organisms response to other organism response to bacterium response to external stimulus response to external biotic stimulus response to molecule of bacterial origin response to biotic stimulus	cell periphery cellular anatomical structure cell surface membrane plasma membrane external side of plasma membrane side of membrane extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space cell periphery cellular anatomical structure cell surface membrane plasma membrane external side of plasma membrane side of membrane extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle protein-containing complex plasma membrane protein complex plasma membrane signaling receptor complex membrane protein complex HFE-transferrin receptor complex receptor complex intracellular anatomical structure cytoplasm cytosol MHC class I protein complex MHC protein complex endosome membrane endosome intracellular vesicle late endosome membrane intracellular membrane-bounded organelle endomembrane system intracellular organelle cytoplasmic vesicle membrane bounding membrane of organelle cytoplasmic vesicle vesicle membrane late endosome organelle membrane phagocytic vesicle phagocytic vesicle membrane endocytic vesicle membrane endocytic vesicle vacuolar membrane lytic vacuole vacuole lytic vacuole membrane lysosomal membrane lysosome Golgi apparatus membrane-enclosed lumen intracellular organelle lumen endoplasmic reticulum lumen organelle lumen endoplasmic reticulum Golgi membrane MHC class I peptide loading complex organelle subcompartment endoplasmic reticulum subcompartment nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum protein-containing complex endoplasmic reticulum membrane vesicle lumen cytoplasmic vesicle lumen secretory granule lumen specific granule lumen secretory granule secretory vesicle specific granule anchoring junction cell junction focal adhesion cell-substrate junction MHC class II protein complex early endosome endosome lumen early endosome lumen recycling endosome recycling endosome membrane tertiary granule lumen tertiary granule early endosome membrane transport vesicle transport vesicle membrane coated vesicle membrane COPII-coated ER to Golgi transport vesicle ER to Golgi transport vesicle membrane coated vesicle

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
C, D	IPR036179	Immunoglobulin-like domain superfamily	Homologous Superfamily
C, D	IPR015468	CD8 alpha subunit	Family
C, D	IPR013783	Immunoglobulin-like fold	Homologous Superfamily
C, D	IPR013106	Immunoglobulin V-set domain	Domain
C, D	IPR003599	Immunoglobulin domain subtype	Domain
C, D	IPR007110	Immunoglobulin-like domain	Domain
A	IPR036179	Immunoglobulin-like domain superfamily	Homologous Superfamily
A	IPR050208	Antigen-presenting and immune regulatory MHC class I-related	Family
A	IPR003597	Immunoglobulin C1-set	Domain
A	IPR011161	MHC class I-like antigen recognition-like	Domain
A	IPR011162	MHC classes I/II-like antigen recognition protein	Homologous Superfamily
A	IPR001039	MHC class I alpha chain, alpha1 alpha2 domains	Domain
A	IPR003006	Immunoglobulin/major histocompatibility complex, conserved site	Conserved Site
A	IPR037055	MHC class I-like antigen recognition-like superfamily	Homologous Superfamily
A	IPR013783	Immunoglobulin-like fold	Homologous Superfamily
A	IPR007110	Immunoglobulin-like domain	Domain
B	IPR036179	Immunoglobulin-like domain superfamily	Homologous Superfamily
B	IPR003006	Immunoglobulin/major histocompatibility complex, conserved site	Conserved Site
B	IPR013783	Immunoglobulin-like fold	Homologous Superfamily
B	IPR007110	Immunoglobulin-like domain	Domain
B	IPR050160	Major Histocompatibility Complex/Immunoglobulin	Family
B	IPR003597	Immunoglobulin C1-set	Domain
B	IPR015707	Beta-2-Microglobulin	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
C, D	Pharos: P01732	susceptibility to respiratory infections associated with CD8alpha chain mutation thrombocytopenia DOID:0081062 urinary bladder disease hepatitis B virus infection vasculitis inflammatory bowel disease kidney disease lung cancer agammaglobulinemia lymphopenia arthritic joint disease mouth disease bone marrow disease ovarian disease susceptibility to respiratory infections associated with CD8alpha chain mutation thrombocytopenia DOID:0081062 urinary bladder disease hepatitis B virus infection vasculitis inflammatory bowel disease kidney disease lung cancer agammaglobulinemia lymphopenia arthritic joint disease mouth disease bone marrow disease ovarian disease psoriasis spondyloarthropathy colonic disease diabetes mellitus transitional cell carcinoma encephalitis uterine disease HIV infectious disease vertebral column disease influenza leishmaniasis lung carcinoma allergic disease lymphoproliferative syndrome asthma neutropenia breast disease pneumonia Sjogren syndrome COVID-19 tetanus diarrheal disease tuberculosis eye disease vaccinia inborn carbohydrate metabolic disorder interstitial lung disease liver disease adult acute respiratory distress syndrome lymphatic system disease anemia malaria autoimmune disease osteosarcoma cancer prostate disease skin disease chronic obstructive pulmonary disease stomach disease cutaneous lupus erythematosus
A	Pharos: Q95460	Creutzfeldt Jacob disease hydrolethalus syndrome lung carcinoma malignant mesothelioma pancreatic intraductal papillary-mucinous neoplasm subependymal giant cell astrocytoma cutaneous lupus erythematosus large cell medulloblastoma malignant ependymoma osteosarcoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia glioblastoma lung cancer malignant glioma ovarian cancer Creutzfeldt Jacob disease hydrolethalus syndrome lung carcinoma malignant mesothelioma pancreatic intraductal papillary-mucinous neoplasm subependymal giant cell astrocytoma cutaneous lupus erythematosus large cell medulloblastoma malignant ependymoma osteosarcoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia glioblastoma lung cancer malignant glioma ovarian cancer plasma cell myeloma
B	Pharos: P61769	familial visceral amyloidosis hypoproteinemia, hypercatabolic diffuse large B-cell lymphoma MHC class I deficiency esophageal squamous cell carcinoma kidney disease amyloidosis mature T-cell and NK-cell non-Hodgkin lymphoma autoimmune disease variant ABeta2M amyloidosis Hypergammaglobulinemia prostate cancer heart disease interstitial cystitis lung carcinoma familial visceral amyloidosis hypoproteinemia, hypercatabolic diffuse large B-cell lymphoma MHC class I deficiency esophageal squamous cell carcinoma kidney disease amyloidosis mature T-cell and NK-cell non-Hodgkin lymphoma autoimmune disease variant ABeta2M amyloidosis Hypergammaglobulinemia prostate cancer heart disease interstitial cystitis lung carcinoma acquired metabolic disease ovarian cancer pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia pilocytic astrocytoma psoriasis Sjogren syndrome glioblastoma juvenile dermatomyositis lung adenocarcinoma lymphatic system disease acute kidney failure pancreatic intraductal papillary-mucinous carcinoma periodic fever syndrome bone marrow disease Down syndrome rheumatoid arthritis subependymal giant cell astrocytoma lung cancer lymphoplasmacytic lymphoma osteosarcoma pancreatic intraductal papillary-mucinous neoplasm cancer schizophrenia ulcerative colitis