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  Domain Name: PTK_Tyk2_rpt1
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2. Protein Tyrosine Kinase (PTK) family; Tyrosine kinase 2 (Tyk2); pseudokinase domain (repeat 1). The PTKc (catalytic domain) family to which this subfamily belongs, is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Tyk2 is widely expressed in many tissues. It is involved in signaling via the cytokine receptors IFN-alphabeta, IL-6, IL-10, IL-12, IL-13, and IL-23. It mediates cell surface urokinase receptor (uPAR) signaling and plays a role in modulating vascular smooth muscle cell (VSMC) functional behavior in response to injury. Tyk2 is also important in dendritic cell function and T helper (Th)1 cell differentiation. A homozygous mutation of Tyk2 was found in a patient with hyper-IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and elevated serum IgE. This suggests that Tyk2 may play important roles in multiple cytokine signaling involved in innate and adaptive immunity.
No pairwise interactions are available for this conserved domain.

Total Mutations Found: 359
Total Disease Mutations Found: 226
This domain occurred 94 times on human genes (235 proteins).



  ADENOCARCINOMA OF LUNG, RESPONSE TO TYROS
  ADENOCARCINOMA OF LUNG, SOMATIC
  AMYOTROPHIC LATERAL SCLEROSIS 19
  B CELL-POSITIVE, NK CELL-NEGATIVE
  BLADDER CANCER, SOMATIC, INCLUDED
  CAMPTODACTYLY, TALL STATURE, AND HEARING LOSS SYNDROME
  CATARACT 6, AGE-RELATED CORTICAL
  CHRONIC MYELOID LEUKEMIA, RESISTANT TO IMATINIB
  CROUZON SYNDROME
  DEFICIENCY
  DIABETES MELLITUS, INSULIN-RESISTANT, WITH ACANTHOSIS NIGRICANS
  DIABETES MELLITUS, NONINSULIN-DEPENDENT
  GASTRIC CANCER, SOMATIC
  GLIOBLASTOMA, SOMATIC
  HARTSFIELD SYNDROME
  HEPATOCELLULAR CARCINOMA, CHILDHOOD TYPE, SOMATIC
  HIRSCHSPRUNG DISEASE, SUSCEPTIBILITY TO, 1
  HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 5
  HYPOCHONDROPLASIA
  HYPOGONADOTROPIC HYPOGONADISM 2 WITH ANOSMIA
  HYPOGONADOTROPIC HYPOGONADISM 2 WITH ANOSMIA, SUSCEPTIBILITY TO
  HYPOGONADOTROPIC HYPOGONADISM 2 WITH OR WITHOUT ANOSMIA, SUSCEPTIBILITY
  HYPOGONADOTROPIC HYPOGONADISM 2 WITHOUT ANOSMIA
  HYPOGONADOTROPIC HYPOGONADISM 2 WITHOUT ANOSMIA, SUSCEPTIBILITY TO
  IN
  INSENSITIVITY TO PAIN, CONGENITAL, WITH ANHIDROSIS
  INSULIN RESISTANCE
  INSULIN RESISTANCE, INCLUDED
  LADD SYNDROME
  LEUKEMIA, PHILADELPHIA CHROMOSOME-POSITIVE, RESISTANT TO IMATINIB
  LYMPHOPROLIFERATIVE SYNDROME 1
  MALFORMATIONS
  MULTIPLE ENDOCRINE NEOPLASIA, TYPE IIA
  MULTIPLE ENDOCRINE NEOPLASIA, TYPE IIB
  MULTIPLE MYELOMA, SOMATIC, INCLUDED;;
  MYASTHENIC SYNDROME, CONGENITAL, ASSOCIATED WITH ACETYLCHOLINE RECEPTOR
  NEUROBLASTOMA, SUSCEPTIBILITY TO, 3
  NONSMALL CELL LUNG CANCER, RESISTANCE TO TYROSINE KINASE INHIBITOR
  NONSMALL CELL LUNG CANCER, RESPONSE TO TYROSINE KINASE INHIBITOR IN,
  OBESITY, HYPERPHAGIA, AND DEVELOPMENTAL DELAY
  PFEIFFER SYNDROME
  PHEOCHROMOCYTOMA, INCLUDED
  PHEOCHROMOCYTOMA, SOMATIC, IN
  PROSTATE CANCER, PROGRESSION AND METASTASIS OF
  RENAL AGENESIS
  RENAL CELL CARCINOMA, PAPILLARY, 1
  RENAL CELL CARCINOMA, PAPILLARY, 1, SOMATIC
  RETINITIS PIGMENTOSA 38
  SADDAN DYSPLASIA
  SCAPHOCEPHALY, MAXILLARY RETRUSION, AND MENTAL RETARDATION, INCLUDED
  SELECTIVE T-CELL DEFECT
  SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE,
  SOMATIC
  SPERMATOCYTIC SEMINOMA, SOMATIC, INCLUDED
  SPONDYLOMETAEPIPHYSEAL DYSPLASIA, SHORT LIMB-HAND TYPE
  T-CELL IMMUNODEFICIENCY, RECURRENT INFECTIONS, AUTOIMMUNITY, AND CARDIAC
  THANATOPHORIC DYSPLASIA, TYPE I
  THANATOPHORIC DYSPLASIA, TYPE I, INCLUDED
  THANATOPHORIC DYSPLASIA, TYPE II
  THYROID CARCINOMA, FAMILIAL MEDULLARY
  THYROID CARCINOMA, FAMILIAL MEDULLARY, INCLUDED
  THYROID CARCINOMA, SPORADIC MEDULLARY, INCLUDED;;
  TO
  VENOUS MALFORMATIONS, MULTIPLE CUTANEOUS AND MUCOSAL


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No Conserved Features/Sites Found for PTK_Tyk2_rpt1












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Please Cite: Peterson, T.A., Adadey, A., Santana-Cruz ,I., Sun, Y., Winder A, Kann, M.G., (2010) DMDM: Domain Mapping of Disease Mutations. Bioinformatics 26 (19), 2458-2459.

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