From NCBI Gene: Lethal congenital contracture syndrome 2From UniProt: Lethal congenital contracture syndrome 2 (LCCS2): A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy, and congenital non-progressive joint contractures (arthrogryposis). The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. LCCS2 patients manifest craniofacial/ocular findings, lack of hydrops, multiple pterygia, and fractures, as well as a normal duration of pregnancy and a unique feature of a markedly distended urinary bladder (neurogenic bladder defect). The phenotype suggests a spinal cord neuropathic etiology. [MIM:607598]

     From NCBI Gene: This gene encodes a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. This membrane-bound protein has a neuregulin binding domain but not an active kinase domain. It therefore can bind this ligand but not convey the signal into the cell through protein phosphorylation. However, it does form heterodimers with other EGF receptor family members which do have kinase activity. Heterodimerization leads to the activation of pathways which lead to cell proliferation or differentiation. Amplification of this gene and/or overexpression of its protein have been reported in numerous cancers, including prostate, bladder, and breast tumors. Alternate transcriptional splice variants encoding different isoforms have been characterized. One isoform lacks the intermembrane region and is secreted outside the cell. This form acts to modulate the activity of the membrane-bound form. Additional splice variants have also been reported, but they have not been thoroughly characterized. [provided by RefSeq, Jul 2008] From UniProt: Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins. Binds to neuregulin-1 (NRG1) and is activated by it; ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase (PubMed:20682778). May also be activated by CSPG5 (PubMed:15358134).

The following transcription factors affect gene expression:

• PPAR-gamma1
• AP-1
• c-Jun
• AP-2gamma
• Hand1

Tissue specificity:

Epithelial tissues and brain.

Developmental stage:

Overexpressed in a subset of human mammary tumors.

Molecular Function:

• Protein Tyrosine Kinase Activity
• Transmembrane Signaling Receptor Activity
• Ras Guanyl-Nucleotide Exchange Factor Activity
• Atp Binding
• Growth Factor Binding
• Protein Tyrosine Kinase Activator Activity
• Neuregulin Binding
• Identical Protein Binding
• Protein Homodimerization Activity
• Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Activity
• Protein Heterodimerization Activity

Biological Processes:

• Mapk Cascade
• Endocardial Cushion Development
• Negative Regulation Of Cell Adhesion
• Signal Transduction
• Transmembrane Receptor Protein Tyrosine Kinase Signaling Pathway
• Peripheral Nervous System Development
• Heart Development
• Negative Regulation Of Signal Transduction
• Positive Regulation Of Gene Expression
• Schwann Cell Differentiation
• Phosphatidylinositol 3-Kinase Signaling
• Regulation Of Phosphatidylinositol 3-Kinase Signaling
• Positive Regulation Of Phosphatidylinositol 3-Kinase Signaling
• Cranial Nerve Development
• Erbb2 Signaling Pathway
• Wound Healing
• Regulation Of Cell Proliferation
• Negative Regulation Of Neuron Apoptotic Process
• Phosphatidylinositol-Mediated Signaling
• Negative Regulation Of Secretion
• Neuron Apoptotic Process
• Positive Regulation Of Cardiac Muscle Tissue Development
• Positive Regulation Of Protein Tyrosine Kinase Activity
• Positive Regulation Of Calcineurin-Nfat Signaling Cascade
• Extrinsic Apoptotic Signaling Pathway In Absence Of Ligand
• Regulation Of Cell Motility