InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: NDRG1

Summary

InnateDB Protein

IDBP-376664.4

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

NDRG1

Protein Name

N-myc downstream regulated 1

Synonyms

CAP43; CMT4D; DRG-1; DRG1; GC4; HMSNL; NDR1; NMSL; PROXY1; RIT42; RTP; TARG1; TDD5;

Species

Homo sapiens

Ensembl Protein

ENSP00000404854

InnateDB Gene

IDBG-36420 (NDRG1)

Protein Structure

UniProt Annotation

Function

Stress-responsive protein involved in hormone responses, cell growth, and differentiation. Acts as a tumor suppressor in many cell types. Necessary but not sufficient for p53/TP53- mediated caspase activation and apoptosis. Has a role in cell trafficking, notably of the Schwann cell, and is necessary for the maintenance and development of the peripheral nerve myelin sheath. Required for vesicular recycling of CDH1 and TF. May also function in lipid trafficking. Protects cells from spindle disruption damage. Functions in p53/TP53-dependent mitotic spindle checkpoint. Regulates microtubule dynamics and maintains euploidy. {ECO:0000269PubMed:15247272, ECO:0000269PubMed:15377670, ECO:0000269PubMed:17786215, ECO:0000269PubMed:9766676}.

Subcellular Localization

Cytoplasm, cytosol. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Nucleus. Cell membrane. Note=Mainly cytoplasmic but differentially localized to other regions. Associates with the plasma membrane in intestinal epithelia and lactating mammary gland. Translocated to the nucleus in a p53/TP53-dependent manner. In prostate epithelium and placental chorion, located in both the cytoplasm and in the nucleus. No nuclear localization in colon epithelium cells. In intestinal mucosa, prostate and renal cortex, located predominantly adjacent to adherens junctions. Cytoplasmic with granular staining in proximal tubular cells of the kidney and salivary gland ducts. Recruits to the membrane of recycling/sorting and late endosomes via binding to phosphatidylinositol 4-phosphate. Associates with microtubules. Colocalizes with TUBG1 in the centrosome. Cytoplasmic location increased with hypoxia. Phosphorylated form found associated with centromeres during S-phase of mitosis and with the plasma membrane.

Disease Associations

Charcot-Marie-Tooth disease 4D (CMT4D) [MIM:601455]: A recessive demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot- Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. By convention autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are designated CMT4. {ECO:0000269PubMed:10831399}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Ubiquitous; expressed most prominently in placental membranes and prostate, kidney, small intestine, and ovary tissues. Also expressed in heart, brain, skeletal muscle, lung, liver and pancreas. Low levels in peripheral blood leukocytes and in tissues of the immune system. Expressed mainly in epithelial cells. Also found in Schwann cells of peripheral neurons. Reduced expression in adenocarcinomas compared to normal tissues. In colon, prostate and placental membranes, the cells that border the lumen show the highest expression. {ECO:0000269PubMed:12432451, ECO:0000269PubMed:8939898, ECO:0000269PubMed:9251681, ECO:0000269PubMed:9605764}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 92 experimentally validated interaction(s) in this database.

Experimentally validated
Total	92 [view]
Protein-Protein	87 [view]
Protein-DNA	5 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding
GO:0008017	microtubule binding
GO:0017137	Rab GTPase binding
GO:0043015	gamma-tubulin binding
GO:0045296	cadherin binding

Biological Process

GO:0008219	cell death
GO:0010038	response to metal ion
GO:0030330	DNA damage response, signal transduction by p53 class mediator
GO:0032287	peripheral nervous system myelin maintenance
GO:0045576	mast cell activation
GO:0071456	cellular response to hypoxia
GO:0090232	positive regulation of spindle checkpoint

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005813	centrosome
GO:0005829	cytosol
GO:0005874	microtubule
GO:0005886	plasma membrane
GO:0005913	cell-cell adherens junction
GO:0015630	microtubule cytoskeleton
GO:0048471	perinuclear region of cytoplasm
GO:0055038	recycling endosome membrane
GO:0070062	extracellular vesicular exosome