Gene Report

Basic Information

Approved Symbol	COL1A1
Approved Name	collagen, type I, alpha 1
Symbol Alias	OI4
Location	17q21.33
Position	chr17:48278875-48279000 (-)
External Links	Entrez Gene: 1277 Ensembl: ENSG00000108821 UCSC: uc002iqm.3 HGNC ID: 2197
No. of Studies (Positive/Negative)	1(1/0)
Type	Literature-origin

Positive relationships between COL1A1 and MDD (count: 0)

Positive relationships between COL1A1 and other components at different levels (count: 1)

Genetic/epigenetic locus					Protein and other molecule			Cell and molecular pathway			Neural system			Cognition and behavior		Symptoms and signs			Environment

Name in Literature	Level	Approved Name (Name in Literature)	Type	Reference	Research Type	Statistical Result	Relation Description	All
Name in Literature	Related Components
Col1a1		Depressed mood(depression)	symptoms	Redei, 2015	animal model		if the same molecular mechanisms are at work in chronic stre...... if the same molecular mechanisms are at work in chronic stress¨Cinduced and genetic susceptibility¨Cinduced depression, transcripts that have lower levels inWMIs than inWLIs should show lower levels in CRS compared to NS animals, and vice versa. However, of the six overlapping genes, only three genes (Col1a1, Mmp14,and Gltscr1l), all in hippocampal tissue, demonstrated these hypothesized directional changes. More...

Positive relationship network of COL1A1 in MK4MDD

Network loading ...

Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between COL1A1 and MDD (count: 0)

Negative relationships between COL1A1 and other components at different levels (count: 0)

COL1A1 related SNPs in MK4MDD (count: 0)

COL1A1 related proteins in MK4MDD (count: 0)

COL1A1 related GO terms (count: 60)

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0042542	response to hydrogen peroxide	biological process	IEA
GO:0034504	protein localization to nucleus	biological process	IDA[20018240]
GO:0071306	cellular response to vitamin E	biological process	IEA
GO:0001957	intramembranous ossification	biological process	IEA
GO:0044344	cellular response to fibroblast growth factor stimulus	biological process	IEA
GO:0046872	metal ion binding	molecular function	IEA
GO:0032355	response to estradiol	biological process	IEA
GO:0060346	bone trabecula formation	biological process	IEA
GO:0071364	cellular response to epidermal growth factor stimulus	biological process	IEA
GO:0030198	extracellular matrix organization	biological process	TAS
GO:0071560	cellular response to transforming growth factor beta stimulus	biological process	IEA
GO:0048407	platelet-derived growth factor binding	molecular function	IDA[8900172]
GO:0005515	protein binding	molecular function	IPI[14749390\|18375391\|20015075]
GO:0090263	positive regulation of canonical Wnt signaling pathway	biological process	IDA[20018240]
GO:0010718	positive regulation of epithelial to mesenchymal transition	biological process	IDA[20018240]
GO:0005615	extracellular space	cellular component	IDA[20551380]
GO:0005788	endoplasmic reticulum lumen	cellular component	TAS
GO:0030141	secretory granule	cellular component	IEA
GO:0051591	response to cAMP	biological process	IEA
GO:0001568	blood vessel development	biological process	IMP[17211858]
GO:0006898	receptor-mediated endocytosis	biological process	TAS
GO:0071300	cellular response to retinoic acid	biological process	IEA
GO:0043589	skin morphogenesis	biological process	IMP[17211858]
GO:0001649	osteoblast differentiation	biological process	IEA
GO:0010812	negative regulation of cell-substrate adhesion	biological process	IEA
GO:0001958	endochondral ossification	biological process	IEA
GO:0005794	Golgi apparatus	cellular component	IEA
GO:0030199	collagen fibril organization	biological process	IMP[14976317\|15095409\|17211858\|18375391]
GO:1902618	cellular response to fluoride	biological process	IEA
GO:0070208	protein heterotrimerization	biological process	IEA
GO:0071356	cellular response to tumor necrosis factor	biological process	IEA
GO:0071230	cellular response to amino acid stimulus	biological process	IEA
GO:0042802	identical protein binding	molecular function	IDA[17211858]
GO:0007605	sensory perception of sound	biological process	IMP[17489845]
GO:0007596	blood coagulation	biological process	TAS
GO:0055093	response to hyperoxia	biological process	IEA
GO:0050776	regulation of immune response	biological process	TAS
GO:0050900	leukocyte migration	biological process	TAS
GO:0060351	cartilage development involved in endochondral bone morphogenesis	biological process	IEA
GO:0032964	collagen biosynthetic process	biological process	IMP[15095409]
GO:0001501	skeletal system development	biological process	IMP[1874719\|8097422\|14976317]
GO:0005201	extracellular matrix structural constituent	molecular function	IEA
GO:0005584	collagen type I trimer	cellular component	IMP[14976317\|17576241]
GO:0007601	visual perception	biological process	IMP[17557158]
GO:0048706	embryonic skeletal system development	biological process	IMP[18553566]
GO:0045893	positive regulation of transcription, DNA-templated	biological process	IDA[20018240]
GO:0015031	protein transport	biological process	IEA
GO:0005576	extracellular region	cellular component	TAS
GO:0034505	tooth mineralization	biological process	IMP[17118335]
GO:0031012	extracellular matrix	cellular component	IDA[23658023]; IDA[20551380]; ISS[22261194]
GO:0030168	platelet activation	biological process	TAS
GO:0022617	extracellular matrix disassembly	biological process	TAS
GO:0030335	positive regulation of cell migration	biological process	IDA[20018240]
GO:0042493	response to drug	biological process	IEA
GO:0071260	cellular response to mechanical stimulus	biological process	IEA
GO:0043434	response to peptide hormone	biological process	IEA
GO:0044691	tooth eruption	biological process	IEA
GO:0031960	response to corticosteroid	biological process	IEA
GO:0030574	collagen catabolic process	biological process	TAS
GO:0060325	face morphogenesis	biological process	IEA

COL1A1 related KEGG pathways (count: 2)

ID	Name	Brief Description	Full Description
Literature-origin KEGG pathway
hsa04510	focal adhesion	Focal adhesion	Cell-matrix adhesions play essential roles in important biol...... Cell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the cell-extracellular matrix contact points, specialized structures are formed and termed focal adhesions, where bundles of actin filaments are anchored to transmembrane receptors of the integrin family through a multi-molecular complex of junctional plaque proteins. Some of the constituents of focal adhesions participate in the structural link between membrane receptors and the actin cytoskeleton, while others are signalling molecules, including different protein kinases and phosphatases, their substrates, and various adapter proteins. Integrin signaling is dependent upon the non-receptor tyrosine kinase activities of the FAK and src proteins as well as the adaptor protein functions of FAK, src and Shc to initiate downstream signaling events. These signalling events culminate in reorganization of the actin cytoskeleton; a prerequisite for changes in cell shape and motility, and gene expression. Similar morphological alterations and modulation of gene expression are initiated by the binding of growth factors to their respective receptors, emphasizing the considerable crosstalk between adhesion- and growth factor-mediated signalling. More...
hsa04512	ecm receptor_interaction	ECM-receptor interaction	The extracellular matrix (ECM) consists of a complex mixture...... The extracellular matrix (ECM) consists of a complex mixture of structural and functional macromolecules and serves an important role in tissue and organ morphogenesis and in the maintenance of cell and tissue structure and function. Specific interactions between cells and the ECM are mediated by transmembrane molecules, mainly integrins and perhaps also proteoglycans, CD36, or other cell-surface-associated components. These interactions lead to a direct or indirect control of cellular activities such as adhesion, migration, differentiation, proliferation, and apoptosis. In addition, integrins function as mechanoreceptors and provide a force-transmitting physical link between the ECM and the cytoskeleton. Integrins are a family of glycosylated, heterodimeric transmembrane adhesion receptors that consist of noncovalently bound alpha- and beta-subunits. More...

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways

COL1A1 related BioCarta pathways (count: 0)

COL1A1 related Reactome pathways (count: 13)

ID	Name	Description
Gene mapped Reactome pathways
REACT_13552	integrin cell_surface_interactions	The extracellular matrix (ECM) is a network of macro-molecul...... The extracellular matrix (ECM) is a network of macro-molecules that underlies all epithelia and endothelia and that surrounds all connective tissue cells. This matrix provides the mechanical strength and also influences the behavior and differentiation state of cells in contact with it. The ECM are diverse in composition, but they generally comprise a mixture of fibrillar proteins, polysaccharides synthesized, secreted and organized by neighboring cells. Collagens, fibronectin, and laminins are the principal components involved in cell matrix interactions; other components, such as vitronectin, thrombospondin, and osteopontin, although less abundant, are also important adhesive molecules. Integrins are the receptors that mediate cell adhesion to ECM. Integrins consists of one alpha and one beta subunit forming a noncovalently bound heterodimer. 18 alpha and 8 beta subunits have been identified in humans that combine to form 24 different receptors. The integrin dimers can be broadly divided into three families consisting of the beta1, beta2/beta7, and beta3/alphaV integrins. beta1 associates with 12 alpha-subunits and can be further divided into RGD-, collagen-, or laminin binding and the related alpha4/alpha9 integrins that recognise both matrix and vascular ligands. beta2/beta7 integrins are restricted to leukocytes and mediate cell-cell rather than cell-matrix interactions, although some recognize fibrinogen. The beta3/alphaV family members are all RGD receptors and comprise aIIbb3, an important receptor on platelets, and the remaining b-subunits, which all associate with alphaV. It is the collagen receptors and leukocyte-specific integrins that contain alpha A-domains. More...
REACT_1230	platelet adhesion_to_exposed_collagen	Initiation is the first step in the formation of the platele...... Initiation is the first step in the formation of the platelet plug. This occurs whenever circulating platelets are arrested and subsequently activated by exposed collagen and vWF. Several collagen binding proteins are expressed on platelets, including integrin Alpha2 Beta1, GP VI, and GP IV. Integrin Alpha2 Beta1, also known on leukocytes as VLA-2, is the major collagen receptor. It requires Mg2+ for interacting with collagen. Binding occurs via the alpha2 subunit I domain to a collagen motif with the sequence Gly-Phe-Hyp-Gly-Glu-Arg. Binding of collagen to Alpha2 Beta1 also generates the intracellular signals that contribute to platelet activation. These facilitate the engagement of the lower-affinity collagen receptor, GP VI. The second platelet receptor for collagen is GP VI. This is part of the immunoglobulin superfamily and is the most potent receptor that generates intracellular signals. Its signaling ability is strictly dependent on its association with the Fc receptor epsilon chain, which contains Immunoreceptor Tyrosine-based Activation Motifs (ITAM). GP VI is the key player in collagen-induced platelet activation. vWF protein is a polymeric structure of variable size. It is secreted in two directions by the endothelium - basolaterally and into the bloodstream. Shear-induced aggregation is achieved when vWF binds via its A1 domain to GPIb (part of GPIb - IX - V), and via its A3 domain mediating collagen binding to the subendothelium. The interaction between vWF and GPIb is regulated by shear force, an increase in the shear stress results in a corresponding increase in the affinity of vWF for GPIb. More...
REACT_16888	signaling by_pdgf	Platelet-derived Growth Factor (PDGF) is a potent stimulator...... Platelet-derived Growth Factor (PDGF) is a potent stimulator of growth and motility of connective tissue cells such as fibroblasts and smooth muscle cells as well as other cells such as capillary endothelial cells and neurons.The PDGF family of growth factors is composed of four different polypeptide chains encoded by four different genes. The classical PDGF chains, PDGF-A and PDGF-B, and more recently discovered PDGF-C and PDGF-D. The four PDGF chains assemble into disulphide-bonded dimers via homo- or heterodimerization, and five different dimeric isoforms have been described so far; PDGF-AA, PDGF-AB, PDGF-BB, PDGF-CC and PDGF-DD. It is notable that no heterodimers involving PDGF-C and PDGF-D chains have been described. PDGF exerts its effects by binding to, and activating, two protein tyrosine kinase (PTK) receptors, alpha and beta. These receptors dimerize and undergo autophosphorylation. The phosphorylation sites then attract downstream effectors to transduct the signal into the cell. More...
REACT_12051	cell surface_interactions_at_the_vascular_wall	Leukocyte extravasation is a rigorously controlled process t...... Leukocyte extravasation is a rigorously controlled process that guides white cell movement from the vascular lumen to sites of tissue inflammation. The powerful adhesive interactions that are required for leukocytes to withstand local flow at the vessel wall is a multistep process mediated by different adhesion molecules. Platelets adhered to injured vessel walls form strong adhesive substrates for leukocytes. For instance, the initial tethering and rolling of leukocytes over the site of injury are mediated by reversible binding of selectins to their cognate cell-surface glycoconjugates. Endothelial cells are tightly connected through various proteins, which regulate the organization of the junctional complex and bind to cytoskeletal proteins or cytoplasmic interaction partners that allow the transfer of intracellular signals. An important role for these junctional proteins in governing the transendothelial migration of leukocytes under normal or inflammatory conditions has been established. This pathway describes some of the key interactions that assist in the process of platelet and leukocyte interaction with the endothelium, in response to injury. More...
REACT_18312	ncam1 interactions	The neural cell adhesion molecule, NCAM1 is generally consid...... The neural cell adhesion molecule, NCAM1 is generally considered as a cell adhesion mediator, but it is also considered to be a signal transducing receptor molecule. NCAM1 is involved in multiple cis- and trans-homophilic interactions. It is also involved in several heterophilic interactions with a broad range of other molecules, thereby modulating diverse biological phenomena including cellular adhesion, migration, proliferation, differentiation, survival and synaptic plasticity. More...
REACT_6900	signaling in_immune_system	Humans are exposed to millions of potential pathogens daily,...... Humans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first critical hours and days of exposure to a new pathogen, our innate immune system. More...
REACT_798	platelet activation	Platelet activation begins with the initial binding of adhes...... Platelet activation begins with the initial binding of adhesive ligands and of the excitatory platelet agonists. Intracellular signaling reactions will then enhance the adhesive and procoagulant properties of tethered platelets or of platelets circulating in the proximity. From the subendothelial adhesive substrates, collagen and possibly vWF are the main inducers of platelet activation. GP VI is the most potent collagen receptor initiating signal generation, an ability derived from its interaction with the FcRI gamma chain. This results in the phosphorylation of the gamma-chain by the non-receptor tyrosine kinases of the Src family. The phosphotyrosine motif is recognized by the SH2 domains of Syk, a tyrosine kinase. This association activates the Syk enzyme, leading to activation. Four PARs are identified, of which PARs 1 ,3 and 4 are substrates for thrombin. PAR 1 is the predominant thrombin receptor, PAR 3 is minimally expressed and PAR 4 is less responsive to thrombin. Platelets do not store PAR1, due to limited protein synthesis, they are capable of responding to thrombin only once. Platelet activation further results in the scramblase-mediated transport of negatively-charged phospholipids to the platelet surface. These phospholipids provide a catalytic surface (with the charge provided by phosphatidylserine and phosphatidylethanolamine) for the tenase complex (formed by the activated forms of the blood coagulation factors factor VIII and factor I). More...
REACT_20	formation of_platelet_plug	Hemostasis is a physiological response that culminates in th...... Hemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Acute vessel injury results in its constriction to reduce the loss of blood. Under normal conditions vascular endothelium supports vasodilation, inhibits platelet adhesion and activation, suppresses coagulation, enhances fibrin cleavage and is anti-inflammatory in character. Under acute vascular trauma vasoconstrictor mechanisms predominate and the endothelium becomes prothrombotic, procoagulatory and proinflammatory in nature. This is achieved by a reduction of endothelial dilating agents: adenosine, NO and prostacyclin; and the direct action of ADP, serotonin and thromboxane on vascular smooth muscle cells to elicit their contraction. The chief trigger for the change in endothelial function that leads to the formation of haemostatic thrombus is the loss of the endothelial cell barrier between blood and ECM components. Circulating platelets identify and discriminate areas of endothelial lesions; here, they adhere to the exposed sub endothelium. Their interaction with the various thrombogenic substrates and locally generated or released agonists results in platelet activation. This process is described as possessing two stages, firstly, adhesion - the initial tethering to a surface, and secondly aggregation - the platelet-platelet cohesion. More...
REACT_1695	collagen mediated_activation_cascade	The GPVI receptor is a complex of the GPVI protein with Fc e...... The GPVI receptor is a complex of the GPVI protein with Fc epsilon R1 gamma (FcR). The Src family kinases Fyn and Lyn constitutively associate with the GPVI-FcR complex in platelets and initiate platelet activation through phosphorylation of the immunoreceptor tyrosine-based activation motif (ITAM) in the FcR gamma chain, leading to binding and activation of the tyrosine kinase Syk. Downstream of Syk, a series of adapter molecules and effectors lead to platelet activation. The GPVI receptor signaling cascade is similar to that of T- and B-cell immune receptors, involving the formation of a signalosome composed of adapter and effector proteins. At the core of the T-cell receptor signalosome is the transmembrane adapter LAT and two cytosolic adapters SLP-76 and Gads. While LAT is essential for signalling to PLCgamma1 downstream of the T-cell receptor, the absence of LAT in platelets only impairs the activation of PLCgamma2, the response to collagen and GPVI receptor ligands remains sufficient to elicit a full aggregation response. In contrast, GPVI signalling is almost entirely abolished in the absence of SLP-76. More...
REACT_18334	ncam signaling_for_neurite_out_growth	The neural cell adhesion molecule, NCAM, is a member of the ...... The neural cell adhesion molecule, NCAM, is a member of the immunoglobulin (Ig) superfamily and is involved in a variety of cellular processes of importance for the formation and maintenance of the nervous system. The role of NCAM in neural differentiation and synaptic plasticity is presumed to depend on the modulation of intracellular signal transduction cascades. NCAM based signaling complexes can initiate downstream intracellular signals by at least two mechanisms: (1) activation of FGFR and (2) formation of intracellular signaling complexes by direct interaction with cytoplasmic interaction partners such as Fyn and FAK. Tyrosine kinases Fyn and FAK interact with NCAM and undergo phosphorylation and this transiently activates the MAPK, ERK 1 and 2, cAMP response element binding protein (CREB) and transcription factors ELK and NFkB. CREB activates transcription of genes which are important for axonal growth, survival, and synaptic plasticity in neurons. NCAM1 mediated intracellular signal transduction is represented in the figure below. The Ig domains in NCAM1 are represented in orange ovals and Fn domains in green squares. The tyrosine residues susceptible to phosphorylation are represented in red circles and their positions are numbered. Phosphorylation is represented by red arrows and dephosphorylation by yellow. Ig, Immunoglobulin domain; Fn, Fibronectin domain; Fyn, Proto-oncogene tyrosine-protein kinase Fyn; FAK, focal adhesion kinase; RPTPalpha, Receptor-type tyrosine-protein phosphatase; Grb2, Growth factor receptor-bound protein 2; SOS, Son of sevenless homolog; Raf, RAF proto-oncogene serine/threonine-protein kinase; MEK, MAPK and ERK kinase; ERK, Extracellular signal-regulated kinase; MSK1, Mitogen and stress activated protein kinase 1; CREB, Cyclic AMP-responsive element-binding protein; CRE, cAMP response elements. More...
REACT_622	platelet activation_triggers	In the initial response to injury, platelets adhere to damag...... In the initial response to injury, platelets adhere to damaged blood vessels, responding to the exposure of collagen from the vascular epithelium. Once adhered they degranulate, releasing agents such as serotonin and ADP and synthesize Thromboxane A2, all of which amplify the response, recruiting further platelets to the area and promoting platelet aggregation. More...
REACT_18266	axon guidance	Axon guidance / axon pathfinding is the process by which neu...... Axon guidance / axon pathfinding is the process by which neurons send out axons to reach the correct targets. Growing axons have a highly motile structure at the growing tip called the growth cone, which senses the guidance cues in the environment through guidance cue receptors and responds by undergoing cytoskeletal changes that determine the direction of axon growth. Guidance cues present in the surrounding environment provide the necessary directional information for the trip. These extrinsic cues have been divided into attractive or repulsive signals that tell the growth cone where and where not to grow. Genetic and biochemical studies have led to the identification of highly conserved families of guidance molecules and their receptors that guide axons. These include netrins, Slits, semaphorins, and ephrins, and their cognate receptors, DCC and or uncoordinated-5 (UNC5), roundabouts (Robo), neuropilin and Eph. In addition, many other classes of adhesion molecules are also used by growth cones to navigate properly which include NCAM and L1CAM. More...
REACT_604	hemostasis	Two principal mechanisms limit blood loss after vascular inj...... Two principal mechanisms limit blood loss after vascular injury. Initially, platelets are activated, adhere to the site of the injury, and aggregate into a plug that limits blood loss. Proteins and small molecules released from activated platelets stimulate the plug formation process, and fibrinogen from the plasma forms bridges between activated platelets. These events allow the initiation of the clotting cascade, the second mechanism to limit blood loss. Negatively charged phospholipids exposed on cell surfaces at the site of injury and on activated platelets interact with tissue factor, setting off a cascade of reactions leading to generation of fibrin and the formation of an insoluble fibrin clot that strengthens the platelet plug. More...

COL1A1 related interactors from protein-protein interaction data in HPRD (count: 29)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
COL1A1	HTRA1	No	yeast 2-hybrid	15101818
COL1A1	PDGFB	No	in vitro	10446987
COL1A1	VWF	No	in vitro	3490481
COL1A1	PRELP	No	in vitro	11847210
COL1A1	CD44	No	in vitro	1730778
COL1A1	TXN	No	in vitro;yeast 2-hybrid	12099690
COL1A1	TGFBI	No	in vitro	12034705 , 11867580
COL1A1	CAPN1	No	yeast 2-hybrid	12358155
COL1A1	TMPRSS6	No	in vitro	12149247
COL1A1	P4HB	No	in vitro	1339453
COL1A1	DDR2	No	in vitro	9659899
COL1A1	MMP2	No	in vitro	11368514
COL1A1	MATN2	No	in vitro;in vivo	12180907
COL1A1	DCN	No	in vitro	9675033 , 1468447
COL1A1	BMP1	No	in vivo	11283002
COL1A1	ITGA5	No	in vitro;in vivo	1693626
COL1A1	NID1	No	in vitro	9733643
COL1A1	FN1	No	in vivo	8468356
COL1A1	CD93	No	in vitro	1377218
COL1A1	MMP9	No	in vivo	9878537
COL1A1	ITGA2	No	in vitro;in vivo	11359786 , 11856343 , 2156854
COL1A1	IGFBP3	No	in vitro;in vivo;yeast 2-hybrid	12735930
COL1A1	CD36	No	in vitro	2468670
COL1A1	SPARC	No	in vitro	7034958
COL1A1	FGF7	No	in vitro	11973338
COL1A1	THBS1	No	in vitro	3571333
COL1A1	COL7A1	No	in vitro	9169408
COL1A1	BGN	No	in vitro	7852349
COL1A1	PAK1	No	in vitro	10772928

Gene Report

Gene mapped GO terms

Literature-origin KEGG pathway

Gene mapped KEGG pathways

Gene mapped Reactome pathways