UniProt functional annotation for P02751



	UniProt functional annotation for P02751

UniProt code: P02751.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3900070, PubMed:3593230, PubMed:7989369). Fibronectins are involved in cell adhesion, cell motility, opsonization, wound healing, and maintenance of cell shape (PubMed:3024962, PubMed:3900070, PubMed:3593230, PubMed:7989369). Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization (By similarity). Participates in the regulation of type I collagen deposition by osteoblasts (By similarity). {ECO:0000250|UniProtKB:P11276, ECO:0000269|PubMed:3024962, ECO:0000269|PubMed:3593230, ECO:0000269|PubMed:3900070, ECO:0000269|PubMed:7989369}.

Function: [Anastellin]: Binds fibronectin and induces fibril formation. This fibronectin polymer, named superfibronectin, exhibits enhanced adhesive properties. Both anastellin and superfibronectin inhibit tumor growth, angiogenesis and metastasis. Anastellin activates p38 MAPK and inhibits lysophospholipid signaling. {ECO:0000269|PubMed:11209058, ECO:0000269|PubMed:15665290, ECO:0000269|PubMed:19379667, ECO:0000269|PubMed:8114919}.

Subunit: Mostly heterodimers or multimers of alternatively spliced variants, connected by 2 disulfide bonds near the carboxyl ends; to a lesser extent homodimers. Interacts with FBLN1, AMBP, TNR, LGALS3BP and COL13A1. Interacts with FBLN7 (By similarity). Interacts with COMP (PubMed:12225811). Interacts with TNR; the interaction inhibits cell adhesion and neurite outgrowth (By similarity). Interacts with FST3 and MYOC. {ECO:0000250, ECO:0000269|PubMed:11773026, ECO:0000269|PubMed:11956183, ECO:0000269|PubMed:12225811, ECO:0000269|PubMed:1400330, ECO:0000269|PubMed:16336961, ECO:0000269|PubMed:18713862, ECO:0000269|PubMed:19251642, ECO:0000269|PubMed:8114919, ECO:0000269|PubMed:9501082}.

Subunit: (Microbial infection) Interacts with S.aureus FnbA. {ECO:0000269|PubMed:12736686}.

Subunit: (Microbial infection) Interacts with M.bovis FbpB via the collagen-binding region. {ECO:0000269|PubMed:8406884}.

Subunit: (Microbial infection) Interacts with recombinant S.pneumoniae PavA (rqcH). {ECO:0000269|PubMed:11580843}.

Subunit: (Microbial infection) Interacts with recombinant S.suis FbpS (rqcH) via fibronectin's N-terminal 30 kDa region. {ECO:0000269|PubMed:27834729}.

Subunit: (Microbial infection) Interacts with fibronectin-binding proteins from other Mycobacteria. {ECO:0000269|PubMed:12736686}.

Subcellular location: Secreted, extracellular space, extracellular matrix {ECO:0000305|PubMed:29100092}.

Tissue specificity: Expressed in the inner limiting membrane and around blood vessels in the retina (at protein level) (PubMed:29777959). Plasma FN (soluble dimeric form) is secreted by hepatocytes. Cellular FN (dimeric or cross-linked multimeric forms), made by fibroblasts, epithelial and other cell types, is deposited as fibrils in the extracellular matrix. Ugl-Y1, Ugl-Y2 and Ugl-Y3 are found in urine (PubMed:17614963). {ECO:0000269|PubMed:17614963, ECO:0000269|PubMed:29777959, ECO:0000269|PubMed:3584091}.

Developmental stage: Expressed between 12 and 19 weeks post-conception (WPC) in Bruch's membrane, with expression in the choroid evident from 14 WPC onwards (at protein level) (PubMed:29777959). Expressed in the inner limiting membrane at 17 WPC (at protein level) (PubMed:29777959). Ugl-Y1, Ugl-Y2 and Ugl-Y3 are present in the urine from 0 to 17 years of age (PubMed:17614963, PubMed:3584091). {ECO:0000269|PubMed:17614963, ECO:0000269|PubMed:29777959, ECO:0000269|PubMed:3584091}.

Ptm: Sulfated. {ECO:0000269|PubMed:2414772}.

Ptm: It is not known whether both or only one of Thr-2155 and Thr-2156 are/is glycosylated. {ECO:0000269|PubMed:11285216, ECO:0000269|PubMed:14760718, ECO:0000269|PubMed:16037490, ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:17614963, ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:2012601, ECO:0000269|PubMed:3584091}.

Ptm: Forms covalent cross-links mediated by a transglutaminase, such as F13A or TGM2, between a glutamine and the epsilon-amino group of a lysine residue, forming homopolymers and heteropolymers (e.g. fibrinogen-fibronectin, collagen-fibronectin heteropolymers). {ECO:0000250|UniProtKB:P11276}.

Ptm: Phosphorylated by FAM20C in the extracellular medium. {ECO:0000269|PubMed:26091039}.

Ptm: Proteolytic processing produces the C-terminal NC1 peptide, anastellin. {ECO:0000305|PubMed:8114919}.

Ptm: Some lysine residues are oxidized to allysine by LOXL3, promoting fibronectin activation and matrix formation. {ECO:0000250|UniProtKB:P11276}.

Ptm: Serotonylated on Gln residues by TGM2 in response to hypoxia. {ECO:0000250|UniProtKB:P07589}.

Disease: Glomerulopathy with fibronectin deposits 2 (GFND2) [MIM:601894]: Genetically heterogeneous autosomal dominant disorder characterized clinically by proteinuria, microscopic hematuria, and hypertension that leads to end-stage renal failure in the second to fifth decade of life. {ECO:0000269|PubMed:18268355}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Spondylometaphyseal dysplasia, corner fracture type (SMDCF) [MIM:184255]: An autosomal dominant form of spondylometaphyseal dysplasia, a group of short stature disorders distinguished by abnormalities in the vertebrae and the metaphyses of the tubular bones. SMDCF is characterized by flake-like, triangular, or curvilinear ossification centers at the edges of irregular metaphyses that simulate fractures. These corner fractures involve the distal tibia, the ulnar aspect of the distal radius, the proximal humerus, and the proximal femur. They represent irregular ossification at the growth plates and secondary ossification centers. {ECO:0000269|PubMed:29100092}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: [Isoform 16]: Expressed by fetal and tumor-associated cells. {ECO:0000305}.

Sequence caution: Sequence=AAA52463.1; Type=Erroneous translation; Evidence={ECO:0000305}; Sequence=AAX76513.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=BAD93077.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAD91166.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAD97964.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAD97965.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAD97984.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAE45847.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAH18136.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3900070, PubMed:3593230, PubMed:7989369). Fibronectins are involved in cell adhesion, cell motility, opsonization, wound healing, and maintenance of cell shape (PubMed:3024962, PubMed:3900070, PubMed:3593230, PubMed:7989369). Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization (By similarity). Participates in the regulation of type I collagen deposition by osteoblasts (By similarity). {ECO:0000250\|UniProtKB:P11276, ECO:0000269\|PubMed:3024962, ECO:0000269\|PubMed:3593230, ECO:0000269\|PubMed:3900070, ECO:0000269\|PubMed:7989369}.



Function:		[Anastellin]: Binds fibronectin and induces fibril formation. This fibronectin polymer, named superfibronectin, exhibits enhanced adhesive properties. Both anastellin and superfibronectin inhibit tumor growth, angiogenesis and metastasis. Anastellin activates p38 MAPK and inhibits lysophospholipid signaling. {ECO:0000269\|PubMed:11209058, ECO:0000269\|PubMed:15665290, ECO:0000269\|PubMed:19379667, ECO:0000269\|PubMed:8114919}.


Subunit:		Mostly heterodimers or multimers of alternatively spliced variants, connected by 2 disulfide bonds near the carboxyl ends; to a lesser extent homodimers. Interacts with FBLN1, AMBP, TNR, LGALS3BP and COL13A1. Interacts with FBLN7 (By similarity). Interacts with COMP (PubMed:12225811). Interacts with TNR; the interaction inhibits cell adhesion and neurite outgrowth (By similarity). Interacts with FST3 and MYOC. {ECO:0000250, ECO:0000269\|PubMed:11773026, ECO:0000269\|PubMed:11956183, ECO:0000269\|PubMed:12225811, ECO:0000269\|PubMed:1400330, ECO:0000269\|PubMed:16336961, ECO:0000269\|PubMed:18713862, ECO:0000269\|PubMed:19251642, ECO:0000269\|PubMed:8114919, ECO:0000269\|PubMed:9501082}.
Subunit:		(Microbial infection) Interacts with S.aureus FnbA. {ECO:0000269\|PubMed:12736686}.
Subunit:		(Microbial infection) Interacts with M.bovis FbpB via the collagen-binding region. {ECO:0000269\|PubMed:8406884}.
Subunit:		(Microbial infection) Interacts with recombinant S.pneumoniae PavA (rqcH). {ECO:0000269\|PubMed:11580843}.
Subunit:		(Microbial infection) Interacts with recombinant S.suis FbpS (rqcH) via fibronectin's N-terminal 30 kDa region. {ECO:0000269\|PubMed:27834729}.
Subunit:		(Microbial infection) Interacts with fibronectin-binding proteins from other Mycobacteria. {ECO:0000269\|PubMed:12736686}.
Subcellular location:		Secreted, extracellular space, extracellular matrix {ECO:0000305\|PubMed:29100092}.
Tissue specificity:		Expressed in the inner limiting membrane and around blood vessels in the retina (at protein level) (PubMed:29777959). Plasma FN (soluble dimeric form) is secreted by hepatocytes. Cellular FN (dimeric or cross-linked multimeric forms), made by fibroblasts, epithelial and other cell types, is deposited as fibrils in the extracellular matrix. Ugl-Y1, Ugl-Y2 and Ugl-Y3 are found in urine (PubMed:17614963). {ECO:0000269\|PubMed:17614963, ECO:0000269\|PubMed:29777959, ECO:0000269\|PubMed:3584091}.
Developmental stage:		Expressed between 12 and 19 weeks post-conception (WPC) in Bruch's membrane, with expression in the choroid evident from 14 WPC onwards (at protein level) (PubMed:29777959). Expressed in the inner limiting membrane at 17 WPC (at protein level) (PubMed:29777959). Ugl-Y1, Ugl-Y2 and Ugl-Y3 are present in the urine from 0 to 17 years of age (PubMed:17614963, PubMed:3584091). {ECO:0000269\|PubMed:17614963, ECO:0000269\|PubMed:29777959, ECO:0000269\|PubMed:3584091}.
Ptm:		Sulfated. {ECO:0000269\|PubMed:2414772}.
Ptm:		It is not known whether both or only one of Thr-2155 and Thr-2156 are/is glycosylated. {ECO:0000269\|PubMed:11285216, ECO:0000269\|PubMed:14760718, ECO:0000269\|PubMed:16037490, ECO:0000269\|PubMed:16335952, ECO:0000269\|PubMed:17614963, ECO:0000269\|PubMed:19139490, ECO:0000269\|PubMed:19159218, ECO:0000269\|PubMed:2012601, ECO:0000269\|PubMed:3584091}.
Ptm:		Forms covalent cross-links mediated by a transglutaminase, such as F13A or TGM2, between a glutamine and the epsilon-amino group of a lysine residue, forming homopolymers and heteropolymers (e.g. fibrinogen-fibronectin, collagen-fibronectin heteropolymers). {ECO:0000250\|UniProtKB:P11276}.
Ptm:		Phosphorylated by FAM20C in the extracellular medium. {ECO:0000269\|PubMed:26091039}.
Ptm:		Proteolytic processing produces the C-terminal NC1 peptide, anastellin. {ECO:0000305\|PubMed:8114919}.
Ptm:		Some lysine residues are oxidized to allysine by LOXL3, promoting fibronectin activation and matrix formation. {ECO:0000250\|UniProtKB:P11276}.
Ptm:		Serotonylated on Gln residues by TGM2 in response to hypoxia. {ECO:0000250\|UniProtKB:P07589}.
Disease:		Glomerulopathy with fibronectin deposits 2 (GFND2) [MIM:601894]: Genetically heterogeneous autosomal dominant disorder characterized clinically by proteinuria, microscopic hematuria, and hypertension that leads to end-stage renal failure in the second to fifth decade of life. {ECO:0000269\|PubMed:18268355}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Spondylometaphyseal dysplasia, corner fracture type (SMDCF) [MIM:184255]: An autosomal dominant form of spondylometaphyseal dysplasia, a group of short stature disorders distinguished by abnormalities in the vertebrae and the metaphyses of the tubular bones. SMDCF is characterized by flake-like, triangular, or curvilinear ossification centers at the edges of irregular metaphyses that simulate fractures. These corner fractures involve the distal tibia, the ulnar aspect of the distal radius, the proximal humerus, and the proximal femur. They represent irregular ossification at the growth plates and secondary ossification centers. {ECO:0000269\|PubMed:29100092}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		[Isoform 16]: Expressed by fetal and tumor-associated cells. {ECO:0000305}.
Sequence caution:		Sequence=AAA52463.1; Type=Erroneous translation; Evidence={ECO:0000305}; Sequence=AAX76513.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=BAD93077.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAD91166.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAD97964.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAD97965.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAD97984.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAE45847.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAH18136.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};