| IED ID | IndEnz0002004181 |
| Enzyme Type ID | protease004181 |
| Protein Name |
Fibrinogen alpha chain Cleaved into: Fibrinopeptide A; Fibrinogen alpha chain |
| Gene Name | FGA |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MFSMRIVCLVLSVVGTAWTADSGEGDFLAEGGGVRGPRVVERHQSACKDSDWPFCSDEDWNYKCPSGCRMKGLIDEVNQDFTNRINKLKNSLFEYQKNNKDSHSLTTNIMEILRGDFSSANNRDNTYNRVSEDLRSRIEVLKRKVIEKVQHIQLLQKNVRAQLVDMKRLEVDIDIKIRSCRGSCSRALAREVDLKDYEDQQKQLEQVIAKDLLPSRDRQHLPLIKMKPVPDLVPGNFKSQLQKVPPEWKALTDMPQMRMELERPGGNEITRGGSTSYGTGSETESPRNPSSAGSWNSGSSGPGSTGNRNPGSSGTGGTATWKPGSSGPGSTGSWNSGSSGTGSTGNQNPGSPRPGSTGTWNPGSSERGSAGHWTSESSVSGSTGQWHSESGSFRPDSPGSGNARPNNPDWGTFEEVSGNVSPGTRREYHTEKLVTSKGDKELRTGKEKVTSGSTTTTRRSCSKTVTKTVIGPDGHKEVTKEVVTSEDGSDCPEAMDLGTLSGIGTLDGFRHRHPDEAAFFDTASTGKTFPGFFSPMLGEFVSETESRGSESGIFTNTKESSSHHPGIAEFPSRGKSSSYSKQFTSSTSYNRGDSTFESKSYKMADEAGSEADHEGTHSTKRGHAKSRPVRDCDDVLQTHPSGTQSGIFNIKLPGSSKIFSVYCDQETSLGGWLLIQQRMDGSLNFNRTWQDYKRGFGSLNDEGEGEFWLGNDYLHLLTQRGSVLRVELEDWAGNEAYAEYHFRVGSEAEGYALQVSSYEGTAGDALIEGSVEEGAEYTSHNNMQFSTFDRDADQWEENCAEVYGGGWWYNNCQAANLNGIYYPGGSYDPRNNSPYEIENGVVWVSFRGADYSLRAVRMKIRPLVTQ |
| Enzyme Length | 866 |
| Uniprot Accession Number | P02671 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in hemostasis as one of the primary components of blood clots. In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re-epithelialization. Was originally thought to be essential for platelet aggregation, based on in vitro studies using anticoagulated blood. However, subsequent studies have shown that it is not absolutely required for thrombus formation in vivo. Enhances expression of SELP in activated platelets via an ITGB3-dependent pathway. Maternal fibrinogen is essential for successful pregnancy. Fibrin deposition is also associated with infection, where it protects against IFNG-mediated hemorrhage. May also facilitate the immune response via both innate and T-cell mediated pathways. {ECO:0000250|UniProtKB:E9PV24}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (2); Beta strand (15); Chain (1); Coiled coil (1); Compositional bias (5); Cross-link (8); Disulfide bond (8); Domain (1); Glycosylation (4); Helix (11); Metal binding (4); Modified residue (16); Natural variant (22); Peptide (1); Region (3); Sequence conflict (6); Signal peptide (1); Site (4); Turn (8) |
| Keywords | 3D-structure;Adaptive immunity;Alternative splicing;Amyloid;Amyloidosis;Blood coagulation;Calcium;Coiled coil;Direct protein sequencing;Disease variant;Disulfide bond;Glycoprotein;Hemostasis;Hydroxylation;Immunity;Innate immunity;Isopeptide bond;Metal-binding;Phosphoprotein;Reference proteome;Secreted;Signal |
| Interact With | Q8IXL6; O00471; P13473-2; Q9Y3L3; Q9Y371; P00441; P61266; P32856-2; Q9UBB9; Q9BTV4; P09493-10; P06753 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:19296670, ECO:0000269|PubMed:9628725}. |
| Modified Residue | MOD_RES 22; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:16807684"; MOD_RES 45; /note="Phosphoserine; by FAM20C"; /evidence="ECO:0000269|PubMed:26091039, ECO:0007744|PubMed:24275569"; MOD_RES 50; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:24275569"; MOD_RES 56; /note="Phosphoserine; by FAM20C"; /evidence="ECO:0000269|PubMed:26091039"; MOD_RES 281; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:24275569"; MOD_RES 291; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:24275569"; MOD_RES 294; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:24275569"; MOD_RES 364; /note="Phosphoserine; by FAM20C"; /evidence="ECO:0000269|PubMed:26091039"; MOD_RES 412; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:24275569"; MOD_RES 451; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:24275569"; MOD_RES 501; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:24275569"; MOD_RES 505; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:24275569"; MOD_RES 524; /note="Phosphoserine; by FAM20C"; /evidence="ECO:0000269|PubMed:26091039"; MOD_RES 560; /note="Phosphoserine; by FAM20C"; /evidence="ECO:0000269|PubMed:26091039"; MOD_RES 565; /note="4-hydroxyproline; by P4HA1"; /evidence="ECO:0000269|PubMed:19696023"; MOD_RES 609; /note="Phosphoserine; by FAM20C"; /evidence="ECO:0000269|PubMed:26091039, ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:24275569" |
| Post Translational Modification | PTM: The alpha chain is normally not N-glycosylated (PubMed:23151259), even though glycosylation at Asn-686 was observed when a fragment of the protein was expressed in insect cells (PubMed:9689040). It is well known that heterologous expression of isolated domains can lead to adventitious protein modifications. Besides, glycosylation at Asn-686 is supported by large-scale glycoproteomics studies (PubMed:16335952 and PubMed:19159218), but the evidence is still quite tenuous. Most likely, Asn-686 is not glycosylated in the healthy human body, or only with low efficiency. {ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:23151259, ECO:0000269|PubMed:9689040, ECO:0000305}.; PTM: O-glycosylated. {ECO:0000269|PubMed:23050552}.; PTM: Forms F13A-mediated cross-links between a glutamine and the epsilon-amino group of a lysine residue, forming fibronectin-fibrinogen heteropolymers.; PTM: About one-third of the alpha chains in the molecules in blood were found to be phosphorylated.; PTM: Conversion of fibrinogen to fibrin is triggered by thrombin, which cleaves fibrinopeptides A and B from alpha and beta chains, and thus exposes the N-terminal polymerization sites responsible for the formation of the soft clot. The soft clot is converted into the hard clot by factor XIIIA which catalyzes the epsilon-(gamma-glutamyl)lysine cross-linking between gamma chains (stronger) and between alpha chains (weaker) of different monomers. {ECO:0000269|PubMed:2143188}.; PTM: Phosphorylated by FAM20C in the extracellular medium. {ECO:0000269|PubMed:26091039}. |
| Signal Peptide | SIGNAL 1..19; /evidence="ECO:0000269|PubMed:518846, ECO:0000269|Ref.10, ECO:0000269|Ref.14" |
| Structure 3D | X-ray crystallography (39) |
| Cross Reference PDB | 1BBR; 1DM4; 1FPH; 1FZA; 1FZB; 1FZC; 1FZD; 1FZE; 1FZF; 1FZG; 1LT9; 1LTJ; 1N86; 1N8E; 1RE3; 1RE4; 1RF0; 1RF1; 1YCP; 2A45; 2FFD; 2H43; 2HLO; 2HOD; 2HPC; 2OYH; 2OYI; 2Q9I; 2XNX; 2XNY; 2Z4E; 3AT0; 3BVH; 3E1I; 3GHG; 3H32; 3HUS; 4F27; 5CFA; |
| Mapped Pubmed ID | 10209122; 10391242; 10409742; 10411933; 10438935; 10446041; 10543983; 10583407; 10605720; 10725339; 10739913; 10777559; 10891492; 10954706; 11054085; 11401442; 11467836; 11476890; 11509636; 11546832; 11562340; 11583334; 11776317; 11858505; 118839; 11914657; 11960013; 12005431; 12009908; 12068308; 12117709; 12138165; 12140561; 12193970; 12297423; 12356313; 12406899; 12447441; 12447442; 12473660; 12501189; 12585966; 12617173; 12637671; 12640026; 12707238; 1270801; 12724322; 12832465; 12871600; 12878203; 14625308; 14636584; 14667819; 14746139; 14754902; 14970219; 14978285; 14992584; 14992585; 15035987; 15157149; 15166913; 15174051; 15217804; 15311936; 15346842; 15520807; 15543157; 15630448; 15637140; 15735812; 15795540; 15795809; 15831156; 15865460; 1587268; 15944945; 15962837; 15968394; 16005629; 16024789; 16040750; 16086292; 16115959; 16135787; 16210568; 16239428; 16263253; 16324093; 16362348; 16364920; 16439361; 16466010; 16468976; 16525568; 16533041; 16581250; 16614319; 16689770; 16698114; 16706972; 16879721; 16881935; 16894470; 16919435; 16928957; 16939214; 16940416; 17115691; 17141195; 1722201; 17241179; 17263791; 17264959; 17275949; 17295221; 17303222; 17339034; 17408411; 17408725; 17411074; 17414213; 17433418; 17485511; 17496912; 17563371; 17565234; 17568659; 17596138; 17603482; 17603483; 17630702; 17650077; 17688324; 17701467; 17726518; 17849064; 17849175; 17878161; 17878374; 17890055; 17893200; 17951283; 17982313; 17994314; 18057060; 18070880; 18070982; 18202324; 18208536; 18227259; 18278190; 18294856; 18331453; 1837051; 18438411; 18449172; 18484335; 1849145; 18500534; 18562239; 18642883; 18669862; 18676163; 18690352; 18692471; 18772067; 18829464; 18842294; 18974108; 18974842; 19075185; 19091303; 19136375; 19143925; 19190816; 19219045; 19224918; 19242111; 19279408; 19350124; 19412134; 19420105; 19429776; 19468208; 19498957; 19506249; 19507189; 19515723; 19572064; 19588915; 19592493; 19592497; 19631771; 19650644; 19698251; 19718467; 19729601; 19750100; 19899640; 19913121; 19923982; 19928926; 19933846; 19948975; 19967163; 20019599; 20031577; 20051841; 20052757; 20059469; 20128871; 20130576; 20141835; 20167083; 20179705; 20217997; 20218626; 20237496; 20360068; 20416077; 20485341; 20526349; 20533267; 20628086; 20677013; 20709368; 20806111; 20807650; 20829681; 20858867; 20966070; 21063468; 2118650; 21190511; 21190668; 21192254; 21224475; 21245743; 21248064; 21258858; 21418524; 21424530; 21459789; 21464904; 21475196; 21502573; 21606490; 21694469; 21779496; 21800001; 21891970; 21911577; 21932842; 2195544; 22100634; 22177953; 22342352; 22397628; 22407772; 22454496; 22489912; 22510884; 22552295; 22569528; 22639050; 22642105; 22705885; 22713578; 22719251; 22745804; 22795623; 22819533; 22826437; 22836683; 23020230; 23056168; 23061815; 23224113; 23238100; 23300094; 23303819; 23352452; 23551149; 23583981; 23612884; 23613522; 23614898; 23640497; 23667175; 23725126; 23852822; 23875798; 23877568; 23894515; 23934108; 23958299; 23969696; 24040290; 24048413; 2409350; 24121058; 24122271; 24135138; 24192574; 24202393; 24316379; 24345920; 24627488; 24651010; 24746704; 24803720; 24821635; 24937142; 24957944; 25083866; 25163824; 25195011; 25204415; 25241761; 25275549; 25280629; 25313996; 25347092; 25393591; 25435214; 25555432; 25569856; 25896761; 25907612; 25914268; 25923092; 25981141; 26083984; 26228839; 26256740; 26349459; 26540126; 26581183; 26951791; 27044366; 27099386; 27105953; 27164460; 27227380; 27231021; 27266621; 2742826; 27519977; 27555433; 27738342; 27760719; 279930; 28119309; 28192448; 28203040; 28219450; 28269756; 28359658; 28425010; 2866798; 28750085; 28816342; 28851981; 28939558; 2900981; 29016666; 29021578; 29089309; 29240685; 29467321; 29540212; 29662311; 29748775; 29874984; 29932420; 30034615; 30039577; 30106150; 3035556; 3053705; 30794926; 3080684; 30838756; 3094007; 31041195; 31253657; 31260799; 31343282; 3142462; 31443619; 31511434; 31515786; 31625351; 31713292; 31725541; 31740226; 31845492; 32126779; 32205365; 32286477; 32497950; 32638959; 3287375; 32877852; 32967043; 33317138; 33374030; 33472402; 33901106; 34061326; 34255402; 3477999; 34830348; 34830419; 6457647; 7356959; 7473646; 7513017; 7565670; 7565795; 7731720; 7929275; 7935411; 7997267; 8051079; 8157000; 8159701; 8464497; 8467233; 8490014; 8621540; 8649368; 8837778; 8870004; 9006323; 9020159; 9054935; 9307032; 9351824; 9430229; 9566877; 9851811; 9858547; 9862427; |
| Motif | |
| Gene Encoded By | |
| Mass | 94,973 |
| Kinetics | |
| Metal Binding | METAL 791; /note="Calcium"; /evidence="ECO:0000269|PubMed:9689040, ECO:0007744|PDB:1FZD"; METAL 793; /note="Calcium"; /evidence="ECO:0000269|PubMed:9689040, ECO:0007744|PDB:1FZD"; METAL 795; /note="Calcium; via carbonyl oxygen"; /evidence="ECO:0000269|PubMed:9689040, ECO:0007744|PDB:1FZD"; METAL 797; /note="Calcium; via carbonyl oxygen"; /evidence="ECO:0000269|PubMed:9689040, ECO:0007744|PDB:1FZD" |
| Rhea ID | |
| Cross Reference Brenda |