ID FIBA_RAT Reviewed; 782 AA.
AC P06399;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 3.
DT 08-NOV-2023, entry version 162.
DE RecName: Full=Fibrinogen alpha chain;
DE Contains:
DE RecName: Full=Fibrinopeptide A;
DE Contains:
DE RecName: Full=Fibrinogen alpha chain;
DE Flags: Precursor;
GN Name=Fga;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8595905; DOI=10.1006/geno.1995.0010;
RA Fu Y., Cao Y., Hertzberg K.M., Grieninger G.;
RT "Fibrinogen alpha genes: conservation of bipartite transcripts and carboxy-
RT terminal-extended alpha subunits in vertebrates.";
RL Genomics 30:71-76(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2).
RX PubMed=4046033; DOI=10.1016/0022-2836(85)90179-2;
RA Crabtree G.R., Comeau C.M., Fowlkes D.M., Fornace A.J. Jr., Malley J.D.,
RA Kant J.A.;
RT "Evolution and structure of the fibrinogen genes. Random insertion of
RT introns or selective loss?";
RL J. Mol. Biol. 185:1-19(1985).
RN [3]
RP PROTEIN SEQUENCE OF 20-36.
RA Blombaeck B., Blombaeck M., Grondahl N.J.;
RT "Studies on fibrinopeptides from mammals.";
RL Acta Chem. Scand. 19:1789-1791(1965).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 458-550 (ISOFORM 2).
RC STRAIN=Wistar; TISSUE=Liver;
RX PubMed=3817019; DOI=10.1016/0014-4827(87)90223-0;
RA Sobczak J., Lotti A.-M., Taroux P., Duguet M.;
RT "Molecular cloning of mRNA sequences transiently induced during rat liver
RT regeneration.";
RL Exp. Cell Res. 169:47-56(1987).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-279; SER-326; SER-470 AND
RP SER-526, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Cleaved by the protease thrombin to yield monomers which,
CC together with fibrinogen beta (FGB) and fibrinogen gamma (FGG),
CC polymerize to form an insoluble fibrin matrix. Fibrin has a major
CC function in hemostasis as one of the primary components of blood clots.
CC In addition, functions during the early stages of wound repair to
CC stabilize the lesion and guide cell migration during re-
CC epithelialization. Was originally thought to be essential for platelet
CC aggregation, based on in vitro studies using anticoagulated blood.
CC However, subsequent studies have shown that it is not absolutely
CC required for thrombus formation in vivo. Enhances expression of SELP in
CC activated platelets via an ITGB3-dependent pathway. Maternal fibrinogen
CC is essential for successful pregnancy. Fibrin deposition is also
CC associated with infection, where it protects against IFNG-mediated
CC hemorrhage. May also facilitate the immune response via both innate and
CC T-cell mediated pathways. {ECO:0000250|UniProtKB:E9PV24}.
CC -!- SUBUNIT: Heterohexamer; disulfide linked. Contains 2 sets of 3 non-
CC identical chains (alpha, beta and gamma). The 2 heterotrimers are in
CC head to head conformation with the N-termini in a small central domain
CC (By similarity). {ECO:0000250|UniProtKB:P02671}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P02671}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Alpha-E;
CC IsoId=P06399-1; Sequence=Displayed;
CC Name=2; Synonyms=Alpha;
CC IsoId=P06399-2; Sequence=VSP_001533, VSP_001534;
CC -!- DOMAIN: A long coiled coil structure formed by 3 polypeptide chains
CC connects the central nodule to the C-terminal domains (distal nodules).
CC The long C-terminal ends of the alpha chains fold back, contributing a
CC fourth strand to the coiled coil structure.
CC {ECO:0000250|UniProtKB:P02671}.
CC -!- PTM: Conversion of fibrinogen to fibrin is triggered by thrombin, which
CC cleaves fibrinopeptides A and B from alpha and beta chains, and thus
CC exposes the N-terminal polymerization sites responsible for the
CC formation of the soft clot. The soft clot is converted into the hard
CC clot by factor XIIIA which catalyzes the epsilon-(gamma-glutamyl)lysine
CC cross-linking between gamma chains (stronger) and between alpha chains
CC (weaker) of different monomers.
CC -!- PTM: Forms F13A-mediated cross-links between a glutamine and the
CC epsilon-amino group of a lysine residue, forming fibronectin-fibrinogen
CC heteropolymers.
CC -!- PTM: Phosphorylated by FAM20C in the extracellular medium.
CC {ECO:0000250|UniProtKB:P02671}.
CC -!- MISCELLANEOUS: [Isoform 2]: Major isoform. {ECO:0000305}.
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DR EMBL; X86561; CAA60264.1; -; Genomic_DNA.
DR EMBL; X86561; CAA60263.1; -; Genomic_DNA.
DR EMBL; M35601; AAA41158.1; -; mRNA.
DR PIR; I53408; I53408.
DR AlphaFoldDB; P06399; -.
DR SMR; P06399; -.
DR STRING; 10116.ENSRNOP00000060007; -.
DR GlyCosmos; P06399; 1 site, No reported glycans.
DR GlyGen; P06399; 2 sites, 1 O-linked glycan (1 site).
DR iPTMnet; P06399; -.
DR PhosphoSitePlus; P06399; -.
DR PaxDb; 10116-ENSRNOP00000060007; -.
DR PeptideAtlas; P06399; -.
DR UCSC; RGD:2603; rat. [P06399-1]
DR AGR; RGD:2603; -.
DR RGD; 2603; Fga.
DR eggNOG; KOG2579; Eukaryota.
DR InParanoid; P06399; -.
DR PhylomeDB; P06399; -.
DR Reactome; R-RNO-114608; Platelet degranulation.
DR Reactome; R-RNO-140875; Common Pathway of Fibrin Clot Formation.
DR Reactome; R-RNO-216083; Integrin cell surface interactions.
DR Reactome; R-RNO-354192; Integrin signaling.
DR Reactome; R-RNO-354194; GRB2:SOS provides linkage to MAPK signaling for Integrins.
DR Reactome; R-RNO-372708; p130Cas linkage to MAPK signaling for integrins.
DR Reactome; R-RNO-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-RNO-5674135; MAP2K and MAPK activation.
DR Reactome; R-RNO-8957275; Post-translational protein phosphorylation.
DR PRO; PR:P06399; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0072562; C:blood microparticle; IDA:RGD.
DR GO; GO:0005938; C:cell cortex; ISO:RGD.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005577; C:fibrinogen complex; ISO:RGD.
DR GO; GO:0031091; C:platelet alpha granule; ISO:RGD.
DR GO; GO:0045202; C:synapse; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005102; F:signaling receptor binding; IEA:InterPro.
DR GO; GO:0005198; F:structural molecule activity; ISO:RGD.
DR GO; GO:0006953; P:acute-phase response; IEP:RGD.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0007596; P:blood coagulation; ISO:RGD.
DR GO; GO:0072377; P:blood coagulation, common pathway; ISO:RGD.
DR GO; GO:0072378; P:blood coagulation, fibrin clot formation; ISO:RGD.
DR GO; GO:0007160; P:cell-matrix adhesion; ISO:RGD.
DR GO; GO:1990643; P:cellular response to granulocyte colony-stimulating factor; IEP:RGD.
DR GO; GO:0071354; P:cellular response to interleukin-6; IEP:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEP:RGD.
DR GO; GO:0044468; P:envenomation resulting in modulation of blood coagulation in another organism; IEP:RGD.
DR GO; GO:0042730; P:fibrinolysis; ISO:RGD.
DR GO; GO:0043152; P:induction of bacterial agglutination; ISO:RGD.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0097421; P:liver regeneration; IEP:RGD.
DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; ISO:RGD.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; ISO:RGD.
DR GO; GO:0031639; P:plasminogen activation; ISO:RGD.
DR GO; GO:0070527; P:platelet aggregation; ISO:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:0045921; P:positive regulation of exocytosis; ISO:RGD.
DR GO; GO:0034116; P:positive regulation of heterotypic cell-cell adhesion; ISO:RGD.
DR GO; GO:0090277; P:positive regulation of peptide hormone secretion; ISO:RGD.
DR GO; GO:0050714; P:positive regulation of protein secretion; ISO:RGD.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IDA:RGD.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; ISO:RGD.
DR GO; GO:0051258; P:protein polymerization; ISO:RGD.
DR GO; GO:0065003; P:protein-containing complex assembly; ISO:RGD.
DR GO; GO:0051592; P:response to calcium ion; ISO:RGD.
DR GO; GO:0046898; P:response to cycloheximide; IEP:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0033595; P:response to genistein; IEP:RGD.
DR GO; GO:0060416; P:response to growth hormone; IEP:RGD.
DR GO; GO:0032868; P:response to insulin; IEP:RGD.
DR GO; GO:0097066; P:response to thyroid hormone; IEP:RGD.
DR GO; GO:0009636; P:response to toxic substance; IEP:RGD.
DR GO; GO:0010165; P:response to X-ray; IEP:RGD.
DR CDD; cd00087; FReD; 1.
DR Gene3D; 1.20.5.50; -; 1.
DR Gene3D; 3.90.215.10; Gamma Fibrinogen, chain A, domain 1; 1.
DR Gene3D; 4.10.530.10; Gamma-fibrinogen Carboxyl Terminal Fragment, domain 2; 1.
DR InterPro; IPR037579; Fibrinogen.
DR InterPro; IPR036056; Fibrinogen-like_C.
DR InterPro; IPR014716; Fibrinogen_a/b/g_C_1.
DR InterPro; IPR002181; Fibrinogen_a/b/g_C_dom.
DR InterPro; IPR012290; Fibrinogen_a/b/g_coil_dom.
DR InterPro; IPR021996; Fibrinogen_aC.
DR InterPro; IPR020837; Fibrinogen_CS.
DR NCBIfam; NF040941; GGGWT_bact; 1.
DR PANTHER; PTHR47221; FIBRINOGEN ALPHA CHAIN; 1.
DR PANTHER; PTHR47221:SF3; FIBRINOGEN ALPHA CHAIN; 1.
DR Pfam; PF08702; Fib_alpha; 1.
DR Pfam; PF12160; Fibrinogen_aC; 1.
DR Pfam; PF00147; Fibrinogen_C; 1.
DR SMART; SM00186; FBG; 1.
DR SMART; SM01212; Fib_alpha; 1.
DR SUPFAM; SSF56496; Fibrinogen C-terminal domain-like; 1.
DR SUPFAM; SSF58010; Fibrinogen coiled-coil and central regions; 1.
DR PROSITE; PS00514; FIBRINOGEN_C_1; 1.
DR PROSITE; PS51406; FIBRINOGEN_C_2; 1.
PE 1: Evidence at protein level;
KW Adaptive immunity; Alternative splicing; Blood coagulation; Calcium;
KW Coiled coil; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Hemostasis; Hydroxylation; Immunity; Innate immunity; Metal-binding;
KW Phosphoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|Ref.3"
FT PEPTIDE 20..36
FT /note="Fibrinopeptide A"
FT /id="PRO_0000009039"
FT CHAIN 37..782
FT /note="Fibrinogen alpha chain"
FT /id="PRO_0000009038"
FT DOMAIN 539..780
FT /note="Fibrinogen C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT REGION 264..374
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 522..542
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 68..547
FT /evidence="ECO:0000250|UniProtKB:P02671"
FT COMPBIAS 308..369
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 707
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P02671"
FT BINDING 709
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P02671"
FT BINDING 711
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P02671"
FT BINDING 713
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P02671"
FT SITE 36..37
FT /note="Cleavage; by thrombin; to release fibrinopeptide A"
FT SITE 101..102
FT /note="Cleavage; by plasmin; to break down fibrin clots"
FT /evidence="ECO:0000250|UniProtKB:P02671"
FT SITE 122..123
FT /note="Cleavage; by hementin; to prevent blood coagulation"
FT /evidence="ECO:0000250|UniProtKB:P02671"
FT SITE 124..125
FT /note="Cleavage; by plasmin; to break down fibrin clots"
FT /evidence="ECO:0000250|UniProtKB:P02671"
FT MOD_RES 279
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 326
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 470
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 499
FT /note="4-hydroxyproline; by P4HA1"
FT /evidence="ECO:0000250|UniProtKB:P02671"
FT MOD_RES 526
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CARBOHYD 602
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 48
FT /note="Interchain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT DISULFID 56
FT /note="Interchain (with beta chain)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT DISULFID 65
FT /note="Interchain (with C-49 in gamma chain)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT DISULFID 69
FT /note="Interchain (with beta chain)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT DISULFID 181
FT /note="Interchain (with C-165 in gamma chain)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT DISULFID 185
FT /note="Interchain (with beta chain)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT DISULFID 404..434
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT DISULFID 715..728
FT /evidence="ECO:0000250|UniProtKB:P02671"
FT VAR_SEQ 547..550
FT /note="DCDD -> GIHA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:3817019"
FT /id="VSP_001533"
FT VAR_SEQ 551..782
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:3817019"
FT /id="VSP_001534"
FT CONFLICT 30..34
FT /note="EAGGD -> DEGAG (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 140
FT /note="Q -> E (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 212
FT /note="D -> E (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 270..276
FT /note="ASRGDLP -> LREEIYQ (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 473
FT /note="S -> K (in Ref. 4; AAA41158)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 782 AA; 86686 MW; 744834DAE76D34C2 CRC64;
MLSLRVACLI LSLASTVWTA DTGTTSEFIE AGGDIRGPRI VERQPSQCKE TDWPFCSDED
WNHKCPSGCR MKGLIDEANQ DFTNRINKLK NSLFDFQKNN KDSNSLTRNI MEYLRGDFAN
ANNFDNTFGQ VSEDLRRRIQ ILKRKVIEKA QQIQVLQKDV RDQLIDMKRL EVDIDIKIRS
CKGSCSRSVS REINLKDYEG QQKQLEQVIA KDLLPAKDRQ YLPAIKMSPV PDLVPGSFKS
QLQEGPPEWK ALTEMRQMRM ELERPGKDGA SRGDLPGDSR GDSATRGPGS KIENPMTPGH
GGSGYWRPGS SGSGSDGNWG SGTTGSDDTG TWGAGSSRPS SGSGNLKPSN PDWGEFSEFG
GSSSPATRKE YHTGKLVTSK GDKELLIGNE KVTSTGTSTT RRSCSKTITK TVLGNDGHRE
VVKEVVTSDD GSDCGDGMDL GLTHSFSGRL DELSRMHPEL GSFYDSRFGS LTSNFKEFGS
KTSDSDIFTD IENPSSHVPE FSSSSKTSTV RKQVTKSYKM ADEAASEAHQ EGDTRTTKRG
RARTMRDCDD VLQTHPSGAQ NGIFSIKLPG SSKIFSVYCD QETSLGGWLL IQQRMDGSLN
FNRTWQDYKR GFGSLNDKGE GEFWLGNDYL HLLTLRGSVL RVELEDWAGK EAYAEYHFRV
GSEAEGYALQ VSSYQGTAGD ALMEGSVEEG TEYTSHSNMQ FSTFDRDADQ WEENCAEVYG
GGWWYNSCQA ANLNGIYYPG GTYDPRNNSP YEIENGVLWV PFRGADYSLW AVRMKIRPLV
GQ
//
