FIBA_BOVIN
ID FIBA_BOVIN Reviewed; 615 AA.
AC P02672; O97642; Q3T049;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 18-APR-2006, sequence version 5.
DT 25-MAY-2022, entry version 143.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Testis;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 174-577.
RA Murakawa M.;
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 412-615.
RA Chung D.W., Rixon M.W., Davie E.W.;
RT "The biosynthesis of fibrinogen and the cloning of its cDNA.";
RL (In) Bradshaw R.A. (eds.);
RL Proteins in biology and medicine, pp.309-328, Academic Press, New York
RL (1982).
RN [4]
RP PROTEIN SEQUENCE OF 20-38.
RA Sjoquist J., Blombaeck B., Wallen P.;
RT "Amino acid sequence of bovine fibrinopeptides.";
RL Ark. Kemi 16:425-436(1960).
RN [5]
RP PROTEIN SEQUENCE OF 20-38.
RX PubMed=13823737;
RA Folk J.E., Gladner J.A., Levin Y.;
RT "Thrombin-induced formation of co-fibrin. III. Acid degradation studies and
RT summary of sequential evidence on peptide A.";
RL J. Biol. Chem. 234:2317-2320(1959).
RN [6]
RP PROTEIN SEQUENCE OF 39-73.
RX PubMed=836881; DOI=10.1016/0005-2795(77)90017-4;
RA Timpl R., Fietzek P.P., Wachter E., van Delden V.;
RT "Disulfide-linked cyanogen bromide peptides of bovine fibrinogen. II.
RT Isolation and sequence analysis of the chain constituents from the amino
RT terminal region.";
RL Biochim. Biophys. Acta 490:420-429(1977).
RN [7]
RP PROTEIN SEQUENCE OF 39-68; 262-287 AND 572-599.
RA Henschen A., Lottspeich F., Topfer-Petersen E., Kehl M., Timpl R.;
RL (In) Peeters H. (eds.);
RL Protides of the biological fluids, Proc. 28th colloquium, pp.47-50,
RL Pergamon Press, Oxford (1980).
RN [8]
RP PROTEIN SEQUENCE OF 42-71.
RX PubMed=434821; DOI=10.1016/0003-9861(79)90068-7;
RA Martinelli R.A., Inglis A.S., Rubira M.R., Hageman T.C., Hurrell J.G.R.,
RA Leach S.J., Scheraga H.A.;
RT "Amino acid sequences of portions of the alpha and beta chains of bovine
RT fibrinogen.";
RL Arch. Biochem. Biophys. 192:27-32(1979).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (3.50 ANGSTROMS) OF 20-409, SUBUNIT, AND COILED COIL
RP DOMAIN.
RX PubMed=10618375; DOI=10.1073/pnas.97.1.85;
RA Brown J.H., Volkmann N., Jun G., Henschen-Edman A.H., Cohen C.;
RT "The crystal structure of modified bovine fibrinogen.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:85-90(2000).
RN [10] {ECO:0007744|PDB:2JOR}
RP STRUCTURE BY NMR OF 438-515, AND DISULFIDE BONDS.
RX PubMed=17590019; DOI=10.1021/bi700606v;
RA Burton R.A., Tsurupa G., Hantgan R.R., Tjandra N., Medved L.;
RT "NMR solution structure, stability, and interaction of the recombinant
RT bovine fibrinogen alphaC-domain fragment.";
RL Biochemistry 46:8550-8560(2007).
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 {ECO:0000269|PubMed:10618375}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
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:0000269|PubMed:10618375}.
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.
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DR EMBL; BC102564; AAI02565.1; -; mRNA.
DR EMBL; AF095463; AAC67562.1; -; Genomic_DNA.
DR PIR; A05294; A05294.
DR PIR; S69114; S69114.
DR RefSeq; NP_001028798.1; NM_001033626.1.
DR PDB; 1DEQ; X-ray; 3.50 A; A/D/N/Q=20-409.
DR PDB; 1JY2; X-ray; 1.40 A; N/Q=48-100.
DR PDB; 1JY3; X-ray; 1.60 A; N/Q=48-100.
DR PDB; 2BAF; NMR; -; A=406-570.
DR PDB; 2JOR; NMR; -; A=438-515.
DR PDBsum; 1DEQ; -.
DR PDBsum; 1JY2; -.
DR PDBsum; 1JY3; -.
DR PDBsum; 2BAF; -.
DR PDBsum; 2JOR; -.
DR AlphaFoldDB; P02672; -.
DR BMRB; P02672; -.
DR SMR; P02672; -.
DR STRING; 9913.ENSBTAP00000002145; -.
DR Allergome; 1112; Bos d Fibrin.
DR PaxDb; P02672; -.
DR PeptideAtlas; P02672; -.
DR PRIDE; P02672; -.
DR GeneID; 522039; -.
DR KEGG; bta:522039; -.
DR CTD; 2243; -.
DR eggNOG; KOG2579; Eukaryota.
DR InParanoid; P02672; -.
DR OrthoDB; 363208at2759; -.
DR EvolutionaryTrace; P02672; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005577; C:fibrinogen complex; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; IEA:InterPro.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0072377; P:blood coagulation, common pathway; IBA:GO_Central.
DR GO; GO:0042730; P:fibrinolysis; IBA:GO_Central.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; IBA:GO_Central.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; IBA:GO_Central.
DR GO; GO:0070527; P:platelet aggregation; IBA:GO_Central.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IBA:GO_Central.
DR GO; GO:0034116; P:positive regulation of heterotypic cell-cell adhesion; IBA:GO_Central.
DR GO; GO:0090277; P:positive regulation of peptide hormone secretion; IBA:GO_Central.
DR GO; GO:0051258; P:protein polymerization; IBA:GO_Central.
DR InterPro; IPR012290; Fibrinogen_a/b/g_coil_dom.
DR InterPro; IPR021996; Fibrinogen_aC.
DR InterPro; IPR037579; Fibrinogen_alpha.
DR PANTHER; PTHR47221; PTHR47221; 1.
DR Pfam; PF08702; Fib_alpha; 1.
DR Pfam; PF12160; Fibrinogen_aC; 1.
DR SMART; SM01212; Fib_alpha; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Blood coagulation; Coiled coil;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Hemostasis;
KW Immunity; Innate immunity; Reference proteome; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:13823737, ECO:0000269|Ref.4"
FT PEPTIDE 20..38
FT /note="Fibrinopeptide A"
FT /evidence="ECO:0000269|PubMed:836881, ECO:0000269|Ref.7"
FT /id="PRO_0000009005"
FT CHAIN 39..615
FT /note="Fibrinogen alpha chain"
FT /id="PRO_0000009006"
FT REGION 267..427
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 530..615
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 71..602
FT /evidence="ECO:0000305|PubMed:10618375"
FT COMPBIAS 292..311
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 373..400
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 408..425
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 535..563
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 566..582
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 38..39
FT /note="Cleavage; by thrombin; to release fibrinopeptide A"
FT CARBOHYD 325
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000250"
FT DISULFID 50
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P02671"
FT DISULFID 58
FT /note="Interchain (with C-72 in beta chain)"
FT /evidence="ECO:0000250|UniProtKB:P14448"
FT DISULFID 67
FT /note="Interchain (with C-47 in gamma chain)"
FT /evidence="ECO:0000250|UniProtKB:P14448"
FT DISULFID 71
FT /note="Interchain (with C-83 in beta chain)"
FT /evidence="ECO:0000250|UniProtKB:P14448"
FT DISULFID 183
FT /note="Interchain (with C-163 in gamma chain)"
FT /evidence="ECO:0000250|UniProtKB:P14448"
FT DISULFID 187
FT /note="Interchain (with C-200 in beta chain)"
FT /evidence="ECO:0000250|UniProtKB:P14448"
FT DISULFID 455..485
FT /evidence="ECO:0000269|PubMed:17590019,
FT ECO:0007744|PDB:2BAF, ECO:0007744|PDB:2JOR"
FT CONFLICT 189
FT /note="R -> K (in Ref. 2; AAC67562)"
FT /evidence="ECO:0000305"
FT CONFLICT 238..239
FT /note="RE -> KK (in Ref. 2; AAC67562)"
FT /evidence="ECO:0000305"
FT CONFLICT 360..372
FT /note="Missing (in Ref. 2; AAC67562)"
FT /evidence="ECO:0000305"
FT CONFLICT 375
FT /note="A -> G (in Ref. 2; AAC67562)"
FT /evidence="ECO:0000305"
FT CONFLICT 457..458
FT /note="KV -> S (in Ref. 3; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 612
FT /note="S -> T (in Ref. 3; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:1JY2"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:1JY2"
FT HELIX 70..95
FT /evidence="ECO:0007829|PDB:1JY2"
FT STRAND 417..419
FT /evidence="ECO:0007829|PDB:2BAF"
FT STRAND 421..423
FT /evidence="ECO:0007829|PDB:2BAF"
FT STRAND 443..445
FT /evidence="ECO:0007829|PDB:2BAF"
FT STRAND 450..453
FT /evidence="ECO:0007829|PDB:2BAF"
FT TURN 454..456
FT /evidence="ECO:0007829|PDB:2BAF"
FT STRAND 457..459
FT /evidence="ECO:0007829|PDB:2BAF"
FT TURN 466..468
FT /evidence="ECO:0007829|PDB:2JOR"
FT STRAND 475..477
FT /evidence="ECO:0007829|PDB:2BAF"
FT STRAND 480..482
FT /evidence="ECO:0007829|PDB:2JOR"
FT STRAND 483..486
FT /evidence="ECO:0007829|PDB:2BAF"
FT STRAND 497..500
FT /evidence="ECO:0007829|PDB:2JOR"
FT STRAND 505..507
FT /evidence="ECO:0007829|PDB:2BAF"
FT TURN 537..539
FT /evidence="ECO:0007829|PDB:2BAF"
FT TURN 555..558
FT /evidence="ECO:0007829|PDB:2BAF"
SQ SEQUENCE 615 AA; 67012 MW; A79B48E292DF627B CRC64;
MFSVRDLCLV LSLVGAIKTE DGSDPPSGDF LTEGGGVRGP RLVERQQSAC KETGWPFCSD
EDWNTKCPSG CRMKGLIDEV DQDFTSRINK LRDSLFNYQK NSKDSNTLTK NIVELMRGDF
AKANNNDNTF KQISEDLRSR IEILRRKVIE QVQRIKVLQK NVRDQLVDMK RLEVDIDIKI
RSCKGSCSRA LEHKVDLEDY KNQQKQLEQV IAINLLPSRD IQYLPLIKMS TITGPVPREF
KSQLQEAPLE WKALLEMQQT KMVLETFGGD GHARGDSVSQ GTGLAPGSPR KPGTSSIGNV
NPGSYGPGSS GTWNPGRPEP GSAGTWNPGR PEPGSAGTWN PGRPEPGSAG TWNPGRPEPG
SAGTWNPGRP EPGSAGTWNT GSSGSSSFRP DSSGHGNIRP SSPDWGTFRE EGSVSSGTKQ
EFHTGKLVTT KGDKELLIDN EKVTSGHTTT TRRSCSKVIT KTVTNADGRT ETTKEVVKSE
DGSDCGDADF DWHHTFPSRG NLDDFFHRDK DDFFTRSSHE FDGRTGLAPE FAALGESGSS
SSKTSTHSKQ FVSSSTTVNR GGSAIESKHF KMEDEAESLE DLGFKGAHGT QKGHTKARPA
RGIHTSPLGE PSLTP
