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Protein

Fibrinogen alpha chain

Gene

Fga

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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 (PubMed:7649481). In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re-epithelialization (PubMed:11389004). Was originally thought to be essential for platelet aggregation, based on in vitro studies using anticoagulated blood (PubMed:7649481). However, subsequent studies have shown that it is not absolutely required for thrombus formation in vivo (PubMed:10930441). Enhances expression of SELP in activated platelets via an ITGB3-dependent pathway (PubMed:19332769). Maternal fibrinogen is essential for successful pregnancy (PubMed:7649481). Fibrin deposition is also associated with infection, where it protects against IFNG-mediated hemorrhage (PubMed:12629066). May also facilitate the immune response via both innate and T-cell mediated pathways (PubMed:23487423).By similarity7 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei36 – 372Cleavage; by thrombin; to release fibrinopeptide ABy similarity
Sitei101 – 1022Cleavage; by plasmin; to break down fibrin clotsBy similarity
Sitei122 – 1232Cleavage; by hementin; to prevent blood coagulationBy similarity
Sitei124 – 1252Cleavage; by plasmin; to break down fibrin clotsBy similarity

GO - Molecular functioni

  1. structural molecule activity Source: MGI

GO - Biological processi

  1. blood coagulation Source: MGI
  2. blood coagulation, common pathway Source: MGI
  3. cell-matrix adhesion Source: MGI
  4. cellular protein complex assembly Source: MGI
  5. innate immune response Source: UniProtKB-KW
  6. negative regulation of endothelial cell apoptotic process Source: MGI
  7. negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: MGI
  8. platelet aggregation Source: MGI
  9. positive regulation of ERK1 and ERK2 cascade Source: MGI
  10. positive regulation of exocytosis Source: MGI
  11. positive regulation of heterotypic cell-cell adhesion Source: MGI
  12. positive regulation of peptide hormone secretion Source: MGI
  13. positive regulation of protein secretion Source: MGI
  14. positive regulation of vasoconstriction Source: MGI
  15. protein polymerization Source: MGI
  16. response to calcium ion Source: MGI
  17. signal transduction Source: InterPro
Complete GO annotation...

Keywords - Biological processi

Adaptive immunity, Blood coagulation, Hemostasis, Immunity, Innate immunity

Enzyme and pathway databases

ReactomeiREACT_286713. Common Pathway.
REACT_307071. Platelet degranulation.
REACT_316753. p130Cas linkage to MAPK signaling for integrins.
REACT_319261. Integrin cell surface interactions.
REACT_330010. Integrin alphaIIb beta3 signaling.
REACT_332492. GRB2:SOS provides linkage to MAPK signaling for Integrins.
REACT_342573. Amyloids.

Names & Taxonomyi

Protein namesi
Recommended name:
Fibrinogen alpha chain
Cleaved into the following 2 chains:
Fibrinopeptide ABy similarity
Gene namesi
Name:FgaImported
OrganismiMus musculus (Mouse)Imported
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1316726. Fga.

Subcellular locationi

Secreted 1 Publication

GO - Cellular componenti

  1. blood microparticle Source: MGI
  2. cell cortex Source: MGI
  3. cell surface Source: MGI
  4. external side of plasma membrane Source: MGI
  5. extracellular space Source: MGI
  6. extracellular vesicular exosome Source: MGI
  7. fibrinogen complex Source: MGI
  8. platelet alpha granule Source: MGI
  9. vesicle Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Disruption phenotypei

Knockout mice are viable but only males are fertile (PubMed:7649481). Neonates frequently develop spontaneous hemorrhages, but in spite of this over 90% of mice survive the neonatal period (PubMed:7649481). However only half survive beyond 70 days of age; lethality is most often due to intra-abdominal hemorrhage (PubMed:7649481). Pregnancy in female mice fails at around 10 days of gestation, associated with severe intrauterine bleeding (PubMed:7649481). Secondary loss of FGB and FGG from circulating blood is observed, although FGB and FGG mRNA is normally expressed in hepatocytes (thought to be the main site of fibrinogen synthesis) (PubMed:7649481). In vitro, blood fails to clot and platelet aggregations do not form (PubMed:7649481). In vivo, platelet aggregation in injured arterioles initially occurs normally although thrombi are unstable and readily embolize (PubMed:10930441). In double knockouts of FGA and VWF, platelet aggregation is delayed and thrombi frequently embolize (PubMed:10930441). Mice succumb more rapidly to Y. pestis infection, associated with increased bacterial loads in liver and lung; however induction of the inflammatory response factors TNF, IFNG, CXCL1, and LCN2 is not affected (PubMed:23487423). Mice succumb more rapidly to T. gondii infection, with increased hemorrhagic pathology; however parasite numbers are not significantly increased and induction of the inflammatory reponse markers IL12, IFNG, TNF, IL10, and nitric oxide is not affected (PubMed:12629066). Mice succumb more rapidly to L. monocytogenes infection, with increased hemorrhagic pathology and increased bacterial burdens in hepatic tissue; however there is little effect on peritoneal bacterial numbers or bacterial dissemination to other tissues, and also no effect on induction of the inflammatory markers IFNG, TNF and NOS2 (PubMed:15972474).5 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1919Sequence AnalysisBy similarityAdd
BLAST
Peptidei20 – 3617Fibrinopeptide ABy similarityPRO_0000430789Add
BLAST
Chaini37 – 789753Fibrinogen alpha chainPRO_0000430790Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi48 – 48InterchainBy similarity
Disulfide bondi56 – 56Interchain (with beta chain)By similarity
Disulfide bondi65 – 65Interchain (with gamma chain)By similarity
Disulfide bondi69 – 69Interchain (with beta chain)By similarity
Disulfide bondi181 – 181Interchain (with gamma chain)By similarity
Disulfide bondi185 – 185Interchain (with C-213 in beta chain)By similarity
Disulfide bondi408 ↔ 438By similarity
Modified residuei504 – 50414-hydroxyproline; by P4HA1By similarity
Modified residuei531 – 5311PhosphoserineBy similarity
Glycosylationi609 – 6091N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

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.By similarity
Forms F13A-mediated cross-links between a glutamine and the epsilon-amino group of a lysine residue, forming fibronectin-fibrinogen heteropolymers.By similarity
Phosphorylation sites are present in the extracellular medium.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Hydroxylation, Phosphoprotein

Proteomic databases

MaxQBiE9PV24.
PRIDEiE9PV24.

Expressioni

Tissue specificityi

Expressed in liver.1 Publication

Gene expression databases

BgeeiE9PV24.
ExpressionAtlasiE9PV24. baseline and differential.

Interactioni

Subunit structurei

Heterohexamer; disulfide linked. Contains 2 sets of 3 non-identical chains (alpha, beta and gamma). The 2 heterotrimers are in head to head conformation with the N-termini in a small central domain.By similarity

Protein-protein interaction databases

IntActiE9PV24. 3 interactions.
MINTiMINT-1863401.

Structurei

3D structure databases

ProteinModelPortaliE9PV24.
SMRiE9PV24. Positions 46-220, 358-483, 549-789.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini546 – 787242Fibrinogen C-terminalPROSITE-ProRule annotationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili132 – 21281Sequence AnalysisAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi266 – 34883Gly-richPROSITE-ProRule annotationAdd
BLAST

Domaini

A long coiled coil structure formed by 3 polypeptide chains connects the central nodule to the C-terminal domains (distal nodules). The long C-terminal ends of the alpha chains fold back, contributing a fourth strand to the coiled coil structure.By similarity

Sequence similaritiesi

Contains 1 fibrinogen C-terminal domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Signal

Phylogenomic databases

GeneTreeiENSGT00770000120463.
HOGENOMiHOG000285947.
HOVERGENiHBG005668.
InParanoidiE9PV24.
KOiK03903.
OMAiYKCPSGC.
OrthoDBiEOG7X9G60.
TreeFamiTF351984.

Family and domain databases

Gene3Di3.90.215.10. 1 hit.
4.10.530.10. 1 hit.
InterProiIPR014716. Fibrinogen_a/b/g_C_1.
IPR014715. Fibrinogen_a/b/g_C_2.
IPR002181. Fibrinogen_a/b/g_C_dom.
IPR012290. Fibrinogen_a/b/g_coil_dom.
IPR021996. Fibrinogen_aC.
IPR020837. Fibrinogen_CS.
[Graphical view]
PfamiPF08702. Fib_alpha. 1 hit.
PF12160. Fibrinogen_aC. 1 hit.
PF00147. Fibrinogen_C. 1 hit.
[Graphical view]
SMARTiSM00186. FBG. 1 hit.
[Graphical view]
SUPFAMiSSF56496. SSF56496. 1 hit.
PROSITEiPS00514. FIBRINOGEN_C_1. 1 hit.
PS51406. FIBRINOGEN_C_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: E9PV24-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLSLRVTCLI LSVASTVWTT DTEDKGEFLS EGGGVRGPRV VERHQSQCKD
60 70 80 90 100
SDWPFCSDDD WNHKCPSGCR MKGLIDEANQ DFTNRINKLK NSLFDFQRNN
110 120 130 140 150
KDSNSLTRNI MEYLRGDFAN ANNFDNTYGQ VSEDLRRRIE ILRRKVIEKA
160 170 180 190 200
QQIQALQSNV RAQLIDMKRL EVDIDIKIRS CKGSCSRAVN REINLQDYEG
210 220 230 240 250
HQKQLQQVIA KELLPTKDRQ YLPALKMSPV PDLVPGSFKS QLQEAPPEWK
260 270 280 290 300
ALTEMRQMRM ELERPGKDGG SRGDSPGDSR GDSRGDFATR GPGSKAENPT
310 320 330 340 350
NPGPGGSGYW RPGNSGSGSD GNRNPGTTGS DGTGDWGTGS PRPGSDSGNF
360 370 380 390 400
RPANPNWGVF SEFGDSSSPA TRKEYHTGKA VTSKGDKELL IGKEKVTSSG
410 420 430 440 450
TSTTHRSCSK TITKTVTGPD GRREVVKEVI TSDDGSDCGD ATELDISHSF
460 470 480 490 500
SGSLDELSER HPDLSGFFDN HFGLISPNFK EFGSKTHSDS DILTNIEDPS
510 520 530 540 550
SHVPEFSSSS KTSTVKKQVT KTYKMADEAG SEAHREGETR NTKRGRARAR
560 570 580 590 600
PTRDCDDVLQ TQTSGAQNGI FSIKPPGSSK VFSVYCDQET SLGGWLLIQQ
610 620 630 640 650
RMDGSLNFNR TWQDYKRGFG SLNDKGEGEF WLGNDYLHLL TLRGSVLRVE
660 670 680 690 700
LEDWAGKEAY AEYHFRVGSE AEGYALQVSS YRGTAGDALV QGSVEEGTEY
710 720 730 740 750
TSHSNMQFST FDRDADQWEE NCAEVYGGGW WYNSCQAANL NGIYYPGGTY
760 770 780
DPRNNSPYEI ENGVVWVPFR GADYSLRAVR MKIRPLVGQ
Length:789
Mass (Da):87,429
Last modified:April 4, 2011 - v1
Checksum:i16B968D6E4952CF7
GO
Isoform 2 (identifier: E9PV24-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     554-557: DCDD → GIDT
     558-789: Missing.

Show »
Length:557
Mass (Da):61,326
Checksum:iC47F496D1BA432DE
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei554 – 5574DCDD → GIDT in isoform 2. 1 PublicationVSP_057097
Alternative sequencei558 – 789232Missing in isoform 2. 1 PublicationVSP_057098Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC138394 Genomic DNA. No translation available.
BC005467 mRNA. Translation: AAH05467.1.
CCDSiCCDS17431.1. [E9PV24-2]
CCDS50939.1. [E9PV24-1]
RefSeqiNP_001104518.1. NM_001111048.1. [E9PV24-1]
NP_034326.1. NM_010196.3. [E9PV24-2]
UniGeneiMm.88793.

Genome annotation databases

EnsembliENSMUST00000029630; ENSMUSP00000029630; ENSMUSG00000028001. [E9PV24-2]
ENSMUST00000166581; ENSMUSP00000133117; ENSMUSG00000028001. [E9PV24-1]
GeneIDi14161.
KEGGimmu:14161.
UCSCiuc008ppf.2. mouse.
uc012cqw.1. mouse. [E9PV24-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC138394 Genomic DNA. No translation available.
BC005467 mRNA. Translation: AAH05467.1.
CCDSiCCDS17431.1. [E9PV24-2]
CCDS50939.1. [E9PV24-1]
RefSeqiNP_001104518.1. NM_001111048.1. [E9PV24-1]
NP_034326.1. NM_010196.3. [E9PV24-2]
UniGeneiMm.88793.

3D structure databases

ProteinModelPortaliE9PV24.
SMRiE9PV24. Positions 46-220, 358-483, 549-789.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiE9PV24. 3 interactions.
MINTiMINT-1863401.

Proteomic databases

MaxQBiE9PV24.
PRIDEiE9PV24.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000029630; ENSMUSP00000029630; ENSMUSG00000028001. [E9PV24-2]
ENSMUST00000166581; ENSMUSP00000133117; ENSMUSG00000028001. [E9PV24-1]
GeneIDi14161.
KEGGimmu:14161.
UCSCiuc008ppf.2. mouse.
uc012cqw.1. mouse. [E9PV24-1]

Organism-specific databases

CTDi2243.
MGIiMGI:1316726. Fga.

Phylogenomic databases

GeneTreeiENSGT00770000120463.
HOGENOMiHOG000285947.
HOVERGENiHBG005668.
InParanoidiE9PV24.
KOiK03903.
OMAiYKCPSGC.
OrthoDBiEOG7X9G60.
TreeFamiTF351984.

Enzyme and pathway databases

ReactomeiREACT_286713. Common Pathway.
REACT_307071. Platelet degranulation.
REACT_316753. p130Cas linkage to MAPK signaling for integrins.
REACT_319261. Integrin cell surface interactions.
REACT_330010. Integrin alphaIIb beta3 signaling.
REACT_332492. GRB2:SOS provides linkage to MAPK signaling for Integrins.
REACT_342573. Amyloids.

Miscellaneous databases

NextBioi285294.
PROiE9PV24.
SOURCEiSearch...

Gene expression databases

BgeeiE9PV24.
ExpressionAtlasiE9PV24. baseline and differential.

Family and domain databases

Gene3Di3.90.215.10. 1 hit.
4.10.530.10. 1 hit.
InterProiIPR014716. Fibrinogen_a/b/g_C_1.
IPR014715. Fibrinogen_a/b/g_C_2.
IPR002181. Fibrinogen_a/b/g_C_dom.
IPR012290. Fibrinogen_a/b/g_coil_dom.
IPR021996. Fibrinogen_aC.
IPR020837. Fibrinogen_CS.
[Graphical view]
PfamiPF08702. Fib_alpha. 1 hit.
PF12160. Fibrinogen_aC. 1 hit.
PF00147. Fibrinogen_C. 1 hit.
[Graphical view]
SMARTiSM00186. FBG. 1 hit.
[Graphical view]
SUPFAMiSSF56496. SSF56496. 1 hit.
PROSITEiPS00514. FIBRINOGEN_C_1. 1 hit.
PS51406. FIBRINOGEN_C_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6JImported.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
  3. "Resolution of spontaneous bleeding events but failure of pregnancy in fibrinogen-deficient mice."
    Suh T.T., Holmback K., Jensen N.J., Daugherty C.C., Small K., Simon D.I., Potter S., Degen J.L.
    Genes Dev. 9:2020-2033(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
  4. "Persistence of platelet thrombus formation in arterioles of mice lacking both von Willebrand factor and fibrinogen."
    Ni H., Denis C.V., Subbarao S., Degen J.L., Sato T.N., Hynes R.O., Wagner D.D.
    J. Clin. Invest. 106:385-392(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  5. "Wound-healing defects in mice lacking fibrinogen."
    Drew A.F., Liu H., Davidson J.M., Daugherty C.C., Degen J.L.
    Blood 97:3691-3698(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "Fibrin-mediated protection against infection-stimulated immunopathology."
    Johnson L.L., Berggren K.N., Szaba F.M., Chen W., Smiley S.T.
    J. Exp. Med. 197:801-806(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  7. "Infection-stimulated fibrin deposition controls hemorrhage and limits hepatic bacterial growth during listeriosis."
    Mullarky I.K., Szaba F.M., Berggren K.N., Parent M.A., Kummer L.W., Chen W., Johnson L.L., Smiley S.T.
    Infect. Immun. 73:3888-3895(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  8. "Fibrinogen is required for maintenance of platelet intracellular and cell-surface P-selectin expression."
    Yang H., Lang S., Zhai Z., Li L., Kahr W.H., Chen P., Brkic J., Spring C.M., Flick M.J., Degen J.L., Freedman J., Ni H.
    Blood 114:425-436(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. Cited for: FUNCTION, DISRUPTION PHENOTYPE.

Entry informationi

Entry nameiFIBA_MOUSE
AccessioniPrimary (citable) accession number: E9PV24
Secondary accession number(s): Q99K47
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 28, 2014
Last sequence update: April 4, 2011
Last modified: March 31, 2015
This is version 40 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.