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Reviewed, UniProtKB/Swiss-Prot P02671 (FIBA_HUMAN)

Last modified November 4, 2008. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Fibrinogen alpha chain
Cleaved into the following chain:
    1- Recommended name:
            Fibrinopeptide A
Gene names
Name: FGA
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length866 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Fibrinogen has a double function: yielding monomers that polymerize into fibrin and acting as a cofactor in platelet aggregation.

Subunit structure

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.

Subcellular location

Secreted.

Domain

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.

Post-translational modification

The alpha chain is not glycosylated.

Forms F13A-mediated cross-links between a glutamine and the epsilon-amino group of a lysine residue, forming fibronectin-fibrinogen heteropolymers.

About one-third of the alpha chains in the molecules in blood were found to be phosphorylated.

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.

Involvement in disease

Defects in FGA are a cause of congenital afibrinogenemia [MIM:202400]. This is a rare autosomal recessive disorder characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen. The majority of cases of afibrinogenemia are due to truncating mutations.

Variations in position Arg-35 (the site of cleavage of fibrinopeptide a by thrombin) leads to alpha-dysfibrinogenemias.

Defects in FGA are a cause of hereditary renal amyloidosis [MIM:105200].

Sequence similarities

Contains 1 fibrinogen C-terminal domain.

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Ontologies

Keywords

   Biological processBlood coagulation
   Cellular componentSecreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   DomainCoiled coil
Signal
   PTMGlycoprotein
Phosphoprotein
   Technical term3D-structure
Direct protein sequencing

Gene Ontology (GO)

   Biological processresponse to calcium ion

Inferred from direct assay. Source: UniProtKB

   Cellular componentexternal side of plasma membrane

Inferred from direct assay. Source: UniProtKB

fibrinogen complex

Traceable author statement. Source: ProtInc

platelet alpha granule lumen

Inferred from Experiment. Source: Reactome

   Molecular functioneukaryotic cell surface binding

Inferred from direct assay. Source: UniProtKB

protein binding

Inferred from physical interaction. Source: UniProtKB

Complete GO annotation...

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Binary interactions

With

Entry

#Exp.

IntAct

Notes

BAT2P486341EBI-348571,EBI-347545

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Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P02671-1)

Also known as: Alpha-E;

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.
Isoform 2 (identifier: P02671-2)

Also known as: Alpha;

The sequence of this isoform differs from the canonical sequence as follows:
     631-644: DCDDVLQTHPSGTQ → GIHTSPLGKPSLSP
     645-866: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier
Sequence conflict640 – 6445PSLSP → LPCPPRLS in AAK31372. Ref.3

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919
Peptide20 – 3516Fibrinopeptide A
PRO_0000009021
Chain36 – 866831Fibrinogen alpha chain
PRO_0000009022

Regions

Domain623 – 864242Fibrinogen C-terminal
Region36 – 383Alpha-chain polymerization, binding distal domain of another fibrin gamma chain
Coiled coil68 – 631564 By similarity

Sites

Site35 – 362Cleavage; by thrombin; to release fibrinopeptide A

Amino acid modifications

Modified residue221Phosphoserine
Modified residue2771Phosphotyrosine
Modified residue3641Phosphoserine
Modified residue4121Phosphothreonine
Modified residue5241Phosphoserine
Modified residue5491Phosphoserine
Modified residue6091Phosphoserine
Glycosylation4531N-linked (GlcNAc...); in variant Caracas-2
Glycosylation6861N-linked (GlcNAc...)
Disulfide bond47Interchain
Disulfide bond55Interchain (with C-95 in beta chain)
Disulfide bond64Interchain (with C-49 in gamma chain)
Disulfide bond68Interchain (with C-106 in beta chain)
Disulfide bond180Interchain (with C-165 in gamma chain)
Disulfide bond184Interchain (with C-223 in beta chain)
Disulfide bond461 ↔ 491
Cross-link322Isoglutamyl lysine isopeptide (Lys-Gln) (interchain with Q-41 in alpha-2-antiplasmin)
Cross-link347Isoglutamyl lysine isopeptide (Gln-Lys) (interchain with K-?)
Cross-link385Isoglutamyl lysine isopeptide (Gln-Lys) (interchain with K-?)
Cross-link527Isoglutamyl lysine isopeptide (Lys-Gln) (interchain with Q-?) Potential
Cross-link558Isoglutamyl lysine isopeptide (Lys-Gln) (interchain with Q-?) Potential
Cross-link575Isoglutamyl lysine isopeptide (Lys-Gln) (interchain with Q-?) Potential
Cross-link581Isoglutamyl lysine isopeptide (Lys-Gln) (interchain with Q-?) Potential
Cross-link599Isoglutamyl lysine isopeptide (Lys-Gln) (interchain with Q-?) Potential

Natural variations

Alternative sequence631 – 64414DCDDV…PSGTQ → GIHTSPLGKPSLSP in isoform 2.
VSP_001531
Alternative sequence645 – 866222Missing in isoform 2.
VSP_001532
Natural variant61I → V: dbSNP rs2070025.
VAR_011609
Natural variant261D → N in Lille-1.
VAR_002390
Natural variant311G → V in Rouen-1.
VAR_002391
Natural variant351R → C in many variants.
VAR_002392
Natural variant351R → H in many variants.
VAR_002393
Natural variant371P → L in Kyoto-2.
VAR_002394
Natural variant381R → G in Aarhus-1.
VAR_002397
Natural variant381R → N in Munich-1; requires 2 nucleotide substitutions.
VAR_002395
Natural variant381R → S in Detroit-1.
VAR_002396
Natural variant391V → D in Canterbury.
VAR_010730
Natural variant661S → T
VAR_002398
Natural variant1601R → S in Lima.
VAR_002399
Natural variant3311T → A: dbSNP rs6050.
VAR_011610
Natural variant4461K → E: dbSNP rs6052.
VAR_014168
Natural variant4531S → N in Caracas-2.
VAR_002400
Natural variant4561T → A: dbSNP rs2070031.
VAR_011611
Natural variant5451E → V in hereditary renal amyloidosis.
VAR_010731
Natural variant5731R → C in Dusart/Paris-5.
VAR_002401
Natural variant5731R → L in hereditary renal amyloidosis.
VAR_010732

Experimental info

Sequence conflict1841C → W in AAA52426. Ref.6
Sequence conflict215 – 2162SR → RS AA sequence Ref.7
Sequence conflict2991S → G AA sequence Ref.7
Sequence conflict3041S → G AA sequence Ref.7
Sequence conflict317 – 3182GT → SG AA sequence Ref.8

Secondary structure

1 .............................................. 866
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Alpha-E) [UniParc].

Last modified October 1, 1996. Version 2.
Checksum: EA73A81204D8AEC4

FASTA86694,973
        10         20         30         40         50         60 
MFSMRIVCLV LSVVGTAWTA DSGEGDFLAE GGGVRGPRVV ERHQSACKDS DWPFCSDEDW 

        70         80         90        100        110        120 
NYKCPSGCRM KGLIDEVNQD FTNRINKLKN SLFEYQKNNK DSHSLTTNIM EILRGDFSSA 

       130        140        150        160        170        180 
NNRDNTYNRV SEDLRSRIEV LKRKVIEKVQ HIQLLQKNVR AQLVDMKRLE VDIDIKIRSC 

       190        200        210        220        230        240 
RGSCSRALAR EVDLKDYEDQ QKQLEQVIAK DLLPSRDRQH LPLIKMKPVP DLVPGNFKSQ 

       250        260        270        280        290        300 
LQKVPPEWKA LTDMPQMRME LERPGGNEIT RGGSTSYGTG SETESPRNPS SAGSWNSGSS 

       310        320        330        340        350        360 
GPGSTGNRNP GSSGTGGTAT WKPGSSGPGS TGSWNSGSSG TGSTGNQNPG SPRPGSTGTW 

       370        380        390        400        410        420 
NPGSSERGSA GHWTSESSVS GSTGQWHSES GSFRPDSPGS GNARPNNPDW GTFEEVSGNV 

       430        440        450        460        470        480 
SPGTRREYH