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P00488 (F13A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 180. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Coagulation factor XIII A chain

Short name=Coagulation factor XIIIa
EC=2.3.2.13
Alternative name(s):
Protein-glutamine gamma-glutamyltransferase A chain
Transglutaminase A chain
Gene names
Name:F13A1
Synonyms:F13A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length732 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Factor XIII is activated by thrombin and calcium ion to a transglutaminase that catalyzes the formation of gamma-glutamyl-epsilon-lysine cross-links between fibrin chains, thus stabilizing the fibrin clot. Also cross-link alpha-2-plasmin inhibitor, or fibronectin, to the alpha chains of fibrin.

Catalytic activity

Protein glutamine + alkylamine = protein N(5)-alkylglutamine + NH3.

Cofactor

Binds 1 calcium ion per subunit.

Subunit structure

Tetramer of two A chains and two B chains.

Subcellular location

Cytoplasm. Secreted. Note: Secreted into the blood plasma. Cytoplasmic in most tissues, but also secreted in the blood plasma.

Post-translational modification

The activation peptide is released by thrombin.

Polymorphism

There are four main allelic forms of this protein; F13A*1A, F13A*1B, F13A*2A and F13A*2B. In addition two other intermediate forms (F13A*2A and F13A*2B) seem to exist. The sequence shown is that of F13A*2B.

Involvement in disease

Factor XIII subunit A deficiency (FA13AD) [MIM:613225]: An autosomal recessive hematologic disorder characterized by a life-long bleeding tendency, impaired wound healing and spontaneous abortion in affected women.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.16

Sequence similarities

Belongs to the transglutaminase superfamily. Transglutaminase family.

Sequence caution

The sequence AAA52489.1 differs from that shown. Reason: Erroneous initiation.

The sequence BAD92089.1 differs from that shown. Reason: Erroneous initiation.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.8 Ref.9
Propeptide2 – 3837Activation peptide
PRO_0000033646
Chain39 – 732694Coagulation factor XIII A chain
PRO_0000033647

Sites

Active site3151
Active site3741
Active site3971
Metal binding4371Calcium
Metal binding4391Calcium
Metal binding4861Calcium
Metal binding4911Calcium
Site38 – 392Cleavage; by thrombin; to produce active factor XIII-A

Amino acid modifications

Modified residue21N-acetylserine
Glycosylation6141N-linked (GlcNAc...) Ref.10

Natural variations

Natural variant351V → L Higher specific activity. Ref.5 Ref.17 Ref.18
Corresponds to variant rs5985 [ dbSNP | Ensembl ].
VAR_013927
Natural variant401V → I. Ref.5
VAR_020910
Natural variant2051Y → F. Ref.5
Corresponds to variant rs3024477 [ dbSNP | Ensembl ].
VAR_020911
Natural variant3511M → K.
Corresponds to variant rs2230848 [ dbSNP | Ensembl ].
VAR_057350
Natural variant5511T → I. Ref.18
Corresponds to variant rs5984 [ dbSNP | Ensembl ].
VAR_013928
Natural variant5651P → L in allele F13A*1A, allele F13A*2A and allele F13*(2)A. Ref.3 Ref.5 Ref.18
Corresponds to variant rs5982 [ dbSNP | Ensembl ].
VAR_007471
Natural variant5891L → Q. Ref.18
Corresponds to variant rs5983 [ dbSNP | Ensembl ].
VAR_013929
Natural variant6501T → I. Ref.7
Corresponds to variant rs17852475 [ dbSNP | Ensembl ].
VAR_060545
Natural variant6511V → I in allele F13A*2A and allele F13A*2B. Ref.1 Ref.5 Ref.18
Corresponds to variant rs5987 [ dbSNP | Ensembl ].
VAR_007472
Natural variant6521Q → E in allele F13A*1A and allele F13A*1B. Ref.4 Ref.5 Ref.6 Ref.7 Ref.18
Corresponds to variant rs5988 [ dbSNP | Ensembl ].
VAR_007473
Natural variant6821R → H in FA13AD. Ref.16
VAR_007474

Experimental info

Sequence conflict361Missing AA sequence Ref.9
Sequence conflict891F → L in AAA52488. Ref.1

Secondary structure

...................................................................................................................................... 732
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P00488 [UniParc].

Last modified January 23, 2007. Version 4.
Checksum: 51A83A9B8B1370D4

FASTA73283,267
        10         20         30         40         50         60 
MSETSRTAFG GRRAVPPNNS NAAEDDLPTV ELQGVVPRGV NLQEFLNVTS VHLFKERWDT 

        70         80         90        100        110        120 
NKVDHHTDKY ENNKLIVRRG QSFYVQIDFS RPYDPRRDLF RVEYVIGRYP QENKGTYIPV 

       130        140        150        160        170        180 
PIVSELQSGK WGAKIVMRED RSVRLSIQSS PKCIVGKFRM YVAVWTPYGV LRTSRNPETD 

       190        200        210        220        230        240 
TYILFNPWCE DDAVYLDNEK EREEYVLNDI GVIFYGEVND IKTRSWSYGQ FEDGILDTCL 

       250        260        270        280        290        300 
YVMDRAQMDL SGRGNPIKVS RVGSAMVNAK DDEGVLVGSW DNIYAYGVPP SAWTGSVDIL 

       310        320        330        340        350        360 
LEYRSSENPV RYGQCWVFAG VFNTFLRCLG IPARIVTNYF SAHDNDANLQ MDIFLEEDGN 

       370        380        390        400        410        420 
VNSKLTKDSV WNYHCWNEAW MTRPDLPVGF GGWQAVDSTP QENSDGMYRC GPASVQAIKH 

       430        440        450        460        470        480 
GHVCFQFDAP FVFAEVNSDL IYITAKKDGT HVVENVDATH IGKLIVTKQI GGDGMMDITD 

       490        500        510        520        530        540 
TYKFQEGQEE ERLALETALM YGAKKPLNTE GVMKSRSNVD MDFEVENAVL GKDFKLSITF 

       550        560        570        580        590        600 
RNNSHNRYTI TAYLSANITF YTGVPKAEFK KETFDVTLEP LSFKKEAVLI QAGEYMGQLL 

       610        620        630        640        650        660 
EQASLHFFVT ARINETRDVL AKQKSTVLTI PEIIIKVRGT QVVGSDMTVT VQFTNPLKET 

       670        680        690        700        710        720 
LRNVWVHLDG PGVTRPMKKM FREIRPNSTV QWEEVCRPWV SGHRKLIASM SSDSLRHVYG 

       730 
ELDVQIQRRP SM 

« Hide

References

« Hide 'large scale' references
[1]"Amino acid sequence of the a subunit of human factor XIII."
Ichinose A., Hendrickson L.E., Fujikawa K., Davie E.W.
Biochemistry 25:6900-6906(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ILE-651.
[2]"Characterization of cDNA coding for human factor XIIIa."
Grundmann U., Amann E., Zettlmeissl G., Kuepper H.A.
Proc. Natl. Acad. Sci. U.S.A. 83:8024-8028(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Characterization of the gene for the a subunit of human factor XIII (plasma transglutaminase), a blood coagulation factor."
Ichinose A., Davie E.W.
Proc. Natl. Acad. Sci. U.S.A. 85:5829-5833(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LEU-565.
[4]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLU-652.
Tissue: Brain.
[5]SeattleSNPs variation discovery resource
Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-35; ILE-40; PHE-205; LEU-565; ILE-651 AND GLU-652.
[6]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLU-652.
[7]"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(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ILE-650 AND GLU-652.
Tissue: Pancreas.
[8]"Primary structure of blood coagulation factor XIIIa (fibrinoligase, transglutaminase) from human placenta."
Takahashi N., Takahashi Y., Putnam F.W.
Proc. Natl. Acad. Sci. U.S.A. 83:8019-8023(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-731.
[9]"Amino acid sequence studies on factor XIII and the peptide released during its activation by thrombin."
Takagi T., Doolittle R.F.
Biochemistry 13:750-756(1974) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-44.
[10]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-614.
Tissue: Plasma.
[11]"Three-dimensional structure of a transglutaminase: human blood coagulation factor XIII."
Yee V.C., Pedersen L.C., Trong I.L., Bishop P.D., Stenkamp R.E., Teller D.C.
Proc. Natl. Acad. Sci. U.S.A. 91:7296-7300(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
[12]"Structural evidence that the activation peptide is not released upon thrombin cleavage of factor XIII."
Yee V.C., Pedersen L.C., Bishop P.D., Stenkamp R.E., Teller D.C.
Thromb. Res. 78:389-397(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
[13]"Two non-proline cis peptide bonds may be important for factor XIII function."
Weiss M.S., Metzner H.J., Hilgenfeld R.
FEBS Lett. 423:291-296(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
[14]"Identification of the calcium binding site and a novel ytterbium site in blood coagulation factor XIII by X-ray crystallography."
Fox B.A., Yee V.C., Pedersen L.C., le Trong I., Bishop P.D., Stenkamp R.E., Teller D.C.
J. Biol. Chem. 274:4917-4923(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
[15]"Molecular basis for subtypic differences of the 'a' subunit of coagulation factor XIII with description of the genesis of the subtypes."
Suzuki K., Iwata M., Ito S., Matsui K., Uchida A., Mizoi Y.
Hum. Genet. 94:129-135(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: POLYMORPHISM.
[16]"Identification of a point mutation in factor XIII A subunit deficiency."
Board P., Coggan M., Miloszewski K.
Blood 80:937-941(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FA13AD HIS-682.
[17]"The Val34Leu polymorphism in the A subunit of coagulation factor XIII contributes to the large normal range in activity and demonstrates that the activation peptide plays a role in catalytic activity."
Kangsadalampai S., Board P.G.
Blood 92:2766-2770(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT LEU-35.
[18]"Characterization of single-nucleotide polymorphisms in coding regions of human genes."
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.
Nat. Genet. 22:231-238(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LEU-35; ILE-551; LEU-565; GLN-589; ILE-651 AND GLU-652.
[19]Erratum
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.
Nat. Genet. 23:373-373(1999)
+Additional computationally mapped references.

Web resources

GeneReviews
SeattleSNPs
SHMPD

The Singapore human mutation and polymorphism database

Wikipedia

Factor XIII entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M14539 mRNA. Translation: AAA52489.1. Different initiation.
M14354 mRNA. Translation: AAA52488.1.
M22001 expand/collapse EMBL AC list , M21987, M21988, M21989, M21990, M21991, M21992, M21993, M21995, M21996, M21997, M21998, M21999, M22000 Genomic DNA. Translation: AAA52415.1.
AB208852 mRNA. Translation: BAD92089.1. Different initiation.
AF418272 Genomic DNA. Translation: AAL12161.1.
AL157775, AL133326, AL391420 Genomic DNA. Translation: CAC36886.3.
AL391420, AL133326, AL157775 Genomic DNA. Translation: CAI39797.2.
AL133326, AL157775, AL391420 Genomic DNA. Translation: CAO03607.1.
BC027963 mRNA. Translation: AAH27963.1.
PIREKHUX. A35583.
RefSeqNP_000120.2. NM_000129.3.
UniGeneHs.335513.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1EVUX-ray2.01A/B2-732[»]
1EX0X-ray2.00A/B2-732[»]
1F13X-ray2.10A/B2-732[»]
1FIEX-ray2.50A/B2-732[»]
1GGTX-ray2.65A/B2-732[»]
1GGUX-ray2.10A/B2-732[»]
1GGYX-ray2.50A/B2-732[»]
1QRKX-ray2.50A/B2-732[»]
4KTYX-ray1.98A/B2-732[»]
ProteinModelPortalP00488.
SMRP00488. Positions 6-729.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108460. 11 interactions.
DIPDIP-377N.
IntActP00488. 9 interactions.
MINTMINT-7966415.
STRING9606.ENSP00000264870.

Chemistry

BindingDBP00488.
ChEMBLCHEMBL4530.
DrugBankDB00130. L-Glutamine.

PTM databases

PhosphoSiteP00488.

Polymorphism databases

DMDM119720.

2D gel databases

OGPP00488.

Proteomic databases

PaxDbP00488.
PRIDEP00488.

Protocols and materials databases

DNASU2162.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264870; ENSP00000264870; ENSG00000124491.
GeneID2162.
KEGGhsa:2162.
UCSCuc003mwv.3. human.

Organism-specific databases

CTD2162.
GeneCardsGC06M006089.
HGNCHGNC:3531. F13A1.
HPACAB002155.
HPA001804.
MIM134570. gene+phenotype.
613225. phenotype.
neXtProtNX_P00488.
Orphanet331. Congenital factor XIII deficiency.
PharmGKBPA162.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG80379.
HOGENOMHOG000231695.
HOVERGENHBG004342.
InParanoidP00488.
KOK03917.
OrthoDBEOG7WT40M.
PhylomeDBP00488.
TreeFamTF324278.

Enzyme and pathway databases

ReactomeREACT_604. Hemostasis.

Gene expression databases

ArrayExpressP00488.
BgeeP00488.
CleanExHS_F13A1.
GenevestigatorP00488.

Family and domain databases

Gene3D2.60.40.10. 3 hits.
3.90.260.10. 1 hit.
InterProIPR023608. Gln_gamma-glutamylTfrase_euk.
IPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002931. Transglutaminase-like.
IPR008958. Transglutaminase_C.
IPR013808. Transglutaminase_CS.
IPR001102. Transglutaminase_N.
[Graphical view]
PANTHERPTHR11590. PTHR11590. 1 hit.
PfamPF00927. Transglut_C. 2 hits.
PF01841. Transglut_core. 1 hit.
PF00868. Transglut_N. 1 hit.
[Graphical view]
PIRSFPIRSF000459. TGM_EBP42. 1 hit.
SMARTSM00460. TGc. 1 hit.
[Graphical view]
SUPFAMSSF49309. SSF49309. 2 hits.
SSF81296. SSF81296. 1 hit.
PROSITEPS00547. TRANSGLUTAMINASES. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP00488.
GeneWikiCoagulation_factor_XIII,_A1_polypeptide.
GenomeRNAi2162.
NextBio8735.
PMAP-CutDBP00488.
PROP00488.
SOURCESearch...

Entry information

Entry nameF13A_HUMAN
AccessionPrimary (citable) accession number: P00488
Secondary accession number(s): Q59HA7 expand/collapse secondary AC list , Q8N6X2, Q96P24, Q9BX29
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 180 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM