P00748 (FA12_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Coagulation factor XII
EC=3.4.21.38

Alternative name(s):
Hageman factor
Short name=HAF

Cleaved into the following 4 chains:

1. Coagulation factor XIIa heavy chain
2. Beta-factor XIIa part 1
3. Beta-factor XIIa part 2
4. Coagulation factor XIIa light chain

Gene names

Name:

F12

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	615 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Factor XII is a serum glycoprotein that participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. Prekallikrein is cleaved by factor XII to form kallikrein, which then cleaves factor XII first to alpha-factor XIIa and then trypsin cleaves it to beta-factor XIIa. Alpha-factor XIIa activates factor XI to factor XIa. Ref.14
Catalytic activity	Selective cleavage of Arg-|-Ile bonds in factor VII to form factor VIIa and factor XI to form factor XIa.
Subunit structure	Interacts with HRG; the interaction, which is enhanced in the presence of zinc ions and inhibited by heparin-binding, inhibits factor XII autoactivation and contact-initiated coagulation. Ref.14
Subcellular location	Secreted.
Post-translational modification	Factor XII is activated by kallikrein in alpha-factor XIIa, which is then further converted by trypsin into beta-factor XIIa. Alpha-factor XIIa is composed of the NH2-terminal heavy chain (Coagulation factor XIIa heavy chain) and the COOH-terminal light chain (Coagulation factor XIIa light chain), connected by a disulfide bond. Beta-factor XIIa is composed of 2 chains linked by a disulfide bond, a light chain (Beta-factor XIIa part 2), corresponding to the COOH-terminal light chain (Coagulation factor XIIa light chain) and a nonapeptide (Beta-factor XIIa part 1). O- and N-glycosylated. The O-linked polysaccharides were not identified, but are probably the mucin type linked to GalNAc. Ref.7 Ref.10
Involvement in disease	Factor XII deficiency (FA12D) [MIM:234000]: An asymptomatic anomaly of in vitro blood coagulation. Its diagnosis is based on finding a low plasma activity of the factor in coagulating assays. It is usually only accidentally discovered through pre-operative blood tests. Factor XII deficiency is divided into two categories, a cross-reacting material (CRM)-negative group (negative F12 antigen detection) and a CRM-positive group (positive F12 antigen detection). Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.13 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Hereditary angioedema 3 (HAE3) [MIM:610618]: An hereditary angioedema occurring only in women. Hereditary angioedema is an autosomal dominant disorder characterized by episodic local swelling involving subcutaneous or submucous tissue of the upper respiratory and gastrointestinal tracts, face, extremities, and genitalia. Hereditary angioedema type 3 differs from types 1 and 2 in that both concentration and function of C1 esterase inhibitor are normal. Hereditary angioedema type 3 is precipitated or worsened by high estrogen levels (e.g., during pregnancy or treatment with oral contraceptives). Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.23 Ref.24
Sequence similarities	Belongs to the peptidase S1 family. Contains 2 EGF-like domains. Contains 1 fibronectin type-I domain. Contains 1 fibronectin type-II domain. Contains 1 kringle domain. Contains 1 peptidase S1 domain.

Ontologies

Keywords
Biological process	Blood coagulation Fibrinolysis Hemostasis
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	EGF-like domain Kringle Repeat Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	Factor XII activation Inferred from direct assay PubMed 18725990. Source: BHF-UCL blood coagulation, intrinsic pathway Inferred by curator PubMed 18725990. Source: BHF-UCL fibrinolysis Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Traceable author statement Ref.16. Source: BHF-UCL positive regulation of blood coagulation Inferred from direct assay PubMed 6793628. Source: BHF-UCL positive regulation of fibrinolysis Inferred from direct assay PubMed 89876. Source: BHF-UCL positive regulation of plasminogen activation Inferred from direct assay PubMed 89876. Source: BHF-UCL protein autoprocessing Inferred from direct assay PubMed 18725990. Source: BHF-UCL proteolysis Inferred from electronic annotation. Source: UniProtKB-KW response to misfolded protein Inferred from direct assay PubMed 18725990. Source: BHF-UCL zymogen activation Inferred from direct assay PubMed 18725990PubMed 6793628PubMed 89876. Source: BHF-UCL
Cellular_component	extracellular space Inferred from direct assay PubMed 6793628. Source: BHF-UCL plasma membrane Traceable author statement. Source: Reactome
Molecular_function	misfolded protein binding Inferred by curator PubMed 18725990. Source: BHF-UCL serine-type aminopeptidase activity Inferred from electronic annotation. Source: Compara serine-type endopeptidase activity Inferred from direct assay PubMed 18725990PubMed 6793628. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
C1QBP	Q07021	2	EBI-6378830,EBI-347528

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

19

Ref.7

Chain

20 – 372

353

Coagulation factor XIIa heavy chain

PRO_0000027833

Chain

354 – 362

9

Beta-factor XIIa part 1

PRO_0000027834

Chain

373 – 615

243

Beta-factor XIIa part 2

PRO_0000027835

Chain

373 – 615

243

Coagulation factor XIIa light chain

PRO_0000027836

Regions

Domain

42 – 90

49

Fibronectin type-II

Domain

94 – 131

38

EGF-like 1

Domain

133 – 173

41

Fibronectin type-I

Domain

174 – 210

37

EGF-like 2

Domain

217 – 295

79

Kringle

Domain

373 – 614

242

Peptidase S1

Compositional bias

296 – 349

54

Pro-rich

Sites

Active site

412

1

Charge relay system By similarity

Active site

461

1

Charge relay system By similarity

Active site

563

1

Charge relay system By similarity

Amino acid modifications

Glycosylation

109

1

O-linked (Fuc) Ref.10

Glycosylation

249

1

N-linked (GlcNAc...) Ref.5 Ref.7 Ref.12

Glycosylation

299

1

O-linked (GalNAc...) Ref.7

Glycosylation

305

1

O-linked (GalNAc...) Ref.7

Glycosylation

308

1

O-linked (GalNAc...) Ref.7

Glycosylation

328

1

O-linked (GalNAc...) Ref.7

Glycosylation

329

1

O-linked (GalNAc...) Ref.7

Glycosylation

337

1

O-linked (GalNAc...) Ref.7

Glycosylation

433

1

N-linked (GlcNAc...) Ref.11 Ref.12

Disulfide bond

47 ↔ 73

By similarity

Disulfide bond

61 ↔ 88

By similarity

Disulfide bond

98 ↔ 110

By similarity

Disulfide bond

104 ↔ 119

By similarity

Disulfide bond

121 ↔ 130

By similarity

Disulfide bond

135 ↔ 163

Ref.15

Disulfide bond

161 ↔ 170

Ref.15

Disulfide bond

178 ↔ 189

Ref.15

Disulfide bond

183 ↔ 198

Ref.15

Disulfide bond

200 ↔ 209

Ref.15

Disulfide bond

217 ↔ 295

By similarity

Disulfide bond

238 ↔ 277

By similarity

Disulfide bond

266 ↔ 290

By similarity

Disulfide bond

359 ↔ 486

By similarity

Disulfide bond

397 ↔ 413

By similarity

Disulfide bond

405 ↔ 475

By similarity

Disulfide bond

436 ↔ 439

By similarity

Disulfide bond

500 ↔ 569

By similarity

Disulfide bond

532 ↔ 548

By similarity

Disulfide bond

559 ↔ 590

By similarity

Natural variations

Natural variant

53

1

Y → C in FA12D; Tenri; inactive. Ref.19

VAR_014426

Natural variant

142

1

R → P in FA12D; CRM-negative phenotype; low levels of accumulation in the cell; not secreted. Ref.20

VAR_031500

Natural variant

207

1

A → P. Ref.1 Ref.2 Ref.4 Ref.5 Ref.6 Ref.7
Corresponds to variant rs17876030 [ dbSNP | Ensembl ].

VAR_014336

Natural variant

328

1

T → K in HAE3. Ref.23 Ref.24

VAR_031501

Natural variant

328

1

T → R in HAE3. Ref.23

VAR_031502

Natural variant

340

1

A → G.
Corresponds to variant rs2230938 [ dbSNP | Ensembl ].

VAR_033649

Natural variant

342

1

P → Q.
Corresponds to variant rs2230939 [ dbSNP | Ensembl ].

VAR_029191

Natural variant

372

1

R → P in FA12D; Locarno; inactive. Ref.17

VAR_006623

Natural variant

411

1

A → T in FA12D; Shizuoka; CRM-negative phenotype; transcribed and synthesized at wild-type levels; not secreted. Ref.22

VAR_031503

Natural variant

414

1

L → M in FA12D; CRM-negative phenotype. Ref.18

VAR_031504

Natural variant

417

1

R → Q in FA12D; CRM-negative phenotype. Ref.18

VAR_031505

Natural variant

440

1

Q → K in FA12D; CRM-negative phenotype; accumulation in the cell; low secretion. Ref.20

VAR_031506

Natural variant

461

1

D → N in FA12D; CRM-positive phenotype. Ref.18

VAR_031507

Natural variant

505

1

W → C in FA12D; CRM-negative phenotype; transcribed and synthesized at wild-type levels; not secreted. Ref.21

VAR_031508

Natural variant

545

1

G → D. Ref.2
Corresponds to variant rs17876034 [ dbSNP | Ensembl ].

VAR_014337

Natural variant

589

1

G → R in FA12D; CRM-positive phenotype. Ref.9 Ref.18

VAR_031509

Natural variant

590

1

C → S in FA12D; Washington D.C.; inactive. Ref.16

VAR_006624

Natural variant

605

1

Y → H. Ref.2
Corresponds to variant rs17876035 [ dbSNP | Ensembl ].

VAR_014338

Experimental info

Sequence conflict

333

1

P → S in AAA51986. Ref.5

Sequence conflict

379

1

A → G in AAA70224. Ref.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

615

Helix Strand Turn

Details...

Beta strand

135 – 137

3

Turn

138 – 141

4

Beta strand

142 – 144

3

Beta strand

149 – 153

5

Beta strand

158 – 163

6

Beta strand

165 – 173

9

Beta strand

188 – 192

5

Beta strand

195 – 199

5

Beta strand

204 – 206

3

Sequences

	Sequence		Length	Mass (Da)
	P00748 [UniParc]. Last modified January 11, 2011. Version 3. Checksum: F5B861BF635EB480	FASTA	615	67,792
	10 20 30 40 50 60 MRALLLLGFL LVSLESTLSI PPWEAPKEHK YKAEEHTVVL TVTGEPCHFP FQYHRQLYHK 70 80 90 100 110 120 CTHKGRPGPQ PWCATTPNFD QDQRWGYCLE PKKVKDHCSK HSPCQKGGTC VNMPSGPHCL 130 140 150 160 170 180 CPQHLTGNHC QKEKCFEPQL LRFFHKNEIW YRTEQAAVAR CQCKGPDAHC QRLASQACRT 190 200 210 220 230 240 NPCLHGGRCL EVEGHRLCHC PVGYTGAFCD VDTKASCYDG RGLSYRGLAR TTLSGAPCQP 250 260 270 280 290 300 WASEATYRNV TAEQARNWGL GGHAFCRNPD NDIRPWCFVL NRDRLSWEYC DLAQCQTPTQ 310 320 330 340 350 360 AAPPTPVSPR LHVPLMPAQP APPKPQPTTR TPPQSQTPGA LPAKREQPPS LTRNGPLSCG 370 380 390 400 410 420 QRLRKSLSSM TRVVGGLVAL RGAHPYIAAL YWGHSFCAGS LIAPCWVLTA AHCLQDRPAP 430 440 450 460 470 480 EDLTVVLGQE RRNHSCEPCQ TLAVRSYRLH EAFSPVSYQH DLALLRLQED ADGSCALLSP 490 500 510 520 530 540 YVQPVCLPSG AARPSETTLC QVAGWGHQFE GAEEYASFLQ EAQVPFLSLE RCSAPDVHGS 550 560 570 580 590 600 SILPGMLCAG FLEGGTDACQ GDSGGPLVCE DQAAERRLTL QGIISWGSGC GDRNKPGVYT 610 DVAYYLAWIR EHTVS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of the human blood coagulation factor XII gene. Intron/exon gene organization and analysis of the 5'-flanking region." Cool D.E., McGillivray R.T.A. J. Biol. Chem. 262:13662-13673(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT PRO-207.
[2]	SeattleSNPs variation discovery resource Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS PRO-207; ASP-545 AND HIS-605.
[3]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"cDNA sequence coding for human coagulation factor XII (Hageman)." Tripodi M., Citarella F., Guida S., Galeffi P., Fantoni A., Cortese R. Nucleic Acids Res. 14:3146-3146(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 4-615, VARIANT PRO-207.
[5]	"Characterization of human blood coagulation factor XII cDNA. Prediction of the primary structure of factor XII and the tertiary structure of beta-factor XIIa." Cool D.E., Edgell C.-J.S., Louie G.V., Zoller M.J., Brayer G.D., McGillivray R.T.A. J. Biol. Chem. 260:13666-13676(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 14-615, VARIANT PRO-207.
[6]	"Characterization of a cDNA coding for human factor XII (Hageman factor)." Que B.G., Davie E.W. Biochemistry 25:1525-1528(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 146-615, VARIANT PRO-207.
[7]	"Amino acid sequence of the heavy chain of human alpha-factor XIIa (activated Hageman factor)." McMullen B.A., Fujikawa K. J. Biol. Chem. 260:5328-5341(1985) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-379, GLYCOSYLATION AT ASN-249; THR-299; THR-305; SER-308; THR-328; THR-329 AND THR-337, VARIANT PRO-207.
[8]	"Amino acid sequence of human beta-factor XIIa." Fujikawa K., McMullen B.A. J. Biol. Chem. 258:10924-10933(1983) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 354-362 AND 373-615.
[9]	"The novel acceptor splice site mutation 11396(G-->A) in the factor XII gene causes a truncated transcript in cross-reacting material negative patients." Schloesser M., Hofferbert S., Bartz U., Lutze G., Lammle B., Engel W. Hum. Mol. Genet. 4:1235-1237(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 561-615, VARIANT FA12D ARG-589. Tissue: Blood.
[10]	"O-linked fucose is present in the first epidermal growth factor domain of factor XII but not protein C." Harris R.J., Ling V.T., Spellman M.W. J. Biol. Chem. 267:5102-5107(1992) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT THR-109.
[11]	"Screening for N-glycosylated proteins by liquid chromatography mass spectrometry." Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R. Proteomics 4:454-465(2004) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-433, MASS SPECTROMETRY. Tissue: Plasma.
[12]	"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-249 AND ASN-433, MASS SPECTROMETRY. Tissue: Plasma.
[13]	"Factor XII gene alteration in Hageman trait detected by TaqI restriction enzyme." Bernardi F., Marchetti G., Patracchini P., del Senno L., Tripodi M., Fantoni A., Bartolai S., Vannini F., Felloni L., Rossi L., Panicucci F., Conconi F. Blood 69:1421-1424(1987) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN FA12D.
[14]	"Histidine-rich glycoprotein binds factor XIIa with high affinity and inhibits contact-initiated coagulation." Macquarrie J.L., Stafford A.R., Yau J.W., Leslie B.A., Vu T.T., Fredenburgh J.C., Weitz J.I. Blood 117:4134-4141(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HRG, FUNCTION.
[15]	"The structure of the FnI-EGF-like tandem domain of coagulation factor XII solved using SIRAS." Beringer D.X., Kroon-Batenburg L.M. Acta Crystallogr. F 69:94-102(2013) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.62 ANGSTROMS) OF 133-213, DISULFIDE BONDS.
[16]	"Coagulation factor XII (Hageman factor) Washington D.C.: inactive factor XIIa results from Cys-571-->Ser substitution." Miyata T., Kawabata S., Iwanaga S., Takahashi I., Alving B., Saito H. Proc. Natl. Acad. Sci. U.S.A. 86:8319-8322(1989) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FA12D SER-590.
[17]	"Coagulation factor XII Locarno: the functional defect is caused by the amino acid substitution Arg-353-->Pro leading to loss of a kallikrein cleavage site." Hovinga J.K., Schaller J., Stricker H., Wuillemin W.A., Furlan M., Laemmle B. Blood 84:1173-1181(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FA12D PRO-372.
[18]	"Mutations in the human factor XII gene." Schloesser M., Zeerleder S., Lutze G., Halbmayer W.-M., Hofferbert S., Hinney B., Koestering H., Laemmle B., Pindur G., Thies K., Koehler M., Engel W. Blood 90:3967-3977(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS FA12D MET-414; GLN-417; ASN-461 AND ARG-589.
[19]	"Factor XII Tenri, a novel cross-reacting material negative factor XII deficiency, occurs through a proteasome-mediated degradation." Kondo S., Tokunaga F., Kawano S., Oono Y., Kumagai S., Koide T. Blood 93:4300-4308(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FA12D CYS-53.
[20]	"Identification and characterization of two novel mutations (Q421K and R123P) in congenital factor XII deficiency." Kanaji T., Kanaji S., Osaki K., Kuroiwa M., Sakaguchi M., Mihara K., Niho Y., Okamura T. Thromb. Haemost. 86:1409-1415(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS FA12D PRO-142 AND LYS-440, CHARACTERIZATION OF VARIANTS FA12D PRO-142 AND LYS-440.
[21]	"Genetic analyses and expression studies identified a novel mutation (W486C) as a molecular basis of congenital coagulation factor XII deficiency." Ishii K., Oguchi S., Moriki T., Yatabe Y., Takeshita E., Murata M., Ikeda Y., Watanabe K. Blood Coagul. Fibrinolysis 15:367-373(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FA12D CYS-505, CHARACTERIZATION OF VARIANT FA12D CYS-505.
[22]	"Factor XII Shizuoka, a novel mutation (Ala392Thr) identified and characterized in a patient with congenital coagulation factor XII deficiency." Oguchi S., Ishii K., Moriki T., Takeshita E., Murata M., Ikeda Y., Watanabe K. Thromb. Res. 115:191-197(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FA12D THR-411, CHARACTERIZATION OF VARIANT FA12D THR-411.
[23]	"Missense mutations in the coagulation factor XII (Hageman factor) gene in hereditary angioedema with normal C1 inhibitor." Dewald G., Bork K. Biochem. Biophys. Res. Commun. 343:1286-1289(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HAE3 LYS-328 AND ARG-328.
[24]	"Increased activity of coagulation factor XII (Hageman factor) causes hereditary angioedema type III." Cichon S., Martin L., Hennies H.C., Mueller F., Van Driessche K., Karpushova A., Stevens W., Colombo R., Renne T., Drouet C., Bork K., Noethen M.M. Am. J. Hum. Genet. 79:1098-1104(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HAE3 LYS-328.
+	Additional computationally mapped references.

Web resources

Wikipedia

Factor XII entry

F12base

F12 mutation db

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M17466, M17464, M17465 Genomic DNA. Translation: AAB59490.1.
AF538691 Genomic DNA. Translation: AAM97932.1.
AC145098 Genomic DNA. No translation available.
M31315 mRNA. Translation: AAA70225.1.
M11723 mRNA. Translation: AAA51986.1.
M13147 mRNA. Translation: AAA70224.1.
U71274 Genomic DNA. Translation: AAB51203.1.

IPI

IPI00019581.

PIR

KFHU12. A29411.

RefSeq

NP_000496.2. NM_000505.3.

UniGene

Hs.1321.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4BDW	X-ray	2.50	A	133-213	[»]
4BDX	X-ray	1.62	A	133-213	[»]

ProteinModelPortal

P00748.

SMR

P00748. Positions 44-611.

ModBase

Search...

Protein-protein interaction databases

IntAct

P00748. 2 interactions.

STRING

9606.ENSP00000253496.

Protein family/group databases

MEROPS

S01.211.

PTM databases

PhosphoSite

P00748.

Polymorphism databases

DMDM

119763.

Proteomic databases

PaxDb

P00748.

PeptideAtlas

P00748.

PRIDE

P00748.

Protocols and materials databases

DNASU

2161.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000253496; ENSP00000253496; ENSG00000131187.

GeneID

2161.

KEGG

hsa:2161.

UCSC

uc003mgo.4. human.

Organism-specific databases

CTD

2161.

GeneCards

GC05M176761.

H-InvDB

HIX0005461.

HGNC

HGNC:3530. F12.

HPA

HPA003825.

MIM

234000. phenotype.
610618. phenotype.
610619. gene.

neXtProt

NX_P00748.

Orphanet

330. Congenital factor XII deficiency.
100054. Hereditary angioedema type 3.

PharmGKB

PA161.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5640.

HOGENOM

HOG000237314.

HOVERGEN

HBG004345.

InParanoid

P00748.

KO

K01328.

OMA

PKKVKDH.

OrthoDB

EOG41G33Q.

Enzyme and pathway databases

BRENDA

3.4.21.38. 2681.

Reactome

REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

P00748.

Bgee

P00748.

CleanEx

HS_F12.

Genevestigator

P00748.

GermOnline

ENSG00000131187. Homo sapiens.

Family and domain databases

Gene3D

2.10.10.10. 1 hit.
2.40.20.10. 1 hit.

InterPro

IPR014394. Coagulation_fac_XIIa/HGFA.
IPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
IPR000083. Fibronectin_type1.
IPR000562. FN_type2_col-bd.
IPR000001. Kringle.
IPR013806. Kringle-like.
IPR018056. Kringle_CS.
IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]

Pfam

PF00008. EGF. 2 hits.
PF00039. fn1. 1 hit.
PF00040. fn2. 1 hit.
PF00051. Kringle. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]

PIRSF

PIRSF001146. Factor_XII_HGFA. 1 hit.

PRINTS

PR00722. CHYMOTRYPSIN.

SMART

SM00181. EGF. 2 hits.
SM00058. FN1. 1 hit.
SM00059. FN2. 1 hit.
SM00130. KR. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]

SUPFAM

SSF57440. Kringle-like. 2 hits.
SSF50494. Pept_Ser_Cys. 1 hit.

PROSITE

PS00022. EGF_1. 2 hits.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 2 hits.
PS01253. FN1_1. 1 hit.
PS51091. FN1_2. 1 hit.
PS00023. FN2_1. 1 hit.
PS51092. FN2_2. 1 hit.
PS00021. KRINGLE_1. 1 hit.
PS50070. KRINGLE_2. 1 hit.
PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P00748.

ChEMBL

CHEMBL2821.

GenomeRNAi

2161.

NextBio

8731.

PMAP-CutDB

P00748.

SOURCE

Search...

Entry information

Entry name

FA12_HUMAN

Accession

Primary (citable) accession number: P00748
Secondary accession number(s): P78339

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 11, 2011
Last modified:	May 1, 2013
This is version 166 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.