The reference OMIM entry for this protein is 603924

Hyaluronan-binding protein 2; habp2
Hyaluronic acid-binding protein 2; habp2
Hyaluronan-binding protein, plasma; phbp
Hepatocyte growth factor activator-like; hgfal
Factor vii-activating protease; fsap

CLONING

Hyaluronic acid is a glycosaminoglycan that is present in the extracellular matrix, connective tissue, cartilage, bone marrow, and synovial fluid. By searching for hyaluronic acid-binding proteins in human plasma, Choi-Miura et al. (1996) identified, purified, and partially sequenced a novel protein, HABP2, which they called PHBP. By SDS-PAGE under nonreducing conditions, they demonstrated that purified HABP2 has a molecular mass of 70 kD; under reducing conditions, HABP2 migrates as 50- and 17-kD polypeptides, indicating that HABP2 is a heterodimer whose subunits are joined by disulfide bonds. By screening a human liver cDNA library using degenerate oligonucleotides based on the HABP2 amino acid sequence, they cloned HABP2. The deduced full-length 560-amino acid protein contains a signal peptide, 3 EGF domains, a kringle domain, and a serine protease domain. HABP2 has a calculated molecular mass of about 63 kD. Northern blot analysis indicated that HABP2 is expressed as 3.0- and 2.3-kb mRNAs in human kidney, liver, and pancreas. Choi-Miura et al. (2001) found that after incubation of HABP2 purified from human plasma, the single 70-kD protein fragmented into a 50-kD N-terminal fragment and a 27-kD C-terminal fragment, and this was followed by cleavage of the 50-kD fragment into two 26-kD fragments and cleavage of the 27-kD fragment into 17- and 8-kD fragments. Because the purified protein contained no other detectable proteins and HABP2 has a typical serine protease domain, Choi-Miura et al. (2001) concluded that fragmentation of HABP2 was caused by autoproteolysis. They further determined that the single-chain form of HABP2 is a precursor, the 2-subunit structure is the active serine protease, and the 3- or 4-chain structures are inactive. Romisch et al. (2001) noted that a protease that they had named factor VII-activating protease (FSAP), due to its potent activation of factor VII, was 'identical or closely related to' PHBP.

GENE FUNCTION

Using SDS-PAGE, Choi-Miura et al. (2001) demonstrated that fibrinogen (see FGA; 134820) and fibronectin (135600) are the major substrates of PHBP. PHBP cleaved the fibrinogen alpha chain (FGA) at multiple sites and the beta chain (FGB; 134830) between lys53 and lys54, but not the gamma chain (FGG; 134850); thus, PHBP does not initiate the formation of fibrin clot and does not cause fibrinolysis directly. PHBP did not cleave prothrombin (176930) or plasminogen (173350), but it converted the inactive single-chain urinary plasminogen activator (UPA; 191840) to the active 2-chain form.

GENE STRUCTURE

Sumiya et al. (1997) determined that the HABP2 gene contains 13 exons and spans 35 kb.

MAPPING

By FISH, Sumiya et al. (1997) mapped the HABP2 gene to chromosome 10q25-q26.

MOLECULAR GENETICS

- Nonmedullary Thyroid Cancer In a large multiplex family with familial nonmedullary thyroid cancer (NMTC5; 616535), Gara et al. (2015) found a heterozygous missense mutation in the HABP2 gene (G534E; 603924.0001) that segregated with disease in the family. Overexpression of the mutant protein caused increased colony formation and cellular migration compared to wildtype. Analysis of data from the Cancer Genome Atlas (TCGA) in 423 patients with papillary thyroid cancer showed that 4.7% carried the HABP2 G534E variant, as compared with 0.7% of individuals with unknown disease status in multiethnic population databases (p less than 0.001). This suggested to Gar ... More on the omim web site

Subscribe to this protein entry history

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 603924 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).