Q14520 (HABP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hyaluronan-binding protein 2
EC=3.4.21.-

Alternative name(s):
Factor VII-activating protease
Factor seven-activating protease
Short name=FSAP
Hepatocyte growth factor activator-like protein
Plasma hyaluronan-binding protein

Cleaved into the following 4 chains:

1. Hyaluronan-binding protein 2 50 kDa heavy chain
2. Hyaluronan-binding protein 2 50 kDa heavy chain alternate form
3. Hyaluronan-binding protein 2 27 kDa light chain
4. Hyaluronan-binding protein 2 27 kDa light chain alternate form

Gene names

Name:	HABP2
Synonyms:	HGFAL, PHBP

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	560 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	Cleaves the alpha-chain at multiple sites and the beta-chain between 'Lys-53' and 'Lys-54' but not the gamma-chain of fibrinogen and therefore does not initiate the formation of the fibrin clot and does not cause the fibrinolysis directly. It does not cleave (activate) prothrombin and plasminogen but converts the inactive single chain urinary plasminogen activator (pro-urokinase) to the active two chain form. Activates coagulation factor VII. Ref.1 Ref.8 Ref.9
Subunit structure	Heterodimer; disulfide-linked. Heterodimer of a 50 kDa heavy and a 27 kDa light chain linked by a disulfide bond By similarity.
Subcellular location	Secreted. Note: Secreted as an inactive single-chain precursor and is then activated to a heterodimeric form. Ref.1
Tissue specificity	Ubiquitously expressed. Ref.1
Post-translational modification	Proteolytic cleavage at Gly-23 or Met-27 can give rise to the 50 kDa heavy chain and cleavage at Arg-313 or Lys-319 can give rise to the 27 kDa light chain. The heavy chain can undergo further proteolytic cleavage at Lys-169 or Arg-170 to give rise to 2 inactive 26 kDa fragments and the light chain can undergo further proteolytic cleavage at Arg-480 to give rise to inactive 17 kDa and 8 kDa fragments By similarity.
Sequence similarities	Belongs to the peptidase S1 family. Contains 3 EGF-like domains. Contains 1 kringle domain. Contains 1 peptidase S1 domain.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	EGF-like domain Kringle Repeat Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	cell adhesion Traceable author statement. Source: ProtInc proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	extracellular space Traceable author statement. Source: ProtInc
Molecular function	glycosaminoglycan binding Traceable author statement. Source: ProtInc serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Ref.1
	Chain	24 – 313	290	Hyaluronan-binding protein 2 50 kDa heavy chain		PRO_0000027899
	Chain	27 – 313	287	Hyaluronan-binding protein 2 50 kDa heavy chain alternate form By similarity		PRO_0000027900
	Chain	314 – 560	247	Hyaluronan-binding protein 2 27 kDa light chain		PRO_0000027901
	Chain	320 – 560	241	Hyaluronan-binding protein 2 27 kDa light chain alternate form By similarity		PRO_0000027902
Regions
	Domain	73 – 109	37	EGF-like 1
	Domain	111 – 148	38	EGF-like 2
	Domain	150 – 188	39	EGF-like 3
	Domain	193 – 276	84	Kringle
	Domain	314 – 555	242	Peptidase S1
Sites
	Active site	362	1	Charge relay system By similarity
	Active site	411	1	Charge relay system By similarity
	Active site	509	1	Charge relay system By similarity
	Site	169 – 170	2	Cleavage By similarity
	Site	170 – 171	2	Cleavage By similarity
	Site	480 – 481	2	Cleavage By similarity
Amino acid modifications
	Glycosylation	54	1	N-linked (GlcNAc...) Potential
	Glycosylation	207	1	N-linked (GlcNAc...) Potential
	Disulfide bond	77 ↔ 88		By similarity
	Disulfide bond	82 ↔ 97		By similarity
	Disulfide bond	99 ↔ 108		By similarity
	Disulfide bond	115 ↔ 125		By similarity
	Disulfide bond	120 ↔ 136		By similarity
	Disulfide bond	138 ↔ 147		By similarity
	Disulfide bond	154 ↔ 165		By similarity
	Disulfide bond	159 ↔ 176		By similarity
	Disulfide bond	178 ↔ 187		By similarity
	Disulfide bond	194 ↔ 276		By similarity
	Disulfide bond	215 ↔ 257		By similarity
	Disulfide bond	246 ↔ 271		By similarity
	Disulfide bond	301 ↔ 435		Interchain (between heavy and light chains) By similarity
	Disulfide bond	347 ↔ 363		By similarity
	Disulfide bond	447 ↔ 515		By similarity
	Disulfide bond	477 ↔ 493		By similarity
	Disulfide bond	505 ↔ 533		By similarity
Natural variations
	Natural variant	90	1	V → I. Ref.3 Corresponds to variant rs11575750 [ dbSNP | Ensembl ].		VAR_023399
	Natural variant	393	1	E → Q in Marburg II polymorphism. Ref.3 Ref.10 Corresponds to variant rs11575688 [ dbSNP | Ensembl ].		VAR_023400
	Natural variant	534	1	G → E in Marburg I polymorphism; impairs the pro-urokinase activating potency; could be a prominent risk predictor of carotid stenosis. Ref.3 Ref.10 Corresponds to variant rs7080536 [ dbSNP | Ensembl ].		VAR_023401

Sequences

	Sequence		Length	Mass (Da)
	Q14520 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 5C1907230784ACD4	FASTA	560	62,672
	10 20 30 40 50 60 MFARMSDLHV LLLMALVGKT ACGFSLMSLL ESLDPDWTPD QYDYSYEDYN QEENTSSTLT 70 80 90 100 110 120 HAENPDWYYT EDQADPCQPN PCEHGGDCLV HGSTFTCSCL APFSGNKCQK VQNTCKDNPC 130 140 150 160 170 180 GRGQCLITQS PPYYRCVCKH PYTGPSCSQV VPVCRPNPCQ NGATCSRHKR RSKFTCACPD 190 200 210 220 230 240 QFKGKFCEIG SDDCYVGDGY SYRGKMNRTV NQHACLYWNS HLLLQENYNM FMEDAETHGI 250 260 270 280 290 300 GEHNFCRNPD ADEKPWCFIK VTNDKVKWEY CDVSACSAQD VAYPEESPTE PSTKLPGFDS 310 320 330 340 350 360 CGKTEIAERK IKRIYGGFKS TAGKHPWQAS LQSSLPLTIS MPQGHFCGGA LIHPCWVLTA 370 380 390 400 410 420 AHCTDIKTRH LKVVLGDQDL KKEEFHEQSF RVEKIFKYSH YNERDEIPHN DIALLKLKPV 430 440 450 460 470 480 DGHCALESKY VKTVCLPDGS FPSGSECHIS GWGVTETGKG SRQLLDAKVK LIANTLCNSR 490 500 510 520 530 540 QLYDHMIDDS MICAGNLQKP GQDTCQGDSG GPLTCEKDGT YYVYGIVSWG LECGKRPGVY 550 560 TQVTKFLNWI KATIKSESGF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Purification and characterization of a novel hyaluronan-binding protein (PHBP) from human plasma: it has three EGF, a kringle and a serine protease domain, similar to hepatocyte growth factor activator." Choi-Miura N.-H., Tobe T., Sumiya J., Nakano Y., Sano Y., Mazda T., Tomita M. J. Biochem. 119:1157-1165(1996) [PubMed: 8827452] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 24-42; 140-169; 174-183; 206-235; 255-260; 314-334; 417-429; 433-459; 500-517 AND 546-551, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Plasma.
[2]	Kitamura N. Submitted (MAR-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	SeattleSNPs variation discovery resource Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ILE-90; GLN-393 AND GLU-534.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Liver.
[5]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon.
[8]	"The FVII activating protease cleaves single-chain plasminogen activators." Roemisch J., Vermoehlen S., Feussner A., Stoehr H.-A. Haemostasis 29:292-299(1999) [PubMed: 10754382] [Abstract] Cited for: FUNCTION.
[9]	"Identification of the substrates for plasma hyaluronan binding protein." Choi-Miura N.H., Yoda M., Saito K., Takahashi K., Tomita M. Biol. Pharm. Bull. 24:140-143(2001) [PubMed: 11217080] [Abstract] Cited for: FUNCTION.
[10]	"Marburg I polymorphism of factor VII-activating protease: a prominent risk predictor of carotid stenosis." Willeit J., Kiechl S., Weimer T., Mair A., Santer P., Wiedermann C.J., Roemisch J. Circulation 107:667-670(2003) [PubMed: 12578864] [Abstract] Cited for: VARIANTS GLN-393 AND GLU-534.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	S83182 mRNA. Translation: AAB46909.1. D49742 mRNA. Translation: BAA08576.1. AY534754 Genomic DNA. Translation: AAS16352.1. AK290832 mRNA. Translation: BAF83521.1. AL390197 Genomic DNA. Translation: CAH71108.1. CH471066 Genomic DNA. Translation: EAW49505.1. BC031412 mRNA. Translation: AAH31412.1.
IPI	IPI00746623.
PIR	JC4795.
RefSeq	NP_001171131.1. NM_001177660.1. NP_004123.1. NM_004132.3.
UniGene	Hs.422542.
3D structure databases
ProteinModelPortal	Q14520.
SMR	Q14520. Positions 37-558.
ModBase	Search...
Protein-protein interaction databases
STRING	Q14520.
Protein family/group databases
MEROPS	S01.033.
PTM databases
PhosphoSite	Q14520.
Polymorphism databases
DMDM	73919921.
Proteomic databases
PeptideAtlas	Q14520.
PRIDE	Q14520.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000351270; ENSP00000277903; ENSG00000148702.
GeneID	3026.
KEGG	hsa:3026.
UCSC	uc001lai.2. human.
Organism-specific databases
CTD	3026.
GeneCards	GC10P115302.
H-InvDB	HIX0009217.
HGNC	HGNC:4798. HABP2.
HPA	HPA019518.
MIM	603924. gene.
neXtProt	NX_Q14520.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG05201.
GeneTree	ENSGT00570000078945.
HOGENOM	HBG755338.
HOVERGEN	HBG106385.
InParanoid	Q14520.
OMA	ITQSPPY.
OrthoDB	EOG4TB49T.
PhylomeDB	Q14520.
Gene expression databases
ArrayExpress	Q14520.
Bgee	Q14520.
CleanEx	HS_HABP2.
Genevestigator	Q14520.
GermOnline	ENSG00000148702. Homo sapiens.
Family and domain databases
InterPro	IPR006209. EGF. IPR006210. EGF-like. IPR013032. EGF-like_reg_CS. IPR000742. EGF_3. IPR000001. Kringle. IPR013806. Kringle-like. IPR018056. Kringle_CS. IPR009003. Pept_cys/ser_Trypsin-like. IPR018114. Peptidase_S1/S6_AS. IPR001254. Peptidase_S1_S6. IPR001314. Peptidase_S1A. [Graphical view]
Gene3D	G3DSA:2.40.20.10. Kringle. 1 hit.
KO	K08648.
Pfam	PF00008. EGF. 2 hits. PF00051. Kringle. 1 hit. PF00089. Trypsin. 1 hit. [Graphical view]
PRINTS	PR00722. CHYMOTRYPSIN. PR00018. KRINGLE.
SMART	SM00181. EGF. 3 hits. SM00130. KR. 1 hit. SM00020. Tryp_SPc. 1 hit. [Graphical view]
SUPFAM	SSF57440. Kringle-like. 1 hit. SSF50494. Pept_Ser_Cys. 1 hit.
PROSITE	PS00022. EGF_1. 3 hits. PS01186. EGF_2. 2 hits. PS50026. EGF_3. 3 hits. 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
NextBio	11980.
SOURCE	Search...

Entry information

Entry name

HABP2_HUMAN

Accession

Primary (citable) accession number: Q14520
Secondary accession number(s): A8K467, O00663

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 30, 2005
Last sequence update:	November 1, 1996
Last modified:	January 25, 2012
This is version 109 of the entry and version 1 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.