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Protein

Hyaluronan-binding protein 2

Gene

HABP2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 (PubMed:8827452, PubMed:10754382, PubMed:11217080). May function as a tumor suppressor negatively regulating cell proliferation and cell migration (PubMed:26222560).4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei362Charge relay systemBy similarity1
Active sitei411Charge relay systemBy similarity1
Active sitei509Charge relay systemBy similarity1

GO - Molecular functioni

  • calcium ion binding Source: InterPro
  • glycosaminoglycan binding Source: ProtInc
  • serine-type endopeptidase activity Source: InterPro

GO - Biological processi

  • cell adhesion Source: ProtInc

Keywordsi

Molecular functionHydrolase, Protease, Serine protease

Enzyme and pathway databases

BRENDAi3.4.21.B1 2681
SABIO-RKiQ14520

Protein family/group databases

MEROPSiS01.033

Names & Taxonomyi

Protein namesi
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:
Gene namesi
Name:HABP2
Synonyms:HGFAL, PHBP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000148702.14
HGNCiHGNC:4798 HABP2
MIMi603924 gene
neXtProtiNX_Q14520

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Thyroid cancer, non-medullary, 5 (NMTC5)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA form of non-medullary thyroid cancer (NMTC), a cancer characterized by tumors originating from the thyroid follicular cells. NMTCs represent approximately 95% of all cases of thyroid cancer and are classified into papillary, follicular, Hurthle cell, and anaplastic neoplasms.
See also OMIM:616535
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_023401534G → E in NMTC5; associated with disease susceptibility; Marburg I polymorphism; could be a prominent risk predictor of carotid stenosis; impairs the pro-urokinase activating potency; increased cell migration and increased cell proliferation; dominant negative effect. 3 PublicationsCorresponds to variant dbSNP:rs7080536EnsemblClinVar.1

Organism-specific databases

DisGeNETi3026
MalaCardsiHABP2
MIMi616535 phenotype
OpenTargetsiENSG00000148702
PharmGKBiPA29172

Chemistry databases

DrugBankiDB08818 Hyaluronic acid

Polymorphism and mutation databases

BioMutaiHABP2
DMDMi73919921

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 231 PublicationAdd BLAST23
ChainiPRO_000002789924 – 313Hyaluronan-binding protein 2 50 kDa heavy chainAdd BLAST290
ChainiPRO_000002790027 – 313Hyaluronan-binding protein 2 50 kDa heavy chain alternate formBy similarityAdd BLAST287
ChainiPRO_0000027901314 – 560Hyaluronan-binding protein 2 27 kDa light chainAdd BLAST247
ChainiPRO_0000027902320 – 560Hyaluronan-binding protein 2 27 kDa light chain alternate formBy similarityAdd BLAST241

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi54N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi77 ↔ 88By similarity
Disulfide bondi82 ↔ 97By similarity
Disulfide bondi99 ↔ 108By similarity
Disulfide bondi115 ↔ 125By similarity
Disulfide bondi120 ↔ 136By similarity
Disulfide bondi138 ↔ 147By similarity
Disulfide bondi154 ↔ 165By similarity
Disulfide bondi159 ↔ 176By similarity
Disulfide bondi178 ↔ 187By similarity
Disulfide bondi194 ↔ 276By similarity
Glycosylationi207N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi215 ↔ 257By similarity
Disulfide bondi246 ↔ 271By similarity
Disulfide bondi301 ↔ 435Interchain (between heavy and light chains)PROSITE-ProRule annotation
Disulfide bondi347 ↔ 363By similarity
Disulfide bondi447 ↔ 515By similarity
Disulfide bondi477 ↔ 493By similarity
Disulfide bondi505 ↔ 533By similarity

Post-translational modificationi

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).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei169 – 170CleavageBy similarity2
Sitei170 – 171CleavageBy similarity2
Sitei480 – 481CleavageBy similarity2

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ14520
MaxQBiQ14520
PaxDbiQ14520
PeptideAtlasiQ14520
PRIDEiQ14520
ProteomicsDBi60020

PTM databases

iPTMnetiQ14520
PhosphoSitePlusiQ14520

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Gene expression databases

BgeeiENSG00000148702
CleanExiHS_HABP2
GenevisibleiQ14520 HS

Organism-specific databases

HPAiHPA019518

Interactioni

Subunit structurei

Heterodimer; disulfide-linked. Heterodimer of a 50 kDa heavy and a 27 kDa light chain linked by a disulfide bond (By similarity).By similarity

Protein-protein interaction databases

IntActiQ14520, 1 interactor
MINTiQ14520
STRINGi9606.ENSP00000277903

Structurei

3D structure databases

ProteinModelPortaliQ14520
SMRiQ14520
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini73 – 109EGF-like 1PROSITE-ProRule annotationAdd BLAST37
Domaini111 – 148EGF-like 2PROSITE-ProRule annotationAdd BLAST38
Domaini150 – 188EGF-like 3PROSITE-ProRule annotationAdd BLAST39
Domaini193 – 276KringlePROSITE-ProRule annotationAdd BLAST84
Domaini314 – 555Peptidase S1PROSITE-ProRule annotationAdd BLAST242

Sequence similaritiesi

Belongs to the peptidase S1 family.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Kringle, Repeat, Signal

Phylogenomic databases

eggNOGiKOG1217 Eukaryota
KOG3627 Eukaryota
COG5640 LUCA
GeneTreeiENSGT00760000119133
HOGENOMiHOG000237314
HOVERGENiHBG106385
InParanoidiQ14520
KOiK08648
OMAiRDEIPHN
OrthoDBiEOG091G0AH5
PhylomeDBiQ14520
TreeFamiTF329901

Family and domain databases

CDDicd00190 Tryp_SPc, 1 hit
Gene3Di2.40.20.10, 1 hit
InterProiView protein in InterPro
IPR001881 EGF-like_Ca-bd_dom
IPR013032 EGF-like_CS
IPR000742 EGF-like_dom
IPR000001 Kringle
IPR013806 Kringle-like
IPR018056 Kringle_CS
IPR038178 Kringle_sf
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR001254 Trypsin_dom
IPR018114 TRYPSIN_HIS
IPR033116 TRYPSIN_SER
PfamiView protein in Pfam
PF00008 EGF, 2 hits
PF00051 Kringle, 1 hit
PF00089 Trypsin, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
SMARTiView protein in SMART
SM00181 EGF, 3 hits
SM00179 EGF_CA, 2 hits
SM00130 KR, 1 hit
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF50494 SSF50494, 1 hit
SSF57440 SSF57440, 1 hit
PROSITEiView protein in 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

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q14520-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MFARMSDLHV LLLMALVGKT ACGFSLMSLL ESLDPDWTPD QYDYSYEDYN
60 70 80 90 100
QEENTSSTLT HAENPDWYYT EDQADPCQPN PCEHGGDCLV HGSTFTCSCL
110 120 130 140 150
APFSGNKCQK VQNTCKDNPC GRGQCLITQS PPYYRCVCKH PYTGPSCSQV
160 170 180 190 200
VPVCRPNPCQ NGATCSRHKR RSKFTCACPD QFKGKFCEIG SDDCYVGDGY
210 220 230 240 250
SYRGKMNRTV NQHACLYWNS HLLLQENYNM FMEDAETHGI GEHNFCRNPD
260 270 280 290 300
ADEKPWCFIK VTNDKVKWEY CDVSACSAQD VAYPEESPTE PSTKLPGFDS
310 320 330 340 350
CGKTEIAERK IKRIYGGFKS TAGKHPWQAS LQSSLPLTIS MPQGHFCGGA
360 370 380 390 400
LIHPCWVLTA AHCTDIKTRH LKVVLGDQDL KKEEFHEQSF RVEKIFKYSH
410 420 430 440 450
YNERDEIPHN DIALLKLKPV DGHCALESKY VKTVCLPDGS FPSGSECHIS
460 470 480 490 500
GWGVTETGKG SRQLLDAKVK LIANTLCNSR QLYDHMIDDS MICAGNLQKP
510 520 530 540 550
GQDTCQGDSG GPLTCEKDGT YYVYGIVSWG LECGKRPGVY TQVTKFLNWI
560
KATIKSESGF
Length:560
Mass (Da):62,672
Last modified:November 1, 1996 - v1
Checksum:i5C1907230784ACD4
GO
Isoform 2 (identifier: Q14520-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-26: Missing.

Note: No experimental confirmation available.
Show »
Length:534
Mass (Da):59,864
Checksum:i7C085D18333DC859
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti157N → S in BAH14081 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02339990V → I1 PublicationCorresponds to variant dbSNP:rs11575750Ensembl.1
Natural variantiVAR_023400393E → Q Polymorphism; Marburg II. 2 PublicationsCorresponds to variant dbSNP:rs11575688EnsemblClinVar.1
Natural variantiVAR_023401534G → E in NMTC5; associated with disease susceptibility; Marburg I polymorphism; could be a prominent risk predictor of carotid stenosis; impairs the pro-urokinase activating potency; increased cell migration and increased cell proliferation; dominant negative effect. 3 PublicationsCorresponds to variant dbSNP:rs7080536EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0445831 – 26Missing in isoform 2. 1 PublicationAdd BLAST26

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S83182 mRNA Translation: AAB46909.1
D49742 mRNA Translation: BAA08576.1
AY534754 Genomic DNA Translation: AAS16352.1
AK290832 mRNA Translation: BAF83521.1
AK303948 mRNA Translation: BAH14081.1
AL390197 Genomic DNA No translation available.
CH471066 Genomic DNA Translation: EAW49505.1
BC031412 mRNA Translation: AAH31412.1
CCDSiCCDS53579.1 [Q14520-2]
CCDS7577.1 [Q14520-1]
PIRiJC4795
RefSeqiNP_001171131.1, NM_001177660.2 [Q14520-2]
NP_004123.1, NM_004132.4 [Q14520-1]
UniGeneiHs.422542

Genome annotation databases

EnsembliENST00000351270; ENSP00000277903; ENSG00000148702 [Q14520-1]
ENST00000542051; ENSP00000443283; ENSG00000148702 [Q14520-2]
GeneIDi3026
KEGGihsa:3026
UCSCiuc001lai.5 human [Q14520-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiHABP2_HUMAN
AccessioniPrimary (citable) accession number: Q14520
Secondary accession number(s): A8K467
, B7Z8U5, F5H5M6, O00663
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: November 1, 1996
Last modified: June 20, 2018
This is version 164 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

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