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Protein

Hyaluronan-binding protein 2

Gene

HABP2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Enzyme and pathway databases

BioCyciZFISH:ENSG00000148702-MONOMER.
BRENDAi3.4.21.B1. 2681.
SABIO-RKQ14520.

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

HGNCiHGNC:4798. HABP2.

Subcellular locationi

GO - Cellular componenti

  • extracellular region Source: UniProtKB
  • extracellular space Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Thyroid cancer, non-medullary, 5 (NMTC5)1 Publication
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; 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 rs7080536dbSNPEnsembl.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...)Sequence 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...)Sequence 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.

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.
MINTiMINT-8201767.
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
Contains 3 EGF-like domains.PROSITE-ProRule annotation
Contains 1 kringle domain.PROSITE-ProRule annotation
Contains 1 peptidase S1 domain.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.
InterProiIPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR000001. Kringle.
IPR013806. Kringle-like.
IPR018056. Kringle_CS.
IPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[Graphical view]
PfamiPF00008. EGF. 2 hits.
PF00051. Kringle. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00181. EGF. 3 hits.
SM00179. EGF_CA. 2 hits.
SM00130. KR. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF57440. SSF57440. 1 hit.
PROSITEiPS00022. 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]

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 → I.1 PublicationCorresponds to variant rs11575750dbSNPEnsembl.1
Natural variantiVAR_023400393E → Q Polymorphism; Marburg II polymorphism. 2 PublicationsCorresponds to variant rs11575688dbSNPEnsembl.1
Natural variantiVAR_023401534G → E in NMTC5; 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 rs7080536dbSNPEnsembl.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. Translation: CAH71108.1.
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

Cross-referencesi

Web resourcesi

SeattleSNPs

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. Translation: CAH71108.1.
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.

3D structure databases

ProteinModelPortaliQ14520.
SMRiQ14520.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ14520. 1 interactor.
MINTiMINT-8201767.
STRINGi9606.ENSP00000277903.

Chemistry databases

DrugBankiDB08818. Hyaluronic acid.

Protein family/group databases

MEROPSiS01.033.

PTM databases

iPTMnetiQ14520.
PhosphoSitePlusiQ14520.

Polymorphism and mutation databases

BioMutaiHABP2.
DMDMi73919921.

Proteomic databases

EPDiQ14520.
MaxQBiQ14520.
PaxDbiQ14520.
PeptideAtlasiQ14520.
PRIDEiQ14520.

Protocols and materials databases

DNASUi3026.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi3026.
DisGeNETi3026.
GeneCardsiHABP2.
HGNCiHGNC:4798. HABP2.
HPAiHPA019518.
MalaCardsiHABP2.
MIMi603924. gene.
616535. phenotype.
neXtProtiNX_Q14520.
OpenTargetsiENSG00000148702.
PharmGKBiPA29172.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000148702-MONOMER.
BRENDAi3.4.21.B1. 2681.
SABIO-RKQ14520.

Miscellaneous databases

GeneWikiiHABP2.
GenomeRNAii3026.
PROiQ14520.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000148702.
CleanExiHS_HABP2.
GenevisibleiQ14520. HS.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
InterProiIPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR000001. Kringle.
IPR013806. Kringle-like.
IPR018056. Kringle_CS.
IPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[Graphical view]
PfamiPF00008. EGF. 2 hits.
PF00051. Kringle. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00181. EGF. 3 hits.
SM00179. EGF_CA. 2 hits.
SM00130. KR. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF57440. SSF57440. 1 hit.
PROSITEiPS00022. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiHABP2_HUMAN
AccessioniPrimary (citable) accession number: Q14520
Secondary accession number(s): A8K467
, B7Z8U5, F5H5M6, O00663
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: November 1, 1996
Last modified: November 2, 2016
This is version 156 of the entry and version 1 of the sequence. [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

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.