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6  structures 49  species 3  interactions 64  sequences 6  architectures

Family: Hepsin-SRCR (PF09272)

Summary: Hepsin, SRCR

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "HPN (gene)". More...

HPN (gene) Edit Wikipedia article

Hepsin-SRCR
PDB 1p57 EBI.jpg
extracellular domain of human hepsin
Identifiers
Symbol Hepsin-SRCR
Pfam PF09272
InterPro IPR015352
SCOP 1p57
SUPERFAMILY 1p57
HPN
Protein HPN PDB 1o5e.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases HPN, TMPRSS1, hepsin
External IDs MGI: 1196620 HomoloGene: 20498 GeneCards: 3249
RNA expression pattern
PBB GE HPN 204934 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_002151
NM_182983

NM_001110252
NM_001276269
NM_008281

RefSeq (protein)

NP_002142.1
NP_892028.1

NP_001103722.1
NP_001263198.1
NP_032307.2

Location (UCSC) Chr 19: 35.04 – 35.07 Mb Chr 7: 31.1 – 31.12 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

Serine protease hepsin is an enzyme that in humans is encoded by the HPN gene.[1][2]

Function

Hepsin is a cell surface serine protease.[2]

Hepson contains a peptidase S1 domain and an SRCR domain. The SRCR domain is located in the extracellular part of the protein, it is formed primarily by three elements of regular secondary structure: a 12-residue alpha helix, a twisted five-stranded antiparallel beta sheet, and a second, two-stranded, antiparallel sheet. The two beta-sheets lie at roughly right angles to each other, with the helix nestled between the two, adopting an SRCR fold. The exact function of this domain has not been identified, though it probably may serve to orient the protease domain or place it in the vicinity of its substrate.[3]

Clinical significance

Hepsin expression is unregulated in prostate cancer and correlates with disease progression.[4]

References

  1. ^ Leytus SP, Loeb KR, Hagen FS, Kurachi K, Davie EW (Feb 1988). "A novel trypsin-like serine protease (hepsin) with a putative transmembrane domain expressed by human liver and hepatoma cells". Biochemistry 27 (3): 1067–74. doi:10.1021/bi00403a032. PMID 2835076. 
  2. ^ a b "Entrez Gene: HPN hepsin (transmembrane protease, serine 1)". 
  3. ^ Somoza JR, Ho JD, Luong C, Ghate M, Sprengeler PA, Mortara K, Shrader WD, Sperandio D, Chan H, McGrath ME, Katz BA (Sep 2003). "The structure of the extracellular region of human hepsin reveals a serine protease domain and a novel scavenger receptor cysteine-rich (SRCR) domain". Structure 11 (9): 1123–31. doi:10.1016/S0969-2126(03)00148-5. PMID 12962630. 
  4. ^ Wu Q, Parry G (2007). "Hepsin and prostate cancer". Frontiers in Bioscience 12: 5052–9. doi:10.2741/2447. PMID 17569629. 

Further reading

  • Wu Q (Feb 2001). "Gene targeting in hemostasis. Hepsin". Frontiers in Bioscience 6: D192–200. PMID 11171558. 
  • Tsuji A, Torres-Rosado A, Arai T, Le Beau MM, Lemons RS, Chou SH, Kurachi K (Sep 1991). "Hepsin, a cell membrane-associated protease. Characterization, tissue distribution, and gene localization". The Journal of Biological Chemistry 266 (25): 16948–53. PMID 1885621. 
  • Kazama Y, Hamamoto T, Foster DC, Kisiel W (Jan 1995). "Hepsin, a putative membrane-associated serine protease, activates human factor VII and initiates a pathway of blood coagulation on the cell surface leading to thrombin formation". The Journal of Biological Chemistry 270 (1): 66–72. doi:10.1074/jbc.270.1.66. PMID 7814421. 
  • Torres-Rosado A, O'Shea KS, Tsuji A, Chou SH, Kurachi K (Aug 1993). "Hepsin, a putative cell-surface serine protease, is required for mammalian cell growth". Proceedings of the National Academy of Sciences of the United States of America 90 (15): 7181–5. doi:10.1073/pnas.90.15.7181. PMC 47100. PMID 8346233. 
  • Chen Z, Fan Z, McNeal JE, Nolley R, Caldwell MC, Mahadevappa M, Zhang Z, Warrington JA, Stamey TA (Apr 2003). "Hepsin and maspin are inversely expressed in laser capture microdissectioned prostate cancer". The Journal of Urology 169 (4): 1316–9. doi:10.1097/01.ju.0000050648.40164.0d. PMID 12629351. 
  • Somoza JR, Ho JD, Luong C, Ghate M, Sprengeler PA, Mortara K, Shrader WD, Sperandio D, Chan H, McGrath ME, Katz BA (Sep 2003). "The structure of the extracellular region of human hepsin reveals a serine protease domain and a novel scavenger receptor cysteine-rich (SRCR) domain". Structure 11 (9): 1123–31. doi:10.1016/S0969-2126(03)00148-5. PMID 12962630. 
  • Kirchhofer D, Peek M, Lipari MT, Billeci K, Fan B, Moran P (Mar 2005). "Hepsin activates pro-hepatocyte growth factor and is inhibited by hepatocyte growth factor activator inhibitor-1B (HAI-1B) and HAI-2". FEBS Letters 579 (9): 1945–50. doi:10.1016/j.febslet.2005.01.085. PMID 15792801. 
  • Pal P, Xi H, Kaushal R, Sun G, Jin CH, Jin L, Suarez BK, Catalona WJ, Deka R (Sep 2006). "Variants in the HEPSIN gene are associated with prostate cancer in men of European origin". Human Genetics 120 (2): 187–92. doi:10.1007/s00439-006-0204-3. PMID 16783571. 
  • Moran P, Li W, Fan B, Vij R, Eigenbrot C, Kirchhofer D (Oct 2006). "Pro-urokinase-type plasminogen activator is a substrate for hepsin". The Journal of Biological Chemistry 281 (41): 30439–46. doi:10.1074/jbc.M605440200. PMID 16908524. 
  • Betsunoh H, Mukai S, Akiyama Y, Fukushima T, Minamiguchi N, Hasui Y, Osada Y, Kataoka H (Apr 2007). "Clinical relevance of hepsin and hepatocyte growth factor activator inhibitor type 2 expression in renal cell carcinoma". Cancer Science 98 (4): 491–8. doi:10.1111/j.1349-7006.2007.00412.x. PMID 17309599. 

This article incorporates text from the public domain Pfam and InterPro IPR015352

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Hepsin, SRCR Provide feedback

Members of this family form an extracellular domain of the serine protease hepsin. They are formed primarily by three elements of regular secondary structure: a 12-residue alpha helix, a twisted five-stranded antiparallel beta sheet, and a second, two-stranded, antiparallel sheet. The two beta-sheets lie at roughly right angles to each other, with the helix nestled between the two, adopting an SRCR fold. The exact function of this domain has not been identified, though it probably may serve to orient the protease domain or place it in the vicinity of its substrate [1].

Literature references

  1. Somoza JR, Ho JD, Luong C, Ghate M, Sprengeler PA, Mortara K, Shrader WD, Sperandio D, Chan H, McGrath ME, Katz BA; , Structure. 2003;11:1123-1131.: The structure of the extracellular region of human hepsin reveals a serine protease domain and a novel scavenger receptor cysteine-rich (SRCR) domain. PUBMED:12962630 EPMC:12962630


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR015352

This entry represents the extracellular domain of the serine protease hepsin. The domain is formed primarily by three elements of regular secondary structure: a 12-residue alpha helix, a twisted five-stranded antiparallel beta sheet, and a second, two-stranded, antiparallel sheet. The two beta-sheets lie at roughly right angles to each other, with the helix nestled between the two, adopting an SRCR fold. The exact function of this domain has not been identified, though it probably may serve to orient the protease domain or place it in the vicinity of its substrate [PUBMED:12962630].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan SRCR (CL0550), which has the following description:

The clan contains the following 3 members:

Hepsin-SRCR SRCR SRCR_2

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(1)
Full
(64)
Representative proteomes UniProt
(87)
NCBI
(235)
Meta
(0)
RP15
(5)
RP35
(15)
RP55
(32)
RP75
(50)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(1)
Full
(64)
Representative proteomes UniProt
(87)
NCBI
(235)
Meta
(0)
RP15
(5)
RP35
(15)
RP55
(32)
RP75
(50)
Alignment:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(1)
Full
(64)
Representative proteomes UniProt
(87)
NCBI
(235)
Meta
(0)
RP15
(5)
RP35
(15)
RP55
(32)
RP75
(50)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download   Download   Download    

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: pdb_1p57
Previous IDs: none
Type: Domain
Author: Sammut SJ
Number in seed: 1
Number in full: 64
Average length of the domain: 102.20 aa
Average identity of full alignment: 63 %
Average coverage of the sequence by the domain: 23.18 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 17690987 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 26.7 26.7
Trusted cut-off 26.8 26.7
Noise cut-off 26.6 26.6
Model length: 110
Family (HMM) version: 8
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 3 interactions for this family. More...

Hepsin-SRCR Trypsin Trypsin

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Hepsin-SRCR domain has been found. There are 6 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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