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.

Wikipedia: HPN (gene)
Pfam
InterPro

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

The Wikipedia text that you see displayed here is a download from Wikipedia. This means that the information we display is a copy of the information from the Wikipedia database. The button next to the article title ("Edit Wikipedia article") takes you to the edit page for the article directly within Wikipedia. You should be aware you are not editing our local copy of this information. Any changes that you make to the Wikipedia article will not be displayed here until we next download the article from Wikipedia. We currently download new content on a nightly basis.

Does Pfam agree with the content of the Wikipedia entry ?

Pfam has chosen to link families to Wikipedia articles. In some case we have created or edited these articles but in many other cases we have not made any direct contribution to the content of the article. The Wikipedia community does monitor edits to try to ensure that (a) the quality of article annotation increases, and (b) vandalism is very quickly dealt with. However, we would like to emphasise that Pfam does not curate the Wikipedia entries and we cannot guarantee the accuracy of the information on the Wikipedia page.

Editing Wikipedia articles

Before you edit for the first time

Wikipedia is a free, online encyclopedia. Although anyone can edit or contribute to an article, Wikipedia has some strong editing guidelines and policies, which promote the Wikipedia standard of style and etiquette. Your edits and contributions are more likely to be accepted (and remain) if they are in accordance with this policy.

You should take a few minutes to view the following pages:

How your contribution will be recorded

Anyone can edit a Wikipedia entry. You can do this either as a new user or you can register with Wikipedia and log on. When you click on the "Edit Wikipedia article" button, your browser will direct you to the edit page for this entry in Wikipedia. If you are a registered user and currently logged in, your changes will be recorded under your Wikipedia user name. However, if you are not a registered user or are not logged on, your changes will be logged under your computer's IP address. This has two main implications. Firstly, as a registered Wikipedia user your edits are more likely seen as valuable contribution (although all edits are open to community scrutiny regardless). Secondly, if you edit under an IP address you may be sharing this IP address with other users. If your IP address has previously been blocked (due to being flagged as a source of 'vandalism') your edits will also be blocked. You can find more information on this and creating a user account at Wikipedia.

If you have problems editing a particular page, contact us at pfam-help@sanger.ac.uk and we will try to help.

Contact us

The community annotation is a new facility of the Pfam web site. If you have problems editing or experience problems with these pages please contact us.

HPN (gene) Edit Wikipedia article

This article is an orphan, as few or no other articles link to it. Please introduce links to this page from related articles; suggestions may be available. (February 2009)

Hepsin-SRCR

extracellular domain of human hepsin

Identifiers

Symbol

Hepsin-SRCR

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

Hepsin

PDB rendering based on 1o5e.

Available structures

PDB

Ortholog search: PDBe, RCSB

List of PDB id codes
1O5E, 1O5E, 1O5F, 1O5F, 1P57, 1P57, 1Z8G, 3T2N

Identifiers

Symbols

HPN; TMPRSS1

External IDs

OMIM: 142440 MGI: 1196620 HomoloGene: 20498 GeneCards: HPN Gene

EC number

3.4.21.106

Gene Ontology
Molecular function	serine-type endopeptidase activity scavenger receptor activity protein binding peptidase activity serine-type peptidase activity calcium-activated potassium channel activity serine-type exopeptidase activity
Cellular component	cytoplasm endoplasmic reticulum membrane plasma membrane integral to plasma membrane cell-cell junction cell surface integral to membrane nuclear membrane neuronal cell body
Biological process	proteolysis regulation of cell shape positive regulation of gene expression negative regulation of epithelial to mesenchymal transition positive regulation of plasminogen activation positive regulation of cell growth basement membrane disassembly negative regulation of apoptotic process positive regulation by host of viral transcription negative regulation of epithelial cell proliferation detection of mechanical stimulus involved in sensory perception of sound potassium ion transmembrane transport cochlea morphogenesis response to thyroid hormone stimulus pilomotor reflex positive regulation of hepatocyte proliferation positive regulation of thyroid hormone generation
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 19:
35.53 35.56 Mb

Chr 7:
31.88 31.9 Mb

PubMed search

[1]

[2]

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

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]

[edit] References

^ Leytus SP, Loeb KR, Hagen FS, Kurachi K, Davie EW (Jun 1988). "A novel trypsin-like serine protease (hepsin) with a putative transmembrane domain expressed by human liver and hepatoma cells". Biochemistry 27 (3): 106774. doi:10.1021/bi00403a032. PMID 2835076.
^ ^a ^b "Entrez Gene: HPN hepsin (transmembrane protease, serine 1)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3249.
^ Somoza JR, Ho JD, Luong C, Ghate M, Sprengeler PA, Mortara K, Shrader WD, Sperandio D, Chan H, McGrath ME, Katz BA (September 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): 112331. doi:10.1016/S0969-2126(03)00148-5. PMID 12962630.

[edit] Further reading

Wu Q (2001). "Gene targeting in hemostasis. Hepsin.". Front. Biosci. 6: D192200. PMID 11171558.
Tsuji A, Torres-Rosado A, Arai T, et al. (1991). "Hepsin, a cell membrane-associated protease. Characterization, tissue distribution, and gene localization.". J. Biol. Chem. 266 (25): 1694853. PMID 1885621.
Kazama Y, Hamamoto T, Foster DC, Kisiel W (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.". J. Biol. Chem. 270 (1): 6672. doi:10.1074/jbc.270.1.66. PMID 7814421.
Torres-Rosado A, O'Shea KS, Tsuji A, et al. (1993). "Hepsin, a putative cell-surface serine protease, is required for mammalian cell growth.". Proc. Natl. Acad. Sci. U.S.A. 90 (15): 71815. doi:10.1073/pnas.90.15.7181. PMC 47100. PMID 8346233. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=47100.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
Chen Z, Fan Z, McNeal JE, et al. (2003). "Hepsin and maspin are inversely expressed in laser capture microdissectioned prostate cancer.". J. Urol. 169 (4): 13169. doi:10.1097/01.ju.0000050648.40164.0d. PMID 12629351.
Somoza JR, Ho JD, Luong C, et al. (2004). "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): 112331. doi:10.1016/S0969-2126(03)00148-5. PMID 12962630.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 405. doi:10.1038/ng1285. PMID 14702039.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 21217. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928.
Kirchhofer D, Peek M, Lipari MT, et al. (2005). "Hepsin activates pro-hepatocyte growth factor and is inhibited by hepatocyte growth factor activator inhibitor-1B (HAI-1B) and HAI-2.". FEBS Lett. 579 (9): 194550. doi:10.1016/j.febslet.2005.01.085. PMID 15792801.
Pal P, Xi H, Kaushal R, et al. (2007). "Variants in the HEPSIN gene are associated with prostate cancer in men of European origin.". Hum. Genet. 120 (2): 18792. doi:10.1007/s00439-006-0204-3. PMID 16783571.
Moran P, Li W, Fan B, et al. (2006). "Pro-urokinase-type plasminogen activator is a substrate for hepsin.". J. Biol. Chem. 281 (41): 3043946. doi:10.1074/jbc.M605440200. PMID 16908524.
Betsunoh H, Mukai S, Akiyama Y, et al. (2007). "Clinical relevance of hepsin and hepatocyte growth factor activator inhibitor type 2 expression in renal cell carcinoma.". Cancer Sci. 98 (4): 4918. doi:10.1111/j.1349-7006.2007.00412.x. PMID 17309599.

PDB gallery

1o5e: Dissecting and Designing Inhibitor Selectivity Determinants at the S1 site Using an Artificial Ala190 Protease (Ala190 uPA)

1o5f: Dissecting and Designing Inhibitor Selectivity Determinants at the S1 site Using an Artificial Ala190 Protease (Ala190 uPA)

1p57: Extracellular domain of human hepsin

1z8g: Crystal structure of the extracellular region of the transmembrane serine protease hepsin with covalently bound preferred substrate.

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

This article on a gene on chromosome 19 is a stub. You can help Wikipedia by expanding it.

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

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

PANDIT:	PF09272
Pseudofam:	PF09272
SCOP:	1p57
SYSTERS:	Hepsin-SRCR

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.

Molecular function	serine-type endopeptidase activity (GO:0004252)
	serine-type exopeptidase activity (GO:0070008)

Domain organisation

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

Loading domain graphics...

Pfam Clan

This family is a member of clan SRCR (CL0550), which 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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.

Alignment types

We make a range of alignments for each Pfam-A family:

seed: the curated alignment from which the HMM for the family is built
full: the alignment generated by searching the sequence database using the HMM
RP15/RP35/RP55/RP75: Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
NCBI: alignment generated by searching the NCBI sequence database using the family HMM
meta: alignment generated by searching the metagenomics sequence database using the family HMM

Viewing

You can see the alignments as HTML or in three different sequence viewers:

jalview: a Java applet developed at the University of Dundee. You will need Java installed before running jalview
HTML: an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
PP/Heatmap: an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.
Pfam viewer: an HTML-based viewer that uses DAS to retrieve alignment fragments on request

Reformatting

You can download (or view in your browser) a text representation of a Pfam alignment in various formats:

Selex
Stockholm
FASTA
MSF

You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.

Downloading

You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.

View options

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 (2)	Full (55)	Representative proteomes				NCBI (43)	Meta (0)
	Seed (2)	Full (55)	RP15 (1)	RP35 (3)	RP55 (9)	RP75 (24)	NCBI (43)	Meta (0)
Jalview	View	View	View	View	View	View	View
HTML	View	View	View	View	View	View
PP/heatmap	₁	View	View	View	View	View
Pfam viewer	View	View

¹Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: available, not generated, — not available.

Format an alignment

	Seed (2)	Full (55)	Representative proteomes				NCBI (43)	Meta (0)
	Seed (2)	Full (55)	RP15 (1)	RP35 (3)	RP55 (9)	RP75 (24)	NCBI (43)	Meta (0)
Alignment:
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

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 (2)	Full (55)	Representative proteomes				NCBI (43)	Meta (0)
	Seed (2)	Full (55)	RP15 (1)	RP35 (3)	RP55 (9)	RP75 (24)	NCBI (43)	Meta (0)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download
Gzipped	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.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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

Seed source:

pdb_1p57

Previous IDs:

none

Type:

Domain

Author:

Sammut SJ

Number in seed:

2

Number in full:

55

Average length of the domain:

105.50 aa

Average identity of full alignment:

65 %

Average coverage of the sequence by the domain:

25.71 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	26.7	26.7
Trusted cut-off	26.8	27.1
Noise cut-off	26.5	26.6

Model length:

110

Family (HMM) version:

5

Download:

download the raw HMM for this family

Species distribution

Sunburst
Tree

Sunburst controls

Show

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.

How the sunburst is generated

The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.

In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:

superkingdom
kingdom
phylum
class
order
family
genus
species

Colouring and labels

Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.

As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.

Anomalies in the taxonomy tree

There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.

Missing taxonomic levels

Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.

Unmapped species names

The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.

So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".

Sub-species

Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.

Too many species/sequences

For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

You can use the tree controls to manipulate how the interactive tree is displayed:

show/hide the summary boxes
highlight species that are represented in the seed alignment
expand/collapse the tree or expand it to a given depth
select a sub-tree or a set of species within the tree and view them graphically or as an alignment
save a plain text representation of the tree

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Interactions

There is 1 interaction for this family. More...

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.

Loading structure mapping...

Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Family: Hepsin-SRCR (PF09272)

Jump to...