Summary: Alpha-2-macroglobulin RAP, N-terminal domain

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Wikipedia: LDL-receptor-related protein associated protein
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LDL-receptor-related protein associated protein Edit Wikipedia article

Low density lipoprotein receptor-related protein associated protein 1

PDB rendering based on 1lre.

Available structures

PDB

Ortholog search: PDBe, RCSB

List of PDB id codes
1LRE, 1NRE, 1OP1, 1OV2, 2FCW, 2FTU, 2FYL, 2P01, 2P03

Identifiers

Symbols

LRPAP1; A2MRAP; A2RAP; HBP44; MRAP; RAP

External IDs

OMIM: 104225 MGI: 96829 HomoloGene: 37612 GeneCards: LRPAP1 Gene

Gene Ontology
Molecular function	asialoglycoprotein receptor activity heparin binding lipase binding receptor antagonist activity low-density lipoprotein particle receptor binding unfolded protein binding very-low-density lipoprotein particle receptor binding
Cellular component	extracellular region endoplasmic reticulum plasma membrane cell surface integral to membrane vesicle rough endoplasmic reticulum lumen
Biological process	protein folding negative regulation of very-low-density lipoprotein particle clearance vesicle-mediated transport negative regulation of protein binding extracellular negative regulation of signal transduction
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 5:
35.09 35.11 Mb

PubMed search

[1]

[2]

Alpha-2-MRAP_N

haddock model of the complex between double module of lrp, cr56, and first domain of receptor associated protein, rap-d1.

Identifiers

Symbol

Alpha-2-MRAP_N

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

Alpha-2-MRAP_C

solution structure of domain 3 of rap

Identifiers

Symbol

Alpha-2-MRAP_C

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

Low density lipoprotein receptor-related protein associated protein 1 also known as LRPAP1 or RAP is a chaperone protein which in humans is encoded by the LRPAP1 gene.^[1]^[2]

[edit] Function

LRPAP1 is involved with trafficking of certain members of the LDL receptor family including LRP1 and LRP2.^[3] It is a glycoprotein that binds to the alpha-2-macroglobulin receptor, as well as to other members of the low density lipoprotein receptor family. It acts to inhibit the binding of all know ligands for these receptors, and may prevent receptor aggregation and degradation in the endoplasmic reticulum, thereby acting as a molecular chaperone.^[4] It may be under the regulatory control of calmodulin, since it is able to bind calmodulin and be phosphorylated by calmodulin-dependent kinase II.

[edit] Interactions

LDL-receptor-related protein associated protein has been shown to interact with LRP2.^[5]^[6]

[edit] References

^ Striekland DK, Ashcom JD, Williams S, Battey F, Behre E, McTigue K, Battey JF, Argraves WS (July 1991). "Primary structure of alpha 2-macroglobulin receptor-associated protein. Human homologue of a Heymann nephritis antigen". J. Biol. Chem. 266 (20): 133649. PMID 1712782. http://www.jbc.org/cgi/content/abstract/266/20/13364.
^ Korenberg JR, Argraves KM, Chen XN, Tran H, Strickland DK, Argraves WS (July 1994). "Chromosomal localization of human genes for the LDL receptor family member glycoprotein 330 (LRP2) and its associated protein RAP (LRPAP1)". Genomics 22 (1): 8893. doi:10.1006/geno.1994.1348. PMID 7959795.
^ "Entrez Gene: LRPAP1 low density lipoprotein receptor-related protein associated protein 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4043.
^ Nielsen PR, Ellgaard L, Etzerodt M, Thogersen HC, Poulsen FM (July 1997). "The solution structure of the N-terminal domain of alpha2-macroglobulin receptor-associated protein". Proc. Natl. Acad. Sci. U.S.A. 94 (14): 75215. doi:10.1073/pnas.94.14.7521. PMC 23854. PMID 9207124. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=23854.
^ Lou, Xiaojing; McQuistan Tammie, Orlando Robert A, Farquhar Marilyn Gist (April 2002). "GAIP, GIPC and Galphai3 are concentrated in endocytic compartments of proximal tubule cells: putative role in regulating megalin's function". J. Am. Soc. Nephrol. (United States) 13 (4): 91827. ISSN 1046-6673. PMID 11912251.
^ Orlando, R A; Farquhar M G (April 1994). "Functional domains of the receptor-associated protein (RAP)". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 91 (8): 31615. doi:10.1073/pnas.91.8.3161. ISSN 0027-8424. PMC 43535. PMID 7512726. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=43535.

[edit] Further reading

Williams SE, Ashcom JD, Argraves WS, Strickland DK (1992). "A novel mechanism for controlling the activity of alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein. Multiple regulatory sites for 39-kDa receptor-associated protein.". J. Biol. Chem. 267 (13): 903540. PMID 1374383.
Kounnas MZ, Argraves WS, Strickland DK (1992). "The 39-kDa receptor-associated protein interacts with two members of the low density lipoprotein receptor family, alpha 2-macroglobulin receptor and glycoprotein 330.". J. Biol. Chem. 267 (29): 211626. PMID 1400426.
Striekland DK, Ashcom JD, Williams S, et al. (1991). "Primary structure of alpha 2-macroglobulin receptor-associated protein. Human homologue of a Heymann nephritis antigen.". J. Biol. Chem. 266 (20): 133649. PMID 1712782.
Herz J, Goldstein JL, Strickland DK, et al. (1991). "39-kDa protein modulates binding of ligands to low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor.". J. Biol. Chem. 266 (31): 212328. PMID 1718973.
Furukawa T, Ozawa M, Huang RP, Muramatsu T (1990). "A heparin binding protein whose expression increases during differentiation of embryonal carcinoma cells to parietal endoderm cells: cDNA cloning and sequence analysis.". J. Biochem. 108 (2): 297302. PMID 2229028.
Herz J, Hamann U, Rogne S, et al. (1989). "Surface location and high affinity for calcium of a 500-kd liver membrane protein closely related to the LDL-receptor suggest a physiological role as lipoprotein receptor.". EMBO J. 7 (13): 411927. PMC 455121. PMID 3266596. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=455121.
Zheng G, Bachinsky DR, Stamenkovic I, et al. (1994). "Organ distribution in rats of two members of the low-density lipoprotein receptor gene family, gp330 and LRP/alpha 2MR, and the receptor-associated protein (RAP).". J. Histochem. Cytochem. 42 (4): 53142. PMID 7510321.
Orlando RA, Farquhar MG (1994). "Functional domains of the receptor-associated protein (RAP).". Proc. Natl. Acad. Sci. U.S.A. 91 (8): 31615. doi:10.1073/pnas.91.8.3161. PMC 43535. PMID 7512726. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=43535.
Jou YS, Goold RD, Myers RM (1995). "Localization of the alpha 2-macroglobulin receptor-associated protein 1 gene (LRPAP1) and other gene fragments to human chromosome 4p16.3 by direct cDNA selection.". Genomics 24 (2): 4103. doi:10.1006/geno.1994.1643. PMID 7535288.
Argraves KM, Battey FD, MacCalman CD, et al. (1995). "The very low density lipoprotein receptor mediates the cellular catabolism of lipoprotein lipase and urokinase-plasminogen activator inhibitor type I complexes.". J. Biol. Chem. 270 (44): 265507. doi:10.1074/jbc.270.44.26550. PMID 7592875.
Bu G, Geuze HJ, Strous GJ, Schwartz AL (1995). "39 kDa receptor-associated protein is an ER resident protein and molecular chaperone for LDL receptor-related protein.". EMBO J. 14 (10): 226980. PMC 398334. PMID 7774585. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=398334.
Van Leuven F, Hilliker C, Serneels L, et al. (1995). "Cloning, characterization, and chromosomal localization to 4p16 of the human gene (LRPAP1) coding for the alpha 2-macroglobulin receptor-associated protein and structural comparison with the murine gene coding for the 44-kDa heparin-binding protein.". Genomics 25 (2): 492500. doi:10.1016/0888-7543(95)80050-V. PMID 7789983.
Medh JD, Fry GL, Bowen SL, et al. (1995). "The 39-kDa receptor-associated protein modulates lipoprotein catabolism by binding to LDL receptors.". J. Biol. Chem. 270 (2): 53640. doi:10.1074/jbc.270.2.536. PMID 7822276.
Korenberg JR, Argraves KM, Chen XN, et al. (1994). "Chromosomal localization of human genes for the LDL receptor family member glycoprotein 330 (LRP2) and its associated protein RAP (LRPAP1).". Genomics 22 (1): 8893. doi:10.1006/geno.1994.1348. PMID 7959795.
Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1-2): 1714. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
Willnow TE, Rohlmann A, Horton J, et al. (1996). "RAP, a specialized chaperone, prevents ligand-induced ER retention and degradation of LDL receptor-related endocytic receptors.". EMBO J. 15 (11): 26329. PMC 450198. PMID 8654360. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=450198.
Jacobsen L, Madsen P, Moestrup SK, et al. (1997). "Molecular characterization of a novel human hybrid-type receptor that binds the alpha2-macroglobulin receptor-associated protein.". J. Biol. Chem. 271 (49): 3137983. doi:10.1074/jbc.271.49.31379. PMID 8940146.
Bu G, Rennke S, Geuze HJ (1997). "ERD2 proteins mediate ER retention of the HNEL signal of LRP's receptor-associated protein (RAP).". J. Cell. Sci.. 110 ( Pt 1): 6573. PMID 9010785.
Petersen CM, Nielsen MS, Nykjaer A, et al. (1997). "Molecular identification of a novel candidate sorting receptor purified from human brain by receptor-associated protein affinity chromatography.". J. Biol. Chem. 272 (6): 3599605. doi:10.1074/jbc.272.6.3599. PMID 9013611.
Nielsen PR, Ellgaard L, Etzerodt M, et al. (1997). "The solution structure of the N-terminal domain of alpha2-macroglobulin receptor-associated protein.". Proc. Natl. Acad. Sci. U.S.A. 94 (14): 75215. doi:10.1073/pnas.94.14.7521. PMC 23854. PMID 9207124. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=23854.

[edit] External links

LDL-Receptor+Related+Protein-Associated+Protein at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the public domain Pfam and InterPro IPR010483

PDB gallery

1lre: RECEPTOR ASSOCIATED PROTEIN (RAP) DOMAIN 1, NMR, 20 STRUCTURES

1nre: RECEPTOR ASSOCIATED PROTEIN (RAP) DOMAIN 1, NMR, MINIMIZED AVERAGE STRUCTURE

1op1: Solution NMR structure of domain 1 of receptor associated protein

1ov2: Ensemble of the solution structures of domain one of receptor associated protein

2fcw: Structure of a Complex Between the Pair of the LDL Receptor Ligand-Binding Modules 3-4 and the Receptor Associated Protein (RAP).

2ftu: solution structure of domain 3 of RAP

2fyl: Haddock model of the complex between double module of LRP, CR56, and first domain of receptor associated protein, RAP-d1.

v t e Protein: cell membrane proteins (other than Cell surface receptor, enzymes, and cytoskeleton)

Arrestin	SAG, ARRB1, ARRB2, ARR3

Membrane-spanning 4A	MS4A1 · MS4A2 · MS4A3 · MS4A4A · MS4A4E · MS4A5 · MS4A6A · MS4A6E · MS4A7 · MS4A8B · MS4A9 · MS4A10 · MS4A12 · MS4A13 · MS4A14 · MS4A15 · MS4A18

Myelin	Myelin basic protein (PMP2) · Myelin proteolipid protein (PLP1) · Myelin oligodendrocyte glycoprotein · Myelin-associated glycoprotein · Myelin protein zero

Pulmonary surfactant	Pulmonary surfactant-associated protein B · Pulmonary surfactant-associated protein C

Tetraspanin	TSPAN1 · TSPAN2 · TSPAN3 · TSPAN4 · TSPAN5 · TSPAN6 · TSPAN7 · TSPAN8 · TSPAN9 · TSPAN10 · TSPAN11 · TSPAN12 · TSPAN13 · TSPAN14 · TSPAN15 · TSPAN16 · TSPAN17 · TSPAN18 · TSPAN19 · TSPAN20 · TSPAN21 · TSPAN22 · TSPAN23 · TSPAN24 · TSPAN25 · TSPAN26 · TSPAN27 · TSPAN28 · TSPAN29 · TSPAN30 · TSPAN31 · TSPAN32 · TSPAN33 · TSPAN34

Other/ungrouped	Calnexin · LDL-receptor-related protein associated protein · Neurofibromin 2 · Presenilin (PSEN1, PSEN2) · HFE · Phospholipid transfer proteins · Dysferlin · STRC · OTOF

see also other cell membrane protein disorders B memb: cead, trns (1A, 1C, 1F, 2A, 3A1, 3A2-3, 3D), othr

Lipids: lipoprotein metabolism

Apolipoproteins

APOA
- 1
- 2
- 4
- 5
APOB
APOC (1
2
3
4)
APOD
APOE
APOH

SAA
- SAA1

Lipoproteins

Extracellular enzymes

Lipid transfer proteins

Cell surface receptors

HDL: SCARB1

LDL: LDLR
LRPAP1

ATP-binding cassette transporter

M: MET

mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m

k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon

m(A16/C10),i(k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)

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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.

Alpha-2-macroglobulin RAP, N-terminal domain Provide feedback

The alpha-2-macroglobulin receptor-associated protein (RAP) is a intracellular glycoprotein that binds to the 2-macroglobulin receptor and other members of the low density lipoprotein receptor family. The protein inhibits binding of all currently known ligands of these receptors [1]. The N-terminal domain is predominately alpha helical [1]. Two different studies have provided conflicted domain boundaries [2,3].

Literature references

Nielsen PR, Ellgaard L, Etzerodt M, Thogersen HC, Poulsen FM; , Proc Natl Acad Sci U S A 1997;94:7521-7525.: The solution structure of the N-terminal domain of alpha2-macroglobulin receptor-associated protein. PUBMED:9207124 EPMC:9207124
Ellgaard L, Holtet TL, Nielsen PR, Etzerodt M, Gliemann J, Thogersen HC; , Eur J Biochem 1997;244:544-551.: Dissection of the domain architecture of the alpha2macroglobulin-receptor-associated protein. PUBMED:9119022 EPMC:9119022
Warshawsky I, Bu G, Schwartz AL; , J Biol Chem 1993;268:22046-22054.: Identification of domains on the 39-kDa protein that inhibit the binding of ligands to the low density lipoprotein receptor-related protein. PUBMED:7691821 EPMC:7691821

External database links

PANDIT:	PF06400
Pseudofam:	PF06400
SCOP:	1lre
SYSTERS:	Alpha-2-MRAP_N

This tab holds annotation information from the InterPro database.

InterPro entry IPR009066

The alpha-2-macroglobulin receptor-associated protein (RAP) is a glycoprotein that binds to the alpha-2-macroglobulin receptor, as well as to other members of the low density lipoprotein receptor family (INTERPRO). RAP acts to inhibit the binding of all know ligands for these receptors, and may prevent receptor aggregation and degradation in the endoplasmic reticulum, thereby acting as a molecular chaperone [PUBMED:9207124]. RAP may be under the regulatory control of calmodulin, since it is able to bind calmodulin and be phosphorylated by calmodulin-dependent kinase II (INTERPRO).

RAP is comprised of three domains. Both domains 1 and 3 are involved in binding to the alpha-2-macroglobulin receptor, while domain 1 is also involved in inhibiting the binding of activated alpha-2-macroglobulin (INTERPRO). Structural studies have revealed the RAP domain 1 to be comprised of a partly opened bundle of three helices, the first one being shorter than the other two.

Domain organisation

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

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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 (10)	Full (108)	Representative proteomes				NCBI (104)	Meta (0)
	Seed (10)	Full (108)	RP15 (12)	RP35 (15)	RP55 (32)	RP75 (51)	NCBI (104)	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 (10)	Full (108)	Representative proteomes				NCBI (104)	Meta (0)
	Seed (10)	Full (108)	RP15 (12)	RP35 (15)	RP55 (32)	RP75 (51)	NCBI (104)	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 (10)	Full (108)	Representative proteomes				NCBI (104)	Meta (0)
	Seed (10)	Full (108)	RP15 (12)	RP35 (15)	RP55 (32)	RP75 (51)	NCBI (104)	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:

Pfam-B_44514 (release 9.0)

Previous IDs:

none

Type:

Domain

Author:

Finn RD

Number in seed:

10

Number in full:

108

Average length of the domain:

113.90 aa

Average identity of full alignment:

50 %

Average coverage of the sequence by the domain:

33.65 %

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	27.3	27.3
Trusted cut-off	27.4	44.4
Noise cut-off	26.4	27.2

Model length:

121

Family (HMM) version:

6

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.

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Tree controls

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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

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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.

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 Alpha-2-MRAP_N domain has been found. There are 7 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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Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Family: Alpha-2-MRAP_N (PF06400)

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Summary: Alpha-2-macroglobulin RAP, N-terminal domain

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Contents

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Alpha-2-macroglobulin RAP, N-terminal domain Provide feedback

Literature references

External database links

InterPro entry IPR009066

Domain organisation

Alignments

Alignment types

Viewing

Reformatting

Downloading

View options

Format an alignment

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External links

HMM logo

Trees

Curation and family details

Curation

HMM information

Species distribution

Sunburst controls

Weight segments by...

Change the size of the sunburst

Colour assignments

Selections

Currently selected:

How the sunburst is generated

Colouring and labels

Anomalies in the taxonomy tree

Missing taxonomic levels

Unmapped species names

Sub-species

Too many species/sequences

Tree controls

Annotation

Download tree

Selected sequences

Species trees

Interactive tree

Structures