Summary: D-lactate dehydrogenase, membrane binding

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Wikipedia: Lactate dehydrogenase
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Lactate dehydrogenase Edit Wikipedia article

Lactate dehydrogenase

Identifiers

Databases

PDB structures

AmiGO / EGO

Search
PMC	articles
PubMed	articles
NCBI	proteins

lactate dehydrogenase A (subunit M)

Human lactate dehydrogenase M₄ (the isoenzyme found in skeletal muscle). From PDB 1I10.
Identifiers
Symbol	LDHA
Alt. symbols	LDHM
Entrez	3939
HUGO	6535
OMIM	150000
RefSeq	NM_005566
UniProt	P00338
Other data
EC number	1.1.1.27
Locus	Chr. 11 p15.4

lactate dehydrogenase B (subunit H)
Identifiers
Symbol	LDHB
Alt. symbols	LDHL
Entrez	3945
HUGO	6541
OMIM	150100
RefSeq	NM_002300
UniProt	P07195
Other data
EC number	1.1.1.27
Locus	Chr. 12 p12.2-12.1

lactate dehydrogenase C
Identifiers
Symbol	LDHC
Entrez	3948
HUGO	6544
OMIM	150150
RefSeq	NM_002301
UniProt	P07864
Other data
EC number	1.1.1.27
Locus	Chr. 11 p15.5-15.3

D-lactate dehydrogenase, membrane binding

crystal structure of d-lactate dehydrogenase, a peripheral membrane respiratory enzyme.

Identifiers

Symbol

Lact-deh-memb

Pfam clan

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

Lactate dehydrogenase (LDH or LD) is an enzyme (EC 1.1.1.27) present in a wide variety of organisms, including plants and animals.

Lactate dehydrogenases exist in four distinct enzyme classes. Two of them are cytochrome c-dependent enzymes, each acting on either D-lactate (EC 1.1.2.4) or L-lactate (EC 1.1.2.3). The other two are NAD(P)-dependent enzymes, each acting on either D-lactate (EC 1.1.1.28) or L-lactate (EC 1.1.1.27). This article is about the NAD(P)-dependent L-lactate dehydrogenase.

[edit] Reactions

Catalytic function of LDH

Lactate dehydrogenase catalyzes the interconversion of pyruvate and lactate with concomitant interconversion of NADH and NAD⁺. It converts pyruvate, the final product of glycolysis, to lactate when oxygen is absent or in short supply, and it performs the reverse reaction during the Cori cycle in the liver. At high concentrations of lactate, the enzyme exhibits feedback inhibition, and the rate of conversion of pyruvate to lactate is decreased.

It also catalyzes the dehydrogenation of 2-Hydroxybutyrate, but it is a much poorer substrate than lactate. There is little to no activity with beta-hydroxybutyrate.

[edit] Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. ^{[§ 1]}

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Glycolysis and Gluconeogenesis edit

^ The interactive pathway map can be edited at WikiPathways: "GlycolysisGluconeogenesis_WP534".

[edit] Enzyme regulation

This protein may use the morpheein model of allosteric regulation.^[1]

[edit] Ethanol-induced hypoglycemia

Ethanol is dehydrogenated to acetaldehyde by alcohol dehydrogenase, and further into acetic acid by acetaldehyde dehydrogenase. During this reaction 2 NADH are produced. If large amounts of ethanol are present, then large amounts of NADH are produced, leading to a depletion of NAD⁺. Thus, the conversion of pyruvate to lactate is increased due to the associated regeneration of NAD⁺. Therefore, hypoglycemia and anion-gap metabolic acidosis (lactic acidosis) may ensue in ethanol poisoning.

[edit] Enzyme isoforms

Functional lactate dehydrogenase are homo or hetero tetramers composed of M and H protein subunits encoded by the LDHA and LDHB genes, respectively:

LDH-1 (4H)—in the heart
LDH-2 (3H1M)—in the reticuloendothelial system
LDH-3 (2H2M)—in the lungs
LDH-4 (1H3M)—in the kidneys, placenta, and pancreas
LDH-5 (4M)—in the liver and striated muscle^[2]

The five isoenzymes that are usually described in the literature each contain four subunits. The major isoenzymes of skeletal muscle and liver, M₄, has four muscle (M) subunits, while H₄ is the main isoenzymes for heart muscle in most species, containing four heart (H) subunits. The other variants contain both types of subunits.

Usually LDH-2 is the predominant form in the serum. A LDH-1 level higher than the LDH-2 level (a "flipped pattern") suggests myocardial infarction (damage to heart tissues releases heart LDH, which is rich in LDH-1, into the bloodstream). The use of this phenomenon to diagnose infarction has been largely superseded by the use of Troponin I or T measurement.

[edit] Genetics in humans

The M and H subunits are encoded by two different genes:

The M subunit is encoded by LDHA, located on chromosome 11p15.4 (Online 'Mendelian Inheritance in Man' (OMIM) 150000)
The H subunit is encoded by LDHB, located on chromosome 12p12.2-p12.1 (Online 'Mendelian Inheritance in Man' (OMIM) 150100)
A third isoform, LDHC or LDHX, is expressed only in the testis (Online 'Mendelian Inheritance in Man' (OMIM) 150150); its gene is likely a duplicate of LDHA and is also located on the eleventh chromosome (11p15.5-p15.3)

Mutations of the M subunit have been linked to the rare disease exertional myoglobinuria (see OMIM article), and mutations of the H subunit have been described but do not appear to lead to disease.

[edit] Medical use

Tissue breakdown releases LDH, and therefore LDH can be measured as a surrogate for tissue breakdown, e.g. hemolysis. Other disorders indicated by elevated LDH include cancer, meningitis, encephalitis, acute pancreatitis, and HIV.

[edit] Hemolysis

In medicine, LDH is often used as a marker of tissue breakdown as LDH is abundant in red blood cells and can function as a marker for hemolysis. A blood sample that has been handled incorrectly can show false-positively high levels of LDH due to erythrocyte damage.

It can also be used as a marker of myocardial infarction. Following a myocardial infarction, levels of LDH peak at 3–4 days and remain elevated for up to 10 days. In this way, elevated levels of LDH (where the level of LDH1 is higher than that of LDH2) can be useful for determining whether a patient has had a myocardial infarction if they come to doctors several days after an episode of chest pain.

[edit] Tissue turnover

Other uses are assessment of tissue breakdown in general; this is possible when there are no other indicators of hemolysis. It is used to follow-up cancer (especially lymphoma) patients, as cancer cells have a high rate of turnover with destroyed cells leading to an elevated LDH activity.

[edit] Exudates and transudates

Measuring LDH in fluid aspirated from a pleural effusion (or pericardial effusion) can help in the distinction between exudates (actively secreted fluid, e.g. due to inflammation) or transudates (passively secreted fluid, due to a high hydrostatic pressure or a low oncotic pressure). The usual criterion is that a ratio of fluid LDH versus upper limit of normal serum LDH of more than 0.6^[3] or $⅔$ ^[4] indicates an exudate, while a ratio of less indicates a transudate. Different laboratories have different values for the upper limit of serum LDH, but examples include 200^[5] and 300^[5] IU/L.^[6] In empyema, the LDH levels, in general, will exceed 1000 IU/L.

[edit] Meningitis and encephalitis

High levels of lactate dehydrogenase in cerebrospinal fluid are often associated with bacterial meningitis. In the case of viral meningitis, high LDH, in general, indicates the presence of encephalitis and poor prognosis.

[edit] HIV

LDH is often measured in HIV patients as a non-specific marker for pneumonia due to Pneumocystis jiroveci (PCP). Elevated LDH in the setting of upper respiratory symptoms in an HIV patient suggests, but is not diagnostic for, PCP. However, in HIV-positive patients with respiratory symptoms, a very high LDH level (>600 IU/L) indicated histoplasmosis (9.33 more likely) in a study of 120 PCP and 30 histoplasmosis patients.^[7]

[edit] Dysgerminoma

Elevated LDH is often the first clinical sign of a dysgerminoma. Not all dysgerminomas produce LDH, and this is often a non-specific finding.

[edit] Prokaryotes

A cap-membrane-binding domain is found in prokaryotic lactate dehydrogenase. This consists of a large seven-stranded antiparallel beta-sheet flanked on both sides by alpha-helices. It allows for membrane association.^[8]

[edit] See also

[edit] References

^ T. Selwood and E. K. Jaffe (2011). "Dynamic dissociating homo-oligomers and the control of protein function". Arch. Biochem. Biophys. 519 (2): 131–43. doi:10.1016/j.abb.2011.11.020. PMC 3298769. PMID 22182754.
^ Van Eerd, J. P. F. M.; Kreutzer, E. K. J. (1996). Klinische Chemie voor Analisten deel 2. pp. 138–139. ISBN 978-90-313-2003-5.
^ Heffner, J.; Brown, L.; Barbieri, C. (1997). "Diagnostic value of tests that discriminate between exudative and transudative pleural effusions Primary Study Investigators". Chest 111 (4): 970–80. doi:10.1378/chest.111.4.970. PMID 9106577.
^ Light, R.; Macgregor, M.; Luchsinger, P.; Ball, W. (1972). "Pleural effusions: the diagnostic separation of transudates and exudates". Ann Intern Med 77 (4): 507–13. PMID 4642731.
^ ^a ^b Joseph, J.; Badrinath, P.; Basran, G. S.; Sahn, S. A. (November 2001). "Is the pleural fluid transudate or exudate? A revisit of the diagnostic criteria". Thorax 56 (11): 867–70. doi:10.1136/thorax.56.11.867. PMC 1745948. PMID 11641512.
^ Joseph, J.; Badrinath, P.; Basran, G. S.; Sahn, S. A. (2002). "Is albumin gradient or fluid to serum albumin ratio better than the pleural fluid lactate dehydroginase in the diagnostic of separation of pleural effusion?". BMC Pulmonary Medicine 2: 1. doi:10.1186/1471-2466-2-1. PMC 101409. PMID 11914151. edit [1]
^ Butt, A. A.; Michaels, S.; Greer, D; Clark, R.; Kissinger, P.; Martin, D. H. (July 2002). "Serum LDH level as a clue to the diagnosis of histoplasmosis". AIDS Read 12 (7): 317–21. PMID 12161854.
^ Dym, O.; Pratt, E. A.; Ho, C.; Eisenberg, D. (August 2000). "The crystal structure of D-lactate dehydrogenase, a peripheral membrane respiratory enzyme". Proc. Natl. Acad. Sci. U.S.A. 97 (17): 9413–8. doi:10.1073/pnas.97.17.9413. PMC 16878. PMID 10944213.

Oxidoreductases: alcohol oxidoreductases (EC 1.1)

1.1.1: NAD/NADP acceptor

Hydroxysteroid dehydrogenase: 3 Beta
- 3-beta-HSD
- NSDHL
11 Beta
- HSD11B1
- HSD11B2
17 Beta

1.1.2: cytochrome acceptor

1.1.3: oxygen acceptor

1.1.4: disulfide as acceptor

1.1.5: quinone/similar acceptor

1.1.99: other acceptors

B
enzm
1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
2.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
2.7.10
2.7.11-12
3.1
- - 3.1.3.48
- 2
- 3
- 4
  - 3.4.21
- 5
- 6
- 7
- 22
- 23
- 24
4.1
- 2
- 3
- 4
- 5
- 6
5.1
- 2
- 3
- 4
- 99
6.1-3
- 4
- 5-6

Metabolism: carbohydrate metabolism: glycolysis/gluconeogenesis enzymes

Glycolysis

Hexokinase (HK1, HK2, HK3, Glucokinase)→/Glucose 6-phosphatase← · Glucose isomerase · Phosphofructokinase 1 (Liver, Muscle, Platelet)→/Fructose 1,6-bisphosphatase←

Fructose-bisphosphate aldolase (Aldolase A, B, C) · Triosephosphate isomerase

Glyceraldehyde 3-phosphate dehydrogenase · Phosphoglycerate kinase · Phosphoglycerate mutase · Enolase · Pyruvate kinase (PKLR, PKM2)

Gluconeogenesis only

to oxaloacetate: Pyruvate carboxylase · Phosphoenolpyruvate carboxykinase

from lactate (Cori cycle): Lactate dehydrogenase

from alanine (Alanine cycle): Alanine transaminase

from glycerol: Glycerol kinase · Glycerol dehydrogenase

Regulatory

Fructose 6-P,2-kinase:fructose 2,6-bisphosphatase (PFKFB1, PFKFB2, PFKFB3, PFKFB4) · Bisphosphoglycerate mutase

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)

Medical test: Serology, reference range: Clinical biochemistry blood tests (including BMP, CMP) (CPT 82000–84999)

Fluid/electrolytes

electrolytes
- Na⁺/K⁺
- Cl^-/HCO₃^-
renal function, BUN-to-creatinine ratio
- BUN/Creatinine
Ca

derived values: Plasma osmolality
Serum osmolal gap

Blood lipids

Cardiovascular

Digestive

Liver function tests: protein tests
- Human serum albumin
- Serum total protein
ALP
transaminases
- ALT
- AST
- AST/ALT ratio
Bilirubin
- Unconjugated
- Conjugated

M: URI

anat/phys/devp/cell

noco/acba/cong/tumr, sysi/epon, urte

proc/itvp, drug (G4B), blte, urte

M: END

anat/phys/devp/horm

noco (d)/cong/tumr, sysi/epon

proc, drug (A10/H1/H2/H3/H5)

M: HRT

anat/phys/devp

noco/cong/tumr, sysi/epon, injr

proc, drug (C1A/1B/1C/1D), blte

M: DIG

anat (t, g, p)/phys/devp/enzy

noco/cong/tumr, sysi/epon

proc, drug (A2A/2B/3/4/5/6/7/14/16), blte

This article incorporates text from the public domain Pfam and InterPro IPR015409

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.

D-lactate dehydrogenase, membrane binding Provide feedback

Members of this family are predominantly found in prokaryotic D-lactate dehydrogenase, forming the cap-membrane-binding domain, which consists of a large seven-stranded antiparallel beta-sheet flanked on both sides by alpha-helices. They allow for membrane association [1].

Literature references

Dym O, Pratt EA, Ho C, Eisenberg D; , Proc Natl Acad Sci U S A. 2000;97:9413-9418.: The crystal structure of D-lactate dehydrogenase, a peripheral membrane respiratory enzyme. PUBMED:10944213 EPMC:10944213

External database links

PANDIT:	PF09330
Pseudofam:	PF09330
SCOP:	1f0x
SYSTERS:	Lact-deh-memb

This tab holds annotation information from the InterPro database.

InterPro entry IPR015409

Members of this entry are predominantly found in prokaryotic D-lactate dehydrogenase, forming the cap-membrane-binding domain, which consists of a large seven-stranded antiparallel beta-sheet flanked on both sides by alpha-helices. They allow for membrane association [PUBMED:10944213].

Gene Ontology

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

Molecular function	flavin adenine dinucleotide binding (GO:0050660)
Biological process	transmembrane transport (GO:0055085)

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 FAD-oxidase_C (CL0277), which contains the following 6 members:

ALO BBE Chol_subst-bind Cytokin-bind FAD-oxidase_C Lact-deh-memb

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
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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 (19)	Full (896)	Representative proteomes				NCBI (550)	Meta (214)
	Seed (19)	Full (896)	RP15 (20)	RP35 (49)	RP55 (82)	RP75 (110)	NCBI (550)	Meta (214)
Jalview	View	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 (19)	Full (896)	Representative proteomes				NCBI (550)	Meta (214)
	Seed (19)	Full (896)	RP15 (20)	RP35 (49)	RP55 (82)	RP75 (110)	NCBI (550)	Meta (214)
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 (19)	Full (896)	Representative proteomes				NCBI (550)	Meta (214)
	Seed (19)	Full (896)	RP15 (20)	RP35 (49)	RP55 (82)	RP75 (110)	NCBI (550)	Meta (214)
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.

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_1f0x

Previous IDs:

none

Type:

Domain

Author:

Sammut SJ

Number in seed:

19

Number in full:

896

Average length of the domain:

277.90 aa

Average identity of full alignment:

68 %

Average coverage of the sequence by the domain:

51.68 %

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	25.0	25.0
Trusted cut-off	70.1	61.0
Noise cut-off	20.7	20.0

Model length:

291

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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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.

Interactions

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

FAD_binding_4

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 Lact-deh-memb domain has been found. There are 2 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: Lact-deh-memb (PF09330)

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Summary: D-lactate dehydrogenase, membrane binding

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Lactate dehydrogenase Edit Wikipedia article

Contents

[edit] Reactions

[edit] Interactive pathway map

[edit] Enzyme regulation

[edit] Ethanol-induced hypoglycemia

[edit] Enzyme isoforms

[edit] Genetics in humans

[edit] Medical use

[edit] Hemolysis

[edit] Tissue turnover

[edit] Exudates and transudates

[edit] Meningitis and encephalitis

[edit] HIV

[edit] Dysgerminoma

[edit] Prokaryotes

[edit] See also

[edit] References

D-lactate dehydrogenase, membrane binding Provide feedback

Literature references

External database links

InterPro entry IPR015409

Gene Ontology

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