INT56985

Context Info Confidence 0.71 First Reported 1993 Last Reported 2010 Negated 5 Speculated 0 Reported most in Body Documents 56 Total Number 56 Disease Relevance 46.71 Pain Relevance 9.47

cytosol (MEFV) cytoskeleton (MEFV) nucleus (MEFV) intracellular (MEFV) cytoplasm (MEFV)

Anatomy Link Frequency monocytes 4 filaments 4 uterus 3 plasma 2 arm 2 MEFV (Homo sapiens)

Pain Link Frequency Relevance Heat Inflammation 2015 100.00 Fibrositis 582 100.00 Dopamine 170 99.40 chemokine 78 99.40 Inflammatory mediators 13 99.28 rheumatoid arthritis 79 99.18 cytokine 100 99.00 Pain 195 98.24 Inflammatory stimuli 9 97.44 Inflammatory response 34 97.20

Disease Link Frequency Relevance Heat Fever 2484 100.00 INFLAMMATION 2068 100.00 Fibromyalgia 582 100.00 Familial Mediterranean Fever 301 100.00 Amyloidosis 116 99.92 Inflammatory Bowel Disease 5 99.88 Disease 1137 99.32 Rheumatoid Arthritis 79 99.18 Obesity 2 98.26 Pain 187 98.24

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Pyrin expression alters PSTPIP1 distribution

Gene_expression (expression) of Pyrin

1) Confidence 0.71 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

In contrast, when pyrin is transfected into cultured cells, it is uniformly distributed throughout the cytoplasm without a filamentous pattern (Figure 1E).

Gene_expression (transfected) of pyrin

2) Confidence 0.71 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

In transfected cells, which endogenously express neither pyrin nor PSTPIP1, transfected PSTPIP1 assembles into delicate filaments (Figure 1C).

Neg (neither) Gene_expression (express) of pyrin in filaments

3) Confidence 0.71 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

Genetic analysis of the MEFV-gene as well as a therapeutic trial with colchicine, may help to detect FMF.

Gene_expression (detect) of FMF

4) Confidence 0.68 Published 2008 Journal Dtsch. Med. Wochenschr. Section Abstract Doc Link 18651363 Disease Relevance 0.86 Pain Relevance 0.16

In contrast, individuals with one or more missense mutations at the MEFV locus produce a pyrin protein with altered or absent function.

Neg (absent) Gene_expression (produce) of pyrin

5) Confidence 0.67 Published 2003 Journal BMC Nephrol Section Body Doc Link PMC194618 Disease Relevance 1.49 Pain Relevance 0.44

As shown in Figure 2, MCP-1, IP-10 and eotaxin plasma levels were elevated, on average, for all FMS patients vs. unrelated controls, except those with the rare alleles for the MEFV gene, who were empirically intermediate, but cannot be statistically distinguished from either controls or other FMS patients.

Gene_expression (gene) of MEFV in plasma associated with fibrositis

6) Confidence 0.67 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2794536 Disease Relevance 0.61 Pain Relevance 0.47

Pyrin, product of the MEFV locus, interacts with the proapoptotic protein, Siva.

Gene_expression (product) of MEFV

7) Confidence 0.65 Published 2008 Journal J. Cell. Physiol. Section Title Doc Link 18330885 Disease Relevance 0.75 Pain Relevance 0.12

Pyrin, the product of the MEFV locus, is a cytosolic protein whose function is unknown.

Gene_expression (product) of MEFV

8) Confidence 0.65 Published 2001 Journal J. Biol. Chem. Section Abstract Doc Link 11498534 Disease Relevance 0.62 Pain Relevance 0.15

The incomplete penetrance and the varying expression of FMF suggest the presence of other, possibly genetic, factors that could influence the expression of illness [4, 19].

Gene_expression (expression) of FMF associated with familial mediterranean fever

9) Confidence 0.65 Published 2010 Journal The Open Rheumatology Journal Section Body Doc Link PMC2825617 Disease Relevance 1.09 Pain Relevance 0.04

When ASC specks form in cells transfected with ASC and pyrin, both proteins are always co-localized in the specks (Figure 9A–D).

Gene_expression (transfected) of pyrin

10) Confidence 0.62 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

Indeed, in earlier studies, we demonstrated that, in HeLa cells (which do not express PSTPIP1) co-transfection of pyrin and ASC promotes ASC speck formation [32].

Gene_expression (transfection) of pyrin in HeLa

11) Confidence 0.62 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0.17 Pain Relevance 0.04

Note also that PSTPIP1 filaments, in the absence of pyrin decoration, are finer and more delicate in nature (compare Figure 4G to Figure 4J)

Gene_expression (decoration) of pyrin in filaments

12) Confidence 0.62 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

A second difference between our findings and those of earlier studies is that we find that pyrin is not sequestered away from ASC by its interaction by PSTPIP1, and does not require PSTPIP1 to interact with ASC.

Neg (not) Gene_expression (sequestered) of pyrin

13) Confidence 0.62 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0.19 Pain Relevance 0.05

The distribution of pyrin in transfected cells that do not express PSTPIP1 is diffusely cytoplasmic (Figure 1E), but pyrin exhibits a course filamentous distribution in human monocytes that express PSTPIP1 (Figure 1D).

Gene_expression (distribution) of pyrin in monocytes

14) Confidence 0.62 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

Modeling PSTPIP1 structure: prediction of separate membrane-interacting and pyrin-interacting surfaces

Gene_expression (structure) of pyrin

15) Confidence 0.62 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

In the presence of pyrin, DiIC16 staining was not perturbed (Figure 7D–F).

Gene_expression (presence) of pyrin

16) Confidence 0.62 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0.07 Pain Relevance 0

We show that Siva and pyrin are indeed co-expressed in human neutrophils, monocytes, and synovial cells.

Gene_expression (co-expressed) of pyrin in synovial cells

17) Confidence 0.61 Published 2008 Journal J. Cell. Physiol. Section Abstract Doc Link 18330885 Disease Relevance 0.78 Pain Relevance 0.10

In contrast, individuals with one or more missense mutations at the MEFV locus produce a pyrin protein with altered or absent function.

Neg (absent) Gene_expression (produce) of MEFV

18) Confidence 0.59 Published 2003 Journal BMC Nephrol Section Body Doc Link PMC194618 Disease Relevance 1.53 Pain Relevance 0.44

Unsurprisingly, pyrin is found in large quantities in neutrophils and released in response to inflammatory stimuli.

Gene_expression (found) of pyrin in neutrophils associated with inflammatory stimuli

19) Confidence 0.59 Published 2003 Journal BMC Nephrol Section Body Doc Link PMC194618 Disease Relevance 1.21 Pain Relevance 0.28

These results support our diagnosis of FMS in this cohort, rather than variant FMF.

Gene_expression (diagnosis) of FMF associated with familial mediterranean fever and fibrositis

20) Confidence 0.58 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2794536 Disease Relevance 1.02 Pain Relevance 0.15

General Comments

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