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12  structures 117  species 0  interactions 264  sequences 8  architectures

Family: Resistin (PF06954)

Summary: Resistin

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This is the Wikipedia entry entitled "Resistin". More...

Resistin Edit Wikipedia article

Resistin is also known as serine/cysteine-rich Adipocyte-Specific Secretory Factor (ADSF or FIZZ3). The length of Resistin pre-peptide in human is 108 aa; in mouse/rat 114 aa and the molecular weight is ~12.5 kDa.
Resistin is secreted by adipocytes and affects several tissues in the body. Evidence from the early studies suggested that there might be a correlation between blood glucose levels and resistin concentrations in mice. This might have provided the link between obesity and Type 2 diabetes.
Later studies, however, did not show increase in blood resistin in obese humans with diabetes.

The research is still in progress as to the importance of resistin in the body.

Resistin has been discovered in 2001 by the group of Mitchell A. Lazar from University of Pennsylvania School of Medicine.

References:

Heilbronn, LK et al.
Relationship between serum resistin concentrations and insulin resistance in nonobese, obese, and obese diabetic subjects. Journal of Clinical Endocrinology and Metabolism. 2004 Apr; vol. 89(4), pp. 1844-8.

Lee, JH et al.
Circulating resistin levels are not associated with obesity or insulin resistance in humans and are not regulated by fasting or leptin administration: cross-sectional and interventional studies in normal, insulin-resistant, and diabetic subjects.
Journal of Clinical Endocrinology and Metabolism. 2003 Oct; vol. 88(10), pp. 4848-56.

Steppan, C. M. et al.
The hormone resistin links obesity to diabetes.
Nature, 2001 Jan; vol. 409, pp. 307-312

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.

Resistin Provide feedback

This family consists of several mammalian resistin proteins. Resistin is a 12.5-kDa cysteine-rich secreted polypeptide first reported from rodent adipocytes. It belongs to a multigene family termed RELMs or FIZZ proteins. Plasma resistin levels are significantly increased in both genetically susceptible and high-fat-diet-induced obese mice. Immunoneutralisation of resistin improves hyperglycemia and insulin resistance in high-fat-diet-induced obese mice, while administration of recombinant resistin impairs glucose tolerance and insulin action in normal mice. It has been demonstrated that increases in circulating resistin levels markedly stimulate glucose production in the presence of fixed physiological insulin levels, whereas insulin suppressed resistin expression. It has been suggested that resistin could be a link between obesity and type 2 diabetes [1].

Literature references

  1. Nogueiras R, Gallego R, Gualillo O, Caminos JE, Garcia-Caballero T, Casanueva FF, Dieguez C; , FEBS Lett 2003;548:21-27.: Resistin is expressed in different rat tissues and is regulated in a tissue- and gender-specific manner. PUBMED:12885401 EPMC:12885401

  2. Maebuchi M, Machidori M, Urade R, Ogawa T, Moriyama T; , Arch Biochem Biophys 2003;416:164-170.: Low resistin levels in adipose tissues and serum in high-fat fed mice and genetically obese mice: development of an ELISA system for quantification of resistin. PUBMED:12893293 EPMC:12893293


This tab holds annotation information from the InterPro database.

InterPro entry IPR009714

RELMs, secreted proteins with roles including insulin resistance and the activation of inflammatory processes, are also known as found in inflammatory zone (FIZZ), and include four members in mouse (RELM-alpha/FIZZ1/HIMF, RELM-beta/FIZZ2, Resistin/FIZZ3, and RELM-gamma/FIZZ4) and two members in human (resistin and RELM-beta). RELMs are potentially implicated in a wide range of physiological and pathological processes including obesity-associated diabetes, cardiovascular system function, cancer development and metastasis [ PUBMED:11201732 , PUBMED:24320036 , PUBMED:28192887 , PUBMED:29866514 ].

There are significant differences between human and rodent RELMs with respect to gene and protein structure, differential gene regulation, different tissue distribution profiles, and insulin resistance induction. Resistin appears to convey insulin resistance in rodents, and to instigate inflammatory processes in humans. In the pathophysiology of obesity-associated diabetes, mouse resistin is secreted by adipocytes and increases hepatic gluconeogenesis, thereby promoting insulin resistance, human resistin is secreted by macrophages and may play a role through inflammatory contributions [ PUBMED:12594039 , PUBMED:26662574 ].

Elevated levels of human resistin have been reported in various cancers including colorectal, endometrial, and postmenopausal breast cancers, and may initiate the production of further inflammatory cytokines, to promote tumor cell progression [ PUBMED:27001185 ]. Resistin has also been shown to cause G1 arrest in colon cancer cells. However, resistin may interfere with chemotherapy [ PUBMED:28417458 ].

Resistin contains an N-terminal signal sequence, a variable middle section, and a conserved C-terminal domain. The C-terminal domain is comprised of a cysteine signature motif sequence shared by all RELM family members, which is proposed to be critical for disulfide bond formation and protein folding [ PUBMED:29866514 ]. Resistin circulates as hexamers and trimers; structural similarity has been noted between the resistin homotrimer and the proprotein convertase subtilisin/kexin type 9, C-terminal cysteine-rich domain [ PUBMED:15155948 , PUBMED:18975914 ].

Gene Ontology

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Domain organisation

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Alignments

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RP55
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RP75
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(28)
Full
(264)
Representative proteomes UniProt
(328)
RP15
(34)
RP35
(68)
RP55
(151)
RP75
(251)
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  Seed
(28)
Full
(264)
Representative proteomes UniProt
(328)
RP15
(34)
RP35
(68)
RP55
(151)
RP75
(251)
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Seed source: Pfam-B_15476 (release 10.0)
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Moxon SJ
Number in seed: 28
Number in full: 264
Average length of the domain: 80.6 aa
Average identity of full alignment: 51 %
Average coverage of the sequence by the domain: 62.94 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild --amino -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.0 25.0
Trusted cut-off 25.8 26.2
Noise cut-off 23.7 23.3
Model length: 88
Family (HMM) version: 14
Download: download the raw HMM for this family

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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 Resistin domain has been found. There are 12 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 sequence.

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