IS Families

Introduction – Prokaryotic Insertion Sequences

Insertion sequences (IS) are the simplest, most abundant transposable elements found in bacteria and archaea. Since their discovery in the late 1960s, the catalogue of known IS has expanded explosively; today, ISfinder curates sequences for > 5,000 distinct elements drawn from nearly every branch of the prokaryotic tree. Far from genetic curiosities, IS act as powerful engines of genome evolution, capturing, shuffling, mutating, and occasionally activating host genes while driving plasmid and chromosomal rearrangements. Their activity underlies rapid adaptation to antibiotics, niche colonization, and metabolic innovation, making them indispensable subjects for comparative genomics and molecular microbiology.

Fig.1.6.1. IS distribution in the prokaryotic world.

Despite their sequence diversity, IS rely on a surprisingly small set of transposition chemistries—cut-and-paste, copy-out–paste-in, peel-and-paste and rolling-circle mechanisms chief among them.

These shared strategies provide a conceptual framework for understanding how seemingly unrelated families achieve similar biological outcomes. They also blur the traditional borders between IS and larger composite transposons or integrative elements, emphasizing that mechanistic convergence, rather than sequence homology alone, now guides TE classification.

How to use this section

Each chapter that follows focuses on a single IS family. For every family you will find:

• Diagnostic features – hallmark transposase motifs, terminal inverted repeats, and target-site duplications.
• Mechanistic synopsis – the transposition pathway(s) employed and any known regulatory controls.
• Representative members – well-characterized elements that exemplify the family’s diversity and biological impact.
• Distribution and host range – taxonomic breadth and notable hotspots across plasmids, chromosomes, and mobile genomic islands.
• Genomic and evolutionary impact – documented roles in gene mobilization, genome plasticity, and adaptive evolution.

Because genome sequencing continues to reveal novel IS at an accelerating pace, family boundaries and definitions remain fluid. These chapters therefore serve not as static taxonomic verdicts but as living reference points that will be updated as new data emerge.

Whether you are annotating a newly sequenced genome, tracking the spread of antibiotic-resistance genes, or probing the evolutionary logic of mobile DNA, this section of TnPedia provides a concise, family-by-family guide to the structure, mechanism, and biological significance of prokaryotic insertion sequences.

Prokaryotic Insertion Sequences (IS)
1. IS1 family IS1 was among the first bacterial insertion sequences to be identified. They are component of several compound transposons.
2. IS1595 family IS1595 was identified in Xanthomonas campestris and are present in high copy number in other Xanthomonas species. Subgroups may contain passenger genes or additional noncoding DNA.
3. IS3 family The IS3 family is one of the most coherent and largest IS families. 3a. Excision: A dedicated enzyme This sub-section explores a mechanistic basis for the precise excision of members of IS3 family in bacteria, focusing on the role of the Insertion Sequence Excision Enhancer (IEE).
4. IS481 family Initially, IS481 appeared to be an IS3 family derivative, however, their presence in high copy number in some species strongly suggests that these represent a distinct transpositionally active family. Importantly, some members include passenger genes including antibiotic resistance, or potential transcriptional regulators.
5. IS1202 family IS1202 was originally isolated from Streptococcus pneumoniae in the mid-1990s and previously tagged as an emerging IS family in the ISfinder database.
6. IS4 and related families, IS701 family, ISH3 family and IS1634 family The IS4 family originally included a diverse collection of IS characterized by three conserved domains in the Tpase
7. IS5 and related IS1182 families Although the majority of members have a single Tpase orf, about 20% of family members may express Tpase by frameshifting because it is distributed between two translation phases.
8. IS6 family The IS6 family of bacterial and archaeal insertion sequences, first identified in the early 1980s, has proved to be instrumental in the rearrangement and spread of multiple antibiotic resistance.
9. IS21 family The IS21 family is fairly homogeneous. This family was discovered in plasmid R68 where it was subsequently observed to undergo a tandem duplication.
10. IS30 family Members of this family are capable of activating neighboring genes by creation of a hybrid promoter on insertion next to a −10 promoter element.
11. IS66 family IS66 was first identified in the Ti plasmid pTi66 of Agrobacterium tumefaciens.
12. IS110 and IS1111 families IS110 was originally identified in 1985 in Streptomyces coelicolor A3(2) as an element present in a derivative of bacteriophage phiC31 carrying a selectable viomycin resistance gene.
13. IS256 family IS256 itself was originally isolated as a component of the compound transposon Tn4001 (201, 202). This family is quite homogeneous.
14. IS630 family
15. IS982 family
16. IS1380 family
17. ISAs1 family
18. ISL3 family
19. ISAzo13 family
20. IS607 family
21. IS91 and related ISCR families
22. IS200/IS605 family
23. ISPa17 family

Quick Access Table

Main Characteristics and Summary of Each IS family and Sub-Groups

Below is a concise summary table of key characteristics for each IS family and their subgroups, including conserved transposase motifs, transposition mechanisms, typical size, hallmark IRs/DRs sequences. Use this as a practical reference guide to quickly locate essential information before diving into individual family chapters.

Characteristics of insertion sequence families. Abbreviations: DR, duplication repeat; IS, insertion sequence; ORF, open reading frame.
Families	Sub-Groups	Typical size-range (bp)	DR (bp)	Ends	IRs	No ORFs	Frameshift	Catalytic residues	Mechanism
IS1	—	740–1180	8–9	GGnnnTG	Y	2	ORFAB	DDE	copy-and-paste and cointegrate
	single ORF	800–1200	0–9		N	1	—
	ISMhu11	900–4600	0–10		Y	2	ORFAB
IS1595	ISPna2	1000–1150	8	GGCnnTG	Y	1	—	DDNK	copy-and-paste (?)
	ISPna2+pass	1500–2600	8	—		1+pass		—
	ISH4	1000	8	CGCTCTT		1		DDNK
	IS1016	700–745	7–9	GGGgctg				DDEK
	IS1595	900–1100	8	CcTGATT				DDNK+ER4R7
	ISSod11	1000–1100	8	nnnGcnTATC				DDHK+ER4R7
	ISNwi1	1080–1200	8	ggnnatTAT				DDEK+ER4
	ISNwi1+pass	1750–4750	8	—		1+pass		—
	ISNha5	3450–7900	8	CGGnnTT		1		DDER/K
IS3	IS150	1200–1600	3–4	TG	Y	2	ORFAB	DDE	copy-and-paste
	IS407	1100–1400	4	TG
	IS51	1000–1400	3–4	TG
	IS3	1150–1750	3–4	TGa/g
	IS2	1300–1400	5	TG
IS481	—	950–1300	4–15	TGT	Y	1	—	DDE	copy-and-paste (?)
IS1202	ISAba32	1450-1870	5-6	TGT	Y	1	—	DDE	copy-and-paste
	ISTde1	1320-1780	16-17	TAT/TGT
	IS1202	1440-1900	27-28	TGT
IS4	IS10	1200–1350	9	CT	Y	1	DDE	hairpin intermediate	cut-and-paste
	IS50	1350–1550	8–9	C				hairpin intermediate
	ISPepr1	1500–1600	7–8	-T-AA				?
	IS4	1400–1600	10–13	-AAT				?
	IS4Sa	1150–1750	8–10	CA				?
	ISH8	1400–1800	10	?
	IS231	1450–5400	10–12	CAT		1 or + *		*passenger genes
IS701	—	1400–1550	4	—	Y	1	—	DDE	—
	ISAba11	—	—
ISH3	—	1225–1500	4–5	C-GT	Y	1	—	DDE	—
IS1634	—	1500–2000	5–6	C	Y	1	—	DDE	—
IS5	IS903	950–1150	9	GG	Y	1	—	DDE	—
	ISL2	850–1200	2–3	—
	ISH1	900–1150	8	-GC
	IS5	1000–1500	4	Ga/g
	IS1031	850–1050	3	GAa/g
	IS427	800–1000	2–4	Ga/g		2	ORFAB
IS1182	—	1330–1950	0–60	—	Y	1	—	DDE	—
IS6	—	700–900	8	GG	Y	1	—	DDE	co-integrate
IS21	—	1750–2600	4–8	TG	Y	2 *	—	DDE	—
IS30	—	1000–1700	2–3	—	Y	1	—	DDE	copy-and-paste
IS66	—	2000–3000	8–9	GTAA	Y	3*	—	DDE*	—
	ISBst12	1350–1900				1		DDE
IS256	—	1200–1500	8–9	Ga/g	Y	1	—	DDE	copy-and-paste
	IS1249	1300	0–10	GG
	ISC1250	1250	0–9	GG
ISH6	—	1450	8	GGT	Y	1	—	DDE	—
ISLre2	—	1500–2000	9	—	Y	1	—	DDE	—
ISKra4	ISAzba1	1400–2900	0	—	Y	1 or + *	—	DDE	—
	ISMich2	1250–1400	8	GGG		1 or 2	ORFAB
	ISKra4	1400–3700	9	GGG		1 or + *	—
IS630	—	1000–1400	2*	—	Y	1 or 2	ORFAB	DDE	cut-and-paste
IS982	—	1000	3–9	AC	Y	1	—	DDE	—
IS1380	—	1550–2000	4–5	CC	Y	1	—	DDE	—
ISAs1	—	1200–1500	8–10	CAGGG	Y	1	—	—	—
ISL3	—	1300–2300	8	GG	Y	1	—	—	—
Tn3	—	>3000	0	GGGG	Y	>1	—	DDE	co-integrate
ISAzo13	—	1250–2200	0–4	Ga/g	Y	1	—	—	—
IS110	—	1200–1550	0	—	N	1	—	DEDD	—
	IS1111	—	—	—	Y*	—	—	—	—
IS91	—	1500–2000	0	—	N	1	—	HUH/Y2	rolling-circle
IS200/IS605	IS200	600–750	0	—	0	1*	—	HUH/Y1	peel-and-paste
	IS605	1300–2000	—	—	—	2*	—	HUH/Y1**
IS607	—	1700–2500	0	—	N	2*	—	Serine**	—
ISPa17	—	2000-2500	5	—	Y	4+pass	—	—	—
ISNCY *	IS892	1600	0–8	CTAG	Y	2	ORFAB	—	—
	ISLbi1	1400–1500	5	—	Y	1
	ISMae2	1400–2400	9	CAG	Y	1
	ISPlu15	800–1000	0	—	N	1
	ISA1214	1000–1200	8–12	—	Y	2
	ISC1217	1200	6–8	TAG	Y	1
	ISM1	1300–1600	8–9	—	Y	1
	ISDol1	1600–1900	6–7	—	Y	1	—	DDE	—

* ISNCY = Insertion Sequence Not Classified Yet