Q9Y5Q6 (INSL5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Insulin-like peptide INSL5
Short name=Insulin-like peptide 5

Cleaved into the following 2 chains:

1. Insulin-like peptide INSL5 B chain
2. Insulin-like peptide INSL5 A chain

Gene names

Name:	INSL5
ORF Names:	UNQ156/PRO182

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	135 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May have a role in gut contractility or in thymic development and regulation. Activates RXFP4 with high potency and appears to be the endogenous ligand for this receptor.
Subunit structure	Heterodimer of a B chain and an A chain linked by two disulfide bonds.
Subcellular location	Secreted.
Tissue specificity	Highly expressed in rectum with lower levels in uterus and ascending and descending colon. Ref.1
Sequence similarities	Belongs to the insulin family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Hormone
PTM	Cleavage on pair of basic residues Disulfide bond Pyrrolidone carboxylic acid
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Cellular_component	extracellular region Traceable author statement. Source: Reactome
Molecular_function	hormone activity Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Ref.5

Peptide

23 – 46

24

Insulin-like peptide INSL5 B chain

PRO_0000016163

Propeptide

49 – 114

66

Connecting peptide Potential

PRO_0000016164

Peptide

115 – 135

21

Insulin-like peptide INSL5 A chain

PRO_0000016165

Amino acid modifications

Modified residue

115

1

Pyrrolidone carboxylic acid

Disulfide bond

29 ↔ 122

Interchain (between B and A chains) Ref.7

Disulfide bond

41 ↔ 135

Interchain (between B and A chains) Ref.7

Disulfide bond

121 ↔ 126

Ref.7

Natural variations

Natural variant

50

1

Q → L. Ref.1 Ref.2 Ref.4
Corresponds to variant rs549148 [ dbSNP | Ensembl ].

VAR_046099

Secondary structure

1

.

.

.

.

.

.

.

135

Helix Strand Turn

Details...

Turn

116 – 118

3

Helix

119 – 123

5

Helix

128 – 131

4

Turn

132 – 134

3

Sequences

	Sequence		Length	Mass (Da)
	Q9Y5Q6 [UniParc]. Last modified September 2, 2008. Version 2. Checksum: A932D7EDE9D173F5	FASTA	135	15,333
	10 20 30 40 50 60 MKGSIFTLFL FSVLFAISEV RSKESVRLCG LEYIRTVIYI CASSRWRRHQ EGIPQAQQAE 70 80 90 100 110 120 TGNSFQLPHK REFSEENPAQ NLPKVDASGE DRLWGGQMPT EELWKSKKHS VMSRQDLQTL 130 CCTDGCSMTD LSALC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of INSL5, a new member of the insulin superfamily." Conklin D., Lofton-Day C.E., Haldeman B.A., Ching A., Whitmore T.E., Lok S., Jaspers S. Genomics 60:50-56(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANT LEU-50. Tissue: Colon.
[2]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LEU-50.
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LEU-50. Tissue: Brain.
[5]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 23-37.
[6]	"INSL5 is a high affinity specific agonist for GPCR142 (GPR100)." Liu C., Kuei C., Sutton S., Chen J., Bonaventure P., Wu J., Nepomuceno D., Kamme F., Tran D.T., Zhu J., Wilkinson T., Bathgate R., Eriste E., Sillard R., Lovenberg T.W. J. Biol. Chem. 280:292-300(2005) [PubMed] [Europe PMC] [Abstract] Cited for: BINDING TO RXFP4.
[7]	"Synthesis, conformation, and activity of human insulin-like peptide 5 (INSL5)." Akhter Hossain M., Bathgate R.A.D., Kong C.K., Shabanpoor F., Zhang S., Haugaard-Joensson L.M., Rosengren K.J., Tregear G.W., Wade J.D. ChemBioChem 9:1816-1822(2008) [PubMed] [Europe PMC] [Abstract] Cited for: SYNTHESIS OF 23-46 AND 115-135, DISULFIDE BONDS, PYROGLUTAMATE FORMATION AT GLN-115.
[8]	"Structure of human insulin-like peptide 5 and characterization of conserved hydrogen bonds and electrostatic interactions within the relaxin framework." Haugaard-Joensson L.M., Hossain M.A., Daly N.L., Craik D.J., Wade J.D., Rosengren K.J. Biochem. J. 419:619-627(2009) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 23-46 AND 115-135.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF133816 mRNA. Translation: AAD29686.1.
AY359030 mRNA. Translation: AAQ89389.1.
AL354978 Genomic DNA. Translation: CAH71844.1.
BC101646 mRNA. Translation: AAI01647.1.
BC101648 mRNA. Translation: AAI01649.1.

IPI

IPI00001717.

RefSeq

NP_005469.2. NM_005478.4.

UniGene

Hs.251380.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2K1V	NMR	-	A	116-135	[»]
2KBC	NMR	-	A	116-135	[»]
			B	23-46	[»]

ProteinModelPortal

Q9Y5Q6.

SMR

Q9Y5Q6. Positions 20-46.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000302724.

Polymorphism databases

DMDM

205371762.

Proteomic databases

PaxDb

Q9Y5Q6.

PRIDE

Q9Y5Q6.

Protocols and materials databases

DNASU

10022.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000304526; ENSP00000302724; ENSG00000172410.

GeneID

10022.

KEGG

hsa:10022.

UCSC

uc001dcw.3. human.

Organism-specific databases

CTD

10022.

GeneCards

GC01M067223.

H-InvDB

HIX0028561.

HGNC

HGNC:6088. INSL5.

HPA

CAB033849.
HPA030100.

MIM

606413. gene.

neXtProt

NX_Q9Y5Q6.

PharmGKB

PA29895.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG38979.

HOGENOM

HOG000111888.

HOVERGEN

HBG052135.

InParanoid

Q9Y5Q6.

OMA

CTEGCSM.

OrthoDB

EOG40S0GZ.

PhylomeDB

Q9Y5Q6.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

Bgee

Q9Y5Q6.

CleanEx

HS_INSL5.

Genevestigator

Q9Y5Q6.

GermOnline

ENSG00000172410. Homo sapiens.

Family and domain databases

InterPro

IPR016179. Insulin-like.
IPR022353. Insulin_CS.
[Graphical view]

Pfam

PF00049. Insulin. 1 hit.
[Graphical view]

SMART

SM00078. IlGF. 1 hit.
[Graphical view]

SUPFAM

SSF56994. Insulin-like. 1 hit.

PROSITE

PS00262. INSULIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9Y5Q6.

GenomeRNAi

10022.

NextBio

37869.

SOURCE

Search...

Entry information

Entry name

INSL5_HUMAN

Accession

Primary (citable) accession number: Q9Y5Q6
Secondary accession number(s): Q3MIY4, Q5VYD8

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	September 2, 2008
Last modified:	April 3, 2013
This is version 109 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.