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Protein

Insulin-like 3

Gene

INSL3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Seems to play a role in testicular function. May be a trophic hormone with a role in testicular descent in fetal life. Is a ligand for LGR8 receptor.

Caution

GO - Molecular functioni

  • hormone activity Source: UniProtKB-KW
  • insulin receptor binding Source: ProtInc
  • protease binding Source: UniProtKB
  • receptor binding Source: ProtInc

GO - Biological processi

  • cell-cell signaling Source: ProtInc
  • G-protein coupled receptor signaling pathway Source: Reactome
  • positive regulation of epithelial cell migration Source: CACAO
  • positive regulation of wound healing Source: CACAO
  • spermatogenesis Source: ProtInc

Keywordsi

Molecular functionHormone

Enzyme and pathway databases

ReactomeiR-HSA-418555 G alpha (s) signalling events
R-HSA-444821 Relaxin receptors

Names & Taxonomyi

Protein namesi
Recommended name:
Insulin-like 3
Alternative name(s):
Leydig insulin-like peptide
Short name:
Ley-I-L
Relaxin-like factor
Cleaved into the following 2 chains:
Gene namesi
Name:INSL3
Synonyms:RLF, RLNL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000248099.3
HGNCiHGNC:6086 INSL3
MIMi146738 gene
neXtProtiNX_P51460

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Cryptorchidism (CRYPTO)3 Publications
The disease may be caused by mutations affecting the gene represented in this entry.
Disease descriptionOne of the most frequent congenital abnormalities in humans, involving 2-5% of male births. Cryptorchidism is associated with increased risk of infertility and testicular cancer.
See also OMIM:219050
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01323593P → L in CRYPTO. 1 PublicationCorresponds to variant dbSNP:rs104894697Ensembl.1
Natural variantiVAR_013236102R → C in CRYPTO. 1 PublicationCorresponds to variant dbSNP:rs104894698Ensembl.1
Natural variantiVAR_017122110N → K in CRYPTO. 1 PublicationCorresponds to variant dbSNP:rs121912555Ensembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi3640
MalaCardsiINSL3
MIMi219050 phenotype
OpenTargetsiENSG00000248099
PharmGKBiPA29893

Polymorphism and mutation databases

BioMutaiINSL3
DMDMi317373369

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 201 PublicationAdd BLAST20
PeptideiPRO_000001614021 – 55Insulin-like 3 B chainAdd BLAST35
PropeptideiPRO_000001614158 – 104C peptide likeSequence analysisAdd BLAST47
PeptideiPRO_0000016142106 – 131Insulin-like 3 A chainAdd BLAST26

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi34 ↔ 116Interchain (between B and A chains)
Disulfide bondi46 ↔ 129Interchain (between B and A chains)
Disulfide bondi115 ↔ 120

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond

Proteomic databases

PaxDbiP51460
PeptideAtlasiP51460
PRIDEiP51460

Expressioni

Tissue specificityi

Expressed in prenatal and postnatal Leydig cells. Found as well in the corpus luteum, trophoblast, fetal membranes and breast.1 Publication

Gene expression databases

BgeeiENSG00000248099
CleanExiHS_INSL3
HS_RLF
ExpressionAtlasiP51460 baseline and differential
GenevisibleiP51460 HS

Organism-specific databases

HPAiHPA028615

Interactioni

Subunit structurei

Heterodimer of a B chain and an A chain linked by two disulfide bonds.2 Publications

GO - Molecular functioni

  • hormone activity Source: UniProtKB-KW
  • insulin receptor binding Source: ProtInc
  • protease binding Source: UniProtKB
  • receptor binding Source: ProtInc

Protein-protein interaction databases

BioGridi1098519 interactors.
IntActiP51460 1 interactor.
STRINGi9606.ENSP00000321724

Structurei

Secondary structure

1131
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi36 – 46Combined sources11
Turni48 – 50Combined sources3
Helixi111 – 117Combined sources7
Helixi122 – 126Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2H8BNMR-A106-131[»]
B25-55[»]
2K6TNMR-A106-131[»]
B25-55[»]
2K6UNMR-A106-131[»]
B25-49[»]
ProteinModelPortaliP51460
SMRiP51460
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP51460

Family & Domainsi

Sequence similaritiesi

Belongs to the insulin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410J0IS Eukaryota
ENOG411140J LUCA
GeneTreeiENSGT00510000050366
HOGENOMiHOG000113077
HOVERGENiHBG052133
InParanoidiP51460
KOiK21999
OMAiCCSGWRD
OrthoDBiEOG091G128J
PhylomeDBiP51460
TreeFamiTF106361

Family and domain databases

InterProiView protein in InterPro
IPR016179 Insulin-like
IPR036438 Insulin-like_sf
IPR022353 Insulin_CS
PfamiView protein in Pfam
PF00049 Insulin, 1 hit
SMARTiView protein in SMART
SM00078 IlGF, 1 hit
SUPFAMiSSF56994 SSF56994, 2 hits
PROSITEiView protein in PROSITE
PS00262 INSULIN, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P51460-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDPRLPAWAL VLLGPALVFA LGPAPTPEMR EKLCGHHFVR ALVRVCGGPR
60 70 80 90 100
WSTEARRPAT GGDRELLQWL ERRHLLHGLV ADSNLTLGPG LQPLPQTSHH
110 120 130
HRHHRAAATN PARYCCLSGC TQQDLLTLCP Y
Length:131
Mass (Da):14,502
Last modified:January 11, 2011 - v2
Checksum:i94788D700524C12A
GO
Isoform 2 (identifier: P51460-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     64-131: RELLQWLERR...QQDLLTLCPY → QRESHSVSQA...ASVAVPNKTC

Note: No experimental confirmation available.
Show »
Length:157
Mass (Da):16,872
Checksum:i0D5CAAD5B548BC7A
GO

Sequence cautioni

The sequence CAA52017 differs from that shown. Reason: Erroneous gene model prediction.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01323124A → G1 PublicationCorresponds to variant dbSNP:rs186828508Ensembl.1
Natural variantiVAR_01323243V → L1 Publication1
Natural variantiVAR_01323349P → S Could be a rare polymorphism; identified in a male with undermasculinised genitalia and intra-abdominal testes. 1 PublicationCorresponds to variant dbSNP:rs751299877Ensembl.1
Natural variantiVAR_01323460T → A Common polymorphism. 11 PublicationsCorresponds to variant dbSNP:rs6523Ensembl.1
Natural variantiVAR_01323593P → L in CRYPTO. 1 PublicationCorresponds to variant dbSNP:rs104894697Ensembl.1
Natural variantiVAR_013236102R → C in CRYPTO. 1 PublicationCorresponds to variant dbSNP:rs104894698Ensembl.1
Natural variantiVAR_013237102R → H1 PublicationCorresponds to variant dbSNP:rs121912556Ensembl.1
Natural variantiVAR_017122110N → K in CRYPTO. 1 PublicationCorresponds to variant dbSNP:rs121912555Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04552664 – 131RELLQ…TLCPY → QRESHSVSQAGLKLLSSSNP PTLTFQSVGISDVSCYSGWR DDICSMGWWPTVISRWDLAC SPCPRPLTITATTVQLPPTL HATAASVAVPNKTC in isoform 2. 1 PublicationAdd BLAST68

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S72482 mRNA Translation: AAB31371.1
X73637 Genomic DNA Translation: CAA52017.1 Sequence problems.
AY082014 mRNA Translation: AAL92559.1
AK302780 mRNA Translation: BAG63984.1
AC005952 Genomic DNA No translation available.
AC007201 Genomic DNA Translation: AAD22740.1
CH471106 Genomic DNA Translation: EAW84635.1
BC032810 mRNA Translation: AAH32810.1
BC053345 mRNA Translation: AAH53345.1
BC071706 mRNA Translation: AAH71706.1
BC106721 mRNA Translation: AAI06722.1
BC106722 mRNA Translation: AAI06723.1
CCDSiCCDS12365.1 [P51460-1]
CCDS58655.1 [P51460-2]
PIRiB53024
RefSeqiNP_001252516.1, NM_001265587.1 [P51460-2]
NP_005534.2, NM_005543.3 [P51460-1]
UniGeneiHs.37062

Genome annotation databases

EnsembliENST00000317306; ENSP00000321724; ENSG00000248099 [P51460-1]
ENST00000379695; ENSP00000369017; ENSG00000248099 [P51460-2]
GeneIDi3640
KEGGihsa:3640
UCSCiuc002nhm.3 human [P51460-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiINSL3_HUMAN
AccessioniPrimary (citable) accession number: P51460
Secondary accession number(s): B4DZ72
, G3XAG0, Q3KPI5, Q3KPI6, Q6YNB5, Q9UEA2, Q9UPH6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 11, 2011
Last modified: February 28, 2018
This is version 161 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome