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Protein

Insulin-like 3

Gene

INSL3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.

GO - Molecular functioni

  • insulin receptor binding Source: ProtInc
  • protease binding Source: UniProtKB
  • receptor binding Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hormone

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

HGNCiHGNC:6086. INSL3.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti93 – 931P → L in CRYPTO. 1 Publication
Corresponds to variant rs104894697 [ dbSNP | Ensembl ].
VAR_013235
Natural varianti102 – 1021R → C in CRYPTO. 1 Publication
Corresponds to variant rs104894698 [ dbSNP | Ensembl ].
VAR_013236
Natural varianti110 – 1101N → K in CRYPTO. 1 Publication
Corresponds to variant rs121912555 [ dbSNP | Ensembl ].
VAR_017122

Keywords - Diseasei

Disease mutation

Organism-specific databases

MalaCardsiINSL3.
MIMi219050. phenotype.
PharmGKBiPA29893.

Polymorphism and mutation databases

BioMutaiINSL3.
DMDMi317373369.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 20201 PublicationAdd
BLAST
Peptidei21 – 5535Insulin-like 3 B chainPRO_0000016140Add
BLAST
Propeptidei58 – 10447C peptide likeSequence analysisPRO_0000016141Add
BLAST
Peptidei106 – 13126Insulin-like 3 A chainPRO_0000016142Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
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

  • insulin receptor binding Source: ProtInc
  • protease binding Source: UniProtKB
  • receptor binding Source: ProtInc

Protein-protein interaction databases

BioGridi109851. 9 interactions.
STRINGi9606.ENSP00000321724.

Structurei

Secondary structure

1
131
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi36 – 4611Combined sources
Turni48 – 503Combined sources
Helixi111 – 1177Combined sources
Helixi122 – 1265Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2H8BNMR-A106-131[»]
B25-55[»]
2K6TNMR-A106-131[»]
B25-55[»]
2K6UNMR-A106-131[»]
B25-49[»]
ProteinModelPortaliP51460.
SMRiP51460. Positions 25-55, 106-131.
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.
KOiK05255.
OMAiCCSGWRD.
OrthoDBiEOG091G128J.
PhylomeDBiP51460.
TreeFamiTF106361.

Family and domain databases

Gene3Di1.10.100.10. 2 hits.
InterProiIPR016179. Insulin-like.
IPR022353. Insulin_CS.
[Graphical view]
PfamiPF00049. Insulin. 1 hit.
[Graphical view]
SMARTiSM00078. IlGF. 1 hit.
[Graphical view]
SUPFAMiSSF56994. SSF56994. 2 hits.
PROSITEiPS00262. INSULIN. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti24 – 241A → G.1 Publication
Corresponds to variant rs186828508 [ dbSNP | Ensembl ].
VAR_013231
Natural varianti43 – 431V → L.1 Publication
VAR_013232
Natural varianti49 – 491P → S Could be a rare polymorphism; identified in a male with undermasculinised genitalia and intra-abdominal testes. 1 Publication
Corresponds to variant rs751299877 [ dbSNP | Ensembl ].
VAR_013233
Natural varianti60 – 601T → A Common polymorphism. 11 Publications
Corresponds to variant rs6523 [ dbSNP | Ensembl ].
VAR_013234
Natural varianti93 – 931P → L in CRYPTO. 1 Publication
Corresponds to variant rs104894697 [ dbSNP | Ensembl ].
VAR_013235
Natural varianti102 – 1021R → C in CRYPTO. 1 Publication
Corresponds to variant rs104894698 [ dbSNP | Ensembl ].
VAR_013236
Natural varianti102 – 1021R → H.1 Publication
Corresponds to variant rs121912556 [ dbSNP | Ensembl ].
VAR_013237
Natural varianti110 – 1101N → K in CRYPTO. 1 Publication
Corresponds to variant rs121912555 [ dbSNP | Ensembl ].
VAR_017122

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei64 – 13168RELLQ…TLCPY → QRESHSVSQAGLKLLSSSNP PTLTFQSVGISDVSCYSGWR DDICSMGWWPTVISRWDLAC SPCPRPLTITATTVQLPPTL HATAASVAVPNKTC in isoform 2. 1 PublicationVSP_045526Add
BLAST

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

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2H8BNMR-A106-131[»]
B25-55[»]
2K6TNMR-A106-131[»]
B25-55[»]
2K6UNMR-A106-131[»]
B25-49[»]
ProteinModelPortaliP51460.
SMRiP51460. Positions 25-55, 106-131.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109851. 9 interactions.
STRINGi9606.ENSP00000321724.

Polymorphism and mutation databases

BioMutaiINSL3.
DMDMi317373369.

Proteomic databases

PaxDbiP51460.
PeptideAtlasiP51460.
PRIDEiP51460.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi3640.
GeneCardsiINSL3.
H-InvDBHIX0014900.
HGNCiHGNC:6086. INSL3.
HPAiHPA028615.
MalaCardsiINSL3.
MIMi146738. gene.
219050. phenotype.
neXtProtiNX_P51460.
PharmGKBiPA29893.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J0IS. Eukaryota.
ENOG411140J. LUCA.
GeneTreeiENSGT00510000050366.
HOGENOMiHOG000113077.
HOVERGENiHBG052133.
InParanoidiP51460.
KOiK05255.
OMAiCCSGWRD.
OrthoDBiEOG091G128J.
PhylomeDBiP51460.
TreeFamiTF106361.

Enzyme and pathway databases

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

Miscellaneous databases

EvolutionaryTraceiP51460.
GeneWikiiINSL3.
GenomeRNAii3640.
PROiP51460.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000248099.
CleanExiHS_INSL3.
HS_RLF.
ExpressionAtlasiP51460. baseline and differential.
GenevisibleiP51460. HS.

Family and domain databases

Gene3Di1.10.100.10. 2 hits.
InterProiIPR016179. Insulin-like.
IPR022353. Insulin_CS.
[Graphical view]
PfamiPF00049. Insulin. 1 hit.
[Graphical view]
SMARTiSM00078. IlGF. 1 hit.
[Graphical view]
SUPFAMiSSF56994. SSF56994. 2 hits.
PROSITEiPS00262. INSULIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiINSL3_HUMAN
AccessioniPrimary (citable) accession number: P51460
Secondary accession number(s): B4DZ72
, G3XAG0, Q3KPI5, Q3KPI6, Q6YNB5, Q9UEA2, Q9UPH6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 11, 2011
Last modified: September 7, 2016
This is version 150 of the entry and version 2 of the sequence. [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

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.