P04090 (REL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Prorelaxin H2

Cleaved into the following 2 chains:

1. Relaxin B chain
2. Relaxin A chain

Gene names

Name:

RLN2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	185 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	Relaxin is an ovarian hormone that acts with estrogen to produce dilatation of the birth canal in many mammals. May be involved in remodeling of connective tissues during pregnancy, promoting growth of pubic ligaments and ripening of the cervix.
Subunit structure	Heterodimer of a B chain and an A chain linked by two disulfide bonds.
Subcellular location	Secreted.
Tissue specificity	Isoform 1 is expressed in the ovary during pregnancy. Also expressed in placenta, decidua and prostate. Isoform 2 is relatively abundant in placenta. It is in much lower abundance in the prostate gland. Not detected in the ovary. Ref.1 Ref.4
Sequence similarities	Belongs to the insulin family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing 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)
Biological process	female pregnancy Traceable author statement. Source: ProtInc
Cellular component	extracellular region Traceable author statement. Source: Reactome
Molecular function	hormone activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P04090-1)

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.

Isoform 2 (identifier: P04090-2)

The sequence of this isoform differs from the canonical sequence as follows:
     71-117: EIVPSFINKD...ALPQLQQHVP → GDFIQTVSLG...HPSSTKIQKP
     118-185: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 24

24

Ref.6 Ref.7

Peptide

25 – 53

29

Relaxin B chain Ref.7

PRO_0000016079

Propeptide

56 – 157

102

Connecting peptide

PRO_0000016080

Peptide

162 – 185

24

Relaxin A chain

PRO_0000016081

Amino acid modifications

Modified residue

162

1

Pyrrolidone carboxylic acid Ref.7

Disulfide bond

35 ↔ 172

Interchain (between B and A chains)

Disulfide bond

47 ↔ 185

Interchain (between B and A chains)

Disulfide bond

171 ↔ 176

Ref.8

Natural variations

Alternative sequence

71 – 117

47

EIVPS…QQHVP → GDFIQTVSLGISPDGGKALR TGSCFTREFLGALSKLCHPS STKIQKP in isoform 2.

VSP_002711

Alternative sequence

118 – 185

68

Missing in isoform 2.

VSP_002712

Natural variant

12

1

V → F.
Corresponds to variant rs2020050 [ dbSNP | Ensembl ].

VAR_050007

Natural variant

28

1

M → K.
Corresponds to variant rs618066 [ dbSNP | Ensembl ].

VAR_034444

Natural variant

68

1

P → Q.
Corresponds to variant rs2273783 [ dbSNP | Ensembl ].

VAR_022124

Secondary structure

1

.

.

.

.

.

.

.

.

.

185

Helix Strand Turn

Details...

Helix

27 – 29

3

Helix

36 – 49

14

Helix

163 – 173

11

Helix

178 – 182

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1986. Version 1. Checksum: AC73DBDE2090091B	FASTA	185	21,043
	10 20 30 40 50 60 MPRLFFFHLL GVCLLLNQFS RAVADSWMEE VIKLCGRELV RAQIAICGMS TWSKRSLSQE 70 80 90 100 110 120 DAPQTPRPVA EIVPSFINKD TETINMMSEF VANLPQELKL TLSEMQPALP QLQQHVPVLK 130 140 150 160 170 180 DSSLLFEEFK KLIRNRQSEA ADSSPSELKY LGLDTHSRKK RQLYSALANK CCHVGCTKRS LARFC
	Isoform 2 [UniParc]. Checksum: 087AE9F24582740A	FASTA	117	12,883
	10 20 30 40 50 60 MPRLFFFHLL GVCLLLNQFS RAVADSWMEE VIKLCGRELV RAQIAICGMS TWSKRSLSQE 70 80 90 100 110 DAPQTPRPVA GDFIQTVSLG ISPDGGKALR TGSCFTREFL GALSKLCHPS STKIQKP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Relaxin gene expression in human ovaries and the predicted structure of a human preprorelaxin by analysis of cDNA clones." Hudson P., John M., Crawford R., Haralambidis J., Scanlon D., Gorman J., Tregear G., Shine J., Niall H. EMBO J. 3:2333-2339(1984) [PubMed: 6548702] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[2]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[4]	"Expression of human relaxin genes: characterization of a novel alternatively-spliced human relaxin mRNA species." Gunnersen J.M., Fu P., Roche P.J., Tregear G.W. Mol. Cell. Endocrinol. 118:85-94(1996) [PubMed: 8735594] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 71-185 (ISOFORM 2), TISSUE SPECIFICITY. Tissue: Prostate.
[5]	"Analysis of the 5'-upstream regions of the human relaxin H1 and H2 genes and their chromosomal localization on chromosome 9p24.1 by radiation hybrid and breakpoint mapping." Garibay-Tupas J.L., Csiszar K., Fox M., Povey S., Bryant-Greenwood G.D. J. Mol. Endocrinol. 23:355-365(1999) [PubMed: 10601981] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-15.
[6]	"Human seminal relaxin is a product of the same gene as human luteal relaxin." Winslow J.W., Shih A., Bourell J.H., Weiss G., Reed B., Stults J.T., Goldsmith L.T. Endocrinology 130:2660-2668(1992) [PubMed: 1572287] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-51. Tissue: Semen.
[7]	"Structural characterization by mass spectrometry of native and recombinant human relaxin." Winslow J.W., Griffin P.R., Rinderknecht E., Vandlen R.L. Biomed. Environ. Mass Spectrom. 19:655-664(1990) [PubMed: 2076464] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-53 AND 162-185 (ISOFORM 1), PYROGLUTAMATE FORMATION AT GLN-162.
[8]	"Total synthesis of human relaxin and human relaxin derivatives by solid-phase peptide synthesis and site-directed chain combination." Buellesbach E.E., Schwabe C. J. Biol. Chem. 266:10754-10761(1991) [PubMed: 2040595] [Abstract] Cited for: SYNTHESIS.
[9]	"X-ray structure of human relaxin at 1.5 A. Comparison to insulin and implications for receptor binding determinants." Eigenbrot C., Randal M., Quan C., Burnier J., O'Connell L., Rinderknecht E., Kossiakoff A.A. J. Mol. Biol. 221:15-21(1991) [PubMed: 1656049] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X00948 mRNA. Translation: CAA25460.1.
AL135786 Genomic DNA. Translation: CAC04177.1.
BC126415 mRNA. Translation: AAI26416.1.
BC126419 mRNA. Translation: AAI26420.1.
S83200 Genomic DNA. Translation: AAD14429.1. Sequence problems.
AF104935 Genomic DNA. Translation: AAD21961.1.

IPI

IPI00021836.
IPI00218018.

PIR

A60982. A05092.

RefSeq

NP_005050.2. NM_005059.2.
NP_604390.1. NM_134441.1.

UniGene

Hs.127032.
Hs.368996.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
6RLX	X-ray	1.50	A/C	163-185	[»]
			B/D	26-53	[»]

ProteinModelPortal

P04090.

SMR

P04090. Positions 26-52, 156-185.

ModBase

Search...

Protein-protein interaction databases

STRING

P04090.

PTM databases

PhosphoSite

P04090.

Polymorphism databases

DMDM

132281.

Proteomic databases

PRIDE

P04090.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000381627; ENSP00000371040; ENSG00000107014.

GeneID

6019.

KEGG

hsa:6019.

UCSC

uc003zja.1. human.

Organism-specific databases

CTD

6019.

GeneCards

GC09M005289.

H-InvDB

HIX0034906.

HGNC

HGNC:10027. RLN2.

MIM

179740. gene.

neXtProt

NX_P04090.

PharmGKB

PA34400.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG21582.

GeneTree

ENSGT00510000048834.

HOGENOM

HBG125785.

HOVERGEN

HBG003234.

InParanoid

P04090.

OMA

MSEFVAN.

OrthoDB

EOG495ZT1.

PhylomeDB

P04090.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P04090.

Bgee

P04090.

CleanEx

HS_RLN2.

Genevestigator

P04090.

GermOnline

ENSG00000107014. Homo sapiens.

Family and domain databases

InterPro

IPR016179. Insulin-like.
IPR022353. Insulin_CS.
IPR022352. Insulin_family.
IPR022421. Relaxin.
[Graphical view]

Gene3D

G3DSA:1.10.100.10. Ins/IGF/relaxin. 2 hits.

KO

K05255.

Pfam

PF00049. Insulin. 1 hit.
[Graphical view]

PRINTS

PR00276. INSULINFAMLY.
PR02004. RELAXIN.

SMART

SM00078. IlGF. 1 hit.
[Graphical view]

SUPFAM

SSF56994. Insulin-like. 1 hit.

PROSITE

PS00262. INSULIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

23483.

SOURCE

Search...

Entry information

Entry name

REL2_HUMAN

Accession

Primary (citable) accession number: P04090
Secondary accession number(s): A0AVM0 , Q99936, Q9UCX3, Q9UQJ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1986
Last sequence update:	November 1, 1986
Last modified:	January 25, 2012
This is version 127 of the entry and version 1 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.