P01236 (PRL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Prolactin
Short name=PRL

Gene names

Name:

PRL

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	227 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	Prolactin acts primarily on the mammary gland by promoting lactation.
Subcellular location	Secreted.
Sequence similarities	Belongs to the somatotropin/prolactin family.
Sequence caution	The sequence CAA38264.1 differs from that shown. Reason: Frameshift at position 8.

Ontologies

Keywords
Biological process	Lactation
Cellular component	Secreted
Domain	Signal
Molecular function	Hormone
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	JAK-STAT cascade involved in growth hormone signaling pathway Traceable author statement. Source: Reactome cell proliferation Traceable author statement PubMed 10854700. Source: ProtInc female pregnancy Non-traceable author statement PubMed 7221563. Source: ProtInc lactation Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of JAK-STAT cascade Inferred from direct assay PubMed 12552091. Source: BHF-UCL regulation of multicellular organism growth Inferred from expression pattern PubMed 8421089. Source: BHF-UCL
Cellular_component	extracellular region Traceable author statement. Source: Reactome
Molecular_function	prolactin receptor binding Traceable author statement PubMed 10854700. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 28

28

Ref.7 Ref.8

Chain

29 – 227

199

Prolactin

PRO_0000032916

Amino acid modifications

Modified residue

54

1

Phosphoserine By similarity

Modified residue

62

1

Phosphoserine By similarity

Modified residue

118

1

Phosphoserine By similarity

Modified residue

163

1

Phosphoserine Ref.9

Modified residue

194

1

Phosphoserine Ref.9

Glycosylation

59

1

N-linked (GlcNAc...); partial

Disulfide bond

32 ↔ 39

Ref.13

Disulfide bond

86 ↔ 202

Ref.13

Disulfide bond

219 ↔ 227

Ref.13

Experimental info

Mutagenesis

157

1

G → D, F, L, N, R, V or Y: Inhibits signaling via PRLR; mutant PRL acts as PRLR antagonist. Ref.12

Sequence conflict

42

1

T → A in AAB70858. Ref.6

Sequence conflict

110 – 111

2

SL → VS AA sequence Ref.7

Sequence conflict

113 – 114

2

VS → L AA sequence Ref.7

Sequence conflict

118

1

S → P in AAB70858. Ref.6

Sequence conflict

148

1

E → Q in BAA00312. Ref.5

Sequence conflict

172

1

N → D AA sequence Ref.7

Sequence conflict

190 – 191

2

ES → SE AA sequence Ref.7

Sequence conflict

206

1

D → H in AAA60173. Ref.5

Sequence conflict

206

1

D → H in BAA00312. Ref.5

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

227

Helix Strand Turn

Details...

Beta strand

31 – 34

4

Helix

43 – 72

30

Turn

73 – 75

3

Helix

78 – 82

5

Turn

87 – 90

4

Helix

97 – 102

6

Helix

105 – 118

14

Helix

120 – 131

12

Beta strand

133 – 135

3

Helix

138 – 165

28

Beta strand

166 – 168

3

Helix

181 – 185

5

Helix

189 – 223

35

Sequences

	Sequence		Length	Mass (Da)
	P01236 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 952BBA1B6A955527	FASTA	227	25,876
	10 20 30 40 50 60 MNIKGSPWKG SLLLLLVSNL LLCQSVAPLP ICPGGAARCQ VTLRDLFDRA VVLSHYIHNL 70 80 90 100 110 120 SSEMFSEFDK RYTHGRGFIT KAINSCHTSS LATPEDKEQA QQMNQKDFLS LIVSILRSWN 130 140 150 160 170 180 EPLYHLVTEV RGMQEAPEAI LSKAVEIEEQ TKRLLEGMEL IVSQVHPETK ENEIYPVWSG 190 200 210 220 LPSLQMADEE SRLSAYYNLL HCLRRDSHKI DNYLKLLKCR IIHNNNC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human prolactin. cDNA structural analysis and evolutionary comparisons." Cooke N.E., Coit D., Shine J., Baxter J.D., Martial J.A. J. Biol. Chem. 256:4007-4016(1981) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Isolation and characterization of the human prolactin gene." Truong A.T., Duez C., Belayew A., Renard A., Pictet R.L., Bell G.I., Martial J.A. EMBO J. 3:429-437(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"A placenta-specific 5'non-coding exon of human prolactin." Hiraoka Y., Tatsumi K., Shiozawa M., Aiso S., Fukasawa T., Yasuda K., Miyai K. Mol. Cell. Endocrinol. 75:71-80(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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]. Tissue: Testis.
[5]	"Molecular cloning and nucleotide sequence of DNA complementary to human decidual prolactin mRNA." Takahashi H., Nabeshima Y., Nabeshima Y., Ogata K., Takeuchi S. J. Biochem. 95:1491-1499(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 11-227.
[6]	"Expression of the prolactin gene in normal and neoplastic human breast tissues and human mammary cell lines: promoter usage and alternative mRNA splicing." Shaw-Bruha C.M., Pirrucello S.J., Shull J.D. Breast Cancer Res. Treat. 44:243-253(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 11-201. Tissue: Mammary gland.
[7]	"Human pituitary prolactin (hPRL): the entire linear amino acid sequence." Shome B., Parlow A.F. J. Clin. Endocrinol. Metab. 45:1112-1115(1977) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 29-227.
[8]	"High sensitivity automated sequence determination of polypeptides." Jacobs J.W., Niall H.D. J. Biol. Chem. 250:3629-3636(1975) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 29-53.
[9]	"Immunoglobulin G subclasses and prolactin (PRL) isoforms in macroprolactinemia due to anti-PRL autoantibodies." Hattori N., Ikekubo K., Nakaya Y., Kitagawa K., Inagaki C. J. Clin. Endocrinol. Metab. 90:3036-3044(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-163 AND SER-194.
[10]	"The tertiary structure and backbone dynamics of human prolactin." Keeler C., Dannies P.S., Hodsdon M.E. J. Mol. Biol. 328:1105-1121(2003) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 29-227.
[11]	"Solution structure of human prolactin." Teilum K., Hoch J.C., Goffin V., Kinet S., Martial J.A., Kragelund B.B. J. Mol. Biol. 351:810-823(2005) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 29-227, INTERACTION WITH PRLR.
[12]	"Structural and thermodynamic bases for the design of pure prolactin receptor antagonists: X-ray structure of Del1-9-G129R-hPRL." Jomain J.-B., Tallet E., Broutin I., Hoos S., van Agthoven J., Ducruix A., Kelly P.A., Kragelund B.B., England P., Goffin V. J. Biol. Chem. 282:33118-33131(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 38-227, MUTAGENESIS OF GLY-157.
[13]	"Crystal structure of a prolactin receptor antagonist bound to the extracellular domain of the prolactin receptor." Svensson L.A., Bondensgaard K., Noerskov-Lauritsen L., Christensen L., Becker P., Andersen M.D., Maltesen M.J., Rand K.D., Breinholt J. J. Biol. Chem. 283:19085-19094(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 41-227 IN COMPLEX WITH PRLR, MASS SPECTROMETRY, DISULFIDE BONDS.
+	Additional computationally mapped references.

Web resources

Wikipedia

Prolactin entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

V00566 mRNA. Translation: CAA23829.1.
X00540 , X00541, X00543, X00544 Genomic DNA. Translation: CAA25214.1.
X54393 mRNA. Translation: CAA38263.1. Frameshift.
X54393 mRNA. Translation: CAA38264.1. Frameshift.
BC015850 mRNA. Translation: AAH15850.1.
M29386 mRNA. Translation: AAA60173.1.
D00411 mRNA. Translation: BAA00312.1.
U75583 mRNA. Translation: AAB70858.1.

IPI

IPI00000871.

PIR

A61402.
LCHU. A90998.

RefSeq

NP_000939.1. NM_000948.5.
NP_001157030.1. NM_001163558.2.

UniGene

Hs.1905.
Hs.735971.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1RW5	NMR	-	A	29-227	[»]
2Q98	X-ray	2.70	A	40-227	[»]
3D48	X-ray	2.50	P	41-227	[»]
3EW3	X-ray	3.80	A	43-227	[»]
3MZG	X-ray	2.10	A	43-227	[»]
3N06	X-ray	2.00	A	43-227	[»]
3N0P	X-ray	2.10	A	43-227	[»]
3NCB	X-ray	2.10	A	43-227	[»]
3NCC	X-ray	2.50	A	43-227	[»]
3NCE	X-ray	2.00	A	43-227	[»]
3NCF	X-ray	2.80	A	43-227	[»]
3NPZ	X-ray	3.35	A	29-227	[»]

ProteinModelPortal

P01236.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-59635N.

STRING

9606.ENSP00000302150.

PTM databases

PhosphoSite

P01236.

Polymorphism databases

DMDM

130930.

Proteomic databases

PaxDb

P01236.

PRIDE

P01236.

Protocols and materials databases

DNASU

5617.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000306482; ENSP00000302150; ENSG00000172179.

GeneID

5617.

KEGG

hsa:5617.

UCSC

uc003ndp.3. human.

Organism-specific databases

CTD

5617.

GeneCards

GC06M022230.

HGNC

HGNC:9445. PRL.

HPA

CAB023353.

MIM

176760. gene.

neXtProt

NX_P01236.

PharmGKB

PA33790.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG47376.

HOGENOM

HOG000264241.

HOVERGEN

HBG104895.

KO

K05439.

OMA

SLQMADE.

OrthoDB

EOG4FFD32.

PhylomeDB

P01236.

Enzyme and pathway databases

Pathway_Interaction_DB

ptp1bpathway. Signaling events mediated by PTP1B.

Reactome

REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P01236.

Bgee

P01236.

CleanEx

HS_PRL.

Genevestigator

P01236.

GermOnline

ENSG00000172179. Homo sapiens.

Family and domain databases

Gene3D

1.20.1250.10. 1 hit.

InterPro

IPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR001400. Somatotropin.
IPR018116. Somatotropin_CS.
[Graphical view]

PANTHER

PTHR11417. PTHR11417. 1 hit.

Pfam

PF00103. Hormone_1. 1 hit.
[Graphical view]

PRINTS

PR00836. SOMATOTROPIN.

SUPFAM

SSF47266. 4_helix_cytokine. 1 hit.

PROSITE

PS00266. SOMATOTROPIN_1. 1 hit.
PS00338. SOMATOTROPIN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

PRL. human.

EvolutionaryTrace

P01236.

GenomeRNAi

5617.

NextBio

21828.

PMAP-CutDB

P01236.

SOURCE

Search...

Entry information

Entry name

PRL_HUMAN

Accession

Primary (citable) accession number: P01236
Secondary accession number(s): Q15199, Q92996

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	May 1, 2013
This is version 141 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.