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P30874 (SSR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Somatostatin receptor type 2

Short name=SS-2-R
Short name=SS2-R
Short name=SS2R
Alternative name(s):
SRIF-1
Gene names
Name:SSTR2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length369 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Receptor for somatostatin-14 and -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. In addition it stimulates phosphotyrosine phosphatase and PLC via pertussis toxin insensitive as well as sensitive G proteins. Inhibits calcium entry by suppressing voltage-dependent calcium channels. Acts as the functionally dominant somatostatin receptor in pancreatic alpha- and beta-cells where it mediates the inhibitory effect of somatostatin-14 on hormone secretion. Inhibits cell growth through enhancement of MAPK1 and MAPK2 phosphorylation and subsequent up-regulation of CDKN1B. Stimulates neuronal migration and axon outgrowth and may participate in neuron development and maturation during brain development. Mediates negative regulation of insulin receptor signaling through PTPN6. Inactivates SSTR3 receptor function following heterodimerization. Ref.10 Ref.11 Ref.12 Ref.13 Ref.14

Subunit structure

Homodimer and heterodimer with SSTR3 and SSTR5. Heterodimerization with SSTR3 inactivates SSTR3 receptor function. Heterodimerization with SSTR5 is enhanced by agonist stimulation of SSTR2 and increases SSTR2 cell growth inhibition activity. Following agonist stimulation, homodimers dissociate into monomers which is required for receptor internalization. Interacts with beta-arrestin; this interaction is necessary for receptor internalization and is destabilized by heterodimerization with SSTR5 which results in increased recycling of SSTR2 to the cell surface. Interacts (via C-terminus) with SHANK1 (via PDZ domain). Ref.9 Ref.10 Ref.11

Subcellular location

Cell membrane; Multi-pass membrane protein. Cytoplasm. Note: Located mainly at the cell surface under basal conditions. Agonist stimulation results in internalization to the cytoplasm. Ref.10 Ref.11 Ref.14

Tissue specificity

Expressed in both pancreatic alpha- and beta-cells (at protein level). Expressed at higher levels in the pancreas than other somatostatin receptors. Also expressed in the cerebrum and kidney and, in lesser amounts, in the jejunum, colon and liver. In the developing nervous system, expressed in the cortex where it is located in the preplate at early stages and is enriched in the outer part of the germinal zone at later stages. In the cerebellum, expressed in the deep part of the external granular layer at gestational week 19. This pattern persists until birth but disappears at adulthood. Ref.12 Ref.13

Post-translational modification

Phosphorylated on serine and threonine residues in response to agonist stimulation, leading to receptor desensitization and rapid internalization. Phosphorylated to a greater extent on serine than threonine residues. Threonine phosphorylation is required for arrestin binding and receptor endocytosis but is not necessary for desensitization By similarity.

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
   Cellular componentCell membrane
Cytoplasm
Membrane
   Coding sequence diversityAlternative splicing
   DomainTransmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Lipoprotein
Palmitate
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger

Traceable author statement PubMed 7914078. Source: ProtInc

adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

cell-cell signaling

Traceable author statement Ref.1. Source: ProtInc

cellular response to estradiol stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to glucocorticoid stimulus

Inferred from electronic annotation. Source: Ensembl

cerebellum development

Inferred from electronic annotation. Source: Ensembl

digestion

Traceable author statement Ref.1. Source: ProtInc

forebrain development

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell proliferation

Traceable author statement PubMed 9892014. Source: ProtInc

peristalsis

Inferred from electronic annotation. Source: Ensembl

regulation of muscle contraction

Inferred from electronic annotation. Source: Ensembl

response to nutrient

Traceable author statement Ref.1. Source: ProtInc

response to starvation

Inferred from electronic annotation. Source: Ensembl

spermatogenesis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of plasma membrane

Traceable author statement PubMed 7914078. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionPDZ domain binding

Inferred from physical interaction Ref.9. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.9. Source: UniProtKB

somatostatin receptor activity

Traceable author statement PubMed 7914078. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PIK3R1P279865EBI-6266898,EBI-79464
SSTR3P327453EBI-6266898,EBI-6266935

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform A (identifier: P30874-1)

Also known as: SSTR2A;

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 B (identifier: P30874-2)

Also known as: SSTR2B;

The sequence of this isoform differs from the canonical sequence as follows:
     332-369: VSGTDDGERSDSKQDKSRLNETTETQRTLLNGDLQTSI → VDNSKSGEEGSCLDMIFRNNKNRKK

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 369369Somatostatin receptor type 2
PRO_0000070120

Regions

Topological domain1 – 4343Extracellular Potential
Transmembrane44 – 6724Helical; Name=1; Potential
Topological domain68 – 7811Cytoplasmic Potential
Transmembrane79 – 10325Helical; Name=2; Potential
Topological domain104 – 11815Extracellular Potential
Transmembrane119 – 13820Helical; Name=3; Potential
Topological domain139 – 16123Cytoplasmic Potential
Transmembrane162 – 18120Helical; Name=4; Potential
Topological domain182 – 20726Extracellular Potential
Transmembrane208 – 22922Helical; Name=5; Potential
Topological domain230 – 25324Cytoplasmic Potential
Transmembrane254 – 27825Helical; Name=6; Potential
Topological domain279 – 28810Extracellular Potential
Transmembrane289 – 30315Helical; Name=7; Potential
Topological domain304 – 36966Cytoplasmic Potential

Sites

Site891Important for ligand binding

Amino acid modifications

Modified residue3411Phosphoserine By similarity
Modified residue3431Phosphoserine By similarity
Modified residue3481Phosphoserine By similarity
Modified residue3531Phosphothreonine By similarity
Modified residue3541Phosphothreonine By similarity
Lipidation3281S-palmitoyl cysteine Potential
Glycosylation91N-linked (GlcNAc...) Potential
Glycosylation221N-linked (GlcNAc...) Potential
Glycosylation291N-linked (GlcNAc...) Potential
Glycosylation321N-linked (GlcNAc...) Potential
Disulfide bond115 ↔ 193 By similarity

Natural variations

Alternative sequence332 – 36938VSGTD…LQTSI → VDNSKSGEEGSCLDMIFRNN KNRKK in isoform B.
VSP_001922

Experimental info

Mutagenesis891D → A: Expression levels reduced by 60%. Ref.14
Mutagenesis891D → L: Expression levels reduced by 80%. Ref.14
Mutagenesis891D → R: Slightly reduced expression levels. Remains localized in membrane. Abolishes ligand binding and G protein-mediated calcium release. Ref.14
Mutagenesis1391D → A: Expression levels reduced by 50%. Significantly reduced ligand binding capacity but increased affinity. Reduced G protein-mediated cAMP release but no effect on G-protein mediated calcium release. Ref.14
Mutagenesis1391D → N: Expression levels reduced by 40%. No significant change in ligand binding capacity or affinity. Reduced G protein-mediated cAMP signaling but no effect on G protein-mediated calcium release. Ref.14
Mutagenesis1401R → A: Slightly reduced expression levels. No significant change in ligand binding capacity or affinity. No significant change in G protein-mediated cAMP or calcium release. Ref.14
Mutagenesis1401R → E: Almost abolishes expression. Abolishes membrane localization. Ref.14
Mutagenesis1401R → L: Slightly reduced expression levels. Significantly reduced ligand binding capacity but increased affinity. Reduced G protein-mediated cAMP release but no effect on G protein-mediated calcium release. Ref.14
Sequence conflict771I → T in BAG36594. Ref.5
Sequence conflict1221D → N in BAG36594. Ref.5
Sequence conflict3561T → A in BAG36594. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Isoform A (SSTR2A) [UniParc].

Last modified July 1, 1993. Version 1.
Checksum: 3B5D7D8A9AC246C6

FASTA36941,333
        10         20         30         40         50         60 
MDMADEPLNG SHTWLSIPFD LNGSVVSTNT SNQTEPYYDL TSNAVLTFIY FVVCIIGLCG 

        70         80         90        100        110        120 
NTLVIYVILR YAKMKTITNI YILNLAIADE LFMLGLPFLA MQVALVHWPF GKAICRVVMT 

       130        140        150        160        170        180 
VDGINQFTSI FCLTVMSIDR YLAVVHPIKS AKWRRPRTAK MITMAVWGVS LLVILPIMIY 

       190        200        210        220        230        240 
AGLRSNQWGR SSCTINWPGE SGAWYTGFII YTFILGFLVP LTIICLCYLF IIIKVKSSGI 

       250        260        270        280        290        300 
RVGSSKRKKS EKKVTRMVSI VVAVFIFCWL PFYIFNVSSV SMAISPTPAL KGMFDFVVVL 

       310        320        330        340        350        360 
TYANSCANPI LYAFLSDNFK KSFQNVLCLV KVSGTDDGER SDSKQDKSRL NETTETQRTL 


LNGDLQTSI 

« Hide

Isoform B (SSTR2B) [UniParc].

Checksum: D10FA237FAED61F3
Show »

FASTA35640,007

References

« Hide 'large scale' references
[1]"Cloning and functional characterization of a family of human and mouse somatostatin receptors expressed in brain, gastrointestinal tract, and kidney."
Yamada Y., Post S.R., Wang K., Tager H.S., Bell G.I., Seino S.
Proc. Natl. Acad. Sci. U.S.A. 89:251-255(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM A).
[2]"Genomic structure and transcriptional regulation of the human somatostatin receptor type 2."
Petersenn S., Rasch A.C., Presch S., Beil F.U., Schulte H.M.
Mol. Cell. Endocrinol. 157:75-85(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS A AND B).
[3]"Isolation of complete coding sequence for somatostatin receptor 2 (SSTR2)."
Kopatz S.A., Aronstam R.S., Sharma S.V.
Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Genome-wide discovery and analysis of human seven transmembrane helix receptor genes."
Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S., Tsutsumi S., Aburatani H., Asai K., Akiyama Y.
Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
[6]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
[7]"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] (ISOFORM A).
Tissue: Eye.
[8]"Multiple gene transcripts of the somatostatin receptor SSTR2: tissue selective distribution and cAMP regulation."
Patel Y.C., Greenwood M., Kent G., Panetta R., Srikant C.B.
Biochem. Biophys. Res. Commun. 192:288-294(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORMS A AND B).
[9]"Somatostatin receptor interacting protein defines a novel family of multidomain proteins present in human and rodent brain."
Zitzer H., Hoenck H.-H., Baechner D., Richter D., Kreienkamp H.-J.
J. Biol. Chem. 274:32997-33001(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SHANK1.
[10]"Agonist-dependent dissociation of human somatostatin receptor 2 dimers: a role in receptor trafficking."
Grant M., Collier B., Kumar U.
J. Biol. Chem. 279:36179-36183(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION.
[11]"Cell growth inhibition and functioning of human somatostatin receptor type 2 are modulated by receptor heterodimerization."
Grant M., Alturaihi H., Jaquet P., Collier B., Kumar U.
Mol. Endocrinol. 22:2278-2292(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, INTERACTION WITH BETA-ARRESTIN, SUBCELLULAR LOCATION.
[12]"The somatostatin 2A receptor is enriched in migrating neurons during rat and human brain development and stimulates migration and axonal outgrowth."
Le Verche V., Kaindl A.M., Verney C., Csaba Z., Peineau S., Olivier P., Adle-Biassette H., Leterrier C., Vitalis T., Renaud J., Dargent B., Gressens P., Dournaud P.
PLoS ONE 4:E5509-E5509(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[13]"SSTR2 is the functionally dominant somatostatin receptor in human pancreatic beta- and alpha-cells."
Kailey B., van de Bunt M., Cheley S., Johnson P.R., MacDonald P.E., Gloyn A.L., Rorsman P., Braun M.
Am. J. Physiol. 303:E1107-E1116(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[14]"Identification of critical residues involved in ligand binding and G protein signaling in human somatostatin receptor subtype 2."
Parry J.J., Chen R., Andrews R., Lears K.A., Rogers B.E.
Endocrinology 153:2747-2755(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-89; ASP-139 AND ARG-140.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M81830 Genomic DNA. Translation: AAA58248.1.
AY236542 Genomic DNA. Translation: AAO92064.1.
AF184174 Genomic DNA. Translation: AAF42809.1.
AF184174 Genomic DNA. Translation: AAF42810.1.
AB065911 Genomic DNA. Translation: BAC06126.1.
AK290745 mRNA. Translation: BAF83434.1.
AK313866 mRNA. Translation: BAG36594.1.
BT019926 mRNA. Translation: AAV38729.1.
BC000256 mRNA. Translation: AAH00256.1.
BC009522 mRNA. Translation: AAH09522.1.
BC019610 mRNA. Translation: AAH19610.1.
BC095495 mRNA. Translation: AAH95495.1.
CCDSCCDS11691.1. [P30874-1]
PIRB41795.
RefSeqNP_001041.1. NM_001050.2. [P30874-1]
UniGeneHs.514451.

3D structure databases

ProteinModelPortalP30874.
SMRP30874. Positions 46-328.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112630. 5 interactions.
IntActP30874. 2 interactions.
MINTMINT-3340293.
STRING9606.ENSP00000350198.

Chemistry

BindingDBP30874.
ChEMBLCHEMBL2111436.
GuidetoPHARMACOLOGY356.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP30874.

Polymorphism databases

DMDM401126.

Proteomic databases

PaxDbP30874.
PRIDEP30874.

Protocols and materials databases

DNASU6752.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000315332; ENSP00000326616; ENSG00000180616. [P30874-2]
ENST00000357585; ENSP00000350198; ENSG00000180616. [P30874-1]
GeneID6752.
KEGGhsa:6752.
UCSCuc002jje.3. human. [P30874-1]

Organism-specific databases

CTD6752.
GeneCardsGC17P071161.
HGNCHGNC:11331. SSTR2.
HPAHPA007264.
MIM182452. gene.
neXtProtNX_P30874.
PharmGKBPA36155.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG274661.
HOGENOMHOG000230485.
HOVERGENHBG106919.
InParanoidP30874.
KOK04218.
OMAVIMPIMI.
OrthoDBEOG7BKCVQ.
PhylomeDBP30874.
TreeFamTF315737.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkP30874.

Gene expression databases

BgeeP30874.
CleanExHS_SSTR2.
GenevestigatorP30874.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR000586. Somatstn_rcpt.
IPR002074. Somatstn_rcpt_2.
[Graphical view]
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00237. GPCRRHODOPSN.
PR00246. SOMATOSTATNR.
PR00588. SOMATOSTTN2R.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSomatostatin_receptor_2.
GenomeRNAi6752.
NextBio26340.
PROP30874.
SOURCESearch...

Entry information

Entry nameSSR2_HUMAN
AccessionPrimary (citable) accession number: P30874
Secondary accession number(s): A8K3Y0 expand/collapse secondary AC list , B2R9P7, Q4VBP0, Q96GE0, Q96TF2, Q9BWH1
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: July 9, 2014
This is version 137 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

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Index of protein domains and families

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Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

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