P48546 (GIPR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Gastric inhibitory polypeptide receptor
Short name=GIP-R

Alternative name(s):
Glucose-dependent insulinotropic polypeptide receptor

Gene names

Name:

GIPR

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	466 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	This is a receptor for GIP. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Subunit structure	May form homodimers and heterodimers with GLP1R. Ref.7
Subcellular location	Cell membrane; Multi-pass membrane protein.
Post-translational modification	N-glycosylation is required for cell surface expression and lengthens receptor half-life by preventing degradation in the ER.
Sequence similarities	Belongs to the G-protein coupled receptor 2 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of adenylate cyclase activity Traceable author statement Ref.2. Source: ProtInc cell surface receptor signaling pathway Traceable author statement Ref.3. Source: ProtInc generation of precursor metabolites and energy Traceable author statement Ref.3. Source: ProtInc response to nutrient Traceable author statement Ref.3. Source: ProtInc
Cellular_component	integral to membrane Traceable author statement Ref.3. Source: ProtInc plasma membrane Traceable author statement. Source: Reactome
Molecular_function	gastric inhibitory peptide receptor activity Inferred from electronic annotation. Source: InterPro transmembrane signaling receptor activity Traceable author statement Ref.3. Source: ProtInc
Complete GO annotation...

Alternative products

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

Isoform Short (identifier: P48546-1)

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 Long (identifier: P48546-2)

The sequence of this isoform differs from the canonical sequence as follows:
     399-399: V → VGRDPAAAPALWRRRGTAPPLSAIVSQV

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Potential

Chain

22 – 466

445

Gastric inhibitory polypeptide receptor

PRO_0000012825

Regions

Topological domain

22 – 138

117

Extracellular Potential

Transmembrane

139 – 161

23

Helical; Name=1; Potential

Topological domain

162 – 169

8

Cytoplasmic Potential

Transmembrane

170 – 189

20

Helical; Name=2; Potential

Topological domain

190 – 217

28

Extracellular Potential

Transmembrane

218 – 242

25

Helical; Name=3; Potential

Topological domain

243 – 254

12

Cytoplasmic Potential

Transmembrane

255 – 278

24

Helical; Name=4; Potential

Topological domain

279 – 293

15

Extracellular Potential

Transmembrane

294 – 319

26

Helical; Name=5; Potential

Topological domain

320 – 341

22

Cytoplasmic Potential

Transmembrane

342 – 362

21

Helical; Name=6; Potential

Topological domain

363 – 377

15

Extracellular Potential

Transmembrane

378 – 398

21

Helical; Name=7; Potential

Topological domain

399 – 466

68

Cytoplasmic Potential

Amino acid modifications

Glycosylation

62

1

N-linked (GlcNAc...) Ref.7

Glycosylation

77

1

N-linked (GlcNAc...) Ref.7

Disulfide bond

46 ↔ 70

Ref.8

Disulfide bond

61 ↔ 103

Ref.8

Disulfide bond

84 ↔ 118

Ref.8

Natural variations

Alternative sequence

399

1

V → VGRDPAAAPALWRRRGTAPP LSAIVSQV in isoform Long.

VSP_002002

Natural variant

136

1

R → W.
Corresponds to variant rs13306402 [ dbSNP | Ensembl ].

VAR_029333

Natural variant

207

1

A → V.
Corresponds to variant rs1800436 [ dbSNP | Ensembl ].

VAR_011808

Natural variant

262

1

L → V.
Corresponds to variant rs5392 [ dbSNP | Ensembl ].

VAR_011809

Natural variant

354

1

E → Q.
Corresponds to variant rs1800437 [ dbSNP | Ensembl ].

VAR_011810

Experimental info

Sequence conflict

12

1

R → G in AAB35419. Ref.2

Sequence conflict

104

1

G → R in AAB35419. Ref.2

Sequence conflict

117

1

Missing in CAA57426. Ref.3

Sequence conflict

337

1

L → V in AAB35419. Ref.2

Sequence conflict

367 – 371

5

GALRF → APCV in CAA57426. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

466

Helix Strand Turn

Details...

Helix

32 – 52

21

Beta strand

78 – 83

6

Helix

91 – 94

4

Beta strand

98 – 103

6

Helix

116 – 118

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform Short [UniParc]. Last modified February 1, 1996. Version 1. Checksum: CA5CF86BA0E32383	FASTA	466	53,157
	10 20 30 40 50 60 MTTSPILQLL LRLSLCGLLL QRAETGSKGQ TAGELYQRWE RYRRECQETL AAAEPPSGLA 70 80 90 100 110 120 CNGSFDMYVC WDYAAPNATA RASCPWYLPW HHHVAAGFVL RQCGSDGQWG LWRDHTQCEN 130 140 150 160 170 180 PEKNEAFLDQ RLILERLQVM YTVGYSLSLA TLLLALLILS LFRRLHCTRN YIHINLFTSF 190 200 210 220 230 240 MLRAAAILSR DRLLPRPGPY LGDQALALWN QALAACRTAQ IVTQYCVGAN YTWLLVEGVY 250 260 270 280 290 300 LHSLLVLVGG SEEGHFRYYL LLGWGAPALF VIPWVIVRYL YENTQCWERN EVKAIWWIIR 310 320 330 340 350 360 TPILMTILIN FLIFIRILGI LLSKLRTRQM RCRDYRLRLA RSTLTLVPLL GVHEVVFAPV 370 380 390 400 410 420 TEEQARGALR FAKLGFEIFL SSFQGFLVSV LYCFINKEVQ SEIRRGWHHC RLRRSLGEEQ 430 440 450 460 RQLPERAFRA LPSGSGPGEV PTSRGLSSGT LPGPGNEASR ELESYC
	Isoform Long [UniParc]. Checksum: A0E53FB8D5458612	FASTA	493	55,953
	10 20 30 40 50 60 MTTSPILQLL LRLSLCGLLL QRAETGSKGQ TAGELYQRWE RYRRECQETL AAAEPPSGLA 70 80 90 100 110 120 CNGSFDMYVC WDYAAPNATA RASCPWYLPW HHHVAAGFVL RQCGSDGQWG LWRDHTQCEN 130 140 150 160 170 180 PEKNEAFLDQ RLILERLQVM YTVGYSLSLA TLLLALLILS LFRRLHCTRN YIHINLFTSF 190 200 210 220 230 240 MLRAAAILSR DRLLPRPGPY LGDQALALWN QALAACRTAQ IVTQYCVGAN YTWLLVEGVY 250 260 270 280 290 300 LHSLLVLVGG SEEGHFRYYL LLGWGAPALF VIPWVIVRYL YENTQCWERN EVKAIWWIIR 310 320 330 340 350 360 TPILMTILIN FLIFIRILGI LLSKLRTRQM RCRDYRLRLA RSTLTLVPLL GVHEVVFAPV 370 380 390 400 410 420 TEEQARGALR FAKLGFEIFL SSFQGFLVSV LYCFINKEVG RDPAAAPALW RRRGTAPPLS 430 440 450 460 470 480 AIVSQVQSEI RRGWHHCRLR RSLGEEQRQL PERAFRALPS GSGPGEVPTS RGLSSGTLPG 490 PGNEASRELE SYC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The human GIP receptor: gene structure, functional expression of its cDNA, and chromosomal location." Usdin T.B., Gruber C., Modi W., Bonner T.I. Submitted (OCT-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
[2]	"Molecular cloning, functional expression, and signal transduction of the GIP-receptor cloned from a human insulinoma." Volz A., Goke R., Lankat-Buttgereit B., Fehmann H.C., Bode H.P., Goke B. FEBS Lett. 373:23-29(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
[3]	"Cloning, functional expression, and chromosomal localization of the human pancreatic islet glucose-dependent insulinotropic polypeptide receptor." Gremlich S., Porret A., Hani E.H., Cherif D., Vionnet N., Froguel P., Thorens B. Diabetes 44:1202-1208(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). Tissue: Pancreas.
[4]	"Human gastric inhibitory polypeptide receptor: cloning of the gene (GIPR) and cDNA." Yamada Y., Hayami T., Nakamura K., Kaisaki P.J., Someya Y., Wang C.Z., Seino S., Seino Y. Genomics 29:773-776(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM SHORT).
[5]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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 SHORT). Tissue: Colon.
[7]	"Regulation of GIP and GLP1 receptor cell surface expression by N-glycosylation and receptor heteromerization." Whitaker G.M., Lynn F.C., McIntosh C.H., Accili E.A. PLoS ONE 7:E32675-E32675(2012) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT ASN-62 AND ASN-77, SUBUNIT.
[8]	"Crystal structure of the incretin-bound extracellular domain of a G protein-coupled receptor." Parthier C., Kleinschmidt M., Neumann P., Rudolph R., Manhart S., Schlenzig D., Fanghanel J., Rahfeld J.-U., Demuth H.-U., Stubbs M.T. Proc. Natl. Acad. Sci. U.S.A. 104:13942-13947(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 24-138 IN COMPLEX WITH GIP, DISULFIDE BONDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U39231 mRNA. Translation: AAA84418.1.
S79852 mRNA. Translation: AAB35419.2.
X81832 mRNA. Translation: CAA57426.1.
D49559 Genomic DNA. Translation: BAA08503.1.
AC006132 Genomic DNA. Translation: AAC97984.1.
AC007191 Genomic DNA. Translation: AAD22674.1.
BC093723 mRNA. Translation: AAH93723.1.
BC101673 mRNA. Translation: AAI01674.1.

IPI

IPI00010172.
IPI00218459.

PIR

G02234.
I37411.
S66676.

RefSeq

NP_000155.1. NM_000164.2.

UniGene

Hs.658534.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2QKH	X-ray	1.90	A	24-138	[»]

ProteinModelPortal

P48546.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-46468N.

STRING

9606.ENSP00000263281.

Protein family/group databases

GPCRDB

Search...

Polymorphism databases

DMDM

1346133.

Proteomic databases

PaxDb

P48546.

PRIDE

P48546.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000590918; ENSP00000467494; ENSG00000010310.

GeneID

2696.

KEGG

hsa:2696.

UCSC

uc002pct.1. human.

Organism-specific databases

CTD

2696.

GeneCards

GC19P046171.

HGNC

HGNC:4271. GIPR.

HPA

CAB022710.

MIM

137241. gene.

neXtProt

NX_P48546.

PharmGKB

PA28682.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG239460.

HOGENOM

HOG000008250.

HOVERGEN

HBG008318.

InParanoid

P48546.

KO

K04580.

OMA

TRQMRCP.

OrthoDB

EOG469QTS.

PhylomeDB

P48546.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P48546.

Bgee

P48546.

CleanEx

HS_GIPR.

Genevestigator

P48546.

GermOnline

ENSG00000010310. Homo sapiens.

Family and domain databases

InterPro

IPR017981. GPCR_2-like.
IPR001879. GPCR_2_extracellular_dom.
IPR001749. GPCR_2_GIP_rcpt.
IPR000832. GPCR_2_secretin-like.
IPR017983. GPCR_2_secretin-like_CS.
[Graphical view]

Pfam

PF00002. 7tm_2. 1 hit.
PF02793. HRM. 1 hit.
[Graphical view]

PRINTS

PR01129. GIPRECEPTOR.
PR00249. GPCRSECRETIN.

SMART

SM00008. HormR. 1 hit.
[Graphical view]

PROSITE

PS00649. G_PROTEIN_RECEP_F2_1. 1 hit.
PS00650. G_PROTEIN_RECEP_F2_2. 1 hit.
PS50227. G_PROTEIN_RECEP_F2_3. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P48546.

ChEMBL

CHEMBL4383.

EvolutionaryTrace

P48546.

GenomeRNAi

2696.

NextBio

10664.

SOURCE

Search...

Entry information

Entry name

GIPR_HUMAN

Accession

Primary (citable) accession number: P48546
Secondary accession number(s): Q14401 , Q16400, Q52M04, Q9UPI1

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	May 1, 2013
This is version 118 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.