ASpdb: an integrative knowledgebase of human protein isoforms from experimental and AI-predicted structures

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	Protein Summary
	AS Summary
	Protein Functional Features
	Gene Isoform Structures and Expression Levels
	Protein Structures
	pLDDT Score Distribution
	Ramachandran Plot of Protein Structures
	Potential Active Site Information
	Protein Structure and Feature Comparision
	Protein-Protein Interaction
	Related Drugs
	Related Diseases
	Clinically Important Variants

Protein:GHR

Protein Summary

Gene summary

Gene name: GHR
ASpdb.0 ID: 2690
	Gene
Gene symbol	GHR
Gene ID	2690
Gene name	growth hormone receptor
Synonyms	GHBP\|GHIP
Cytomap	5p13.1-p12
Type of gene	protein-coding
Description	growth hormone receptorGH receptorgrowth hormone binding proteinmutant growth hormone receptorserum binding proteinsomatotropin receptor
Modification date	20240411
UniProtAcc	P10912

Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez

Partner	Gene	GO ID	GO term	PubMed ID
Gene	GHR	GO:0005615	extracellular space	8137822
Gene	GHR	GO:0005829	cytosol	-
Gene	GHR	GO:0005886	plasma membrane	8137822
Gene	GHR	GO:0009986	cell surface	8137822
Gene	GHR	GO:0016020	membrane	1549776
Gene	GHR	GO:0036464	cytoplasmic ribonucleoprotein granule	-
Gene	GHR	GO:0042803	protein homodimerization activity	1549776\|8137822\|8943276
Gene	GHR	GO:0043235	receptor complex	8137822
Gene	GHR	GO:0070195	growth hormone receptor complex	1549776\|8137822\|8943276\|9571026

AS Summary

Information of the canonical protein with experimentally identified structure from PDB (2023).

UniProt Acc	File name	PDB ID	Method	Resolution	Chain	Start	End
P10912-1	P10912-1_1hwg_C.pdb	1HWG	X-ray	2.5	C	50	255

ASpdb's canonical and alternatively spliced isoform information.

accession_id

gene_name

canonical_id

alternative_id

canonical_length

alternative_length

canonical_start

canonical_end

type

originalSEQ

variationSEQ

alternative_start

alternative_end

P10912

GHR

P10912-1

P10912-2

638

297

292

297

Substitution

RIKMLI

SSSSKD

292

297

P10912

GHR

P10912-1

P10912-2

638

297

298

638

Deletion

none

297

P10912

GHR

P10912-1

P10912-3

638

294

292

294

Substitution

RIK

KEN

292

294

P10912

GHR

P10912-1

P10912-3

638

294

295

638

Deletion

none

294

P10912

GHR

P10912-1

P10912-4

638

616

Substitution

P10912

GHR

P10912-1

P10912-4

638

616

Deletion

none

Multiple sequence alignment of our canonical and alternatively spliced GHR

Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of GHR

UniProt-id	ENSG	ENST	ENSP
P10912-1	ENSG00000112964.14	ENST00000230882.9	ENSP00000230882.4
P10912-1	ENSG00000112964.14	ENST00000537449.5	ENSP00000442206.2
P10912-1	ENSG00000112964.14	ENST00000612382.4	ENSP00000478332.1
P10912-1	ENSG00000112964.14	ENST00000612626.4	ENSP00000479846.1
P10912-1	ENSG00000112964.14	ENST00000615111.4	ENSP00000478291.1
P10912-1	ENSG00000112964.14	ENST00000618088.4	ENSP00000482373.1
P10912-4	ENSG00000112964.14	ENST00000357703.6	ENSP00000350335.3

UniProt-id	NM ID	NP ID
P10912-1	NM_000163.4	NP_000154.1
P10912-1	NM_001242400.2	NP_001229329.1
P10912-1	NM_001242401.3	NP_001229330.1
P10912-1	NM_001242402.2	NP_001229331.1
P10912-1	NM_001242403.2	NP_001229332.1
P10912-1	NM_001242404.2	NP_001229333.1
P10912-1	NM_001242405.2	NP_001229334.1
P10912-1	NM_001242406.2	NP_001229335.1
P10912-4	NM_001242460.1	NP_001229389.1

Amino acid sequences of our canonical and alternatively spliced GHR

accession_id	Protein sequence
P10912-1	MDLWQLLLTLALAGSSDAFSGSEATAAILSRAPWSLQSVNPGLKTNSSKEPKFTKCRSPERETFSCHWTDEVHHGTKNLGPIQLFYTRRN TQEWTQEWKECPDYVSAGENSCYFNSSFTSIWIPYCIKLTSNGGTVDEKCFSVDEIVQPDPPIALNWTLLNVSLTGIHADIQVRWEAPRN ADIQKGWMVLEYELQYKEVNETKWKMMDPILTTSVPVYSLKVDKEYEVRVRSKQRNSGNYGEFSEVLYVTLPQMSQFTCEEDFYFPWLLI IIFGIFGLTVMLFVFLFSKQQRIKMLILPPVPVPKIKGIDPDLLKEGKLEEVNTILAIHDSYKPEFHSDDSWVEFIELDIDEPDEKTEES DTDRLLSSDHEKSHSNLGVKDGDSGRTSCCEPDILETDFNANDIHEGTSEVAQPQRLKGEADLLCLDQKNQNNSPYHDACPATQQPSVIQ AEKNKPQPLPTEGAESTHQAAHIQLSNPSSLSNIDFYAQVSDITPAGSVVLSPGQKNKAGMSQCDMHPEMVSLCQENFLMDNAYFCEADA KKCIPVAPHIKVESHIQPSLNQEDIYITTESLTTAAGRPGTGEHVPGSEMPVPDYTSIHIVQSPQGLILNATALPLPDKEFLSSCGYVST
P10912-2	MDLWQLLLTLALAGSSDAFSGSEATAAILSRAPWSLQSVNPGLKTNSSKEPKFTKCRSPERETFSCHWTDEVHHGTKNLGPIQLFYTRRN TQEWTQEWKECPDYVSAGENSCYFNSSFTSIWIPYCIKLTSNGGTVDEKCFSVDEIVQPDPPIALNWTLLNVSLTGIHADIQVRWEAPRN ADIQKGWMVLEYELQYKEVNETKWKMMDPILTTSVPVYSLKVDKEYEVRVRSKQRNSGNYGEFSEVLYVTLPQMSQFTCEEDFYFPWLLI
P10912-3	MDLWQLLLTLALAGSSDAFSGSEATAAILSRAPWSLQSVNPGLKTNSSKEPKFTKCRSPERETFSCHWTDEVHHGTKNLGPIQLFYTRRN TQEWTQEWKECPDYVSAGENSCYFNSSFTSIWIPYCIKLTSNGGTVDEKCFSVDEIVQPDPPIALNWTLLNVSLTGIHADIQVRWEAPRN ADIQKGWMVLEYELQYKEVNETKWKMMDPILTTSVPVYSLKVDKEYEVRVRSKQRNSGNYGEFSEVLYVTLPQMSQFTCEEDFYFPWLLI
P10912-4	MDLWQLLLTLALAGSSDAFSGSEDSSKEPKFTKCRSPERETFSCHWTDEVHHGTKNLGPIQLFYTRRNTQEWTQEWKECPDYVSAGENSC YFNSSFTSIWIPYCIKLTSNGGTVDEKCFSVDEIVQPDPPIALNWTLLNVSLTGIHADIQVRWEAPRNADIQKGWMVLEYELQYKEVNET KWKMMDPILTTSVPVYSLKVDKEYEVRVRSKQRNSGNYGEFSEVLYVTLPQMSQFTCEEDFYFPWLLIIIFGIFGLTVMLFVFLFSKQQR IKMLILPPVPVPKIKGIDPDLLKEGKLEEVNTILAIHDSYKPEFHSDDSWVEFIELDIDEPDEKTEESDTDRLLSSDHEKSHSNLGVKDG DSGRTSCCEPDILETDFNANDIHEGTSEVAQPQRLKGEADLLCLDQKNQNNSPYHDACPATQQPSVIQAEKNKPQPLPTEGAESTHQAAH IQLSNPSSLSNIDFYAQVSDITPAGSVVLSPGQKNKAGMSQCDMHPEMVSLCQENFLMDNAYFCEADAKKCIPVAPHIKVESHIQPSLNQ

Protein Functional Features

Main function of this protein. (from UniProt)

GHR (go to UniProt):P10912

Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at
download page
* Minus value of BPloci means that the break pointn is located before the CDS.

- Retained protein feature among the 13 regional features.

Accession_id	Subsection	Start	End	Funcitonal feature	Splicing information
P10912	Topological domain	19	264	Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Substitution;Start=24;End=24
P10912	Topological domain	19	264	Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=25;End=46
P10912	Topological domain	289	638	Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Substitution;Start=292;End=297
P10912	Topological domain	289	638	Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=298;End=638
P10912	Topological domain	289	638	Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Substitution;Start=292;End=294
P10912	Topological domain	289	638	Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=295;End=638
P10912	Region	353	391	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=298;End=638
P10912	Region	353	391	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=295;End=638
P10912	Motif	297	305	Note=Box 1 motif	Type=Substitution;Start=292;End=297
P10912	Motif	297	305	Note=Box 1 motif	Type=Deletion;Start=298;End=638
P10912	Motif	297	305	Note=Box 1 motif	Type=Deletion;Start=295;End=638
P10912	Motif	340	349	Note=UbE motif	Type=Deletion;Start=298;End=638
P10912	Motif	340	349	Note=UbE motif	Type=Deletion;Start=295;End=638
P10912	Compositional bias	359	379	Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=298;End=638
P10912	Compositional bias	359	379	Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=295;End=638

Gene Isoform Structures and Expression Levels for GHR

Gene structures of our canonical and alternative spliced genes of GHR
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Expression levels of gene isoforms across GTEx.

Expression levels of gene isoforms across TCGA.

Protein Structures

PDB and CIF files of the predicted protein structures
* Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.

3D view using mol* of P10912-1

3D view using mol* of P10912-2

3D view using mol* of P10912-3

3D view using mol* of P10912-4

pLDDT Score Distribution

pLDDT score distribution of the predicted protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.

pLDDT distribution across the protein length of P10912-1

pLDDT distribution across the protein length of P10912-2

pLDDT distribution across the protein length of P10912-3

pLDDT distribution across the protein length of P10912-4

Ramachandran Plot of Protein Structures

Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide.

Ramachandran plot of P10912-1

Ramachandran plot of P10912-2

Ramachandran plot of P10912-3

Potential Active Site Information

The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite.

UniProt-id	Site score	Size	D score	Volume	Exposure	Enclosure	Contact	Phobic	Philic	Balance	Don/Acc	Residues
P10912-1	0.942	115	0.96	267.883	0.574	0.611	0.857	0.218	1.064	0.205	1.014	46,47,48,49,50,51,52,69,70,71,72,73,74,75,76,77,78 ,79,80,81,82,131
P10912-2	0.899	88	0.855	214.718	0.633	0.615	0.885	0.193	1.213	0.159	1.353	47,49,50,71,72,73,74,75,76,77,78,79,80,81,82,131,1 36
P10912-3	0.68	40	0.533	115.591	0.685	0.623	0.909	0.009	1.336	0.007	1.011	86,87,88,89,90,93,96,97,99,123
P10912-4	1.021	145	1.069	408.17	0.582	0.673	0.884	0.756	0.843	0.897	0.872	139,140,141,142,143,145,146,147,148,196,197,239,57 3,574,575,576,577,578,580,584,585,586,587,588,589, 592,603,604,605,606,611,614,615

Protein Structure and Feature Comparision

Protein Structure Comparision Using Template Modeling Scores (TM-score).

Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green)

3D view using mol* of P10912-1_P10912-1_1hwg_C.pdb

Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green)

3D view using mol* of P10912-1_1hwg_C_P10912-2.pdb

3D view using mol* of P10912-1_1hwg_C_P10912-3.pdb

3D view using mol* of P10912-1_1hwg_C_P10912-4.pdb

Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green)

3D view using mol* of P10912-1_P10912-2.pdb

3D view using mol* of P10912-1_P10912-3.pdb

3D view using mol* of P10912-1_P10912-4.pdb

Protein Feature Comparison of the protein sequendary structures among the protiens.

./stats/secondary_structure/figure/P10912-1_vs_P10912-2.png

./stats/secondary_structure/figure/P10912-1_vs_P10912-3.png

./stats/secondary_structure/figure/P10912-1_vs_P10912-4.png

Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens.

./stats/relative_asa/P10912-1_vs_P10912-2.png

./stats/relative_asa/P10912-1_vs_P10912-3.png

./stats/relative_asa/P10912-1_vs_P10912-4.png

Protein-Protein Interaction

Interactors from UniProt.

Accession_id

Subsection

Start

End

Funcitonal feature

Splicing information

Interactors from STRING.

Gene name

Interactors

Related Drugs to GHR

Drugs targeting this gene/protein.
(DrugBank)

UniProt accession	Gene name	DrugBank ID	Drug name	Drug group	Actions
P10912	GHR	DB16220	Lonapegsomatropin	approved, investigational	ligand
P10912	GHR	DB14960	Somatrogon	approved	binder
P10912	GHR	DB00082	Pegvisomant	approved	antagonist
P10912	GHR	DB15093	Somapacitan	approved, investigational	agonist
P10912	GHR	DB09098	Somatrem	approved, investigational, withdrawn	agonist
P10912	GHR	DB00052	Somatotropin	approved, investigational	ligand

Related Diseases to GHR

Previous studies relating to the alternative splicing of GHR and disease information from the MeSH term (PubMed)

Gene

PMID

Title

Abstract

MeSH ID

MeSH term

Clinically important variants in GHR

(ClinVar, 04/20/2024)

accession_id

uniprot_id

gene_name

Type

Variant

Clinical_significance