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:KCNMA1

Protein Summary

Gene summary

Gene name: KCNMA1
ASpdb.0 ID: 3778
	Gene
Gene symbol	KCNMA1
Gene ID	3778
Gene name	potassium calcium-activated channel subfamily M alpha 1
Synonyms	BKTM\|CADEDS\|IEG16\|KCa1.1\|LIWAS\|MaxiK\|PNKD3\|SAKCA\|SLO\|SLO-ALPHA\|SLO1\|bA205K10.1\|hSlo\|mSLO1
Cytomap	10q22.3
Type of gene	protein-coding
Description	Calcium-activated potassium channel subunit alpha-1calcium-activated potassium channel subunit alpha-1BK channel alpha subunitBKCA alpha subunitbig potassium channel alpha subunitcalcium-activated potassium channel, subfamily M subunit alpha-1k(VCA)
Modification date	20240403
UniProtAcc	Q12791

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

Partner	Gene	GO ID	GO term	PubMed ID
Gene	KCNMA1	GO:0001666	response to hypoxia	15528406
Gene	KCNMA1	GO:0003779	actin binding	15703204
Gene	KCNMA1	GO:0005249	voltage-gated potassium channel activity	7877450\|12388065
Gene	KCNMA1	GO:0005901	caveola	15703204
Gene	KCNMA1	GO:0006813	potassium ion transport	7573516\|7877450\|11245614\|12388065\|17706472\|18458941
Gene	KCNMA1	GO:0006970	response to osmotic stress	10840032\|12388065
Gene	KCNMA1	GO:0008076	voltage-gated potassium channel complex	7573516\|7877450
Gene	KCNMA1	GO:0015269	calcium-activated potassium channel activity	7573516\|7877450\|11245614\|17706472\|18458941
Gene	KCNMA1	GO:0016020	membrane	7573516\|7877450
Gene	KCNMA1	GO:0016324	apical plasma membrane	10840032
Gene	KCNMA1	GO:0030007	intracellular potassium ion homeostasis	11245614
Gene	KCNMA1	GO:0034465	response to carbon monoxide	15528406
Gene	KCNMA1	GO:0042391	regulation of membrane potential	7877450\|7993625
Gene	KCNMA1	GO:0045794	negative regulation of cell volume	12388065
Gene	KCNMA1	GO:0051592	response to calcium ion	12388065\|18458941
Gene	KCNMA1	GO:0060072	large conductance calcium-activated potassium channel activity	7993625
Gene	KCNMA1	GO:0060073	micturition	11641143
Gene	KCNMA1	GO:0060083	smooth muscle contraction involved in micturition	11641143

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
Q12791-1	Q12791-1_6v22_A.pdb	6V22	EM	3.2	A	81	1179

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

Q12791

KCNMA1

Q12791-1

Q12791-6

1236

168

127

168

Substitution

EAQKINNGSSQADGTLKPVDEKEEAVAAEVGWMTSVKDWAGV

ATHFGSPEMPPAARSWSGSPPEAAVLRGASSLALEVARCRRL

127

168

Q12791

KCNMA1

Q12791-1

Q12791-6

1236

168

169

1236

Deletion

none

168

Multiple sequence alignment of our canonical and alternatively spliced KCNMA1

Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of KCNMA1

UniProt-id	ENSG	ENST	ENSP
Q12791-1	ENSG00000156113.25	ENST00000286628.14	ENSP00000286628.8
Q12791-6	ENSG00000156113.25	ENST00000480683.2	ENSP00000474686.1

UniProt-id	NM ID	NP ID
Q12791-1	NM_001161352.1	NP_001154824.1
Q12791-6	NM_001271522.1	NP_001258451.1

Amino acid sequences of our canonical and alternatively spliced KCNMA1

accession_id	Protein sequence
Q12791-1	MANGGGGGGGSSGGGGGGGGSSLRMSSNIHANHLSLDASSSSSSSSSSSSSSSSSSSSSSVHEPKMDALIIPVTMEVPCDSRGQRMWWAF LASSMVTFFGGLFIILLWRTLKYLWTVCCHCGGKTKEAQKINNGSSQADGTLKPVDEKEEAVAAEVGWMTSVKDWAGVMISAQTLTGRVL VVLVFALSIGALVIYFIDSSNPIESCQNFYKDFTLQIDMAFNVFFLLYFGLRFIAANDKLWFWLEVNSVVDFFTVPPVFVSVYLNRSWLG LRFLRALRLIQFSEILQFLNILKTSNSIKLVNLLSIFISTWLTAAGFIHLVENSGDPWENFQNNQALTYWECVYLLMVTMSTVGYGDVYA KTTLGRLFMVFFILGGLAMFASYVPEIIELIGNRKKYGGSYSAVSGRKHIVVCGHITLESVSNFLKDFLHKDRDDVNVEIVFLHNISPNL ELEALFKRHFTQVEFYQGSVLNPHDLARVKIESADACLILANKYCADPDAEDASNIMRVISIKNYHPKIRIITQMLQYHNKAHLLNIPSW NWKEGDDAICLAELKLGFIAQSCLAQGLSTMLANLFSMRSFIKIEEDTWQKYYLEGVSNEMYTEYLSSAFVGLSFPTVCELCFVKLKLLM IAIEYKSANRESRILINPGNHLKIQEGTLGFFIASDAKEVKRAFFYCKACHDDITDPKRIKKCGCKRPKMSIYKRMRRACCFDCGRSERD CSCMSGRVRGNVDTLERAFPLSSVSVNDCSTSFRAFEDEQPSTLSPKKKQRNGGMRNSPNTSPKLMRHDPLLIPGNDQIDNMDSNVKKYD STGMFHWCAPKEIEKVILTRSEAAMTVLSGHVVVCIFGDVSSALIGLRNLVMPLRASNFHYHELKHIVFVGSIEYLKREWETLHNFPKVS ILPGTPLSRADLRAVNINLCDMCVILSANQNNIDDTSLQDKECILASLNIKSMQFDDSIGVLQANSQGFTPPGMDRSSPDNSPVHGMLRQ PSITTGVNIPIITELVNDTNVQFLDQDDDDDPDTELYLTQPFACGTAFAVSVLDSLMSATYFNDNILTLIRTLVTGGATPELEALIAEEN ALRGGYSTPQTLANRDRCRVAQLALLDGPFADLGDGGCYGDLFCKALKTYNMLCFGIYRLRDAHLSTPSQCTKRYVITNPPYEFELVPTD
Q12791-6	MANGGGGGGGSSGGGGGGGGSSLRMSSNIHANHLSLDASSSSSSSSSSSSSSSSSSSSSSVHEPKMDALIIPVTMEVPCDSRGQRMWWAF

Protein Functional Features

Main function of this protein. (from UniProt)

KCNMA1 (go to UniProt):Q12791

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
Q12791	Topological domain	108	178	Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Substitution;Start=127;End=168
Q12791	Topological domain	108	178	Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=169;End=1236
Q12791	Transmembrane	179	199	Note=Helical%3B Name%3DSegment S1;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=169;End=1236
Q12791	Topological domain	200	214	Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=169;End=1236
Q12791	Transmembrane	215	235	Note=Helical%3B Name%3DSegment S2;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=169;End=1236
Q12791	Topological domain	236	239	Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=169;End=1236
Q12791	Transmembrane	240	260	Note=Helical%3B Name%3DSegment S3;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=169;End=1236
Q12791	Topological domain	261	264	Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=169;End=1236
Q12791	Transmembrane	265	285	Note=Helical%3B Name%3DSegment S4;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=169;End=1236
Q12791	Topological domain	286	300	Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=169;End=1236
Q12791	Transmembrane	301	321	Note=Helical%3B Name%3DSegment S5;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=169;End=1236
Q12791	Topological domain	322	335	Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=169;End=1236
Q12791	Intramembrane	336	358	Note=Pore-forming%3B Name%3DP region;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=169;End=1236
Q12791	Topological domain	359	367	Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=169;End=1236
Q12791	Transmembrane	368	388	Note=Helical%3B Name%3DSegment S6;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=169;End=1236
Q12791	Topological domain	389	1236	Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=169;End=1236
Q12791	Domain	415	558	Note=RCK N-terminal	Type=Deletion;Start=169;End=1236
Q12791	Region	556	576	Note=Segment S7	Type=Deletion;Start=169;End=1236
Q12791	Region	613	633	Note=Segment S8	Type=Deletion;Start=169;End=1236
Q12791	Region	677	681	Note=Heme-binding motif	Type=Deletion;Start=169;End=1236
Q12791	Region	757	787	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=169;End=1236
Q12791	Region	837	857	Note=Segment S9	Type=Deletion;Start=169;End=1236
Q12791	Region	1032	1052	Note=Segment S10	Type=Deletion;Start=169;End=1236
Q12791	Region	1186	1236	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=169;End=1236
Q12791	Motif	352	355	Note=Selectivity for potassium	Type=Deletion;Start=169;End=1236
Q12791	Motif	1003	1025	Note=Calcium bowl	Type=Deletion;Start=169;End=1236
Q12791	Compositional bias	766	784	Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=169;End=1236
Q12791	Compositional bias	1186	1217	Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=169;End=1236
Q12791	Compositional bias	1218	1236	Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=169;End=1236

Gene Isoform Structures and Expression Levels for KCNMA1

Gene structures of our canonical and alternative spliced genes of KCNMA1
* 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 Q12791-1

3D view using mol* of Q12791-6

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 Q12791-1

pLDDT distribution across the protein length of Q12791-6

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 Q12791-1

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
Q12791-1	1.142	88	0.988	123.823	0.228	0.979	1.264	0.277	1.475	0.187	0.747	493,494,498,526,527,551,552,555,852,853,854,855,92 8,930,931,1004,1006,1040
Q12791-6	0.783	38	0.776	90.895	0.573	0.683	1.006	1.848	0.655	2.822	0.503	108,111,112,115,116,119,162,165,166

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 Q12791-1_Q12791-1_6v22_A.pdb

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

3D view using mol* of Q12791-1_6v22_A_Q12791-6.pdb

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

3D view using mol* of Q12791-1_Q12791-6.pdb

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

./stats/secondary_structure/figure/Q12791-1_vs_Q12791-6.png

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

./stats/relative_asa/Q12791-1_vs_Q12791-6.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 KCNMA1

Drugs targeting this gene/protein.
(DrugBank)

UniProt accession	Gene name	DrugBank ID	Drug name	Drug group	Actions
Q12791	KCNMA1	DB09089	Trimebutine	approved	inhibitor
Q12791	KCNMA1	DB00356	Chlorzoxazone	approved
Q12791	KCNMA1	DB02587	Colforsin	experimental, investigational	activator
Q12791	KCNMA1	DB01054	Nitrendipine	approved, investigational	inhibitor
Q12791	KCNMA1	DB00999	Hydrochlorothiazide	approved, vet_approved	inhibitor
Q12791	KCNMA1	DB04209	Dequalinium	approved, investigational	inhibitor
Q12791	KCNMA1	DB00721	Procaine	approved, investigational, vet_approved	blocker
Q12791	KCNMA1	DB01159	Halothane	approved, vet_approved	inhibitor
Q12791	KCNMA1	DB00867	Ritodrine	approved, investigational	activator
Q12791	KCNMA1	DB01110	Miconazole	approved, investigational, vet_approved	inhibitor
Q12791	KCNMA1	DB00774	Hydroflumethiazide	approved, investigational, withdrawn	inducer
Q12791	KCNMA1	DB00436	Bendroflumethiazide	approved	inducer

Related Diseases to KCNMA1

Previous studies relating to the alternative splicing of KCNMA1 and disease information from the MeSH term (PubMed)

Gene	PMID	Title	Abstract	MeSH ID	MeSH term
KCNMA1	11880513	Cloning and characterization of glioma BK, a novel BK channel isoform highly expressed in human glioma cells.	Voltage-dependent large-conductance Ca2+-activated K+ channels (BK channels) are widely expressed in excitable and nonexcitable cells. BK channels exhibit diverse electrophysiological properties, which are attributable in part to alternative splicing of their alpha-subunits. BK currents have been implicated in the growth control of glial cells, and BK channels with novel biophysical properties have recently been characterized in human glioma cells. Here we report the isolation, cloning, and functional characterization of glioma BK (gBK), a novel splice isoform of hSlo, the gene that encodes the alpha-subunits of human BK channels. The primary sequence of gBK is 97% identical to its closest homolog hbr5, but it contains an additional 34-amino-acid exon at splice site 2 in the C-terminal tail of BK channels. hSlo transcripts containing this novel exon are expressed ubiquitously in various normal tissues as well as in neoplasmic samples, suggesting that the novel exon may modulate important physiological functions of BK channels. Expression of gBK in Xenopus oocytes gives rise to iberiotoxin-sensitive (IbTX) currents, with an IC(50) for IbTX of 5.7 nm and a Hill coefficient of 0.76. Single gBK channels have a unitary conductance of similar250 pS, and the currents show significantly slower activation and higher Ca2+ sensitivity than hbr5. Ca2+ sensitivity was enhanced specifically at physiologically relevant [Ca2+]i (100-500 nm). Examination of biopsies from patients with malignant gliomas has revealed specific overexpression of BK channels in gliomas compared with nonmalignant human cortical tissues. Importantly, tumor malignancy grades have correlated positively with BK channel expression, suggesting an important role for the gBK channel in glioma biology.	D001254	Astrocytoma
KCNMA1	11880513	Cloning and characterization of glioma BK, a novel BK channel isoform highly expressed in human glioma cells.	Voltage-dependent large-conductance Ca2+-activated K+ channels (BK channels) are widely expressed in excitable and nonexcitable cells. BK channels exhibit diverse electrophysiological properties, which are attributable in part to alternative splicing of their alpha-subunits. BK currents have been implicated in the growth control of glial cells, and BK channels with novel biophysical properties have recently been characterized in human glioma cells. Here we report the isolation, cloning, and functional characterization of glioma BK (gBK), a novel splice isoform of hSlo, the gene that encodes the alpha-subunits of human BK channels. The primary sequence of gBK is 97% identical to its closest homolog hbr5, but it contains an additional 34-amino-acid exon at splice site 2 in the C-terminal tail of BK channels. hSlo transcripts containing this novel exon are expressed ubiquitously in various normal tissues as well as in neoplasmic samples, suggesting that the novel exon may modulate important physiological functions of BK channels. Expression of gBK in Xenopus oocytes gives rise to iberiotoxin-sensitive (IbTX) currents, with an IC(50) for IbTX of 5.7 nm and a Hill coefficient of 0.76. Single gBK channels have a unitary conductance of similar250 pS, and the currents show significantly slower activation and higher Ca2+ sensitivity than hbr5. Ca2+ sensitivity was enhanced specifically at physiologically relevant [Ca2+]i (100-500 nm). Examination of biopsies from patients with malignant gliomas has revealed specific overexpression of BK channels in gliomas compared with nonmalignant human cortical tissues. Importantly, tumor malignancy grades have correlated positively with BK channel expression, suggesting an important role for the gBK channel in glioma biology.	D005909	Glioblastoma
KCNMA1	11880513	Cloning and characterization of glioma BK, a novel BK channel isoform highly expressed in human glioma cells.	Voltage-dependent large-conductance Ca2+-activated K+ channels (BK channels) are widely expressed in excitable and nonexcitable cells. BK channels exhibit diverse electrophysiological properties, which are attributable in part to alternative splicing of their alpha-subunits. BK currents have been implicated in the growth control of glial cells, and BK channels with novel biophysical properties have recently been characterized in human glioma cells. Here we report the isolation, cloning, and functional characterization of glioma BK (gBK), a novel splice isoform of hSlo, the gene that encodes the alpha-subunits of human BK channels. The primary sequence of gBK is 97% identical to its closest homolog hbr5, but it contains an additional 34-amino-acid exon at splice site 2 in the C-terminal tail of BK channels. hSlo transcripts containing this novel exon are expressed ubiquitously in various normal tissues as well as in neoplasmic samples, suggesting that the novel exon may modulate important physiological functions of BK channels. Expression of gBK in Xenopus oocytes gives rise to iberiotoxin-sensitive (IbTX) currents, with an IC(50) for IbTX of 5.7 nm and a Hill coefficient of 0.76. Single gBK channels have a unitary conductance of similar250 pS, and the currents show significantly slower activation and higher Ca2+ sensitivity than hbr5. Ca2+ sensitivity was enhanced specifically at physiologically relevant [Ca2+]i (100-500 nm). Examination of biopsies from patients with malignant gliomas has revealed specific overexpression of BK channels in gliomas compared with nonmalignant human cortical tissues. Importantly, tumor malignancy grades have correlated positively with BK channel expression, suggesting an important role for the gBK channel in glioma biology.	D005910	Glioma
KCNMA1	17150299	Diabetes-induced changes in the alternative splicing of the slo gene in corporal tissue.	Erectile dysfunction is a common diabetic complication. Preclinical studies have documented that the Slo gene (encoding the BK or Maxi-K channel alpha-subunit) plays a critical role in erectile function. Therefore, we determined whether diabetes induces changes in the splicing of the Slo gene relevant to erectile function.	D048909	Diabetes Complications
KCNMA1	17150299	Diabetes-induced changes in the alternative splicing of the slo gene in corporal tissue.	Erectile dysfunction is a common diabetic complication. Preclinical studies have documented that the Slo gene (encoding the BK or Maxi-K channel alpha-subunit) plays a critical role in erectile function. Therefore, we determined whether diabetes induces changes in the splicing of the Slo gene relevant to erectile function.	D003921	Diabetes Mellitus, Experimental
KCNMA1	17150299	Diabetes-induced changes in the alternative splicing of the slo gene in corporal tissue.	Erectile dysfunction is a common diabetic complication. Preclinical studies have documented that the Slo gene (encoding the BK or Maxi-K channel alpha-subunit) plays a critical role in erectile function. Therefore, we determined whether diabetes induces changes in the splicing of the Slo gene relevant to erectile function.	D007172	Erectile Dysfunction

Clinically important variants in KCNMA1

(ClinVar, 04/20/2024)

accession_id

uniprot_id

gene_name

Type

Variant

Clinical_significance