P78508 (IRK10_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
ATP-sensitive inward rectifier potassium channel 10

Alternative name(s):
ATP-dependent inwardly rectifying potassium channel Kir4.1
Inward rectifier K(+) channel Kir1.2
Potassium channel, inwardly rectifying subfamily J member 10

Gene names

Name:

KCNJ10

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	379 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May be responsible for potassium buffering action of glial cells in the brain. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium and cesium By similarity.
Subunit structure	Seems to form heterodimer with Kir5.1/KCNJ16. Interacts with INADL By similarity.
Subcellular location	Membrane; Multi-pass membrane protein.
Involvement in disease	Defects in KCNJ10 are the cause of seizures-sensorineural deafness-ataxia-mental retardation-electrolyte imbalance (SESAME) [MIM:612780]. A complex disorder characterized by generalized seizures with onset in infancy, delayed psychomotor development, ataxia, sensorineural hearing loss, hypokalemia, metabolic alkalosis, and hypomagnesemia. Ref.6 Ref.7
Sequence similarities	Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ10 subfamily. [View classification]
Sequence caution	The sequence AAH34036.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Ion transport Potassium transport Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Deafness Disease mutation Epilepsy Mental retardation
Domain	Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding Potassium
Molecular function	Ionic channel Voltage-gated channel
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular component	integral to plasma membrane Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATP-activated inward rectifier potassium channel activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 379	379	ATP-sensitive inward rectifier potassium channel 10		PRO_0000154953
Regions
	Topological domain	1 – 64	64	Cytoplasmic By similarity
	Transmembrane	65 – 89	25	Helical; Name=M1; By similarity
	Topological domain	90 – 114	25	Extracellular By similarity
	Intramembrane	115 – 126	12	Helical; Pore-forming; Name=H5; By similarity
	Intramembrane	127 – 133	7	Pore-forming; By similarity
	Topological domain	134 – 142	9	Extracellular By similarity
	Transmembrane	143 – 164	22	Helical; Name=M2; By similarity
	Topological domain	165 – 379	215	Cytoplasmic By similarity
	Nucleotide binding	210 – 217	8	ATP Potential
	Motif	128 – 133	6	Selectivity filter By similarity
Sites
	Site	158	1	Role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesium By similarity
Natural variations
	Natural variant	65	1	R → P in SESAME. Ref.6 Ref.7		VAR_063059
	Natural variant	77	1	G → R in SESAME. Ref.6		VAR_063060
	Natural variant	140	1	C → R in SESAME. Ref.7		VAR_063061
	Natural variant	164	1	T → I in SESAME. Ref.7		VAR_063062
	Natural variant	167	1	A → V in SESAME. Ref.7		VAR_063063
	Natural variant	271	1	R → C. Ref.2 Corresponds to variant rs1130183 [ dbSNP | Ensembl ].		VAR_034018
	Natural variant	271	1	R → H. Corresponds to variant rs3795339 [ dbSNP | Ensembl ].		VAR_020339
	Natural variant	297	1	R → C in SESAME. Ref.7		VAR_063064
Experimental info
	Sequence conflict	50	1	L → P in AAB07046. Ref.2
	Sequence conflict	83	1	G → V in AAH34036. Ref.5
	Sequence conflict	166	1	L → Q in AAB07046. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P78508 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: D9DA013FF4003533	FASTA	379	42,508
	10 20 30 40 50 60 MTSVAKVYYS QTTQTESRPL MGPGIRRRRV LTKDGRSNVR MEHIADKRFL YLKDLWTTFI 70 80 90 100 110 120 DMQWRYKLLL FSATFAGTWF LFGVVWYLVA VAHGDLLELD PPANHTPCVV QVHTLTGAFL 130 140 150 160 170 180 FSLESQTTIG YGFRYISEEC PLAIVLLIAQ LVLTTILEIF ITGTFLAKIA RPKKRAETIR 190 200 210 220 230 240 FSQHAVVASH NGKPCLMIRV ANMRKSLLIG CQVTGKLLQT HQTKEGENIR LNQVNVTFQV 250 260 270 280 290 300 DTASDSPFLI LPLTFYHVVD ETSPLKDLPL RSGEGDFELV LILSGTVEST SATCQVRTSY 310 320 330 340 350 360 LPEEILWGYE FTPAISLSAS GKYIADFSLF DQVVKVASPS GLRDSTVRYG DPEKLKLEES 370 LREQAEKEGS ALSVRISNV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of two K+ inward rectifier (Kir) 1.1 potassium channel homologs from human kidney (Kir1.2 and Kir1.3)." Shuck M.E., Piser T.M., Bock J.H., Slightom J.L., Lee K.S., Bienkowski M.J. J. Biol. Chem. 272:586-593(1997) [PubMed: 8995301] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], NUCLEOTIDE SEQUENCE [MRNA] OF 143-379. Tissue: Kidney.
[2]	"Co-expression of human Kir3 subunits can yield channels with different functional properties." Schoots O., Wilson J.M., Ethier N., Bigras E., Hebert T.E., Van Tol H.H.M. Cell. Signal. 11:871-883(1999) [PubMed: 10659995] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT CYS-271. Tissue: Cerebellum.
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[6]	"Epilepsy, ataxia, sensorineural deafness, tubulopathy, and KCNJ10 mutations." Bockenhauer D., Feather S., Stanescu H.C., Bandulik S., Zdebik A.A., Reichold M., Tobin J., Lieberer E., Sterner C., Landoure G., Arora R., Sirimanna T., Thompson D., Cross J.H., van't Hoff W., Al Masri O., Tullus K., Yeung S. , Anikster Y., Klootwijk E., Hubank M., Dillon M.J., Heitzmann D., Arcos-Burgos M., Knepper M.A., Dobbie A., Gahl W.A., Warth R., Sheridan E., Kleta R. N. Engl. J. Med. 360:1960-1970(2009) [PubMed: 19420365] [Abstract] Cited for: VARIANTS SESAME PRO-65 AND ARG-77.
[7]	"Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SeSAME syndrome) caused by mutations in KCNJ10." Scholl U.I., Choi M., Liu T., Ramaekers V.T., Hausler M.G., Grimmer J., Tobe S.W., Farhi A., Nelson-Williams C., Lifton R.P. Proc. Natl. Acad. Sci. U.S.A. 106:5842-5847(2009) [PubMed: 19289823] [Abstract] Cited for: VARIANTS SESAME PRO-65; ARG-140; ILE-164; VAL-167 AND CYS-297.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U73192 Genomic DNA. Translation: AAC50923.1. U73193 mRNA. Translation: AAC50924.1. U52155 mRNA. Translation: AAB07046.1. AL513302 Genomic DNA. Translation: CAH71493.1. CH471121 Genomic DNA. Translation: EAW52749.1. BC034036 mRNA. Translation: AAH34036.2. Different initiation. BC131627 mRNA. Translation: AAI31628.1.
IPI	IPI00020273.
RefSeq	NP_002232.2. NM_002241.4.
UniGene	Hs.408960.
3D structure databases
ProteinModelPortal	P78508.
SMR	P78508. Positions 27-353.
ModBase	Search...
Protein-protein interaction databases
STRING	P78508.
PTM databases
PhosphoSite	P78508.
Polymorphism databases
DMDM	2493605.
Proteomic databases
PRIDE	P78508.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000368089; ENSP00000357068; ENSG00000177807.
GeneID	3766.
KEGG	hsa:3766.
UCSC	uc001fuw.1. human.
Organism-specific databases
CTD	3766.
GeneCards	GC01M160007.
H-InvDB	HIX0001207.
HGNC	HGNC:6256. KCNJ10.
HPA	CAB022636.
MIM	602208. gene. 612780. phenotype.
neXtProt	NX_P78508.
Orphanet	90636. Autosomal recessive nonsyndromic sensorineural deafness type DFNB. 199343. SeSAME syndrome.
PharmGKB	PA30043.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HBG716702.
HOVERGEN	HBG006178.
InParanoid	P78508.
OMA	LGPPANH.
OrthoDB	EOG483D4R.
PhylomeDB	P78508.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System.
Gene expression databases
ArrayExpress	P78508.
Bgee	P78508.
CleanEx	HS_KCNJ10.
Genevestigator	P78508.
GermOnline	ENSG00000177807. Homo sapiens.
Family and domain databases
InterPro	IPR014756. Ig_E-set. IPR016449. K_chnl_inward-rec_Kir. IPR001838. K_chnl_inward-rec_Kir-like. IPR003269. K_chnl_inward-rec_Kir1.2. IPR013521. K_chnl_inward-rec_Kir_Cr2. IPR013518. K_chnl_inward-rec_Kir_cyto. [Graphical view]
Gene3D	G3DSA:2.60.40.1400. IR_K+channel_cytopl. 1 hit.
KO	K05003.
PANTHER	PTHR11767. K+channel_IR. 1 hit. PTHR11767:SF21. KIR12_channel. 1 hit.
Pfam	PF01007. IRK. 1 hit. [Graphical view]
PIRSF	PIRSF005465. GIRK_kir. 1 hit.
PRINTS	PR01322. KIR12CHANNEL. PR01320. KIRCHANNEL.
SUPFAM	SSF81296. Ig_E-set. 1 hit.
ProtoNet	Search...
Other
NextBio	14767.
SOURCE	Search...

Entry information

Entry name

IRK10_HUMAN

Accession

Primary (citable) accession number: P78508
Secondary accession number(s): A3KME7 , Q5VUT9, Q8N4I7, Q92808

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	May 1, 1997
Last modified:	January 25, 2012
This is version 113 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.