P35626 (ARBK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Beta-adrenergic receptor kinase 2
Short name=Beta-ARK-2
EC=2.7.11.15

Alternative name(s):
G-protein-coupled receptor kinase 3

Gene names

Name:	ADRBK2
Synonyms:	BARK2, GRK3

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	688 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors.
Catalytic activity	ATP + [beta-adrenergic receptor] = ADP + [beta-adrenergic receptor] phosphate.
Sequence similarities	Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. GPRK subfamily. Contains 1 AGC-kinase C-terminal domain. Contains 1 PH domain. Contains 1 protein kinase domain. Contains 1 RGS domain.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	receptor internalization Inferred from direct assay PubMed 20074556. Source: UniProtKB signal transduction Traceable author statement Ref.1. Source: ProtInc termination of G-protein coupled receptor signaling pathway Inferred from electronic annotation. Source: InterPro
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW G-protein coupled receptor kinase activity Inferred from electronic annotation. Source: Compara beta-adrenergic receptor kinase activity Inferred from electronic annotation. Source: EC phospholipid binding Inferred from electronic annotation. Source: InterPro protein kinase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 688	688	Beta-adrenergic receptor kinase 2		PRO_0000085632
Regions
	Domain	54 – 175	122	RGS
	Domain	191 – 453	263	Protein kinase
	Domain	454 – 521	68	AGC-kinase C-terminal
	Domain	558 – 652	95	PH
	Nucleotide binding	197 – 205	9	ATP By similarity
	Region	1 – 190	190	N-terminal
Sites
	Active site	317	1	Proton acceptor By similarity
	Binding site	220	1	ATP By similarity
Natural variations
	Natural variant	50	1	R → S. Ref.3 Corresponds to variant rs55700971 [ dbSNP | Ensembl ].		VAR_040380
	Natural variant	60	1	N → S. Ref.3 Corresponds to variant rs55740593 [ dbSNP | Ensembl ].		VAR_040381
	Natural variant	104	1	R → K in a lung bronchoalveolar carcinoma sample; somatic mutation. Ref.3		VAR_040382
	Natural variant	409	1	V → M. Corresponds to variant rs2272859 [ dbSNP | Ensembl ].		VAR_028005
Experimental info
	Sequence conflict	308	1	M → V in CAA48870. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P35626 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: 50844236A01C1423	FASTA	688	79,710
	10 20 30 40 50 60 MADLEAVLAD VSYLMAMEKS KATPAARASK RIVLPEPSIR SVMQKYLAER NEITFDKIFN 70 80 90 100 110 120 QKIGFLLFKD FCLNEINEAV PQVKFYEEIK EYEKLDNEED RLCRSRQIYD AYIMKELLSC 130 140 150 160 170 180 SHPFSKQAVE HVQSHLSKKQ VTSTLFQPYI EEICESLRGD IFQKFMESDK FTRFCQWKNV 190 200 210 220 230 240 ELNIHLTMNE FSVHRIIGRG GFGEVYGCRK ADTGKMYAMK CLDKKRIKMK QGETLALNER 250 260 270 280 290 300 IMLSLVSTGD CPFIVCMTYA FHTPDKLCFI LDLMNGGDLH YHLSQHGVFS EKEMRFYATE 310 320 330 340 350 360 IILGLEHMHN RFVVYRDLKP ANILLDEHGH ARISDLGLAC DFSKKKPHAS VGTHGYMAPE 370 380 390 400 410 420 VLQKGTAYDS SADWFSLGCM LFKLLRGHSP FRQHKTKDKH EIDRMTLTVN VELPDTFSPE 430 440 450 460 470 480 LKSLLEGLLQ RDVSKRLGCH GGGSQEVKEH SFFKGVDWQH VYLQKYPPPL IPPRGEVNAA 490 500 510 520 530 540 DAFDIGSFDE EDTKGIKLLD CDQELYKNFP LVISERWQQE VTETVYEAVN ADTDKIEARK 550 560 570 580 590 600 RAKNKQLGHE EDYALGKDCI MHGYMLKLGN PFLTQWQRRY FYLFPNRLEW RGEGESRQNL 610 620 630 640 650 660 LTMEQILSVE ETQIKDKKCI LFRIKGGKQF VLQCESDPEF VQWKKELNET FKEAQRLLRR 670 680 APKFLNKPRS GTVELPKPSL CHRNSNGL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning, functional expression and mRNA analysis of human beta-adrenergic receptor kinase 2." Parruti G., Ambrosini G., Sallese M., de Blasi A. Biochem. Biophys. Res. Commun. 190:475-481(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-50; SER-60 AND LYS-104.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X69117 mRNA. Translation: CAA48870.1. AL022329 Genomic DNA. Translation: CAB45657.1.
IPI	IPI00019926.
PIR	JC1469.
RefSeq	NP_005151.2. NM_005160.3.
UniGene	Hs.657494.
3D structure databases
ProteinModelPortal	P35626.
ModBase	Search...
Protein-protein interaction databases
IntAct	P35626. 2 interactions.
STRING	9606.ENSP00000317578.
PTM databases
PhosphoSite	P35626.
Polymorphism databases
DMDM	116241253.
Proteomic databases
PaxDb	P35626.
PRIDE	P35626.
Protocols and materials databases
DNASU	157.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000324198; ENSP00000317578; ENSG00000100077.
GeneID	157.
KEGG	hsa:157.
UCSC	uc003abw.2. human.
Organism-specific databases
CTD	157.
GeneCards	GC22P025960.
H-InvDB	HIX0041309.
HGNC	HGNC:290. ADRBK2.
HPA	HPA000804.
MIM	109636. gene.
neXtProt	NX_P35626.
PharmGKB	PA41.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000006742.
HOVERGEN	HBG050559.
InParanoid	P35626.
KO	K00910.
OMA	DIFQKFM.
OrthoDB	EOG4W3SMD.
PhylomeDB	P35626.
Enzyme and pathway databases
BRENDA	2.7.11.15. 2681.
Pathway_Interaction_DB	txa2pathway. Thromboxane A2 receptor signaling.
Gene expression databases
ArrayExpress	P35626.
Bgee	P35626.
CleanEx	HS_ADRBK2.
Genevestigator	P35626.
GermOnline	ENSG00000100077. Homo sapiens.
Family and domain databases
Gene3D	2.30.29.30. 1 hit.
InterPro	IPR000961. AGC-kinase_C. IPR000239. GPCR_kinase. IPR011009. Kinase-like_dom. IPR011993. PH_like_dom. IPR001849. Pleckstrin_homology. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR000342. Regulat_G_prot_signal. IPR016137. Regulat_G_prot_signal_superfam. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00169. PH. 1 hit. PF00069. Pkinase. 1 hit. PF00615. RGS. 1 hit. [Graphical view]
PRINTS	PR00717. GPCRKINASE.
SMART	SM00233. PH. 1 hit. SM00315. RGS. 1 hit. SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit. SSF48097. Regulat_G_prot_signal_superfam. 1 hit.
PROSITE	PS51285. AGC_KINASE_CTER. 1 hit. PS50003. PH_DOMAIN. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. PS50132. RGS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P35626.
ChEMBL	CHEMBL1075166.
DrugBank	DB00171. Adenosine triphosphate.
GenomeRNAi	157.
NextBio	625.
SOURCE	Search...

Entry information

Entry name

ARBK2_HUMAN

Accession

Primary (citable) accession number: P35626
Secondary accession number(s): Q9UGW9

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	October 17, 2006
Last modified:	May 1, 2013
This is version 135 of the entry and version 2 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.