Q8N568 (DCLK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase DCLK2
EC=2.7.11.1

Alternative name(s):
CaMK-like CREB regulatory kinase 2
Short name=CL2
Short name=CLICK-II
Short name=CLICK2
Doublecortin domain-containing protein 3B
Doublecortin-like and CAM kinase-like 2
Doublecortin-like kinase 2

Gene names

Name:	DCLK2
Synonyms:	DCAMKL2, DCDC3B, DCK2

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

General annotation (Comments)

Function	Protein kinase with a significantly reduced C(a2+)/CAM affinity and dependence compared to other members of the CaMK family. May play a role in the down-regulation of CRE-dependent gene activation probably by phosphorylation of the CREB coactivator CRTC2/TORC2 and the resulting retention of TORC2 in the cytoplasm By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	Binds to and stabilizes microtubules By similarity. Interacts with MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK9/JNK2, PPP1R9B/NEURABIN-2 and actin By similarity.
Subcellular location	Cytoplasm › cytoskeleton. Note: Colocalizes with microtubules By similarity.
Tissue specificity	Expressed in the brain, heart and eyes. Ref.5
Developmental stage	Expressed in fetal brain, and, to a lower extent, in fetal kidney. Ref.5
Domain	The doublecortin domains are involved in the colocalization with microtubules By similarity.
Post-translational modification	Autophosphorylated By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily. Contains 2 doublecortin domains. Contains 1 protein kinase domain.
Sequence caution	The sequence BAD92418.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoskeleton
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	intracellular signal transduction Inferred from electronic annotation. Source: InterPro
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8N568-1)

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 2 (identifier: Q8N568-2)

The sequence of this isoform differs from the canonical sequence as follows:
     353-353: Missing.

Note: By homology to mouse isoform 2.

Isoform 3 (identifier: Q8N568-3)

The sequence of this isoform differs from the canonical sequence as follows:
     321-321: V → VKRGGHYSSAYSTAKSPV

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 766	766	Serine/threonine-protein kinase DCLK2		PRO_0000085922
Regions
	Domain	72 – 158	87	Doublecortin 1
	Domain	197 – 280	84	Doublecortin 2
	Domain	394 – 651	258	Protein kinase
	Nucleotide binding	400 – 408	9	ATP By similarity
	Compositional bias	293 – 362	70	Ser-rich
	Compositional bias	713 – 753	41	Pro-rich
Sites
	Active site	515	1	Proton acceptor By similarity
	Binding site	423	1	ATP By similarity
Amino acid modifications
	Modified residue	6	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	321	1	V → VKRGGHYSSAYSTAKSPV in isoform 3.		VSP_012793
	Alternative sequence	353	1	Missing in isoform 2.		VSP_012794
	Natural variant	119	1	G → C. Ref.7 Corresponds to variant rs56327537 [ dbSNP | Ensembl ].		VAR_040441
	Natural variant	372	1	R → H. Ref.7 Corresponds to variant rs34386880 [ dbSNP | Ensembl ].		VAR_040442
	Natural variant	583	1	I → V. Ref.7 Corresponds to variant rs35745104 [ dbSNP | Ensembl ].		VAR_040443
Experimental info
	Sequence conflict	694	1	A → V in CAD39156. Ref.3
	Sequence conflict	748	1	P → C in BAD92418. Ref.1
	Sequence conflict	748	1	P → C in CAD39156. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 18, 2010. Version 4. Checksum: 024F3223874AE83C	FASTA	766	83,606
	10 20 30 40 50 60 MASTRSIELE HFEERDKRPR PGSRRGAPSS SGGSSSSGPK GNGLIPSPAH SAHCSFYRTR 70 80 90 100 110 120 TLQALSSEKK AKKARFYRNG DRYFKGLVFA ISSDRFRSFD ALLIELTRSL SDNVNLPQGV 130 140 150 160 170 180 RTIYTIDGSR KVTSLDELLE GESYVCASNE PFRKVDYTKN INPNWSVNIK GGTSRALAAA 190 200 210 220 230 240 SSVKSEVKES KDFIKPKLVT VIRSGVKPRK AVRILLNKKT AHSFEQVLTD ITEAIKLDSG 250 260 270 280 290 300 VVKRLCTLDG KQVTCLQDFF GDDDVFIACG PEKFRYAQDD FVLDHSECRV LKSSYSRSSA 310 320 330 340 350 360 VKYSGSKSPG PSRRSKSPAS VNGTPSSQLS TPKSTKSSSS SPTSPGSFRG LKQISAHGRS 370 380 390 400 410 420 SSNVNGGPEL DRCISPEGVN GNRCSESSTL LEKYKIGKVI GDGNFAVVKE CIDRSTGKEF 430 440 450 460 470 480 ALKIIDKAKC CGKEHLIENE VSILRRVKHP NIIMLVEEME TATELFLVME LVKGGDLFDA 490 500 510 520 530 540 ITSSTKYTER DGSAMVYNLA NALRYLHGLS IVHRDIKPEN LLVCEYPDGT KSLKLGDFGL 550 560 570 580 590 600 ATVVEGPLYT VCGTPTYVAP EIIAETGYGL KVDIWAAGVI TYILLCGFPP FRSENNLQED 610 620 630 640 650 660 LFDQILAGKL EFPAPYWDNI TDSAKELISQ MLQVNVEARC TAGQILSHPW VSDDASQENN 670 680 690 700 710 720 MQAEVTGKLK QHFNNALPKQ NSTTTGVSVI MNTALDKEGQ IFCSKHCQDS GRPGMEPISP 730 740 750 760 VPPSVEEIPV PGEAVPAPTP PESPTPHPPP AAPGGERAGT WRRHRD
	Isoform 2 [UniParc]. Checksum: 48EE55037EFF8AD8	FASTA	765	83,478
	10 20 30 40 50 60 MASTRSIELE HFEERDKRPR PGSRRGAPSS SGGSSSSGPK GNGLIPSPAH SAHCSFYRTR 70 80 90 100 110 120 TLQALSSEKK AKKARFYRNG DRYFKGLVFA ISSDRFRSFD ALLIELTRSL SDNVNLPQGV 130 140 150 160 170 180 RTIYTIDGSR KVTSLDELLE GESYVCASNE PFRKVDYTKN INPNWSVNIK GGTSRALAAA 190 200 210 220 230 240 SSVKSEVKES KDFIKPKLVT VIRSGVKPRK AVRILLNKKT AHSFEQVLTD ITEAIKLDSG 250 260 270 280 290 300 VVKRLCTLDG KQVTCLQDFF GDDDVFIACG PEKFRYAQDD FVLDHSECRV LKSSYSRSSA 310 320 330 340 350 360 VKYSGSKSPG PSRRSKSPAS VNGTPSSQLS TPKSTKSSSS SPTSPGSFRG LKISAHGRSS 370 380 390 400 410 420 SNVNGGPELD RCISPEGVNG NRCSESSTLL EKYKIGKVIG DGNFAVVKEC IDRSTGKEFA 430 440 450 460 470 480 LKIIDKAKCC GKEHLIENEV SILRRVKHPN IIMLVEEMET ATELFLVMEL VKGGDLFDAI 490 500 510 520 530 540 TSSTKYTERD GSAMVYNLAN ALRYLHGLSI VHRDIKPENL LVCEYPDGTK SLKLGDFGLA 550 560 570 580 590 600 TVVEGPLYTV CGTPTYVAPE IIAETGYGLK VDIWAAGVIT YILLCGFPPF RSENNLQEDL 610 620 630 640 650 660 FDQILAGKLE FPAPYWDNIT DSAKELISQM LQVNVEARCT AGQILSHPWV SDDASQENNM 670 680 690 700 710 720 QAEVTGKLKQ HFNNALPKQN STTTGVSVIM NTALDKEGQI FCSKHCQDSG RPGMEPISPV 730 740 750 760 PPSVEEIPVP GEAVPAPTPP ESPTPHPPPA APGGERAGTW RRHRD
	Isoform 3 [UniParc]. Checksum: D69154961F0CFF77	FASTA	783	85,384
	10 20 30 40 50 60 MASTRSIELE HFEERDKRPR PGSRRGAPSS SGGSSSSGPK GNGLIPSPAH SAHCSFYRTR 70 80 90 100 110 120 TLQALSSEKK AKKARFYRNG DRYFKGLVFA ISSDRFRSFD ALLIELTRSL SDNVNLPQGV 130 140 150 160 170 180 RTIYTIDGSR KVTSLDELLE GESYVCASNE PFRKVDYTKN INPNWSVNIK GGTSRALAAA 190 200 210 220 230 240 SSVKSEVKES KDFIKPKLVT VIRSGVKPRK AVRILLNKKT AHSFEQVLTD ITEAIKLDSG 250 260 270 280 290 300 VVKRLCTLDG KQVTCLQDFF GDDDVFIACG PEKFRYAQDD FVLDHSECRV LKSSYSRSSA 310 320 330 340 350 360 VKYSGSKSPG PSRRSKSPAS VKRGGHYSSA YSTAKSPVNG TPSSQLSTPK STKSSSSSPT 370 380 390 400 410 420 SPGSFRGLKQ ISAHGRSSSN VNGGPELDRC ISPEGVNGNR CSESSTLLEK YKIGKVIGDG 430 440 450 460 470 480 NFAVVKECID RSTGKEFALK IIDKAKCCGK EHLIENEVSI LRRVKHPNII MLVEEMETAT 490 500 510 520 530 540 ELFLVMELVK GGDLFDAITS STKYTERDGS AMVYNLANAL RYLHGLSIVH RDIKPENLLV 550 560 570 580 590 600 CEYPDGTKSL KLGDFGLATV VEGPLYTVCG TPTYVAPEII AETGYGLKVD IWAAGVITYI 610 620 630 640 650 660 LLCGFPPFRS ENNLQEDLFD QILAGKLEFP APYWDNITDS AKELISQMLQ VNVEARCTAG 670 680 690 700 710 720 QILSHPWVSD DASQENNMQA EVTGKLKQHF NNALPKQNST TTGVSVIMNT ALDKEGQIFC 730 740 750 760 770 780 SKHCQDSGRP GMEPISPVPP SVEEIPVPGE AVPAPTPPES PTPHPPPAAP GGERAGTWRR HRD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 68-766 (ISOFORM 3). Tissue: Amygdala.
[4]	"The evolving doublecortin (DCX) superfamily." Reiner O., Coquelle F.M., Peter B., Levy T., Kaplan A., Sapir T., Orr I., Barkai N., Eichele G., Bergmann S. BMC Genomics 7:188-188(2006) [PubMed] [Europe PMC] [Abstract] Cited for: GENE FAMILY.
[5]	"Alternative transcripts of Dclk1 and Dclk2 and their expression in doublecortin knockout mice." Tuy F.P.D., Saillour Y., Kappeler C., Chelly J., Francis F. Dev. Neurosci. 30:171-186(2008) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[6]	"The doublecortin gene family and disorders of neuronal structure." Dijkmans T.F., van Hooijdonk L.W.A., Fitzsimons C.P., Vreugdenhil E. Cent. Nerv. Syst. Agents Med. Chem. 10:32-46(2010) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW, GENE FAMILY.
[7]	"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] CYS-119; HIS-372 AND VAL-583.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB209181 mRNA. Translation: BAD92418.1. Different initiation. AC093748 Genomic DNA. No translation available. AC105343 Genomic DNA. No translation available. AC108934 Genomic DNA. No translation available. AC118064 Genomic DNA. No translation available. AL834498 mRNA. Translation: CAD39156.1.
IPI	IPI00296360. IPI00552471. IPI00552604.
RefSeq	NP_001035350.2. NM_001040260.3. NP_001035351.4. NM_001040261.4.
UniGene	Hs.591683.
3D structure databases
ProteinModelPortal	Q8N568.
SMR	Q8N568. Positions 64-169, 367-674.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8N568. 2 interactions.
STRING	9606.ENSP00000296550.
PTM databases
PhosphoSite	Q8N568.
Polymorphism databases
DMDM	296439470.
Proteomic databases
PaxDb	Q8N568.
PRIDE	Q8N568.
Protocols and materials databases
DNASU	166614.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000296550; ENSP00000296550; ENSG00000170390. ENST00000302176; ENSP00000303887; ENSG00000170390. ENST00000506325; ENSP00000427235; ENSG00000170390.
GeneID	166614.
KEGG	hsa:166614.
UCSC	uc003ilm.4. human. uc003ilo.4. human.
Organism-specific databases
CTD	166614.
GeneCards	GC04P150999.
HGNC	HGNC:19002. DCLK2.
HPA	HPA015770.
MIM	613166. gene.
neXtProt	NX_Q8N568.
PharmGKB	PA162383366.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000230855.
HOVERGEN	HBG003790.
KO	K08805.
OMA	DYTKNIN.
OrthoDB	EOG4WH8KG.
Gene expression databases
ArrayExpress	Q8N568.
Bgee	Q8N568.
CleanEx	HS_DCLK2.
Genevestigator	Q8N568.
GermOnline	ENSG00000170390. Homo sapiens.
Family and domain databases
Gene3D	3.10.20.230. 2 hits.
InterPro	IPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase. IPR003533. Doublecortin_dom. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
PANTHER	PTHR24347. PTHR24347. 1 hit.
Pfam	PF03607. DCX. 2 hits. PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00537. DCX. 2 hits. SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF89837. Doublecortin_dom. 2 hits. SSF56112. Kinase_like. 1 hit.
PROSITE	PS50309. DC. 2 hits. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL5519.
GenomeRNAi	166614.
NextBio	88597.
SOURCE	Search...

Entry information

Entry name

DCLK2_HUMAN

Accession

Primary (citable) accession number: Q8N568
Secondary accession number(s): C9J5Q9, Q59GC8, Q8N399

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 15, 2005
Last sequence update:	May 18, 2010
Last modified:	May 1, 2013
This is version 99 of the entry and version 4 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.