Reviewed, UniProtKB/Swiss-Prot Q13627 (DYR1A_HUMAN)

Names and origin

Protein names

Recommended name:
    Dual specificity tyrosine-phosphorylation-regulated kinase 1A
    EC=2.7.12.1
Alternative name(s):
    Protein kinase minibrain homolog
      Short name=MNBH
      Short name=hMNB
    HP86
    Dual specificity YAK1-related kinase

Gene names

Name:	DYRK1A
Synonyms:	DYRK, MNB, MNBH

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	763 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	May play a role in a signaling pathway regulating nuclear functions of cell proliferation. Phosphorylates serine, threonine and tyrosine residues in its sequence and in exogenous substrates.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Inhibited by RANBP9.
Subunit structure	Interacts RAD54L2/ARIP4 By similarity. Interacts with RANBP9.
Subcellular location	Nucleus speckle.
Tissue specificity	Ubiquitous. Highest levels in skeletal muscle, testis, fetal lung and fetal kidney.
Developmental stage	Expressed in the developing central nervous system.
Post-translational modification	Autophosphorylated on tyrosine residues.
Involvement in disease	Overexpressed 1.5-fold in fetal Down syndrome brain.
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MNB/DYRK subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	nervous system development Ref.3 Traceable author statement. Source: ProtInc peptidyl-tyrosine phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB protein amino acid autophosphorylation Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	nuclear speck Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	protein self-association Inferred from sequence or structural similarity. Source: UniProtKB protein serine/threonine kinase activity Ref.3 Inferred from sequence or structural similarity. Source: UniProtKB protein tyrosine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
YWHAB	P31946	3	EBI-1053621,EBI-359815

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Notes: Additional isoforms seem to exist.

Isoform Long (identifier: Q13627-1)

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 1 (identifier: Q13627-2)

The sequence of this isoform differs from the canonical sequence as follows:
     70-78: Missing.

Isoform 2 (identifier: Q13627-3)

The sequence of this isoform differs from the canonical sequence as follows:
     516-529: GGSSGTSNSGRARS → GASAISCSSWLVRH
     530-763: Missing.

Isoform 3 (identifier: Q13627-4)

The sequence of this isoform differs from the canonical sequence as follows:
     516-540: GGSSGTSNSGRARSDPTHQHRHSGG → VEQHWMPGAFRMTVSFTLEVHDVPV
     541-763: Missing.

Isoform 4 (identifier: Q13627-5)

The sequence of this isoform differs from the canonical sequence as follows:
     559-584: RQQFPAPLGWSGTEAPTQVTVETHPV → SSHVVHLLVSPAILRWSSTGCQVPLE
     585-763: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 763	763	Dual specificity tyrosine-phosphorylation-regulated kinase 1A
Regions
	Domain	159 – 479	321	Protein kinase
	Nucleotide binding	165 – 173	9	ATP By similarity
	Motif	117 – 134	18	Bipartite nuclear localization signal Potential
	Compositional bias	509 – 515	7	Poly-Ser
	Compositional bias	599 – 602	4	Poly-His
	Compositional bias	607 – 619	13	Poly-His
	Compositional bias	656 – 672	17	Ser/Thr-rich
	Compositional bias	664 – 671	8	Poly-Ser
Sites
	Active site	287	1	Proton acceptor By similarity
	Binding site	188	1	ATP By similarity
Amino acid modifications
	Modified residue	145	1	Phosphotyrosine
	Modified residue	219	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	319	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	321	1	Phosphotyrosine; by autocatalysis
Natural variations
	Alternative sequence	70 – 78	9	Missing in isoform 1.
	Alternative sequence	516 – 540	25	GGSSG…RHSGG → VEQHWMPGAFRMTVSFTLEV HDVPV in isoform 3.
	Alternative sequence	516 – 529	14	GGSSG…GRARS → GASAISCSSWLVRH in isoform 2.
	Alternative sequence	530 – 763	234	Missing in isoform 2.
	Alternative sequence	541 – 763	223	Missing in isoform 3.
	Alternative sequence	559 – 584	26	RQQFP…ETHPV → SSHVVHLLVSPAILRWSSTG CQVPLE in isoform 4.
	Alternative sequence	585 – 763	179	Missing in isoform 4.
	Natural variant	415	1	Y → F
	Natural variant	679	1	A → P
	Natural variant	681	1	Q → H
Experimental info
	Sequence conflict	32	1	G → A in AAC50939. Ref.1
	Sequence conflict	47	1	N → S in AAC50939. Ref.1
	Sequence conflict	57	1	S → P in AAC50939. Ref.1
	Sequence conflict	123	1	Q → R in AAC50939. Ref.1
	Sequence conflict	266	1	A → V in CAA05059. Ref.6
	Sequence conflict	357	1	G → R in CAA05059. Ref.6
	Sequence conflict	397	1	K → N in AAC50939. Ref.1
	Sequence conflict	592	1	A → G in AAC50939. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified July 15, 1998. Version 2. Checksum: 7C3A52A3CBB04FB5	FASTA	763	85,584
	10 20 30 40 50 60 MHTGGETSAC KPSSVRLAPS FSFHAAGLQM AGQMPHSHQY SDRRQPNISD QQVSALSYSD 70 80 90 100 110 120 QIQQPLTNQV MPDIVMLQRR MPQTFRDPAT APLRKLSVDL IKTYKHINEV YYAKKKRRHQ 130 140 150 160 170 180 QGQGDDSSHK KERKVYNDGY DDDNYDYIVK NGEKWMDRYE IDSLIGKGSF GQVVKAYDRV 190 200 210 220 230 240 EQEWVAIKII KNKKAFLNQA QIEVRLLELM NKHDTEMKYY IVHLKRHFMF RNHLCLVFEM 250 260 270 280 290 300 LSYNLYDLLR NTNFRGVSLN LTRKFAQQMC TALLFLATPE LSIIHCDLKP ENILLCNPKR 310 320 330 340 350 360 SAIKIVDFGS SCQLGQRIYQ YIQSRFYRSP EVLLGMPYDL AIDMWSLGCI LVEMHTGEPL 370 380 390 400 410 420 FSGANEVDQM NKIVEVLGIP PAHILDQAPK ARKFFEKLPD GTWNLKKTKD GKREYKPPGT 430 440 450 460 470 480 RKLHNILGVE TGGPGGRRAG ESGHTVADYL KFKDLILRML DYDPKTRIQP YYALQHSFFK 490 500 510 520 530 540 KTADEGTNTS NSVSTSPAME QSQSSGTTSS TSSSSGGSSG TSNSGRARSD PTHQHRHSGG 550 560 570 580 590 600 HFTAAVQAMD CETHSPQVRQ QFPAPLGWSG TEAPTQVTVE THPVQETTFH VAPQQNALHH 610 620 630 640 650 660 HHGNSSHHHH HHHHHHHHHG QQALGNRTRP RVYNSPTNSS STQDSMEVGH SHHSMTSLSS 670 680 690 700 710 720 STTSSSTSSS STGNQGNQAY QNRPVAANTL DFGQNGAMDV NLTVYSNPRQ ETGIAGHPTY 730 740 750 760 QFSANTGPAH YMTEGHLTMR QGADREESPM TGVCVQQSPV ASS
	Isoform 1 [UniParc]. Checksum: 59518E25F1D4FF96		754	84,556
	10 20 30 40 50 60 MHTGGETSAC KPSSVRLAPS FSFHAAGLQM AGQMPHSHQY SDRRQPNISD QQVSALSYSD 70 80 90 100 110 120 QIQQPLTNQR RMPQTFRDPA TAPLRKLSVD LIKTYKHINE VYYAKKKRRH QQGQGDDSSH 130 140 150 160 170 180 KKERKVYNDG YDDDNYDYIV KNGEKWMDRY EIDSLIGKGS FGQVVKAYDR VEQEWVAIKI 190 200 210 220 230 240 IKNKKAFLNQ AQIEVRLLEL MNKHDTEMKY YIVHLKRHFM FRNHLCLVFE MLSYNLYDLL 250 260 270 280 290 300 RNTNFRGVSL NLTRKFAQQM CTALLFLATP ELSIIHCDLK PENILLCNPK RSAIKIVDFG 310 320 330 340 350 360 SSCQLGQRIY QYIQSRFYRS PEVLLGMPYD LAIDMWSLGC ILVEMHTGEP LFSGANEVDQ 370 380 390 400 410 420 MNKIVEVLGI PPAHILDQAP KARKFFEKLP DGTWNLKKTK DGKREYKPPG TRKLHNILGV 430 440 450 460 470 480 ETGGPGGRRA GESGHTVADY LKFKDLILRM LDYDPKTRIQ PYYALQHSFF KKTADEGTNT 490 500 510 520 530 540 SNSVSTSPAM EQSQSSGTTS STSSSSGGSS GTSNSGRARS DPTHQHRHSG GHFTAAVQAM 550 560 570 580 590 600 DCETHSPQVR QQFPAPLGWS GTEAPTQVTV ETHPVQETTF HVAPQQNALH HHHGNSSHHH 610 620 630 640 650 660 HHHHHHHHHH GQQALGNRTR PRVYNSPTNS SSTQDSMEVG HSHHSMTSLS SSTTSSSTSS 670 680 690 700 710 720 SSTGNQGNQA YQNRPVAANT LDFGQNGAMD VNLTVYSNPR QETGIAGHPT YQFSANTGPA 730 740 750 HYMTEGHLTM RQGADREESP MTGVCVQQSP VASS
	Isoform 2 [UniParc]. Checksum: F639B3152ACC7750		529	60,330
	10 20 30 40 50 60 MHTGGETSAC KPSSVRLAPS FSFHAAGLQM AGQMPHSHQY SDRRQPNISD QQVSALSYSD 70 80 90 100 110 120 QIQQPLTNQV MPDIVMLQRR MPQTFRDPAT APLRKLSVDL IKTYKHINEV YYAKKKRRHQ 130 140 150 160 170 180 QGQGDDSSHK KERKVYNDGY DDDNYDYIVK NGEKWMDRYE IDSLIGKGSF GQVVKAYDRV 190 200 210 220 230 240 EQEWVAIKII KNKKAFLNQA QIEVRLLELM NKHDTEMKYY IVHLKRHFMF RNHLCLVFEM 250 260 270 280 290 300 LSYNLYDLLR NTNFRGVSLN LTRKFAQQMC TALLFLATPE LSIIHCDLKP ENILLCNPKR 310 320 330 340 350 360 SAIKIVDFGS SCQLGQRIYQ YIQSRFYRSP EVLLGMPYDL AIDMWSLGCI LVEMHTGEPL 370 380 390 400 410 420 FSGANEVDQM NKIVEVLGIP PAHILDQAPK ARKFFEKLPD GTWNLKKTKD GKREYKPPGT 430 440 450 460 470 480 RKLHNILGVE TGGPGGRRAG ESGHTVADYL KFKDLILRML DYDPKTRIQP YYALQHSFFK 490 500 510 520 KTADEGTNTS NSVSTSPAME QSQSSGTTSS TSSSSGASAI SCSSWLVRH
	Isoform 3 [UniParc]. Checksum: E02CE08DF1AE0AED		540	61,770
	10 20 30 40 50 60 MHTGGETSAC KPSSVRLAPS FSFHAAGLQM AGQMPHSHQY SDRRQPNISD QQVSALSYSD 70 80 90 100 110 120 QIQQPLTNQV MPDIVMLQRR MPQTFRDPAT APLRKLSVDL IKTYKHINEV YYAKKKRRHQ 130 140 150 160 170 180 QGQGDDSSHK KERKVYNDGY DDDNYDYIVK NGEKWMDRYE IDSLIGKGSF GQVVKAYDRV 190 200 210 220 230 240 EQEWVAIKII KNKKAFLNQA QIEVRLLELM NKHDTEMKYY IVHLKRHFMF RNHLCLVFEM 250 260 270 280 290 300 LSYNLYDLLR NTNFRGVSLN LTRKFAQQMC TALLFLATPE LSIIHCDLKP ENILLCNPKR 310 320 330 340 350 360 SAIKIVDFGS SCQLGQRIYQ YIQSRFYRSP EVLLGMPYDL AIDMWSLGCI LVEMHTGEPL 370 380 390 400 410 420 FSGANEVDQM NKIVEVLGIP PAHILDQAPK ARKFFEKLPD GTWNLKKTKD GKREYKPPGT 430 440 450 460 470 480 RKLHNILGVE TGGPGGRRAG ESGHTVADYL KFKDLILRML DYDPKTRIQP YYALQHSFFK 490 500 510 520 530 540 KTADEGTNTS NSVSTSPAME QSQSSGTTSS TSSSSVEQHW MPGAFRMTVS FTLEVHDVPV
	Isoform 4 [UniParc]. Checksum: BA2480B34BAB2878		584	66,099
	10 20 30 40 50 60 MHTGGETSAC KPSSVRLAPS FSFHAAGLQM AGQMPHSHQY SDRRQPNISD QQVSALSYSD 70 80 90 100 110 120 QIQQPLTNQV MPDIVMLQRR MPQTFRDPAT APLRKLSVDL IKTYKHINEV YYAKKKRRHQ 130 140 150 160 170 180 QGQGDDSSHK KERKVYNDGY DDDNYDYIVK NGEKWMDRYE IDSLIGKGSF GQVVKAYDRV 190 200 210 220 230 240 EQEWVAIKII KNKKAFLNQA QIEVRLLELM NKHDTEMKYY IVHLKRHFMF RNHLCLVFEM 250 260 270 280 290 300 LSYNLYDLLR NTNFRGVSLN LTRKFAQQMC TALLFLATPE LSIIHCDLKP ENILLCNPKR 310 320 330 340 350 360 SAIKIVDFGS SCQLGQRIYQ YIQSRFYRSP EVLLGMPYDL AIDMWSLGCI LVEMHTGEPL 370 380 390 400 410 420 FSGANEVDQM NKIVEVLGIP PAHILDQAPK ARKFFEKLPD GTWNLKKTKD GKREYKPPGT 430 440 450 460 470 480 RKLHNILGVE TGGPGGRRAG ESGHTVADYL KFKDLILRML DYDPKTRIQP YYALQHSFFK 490 500 510 520 530 540 KTADEGTNTS NSVSTSPAME QSQSSGTTSS TSSSSGGSSG TSNSGRARSD PTHQHRHSGG 550 560 570 580 HFTAAVQAMD CETHSPQVSS HVVHLLVSPA ILRWSSTGCQ VPLE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation of human and murine homologues of the Drosophila minibrain gene: human homologue maps to 21q22.2 in the Down syndrome 'critical region'." Song W.J., Sternberg L.R., Kasten-Sportes C., van Keuren M.L., Chung S.H., Slack A.C., Miller D.E., Glover T.W., Chiang P.W., Lou L., Kurnit D.W. Genomics 38:331-339(1996) [PubMed: 8975710] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), VARIANT PRO-679, TISSUE SPECIFICITY. Tissue: Fetal brain.
[2]	"A human homologue of Drosophila minibrain (MNB) is expressed in the neuronal regions affected in Down syndrome and maps to the critical region." Guimera J., Casas C., Pucharcos C., Solans A., Domenech A., Planas A.M., Ashley J., Lovett M., Estivill X., Pritchard M.A. Hum. Mol. Genet. 5:1305-1310(1996) [PubMed: 8872470] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), TISSUE SPECIFICITY, POSSIBLE INVOLVEMENT IN DOWN SYNDROME.
[3]	"Cloning of a human homolog of the Drosophila minibrain/rat Dyrk gene from 'the Down syndrome critical region' of chromosome 21." Shindoh N., Kudoh J., Maeda H., Yamaki A., Minoshima S., Shimizu Y., Shimizu N. Biochem. Biophys. Res. Commun. 225:92-99(1996) [PubMed: 8769099] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. Tissue: Fetal brain.
[4]	"Gene identification in 1.6-Mb region of the Down syndrome region on chromosome 21." Ohira M., Seki N., Nagase T., Suzuki E., Nomura N., Ohara O., Hattori M., Sakaki Y., Eki T., Murakami Y., Saito T., Ichikawa H., Ohki M. Genome Res. 7:47-58(1997) [PubMed: 9037601] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Promyelocytic leukemia.
[5]	"Human minibrain homologue (MNBH/DYRK1): characterization, alternative splicing, differential tissue expression, and overexpression in Down syndrome." Guimera J., Casas C., Estivill X., Pritchard M.A. Genomics 57:407-418(1999) [PubMed: 10329007] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), TISSUE SPECIFICITY, POSSIBLE INVOLVEMENT IN DOWN SYNDROME, VARIANTS PHE-415 AND HIS-681, ALTERNATIVE SPLICING.
[6]	"Transcriptional map of the 2.5-Mb CBR-ERG region of chromosome 21 involved in Down syndrome." Dahmane N., Ait Ghezala G., Gosset P., Chamoun Z., Dufresne-Zacharia M.-C., Lopes C., Rabatel N., Gassanova-Maugenre S., Chettouh Z., Abramowski V., Fayet E., Yaspo M.-L., Korn B., Blouin J.-L., Lehrach H., Poustka A., Antonarakis S.E., Sinet P.-M., Creau N., Delabar J.-M. Genomics 48:12-23(1998) [PubMed: 9503011] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 234-380. Tissue: Fetal brain.
[7]	"Serine/threonine kinase Mirk/Dyrk1B is an inhibitor of epithelial cell migration and is negatively regulated by the Met adaptor Ran-binding protein M." Zou Y., Lim S., Lee K., Deng X., Friedman E. J. Biol. Chem. 278:49573-49581(2003) [PubMed: 14500717] [Abstract] Cited for: INTERACTION WITH RANBP9, ENZYME REGULATION.
[8]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-145 AND TYR-321, MASS SPECTROMETRY.
[9]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-145, MASS SPECTROMETRY.
[10]	"Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry." Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., Keri G., Wehland J., Daub H. Mol. Cell. Proteomics 6:537-547(2007) [PubMed: 17192257] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-321, MASS SPECTROMETRY.
[11]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-321, MASS SPECTROMETRY. Tissue: Platelet.
[12]	"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: 17344846] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] PRO-679.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U58496 mRNA. Translation: AAC50939.1. U52373 mRNA. Translation: AAB18639.1. D85759 mRNA. Translation: BAA12866.1. D86550 mRNA. Translation: BAA13110.1. AF108830 mRNA. Translation: AAD31169.1. AJ001870 mRNA. Translation: CAA05059.1.
PIR	JC4898.
RefSeq	NP_001387.2. NP_567824.1. NP_569120.1. NP_569121.1. NP_569122.1.
UniGene	Hs.705437
3D structure databases
HSSP	HSSP built from PDB template 1I09 based on UniProtKB P49841.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q13627.
PTM databases
PhosphoSite	Q13627.
Genome annotation databases
Ensembl	ENSG00000157540. Homo sapiens. [Contig view]