Reviewed, UniProtKB/Swiss-Prot Q15208 (STK38_HUMAN)

Names and origin

Protein names

Recommended name:
    Serine/threonine-protein kinase 38
    EC=2.7.11.1
Alternative name(s):
    NDR1 protein kinase
    Nuclear Dbf2-related kinase 1

Gene names

Name:	STK38
Synonyms:	NDR1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	465 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium. Ref.5 Ref.7 Ref.1
Enzyme regulation	Activated by binding of S100B which releases autoinhibitory N-lobe interactions, enabling ATP to bind and the autophosphorylation of Ser-281. Thr-444 then undergoes calcium-dependent phosphorylation by an upstream kinase. Interactions between phosphorylated Thr-444 and the N-lobe promote additional structural changes that complete the activation of the kinase. Autoinhibition is also released by the binding of MOB1/MOBKL1A and MOB2/HCCA2 to the N-terminal of STK38. Ref.5 Ref.6 Ref.7 Ref.11
Subunit structure	Homodimeric S100B binds two molecules of STK38. Component of the MLL5-L complex, at least composed of MLL5, STK38, PPP1CA, PPP1CB, PPP1CC, HCFC1, ACTB and OGT. Interacts with MOB1 and MOB2. Ref.5 Ref.6 Ref.7 Ref.11
Subcellular location	Nucleus. Cytoplasm. Note: Low levels present in the cytoplasm. Ref.7 Ref.1
Tissue specificity	Ubiquitously expressed with highest levels observed in peripheral blood leukocytes. Ref.7 Ref.1
Sequence similarities	Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. Contains 1 AGC-kinase C-terminal domain. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	protein amino acid phosphorylation Ref.5 Inferred from direct assay. Source: UniProtKB protein kinase cascade Ref.5 Inferred from direct assay. Source: UniProtKB
Cellular component	MLL5-L complex Ref.10 Inferred from direct assay. Source: UniProtKB cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Ref.5 Inferred from direct assay. Source: UniProtKB magnesium ion binding Ref.5 Inferred from direct assay. Source: UniProtKB protein binding Ref.7 Inferred from physical interaction. Source: IntAct protein serine/threonine kinase activity Ref.1 Ref.5 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ARRB1	P49407	1	EBI-458376,EBI-743313
ARRB2	P32121	1	EBI-458376,EBI-714559
MOBKL1B	Q9H8S9	1	EBI-458376,EBI-748229

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.4

Chain

2 – 465

464

Serine/threonine-protein kinase 38

PRO_0000086718

Regions

Domain

89 – 382

294

Protein kinase

Domain

383 – 455

73

AGC-kinase C-terminal

Nucleotide binding

95 – 103

9

ATP By similarity UniProtKB O95835

Region

62 – 87

26

Interaction with S100B

Sites

Active site

212

1

Proton acceptor By similarity UniProtKB O95835

Binding site

118

1

ATP Ref.5 Ref.1

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.4

Modified residue

26

1

Phosphothreonine Ref.8

Modified residue

74

1

Phosphothreonine Ref.5

Modified residue

281

1

Phosphoserine; by autocatalysis Ref.5

Modified residue

444

1

Phosphothreonine Ref.5

Natural variations

Natural variant

18

1

E → K in a metastatic melanoma sample; somatic mutation. Ref.12

VAR_041196

Natural variant

145

1

D → N: dbSNP rs56005153. Ref.12

VAR_041197

Natural variant

267

1

K → R: dbSNP rs56105564. Ref.12

VAR_041198

Experimental info

Mutagenesis

74

1

T → A: Decreases autophosphorylation and kinase activity. Reduced binding of S100B. Ref.5

Mutagenesis

118

1

K → A: Loss of autophosphorylation and kinase activity. Ref.5 Ref.1

Mutagenesis

281

1

S → A: Loss of autophosphorylation and kinase activity. Ref.5

Mutagenesis

444

1

T → A: Decreases autophosphorylation and kinase activity. Ref.5

Secondary structure

1

.

.

.

465

Helix Strand Turn

Details...

Helix

74 – 85

12

Sequences

	Sequence		Length	Mass (Da)
	Q15208-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 7262221DBFFAF83C	FASTA	465	54,190
	10 20 30 40 50 60 MAMTGSTPCS SMSNHTKERV TMTKVTLENF YSNLIAQHEE REMRQKKLEK VMEEEGLKDE 70 80 90 100 110 120 EKRLRRSAHA RKETEFLRLK RTRLGLEDFE SLKVIGRGAF GEVRLVQKKD TGHVYAMKIL 130 140 150 160 170 180 RKADMLEKEQ VGHIRAERDI LVEADSLWVV KMFYSFQDKL NLYLIMEFLP GGDMMTLLMK 190 200 210 220 230 240 KDTLTEEETQ FYIAETVLAI DSIHQLGFIH RDIKPDNLLL DSKGHVKLSD FGLCTGLKKA 250 260 270 280 290 300 HRTEFYRNLN HSLPSDFTFQ NMNSKRKAET WKRNRRQLAF STVGTPDYIA PEVFMQTGYN 310 320 330 340 350 360 KLCDWWSLGV IMYEMLIGYP PFCSETPQET YKKVMNWKET LTFPPEVPIS EKAKDLILRF 370 380 390 400 410 420 CCEWEHRIGA PGVEEIKSNS FFEGVDWEHI RERPAAISIE IKSIDDTSNF DEFPESDILK 430 440 450 460 PTVATSNHPE TDYKNKDWVF INYTYKRFEG LTARGAIPSY MKAAK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and characterization of a conserved nuclear serine/threonine protein kinase." Millward T.A., Cron P., Hemmings B.A. Proc. Natl. Acad. Sci. U.S.A. 92:5022-5026(1995) [PubMed: 7761441] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-118. Tissue: Fetal brain.
[2]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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: Placenta and Uterus.
[4]	Bienvenut W.V., Calvo F., Kolch W. Submitted (MAR-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-17; 25-44; 51-63; 72-78; 82-97; 110-118; 122-159; 182-239; 248-266; 277-301; 334-391; 394-402 AND 437-454, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[5]	"Mechanism of Ca2+-mediated regulation of NDR protein kinase through autophosphorylation and phosphorylation by an upstream kinase." Tamaskovic R., Bichsel S.J., Rogniaux H., Stegert M.R., Hemmings B.A. J. Biol. Chem. 278:6710-6718(2003) [PubMed: 12493777] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT THR-74; SER-281 AND THR-444, MUTAGENESIS OF THR-74; LYS-118; SER-281 AND THR-444.
[6]	"Human Mob proteins regulate the NDR1 and NDR2 serine-threonine kinases." Devroe E., Erdjument-Bromage H., Tempst P., Silver P.A. J. Biol. Chem. 279:24444-24451(2004) [PubMed: 15067004] [Abstract] Cited for: ENZYME REGULATION, INTERACTION WITH MOB1 AND MOB2.
[7]	"Mechanism of activation of NDR (nuclear Dbf2-related) protein kinase by the hMOB1 protein." Bichsel S.J., Tamaskovic R., Stegert M.R., Hemmings B.A. J. Biol. Chem. 279:35228-35235(2004) [PubMed: 15197186] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, ENZYME REGULATION, INTERACTION WITH MOB1 AND MOB2.
[8]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-26, MASS SPECTROMETRY.
[9]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[10]	"GlcNAcylation of a histone methyltransferase in retinoic-acid-induced granulopoiesis." Fujiki R., Chikanishi T., Hashiba W., Ito H., Takada I., Roeder R.G., Kitagawa H., Kato S. Nature 459:455-459(2009) [PubMed: 19377461] [Abstract] Cited for: IDENTIFICATION IN THE MLL5-L COMPLEX.
[11]	"Structure of the Ca2+/S100B/NDR kinase peptide complex: insights into S100 target specificity and activation of the kinase." Bhattacharya S., Large E., Heizmann C.W., Hemmings B.A., Chazin W.J. Biochemistry 42:14416-14426(2003) [PubMed: 14661952] [Abstract] Cited for: STRUCTURE BY NMR OF 62-84, ENZYME REGULATION, INTERACTION WITH S100B.
[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: VARIANTS [LARGE SCALE ANALYSIS] LYS-18; ASN-145 AND ARG-267.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z35102 mRNA. Translation: CAA84485.1.
Z85986 Genomic DNA. Translation: CAB39180.1.
BC012085 mRNA. Translation: AAH12085.1.
BC095413 mRNA. Translation: AAH95413.1.

IPI

IPI00027251.

PIR

I38133.

RefSeq

NP_009202.1.

UniGene

Hs.409578

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1PSB	NMR	-	C/D	62-87	[»]

SMR

Q15208. Positions 71-449.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q15208. 5 interactions.

STRING

Q15208.

PTM databases

PhosphoSite

Q15208.

Proteomic databases

PRIDE

Q15208.

Genome annotation databases

Ensembl

ENST00000229812; ENSP00000229812; ENSG00000112079; Homo sapiens. [Genome view]
ENST00000407753; ENSP00000385174; ENSG00000112079; Homo sapiens. [Genome view]

GeneID

11329.

KEGG

hsa:11329.

UCSC

uc003omg.1. human.

Organism-specific databases

CTD

11329.

GeneCards

GC06M036569.

H-InvDB

HIX0005821.

HGNC

HGNC:17847. STK38.

HPA

CAB004673.

MIM

606964. gene.

PharmGKB

PA38251.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG09671.

HOGENOM

HBG755340.

HOVERGEN

Q15208.

InParanoid

Q15208.

OMA

GVDWDHI.

PhylomeDB

Q15208.

Enzyme and pathway databases

BRENDA

2.7.11.1. 247.

Gene expression databases

ArrayExpress

Q15208.

Bgee

Q15208.

CleanEx

HS_STK38.

Genevestigator

Q15208.

GermOnline

ENSG00000112079. Homo sapiens.

Family and domain databases

InterPro

IPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_prot_kinase-like_dom.
IPR008271. Ser/Thr_prot_kinase_AS.
IPR002290. Ser/Thr_prot_kinase_dom.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]

SMART

SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]

PROSITE

PS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

43035.

SOURCE

Search...

Entry information

Entry name

STK38_HUMAN

Accession

Primary (citable) accession number: Q15208
Secondary accession number(s): Q503A1

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 21, 2004
Last sequence update:	November 1, 1996
Last modified:	January 19, 2010
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.