O75716 (STK16_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase 16
EC=2.7.11.1

Alternative name(s):
Myristoylated and palmitoylated serine/threonine-protein kinase
Short name=MPSK
Protein kinase PKL12
TGF-beta-stimulated factor 1
Short name=TSF-1
Tyrosine-protein kinase STK16
EC=2.7.10.2
hPSK

Gene names

Name:	STK16
Synonyms:	MPSK1, PKL12, TSF1

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	305 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Membrane-associated protein kinase that phosphorylates on serine and threonine residues. In vitro substrates include DRG1, ENO1 and EIF4EBP1. Also autophosphorylates. May be involved in secretory vesicle trafficking or intracellular signaling. May have a role in regulating stromal-epithelial interactions that occur during ductal morphogenesis in the mammary gland. May be involved in TGF-beta signaling. Able to autophosphorylate on Tyr residue; it is however unclear whether it has tyrosine-protein kinase toward other proteins. Ref.2
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Monomer. Interacts with DRG1 (via its N-terminal); the interaction phosphorylates DRG1. Ref.10
Subcellular location	Cytoplasm › perinuclear region. Membrane; Lipid-anchor By similarity. Note: Associates with Golgi and Golgi-derived vesicles By similarity.
Tissue specificity	Ubiquitously expressed at very low levels. Ref.2
Post-translational modification	Mainly autophosphorylated on serine/threonine residues. Also autophosphorylated on Tyr-198. Ref.2 Ref.10 It is uncertain whether palmitoylation is on Cys-6 and/or Cys-8. Ref.2
Sequence similarities	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Contains 1 protein kinase domain.
Sequence caution	The sequence AAV38392.1 differs from that shown. Reason: Frameshift at position 305. The sequence CAA06700.1 differs from that shown. Reason: Frameshift at position 305.

Ontologies

Keywords
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Lipoprotein Myristate Palmitate Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to transforming growth factor beta stimulus Inferred from electronic annotation. Source: Compara protein autophosphorylation Inferred from direct assay Ref.10. Source: UniProtKB
Cellular_component	Golgi-associated vesicle Inferred from electronic annotation. Source: Compara membrane Inferred from electronic annotation. Source: UniProtKB-SubCell perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Inferred from electronic annotation. Source: Compara non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ADAMTSL4	Q6UY14	3	EBI-749295,EBI-742002

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 305

305

Serine/threonine-protein kinase 16

PRO_0000086701

Regions

Domain

20 – 293

274

Protein kinase

Nucleotide binding

26 – 34

9

ATP By similarity

Region

166 – 202

37

Activation loop

Sites

Active site

148

1

Proton acceptor By similarity

Binding site

49

1

ATP By similarity

Amino acid modifications

Modified residue

185

1

Phosphothreonine; by autocatalysis Ref.10

Modified residue

197

1

Phosphoserine; by autocatalysis Ref.10

Modified residue

198

1

Phosphotyrosine; by autocatalysis Ref.10

Lipidation

2

1

N-myristoyl glycine Ref.2

Lipidation

6

1

S-palmitoyl cysteine Probable

Lipidation

8

1

S-palmitoyl cysteine Probable

Natural variations

Natural variant

41

1

H → R. Ref.11
Corresponds to variant rs34799131 [ dbSNP | Ensembl ].

VAR_041140

Natural variant

55

1

E → K. Ref.11
Corresponds to variant rs35947471 [ dbSNP | Ensembl ].

VAR_041141

Natural variant

77

1

I → V. Ref.11
Corresponds to variant rs34282267 [ dbSNP | Ensembl ].

VAR_041142

Natural variant

266

1

R → W. Ref.8 Ref.9 Ref.11
Corresponds to variant rs17849638 [ dbSNP | Ensembl ].

VAR_041143

Natural variant

277

1

P → L. Ref.11
Corresponds to variant rs35454203 [ dbSNP | Ensembl ].

VAR_041144

Experimental info

Mutagenesis

2

1

G → A: Loss of myristoylation. Ref.2

Mutagenesis

6

1

C → S: Loss of palmitoylation. Ref.2

Mutagenesis

8

1

C → S: Loss of palmitoylation. Ref.2

Sequence conflict

59

1

R → L in AAV38392. Ref.6

Sequence conflict

180

1

S → P in BAF85383. Ref.7

Sequence conflict

213

1

D → G in CAA06700. Ref.1

Sequence conflict

213

1

D → G in CAA09387. Ref.4

Sequence conflict

221

1

L → F in AAC28337. Ref.2

Sequence conflict

222

1

G → S in CAA09387. Ref.4

Secondary structure

1

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305

Helix Strand Turn

Details...

Beta strand

13 – 15

3

Beta strand

18 – 27

10

Beta strand

32 – 39

8

Turn

40 – 42

3

Beta strand

45 – 55

11

Helix

56 – 70

15

Beta strand

82 – 88

7

Beta strand

91 – 99

9

Helix

106 – 114

9

Turn

115 – 117

3

Helix

122 – 141

20

Helix

151 – 153

3

Beta strand

154 – 156

3

Beta strand

162 – 164

3

Beta strand

171 – 173

3

Beta strand

175 – 179

5

Helix

180 – 193

14

Helix

196 – 198

3

Helix

201 – 203

3

Beta strand

208 – 212

5

Helix

215 – 230

16

Helix

236 – 240

5

Helix

245 – 250

6

Helix

263 – 272

10

Helix

277 – 279

3

Helix

283 – 292

10

Sequences

	Sequence		Length	Mass (Da)
	O75716 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 593B2AEB8505009C	FASTA	305	34,656
	10 20 30 40 50 60 MGHALCVCSR GTVIIDNKRY LFIQKLGEGG FSYVDLVEGL HDGHFYALKR ILCHEQQDRE 70 80 90 100 110 120 EAQREADMHR LFNHPNILRL VAYCLRERGA KHEAWLLLPF FKRGTLWNEI ERLKDKGNFL 130 140 150 160 170 180 TEDQILWLLL GICRGLEAIH AKGYAHRDLK PTNILLGDEG QPVLMDLGSM NQACIHVEGS 190 200 210 220 230 240 RQALTLQDWA AQRCTISYRA PELFSVQSHC VIDERTDVWS LGCVLYAMMF GEGPYDMVFQ 250 260 270 280 290 300 KGDSVALAVQ NQLSIPQSPR HSSALRQLLN SMMTVDPHQR PHIPLLLSQL EALQPPAPGQ HTTQI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, expression analysis, and functional characterization of PKL12, a member of a new subfamily of ser/thr kinases." Ligos J.M., Gerwin N., Fernandez P., Gutierrez-Ramos J.-C., Bernad A. Biochem. Biophys. Res. Commun. 249:380-384(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Identification and characterization of a myristylated and palmitylated serine/threonine protein kinase." Berson A.E., Young C., Morrison S.L., Fujii G.H., Sheung J., Wu B., Bolen J.B., Burkhardt A.L. Biochem. Biophys. Res. Commun. 259:533-538(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, FUNCTION, AUTOPHOSPHORYLATION, MYRISTOYLATION AT GLY-2, PALMITOYLATION AT CYS-6 AND CYS-8, MUTAGENESIS OF GLY-2; CYS-6 AND CYS-8. Tissue: Dendritic cell.
[3]	"A novel transcriptional factor with Ser/Thr kinase activity involved in the transforming growth factor (TGF)-beta signalling pathway." Ohta S., Takeuchi M., Deguchi M., Tsuji T., Gahara Y., Nagata K. Biochem. J. 350:395-404(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Characterization of a ubiquitous expressed human serine/threonine kinase." Wabakken T.K., Aasheim H.-C. Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Blood.
[5]	Stairs D.B., Ha S.I., Chodosh L.A. Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[6]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Thymus.
[8]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT TRP-266.
[9]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT TRP-266. Tissue: Colon and Lymph.
[10]	"Structure of the human protein kinase MPSK1 reveals an atypical activation loop architecture." Eswaran J., Bernad A., Ligos J.M., Guinea B., Debreczeni J.E., Sobott F., Parker S.A., Najmanovich R., Turk B.E., Knapp S. Structure 16:115-124(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 13-304 OF WILD TYPE AND IN COMPLEX WITH STAUROSPORINE, SUBUNIT, INTERACTION WITH DRG1, AUTOPHOSPHORYLATION AT THR-185; SER-197 AND TYR-198, MASS SPECTROMETRY.
[11]	"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] ARG-41; LYS-55; VAL-77; TRP-266 AND LEU-277.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AJ005791 mRNA. Translation: CAA06700.1. Frameshift.
AF060798 mRNA. Translation: AAC28337.1.
AB020739 mRNA. Translation: BAB16311.1.
AJ010872 mRNA. Translation: CAA09387.1.
AF203910 mRNA. Translation: AAG23728.1.
BT019585 mRNA. Translation: AAV38392.1. Frameshift.
AK292694 mRNA. Translation: BAF85383.1.
CR407675 mRNA. Translation: CAG28603.1.
BC002618 mRNA. Translation: AAH02618.1.
BC053998 mRNA. Translation: AAH53998.1.

IPI

IPI00306833.

RefSeq

NP_001008910.1. NM_001008910.2.

UniGene

Hs.153003.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2BUJ	X-ray	2.60	A/B	13-304	[»]

ProteinModelPortal

O75716.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29598N.

IntAct

O75716. 3 interactions.

MINT

MINT-3001680.

STRING

9606.ENSP00000379964.

PTM databases

PhosphoSite

O75716.

Proteomic databases

PaxDb

O75716.

PRIDE

O75716.

Protocols and materials databases

DNASU

8576.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000396738; ENSP00000379964; ENSG00000115661.
ENST00000409638; ENSP00000386928; ENSG00000115661.

GeneID

8576.

KEGG

hsa:8576.

UCSC

uc002vko.2. human.

Organism-specific databases

CTD

8576.

GeneCards

GC02P220110.

HGNC

HGNC:11394. STK16.

HPA

HPA029450.

MIM

604719. gene.

neXtProt

NX_O75716.

PharmGKB

PA36202.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOVERGEN

HBG054359.

KO

K08856.

OrthoDB

EOG402WSS.

Enzyme and pathway databases

BRENDA

2.7.11.1. 2681.

Gene expression databases

ArrayExpress

O75716.

Bgee

O75716.

CleanEx

HS_STK16.

Genevestigator

O75716.

GermOnline

ENSG00000115661. Homo sapiens.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. False negative.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

O75716.

ChEMBL

CHEMBL3938.

ChiTaRS

STK16. human.

EvolutionaryTrace

O75716.

GenomeRNAi

8576.

NextBio

32169.

SOURCE

Search...

Entry information

Entry name

STK16_HUMAN

Accession

Primary (citable) accession number: O75716
Secondary accession number(s): A8K9H9 , Q5U0F8, Q96KI2, Q9BUH4, Q9UEN3, Q9UP78

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 130 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.