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Q99ML2 (TNK1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 107. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Non-receptor tyrosine-protein kinase TNK1

EC=2.7.10.2
Alternative name(s):
Kinase of embryonic stem cells
Gene names
Name:Tnk1
Synonyms:Kos1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length666 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May function in signaling pathways utilized broadly during fetal development and more selectively in adult tissues and in cells of the lymphohematopoietic system. Could specifically be involved in phospholipid signal transduction By similarity. Involved in negative regulation of cell growth. Has tumor suppressor properties. Plays a negative regulatory role in the Ras-MAPK pathway. Ref.1 Ref.5

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Subunit structure

Interacts with the SH3 domain of PLCG1 via its Pro-rich domain By similarity. UniProtKB Q13470

Subcellular location

Membrane By similarity. Cytoplasm Ref.1.

Tissue specificity

Expressed in whole embryo and all adult tissues examined including liver, kidney, heart, brain, skeletal muscle and intestine. Also detected in various myeloid- and lymphoid-derived cell lines. Ref.1

Developmental stage

Expression during embryogenesis increases between E7 and E11. Levels of expression subsequently decrease and reach a steady-state level by E17. Ref.1

Post-translational modification

Autophosphorylated on tyrosine residues. Ref.1

Disruption phenotype

Mice develop spontaneous tumors, including lymphomas and carcinomas at high rates. Ref.5

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family.

Contains 1 protein kinase domain.

Contains 1 SH3 domain.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 Ref.2 (identifier: Q99ML2-1)

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 Ref.1 (identifier: Q99ML2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     381-434: AWLSEGRCVR...TLKVGNFPAS → VRIPNSPYTH...QSLPAGSAEP
     435-666: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 666666Non-receptor tyrosine-protein kinase TNK1
PRO_0000088174

Regions

Domain116 – 383268Protein kinase
Domain387 – 43953SH3
Nucleotide binding122 – 1309ATP By similarity UniProtKB P12931
Compositional bias507 – 56054Pro-rich

Sites

Active site2451Proton acceptor By similarity UniProtKB P12931
Binding site1481ATP By similarity UniProtKB P12931

Amino acid modifications

Modified residue2551Phosphoserine By similarity
Modified residue4981Phosphoserine By similarity
Modified residue5101Phosphothreonine By similarity
Modified residue5151Phosphoserine By similarity
Modified residue5821Phosphoserine By similarity

Natural variations

Alternative sequence381 – 43454AWLSE…NFPAS → VRIPNSPYTHIAFLPCILSP SVPCRRQTRLGAWAGIWNSA QNQVQSLPAGSAEP in isoform 2. Ref.1
VSP_051664
Alternative sequence435 – 666232Missing in isoform 2. Ref.1
VSP_051665

Experimental info

Mutagenesis1481K → A: Loss of autophosphorylation. Ref.1
Sequence conflict461L → V in AAK35164. Ref.2
Sequence conflict591L → I in AAK35164. Ref.2
Sequence conflict2061A → T in AAH29623. Ref.3
Sequence conflict2061A → T in AAH55303. Ref.3
Sequence conflict5341P → S in AAK35164. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 15, 2005. Version 2.
Checksum: 5AE6A48D99BADE8B

FASTA66673,099
        10         20         30         40         50         60 
MLPEASSLWL LRLLRDVQLA QFYRPILEEL NVTRPEHFDF VRPEDLDNIG MGRPAQRRLN 

        70         80         90        100        110        120 
EALKRYRSGV KSKNWVYKIL GGFAPEQKEI PPRSDSPLCF HEPEGGLKCL IPEGAVRRGE 

       130        140        150        160        170        180 
LLGSGCFGVV HRGLWTLPSG QSIPVAVKSL RVGPEGPMGT ELGDFLREVS VMMKLEHPHV 

       190        200        210        220        230        240 
LRLHGLVLGQ PLQMVMELAP LGSLHARLTA PAPTPPLPVA LLCLFLRQLA GAMAYLGSCG 

       250        260        270        280        290        300 
LVHRDLATRN LLLASPRMIK VADFGLVRPL GGARGRYVMG GPRPIPYAWC APESLRQGAF 

       310        320        330        340        350        360 
SSASDVWMFG VTLWEMFSGG EEPWAGVPPY LILQRLEKDR ARLPKPPLCS RALYSLALRC 

       370        380        390        400        410        420 
WAPHPADRPS FSNLEGLLQE AWLSEGRCVR EVTEPGALRM EPGDPITIIE GSLDTATWKG 

       430        440        450        460        470        480 
QNGRTLKVGN FPASAVTLAD LGGSPVTHPA HRGSPAHGEK CRGGTDGDRE KATLQDLPPA 

       490        500        510        520        530        540 
RSHRTKMPLQ RMRGISKSLE SVLSLGPRPT GGGSSPPELR RTRAMPQRLP DLPPRPPDLP 

       550        560        570        580        590        600 
PRPPIICNSS QPTQPHKARP KRESSHNHRT GAPGASKATV PSGGPLSDPE WQRKVVEVEL 

       610        620        630        640        650        660 
SVHGVTYQEC QVALRTTGGD VASAIRNLKV DQLFHLSNRS RADCRRILEH HQWDLSAASR 


YILARS 

« Hide

Isoform 2 [UniParc].

Checksum: E1F1BBF451401FBC
Show »

FASTA43447,926

References

« Hide 'large scale' references
[1]"Kos1, a nonreceptor tyrosine kinase that suppresses Ras signaling."
Hoare K., Hoare S., Smith O.M., Kalmaz G., Small D., May W.S. Jr.
Oncogene 22:3562-3577(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 2), FUNCTION, AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-148, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Strain: 129/Sv.
Tissue: Embryonic stem cell.
[2]"Cloning of the murine Tnk1 tyrosine kinase and evidence that it plays a role in cell adhesion."
Hoehn G.T., Felschow D.M., Civin C.I.
Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Strain: FVB/N-3.
Tissue: Mammary gland.
[4]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 151-666 (ISOFORM 1).
Strain: C57BL/6J.
Tissue: Colon.
[5]"Tnk1/Kos1 knockout mice develop spontaneous tumors."
Hoare S., Hoare K., Reinhard M.K., Lee Y.J., Oh S.P., May W.S. Jr.
Cancer Res. 68:8723-8732(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF307745 Genomic DNA. Translation: AAL09412.1.
AF307746 mRNA. Translation: AAL09413.1.
AF332512 mRNA. Translation: AAK35164.1.
BC029623 mRNA. Translation: AAH29623.1.
BC055303 mRNA. Translation: AAH55303.1.
AK033440 mRNA. Translation: BAC28288.1.
CCDSCCDS24917.1. [Q99ML2-1]
RefSeqNP_114086.3. NM_031880.3. [Q99ML2-1]
XP_006534617.1. XM_006534554.1. [Q99ML2-1]
UniGeneMm.28874.
Mm.358793.

3D structure databases

ProteinModelPortalQ99ML2.
SMRQ99ML2. Positions 107-437.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteQ99ML2.

Proteomic databases

PRIDEQ99ML2.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000001626; ENSMUSP00000001626; ENSMUSG00000001583. [Q99ML2-1]
ENSMUST00000108626; ENSMUSP00000104266; ENSMUSG00000001583. [Q99ML2-2]
GeneID83813.
KEGGmmu:83813.
UCSCuc007jsb.2. mouse. [Q99ML2-1]

Organism-specific databases

CTD8711.
MGIMGI:1930958. Tnk1.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00740000115195.
HOGENOMHOG000231055.
HOVERGENHBG055513.
KOK08885.
OMAYTHIAFL.
OrthoDBEOG71G9T3.
TreeFamTF316643.

Gene expression databases

ArrayExpressQ99ML2.
BgeeQ99ML2.
CleanExMM_TNK1.
GenevestigatorQ99ML2.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR001452. SH3_domain.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PfamPF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSPR00109. TYRKINASE.
SMARTSM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF50044. SSF50044. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio350786.
PROQ99ML2.
SOURCESearch...

Entry information

Entry nameTNK1_MOUSE
AccessionPrimary (citable) accession number: Q99ML2
Secondary accession number(s): Q8CCC4, Q8K0X9, Q91V11
Entry history
Integrated into UniProtKB/Swiss-Prot: February 15, 2005
Last sequence update: February 15, 2005
Last modified: July 9, 2014
This is version 107 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot