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Q99ML2

- TNK1_MOUSE

UniProt

Q99ML2 - TNK1_MOUSE

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Protein

Non-receptor tyrosine-protein kinase TNK1

Gene

Tnk1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.By similarity2 Publications

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei148 – 1481ATPBy similarityPROSITE-ProRule annotation
Active sitei245 – 2451Proton acceptorBy similarityPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi122 – 1309ATPBy similarityPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB
  2. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB

GO - Biological processi

  1. negative regulation of cell growth Source: UniProtKB
  2. negative regulation of Ras protein signal transduction Source: UniProtKB
  3. peptidyl-tyrosine phosphorylation Source: GOC
  4. protein autophosphorylation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Non-receptor tyrosine-protein kinase TNK1 (EC:2.7.10.2)
Alternative name(s):
Kinase of embryonic stem cells
Gene namesi
Name:Tnk1Imported
Synonyms:Kos1Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 11

Organism-specific databases

MGIiMGI:1930958. Tnk1.

Subcellular locationi

Membrane By similarity. Cytoplasm 1 Publication

GO - Cellular componenti

  1. cell junction Source: Ensembl
  2. cytosol Source: UniProtKB
  3. membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice develop spontaneous tumors, including lymphomas and carcinomas at high rates.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi148 – 1481K → A: Loss of autophosphorylation. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 666666Non-receptor tyrosine-protein kinase TNK1PRO_0000088174Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei255 – 2551PhosphoserineBy similarity
Modified residuei498 – 4981PhosphoserineBy similarity
Modified residuei510 – 5101PhosphothreonineBy similarity
Modified residuei515 – 5151PhosphoserineBy similarity
Modified residuei582 – 5821PhosphoserineBy similarity

Post-translational modificationi

Autophosphorylated on tyrosine residues.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PRIDEiQ99ML2.

PTM databases

PhosphoSiteiQ99ML2.

Expressioni

Tissue specificityi

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.1 Publication

Developmental stagei

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

Gene expression databases

BgeeiQ99ML2.
CleanExiMM_TNK1.
ExpressionAtlasiQ99ML2. baseline and differential.
GenevestigatoriQ99ML2.

Interactioni

Subunit structurei

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

Structurei

3D structure databases

ProteinModelPortaliQ99ML2.
SMRiQ99ML2. Positions 107-437.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini116 – 383268Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini387 – 43953SH3Sequence AnalysisAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi507 – 56054Pro-richAdd
BLAST

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 SH3 domain.Sequence Analysis

Keywords - Domaini

SH3 domain

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118799.
HOGENOMiHOG000231055.
HOVERGENiHBG055513.
InParanoidiQ99ML2.
KOiK08885.
OMAiYTHIAFL.
OrthoDBiEOG71G9T3.
TreeFamiTF316643.

Family and domain databases

InterProiIPR011009. 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]
PfamiPF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSiPR00109. TYRKINASE.
SMARTiSM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 11 Publication (identifier: Q99ML2-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MLPEASSLWL LRLLRDVQLA QFYRPILEEL NVTRPEHFDF VRPEDLDNIG
60 70 80 90 100
MGRPAQRRLN EALKRYRSGV KSKNWVYKIL GGFAPEQKEI PPRSDSPLCF
110 120 130 140 150
HEPEGGLKCL IPEGAVRRGE LLGSGCFGVV HRGLWTLPSG QSIPVAVKSL
160 170 180 190 200
RVGPEGPMGT ELGDFLREVS VMMKLEHPHV LRLHGLVLGQ PLQMVMELAP
210 220 230 240 250
LGSLHARLTA PAPTPPLPVA LLCLFLRQLA GAMAYLGSCG LVHRDLATRN
260 270 280 290 300
LLLASPRMIK VADFGLVRPL GGARGRYVMG GPRPIPYAWC APESLRQGAF
310 320 330 340 350
SSASDVWMFG VTLWEMFSGG EEPWAGVPPY LILQRLEKDR ARLPKPPLCS
360 370 380 390 400
RALYSLALRC WAPHPADRPS FSNLEGLLQE AWLSEGRCVR EVTEPGALRM
410 420 430 440 450
EPGDPITIIE GSLDTATWKG QNGRTLKVGN FPASAVTLAD LGGSPVTHPA
460 470 480 490 500
HRGSPAHGEK CRGGTDGDRE KATLQDLPPA RSHRTKMPLQ RMRGISKSLE
510 520 530 540 550
SVLSLGPRPT GGGSSPPELR RTRAMPQRLP DLPPRPPDLP PRPPIICNSS
560 570 580 590 600
QPTQPHKARP KRESSHNHRT GAPGASKATV PSGGPLSDPE WQRKVVEVEL
610 620 630 640 650
SVHGVTYQEC QVALRTTGGD VASAIRNLKV DQLFHLSNRS RADCRRILEH
660
HQWDLSAASR YILARS
Length:666
Mass (Da):73,099
Last modified:February 15, 2005 - v2
Checksum:i5AE6A48D99BADE8B
GO
Isoform 21 Publication (identifier: Q99ML2-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:434
Mass (Da):47,926
Checksum:iE1F1BBF451401FBC
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti46 – 461L → V in AAK35164. 1 PublicationCurated
Sequence conflicti59 – 591L → I in AAK35164. 1 PublicationCurated
Sequence conflicti206 – 2061A → T in AAH29623. (PubMed:15489334)Curated
Sequence conflicti206 – 2061A → T in AAH55303. (PubMed:15489334)Curated
Sequence conflicti534 – 5341P → S in AAK35164. 1 PublicationCurated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei381 – 43454AWLSE…NFPAS → VRIPNSPYTHIAFLPCILSP SVPCRRQTRLGAWAGIWNSA QNQVQSLPAGSAEP in isoform 2. 1 PublicationVSP_051664Add
BLAST
Alternative sequencei435 – 666232Missing in isoform 2. 1 PublicationVSP_051665Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS24917.1. [Q99ML2-1]
RefSeqiNP_114086.3. NM_031880.3. [Q99ML2-1]
XP_006534617.1. XM_006534554.1. [Q99ML2-1]
UniGeneiMm.28874.
Mm.358793.

Genome annotation databases

EnsembliENSMUST00000001626; ENSMUSP00000001626; ENSMUSG00000001583. [Q99ML2-1]
ENSMUST00000108626; ENSMUSP00000104266; ENSMUSG00000001583. [Q99ML2-2]
GeneIDi83813.
KEGGimmu:83813.
UCSCiuc007jsb.2. mouse. [Q99ML2-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 .
CCDSi CCDS24917.1. [Q99ML2-1 ]
RefSeqi NP_114086.3. NM_031880.3. [Q99ML2-1 ]
XP_006534617.1. XM_006534554.1. [Q99ML2-1 ]
UniGenei Mm.28874.
Mm.358793.

3D structure databases

ProteinModelPortali Q99ML2.
SMRi Q99ML2. Positions 107-437.
ModBasei Search...
MobiDBi Search...

PTM databases

PhosphoSitei Q99ML2.

Proteomic databases

PRIDEi Q99ML2.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000001626 ; ENSMUSP00000001626 ; ENSMUSG00000001583 . [Q99ML2-1 ]
ENSMUST00000108626 ; ENSMUSP00000104266 ; ENSMUSG00000001583 . [Q99ML2-2 ]
GeneIDi 83813.
KEGGi mmu:83813.
UCSCi uc007jsb.2. mouse. [Q99ML2-1 ]

Organism-specific databases

CTDi 8711.
MGIi MGI:1930958. Tnk1.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00760000118799.
HOGENOMi HOG000231055.
HOVERGENi HBG055513.
InParanoidi Q99ML2.
KOi K08885.
OMAi YTHIAFL.
OrthoDBi EOG71G9T3.
TreeFami TF316643.

Miscellaneous databases

NextBioi 350786.
PROi Q99ML2.
SOURCEi Search...

Gene expression databases

Bgeei Q99ML2.
CleanExi MM_TNK1.
ExpressionAtlasi Q99ML2. baseline and differential.
Genevestigatori Q99ML2.

Family and domain databases

InterProi IPR011009. 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 ]
Pfami PF07714. Pkinase_Tyr. 1 hit.
[Graphical view ]
PRINTSi PR00109. TYRKINASE.
SMARTi SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view ]
SUPFAMi SSF50044. SSF50044. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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/SvImported.
    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-3Imported.
    Tissue: Mammary glandImported.
  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.
    , 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. Cited for: FUNCTION, DISRUPTION PHENOTYPE.

Entry informationi

Entry nameiTNK1_MOUSE
AccessioniPrimary (citable) accession number: Q99ML2
Secondary accession number(s): Q8CCC4, Q8K0X9, Q91V11
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 15, 2005
Last sequence update: February 15, 2005
Last modified: October 29, 2014
This is version 109 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3