LOCUS       NP_003309                857 aa            linear   PRI 08-OCT-2024
DEFINITION  dual specificity protein kinase TTK isoform 1 [Homo sapiens].
ACCESSION   NP_003309
VERSION     NP_003309.2
DBSOURCE    REFSEQ: accession NM_003318.5
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 857)
  AUTHORS   Lee,C.C., Tsai,K.Y., Lee,A.W., Wei,P.L., Huang,C.Y., Batzorig,U.
            and Chang,Y.J.
  TITLE     CWH43 Is a Novel Tumor Suppressor Gene with Negative Regulation of
            TTK in Colorectal Cancer
  JOURNAL   Int J Mol Sci 24 (20), 15262 (2023)
   PUBMED   37894942
  REMARK    GeneRIF: CWH43 Is a Novel Tumor Suppressor Gene with Negative
            Regulation of TTK in Colorectal Cancer.
            Publication Status: Online-Only
REFERENCE   2  (residues 1 to 857)
  AUTHORS   Ma,J.J., Xiang,C. and Wang,J.W.
  TITLE     TTK is a potential regulator of tumor progression correlated with
            dedifferentiation and immune cell infiltration in papillary thyroid
            cancer
  JOURNAL   Aging (Albany NY) 15 (19), 10607-10626 (2023)
   PUBMED   37815894
  REMARK    GeneRIF: TTK is a potential regulator of tumor progression
            correlated with dedifferentiation and immune cell infiltration in
            papillary thyroid cancer.
REFERENCE   3  (residues 1 to 857)
  AUTHORS   Yu,J., Gao,G., Wei,X. and Wang,Y.
  TITLE     TTK Protein Kinase promotes temozolomide resistance through
            inducing autophagy in glioblastoma
  JOURNAL   BMC Cancer 22 (1), 786 (2022)
   PUBMED   35850753
  REMARK    GeneRIF: TTK Protein Kinase promotes temozolomide resistance
            through inducing autophagy in glioblastoma.
            Publication Status: Online-Only
REFERENCE   4  (residues 1 to 857)
  AUTHORS   Gao,Y.H., Qu,S.S., Cao,L.Q. and Yao,M.
  TITLE     TTK predicts triple positive breast cancer prognosis and regulates
            tumor proliferation and invasion
  JOURNAL   Neoplasma 69 (2), 274-282 (2022)
   PUBMED   34846157
  REMARK    GeneRIF: TTK predicts triple positive breast cancer prognosis and
            regulates tumor proliferation and invasion.
REFERENCE   5  (residues 1 to 857)
  AUTHORS   Yao,Z.P., Zhu,H., Shen,F. and Gong,D.
  TITLE     Hsp90 regulates the tumorigenic function of tyrosine protein kinase
            in osteosarcoma
  JOURNAL   Clin Exp Pharmacol Physiol 49 (3), 380-390 (2022)
   PUBMED   34767669
  REMARK    GeneRIF: Hsp90 regulates the tumorigenic function of tyrosine
            protein kinase in osteosarcoma.
REFERENCE   6  (residues 1 to 857)
  AUTHORS   Stucke,V.M., Sillje,H.H., Arnaud,L. and Nigg,E.A.
  TITLE     Human Mps1 kinase is required for the spindle assembly checkpoint
            but not for centrosome duplication
  JOURNAL   EMBO J 21 (7), 1723-1732 (2002)
   PUBMED   11927556
  REMARK    GeneRIF: human Mps1(TTK kinase) is essential for the establishment
            and/or maintenance of the spindle assembly checkpoint, but
            dispensable for centrosome duplication.
REFERENCE   7  (residues 1 to 857)
  AUTHORS   Cahill,D.P., da Costa,L.T., Carson-Walter,E.B., Kinzler,K.W.,
            Vogelstein,B. and Lengauer,C.
  TITLE     Characterization of MAD2B and other mitotic spindle checkpoint
            genes
  JOURNAL   Genomics 58 (2), 181-187 (1999)
   PUBMED   10366450
REFERENCE   8  (residues 1 to 857)
  AUTHORS   Lindberg,R.A., Fischer,W.H. and Hunter,T.
  TITLE     Characterization of a human protein threonine kinase isolated by
            screening an expression library with antibodies to phosphotyrosine
  JOURNAL   Oncogene 8 (2), 351-359 (1993)
   PUBMED   7678926
REFERENCE   9  (residues 1 to 857)
  AUTHORS   Mills,G.B., Schmandt,R., McGill,M., Amendola,A., Hill,M.,
            Jacobs,K., May,C., Rodricks,A.M., Campbell,S. and Hogg,D.
  TITLE     Expression of TTK, a novel human protein kinase, is associated with
            cell proliferation
  JOURNAL   J Biol Chem 267 (22), 16000-16006 (1992)
   PUBMED   1639825
REFERENCE   10 (residues 1 to 857)
  AUTHORS   Hanks,S.K. and Quinn,A.M.
  TITLE     Protein kinase catalytic domain sequence database: identification
            of conserved features of primary structure and classification of
            family members
  JOURNAL   Methods Enzymol 200, 38-62 (1991)
   PUBMED   1956325
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA853919.1, AK315696.1 and
            AU154042.1.
            
            On Sep 25, 2002 this sequence version replaced NP_003309.1.
            
            Summary: This gene encodes a dual specificity protein kinase with
            the ability to phosphorylate tyrosine, serine and threonine.
            Associated with cell proliferation, this protein is essential for
            chromosome alignment at the centromere during mitosis and is
            required for centrosome duplication. It has been found to be a
            critical mitotic checkpoint protein for accurate segregation of
            chromosomes during mitosis. Tumorigenesis may occur when this
            protein fails to degrade and produces excess centrosomes resulting
            in aberrant mitotic spindles. Alternative splicing results in
            multiple transcript variants. [provided by RefSeq, Nov 2009].
            
            Transcript Variant: This variant (1) represents the shorter
            transcript and encodes the longer isoform (1).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: BC000633.2, SRR5189661.103703.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000369798.7/ ENSP00000358813.2
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..857
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="6"
                     /map="6q14.1"
     Protein         1..857
                     /product="dual specificity protein kinase TTK isoform 1"
                     /EC_number="2.7.12.1"
                     /note="cancer/testis antigen 96; monopolar spindle 1-like
                     1; phosphotyrosine picked threonine kinase; dual
                     specificity protein kinase TTK; phosphotyrosine picked
                     threonine-protein kinase; monopolar spindle 1 kinase"
                     /calculated_mol_wt=96942
     Site            1
                     /site_type="acetylation"
                     /note="N-acetylmethionine.
                     /evidence=ECO:0007744|PubMed:19369195,
                     ECO:0007744|PubMed:22814378; propagated from
                     UniProtKB/Swiss-Prot (P33981.2)"
     Site            7
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:18691976,
                     ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163;
                     propagated from UniProtKB/Swiss-Prot (P33981.2)"
     Site            33
                     /site_type="phosphorylation"
                     /note="Phosphothreonine, by TTK.
                     /evidence=ECO:0000269|PubMed:28441529,
                     ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976,
                     ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:20068231,
                     ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (P33981.2)"
     Site            37
                     /site_type="phosphorylation"
                     /note="Phosphoserine, by TTK.
                     /evidence=ECO:0000269|PubMed:28441529,
                     ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:20068231;
                     propagated from UniProtKB/Swiss-Prot (P33981.2)"
     Region          <54..188
                     /region_name="LapB"
                     /note="Lipopolysaccharide biosynthesis regulator
                     YciM/LapB, contains six TPR domains and a C-terminal
                     metal-binding domain [Cell wall/membrane/envelope
                     biogenesis]; COG2956"
                     /db_xref="CDD:442196"
     Site            80
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:18691976; propagated from
                     UniProtKB/Swiss-Prot (P33981.2)"
     Site            281
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:18691976,
                     ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:20068231;
                     propagated from UniProtKB/Swiss-Prot (P33981.2)"
     Site            317
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:18691976; propagated from
                     UniProtKB/Swiss-Prot (P33981.2)"
     Site            321
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:18669648,
                     ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163;
                     propagated from UniProtKB/Swiss-Prot (P33981.2)"
     Site            360
                     /site_type="phosphorylation"
                     /note="Phosphothreonine, by autocatalysis.
                     /evidence=ECO:0000269|PubMed:28441529; propagated from
                     UniProtKB/Swiss-Prot (P33981.2)"
     Site            363
                     /site_type="phosphorylation"
                     /note="Phosphoserine, by autocatalysis.
                     /evidence=ECO:0000269|PubMed:28441529; propagated from
                     UniProtKB/Swiss-Prot (P33981.2)"
     Region          371..410
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (P33981.2)"
     Site            393
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:18669648,
                     ECO:0007744|PubMed:18691976; propagated from
                     UniProtKB/Swiss-Prot (P33981.2)"
     Site            436
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:18691976,
                     ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163;
                     propagated from UniProtKB/Swiss-Prot (P33981.2)"
     Site            455
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (P33981.2)"
     Region          523..791
                     /region_name="PKc_Mps1"
                     /note="Catalytic domain of the Dual-specificity Mitotic
                     checkpoint protein kinase, Monopolar spindle 1 (also
                     called TTK); cd14131"
                     /db_xref="CDD:271033"
     Site            order(531..535,539,551,553,586,602..605,608,610,647,649,
                     651..652,654,664,667,685..688)
                     /site_type="active"
                     /db_xref="CDD:271033"
     Site            order(531..535,539,551,553,586,602..605,608,647,649,
                     651..652,654,664)
                     /site_type="other"
                     /note="ATP binding site [chemical binding]"
                     /db_xref="CDD:271033"
     Site            order(535,608,610,647,649,651,667,685..688)
                     /site_type="other"
                     /note="polypeptide substrate binding site [polypeptide
                     binding]"
                     /db_xref="CDD:271033"
     Site            order(537,553,555,568,571,600,663)
                     /site_type="other"
                     /note="secondary chemical binding site [chemical binding]"
                     /db_xref="CDD:271033"
     Site            663..688
                     /site_type="other"
                     /note="activation loop (A-loop)"
                     /db_xref="CDD:271033"
     Site            821
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:17924679,
                     ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976,
                     ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:20068231,
                     ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (P33981.2)"
     Region          836..857
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (P33981.2)"
     CDS             1..857
                     /gene="TTK"
                     /gene_synonym="CT96; ESK; MPH1; MPS1; MPS1L1; PYT"
                     /coded_by="NM_003318.5:68..2641"
                     /note="isoform 1 is encoded by transcript variant 1"
                     /db_xref="CCDS:CCDS4993.1"
                     /db_xref="GeneID:7272"
                     /db_xref="HGNC:HGNC:12401"
                     /db_xref="MIM:604092"
ORIGIN      
        1 mesedlsgre ltidsimnkv rdiknkfkne dltdelslnk isadttdnsg tvnqimmman
       61 npedwlslll kleknsvpls dallnkligr ysqaiealpp dkygqnesfa riqvrfaelk
      121 aiqepddard yfqmaranck kfafvhisfa qfelsqgnvk kskqllqkav ergavpleml
      181 eialrnlnlq kkqllseeek knlsastvlt aqesfsgslg hlqnrnnscd srgqttkarf
      241 lygenmppqd aeigyrnslr qtnktkqscp fgrvpvnlln spdcdvktdd svvpcfmkrq
      301 tsrsecrdlv vpgskpsgnd scelrnlksv qnshfkeplv sdeksselii tdsitlknkt
      361 essllaklee tkeyqepevp esnqkqwqsk rksecinqnp aassnhwqip elarkvnteq
      421 khttfeqpvf svskqsppis tskwfdpksi cktpssntld dymscfrtpv vkndfppacq
      481 lstpygqpac fqqqqhqila tplqnlqvla sssanecisv kgriysilkq igsggsskvf
      541 qvlnekkqiy aikyvnleea dnqtldsyrn eiaylnklqq hsdkiirlyd yeitdqyiym
      601 vmecgnidln swlkkkksid pwerksywkn mleavhtihq hgivhsdlkp anflivdgml
      661 klidfgianq mqpdttsvvk dsqvgtvnym ppeaikdmss srengksksk ispksdvwsl
      721 gcilyymtyg ktpfqqiinq isklhaiidp nheiefpdip ekdlqdvlkc clkrdpkqri
      781 sipellahpy vqiqthpvnq makgtteemk yvlgqlvgln spnsilkaak tlyehysgge
      841 shnssssktf ekkrgkk
//
