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Protein

Protein-glutamine gamma-glutamyltransferase 6

Gene

TGM6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins.By similarity

Catalytic activityi

Protein glutamine + alkylamine = protein N(5)-alkylglutamine + NH3.PROSITE-ProRule annotation

Cofactori

Ca2+By similarityNote: Binds up to 3 Ca2+ cations per subunit.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi223 – 2231Calcium 1; via carbonyl oxygenSequence Analysis
Metal bindingi226 – 2261Calcium 1Sequence Analysis
Metal bindingi228 – 2281Calcium 1; via carbonyl oxygenSequence Analysis
Active sitei274 – 2741PROSITE-ProRule annotation
Metal bindingi303 – 3031Calcium 2By similarity
Metal bindingi305 – 3051Calcium 2By similarity
Metal bindingi307 – 3071Calcium 2By similarity
Metal bindingi309 – 3091Calcium 2; via carbonyl oxygenBy similarity
Metal bindingi327 – 3271Calcium 2By similarity
Active sitei333 – 3331PROSITE-ProRule annotation
Active sitei356 – 3561PROSITE-ProRule annotation
Metal bindingi396 – 3961Calcium 3By similarity
Metal bindingi417 – 4171Calcium 3; via carbonyl oxygenBy similarity
Metal bindingi445 – 4451Calcium 3By similarity
Metal bindingi450 – 4501Calcium 3By similarity

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • protein-glutamine gamma-glutamyltransferase activity Source: MGI

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Acyltransferase, Transferase

Keywords - Ligandi

Calcium, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Protein-glutamine gamma-glutamyltransferase 6 (EC:2.3.2.13)
Alternative name(s):
Transglutaminase Y
Short name:
TGY
Short name:
TGase Y
Transglutaminase-3-like
Short name:
TGase-3-like
Transglutaminase-6
Short name:
TG6
Short name:
TGase-6
Gene namesi
Name:TGM6
Synonyms:TGM3L
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:16255. TGM6.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Spinocerebellar ataxia 35 (SCA35)4 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA35 patients commonly show upper limb involvement and torticollis. There is no cognitive impairment.

See also OMIM:613908
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti111 – 1111R → C in SCA35; impairs transglutaminase activity. 1 Publication
VAR_072179
Natural varianti327 – 3271D → G in SCA35; decreased transglutaminase activity; decreased protein stability. 2 Publications
VAR_065360
Natural varianti510 – 5101D → H in SCA35; impairs transglutaminase activity. 2 Publications
VAR_072180
Natural varianti517 – 5171L → W in SCA35; decreased transglutaminase activity; decreased protein stability. 2 Publications
VAR_065361
Natural varianti574 – 5741Missing in SCA35; impairs transglutaminase activity. 1 Publication
VAR_072181

Keywords - Diseasei

Disease mutation, Neurodegeneration, Spinocerebellar ataxia

Organism-specific databases

MIMi613908. phenotype.
Orphaneti319465. Inherited acute myeloid leukemia.
276193. Spinocerebellar ataxia type 35.
PharmGKBiPA38098.

Chemistry

DrugBankiDB00130. L-Glutamine.

Polymorphism and mutation databases

BioMutaiTGM6.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 706706Protein-glutamine gamma-glutamyltransferase 6PRO_0000213715Add
BLAST

Proteomic databases

PaxDbiO95932.
PRIDEiO95932.

PTM databases

PhosphoSiteiO95932.

Expressioni

Gene expression databases

BgeeiO95932.
CleanExiHS_TGM6.
GenevisibleiO95932. HS.

Organism-specific databases

HPAiHPA059196.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000202625.

Structurei

3D structure databases

ProteinModelPortaliO95932.
SMRiO95932. Positions 2-703.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiNOG80379.
GeneTreeiENSGT00760000119108.
HOGENOMiHOG000231695.
HOVERGENiHBG004342.
InParanoidiO95932.
KOiK05624.
OMAiHTKAVFQ.
OrthoDBiEOG7WT40M.
PhylomeDBiO95932.
TreeFamiTF324278.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
3.90.260.10. 1 hit.
InterProiIPR023608. Gln_gamma-glutamylTfrase_euk.
IPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002931. Transglutaminase-like.
IPR008958. Transglutaminase_C.
IPR013808. Transglutaminase_CS.
IPR001102. Transglutaminase_N.
[Graphical view]
PANTHERiPTHR11590. PTHR11590. 1 hit.
PfamiPF00927. Transglut_C. 2 hits.
PF01841. Transglut_core. 1 hit.
PF00868. Transglut_N. 1 hit.
[Graphical view]
PIRSFiPIRSF000459. TGM_EBP42. 1 hit.
SMARTiSM00460. TGc. 1 hit.
[Graphical view]
SUPFAMiSSF49309. SSF49309. 2 hits.
SSF81296. SSF81296. 1 hit.
PROSITEiPS00547. TRANSGLUTAMINASES. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O95932-1) [UniParc]FASTAAdd to basket

Also known as: Long

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
MAGIRVTKVD WQRSRNGAAH HTQEYPCPEL VVRRGQSFSL TLELSRALDC
60 70 80 90 100
EEILIFTMET GPRASEALHT KAVFQTSELE RGEGWTAARE AQMEKTLTVS
110 120 130 140 150
LASPPSAVIG RYLLSIRLSS HRKHSNRRLG EFVLLFNPWC AEDDVFLASE
160 170 180 190 200
EERQEYVLSD SGIIFRGVEK HIRAQGWNYG QFEEDILNIC LSILDRSPGH
210 220 230 240 250
QNNPATDVSC RHNPIYVTRV ISAMVNSNND RGVVQGQWQG KYGGGTSPLH
260 270 280 290 300
WRGSVAILQK WLKGRYKPVK YGQCWVFAGV LCTVLRCLGI ATRVVSNFNS
310 320 330 340 350
AHDTDQNLSV DKYVDSFGRT LEDLTEDSMW NFHVWNESWF ARQDLGPSYN
360 370 380 390 400
GWQVLDATPQ EESEGVFRCG PASVTAIREG DVHLAHDGPF VFAEVNADYI
410 420 430 440 450
TWLWHEDESR ERVYSNTKKI GRCISTKAVG SDSRVDITDL YKYPEGSRKE
460 470 480 490 500
RQVYSKAVNR LFGVEASGRR IWIRRAGGRC LWRDDLLEPA TKPSIAGKFK
510 520 530 540 550
VLEPPMLGHD LRLALCLANL TSRAQRVRVN LSGATILYTR KPVAEILHES
560 570 580 590 600
HAVRLGPQEE KRIPITISYS KYKEDLTEDK KILLAAMCLV TKGEKLLVEK
610 620 630 640 650
DITLEDFITI KVLGPAMVGV AVTVEVTVVN PLIERVKDCA LMVEGSGLLQ
660 670 680 690 700
EQLSIDVPTL EPQERASVQF DITPSKSGPR QLQVDLVSPH FPDIKGFVIV

HVATAK
Length:706
Mass (Da):79,312
Last modified:August 16, 2005 - v3
Checksum:i97BBE2043C5FF834
GO
Isoform 2 (identifier: O95932-2) [UniParc]FASTAAdd to basket

Also known as: Short

The sequence of this isoform differs from the canonical sequence as follows:
     612-625: VLGPAMVGVAVTVE → RAYPGASGEGLSPV
     626-706: Missing.

Show »
Length:625
Mass (Da):70,516
Checksum:i4E91DB6E8EFBEBAA
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti58 – 581M → V.1 Publication
Corresponds to variant rs2076405 [ dbSNP | Ensembl ].
VAR_013250
Natural varianti111 – 1111R → C in SCA35; impairs transglutaminase activity. 1 Publication
VAR_072179
Natural varianti327 – 3271D → G in SCA35; decreased transglutaminase activity; decreased protein stability. 2 Publications
VAR_065360
Natural varianti510 – 5101D → H in SCA35; impairs transglutaminase activity. 2 Publications
VAR_072180
Natural varianti517 – 5171L → W in SCA35; decreased transglutaminase activity; decreased protein stability. 2 Publications
VAR_065361
Natural varianti574 – 5741Missing in SCA35; impairs transglutaminase activity. 1 Publication
VAR_072181

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei612 – 62514VLGPA…AVTVE → RAYPGASGEGLSPV in isoform 2. 1 PublicationVSP_015103Add
BLAST
Alternative sequencei626 – 70681Missing in isoform 2. 1 PublicationVSP_015104Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF540969 mRNA. Translation: AAQ10751.1.
AF540970 mRNA. Translation: AAQ10752.1.
AL049650, AL031678 Genomic DNA. Translation: CAI22576.1.
AL049650, AL031678 Genomic DNA. Translation: CAI22577.1.
AL031678, AL049650 Genomic DNA. Translation: CAI22900.1.
AL031678, AL049650 Genomic DNA. Translation: CAI22901.1.
CCDSiCCDS13025.1. [O95932-1]
CCDS58761.1. [O95932-2]
RefSeqiNP_001241663.1. NM_001254734.1. [O95932-2]
NP_945345.2. NM_198994.2. [O95932-1]
UniGeneiHs.452039.

Genome annotation databases

EnsembliENST00000202625; ENSP00000202625; ENSG00000166948.
ENST00000381423; ENSP00000370831; ENSG00000166948. [O95932-2]
GeneIDi343641.
KEGGihsa:343641.
UCSCiuc002wfy.1. human. [O95932-1]
uc010gal.1. human. [O95932-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF540969 mRNA. Translation: AAQ10751.1.
AF540970 mRNA. Translation: AAQ10752.1.
AL049650, AL031678 Genomic DNA. Translation: CAI22576.1.
AL049650, AL031678 Genomic DNA. Translation: CAI22577.1.
AL031678, AL049650 Genomic DNA. Translation: CAI22900.1.
AL031678, AL049650 Genomic DNA. Translation: CAI22901.1.
CCDSiCCDS13025.1. [O95932-1]
CCDS58761.1. [O95932-2]
RefSeqiNP_001241663.1. NM_001254734.1. [O95932-2]
NP_945345.2. NM_198994.2. [O95932-1]
UniGeneiHs.452039.

3D structure databases

ProteinModelPortaliO95932.
SMRiO95932. Positions 2-703.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000202625.

Chemistry

BindingDBiO95932.
ChEMBLiCHEMBL2079852.
DrugBankiDB00130. L-Glutamine.

PTM databases

PhosphoSiteiO95932.

Polymorphism and mutation databases

BioMutaiTGM6.

Proteomic databases

PaxDbiO95932.
PRIDEiO95932.

Protocols and materials databases

DNASUi343641.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000202625; ENSP00000202625; ENSG00000166948.
ENST00000381423; ENSP00000370831; ENSG00000166948. [O95932-2]
GeneIDi343641.
KEGGihsa:343641.
UCSCiuc002wfy.1. human. [O95932-1]
uc010gal.1. human. [O95932-2]

Organism-specific databases

CTDi343641.
GeneCardsiGC20P002309.
H-InvDBHIX0040537.
HGNCiHGNC:16255. TGM6.
HPAiHPA059196.
MIMi613900. gene.
613908. phenotype.
neXtProtiNX_O95932.
Orphaneti319465. Inherited acute myeloid leukemia.
276193. Spinocerebellar ataxia type 35.
PharmGKBiPA38098.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG80379.
GeneTreeiENSGT00760000119108.
HOGENOMiHOG000231695.
HOVERGENiHBG004342.
InParanoidiO95932.
KOiK05624.
OMAiHTKAVFQ.
OrthoDBiEOG7WT40M.
PhylomeDBiO95932.
TreeFamiTF324278.

Miscellaneous databases

GenomeRNAii343641.
NextBioi98594.
PROiO95932.
SOURCEiSearch...

Gene expression databases

BgeeiO95932.
CleanExiHS_TGM6.
GenevisibleiO95932. HS.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
3.90.260.10. 1 hit.
InterProiIPR023608. Gln_gamma-glutamylTfrase_euk.
IPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002931. Transglutaminase-like.
IPR008958. Transglutaminase_C.
IPR013808. Transglutaminase_CS.
IPR001102. Transglutaminase_N.
[Graphical view]
PANTHERiPTHR11590. PTHR11590. 1 hit.
PfamiPF00927. Transglut_C. 2 hits.
PF01841. Transglut_core. 1 hit.
PF00868. Transglut_N. 1 hit.
[Graphical view]
PIRSFiPIRSF000459. TGM_EBP42. 1 hit.
SMARTiSM00460. TGc. 1 hit.
[Graphical view]
SUPFAMiSSF49309. SSF49309. 2 hits.
SSF81296. SSF81296. 1 hit.
PROSITEiPS00547. TRANSGLUTAMINASES. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A novel transglutaminase expressed in the nervous system."
    Thomas H., Aeschlimann D.
    Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANT VAL-58.
    Tissue: Lung.
  2. "The DNA sequence and comparative analysis of human chromosome 20."
    Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E.
    , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
    Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "TGM6 identified as a novel causative gene of spinocerebellar ataxias using exome sequencing."
    Wang J.L., Yang X., Xia K., Hu Z.M., Weng L., Jin X., Jiang H., Zhang P., Shen L., Guo J.F., Li N., Li Y.R., Lei L.F., Zhou J., Du J., Zhou Y.F., Pan Q., Wang J.
    , Wang J., Li R.Q., Tang B.S.
    Brain 133:3510-3518(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS SCA35 GLY-327 AND TRP-517.
  4. "Spinocerebellar ataxia type 35 (SCA35)-associated transglutaminase 6 mutants sensitize cells to apoptosis."
    Guan W.J., Wang J.L., Liu Y.T., Ma Y.T., Zhou Y., Jiang H., Shen L., Guo J.F., Xia K., Li J.D., Tang B.S.
    Biochem. Biophys. Res. Commun. 430:780-786(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS SCA35 GLY-327 AND TRP-517.
  5. "Whole exome sequencing identifies a novel mutation in the transglutaminase 6 gene for spinocerebellar ataxia in a Chinese family."
    Li M., Pang S.Y., Song Y., Kung M.H., Ho S.L., Sham P.C.
    Clin. Genet. 83:269-273(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT SCA35 HIS-510.
  6. "Spinocerebellar ataxia 35: Novel mutations in TGM6 with clinical and genetic characterization."
    Guo Y.C., Lin J.J., Liao Y.C., Tsai P.C., Lee Y.C., Soong B.W.
    Neurology 83:1554-1561(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS SCA35 CYS-111; HIS-510 AND GLU-574 DEL, CHARACTERIZATION OF VARIANTS SCA35 CYS-111; HIS-510 AND GLU-574 DEL, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiTGM3L_HUMAN
AccessioniPrimary (citable) accession number: O95932
Secondary accession number(s): Q5JXU4
, Q5JXU5, Q719M2, Q719M3, Q9Y4U8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 10, 2002
Last sequence update: August 16, 2005
Last modified: July 22, 2015
This is version 133 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.