TGM5_HUMAN
ID TGM5_HUMAN Reviewed; 720 AA.
AC O43548; O43549; Q0VF40; Q9UEZ4;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Protein-glutamine gamma-glutamyltransferase 5;
DE EC=2.3.2.13;
DE AltName: Full=Transglutaminase X;
DE Short=TG(X);
DE Short=TGX;
DE Short=TGase X;
DE AltName: Full=Transglutaminase-5;
DE Short=TGase-5;
GN Name=TGM5; Synonyms=TGMX;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT).
RC TISSUE=Foreskin;
RX PubMed=9452468; DOI=10.1074/jbc.273.6.3452;
RA Aeschlimann D., Koeller M.K., Allen-Hoffmann B.L., Mosher D.F.;
RT "Isolation of a cDNA encoding a novel member of the transglutaminase gene
RT family from human keratinocytes. Detection and identification of
RT transglutaminase gene products based on reverse transcription-polymerase
RT chain reaction with degenerate primers.";
RL J. Biol. Chem. 273:3452-3460(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-67 AND GLY-352.
RX PubMed=11390390; DOI=10.1074/jbc.m102553200;
RA Grenard P., Bates M.K., Aeschlimann D.;
RT "Evolution of transglutaminase genes: identification of a transglutaminase
RT gene cluster on human chromosome 15q15. Structure of the gene encoding
RT transglutaminase X and a novel gene family member, transglutaminase Z.";
RL J. Biol. Chem. 276:33066-33078(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 2-16, SUBCELLULAR LOCATION, ACETYLATION AT ALA-2,
RP INDUCTION BY TPA AND CALCIUM, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=15290349; DOI=10.1007/s00726-004-0093-5;
RA Rufini A., Vilbois F., Paradisi A., Oddi S., Tartaglione R., Leta A.,
RA Bagetta G., Guerrieri P., Finazzi-Agro' A., Melino G., Candi E.;
RT "Transglutaminase 5 is acetylated at the N-terminal end.";
RL Amino Acids 26:425-430(2004).
RN [5]
RP VARIANT PSS2 CYS-113, VARIANT MET-109, CHARACTERIZATION OF VARIANT PSS2
RP CYS-113, AND CHARACTERIZATION OF VARIANT MET-109.
RX PubMed=16380904; DOI=10.1086/497707;
RA Cassidy A.J., van Steensel M.A.M., Steijlen P.M., van Geel M.,
RA van der Velden J., Morley S.M., Terrinoni A., Melino G., Candi E.,
RA McLean W.H.I.;
RT "A homozygous missense mutation in TGM5 abolishes epidermal
RT transglutaminase 5 activity and causes acral peeling skin syndrome.";
RL Am. J. Hum. Genet. 77:909-917(2005).
CC -!- FUNCTION: Catalyzes the cross-linking of proteins and the conjugation
CC of polyamines to proteins. Contributes to the formation of the
CC cornified cell envelope of keratinocytes.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-glutaminyl-[protein] + L-lysyl-[protein] = [protein]-L-
CC lysyl-N(6)-5-L-glutamyl-[protein] + NH4(+); Xref=Rhea:RHEA:54816,
CC Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10207, Rhea:RHEA-COMP:14005,
CC ChEBI:CHEBI:28938, ChEBI:CHEBI:29969, ChEBI:CHEBI:30011,
CC ChEBI:CHEBI:138370; EC=2.3.2.13; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU10024};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000250};
CC -!- INTERACTION:
CC O43548; P55212: CASP6; NbExp=3; IntAct=EBI-12027348, EBI-718729;
CC O43548; Q14451-3: GRB7; NbExp=3; IntAct=EBI-12027348, EBI-11991632;
CC O43548; O00291: HIP1; NbExp=3; IntAct=EBI-12027348, EBI-473886;
CC O43548; Q63ZY3: KANK2; NbExp=3; IntAct=EBI-12027348, EBI-2556193;
CC O43548; P13473-2: LAMP2; NbExp=3; IntAct=EBI-12027348, EBI-21591415;
CC O43548; Q6P4E2: LARP4; NbExp=3; IntAct=EBI-12027348, EBI-12079790;
CC O43548; P47929: LGALS7B; NbExp=3; IntAct=EBI-12027348, EBI-357504;
CC O43548; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-12027348, EBI-5280197;
CC O43548; Q96IZ5: RBM41; NbExp=3; IntAct=EBI-12027348, EBI-740773;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15290349}.
CC Note=Associated with intermediate filaments.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=O43548-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=O43548-2; Sequence=VSP_006415;
CC -!- TISSUE SPECIFICITY: Expressed in foreskin keratinocytes.
CC -!- INDUCTION: By 12-O-tetradecanoylphorbol-13-acetate (TPA) and calcium in
CC NHEK cells. {ECO:0000269|PubMed:15290349}.
CC -!- DISEASE: Peeling skin syndrome 2 (PSS2) [MIM:609796]: A non-
CC inflammatory and localized form of peeling skin syndrome, a
CC genodermatosis characterized by the continuous shedding of the outer
CC layers of the epidermis. In PSS2 patients, skin peeling is painless and
CC strictly limited to the dorsa of the hands and feet. It is accompanied
CC by painless erythema and spontaneous non-scarring healing.
CC Ultrastructural and histological analysis shows a level of blistering
CC high in the epidermis at the stratum granulosum-stratum corneum
CC junction. {ECO:0000269|PubMed:16380904}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the transglutaminase superfamily.
CC Transglutaminase family. {ECO:0000305}.
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DR EMBL; AF035960; AAC02978.1; -; mRNA.
DR EMBL; AF035961; AAC02979.1; -; mRNA.
DR EMBL; AF206510; AAF23981.1; -; Genomic_DNA.
DR EMBL; AF206502; AAF23981.1; JOINED; Genomic_DNA.
DR EMBL; AF206503; AAF23981.1; JOINED; Genomic_DNA.
DR EMBL; AF206504; AAF23981.1; JOINED; Genomic_DNA.
DR EMBL; AF206505; AAF23981.1; JOINED; Genomic_DNA.
DR EMBL; AF206506; AAF23981.1; JOINED; Genomic_DNA.
DR EMBL; AF206507; AAF23981.1; JOINED; Genomic_DNA.
DR EMBL; AF206508; AAF23981.1; JOINED; Genomic_DNA.
DR EMBL; AF206509; AAF23981.1; JOINED; Genomic_DNA.
DR EMBL; BC119009; AAI19010.1; -; mRNA.
DR CCDS; CCDS32211.1; -. [O43548-2]
DR CCDS; CCDS32212.1; -. [O43548-1]
DR RefSeq; NP_004236.1; NM_004245.3. [O43548-2]
DR RefSeq; NP_963925.2; NM_201631.3. [O43548-1]
DR AlphaFoldDB; O43548; -.
DR SMR; O43548; -.
DR BioGRID; 114742; 44.
DR IntAct; O43548; 21.
DR STRING; 9606.ENSP00000220420; -.
DR DrugBank; DB00130; L-Glutamine.
DR iPTMnet; O43548; -.
DR PhosphoSitePlus; O43548; -.
DR BioMuta; TGM5; -.
DR EPD; O43548; -.
DR jPOST; O43548; -.
DR MassIVE; O43548; -.
DR MaxQB; O43548; -.
DR PaxDb; O43548; -.
DR PeptideAtlas; O43548; -.
DR PRIDE; O43548; -.
DR ProteomicsDB; 49043; -. [O43548-1]
DR ProteomicsDB; 49044; -. [O43548-2]
DR Antibodypedia; 23845; 191 antibodies from 27 providers.
DR DNASU; 9333; -.
DR Ensembl; ENST00000220420.10; ENSP00000220420.5; ENSG00000104055.17. [O43548-1]
DR Ensembl; ENST00000349114.8; ENSP00000220419.8; ENSG00000104055.17. [O43548-2]
DR GeneID; 9333; -.
DR KEGG; hsa:9333; -.
DR MANE-Select; ENST00000220420.10; ENSP00000220420.5; NM_201631.4; NP_963925.2.
DR UCSC; uc001zrd.2; human. [O43548-1]
DR CTD; 9333; -.
DR DisGeNET; 9333; -.
DR GeneCards; TGM5; -.
DR GeneReviews; TGM5; -.
DR HGNC; HGNC:11781; TGM5.
DR HPA; ENSG00000104055; Tissue enhanced (esophagus, skin).
DR MalaCards; TGM5; -.
DR MIM; 603805; gene.
DR MIM; 609796; phenotype.
DR neXtProt; NX_O43548; -.
DR OpenTargets; ENSG00000104055; -.
DR Orphanet; 263534; Acral peeling skin syndrome.
DR PharmGKB; PA36494; -.
DR VEuPathDB; HostDB:ENSG00000104055; -.
DR eggNOG; ENOG502QTRA; Eukaryota.
DR GeneTree; ENSGT01050000244866; -.
DR HOGENOM; CLU_013435_1_0_1; -.
DR InParanoid; O43548; -.
DR OMA; RSSWNNV; -.
DR PhylomeDB; O43548; -.
DR TreeFam; TF324278; -.
DR BRENDA; 2.3.2.13; 2681.
DR PathwayCommons; O43548; -.
DR Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR SignaLink; O43548; -.
DR BioGRID-ORCS; 9333; 7 hits in 1060 CRISPR screens.
DR ChiTaRS; TGM5; human.
DR GenomeRNAi; 9333; -.
DR Pharos; O43548; Tbio.
DR PRO; PR:O43548; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; O43548; protein.
DR Bgee; ENSG00000104055; Expressed in skin of leg and 124 other tissues.
DR ExpressionAtlas; O43548; baseline and differential.
DR Genevisible; O43548; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003810; F:protein-glutamine gamma-glutamyltransferase activity; IBA:GO_Central.
DR GO; GO:0008544; P:epidermis development; TAS:ProtInc.
DR GO; GO:0018149; P:peptide cross-linking; IBA:GO_Central.
DR GO; GO:0036211; P:protein modification process; TAS:ProtInc.
DR Gene3D; 2.60.40.10; -; 3.
DR Gene3D; 3.90.260.10; -; 1.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR002931; Transglutaminase-like.
DR InterPro; IPR036985; Transglutaminase-like_sf.
DR InterPro; IPR023608; Transglutaminase_animal.
DR InterPro; IPR013808; Transglutaminase_AS.
DR InterPro; IPR008958; Transglutaminase_C.
DR InterPro; IPR036238; Transglutaminase_C_sf.
DR InterPro; IPR001102; Transglutaminase_N.
DR Pfam; PF00927; Transglut_C; 2.
DR Pfam; PF01841; Transglut_core; 1.
DR Pfam; PF00868; Transglut_N; 1.
DR PIRSF; PIRSF000459; TGM_EBP42; 1.
DR SMART; SM00460; TGc; 1.
DR SUPFAM; SSF49309; SSF49309; 2.
DR SUPFAM; SSF54001; SSF54001; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
DR PROSITE; PS00547; TRANSGLUTAMINASES; 1.
PE 1: Evidence at protein level;
KW Acetylation; Acyltransferase; Alternative splicing; Calcium; Cytoplasm;
KW Direct protein sequencing; Disease variant; Metal-binding;
KW Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:15290349"
FT CHAIN 2..720
FT /note="Protein-glutamine gamma-glutamyltransferase 5"
FT /id="PRO_0000213713"
FT REGION 470..499
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 474..499
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 278
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10024"
FT ACT_SITE 337
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10024"
FT ACT_SITE 360
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10024"
FT BINDING 400
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 402
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 448
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 453
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|PubMed:15290349"
FT VAR_SEQ 64..145
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:9452468"
FT /id="VSP_006415"
FT VARIANT 67
FT /note="P -> S (in dbSNP:rs757598618)"
FT /evidence="ECO:0000269|PubMed:11390390"
FT /id="VAR_013248"
FT VARIANT 109
FT /note="T -> M (in dbSNP:rs113463533)"
FT /evidence="ECO:0000269|PubMed:16380904"
FT /id="VAR_025848"
FT VARIANT 113
FT /note="G -> C (in PSS2; completely abolishes the enzyme
FT activity; dbSNP:rs112292549)"
FT /evidence="ECO:0000269|PubMed:16380904"
FT /id="VAR_025849"
FT VARIANT 352
FT /note="A -> G (in dbSNP:rs28756768)"
FT /evidence="ECO:0000269|PubMed:11390390"
FT /id="VAR_013249"
FT VARIANT 504
FT /note="V -> M (in dbSNP:rs7171797)"
FT /id="VAR_052564"
FT VARIANT 521
FT /note="Q -> R (in dbSNP:rs35985214)"
FT /id="VAR_052565"
SQ SEQUENCE 720 AA; 80778 MW; 9CF68884B48BAE1C CRC64;
MAQGLEVALT DLQSSRNNVR HHTEEITVDH LLVRRGQAFN LTLYFRNRSF QPGLDNIIFV
VETGPLPDLA LGTRAVFSLA RHHSPSPWIA WLETNGATST EVSLCAPPTA AVGRYLLKIH
IDSFQGSVTA YQLGEFILLF NPWCPEDAVY LDSEPQRQEY VMNDYGFIYQ GSKNWIRPCP
WNYGQFEDKI IDICLKLLDK SLHFQTDPAT DCALRGSPVY VSRVVCAMIN SNDDNGVLNG
NWSENYTDGA NPAEWTGSVA ILKQWNATGC QPVRYGQCWV FAAVMCTVMR CLGIPTRVIT
NFDSGHDTDG NLIIDEYYDN TGRILGNKKK DTIWNFHVWN ECWMARKDLP PAYGGWQVLD
ATPQEMSNGV YCCGPASVRA IKEGEVDLNY DTPFVFSMVN ADCMSWLVQG GKEQKLHQDT
SSVGNFISTK SIQSDERDDI TENYKYEEGS LQERQVFLKA LQKLKARSFH GSQRGAELQP
SRPTSLSQDS PRSLHTPSLR PSDVVQVSLK FKLLDPPNMG QDICFVLLAL NMSSQFKDLK
VNLSAQSLLH DGSPLSPFWQ DTAFITLSPK EAKTYPCKIS YSQYSQYLST DKLIRISALG
EEKSSPEKIL VNKIITLSYP SITINVLGAA VVNQPLSIQV IFSNPLSEQV EDCVLTVEGS
GLFKKQQKVF LGVLKPQHQA SIILETVPFK SGQRQIQANM RSNKFKDIKG YRNVYVDFAL
