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   27-MAR-2024, entry version 193.
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; 47.
DR   IntAct; O43548; 21.
DR   STRING; 9606.ENSP00000220420; -.
DR   DrugBank; DB00130; L-Glutamine.
DR   GlyGen; O43548; 2 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; O43548; -.
DR   PhosphoSitePlus; O43548; -.
DR   BioMuta; TGM5; -.
DR   EPD; O43548; -.
DR   jPOST; O43548; -.
DR   MassIVE; O43548; -.
DR   MaxQB; O43548; -.
DR   PaxDb; 9606-ENSP00000220420; -.
DR   PeptideAtlas; O43548; -.
DR   ProteomicsDB; 49043; -. [O43548-1]
DR   ProteomicsDB; 49044; -. [O43548-2]
DR   Antibodypedia; 23845; 218 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   AGR; HGNC:11781; -.
DR   CTD; 9333; -.
DR   DisGeNET; 9333; -.
DR   GeneCards; 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   OrthoDB; 5344745at2759; -.
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 1136 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 126 other cell types or tissues.
DR   ExpressionAtlas; O43548; baseline and differential.
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:0036211; P:protein modification process; TAS:ProtInc.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 3.
DR   Gene3D; 3.90.260.10; Transglutaminase-like; 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   PANTHER; PTHR11590; PROTEIN-GLUTAMINE GAMMA-GLUTAMYLTRANSFERASE; 1.
DR   PANTHER; PTHR11590:SF38; PROTEIN-GLUTAMINE GAMMA-GLUTAMYLTRANSFERASE 5; 1.
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; SSF54001; Cysteine proteinases; 1.
DR   SUPFAM; SSF81296; E set domains; 1.
DR   SUPFAM; SSF49309; Transglutaminase, two C-terminal domains; 2.
DR   PROSITE; PS00547; TRANSGLUTAMINASES; 1.
DR   Genevisible; O43548; HS.
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
//