TMG2_HUMAN
ID TMG2_HUMAN Reviewed; 202 AA.
AC O14669; Q6IBF8;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Transmembrane gamma-carboxyglutamic acid protein 2;
DE AltName: Full=Proline-rich gamma-carboxyglutamic acid protein 2;
DE Short=Proline-rich Gla protein 2;
DE Flags: Precursor;
GN Name=PRRG2 {ECO:0000312|HGNC:HGNC:9470};
GN Synonyms=PRGP2 {ECO:0000303|PubMed:17502622}, TMG2;
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], AND TISSUE SPECIFICITY.
RX PubMed=9256434; DOI=10.1073/pnas.94.17.9058;
RA Kulman J.D., Harris J.E., Haldeman B.A., Davie E.W.;
RT "Primary structure and tissue distribution of two novel proline-rich gamma-
RT carboxyglutamic acid proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:9058-9062(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP INTERACTION WITH YAP1, SUBCELLULAR LOCATION, GAMMA-CARBOXYGLUTAMATION, LPXY
RP AND PPXY MOTIFS, AND MUTAGENESIS OF PHE-31; ARG-49; PRO-173; GLY-174;
RP LEU-175; PRO-176; THR-177; TYR-178; GLU-179; GLN-180 AND TYR-195.
RX PubMed=17502622; DOI=10.1073/pnas.0703195104;
RA Kulman J.D., Harris J.E., Xie L., Davie E.W.;
RT "Proline-rich Gla protein 2 is a cell-surface vitamin K-dependent protein
RT that binds to the transcriptional coactivator Yes-associated protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:8767-8772(2007).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=23873930; DOI=10.1074/jbc.m113.484683;
RA Yazicioglu M.N., Monaldini L., Chu K., Khazi F.R., Murphy S.L., Huang H.,
RA Margaritis P., High K.A.;
RT "Cellular localization and characterization of cytosolic binding partners
RT for Gla domain-containing proteins PRRG4 and PRRG2.";
RL J. Biol. Chem. 288:25908-25914(2013).
CC -!- SUBUNIT: Interacts with NEDD4 (By similarity). Interacts (via
CC cytoplasmic domain) with transcriptional coactivator YAP1
CC (PubMed:17502622). {ECO:0000250|UniProtKB:Q8R182,
CC ECO:0000269|PubMed:17502622}.
CC -!- INTERACTION:
CC O14669; Q96PU5: NEDD4L; NbExp=2; IntAct=EBI-9824765, EBI-717962;
CC O14669; P46937: YAP1; NbExp=6; IntAct=EBI-9824765, EBI-1044059;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17502622};
CC Single-pass type I membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels in kidney
CC (PubMed:23873930). Also highly expressed in the thyroid
CC (PubMed:9256434, PubMed:23873930). {ECO:0000269|PubMed:23873930,
CC ECO:0000269|PubMed:9256434}.
CC -!- PTM: Gamma-carboxyglutamate residues are formed by vitamin K dependent
CC carboxylation. These residues are essential for the binding of calcium.
CC {ECO:0000255|PROSITE-ProRule:PRU00463, ECO:0000269|PubMed:17502622}.
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DR EMBL; AF009243; AAB67071.1; -; mRNA.
DR EMBL; CR456846; CAG33127.1; -; mRNA.
DR CCDS; CCDS12773.1; -.
DR RefSeq; NP_000942.1; NM_000951.2.
DR RefSeq; XP_006723349.1; XM_006723286.2.
DR AlphaFoldDB; O14669; -.
DR SMR; O14669; -.
DR BioGRID; 111622; 9.
DR DIP; DIP-60947N; -.
DR IntAct; O14669; 5.
DR MINT; O14669; -.
DR STRING; 9606.ENSP00000246794; -.
DR iPTMnet; O14669; -.
DR PhosphoSitePlus; O14669; -.
DR BioMuta; PRRG2; -.
DR MassIVE; O14669; -.
DR PaxDb; O14669; -.
DR PeptideAtlas; O14669; -.
DR PRIDE; O14669; -.
DR Antibodypedia; 2418; 73 antibodies from 25 providers.
DR DNASU; 5639; -.
DR Ensembl; ENST00000246794.10; ENSP00000246794.4; ENSG00000126460.11.
DR GeneID; 5639; -.
DR KEGG; hsa:5639; -.
DR MANE-Select; ENST00000246794.10; ENSP00000246794.4; NM_000951.3; NP_000942.1.
DR UCSC; uc002pon.4; human.
DR CTD; 5639; -.
DR DisGeNET; 5639; -.
DR GeneCards; PRRG2; -.
DR HGNC; HGNC:9470; PRRG2.
DR HPA; ENSG00000126460; Tissue enhanced (parathyroid).
DR MIM; 604429; gene.
DR neXtProt; NX_O14669; -.
DR OpenTargets; ENSG00000126460; -.
DR PharmGKB; PA33825; -.
DR VEuPathDB; HostDB:ENSG00000126460; -.
DR eggNOG; ENOG502RZZF; Eukaryota.
DR GeneTree; ENSGT00950000183084; -.
DR HOGENOM; CLU_084796_1_0_1; -.
DR InParanoid; O14669; -.
DR OMA; NRSGQHD; -.
DR OrthoDB; 1420559at2759; -.
DR PhylomeDB; O14669; -.
DR TreeFam; TF332123; -.
DR PathwayCommons; O14669; -.
DR SignaLink; O14669; -.
DR BioGRID-ORCS; 5639; 11 hits in 1072 CRISPR screens.
DR ChiTaRS; PRRG2; human.
DR GenomeRNAi; 5639; -.
DR Pharos; O14669; Tbio.
DR PRO; PR:O14669; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; O14669; protein.
DR Bgee; ENSG00000126460; Expressed in lower esophagus mucosa and 103 other tissues.
DR ExpressionAtlas; O14669; baseline and differential.
DR Genevisible; O14669; HS.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR Gene3D; 4.10.740.10; -; 1.
DR InterPro; IPR017857; Coagulation_fac-like_Gla_dom.
DR InterPro; IPR035972; GLA-like_dom_SF.
DR InterPro; IPR000294; GLA_domain.
DR Pfam; PF00594; Gla; 1.
DR PRINTS; PR00001; GLABLOOD.
DR SMART; SM00069; GLA; 1.
DR SUPFAM; SSF57630; SSF57630; 1.
DR PROSITE; PS00011; GLA_1; 1.
DR PROSITE; PS50998; GLA_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Gamma-carboxyglutamic acid; Membrane;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT PROPEP 24..49
FT /id="PRO_0000022543"
FT CHAIN 50..202
FT /note="Transmembrane gamma-carboxyglutamic acid protein 2"
FT /id="PRO_0000022544"
FT TOPO_DOM 50..109
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 110..130
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 131..202
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 50..96
FT /note="Gla"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463"
FT REGION 143..202
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 175..178
FT /note="LPXY motif; mediates binding to WW domain-containing
FT proteins"
FT /evidence="ECO:0000269|PubMed:17502622"
FT MOTIF 192..195
FT /note="PPXY motif; mediates binding to WW domain-containing
FT proteins"
FT /evidence="ECO:0000269|PubMed:17502622"
FT COMPBIAS 155..177
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 70
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463"
FT DISULFID 67..72
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463"
FT VARIANT 22
FT /note="P -> S (in dbSNP:rs35016366)"
FT /id="VAR_051442"
FT VARIANT 116
FT /note="G -> C (in dbSNP:rs2288920)"
FT /id="VAR_020332"
FT MUTAGEN 31
FT /note="F->A: Abolishes gamma-carboxylation."
FT /evidence="ECO:0000269|PubMed:17502622"
FT MUTAGEN 49
FT /note="R->A: Impairs propeptide removal."
FT /evidence="ECO:0000269|PubMed:17502622"
FT MUTAGEN 173
FT /note="P->A: No effect on interaction with YAP1."
FT /evidence="ECO:0000269|PubMed:17502622"
FT MUTAGEN 174
FT /note="G->A: No effect on interaction with YAP1."
FT /evidence="ECO:0000269|PubMed:17502622"
FT MUTAGEN 175
FT /note="L->A: Abolishes interaction with YAP1."
FT /evidence="ECO:0000269|PubMed:17502622"
FT MUTAGEN 176
FT /note="P->A: Abolishes interaction with YAP1."
FT /evidence="ECO:0000269|PubMed:17502622"
FT MUTAGEN 177
FT /note="T->A: Abolishes interaction with YAP1."
FT /evidence="ECO:0000269|PubMed:17502622"
FT MUTAGEN 178
FT /note="Y->A: Abolishes interaction with YAP1."
FT /evidence="ECO:0000269|PubMed:17502622"
FT MUTAGEN 179
FT /note="E->A: Significantly impairs interaction with YAP1."
FT /evidence="ECO:0000269|PubMed:17502622"
FT MUTAGEN 180
FT /note="Q->A: Significantly impairs interaction with YAP1."
FT /evidence="ECO:0000269|PubMed:17502622"
FT MUTAGEN 195
FT /note="Y->A: Significantly impairs interaction with YAP1."
FT /evidence="ECO:0000269|PubMed:17502622"
SQ SEQUENCE 202 AA; 22393 MW; BC79400C98492060 CRC64;
MRGHPSLLLL YMALTTCLDT SPSEETDQEV FLGPPEAQSF LSSHTRIPRA NHWDLELLTP
GNLERECLEE RCSWEEAREY FEDNTLTERF WESYIYNGKG GRGRVDVASL AVGLTGGILL
IVLAGLGAFW YLRWRQHRGQ QPCPQEAGLI SPLSPLNPLG PPTPLPPPPP PPPGLPTYEQ
ALAASGVHDA PPPPYTSLRR PH
