TMG4_HUMAN
ID TMG4_HUMAN Reviewed; 226 AA.
AC Q9BZD6;
DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Transmembrane gamma-carboxyglutamic acid protein 4 {ECO:0000305};
DE AltName: Full=Proline-rich gamma-carboxyglutamic acid protein 4;
DE Short=Proline-rich Gla protein 4;
DE Flags: Precursor;
GN Name=PRRG4 {ECO:0000303|PubMed:28859078, ECO:0000312|HGNC:HGNC:30799};
GN Synonyms=PRGP4, TMG4;
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=11171957; DOI=10.1073/pnas.98.4.1370;
RA Kulman J.D., Harris J.E., Xie L., Davie E.W.;
RT "Identification of two novel transmembrane gamma-carboxyglutamic acid
RT proteins expressed broadly in fetal and adult tissues.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:1370-1375(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-163, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=28859078; DOI=10.1371/journal.pgen.1006865;
RA Justice E.D., Barnum S.J., Kidd T.;
RT "The WAGR syndrome gene PRRG4 is a functional homologue of the
RT commissureless axon guidance gene.";
RL PLoS Genet. 13:E1006865-E1006865(2017).
RN [5]
RP ERRATUM OF PUBMED:28859078.
RX PubMed=29059187; DOI=10.1371/journal.pgen.1007061;
RA Justice E.D., Barnum S.J., Kidd T.;
RL PLoS Genet. 13:e1007061-e1007061(2017).
RN [6]
RP INTERACTION WITH MAGI1; MAGI3; NEDD4; NEDD4L; WWTR1 AND YAP1, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, GAMMA-CARBOXYGLUTAMATION, LPXY AND PPXY
RP MOTIFS, AND MUTAGENESIS OF TYR-189 AND TYR-207.
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 -!- FUNCTION: May control axon guidance across the CNS (PubMed:28859078).
CC Prevents the delivery of ROBO1 at the cell surface and down-regulates
CC its expression (PubMed:28859078). {ECO:0000269|PubMed:28859078}.
CC -!- SUBUNIT: Interacts (via cytoplasmic domain) with WW domain-containing
CC proteins MAGI1, MAGI3, NEDD4, NEDD4L, WWTR1/TAZ and YAP1.
CC {ECO:0000269|PubMed:23873930}.
CC -!- INTERACTION:
CC Q9BZD6; Q5TCQ9: MAGI3; NbExp=2; IntAct=EBI-3918643, EBI-310506;
CC Q9BZD6; P46934: NEDD4; NbExp=3; IntAct=EBI-3918643, EBI-726944;
CC Q9BZD6; Q96PU5: NEDD4L; NbExp=2; IntAct=EBI-3918643, EBI-717962;
CC Q9BZD6; Q9GZV5: WWTR1; NbExp=4; IntAct=EBI-3918643, EBI-747743;
CC Q9BZD6; P46937: YAP1; NbExp=2; IntAct=EBI-3918643, EBI-1044059;
CC Q9BZD6; P46937-1: YAP1; NbExp=2; IntAct=EBI-3918643, EBI-26604877;
CC Q9BZD6; P46937-3: YAP1; NbExp=3; IntAct=EBI-3918643, EBI-6558686;
CC Q9BZD6; Q6RHR9-1: Magi1; Xeno; NbExp=2; IntAct=EBI-3918643, EBI-7441112;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum-Golgi intermediate
CC compartment membrane {ECO:0000269|PubMed:28859078}; Single-pass type I
CC membrane protein {ECO:0000255}. Cell membrane
CC {ECO:0000269|PubMed:23873930}; Single-pass type I membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels in kidney.
CC {ECO:0000269|PubMed:11171957, ECO:0000269|PubMed:23873930}.
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:23873930}.
CC -!- SIMILARITY: Belongs to the commissureless family. {ECO:0000305}.
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DR EMBL; AF326351; AAK00956.1; -; mRNA.
DR EMBL; BC010052; AAH10052.1; -; mRNA.
DR EMBL; BC063393; AAH63393.1; -; mRNA.
DR CCDS; CCDS7881.1; -.
DR RefSeq; NP_076986.1; NM_024081.5.
DR RefSeq; XP_006718377.1; XM_006718314.3.
DR AlphaFoldDB; Q9BZD6; -.
DR SMR; Q9BZD6; -.
DR BioGRID; 122514; 39.
DR IntAct; Q9BZD6; 35.
DR STRING; 9606.ENSP00000257836; -.
DR iPTMnet; Q9BZD6; -.
DR PhosphoSitePlus; Q9BZD6; -.
DR BioMuta; PRRG4; -.
DR DMDM; 20140760; -.
DR EPD; Q9BZD6; -.
DR MassIVE; Q9BZD6; -.
DR MaxQB; Q9BZD6; -.
DR PaxDb; Q9BZD6; -.
DR PeptideAtlas; Q9BZD6; -.
DR PRIDE; Q9BZD6; -.
DR ProteomicsDB; 79816; -.
DR Antibodypedia; 2457; 42 antibodies from 13 providers.
DR DNASU; 79056; -.
DR Ensembl; ENST00000257836.4; ENSP00000257836.3; ENSG00000135378.4.
DR GeneID; 79056; -.
DR KEGG; hsa:79056; -.
DR MANE-Select; ENST00000257836.4; ENSP00000257836.3; NM_024081.6; NP_076986.1.
DR UCSC; uc001mtx.4; human.
DR CTD; 79056; -.
DR DisGeNET; 79056; -.
DR GeneCards; PRRG4; -.
DR HGNC; HGNC:30799; PRRG4.
DR HPA; ENSG00000135378; Low tissue specificity.
DR MIM; 611690; gene.
DR neXtProt; NX_Q9BZD6; -.
DR OpenTargets; ENSG00000135378; -.
DR PharmGKB; PA134974592; -.
DR VEuPathDB; HostDB:ENSG00000135378; -.
DR eggNOG; ENOG502S0JP; Eukaryota.
DR GeneTree; ENSGT00940000158268; -.
DR HOGENOM; CLU_084796_0_0_1; -.
DR InParanoid; Q9BZD6; -.
DR OMA; FWKDYST; -.
DR OrthoDB; 1354567at2759; -.
DR PhylomeDB; Q9BZD6; -.
DR TreeFam; TF332123; -.
DR PathwayCommons; Q9BZD6; -.
DR SignaLink; Q9BZD6; -.
DR BioGRID-ORCS; 79056; 6 hits in 1060 CRISPR screens.
DR GenomeRNAi; 79056; -.
DR Pharos; Q9BZD6; Tdark.
DR PRO; PR:Q9BZD6; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9BZD6; protein.
DR Bgee; ENSG00000135378; Expressed in gingival epithelium and 160 other tissues.
DR ExpressionAtlas; Q9BZD6; baseline and differential.
DR Genevisible; Q9BZD6; HS.
DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:InterPro.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0050699; F:WW domain binding; IDA:UniProtKB.
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; Cleavage on pair of basic residues; Disulfide bond;
KW Gamma-carboxyglutamic acid; Membrane; Phosphoprotein; Reference proteome;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT PROPEP 18..49
FT /evidence="ECO:0000255"
FT /id="PRO_0000022551"
FT CHAIN 50..226
FT /note="Transmembrane gamma-carboxyglutamic acid protein 4"
FT /id="PRO_0000022552"
FT TOPO_DOM 50..113
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 114..134
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 135..226
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 52..98
FT /note="Gla"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOTIF 186..189
FT /note="LPXY motif; mediates binding to WW domain-containing
FT proteins"
FT /evidence="ECO:0000269|PubMed:23873930"
FT MOTIF 204..207
FT /note="PPXY motif; mediates binding to WW domain-containing
FT proteins"
FT /evidence="ECO:0000269|PubMed:23873930"
FT MOD_RES 72
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 163
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT DISULFID 69..74
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463"
FT VARIANT 33
FT /note="E -> K (in dbSNP:rs33962176)"
FT /id="VAR_051443"
FT VARIANT 143
FT /note="C -> R (in dbSNP:rs34736080)"
FT /id="VAR_051444"
FT VARIANT 176
FT /note="P -> Q (in dbSNP:rs34139105)"
FT /id="VAR_051445"
FT MUTAGEN 189
FT /note="Y->A: Reduced binding to MAGI1, MAGI3, NEDD4,
FT NEDD4L, WWTR1 and YAP1."
FT /evidence="ECO:0000269|PubMed:23873930"
FT MUTAGEN 207
FT /note="Y->A: Reduced binding to MAGI1. No effect on binding
FT to MAGI3, NEDD4, NEDD4L, WWTR1 or YAP1."
FT /evidence="ECO:0000269|PubMed:23873930"
SQ SEQUENCE 226 AA; 25403 MW; 45C783E3825797EE CRC64;
MFTLLVLLSQ LPTVTLGFPH CARGPKASKH AGEEVFTSKE EANFFIHRRL LYNRFDLELF
TPGNLERECN EELCNYEEAR EIFVDEDKTI AFWQEYSAKG PTTKSDGNRE KIDVMGLLTG
LIAAGVFLVI FGLLGYYLCI TKCNRLQHPC SSAVYERGRH TPSIIFRRPE EAALSPLPPS
VEDAGLPSYE QAVALTRKHS VSPPPPYPGH TKGFRVFKKS MSLPSH
