FACE2_HUMAN
ID FACE2_HUMAN Reviewed; 329 AA.
AC Q9Y256; Q52LZ9;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=CAAX prenyl protease 2;
DE EC=3.4.-.-;
DE AltName: Full=Farnesylated proteins-converting enzyme 2;
DE Short=FACE-2;
DE AltName: Full=Prenyl protein-specific endoprotease 2;
DE AltName: Full=RCE1 homolog;
DE Short=hRCE1;
GN Name=RCE1; Synonyms=FACE2, RCE1A, RCE1B;
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].
RC TISSUE=Ovary;
RX PubMed=10373325; DOI=10.1006/geno.1999.5834;
RA Freije J.M.P., Blay P., Pendas A.M., Cadinanos J., Crespo P.,
RA Lopez-Otin C.;
RT "Identification and chromosomal location of two human genes encoding
RT enzymes potentially involved in proteolytic maturation of farnesylated
RT proteins.";
RL Genomics 58:270-280(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, FUNCTION, AND TISSUE
RP SPECIFICITY.
RX PubMed=10085068; DOI=10.1074/jbc.274.13.8379;
RA Otto J.C., Kim E., Young S.G., Casey P.J.;
RT "Cloning and characterization of a mammalian prenyl protein-specific
RT protease.";
RL J. Biol. Chem. 274:8379-8382(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 CHARACTERIZATION, AND FUNCTION.
RX PubMed=11038283; DOI=10.1006/abio.2000.4795;
RA Hollander I., Frommer E., Mallon R.;
RT "Human ras-converting enzyme (hRCE1) endoproteolytic activity on K-ras-
RT derived peptides.";
RL Anal. Biochem. 286:129-137(2000).
RN [5]
RP UBIQUITINATION, DEUBIQUITINATION BY USP17L2, SUBCELLULAR LOCATION, ACTIVITY
RP REGULATION, AND FUNCTION.
RX PubMed=19188362; DOI=10.1074/jbc.m807216200;
RA Burrows J.F., Kelvin A.A., McFarlane C., Burden R.E., McGrattan M.J.,
RA De la Vega M., Govender U., Quinn D.J., Dib K., Gadina M., Scott C.J.,
RA Johnston J.A.;
RT "USP17 regulates Ras activation and cell proliferation by blocking RCE1
RT activity.";
RL J. Biol. Chem. 284:9587-9595(2009).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [7]
RP VARIANT [LARGE SCALE ANALYSIS] ALA-326.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Proteolytically removes the C-terminal three residues of
CC farnesylated and geranylated proteins. Seems to be able to process K-
CC Ras, N-Ras, H-Ras, RAP1B and G-gamma-1 (PubMed:10085068).
CC {ECO:0000269|PubMed:10085068, ECO:0000269|PubMed:11038283,
CC ECO:0000269|PubMed:19188362}.
CC -!- ACTIVITY REGULATION: Deubiquitination by USP17L2/USP17 negatively
CC regulates the proteolytic activity toward Ras GTPases.
CC {ECO:0000269|PubMed:19188362}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:19188362}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:19188362}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:10085068}.
CC -!- PTM: Ubiquitinated. Undergoes 'Lys-48'- and 'Lys-63'-linked
CC ubiquitination. 'Lys-48' ubiquitination induces its degradation.
CC Deubiquitinated by USP17L2/USP17 that cleaves 'Lys-63'-linked ubiquitin
CC chains. {ECO:0000269|PubMed:19188362}.
CC -!- SIMILARITY: Belongs to the peptidase U48 family. {ECO:0000305}.
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DR EMBL; Y13835; CAB46278.1; -; mRNA.
DR EMBL; AF121951; AAD22632.1; -; mRNA.
DR EMBL; BC093726; AAH93726.1; -; mRNA.
DR EMBL; BC093728; AAH93728.1; -; mRNA.
DR CCDS; CCDS8151.1; -.
DR RefSeq; NP_001027450.1; NM_001032279.1.
DR RefSeq; NP_005124.1; NM_005133.2.
DR AlphaFoldDB; Q9Y256; -.
DR BioGRID; 115307; 11.
DR IntAct; Q9Y256; 3.
DR STRING; 9606.ENSP00000309163; -.
DR BindingDB; Q9Y256; -.
DR ChEMBL; CHEMBL3411; -.
DR DrugCentral; Q9Y256; -.
DR GuidetoPHARMACOLOGY; 2412; -.
DR MEROPS; G05.002; -.
DR iPTMnet; Q9Y256; -.
DR PhosphoSitePlus; Q9Y256; -.
DR SwissPalm; Q9Y256; -.
DR BioMuta; RCE1; -.
DR DMDM; 13431529; -.
DR EPD; Q9Y256; -.
DR jPOST; Q9Y256; -.
DR MassIVE; Q9Y256; -.
DR MaxQB; Q9Y256; -.
DR PaxDb; Q9Y256; -.
DR PeptideAtlas; Q9Y256; -.
DR PRIDE; Q9Y256; -.
DR ProteomicsDB; 85658; -.
DR Antibodypedia; 16385; 130 antibodies from 26 providers.
DR DNASU; 9986; -.
DR Ensembl; ENST00000309657.8; ENSP00000309163.3; ENSG00000173653.8.
DR GeneID; 9986; -.
DR KEGG; hsa:9986; -.
DR MANE-Select; ENST00000309657.8; ENSP00000309163.3; NM_005133.3; NP_005124.1.
DR UCSC; uc001ojk.2; human.
DR CTD; 9986; -.
DR DisGeNET; 9986; -.
DR GeneCards; RCE1; -.
DR HGNC; HGNC:13721; RCE1.
DR HPA; ENSG00000173653; Low tissue specificity.
DR MIM; 605385; gene.
DR neXtProt; NX_Q9Y256; -.
DR OpenTargets; ENSG00000173653; -.
DR PharmGKB; PA34302; -.
DR VEuPathDB; HostDB:ENSG00000173653; -.
DR eggNOG; KOG4130; Eukaryota.
DR GeneTree; ENSGT00390000004124; -.
DR HOGENOM; CLU_049909_3_0_1; -.
DR InParanoid; Q9Y256; -.
DR OMA; HSFCNWC; -.
DR OrthoDB; 1607650at2759; -.
DR PhylomeDB; Q9Y256; -.
DR TreeFam; TF313800; -.
DR BRENDA; 3.4.99.B1; 2681.
DR PathwayCommons; Q9Y256; -.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR Reactome; R-HSA-9648002; RAS processing.
DR SignaLink; Q9Y256; -.
DR BioGRID-ORCS; 9986; 38 hits in 1074 CRISPR screens.
DR ChiTaRS; RCE1; human.
DR GeneWiki; RCE1; -.
DR GenomeRNAi; 9986; -.
DR Pharos; Q9Y256; Tchem.
DR PRO; PR:Q9Y256; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9Y256; protein.
DR Bgee; ENSG00000173653; Expressed in lower esophagus mucosa and 156 other tissues.
DR ExpressionAtlas; Q9Y256; baseline and differential.
DR Genevisible; Q9Y256; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; TAS:Reactome.
DR GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0008238; F:exopeptidase activity; IDA:GO_Central.
DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR GO; GO:0071586; P:CAAX-box protein processing; IDA:GO_Central.
DR GO; GO:0000165; P:MAPK cascade; TAS:Reactome.
DR GO; GO:0018342; P:protein prenylation; IDA:GO_Central.
DR InterPro; IPR039731; Rce1.
DR InterPro; IPR003675; Rce1-like.
DR PANTHER; PTHR13046; PTHR13046; 1.
DR Pfam; PF02517; Rce1-like; 1.
PE 1: Evidence at protein level;
KW Acetylation; Endoplasmic reticulum; Hydrolase; Membrane; Protease;
KW Reference proteome; Transmembrane; Transmembrane helix; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..329
FT /note="CAAX prenyl protease 2"
FT /id="PRO_0000194830"
FT TRANSMEM 25..45
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 75..95
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 112..132
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 186..206
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 229..249
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 254..274
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 283..303
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 175
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q6LZY8"
FT ACT_SITE 208
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q6LZY8"
FT SITE 261
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:Q6LZY8"
FT SITE 265
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:Q6LZY8"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT VARIANT 326
FT /note="P -> A (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036407"
SQ SEQUENCE 329 AA; 35833 MW; BA8F764651172BFA CRC64;
MAALGGDGLR LLSVSRPERP PESAALGGLG PGLCCWVSVF SCLSLACSYV GSLYVWKSEL
PRDHPAVIKR RFTSVLVVSS LSPLCVLLWR ELTGIQPGTS LLTLMGFRLE GIFPAALLPL
LLTMILFLGP LMQLSMDCPC DLADGLKVVL APRSWARCLT DMRWLRNQVI APLTEELVFR
ACMLPMLAPC MGLGPAVFTC PLFFGVAHFH HIIEQLRFRQ SSVGNIFLSA AFQFSYTAVF
GAYTAFLFIR TGHLIGPVLC HSFCNYMGFP AVCAALEHPQ RRPLLAGYAL GVGLFLLLLQ
PLTDPKLYGS LPLCVLLERA GDSEAPLCS
