RHBL3_HUMAN
ID RHBL3_HUMAN Reviewed; 404 AA.
AC P58872; A6NMH1; Q495Y4; Q495Y5; Q495Y6;
DT 20-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT 20-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Rhomboid-related protein 3;
DE EC=3.4.21.105;
DE AltName: Full=Ventrhoid transmembrane protein;
GN Name=RHBDL3; Synonyms=RHBDL4, VRHO;
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] (ISOFORM 1).
RC TISSUE=Fetal brain;
RX PubMed=11900977; DOI=10.1016/s0925-4773(01)00655-4;
RA Jaszai J., Brand M.;
RT "Cloning and expression of Ventrhoid, a novel vertebrate homologue of the
RT Drosophila EGF pathway gene Rhomboid.";
RL Mech. Dev. 113:73-77(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
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).
CC -!- FUNCTION: May be involved in regulated intramembrane proteolysis and
CC the subsequent release of functional polypeptides from their membrane
CC anchors. {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleaves type-1 transmembrane domains using a catalytic dyad
CC composed of serine and histidine that are contributed by different
CC transmembrane domains.; EC=3.4.21.105;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P58872-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P58872-2; Sequence=VSP_056259;
CC Name=3;
CC IsoId=P58872-3; Sequence=VSP_056260;
CC -!- SIMILARITY: Belongs to the peptidase S54 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AJ313480; CAC86145.1; -; mRNA.
DR EMBL; AK124570; BAG54052.1; -; mRNA.
DR EMBL; AC005899; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC026620; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC100975; AAI00976.1; -; mRNA.
DR EMBL; BC100977; AAI00978.1; -; mRNA.
DR EMBL; BC100978; AAI00979.1; -; mRNA.
DR CCDS; CCDS32613.1; -. [P58872-1]
DR CCDS; CCDS82103.1; -. [P58872-3]
DR RefSeq; NP_001317110.1; NM_001330181.1. [P58872-3]
DR RefSeq; NP_612201.1; NM_138328.2. [P58872-1]
DR RefSeq; XP_016879768.1; XM_017024279.1. [P58872-2]
DR AlphaFoldDB; P58872; -.
DR SMR; P58872; -.
DR BioGRID; 127820; 4.
DR STRING; 9606.ENSP00000269051; -.
DR MEROPS; S54.006; -.
DR iPTMnet; P58872; -.
DR PhosphoSitePlus; P58872; -.
DR BioMuta; RHBDL3; -.
DR DMDM; 21542300; -.
DR MassIVE; P58872; -.
DR PaxDb; P58872; -.
DR PeptideAtlas; P58872; -.
DR PRIDE; P58872; -.
DR ProteomicsDB; 57104; -. [P58872-1]
DR ProteomicsDB; 61980; -.
DR Antibodypedia; 71802; 6 antibodies from 6 providers.
DR DNASU; 162494; -.
DR Ensembl; ENST00000269051.9; ENSP00000269051.4; ENSG00000141314.13. [P58872-1]
DR Ensembl; ENST00000536287.2; ENSP00000466508.1; ENSG00000141314.13. [P58872-2]
DR Ensembl; ENST00000538145.5; ENSP00000442092.1; ENSG00000141314.13. [P58872-3]
DR GeneID; 162494; -.
DR KEGG; hsa:162494; -.
DR MANE-Select; ENST00000269051.9; ENSP00000269051.4; NM_138328.3; NP_612201.1.
DR UCSC; uc002hhe.1; human. [P58872-1]
DR CTD; 162494; -.
DR DisGeNET; 162494; -.
DR GeneCards; RHBDL3; -.
DR HGNC; HGNC:16502; RHBDL3.
DR HPA; ENSG00000141314; Tissue enhanced (brain, retina).
DR MIM; 619017; gene.
DR neXtProt; NX_P58872; -.
DR OpenTargets; ENSG00000141314; -.
DR PharmGKB; PA34384; -.
DR VEuPathDB; HostDB:ENSG00000141314; -.
DR eggNOG; KOG0027; Eukaryota.
DR eggNOG; KOG2289; Eukaryota.
DR GeneTree; ENSGT00940000158838; -.
DR HOGENOM; CLU_048023_2_1_1; -.
DR InParanoid; P58872; -.
DR OMA; KFDPGST; -.
DR OrthoDB; 1253228at2759; -.
DR PhylomeDB; P58872; -.
DR TreeFam; TF313540; -.
DR PathwayCommons; P58872; -.
DR BioGRID-ORCS; 162494; 10 hits in 1062 CRISPR screens.
DR ChiTaRS; RHBDL3; human.
DR GenomeRNAi; 162494; -.
DR Pharos; P58872; Tdark.
DR PRO; PR:P58872; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P58872; protein.
DR Bgee; ENSG00000141314; Expressed in right frontal lobe and 88 other tissues.
DR ExpressionAtlas; P58872; baseline and differential.
DR Genevisible; P58872; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 1.20.1540.10; -; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR022764; Peptidase_S54_rhomboid_dom.
DR InterPro; IPR017213; Peptidase_S54_rhomboid_met.
DR InterPro; IPR035952; Rhomboid-like_sf.
DR Pfam; PF13499; EF-hand_7; 1.
DR Pfam; PF01694; Rhomboid; 1.
DR PIRSF; PIRSF037470; Rhomboid; 1.
DR SUPFAM; SSF144091; SSF144091; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS50222; EF_HAND_2; 2.
PE 2: Evidence at transcript level;
KW Alternative splicing; Hydrolase; Membrane; Protease; Reference proteome;
KW Repeat; Serine protease; Transmembrane; Transmembrane helix.
FT CHAIN 1..404
FT /note="Rhomboid-related protein 3"
FT /id="PRO_0000206177"
FT TRANSMEM 164..184
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 218..238
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 250..270
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 274..294
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 303..325
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 338..358
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 371..391
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 34..69
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 70..105
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT ACT_SITE 278
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 343
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..98
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_056259"
FT VAR_SEQ 38..45
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056260"
FT VARIANT 255
FT /note="V -> M (in dbSNP:rs4795690)"
FT /id="VAR_024593"
SQ SEQUENCE 404 AA; 45245 MW; BAE7319D4E2AB5AC CRC64;
MGEHPSPGPA VAACAEAERI EELEPEAEER LPAAPEDHWK VLFDQFDPGN TGYISTGKFR
SLLESHSSKL DPHKREVLLA LADSHADGQI GYQDFVSLMS NKRSNSFRQA ILQGNRRLSS
KALLEEKGLS LSQRLIRHVA YETLPREIDR KWYYDSYTCC PPPWFMITVT LLEVAFFLYN
GVSLGQFVLQ VTHPRYLKNS LVYHPQLRAQ VWRYLTYIFM HAGIEHLGLN VVLQLLVGVP
LEMVHGATRI GLVYVAGVVA GSLAVSVADM TAPVVGSSGG VYALVSAHLA NIVMNWSGMK
CQFKLLRMAV ALICMSMEFG RAVWLRFHPS AYPPCPHPSF VAHLGGVAVG ITLGVVVLRN
YEQRLQDQSL WWIFVAMYTV FVLFAVFWNI FAYTLLDLKL PPPP
