RBCC Red Blood Cell Collection

ADRM1 (GP110) [Confidence: low (only semi-automatic identification from reviews)]
Proteasomal ubiquitin receptor ADRM1 (110 kDa cell membrane glycoprotein; Gp110; Adhesion-regulating molecule 1; ARM-1; Proteasome regulatory particle non-ATPase 13; hRpn13; Rpn13 homolog)
Note: presumably soluble (membrane word is not in UniProt keywords or features)

UniProt Q16186
ID ADRM1_HUMAN Reviewed; 407 AA.
AC Q16186; A0PKB1; Q96FJ7; Q9H1P2;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2002, sequence version 2.
DT 22-JAN-2014, entry version 117.
DE RecName: Full=Proteasomal ubiquitin receptor ADRM1;
DE AltName: Full=110 kDa cell membrane glycoprotein;
DE Short=Gp110;
DE AltName: Full=Adhesion-regulating molecule 1;
DE Short=ARM-1;
DE AltName: Full=Proteasome regulatory particle non-ATPase 13;
DE Short=hRpn13;
DE AltName: Full=Rpn13 homolog;
GN Name=ADRM1; Synonyms=GP110;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8033103;
RA Shimada S., Ogawa M., Takahashi M., Schlom J., Greiner J.W.;
RT "Molecular cloning and characterization of the complementary DNA of an
RT M(r) 110,000 antigen expressed by human gastric carcinoma cells and
RT upregulated by gamma-interferon.";
RL Cancer Res. 54:3831-3836(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH PSMD1 AND
RP UCHL5, SUBCELLULAR LOCATION, AND MASS SPECTROMETRY.
RX PubMed=16990800; DOI=10.1038/sj.emboj.7601338;
RA Hamazaki J., Iemura S., Natsume T., Yashiroda H., Tanaka K.,
RA Murata S.;
RT "A novel proteasome-interacting protein recruits the deubiquitinating
RT enzyme UCH37 to 26S proteasomes.";
RL EMBO J. 25:4524-4536(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Pancreas;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, INTERACTION WITH UCHL5, SUBCELLULAR LOCATION, AND MASS
RP SPECTROMETRY.
RX PubMed=17139257; DOI=10.1038/sj.emboj.7601450;
RA Qiu X.-B., Ouyang S.-Y., Li C.-J., Miao S., Wang L., Goldberg A.L.;
RT "hRpn13/ADRM1/GP110 is a novel proteasome subunit that binds the
RT deubiquitinating enzyme, UCH37.";
RL EMBO J. 25:5742-5753(2006).
RN [6]
RP FUNCTION, INTERACTION WITH 26S PROTEASOME, SUBCELLULAR LOCATION, AND
RP MASS SPECTROMETRY.
RX PubMed=16815440; DOI=10.1016/j.jmb.2006.06.011;
RA Joergensen J.P., Lauridsen A.-M., Kristensen P., Dissing K.,
RA Johnsen A.H., Hendil K.B., Hartmann-Petersen R.;
RT "Adrm1, a putative cell adhesion regulating protein, is a novel
RT proteasome-associated factor.";
RL J. Mol. Biol. 360:1043-1052(2006).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-217, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [8]
RP FUNCTION, INTERACTION WITH PSMD1 AND UCHL5, AND MASS SPECTROMETRY.
RX PubMed=16906146; DOI=10.1038/ncb1460;
RA Yao T., Song L., Xu W., DeMartino G.N., Florens L., Swanson S.K.,
RA Washburn M.P., Conaway R.C., Conaway J.W., Cohen R.E.;
RT "Proteasome recruitment and activation of the Uch37 deubiquitinating
RT enzyme by Adrm1.";
RL Nat. Cell Biol. 8:994-1002(2006).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17323924; DOI=10.1021/bi061994u;
RA Wang X., Chen C.-F., Baker P.R., Chen P.-L., Kaiser P., Huang L.;
RT "Mass spectrometric characterization of the affinity-purified human
RT 26S proteasome complex.";
RL Biochemistry 46:3553-3565(2007).
RN [10]
RP FUNCTION, AND INTERACTION WITH UBIQUITIN.
RX PubMed=18497817; DOI=10.1038/nature06926;
RA Husnjak K., Elsasser S., Zhang N., Chen X., Randles L., Shi Y.,
RA Hofmann K., Walters K.J., Finley D., Dikic I.;
RT "Proteasome subunit Rpn13 is a novel ubiquitin receptor.";
RL Nature 453:481-488(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-211 AND THR-217, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, AND MASS SPECTROMETRY.
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Functions as a proteasomal ubiquitin receptor. Recruits
CC the deubiquitinating enzyme UCHL5 at the 26S proteasome and
CC promotes its activity.
CC -!- SUBUNIT: Interacts with PSMD1, ubiquitin and UCHL5.
CC -!- INTERACTION:
CC P48510:DSK2 (xeno); NbExp=4; IntAct=EBI-954387, EBI-6174;
CC O35593:Psmd14 (xeno); NbExp=2; IntAct=EBI-954387, EBI-772796;
CC P55036:PSMD4; NbExp=2; IntAct=EBI-954387, EBI-359318;
CC P54727:RAD23B; NbExp=2; IntAct=EBI-954387, EBI-954531;
CC P0CG48:UBC; NbExp=10; IntAct=EBI-954387, EBI-3390054;
CC Q9UMX0:UBQLN1; NbExp=4; IntAct=EBI-954387, EBI-741480;
CC Q9UHD9:UBQLN2; NbExp=3; IntAct=EBI-954387, EBI-947187;
CC Q9Y5K5:UCHL5; NbExp=17; IntAct=EBI-954387, EBI-1051183;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- DOMAIN: The PH domain mediates interactions with PSMD1 and
CC ubiquitin. Preferential binding to the proximal subunit of K48-
CC linked diubiquitin allows UCHL5 access to the distal subunit (By
CC similarity).
CC -!- SIMILARITY: Belongs to the ADRM1 family.
CC -!- SIMILARITY: Contains 1 PH domain.
CC -!- CAUTION: Although initially described as a cell membrane
CC glycoprotein, ADRM1 is intracellular and non-glycosylated, and has
CC probably no direct role in cell adhesion.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; D64154; BAA11023.1; -; mRNA.
DR EMBL; AL354836; CAC22308.1; -; Genomic_DNA.
DR EMBL; BR000321; FAA00246.1; -; mRNA.
DR EMBL; BC010733; AAH10733.1; -; mRNA.
DR EMBL; BC017245; AAH17245.1; -; mRNA.
DR PIR; I52703; I52703.
DR RefSeq; NP_001268366.1; NM_001281437.1.
DR RefSeq; NP_001268367.1; NM_001281438.1.
DR RefSeq; NP_008933.2; NM_007002.3.
DR RefSeq; NP_783163.1; NM_175573.2.
DR RefSeq; XP_005260314.1; XM_005260257.1.
DR UniGene; Hs.90107; -.
DR PDB; 2KQZ; NMR; -; A=253-407.
DR PDB; 2KR0; NMR; -; A=1-407.
DR PDB; 2L5V; NMR; -; A=260-407.
DR PDBsum; 2KQZ; -.
DR PDBsum; 2KR0; -.
DR PDBsum; 2L5V; -.
DR ProteinModelPortal; Q16186; -.
DR SMR; Q16186; 1-407.
DR DIP; DIP-42668N; -.
DR IntAct; Q16186; 29.
DR MINT; MINT-2869171; -.
DR STRING; 9606.ENSP00000253003; -.
DR PhosphoSite; Q16186; -.
DR DMDM; 20141265; -.
DR PaxDb; Q16186; -.
DR PRIDE; Q16186; -.
DR DNASU; 11047; -.
DR Ensembl; ENST00000253003; ENSP00000253003; ENSG00000130706.
DR GeneID; 11047; -.
DR KEGG; hsa:11047; -.
DR UCSC; uc002ycn.3; human.
DR CTD; 11047; -.
DR GeneCards; GC20P060877; -.
DR HGNC; HGNC:15759; ADRM1.
DR HPA; HPA042266; -.
DR MIM; 610650; gene.
DR neXtProt; NX_Q16186; -.
DR PharmGKB; PA24599; -.
DR eggNOG; NOG288027; -.
DR HOGENOM; HOG000005947; -.
DR HOVERGEN; HBG073518; -.
DR InParanoid; Q16186; -.
DR OMA; QNNAKPE; -.
DR OrthoDB; EOG70KGQZ; -.
DR EvolutionaryTrace; Q16186; -.
DR GeneWiki; ADRM1; -.
DR GenomeRNAi; 11047; -.
DR NextBio; 41984; -.
DR PRO; PR:Q16186; -.
DR Bgee; Q16186; -.
DR CleanEx; HS_ADRM1; -.
DR Genevestigator; Q16186; -.
DR GO; GO:0005737; C:cytoplasm; IDA:HPA.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0000502; C:proteasome complex; IDA:UniProtKB.
DR GO; GO:0061133; F:endopeptidase activator activity; IDA:UniProtKB.
DR GO; GO:0070628; F:proteasome binding; IDA:UniProtKB.
DR GO; GO:0043248; P:proteasome assembly; IDA:UniProtKB.
DR GO; GO:0006368; P:transcription elongation from RNA polymerase II promoter; IMP:UniProtKB.
DR InterPro; IPR006773; 26S_Psome_Ubiquitin-recp_Rpn13.
DR PANTHER; PTHR12225; PTHR12225; 1.
DR Pfam; PF04683; Proteasom_Rpn13; 1.
DR PROSITE; PS50003; PH_DOMAIN; FALSE_NEG.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Isopeptide bond; Nucleus; Phosphoprotein; Proteasome;
KW Reference proteome; Ubl conjugation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 407 Proteasomal ubiquitin receptor ADRM1.
FT /FTId=PRO_0000020631.
FT DOMAIN 22 130 PH.
FT REGION 2 132 Interaction with PSMD1.
FT REGION 362 407 Interaction with UCHL5.
FT COMPBIAS 135 202 Gly-rich.
FT COMPBIAS 193 257 Ser-rich.
FT COMPBIAS 203 213 Poly-Ser.
FT MOD_RES 2 2 N-acetylthreonine.
FT MOD_RES 211 211 Phosphoserine.
FT MOD_RES 217 217 Phosphothreonine.
FT CROSSLNK 34 34 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT CONFLICT 142 142 S -> T (in Ref. 1; BAA11023).
FT STRAND 23 26
FT STRAND 28 40
FT STRAND 45 51
FT STRAND 57 66
FT STRAND 69 75
FT STRAND 79 84
FT STRAND 89 91
FT STRAND 93 98
FT TURN 99 101
FT STRAND 104 109
FT HELIX 114 116
FT HELIX 117 129
FT TURN 191 195
FT STRAND 202 204
FT STRAND 249 253
FT TURN 254 256
FT HELIX 266 273
FT STRAND 276 278
FT STRAND 282 284
FT HELIX 285 291
FT TURN 294 296
FT HELIX 298 302
FT HELIX 304 313
FT HELIX 324 328
FT HELIX 334 348
FT STRAND 350 352
FT HELIX 353 358
FT HELIX 363 371
FT HELIX 374 384
FT STRAND 386 388
SQ SEQUENCE 407 AA; 42153 MW; 2D38811DCA231864 CRC64;
MTTSGALFPS LVPGSRGASN KYLVEFRAGK MSLKGTTVTP DKRKGLVYIQ QTDDSLIHFC
WKDRTSGNVE DDLIIFPDDC EFKRVPQCPS GRVYVLKFKA GSKRLFFWMQ EPKTDQDEEH
CRKVNEYLNN PPMPGALGAS GSSGHELSAL GGEGGLQSLL GNMSHSQLMQ LIGPAGLGGL
GGLGALTGPG LASLLGSSGP PGSSSSSSSR SQSAAVTPSS TTSSTRATPA PSAPAAASAT
SPSPAPSSGN GASTAASPTQ PIQLSDLQSI LATMNVPAGP AGGQQVDLAS VLTPEIMAPI
LANADVQERL LPYLPSGESL PQTADEIQNT LTSPQFQQAL GMFSAALASG QLGPLMCQFG
LPAEAVEAAN KGDVEAFAKA MQNNAKPEQK EGDTKDKKDE EEDMSLD
//

MIM 610650
*RECORD*
*FIELD* NO
610650
*FIELD* TI
*610650 ADHESION-REGULATING MOLECULE 1; ADRM1
;;ARM1;;
RPN13, S. CEREVISIAE, HOMOLOG OF; RPN13
read more*FIELD* TX

DESCRIPTION

Ubiquitination targets proteins for degradation by the 26S proteasome.
The 26S proteasome contains a 20S catalytic core particle (see 602175)
capped at either or both ends by 19S regulatory particles, which prepare
substrates for hydrolysis in the core region. ADRM1 is a component of
the regulatory particle that functions as a polyubiquitin receptor and
captures substrates by recognizing their covalently attached ubiquitin
chains (Zhang et al., 2009).

CLONING

Shimada et al. (1994) identified ADRM1 as a 110-kD antigen that
cross-reacted with 2 different anti-CEA (CEACAM5; 114890) monoclonal
antibodies and was upregulated following gamma-interferon (IFNG; 147570)
treatment in human gastric cancer cell lines. By immunoscreening
IFNG-treated GaCa gastric cancer cells, Shimada et al. (1994) obtained a
full-length cDNA encoding ADRM1. The 5-prime end of the cDNA is GC rich.
The deduced 407-amino acid ADRM1 protein has a calculated molecular mass
of 41.2 kD. It has a putative N-terminal signal sequence, a potential
C-terminal transmembrane region, and numerous sites for O- and
N-glycosylation. Northern blot analysis detected a 1.5-kb ADRM1
transcript in GaCa cells.

Simins et al. (1999) cloned mouse Adrm1, which they called Arm1. The
deduced 407-amino acid mouse protein shares 96% identity with the human
protein. Northern blot analysis detected expression of Arm1 in all mouse
tissues examined.

Using semiquantitative RT-PCR, Lamerant and Kieda (2005) detected ARM1
expression in human and mouse endothelial cell lines from various
tissues, but not in human skin microvascular endothelial cells. ARM1
expression was also detected in mouse and human lymphocyte cell lines.
In transfected COS cells, ARM1 was expressed predominantly as a 50-kD
protein and more weakly as a 42-kD protein. Epitope-tagged ARM1 was
expressed in the cytoplasm and beneath the plasma membrane of human skin
microvascular endothelial cells, but it was not expressed on the cell
surface. ARM1 was also secreted into the culture medium. Deglycosylation
experiments indicated that ARM1 is not a glycoprotein.

By SDS-PAGE of HeLa cell extracts, Jorgensen et al. (2006) found that
endogenous ADRM1 had an apparent molecular mass of 42 kD. Western blot
analysis detected Adrm1 at a similar molecular mass in all mouse tissues
examined.

GENE FUNCTION

Using Northern and Western blot analyses, Shimada et al. (1994) showed
that IFNG treatment increased both ADRM1 mRNA and protein expression in
GaCa cells.

Simins et al. (1999) found that expression of mouse Arm1 in transfected
293T cells substantially increased their adhesion to endothelial cells.
Increased adhesion was not due to altered expression or activity of
integrins in 293T cells.

Lamerant and Kieda (2005) found that human T cells, natural killer
lymphocytes, and primary peripheral leukocytes showed increased adhesion
to human skin endothelial cells overexpressing ARM1. Since ARM1 is not
expressed on the cell surface, they proposed that it has an indirect
role in cell-cell adhesion.

By immunoprecipitation and protein pull-down assays, Jorgensen et al.
(2006) found that ADRM1 was present almost exclusively in soluble 26S
proteasomes in HeLa cells, although a small fraction was membrane
associated. HeLa cells did not contain a pool of free ADRM1, but
recombinant ADRM1 could bind preexisting 26S proteasomes in cell
extracts. Knockdown of ADRM1 in HeLa cells had no apparent effect on the
amount of proteasomes or on proteasome function.

Yao et al. (2006) found that the deubiquitinating enzyme UCH37 (UCHL5)
bound proteasomal proteins in HEK293 cell extracts, and ADRM1
consistently coimmunoprecipitated with UCH37 and copurified with bovine
26S and 19S proteasome complexes. Yeast 2-hybrid analysis showed that
ADRM1 interacted with the C terminus of UCH37. Knockdown of ADRM1 in
HEK293 cells reduced the amount of proteasome-bound UCH37. ADRM1
accelerated UCH37-catalyzed hydrolysis of a ubiquitinated synthetic
substrate. Incorporation of UCH37 and ADRM1, but not UCH37 alone, into
the 19S complex allowed processing of polyubiquitin chains by UCH37. Yao
et al. (2006) found that the C-terminal tail domain of UCH37 was
autoinhibitory, and by binding this domain, ADRM1 relieved the
autoinhibition.

Husnjak et al. (2008) reported the identification of Rpn13/ARM1, a
component of the proteasome, as a ubiquitin receptor. Rpn13 binds
ubiquitin through a conserved amino-terminal region termed the
pleckstrin-like receptor for ubiquitin domain (Pru), which binds lys48
(K48)-linked diubiquitin with an affinity of approximately 90 nanomolar.
Like proteasomal ubiquitin receptor Rpn10/S5a (PSMD4; 601648), Rpn13
also binds ubiquitin-like domains of ubiquitin-like ubiquitin-associated
proteins. In yeast, a synthetic phenotype results when specific
mutations of the ubiquitin binding sites of Rpn10 and Rpn13 are
combined, indicating functional linkage between these ubiquitin
receptors. Because Rpn13 is also the proteasomal receptor for Uch37
(610667), a deubiquitinating enzyme, Husnjak et al. (2008) concluded
that their findings suggested a coupling of chain recognition and
disassembly at the proteasome.

BIOCHEMICAL FEATURES

Schreiner et al. (2008) merged crystallography and nuclear magnetic
resonance (NMR) data to describe the ubiquitin-binding mechanism of
Rpn13. They determined the structure of Rpn13 alone and complexed with
ubiquitin. The co-complex revealed a novel ubiquitin-binding mode in
which loops rather than secondary structural elements are used to
capture ubiquitin. Further support for the role of Rpn13 as a
proteasomal ubiquitin receptor was demonstrated by its ability to bind
ubiquitin and proteasome subunit Rpn2/S1 simultaneously. Finally,
Schreiner et al. (2008) provided a model structure of Rpn13 complexed to
diubiquitin, which provided insights into how Rpn13 as a ubiquitin
receptor is coupled to substrate deubiquitination by Uch37.

Using nuclear magnetic resonance and analytical ultracentrifugation,
Zhang et al. (2009) showed that S5A and RPN13 could bind a common
diubiquitin chain in which K48 of the proximal ubiquitin subunit was
covalently bound to gly76 of the distal subunit. In these complexes,
RPN13 preferentially bound the proximal subunit, and the 2
ubiquitin-interacting motifs (UIMs) of S5A competed for the distal
subunit. In the absence of RPN13, the 2 UIMs of S5A preferentially bound
separate ubiquitin subunits in diubiquitin, suggesting that the UIMs of
S5A would likely occupy separate ubiquitin subunits in longer ubiquitin
chains.

MAPPING

The International Radiation Hybrid Mapping Consortium mapped the ADRM1
gene to chromosome 20 (TMAP RH79208).

*FIELD* RF
1. Husnjak, K.; Elsasser, S.; Zhang, N.; Chen, X.; Randles, L.; Shi,
Y.; Hofmann, K.; Walters, K. J.; Finley, D.; Dikic, I.: Proteasome
subunit Rpn13 is a novel ubiquitin receptor. Nature 453: 481-488,
2008.

2. Jorgensen, J. P.; Lauridsen, A.-M.; Kristensen, P.; Dissing, K.;
Johnsen, A. H.; Hendil, K. B.; Hartmann-Petersen, R.: Adrm1, a putative
cell adhesion regulating protein, is a novel proteasome-associated
factor. J. Molec. Biol. 360: 1043-1052, 2006.

3. Lamerant, N.; Kieda, C.: Adhesion properties of adhesion-regulating
molecule 1 protein on endothelial cells. FEBS J. 272: 1833-1844,
2005.

4. Schreiner, P.; Chen, X.; Husnjak, K.; Randles, L.; Zhang, N.; Elsasser,
S.; Finley, D.; Dikic, I.; Walters, K. J.; Groll, M.: Ubiquitin docking
at the proteasome through a novel pleckstrin-homology domain interaction. Nature 453:
548-552, 2008.

5. Shimada, S.; Ogawa, M.; Takahashi, M.; Schlom, J.; Greiner, J.
W.: Molecular cloning and characterization of the complementary DNA
of an M(r) 110,000 antigen expressed by human gastric carcinoma cells
and upregulated by gamma-interferon. Cancer Res. 54: 3831-3836,
1994.

6. Simins, A. B.; Weighardt, H.; Weidner, K. M.; Weidle, U. H.; Holzmann,
B.: Functional cloning of ARM-1, an adhesion-regulating molecule
upregulated in metastatic tumor cells. Clin. Exp. Metastasis 17:
641-648, 1999.

7. Yao, T.; Song, L.; Xu, W.; DeMartino, G. N.; Florens, L.; Swanson,
S. K.; Washburn, M. P.; Conaway, R. C.; Conaway, J. W.; Cohen, R.
E.: Proteasome recruitment and activation of the Uch37 deubiquitinating
enzyme by Adrm1. Nature Cell Biol. 8: 994-1002, 2006.

8. Zhang, N.; Wang, Q.; Ehlinger, A.; Randles, L.; Lary, J. W.; Kang,
Y.; Haririnia, A.; Storaska, A. J.; Cole, J. L.; Fushman, D.; Walters,
K. J.: Structure of the S5a:K48-linked diubiquitin complex and its
interactions with Rpn13. Molec. Cell 35: 280-290, 2009.

*FIELD* CN
Patricia A. Hartz - updated: 9/21/2009
Ada Hamosh - updated: 6/3/2008

*FIELD* CD
Patricia A. Hartz: 12/13/2006

*FIELD* ED
mgross: 10/05/2009
mgross: 10/5/2009
terry: 9/21/2009
alopez: 6/3/2008
terry: 6/3/2008
mgross: 12/13/2006