Reviewed, UniProtKB/Swiss-Prot P55036 (PSMD4_HUMAN)

Names and origin

Protein names

Recommended name:
    26S proteasome non-ATPase regulatory subunit 4
Alternative name(s):
    26S proteasome regulatory subunit S5A
    Rpn10
    Multiubiquitin chain-binding protein
    Antisecretory factor 1
      Short name=ASF
      Short name=AF

Gene names

Name:	PSMD4
Synonyms:	MCB1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	377 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Binds and presumably selects ubiquitin-conjugates for destruction. Displays selectivity for longer polyubiquitin chains. Modulates intestinal fluid secretion.
Subunit structure	The 26S proteasome is composed of a core protease, known as the 20S proteasome, capped at one or both ends by the 19S regulatory complex (RC). The RC is composed of at least 18 different subunits in two subcomplexes, the base and the lid, which form the portions proximal and distal to the 20S proteolytic core, respectively. Directly interacts with NUB1. Interacts with SQSTM1. Ref.10 Ref.12
Domain	The 2 UIM motifs are involved in the binding to a multi-ubiquitin chain in a cooperative way. Ref.17 Ref.18
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.13 Ref.14 Ref.15
Sequence similarities	Belongs to the proteasome subunit S5A family. Contains 2 UIM (ubiquitin-interacting motif) repeats. Contains 1 VWFA domain.

Ontologies

Keywords
Cellular component	Proteasome
Coding sequence diversity	Alternative splicing
Domain	Repeat
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process Inferred from Experiment. Source: Reactome negative regulation of ubiquitin-protein ligase activity during mitotic cell cycle Inferred from Experiment. Source: Reactome positive regulation of ubiquitin-protein ligase activity during mitotic cell cycle Inferred from Experiment. Source: Reactome
Cellular component	cytosol Inferred from electronic annotation. Source: UniProtKB-KW proteasome complex Traceable author statement. Source: ProtInc
Molecular function	protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ID1	P41134	1	EBI-359318,EBI-1215527
Pax3	P24610	1	EBI-359318,EBI-1208116	From a different organism.
PSMD10	O75832	1	EBI-359318,EBI-752185
PSMD6	Q15008	1	EBI-359318,EBI-359701

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform Rpn10A (identifier: P55036-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Rpn10E (identifier: P55036-2)

The sequence of this isoform differs from the canonical sequence as follows:
     255-268: DSDDALLKMTISQQ → GERGGIRSPGTAGC
     269-377: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.13

Chain

2 – 377

376

26S proteasome non-ATPase regulatory subunit 4

PRO_0000173828

Regions

Domain

5 – 188

184

VWFA

Repeat

211 – 230

20

UIM 1

Repeat

282 – 301

20

UIM 2

Region

216 – 220

5

Essential for ubiquitin-binding

Region

287 – 291

5

Essential for ubiquitin-binding

Compositional bias

238 – 246

9

Poly-Ala

Amino acid modifications

Modified residue

250

1

Phosphothreonine By similarity

Modified residue

256

1

Phosphoserine By similarity

Modified residue

266

1

Phosphoserine Ref.13 Ref.14 Ref.15

Modified residue

358

1

Phosphoserine Ref.13

Modified residue

361

1

Phosphoserine Ref.13

Natural variations

Alternative sequence

255 – 268

14

DSDDA…TISQQ → GERGGIRSPGTAGC in isoform Rpn10E.

VSP_005291

Alternative sequence

269 – 377

109

Missing in isoform Rpn10E.

VSP_005292

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

377

Helix Strand Turn

Details...

Beta strand

201 – 203

3

Helix

210 – 212

3

Helix

214 – 244

31

Beta strand

245 – 249

5

Helix

257 – 272

16

Beta strand

273 – 275

3

Helix

278 – 294

17

Beta strand

296 – 300

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform Rpn10A [UniParc]. Last modified October 1, 1996. Version 1. Checksum: EC712EC4DB1CE9AB	FASTA	377	40,737
	10 20 30 40 50 60 MVLESTMVCV DNSEYMRNGD FLPTRLQAQQ DAVNIVCHSK TRSNPENNVG LITLANDCEV 70 80 90 100 110 120 LTTLTPDTGR ILSKLHTVQP KGKITFCTGI RVAHLALKHR QGKNHKMRII AFVGSPVEDN 130 140 150 160 170 180 EKDLVKLAKR LKKEKVNVDI INFGEEEVNT EKLTAFVNTL NGKDGTGSHL VTVPPGPSLA 190 200 210 220 230 240 DALISSPILA GEGGAMLGLG ASDFEFGVDP SADPELALAL RVSMEEQRQR QEEEARRAAA 250 260 270 280 290 300 ASAAEAGIAT TGTEDSDDAL LKMTISQQEF GRTGLPDLSS MTEEEQIAYA MQMSLQGAEF 310 320 330 340 350 360 GQAESADIDA SSAMDTSEPA KEEDDYDVMQ DPEFLQSVLE NLPGVDPNNE AIRNAMGSLA 370 SQATKDGKKD KKEEDKK
	Isoform Rpn10E. Checksum: 6640BF4CD5C91C6E	FASTA	268	28,612
	10 20 30 40 50 60 MVLESTMVCV DNSEYMRNGD FLPTRLQAQQ DAVNIVCHSK TRSNPENNVG LITLANDCEV 70 80 90 100 110 120 LTTLTPDTGR ILSKLHTVQP KGKITFCTGI RVAHLALKHR QGKNHKMRII AFVGSPVEDN 130 140 150 160 170 180 EKDLVKLAKR LKKEKVNVDI INFGEEEVNT EKLTAFVNTL NGKDGTGSHL VTVPPGPSLA 190 200 210 220 230 240 DALISSPILA GEGGAMLGLG ASDFEFGVDP SADPELALAL RVSMEEQRQR QEEEARRAAA 250 260 ASAAEAGIAT TGTEGERGGI RSPGTAGC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and expression of a pituitary gland protein modulating intestinal fluid secretion." Johansson E., Loennroth I., Lange S., Jonson I., Jennische E., Loennroth C. J. Biol. Chem. 270:20615-20620(1995) [PubMed: 7657640] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 63-75 AND 130-140. Tissue: Pituitary.
[2]	Loennroth I. Submitted (MAY-1997) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	"Molecular cloning and expression of a multiubiquitin chain binding subunit of the human 26S protease." Ferrell K., Deveraux Q., van Nocker S., Rechsteiner M. FEBS Lett. 381:143-148(1996) [PubMed: 8641424] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
[4]	"Developmentally regulated, alternative splicing of the Rpn10 gene generates multiple forms of 26S proteasomes." Kawahara H., Kasahara M., Nishiyama A., Ohsumi K., Goto T., Kishimoto T., Saeki Y., Yokosawa H., Shimbara N., Murata S., Chiba T., Suzuki K., Tanaka K. EMBO J. 19:4144-4153(2000) [PubMed: 10921894] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING. Tissue: Fetal brain.
[5]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Liver and Lung.
[7]	"Proteolysis of presenilin 1 is associated with the 26S proteasome and is altered in Alzheimer's disease." Fraser P.E., Levesque G., Rogaeva E.A., Yu G., St George-Hyslop P.H. Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 70-377. Tissue: Brain.
[8]	"Purification and characterization of the antisecretory factor: a protein in the central nervous system and in the gut which inhibits intestinal hypersecretion induced by cholera toxin." Loennroth I., Lange S. Biochim. Biophys. Acta 883:138-144(1986) [PubMed: 3524692] [Abstract] Cited for: CHARACTERIZATION.
[9]	"Characterization of two polyubiquitin binding sites in the 26 S protease subunit 5a." Young P., Deveraux Q., Beal R.E., Pickart C.M., Rechsteiner M. J. Biol. Chem. 273:5461-5467(1998) [PubMed: 9488668] [Abstract] Cited for: POLYUBIQUITIN BINDING SITES.
[10]	"Targeting of NEDD8 and its conjugates for proteasomal degradation by NUB1." Kamitani T., Kito K., Fukuda-Kamitani T., Yeh E.T.H. J. Biol. Chem. 276:46655-46660(2001) [PubMed: 11585840] [Abstract] Cited for: INTERACTION WITH NUB1.
[11]	"An unappreciated role for RNA surveillance." Hillman R.T., Green R.E., Brenner S.E. Genome Biol. 5:RESEARCH008.1-RESEARCH008.16(2004) [PubMed: 14759258] [Abstract] Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[12]	"Sequestosome 1/p62 is a polyubiquitin chain binding protein involved in ubiquitin proteasome degradation." Seibenhener M.L., Babu J.R., Geetha T., Wong H.C., Krishna N.R., Wooten M.W. Mol. Cell. Biol. 24:8055-8068(2004) [PubMed: 15340068] [Abstract] Cited for: INTERACTION WITH SQSTM1.
[13]	"Mass spectrometric characterization of the affinity-purified human 26S proteasome complex." Wang X., Chen C.-F., Baker P.R., Chen P.-L., Kaiser P., Huang L. Biochemistry 46:3553-3565(2007) [PubMed: 17323924] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-266; SER-358 AND SER-361, CLEAVAGE OF INITIATOR METHIONINE, MASS SPECTROMETRY.
[14]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-266, MASS SPECTROMETRY.
[15]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-266, MASS SPECTROMETRY.
[16]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[17]	"Structural determinants for the binding of ubiquitin-like domains to the proteasome." Mueller T.D., Feigon J. EMBO J. 22:4634-4645(2003) [PubMed: 12970176] [Abstract] Cited for: STRUCTURE BY NMR OF 263-306 IN COMPLEX WITH HR23A UBIQUITIN-LIKE DOMAIN.
[18]	"Structure of the ubiquitin-interacting motif of S5a bound to the ubiquitin-like domain of HR23B." Fujiwara K., Tenno T., Sugasawa K., Jee J.-G., Ohki I., Kojima C., Tochio H., Hiroaki H., Hanaoka F., Shirakawa M. J. Biol. Chem. 279:4760-4767(2004) [PubMed: 14585839] [Abstract] Cited for: STRUCTURE BY NMR OF 260-307 IN COMPLEX WITH HR23B UBIQUITIN-LIKE DOMAIN.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

U51007 mRNA. Translation: AAC50433.1.
U24704 mRNA. Translation: AAB54057.1.
AB033605 mRNA. Translation: BAA97581.1.
AL391069, AL592424 Genomic DNA. Translation: CAH70329.1.
AL592424, AL391069 Genomic DNA. Translation: CAI16390.1.
BC002365 mRNA. Translation: AAH02365.1.
BC072008 mRNA. Translation: AAH72008.1.
U72664 mRNA. Translation: AAB68598.1.

IPI

IPI00022694.
IPI00216247.

PIR

S63671.

RefSeq

NP_002801.1.

UniGene

Hs.505059

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1P9C	NMR	-	A	263-307	[»]
1P9D	NMR	-	S	263-307	[»]
1UEL	NMR	-	B	263-307	[»]
1YX4	NMR	-	A	196-306	[»]
1YX5	NMR	-	A	196-306	[»]
1YX6	NMR	-	A	196-306	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P55036. 14 interactions.

PTM databases

PhosphoSite

P55036.

Proteomic databases

PRIDE

P55036.

Genome annotation databases

Ensembl

ENSG00000159352. Homo sapiens. [Contig view]

GeneID

5710.

KEGG

hsa:5710.

NMPDR

fig|9606.3.peg.2018.

UCSC

uc001exl.1. human.

Organism-specific databases

GeneCards

GC01P149493.

H-InvDB

HIX0001054.

HGNC

HGNC:9561. PSMD4.

MIM

601648. gene.

PharmGKB

PA33907.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P55036.

Enzyme and pathway databases

Reactome

REACT_11045. Signaling by Wnt.
REACT_13. Metabolism of amino acids.
REACT_13635. Regulation of activated PAK-2p34 by proteasome mediated degradation.
REACT_152. Cell Cycle, Mitotic.
REACT_1538. Cell Cycle Checkpoints.
REACT_383. DNA Replication.
REACT_578. Apoptosis.
REACT_6185. HIV Infection.
REACT_6850. Cdc20:Phospho-APC/C mediated degradation of Cyclin A.
REACT_9035. APC/C:Cdh1-mediated degradation of Skp2.

Gene expression databases

Bgee

P55036.

CleanEx

HS_PSMD4.

GermOnline

ENSG00000159352. Homo sapiens.

Family and domain databases

InterPro

IPR003903. Ubiquitin-int_motif.
IPR002035. VWF_A.
[Graphical view]

Pfam

PF02809. UIM. 2 hits.
[Graphical view]

SMART

SM00726. UIM. 2 hits.
SM00327. VWA. 1 hit.
[Graphical view]

PROSITE

PS50330. UIM. 2 hits.
PS50234. VWFA. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

22186.

SOURCE

Search...

Entry information

Entry name

PSMD4_HUMAN

Accession

Primary (citable) accession number: P55036
Secondary accession number(s): Q5VWC5, Q9NS92

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	July 7, 2009
This is version 96 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)