Q9UHD9 (UBQL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ubiquilin-2

Alternative name(s):
Chap1
DSK2 homolog
Protein linking IAP with cytoskeleton 2
Short name=PLIC-2
Short name=hPLIC-2
Ubiquitin-like product Chap1/Dsk2

Gene names

Name:	UBQLN2
Synonyms:	N4BP4, PLIC2
ORF Names:	HRIHFB2157

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	624 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Increases the half-life of proteins destined to be degraded by the proteasome; may modulate proteasome-mediated protein degradation. Ref.2
Subunit structure	Binds UBE3A and BTRC. Interacts with the 19S proteasome subunit. Ref.1 Ref.2
Subcellular location	Cytoplasm. Nucleus. Note: Where it colocalizes with the proteasome. Associated with fibers in mitotic cells. Ref.2 Ref.7
Induction	Highly expressed in mitotic cells from metaphase to telophase. Expression in non-mitotic cells is very low.
Involvement in disease	Amyotrophic lateral sclerosis 15, with or without frontotemporal dementia (ALS15) [MIM:300857]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. Patients with ALS15 may develop frontotemporal dementia. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.11 Ref.12 Ref.13
Sequence similarities	Contains 1 UBA domain. Contains 1 ubiquitin-like domain.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Disease	Amyotrophic lateral sclerosis Disease mutation Neurodegeneration
Domain	Repeat
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell death Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from direct assay. Source: HPA nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from direct assay. Source: HPA
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RAD23A	P54725	3	EBI-947187,EBI-746453

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 624

624

Ubiquilin-2

PRO_0000211011

Regions

Domain

33 – 107

75

Ubiquitin-like

Repeat

491 – 493

3

1

Repeat

494 – 496

3

2

Repeat

497 – 499

3

3

Repeat

500 – 502

3

4

Repeat

503 – 505

3

5

Repeat

506 – 508

3

6

Repeat

509 – 511

3

7

Repeat

512 – 514

3

8

Repeat

515 – 517

3

9

Repeat

518 – 520

3

10

Repeat

521 – 523

3

11

Repeat

524 – 526

3

12

Domain

581 – 621

41

UBA

Region

491 – 526

36

12 X 3 AA tandem repeats of P-X-X

Natural variations

Natural variant

155

1

S → N in ALS15; uncertain pathological significance. Ref.13

VAR_068892

Natural variant

189

1

P → T in ALS15; uncertain pathological significance. Ref.13

VAR_068893

Natural variant

235

1

L → H.
Corresponds to variant rs17002693 [ dbSNP | Ensembl ].

VAR_052680

Natural variant

282

1

A → V Probable disease-associated mutation found in a patient with frontotemporal dementia. Ref.11

VAR_068894

Natural variant

283

1

A → T in ALS15. Ref.11

VAR_068895

Natural variant

425

1

Q → R in ALS15. Ref.11

VAR_068896

Natural variant

487

1

T → I in ALS15. Ref.12

VAR_068897

Natural variant

497

1

P → H in ALS15; leads to defective ubiquitin-mediated proteasomal degradation. Ref.10

VAR_066562

Natural variant

497

1

P → S in ALS15. Ref.10

VAR_066563

Natural variant

506

1

P → T in ALS15; leads to defective ubiquitin-mediated proteasomal degradation. Ref.10

VAR_066564

Natural variant

509

1

P → S in ALS15. Ref.10

VAR_066565

Natural variant

525

1

P → S in ALS15. Ref.10

VAR_066566

Experimental info

Sequence conflict

544

1

S → R Ref.1

Sequence conflict

544

1

S → R Ref.5

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

624

Helix Strand Turn

Details...

Beta strand

23 – 25

3

Beta strand

33 – 38

6

Beta strand

43 – 48

6

Helix

54 – 65

12

Beta strand

69 – 76

8

Beta strand

79 – 82

4

Helix

87 – 91

5

Beta strand

93 – 102

10

Sequences

	Sequence		Length	Mass (Da)
	Q9UHD9 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: DF7DF8C4D7B71AC3	FASTA	624	65,696
	10 20 30 40 50 60 MAENGESSGP PRPSRGPAAA QGSAAAPAEP KIIKVTVKTP KEKEEFAVPE NSSVQQFKEA 70 80 90 100 110 120 ISKRFKSQTD QLVLIFAGKI LKDQDTLIQH GIHDGLTVHL VIKSQNRPQG QSTQPSNAAG 130 140 150 160 170 180 TNTTSASTPR SNSTPISTNS NPFGLGSLGG LAGLSSLGLS STNFSELQSQ MQQQLMASPE 190 200 210 220 230 240 MMIQIMENPF VQSMLSNPDL MRQLIMANPQ MQQLIQRNPE ISHLLNNPDI MRQTLEIARN 250 260 270 280 290 300 PAMMQEMMRN QDLALSNLES IPGGYNALRR MYTDIQEPML NAAQEQFGGN PFASVGSSSS 310 320 330 340 350 360 SGEGTQPSRT ENRDPLPNPW APPPATQSSA TTSTTTSTGS GSGNSSSNAT GNTVAAANYV 370 380 390 400 410 420 ASIFSTPGMQ SLLQQITENP QLIQNMLSAP YMRSMMQSLS QNPDLAAQMM LNSPLFTANP 430 440 450 460 470 480 QLQEQMRPQL PAFLQQMQNP DTLSAMSNPR AMQALMQIQQ GLQTLATEAP GLIPSFTPGV 490 500 510 520 530 540 GVGVLGTAIG PVGPVTPIGP IGPIVPFTPI GPIGPIGPTG PAAPPGSTGS GGPTGPTVSS 550 560 570 580 590 600 AAPSETTSPT SESGPNQQFI QQMVQALAGA NAPQLPNPEV RFQQQLEQLN AMGFLNREAN 610 620 LQALIATGGD INAAIERLLG SQPS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A family of ubiquitin-like proteins binds the ATPase domain of Hsp70-like Stch." Kaye F.J., Modi S., Ivanovska I., Koonin E.V., Thress K., Kubo A., Kornbluth S., Rose M.D. FEBS Lett. 467:348-355(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH STCH. Tissue: Lung.
[2]	"The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome." Kleijnen M.F., Shih A.H., Zhou P., Kumar S., Soccio R.E., Kedersha N.L., Gill G., Howley P.M. Mol. Cell 6:409-419(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH THE PROTEASOME AND UBE3A. Tissue: B-cell.
[3]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[6]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 37-624. Tissue: Amygdala.
[7]	"Selection system for genes encoding nuclear-targeted proteins." Ueki N., Oda T., Kondo M., Yano K., Noguchi T., Muramatsu M.-A. Nat. Biotechnol. 16:1338-1342(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 217-624, SUBCELLULAR LOCATION. Tissue: Fetal brain.
[8]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]	"Structural studies of the interaction between ubiquitin family proteins and proteasome subunit S5a." Walters K.J., Kleijnen M.F., Goh A.M., Wagner G., Howley P.M. Biochemistry 41:1767-1777(2002) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 1-103.
[10]	"Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia." Deng H.X., Chen W., Hong S.T., Boycott K.M., Gorrie G.H., Siddique N., Yang Y., Fecto F., Shi Y., Zhai H., Jiang H., Hirano M., Rampersaud E., Jansen G.H., Donkervoort S., Bigio E.H., Brooks B.R., Ajroud K. , Sufit R.L., Haines J.L., Mugnaini E., Pericak-Vance M.A., Siddique T. Nature 477:211-215(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ALS15 HIS-497; SER-497; THR-506; SER-509 AND SER-525, CHARACTERIZATION OF VARIANTS ALS15 HIS-497 AND THR-506.
[11]	"Screening in ALS and FTD patients reveals 3 novel UBQLN2 mutations outside the PXX domain and a pure FTD phenotype." Synofzik M., Maetzler W., Grehl T., Prudlo J., Vom Hagen J.M., Haack T., Rebassoo P., Munz M., Schols L., Biskup S. Neurobiol. Aging 33:E13-E17(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ALS15 THR-283 AND ARG-425, VARIANT VAL-282.
[12]	"UBQLN2/ubiquilin 2 mutation and pathology in familial amyotrophic lateral sclerosis." Williams K.L., Warraich S.T., Yang S., Solski J.A., Fernando R., Rouleau G.A., Nicholson G.A., Blair I.P. Neurobiol. Aging 33:E3-E10(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ALS15 ILE-487.
[13]	"UBQLN2 mutations are rare in French and French-Canadian amyotrophic lateral sclerosis." Daoud H., Suhail H., Szuto A., Camu W., Salachas F., Meininger V., Bouchard J.P., Dupre N., Dion P.A., Rouleau G.A. Neurobiol. Aging 33:E1-E5(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ALS15 ASN-155 AND THR-189.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF189009 mRNA. Translation: AAF17237.1.
AF293385 mRNA. Translation: AAG02474.1.
AL354793 Genomic DNA. Translation: CAD13519.1.
CH471154 Genomic DNA. Translation: EAW93233.1.
BC069237 mRNA. Translation: AAH69237.1.
AL442081 mRNA. Translation: CAC09446.1.
AB015344 mRNA. Translation: BAA34801.1.

IPI

IPI00409659.

RefSeq

NP_038472.2. NM_013444.3.

UniGene

Hs.179309.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1J8C	NMR	-	A	1-103	[»]

ProteinModelPortal

Q9UHD9.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UHD9. 5 interactions.

MINT

MINT-1192483.

STRING

9606.ENSP00000345195.

PTM databases

PhosphoSite

Q9UHD9.

Polymorphism databases

DMDM

124056593.

Proteomic databases

PaxDb

Q9UHD9.

PeptideAtlas

Q9UHD9.

PRIDE

Q9UHD9.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000338222; ENSP00000345195; ENSG00000188021.

GeneID

29978.

KEGG

hsa:29978.

UCSC

uc004dus.3. human.

Organism-specific databases

CTD

29978.

GeneCards

GC0XP056606.

HGNC

HGNC:12509. UBQLN2.

HPA

CAB013481.
HPA006431.

MIM

300264. gene.
300857. phenotype.

neXtProt

NX_Q9UHD9.

Orphanet

803. Amyotrophic lateral sclerosis.

PharmGKB

PA37156.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5272.

HOGENOM

HOG000234878.

HOVERGEN

HBG064537.

InParanoid

Q9UHD9.

KO

K04523.

OMA

NRPQGQS.

OrthoDB

EOG48KRBD.

PhylomeDB

Q9UHD9.

Gene expression databases

Bgee

Q9UHD9.

CleanEx

HS_UBQLN2.

Genevestigator

Q9UHD9.

GermOnline

ENSG00000188021. Homo sapiens.

Family and domain databases

InterPro

IPR016024. ARM-type_fold.
IPR006636. STI1_HS-bd.
IPR009060. UBA-like.
IPR000449. UBA/transl_elong_EF1B_N.
IPR015940. UBA/transl_elong_EF1B_N_euk.
IPR015496. Ubiquilin.
IPR000626. Ubiquitin.
IPR019955. Ubiquitin_supergroup.
[Graphical view]

PANTHER

PTHR10677. PTHR10677. 1 hit.

Pfam

PF00627. UBA. 1 hit.
PF00240. ubiquitin. 1 hit.
[Graphical view]

SMART

SM00727. STI1. 4 hits.
SM00165. UBA. 1 hit.
SM00213. UBQ. 1 hit.
[Graphical view]

SUPFAM

SSF48371. ARM-type_fold. 1 hit.
SSF46934. UBA_like. 1 hit.

PROSITE

PS50030. UBA. 1 hit.
PS00299. UBIQUITIN_1. False negative.
PS50053. UBIQUITIN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9UHD9.

GenomeRNAi

29978.

NextBio

52728.

SOURCE

Search...

Entry information

Entry name

UBQL2_HUMAN

Accession

Primary (citable) accession number: Q9UHD9
Secondary accession number(s): O94798 , Q5D027, Q9H3W6, Q9HAZ4

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 29, 2004
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 108 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.