Q9NRR5 (UBQL4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ubiquilin-4

Alternative name(s):
Ataxin-1 interacting ubiquitin-like protein
Short name=A1Up
Ataxin-1 ubiquitin-like-interacting protein A1U
Connexin43-interacting protein of 75 kDa
Short name=CIP75

Gene names

Name:	UBQLN4
Synonyms:	C1orf6, CIP75, UBIN

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	601 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays a role in the regulation of proteasomal protein degradation. Depending on the case, may promote or inhibit proteasomal protein degradation. Ref.6
Subunit structure	Binds signal sequences of proteins that are targeted to the endoplasmic reticulum. Interacts (via UBA domain) with GJA1 (not ubiquitinated) and with ubiquitin; both compete for the same binding site By similarity. Homodimer. Interacts (via UBA domain) with ubiquitin and with polyubiquitin chains. Interacts (via ubiquitin-like domain) with PSMD4, a regulatory subunit of the 26S proteasome. Interacts with ATXN1/SCA1. Interaction with ATXN1 inhibits polyubiquitination of UBQLN4 and interferes with PSMD4 binding. Ref.1 Ref.6
Subcellular location	Nucleus. Cytoplasm. Endoplasmic reticulum Probable. Cytoplasm › perinuclear region By similarity. Note: Colocalizes with the proteasome, both in nucleus and cytoplasm. May associate with the endoplasmic reticulum. Ref.1 Ref.6
Tissue specificity	Highly expressed in pancreas, kidney, skeletal muscle, heart and throughout the brain, and at lower levels in placenta, lung and liver. Ref.1
Post-translational modification	Ubiquitinated; this does not lead to proteasomal degradation. May undergo both 'Lys-48'- and 'Lys-63'-linked polyubiquitination. Ref.6
Sequence similarities	Contains 1 UBA domain. Contains 1 ubiquitin-like domain.
Sequence caution	The sequence AAF19084.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence AAH06410.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Cellular component	Cytoplasm Endoplasmic reticulum Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	regulation of proteasomal ubiquitin-dependent protein catabolic process Inferred from mutant phenotype Ref.6. Source: UniProtKB
Cellular_component	cytosol Inferred from sequence or structural similarity. Source: UniProtKB endoplasmic reticulum membrane Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from direct assay Ref.1. Source: UniProtKB perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	polyubiquitin binding Inferred from direct assay Ref.6. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ATXN1	P54253	6	EBI-711226,EBI-930964
FKBP2	P26885	2	EBI-711226,EBI-719873
MLLT6	P55198	2	EBI-711226,EBI-740216
PDLIM7	Q9NR12	2	EBI-711226,EBI-350517
RAI2	Q9Y5P3	3	EBI-711226,EBI-746228
TRIM32	Q13049	3	EBI-711226,EBI-742790
ZNF205	O95201	2	EBI-711226,EBI-747343

Alternative products

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

Isoform 1 (identifier: Q9NRR5-1)

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 2 (identifier: Q9NRR5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     93-226: AATASSPSTP...HMIMANPQMQ → PPAAPSLPAA...AAQLHGLHQS
     227-601: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 601	601	Ubiquilin-4		PRO_0000211015
Regions
	Domain	13 – 87	75	Ubiquitin-like
	Domain	553 – 598	46	UBA
Amino acid modifications
	Modified residue	98	1	Phosphoserine Ref.8
Natural variations
	Alternative sequence	93 – 226	134	AATAS…NPQMQ → PPAAPSLPAADAEPRVTLHP YQSPSHAGIAADPAGTTDLA DRGPWAGTQPWLLWDIPDPS TLSRQQRRVYARGPHFLTSH ASHIFSNRGFQRPAATHAAD DPAFGWKWKLTGADARSEIS AAAGAAQLHGLHQS in isoform 2.		VSP_041187
	Alternative sequence	227 – 601	375	Missing in isoform 2.		VSP_041188
	Natural variant	495	1	I → M. Ref.2 Ref.5 Corresponds to variant rs2297792 [ dbSNP | Ensembl ].		VAR_052685
Experimental info
	Sequence conflict	188 – 189	2	QL → HV in AAF80171. Ref.1
	Sequence conflict	298	1	R → Q in AAF80171. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 15, 2004. Version 2. Checksum: E57B9FFEF90793FE	FASTA	601	63,853
	10 20 30 40 50 60 MAEPSGAETR PPIRVTVKTP KDKEEIVICD RASVKEFKEE ISRRFKAQQD QLVLIFAGKI 70 80 90 100 110 120 LKDGDTLNQH GIKDGLTVHL VIKTPQKAQD PAAATASSPS TPDPASAPST TPASPATPAQ 130 140 150 160 170 180 PSTSGSASSD AGSGSRRSSG GGPSPGAGEG SPSATASILS GFGGILGLGS LGLGSANFME 190 200 210 220 230 240 LQQQMQRQLM SNPEMLSQIM ENPLVQDMMS NPDLMRHMIM ANPQMQQLME RNPEISHMLN 250 260 270 280 290 300 NPELMRQTME LARNPAMMQE MMRNQDRALS NLESIPGGYN ALRRMYTDIQ EPMFSAAREQ 310 320 330 340 350 360 FGNNPFSSLA GNSDSSSSQP LRTENREPLP NPWSPSPPTS QAPGSGGEGT GGSGTSQVHP 370 380 390 400 410 420 TVSNPFGINA ASLGSGMFNS PEMQALLQQI SENPQLMQNV ISAPYMRSMM QTLAQNPDFA 430 440 450 460 470 480 AQMMVNVPLF AGNPQLQEQL RLQLPVFLQQ MQNPESLSIL TNPRAMQALL QIQQGLQTLQ 490 500 510 520 530 540 TEAPGLVPSL GSFGISRTPA PSAGSNAGST PEAPTSSPAT PATSSPTGAS SAQQQLMQQM 550 560 570 580 590 600 IQLLAGSGNS QVQTPEVRFQ QQLEQLNSMG FINREANLQA LIATGGDINA AIERLLGSQL S
	Isoform 2 [UniParc]. Checksum: 69101551F1551A93	FASTA	226	24,527
	10 20 30 40 50 60 MAEPSGAETR PPIRVTVKTP KDKEEIVICD RASVKEFKEE ISRRFKAQQD QLVLIFAGKI 70 80 90 100 110 120 LKDGDTLNQH GIKDGLTVHL VIKTPQKAQD PAPPAAPSLP AADAEPRVTL HPYQSPSHAG 130 140 150 160 170 180 IAADPAGTTD LADRGPWAGT QPWLLWDIPD PSTLSRQQRR VYARGPHFLT SHASHIFSNR 190 200 210 220 GFQRPAATHA ADDPAFGWKW KLTGADARSE ISAAAGAAQL HGLHQS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and characterization of an ataxin-1-interacting protein: A1Up, a ubiquitin-like nuclear protein." Davidson J.D., Riley B., Burright E.N., Duvick L.A., Zoghbi H.Y., Orr H.T. Hum. Mol. Genet. 9:2305-2312(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, INTERACTION WITH ATXN1/SCA1, TISSUE SPECIFICITY. Tissue: Brain.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT MET-495. Tissue: Brain.
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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] (ISOFORM 1). Tissue: Brain, Colon and PNS.
[5]	"Identification of two paralogous regions mapping to the short and long arms of human chromosome 2 comprising LIS1 pseudogenes." Fogli A., Giglio S., Lo Nigro C., Zollo M., Viggiano L., Rocchi M., Archidiacono N., Zuffardi O., Carrozzo R. Cytogenet. Cell Genet. 86:225-232(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 161-601 (ISOFORM 1), VARIANT MET-495.
[6]	"The effects of the polyglutamine repeat protein ataxin-1 on the UbL-UBA protein A1Up." Riley B.E., Xu Y., Zoghbi H.Y., Orr H.T. J. Biol. Chem. 279:42290-42301(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH UBIQUITIN; ATXN1 AND PSMD4, SUBUNIT, SUBCELLULAR LOCATION, UBIQUITINATION.
[7]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Embryonic kidney.
[8]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"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].

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF188240 mRNA. Translation: AAF80171.1. AK098368 mRNA. No translation available. AK314413 mRNA. Translation: BAG37034.1. AL355388 Genomic DNA. Translation: CAH72633.1. AL355388 Genomic DNA. Translation: CAH72634.1. BC006410 mRNA. Translation: AAH06410.1. Different initiation. BC018403 mRNA. Translation: AAH18403.1. BC063841 mRNA. Translation: AAH63841.1. AF113544 mRNA. Translation: AAF19084.1. Different initiation.
IPI	IPI00024502. IPI00477826.
RefSeq	NP_064516.2. NM_020131.3.
UniGene	Hs.283739.
3D structure databases
ProteinModelPortal	Q9NRR5.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NRR5. 145 interactions.
MINT	MINT-1373057.
STRING	9606.ENSP00000357292.
PTM databases
PhosphoSite	Q9NRR5.
Polymorphism databases
DMDM	45476982.
Proteomic databases
PaxDb	Q9NRR5.
PRIDE	Q9NRR5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000368307; ENSP00000357290; ENSG00000160803. ENST00000368309; ENSP00000357292; ENSG00000160803.
GeneID	56893.
KEGG	hsa:56893.
UCSC	uc001fna.3. human.
Organism-specific databases
CTD	56893.
GeneCards	GC01M156005.
HGNC	HGNC:1237. UBQLN4.
HPA	HPA027920.
MIM	605440. gene.
neXtProt	NX_Q9NRR5.
PharmGKB	PA25619.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5272.
HOVERGEN	HBG064537.
InParanoid	Q9NRR5.
KO	K04523.
OMA	FGMSRTT.
OrthoDB	EOG48KRBD.
PhylomeDB	Q9NRR5.
Gene expression databases
Bgee	Q9NRR5.
CleanEx	HS_UBQLN4.
Genevestigator	Q9NRR5.
GermOnline	ENSG00000160803. Homo sapiens.
Family and domain databases
InterPro	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	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
ChiTaRS	UBQLN4. human.
GenomeRNAi	56893.
NextBio	62315.
SOURCE	Search...

Entry information

Entry name

UBQL4_HUMAN

Accession

Primary (citable) accession number: Q9NRR5
Secondary accession number(s): A6ND44 , B2RAY7, Q5VYA0, Q5VYA1, Q9BR98, Q9UHX4

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2004
Last sequence update:	March 15, 2004
Last modified:	May 1, 2013
This is version 110 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.