Reviewed, UniProtKB/Swiss-Prot Q13501 (SQSTM_HUMAN)

Names and origin

Protein names

Recommended name:
    Sequestosome-1
Alternative name(s):
    Phosphotyrosine-independent ligand for the Lck SH2 domain of 62 kDa
    Ubiquitin-binding protein p62
    EBI3-associated protein of 60 kDa
      Short name=EBIAP
      Short name=p60

Gene names

Name:	SQSTM1
Synonyms:	ORCA, OSIL

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

General annotation (Comments)

Function	Adapter protein which binds ubiquitin and may regulate the activation of NFKB1 by TNF-alpha, nerve growth factor (NGF) and interleukin-1. May play a role in titin/TTN downstream signaling in muscle cells. May regulate signaling cascades through ubiquitination. May be involved in cell differentiation, apoptosis, immune response and regulation of K+ channels. Ref.12 Ref.14 Ref.15 Ref.19 Ref.24 Ref.25 Ref.28 Ref.30 Ref.31
Subunit structure	Homooligomer or heterooligomer; may form homotypic arrays. Interacts directly with PRKCI and PRKCZ Probable. Forms ternary complexes with PRKCZ and KCNAB2 or PRKCZ and GABBR3. Also interacts with KCNAB1, GABRR1, GABRR2 and GABRR3. Forms an NGF-induced complex with IKBKB, PRKCI and TRAF6 By similarity. Interacts with EBI3, LCK, RASA1, PRKCZ, PRKCI, NR2F2, NTRK1, NTRK2, NTRK3, NBR1, MAP2K5, TRIM55 and MAPKAPK5. Interacts with the proteasome subunits PSMD4 and PSMC2. Interacts with K63-polyubiquitinated MAPT/TAU. Interacts with IKBKB through PRKCZ and PRKCI. Interacts with NGFR through TRAF6 and bridges that complex to NTRK1. Forms a complex with MAP2K5 and PRKCZ or PRKCI. Component of a ternary complex with PAWR and PRKCZ. Upon TNF-alpha stimulation, interacts with RIPK1 problably bridging IKBKB to the TNF-R1 complex composed of TNF-R1/TNFRSF1A, TRADD and RIPK1. Forms a complex with JUB/Ajuba, PRKCZ and TRAF6. Ref.12 Ref.14 Ref.15 Ref.19 Ref.24 Ref.25 Ref.31 Ref.1 Ref.2 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13 Ref.17 Ref.20 Ref.21 Ref.29
Subcellular location	Cytoplasm. Late endosome. Nucleus. Note: Sarcomere By similarity. In cardiac muscles localizes to the sarcomeric band By similarity. Localizes to late endosomes. May also localize to the nucleus. Accumulates in neurofibrillary tangles and in Lewy bodies of neurons from individuals with Alzheimer and Parkinson disease respectively. Enriched in Rosenthal fibers of pilocytic astrocytoma. In liver cells, accumulates in Mallory bodies associated with alcoholic hepatitis, Wilson disease, indian childhood cirrhosis and in hyaline bodies associated with hepatocellular carcinoma. Ref.19 Ref.25 Ref.11 Ref.13 Ref.7 Ref.16 Ref.18 Ref.23
Tissue specificity	Ubiquitously expressed. Ref.2
Induction	By proteasomal inhibitor PSI and prostaglandin J2 (PGJ2) (at protein level). By Phorbol 12-myristate 13-acetate (PMA). Ref.30 Ref.6 Ref.22
Domain	The UBA domain binds specifically 'Lys-63'-linked polyubiquitin chains of polyubiquitinated substrates. Mediates the interaction with TRIM55. Ref.14 Ref.24 Ref.25 Ref.31 Ref.20 Ref.21 Ref.44 The OPR domain mediates homooligomerization and interactions with PRKCZ, PRKCI, MAP2K5 and NBR1. Ref.14 Ref.24 Ref.25 Ref.31 Ref.20 Ref.21 Ref.44 The ZZ-type zinc finger mediates the interaction with RIPK1. Ref.14 Ref.24 Ref.25 Ref.31 Ref.20 Ref.21 Ref.44
Post-translational modification	Phosphorylated. May be phosphorylated by PRKCZ By similarity. Phosphorylated in vitro by TTN. Ref.31 Ref.26 Ref.27 Ref.32 Ref.33 Ref.34 Ref.35 Ref.36 Ref.37 Ref.38 Ref.39 Ref.41 Ref.43
Involvement in disease	Defects in SQSTM1 are a cause of Paget disease of bone (PDB) [MIM:602080]. PDB is a metabolic bone disease affecting the axial skeleton and characterized by focal areas of increased and disorganized bone turn-over due to activated osteoclasts. Manifestations of the disease include bone pain, deformity, pathological fractures, deafness, neurological complications and increased risk of osteosarcoma. PDB is a chronic disease affecting 2 to 3% of the population above the age of 40 years. Ref.45 Ref.46 Ref.47 Ref.48 Ref.49 Ref.50 Ref.51
Sequence similarities	Contains 1 OPR domain. Contains 1 UBA domain. Contains 1 ZZ-type zinc finger.

Ontologies

Keywords
Biological process	Apoptosis Differentiation Immune response
Cellular component	Cytoplasm Endosome Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Zinc-finger
Ligand	Metal-binding Zinc
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	anti-apoptosis Inferred from Experiment. Source: Reactome apoptosis Inferred from Experiment. Source: Reactome cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW endosome transport Ref.44 Traceable author statement. Source: UniProtKB immune response Inferred from electronic annotation. Source: UniProtKB-KW induction of apoptosis by extracellular signals Inferred from Experiment. Source: Reactome intracellular signaling cascade Ref.2 Traceable author statement. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Ref.44 Traceable author statement. Source: UniProtKB protein localization Ref.2 Traceable author statement. Source: UniProtKB regulation of I-kappaB kinase/NF-kappaB cascade Ref.44 Inferred from mutant phenotype. Source: UniProtKB response to stress Ref.44 Traceable author statement. Source: UniProtKB ubiquitin-dependent protein catabolic process Ref.9 Traceable author statement. Source: ProtInc
Cellular component	cytosol Ref.2 Ref.15 Traceable author statement. Source: UniProtKB late endosome Inferred from electronic annotation. Source: UniProtKB-SubCell nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	SH2 domain binding Ref.2 Inferred from direct assay. Source: UniProtKB protein kinase C binding Inferred from physical interaction. Source: UniProtKB receptor tyrosine kinase binding Ref.2 Traceable author statement. Source: ProtInc ubiquitin binding Ref.44 Inferred from direct assay. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CASP8	Q14790	1	EBI-307104,EBI-78060
MAP1LC3B	Q9GZQ8	1	EBI-307104,EBI-373144
RAD23A	P54725	1	EBI-307104,EBI-746453

Alternative products

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

Isoform 1 (identifier: Q13501-1)

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: Q13501-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-84: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 440

440

Sequestosome-1

PRO_0000072176

Regions

Domain

20 – 102

83

OPR

Domain

389 – 434

46

UBA

Zinc finger

122 – 167

46

ZZ-type

Region

1 – 50

50

Interaction with LCK

Region

43 – 107

65

Interaction with PRKCZ and dimerization By similarity

Region

50 – 80

31

Interaction with PAWR

Region

122 – 224

103

Interaction with GABRR3 By similarity

Region

170 – 220

51

LIM protein-binding (LB)

Region

269 – 440

172

Interaction with NTRK1 By similarity

Motif

228 – 233

6

TRAF6-binding

Compositional bias

272 – 294

23

Ser-rich

Amino acid modifications

Modified residue

24

1

Phosphoserine By similarity

Modified residue

148

1

Phosphotyrosine Ref.27

Modified residue

170

1

Phosphoserine Ref.37 Ref.39

Modified residue

176

1

Phosphoserine Ref.35

Modified residue

207

1

Phosphoserine Ref.39

Modified residue

266

1

Phosphoserine Ref.37

Modified residue

269

1

Phosphothreonine Ref.26 Ref.32 Ref.33 Ref.34 Ref.36 Ref.38 Ref.39 Ref.41

Modified residue

272

1

Phosphoserine Ref.26 Ref.32 Ref.33 Ref.34 Ref.37 Ref.38 Ref.39 Ref.41 Ref.43

Modified residue

276

1

Phosphoserine Ref.39

Modified residue

277

1

Phosphoserine Ref.41

Modified residue

328

1

Phosphoserine Ref.39

Modified residue

332

1

Phosphoserine Ref.32 Ref.39

Modified residue

355

1

Phosphoserine Ref.39 Ref.43

Modified residue

361

1

Phosphoserine Ref.36 Ref.43

Modified residue

365

1

Phosphoserine Ref.36

Modified residue

366

1

Phosphoserine Ref.36 Ref.37 Ref.39 Ref.41

Modified residue

370

1

Phosphoserine Ref.41

Natural variations

Alternative sequence

1 – 84

84

Missing in isoform 2.

VSP_015841

Natural variant

117

1

A → V

VAR_023590

Natural variant

274

1

E → D: dbSNP rs55793208.

VAR_061707

Natural variant

274

1

E → Q

VAR_023591

Natural variant

387

1

P → L in PDB. Ref.47

VAR_023592

Natural variant

392

1

P → L in PDB; no effect on polyubiquitin-binding. Ref.44 Ref.45 Ref.46 Ref.48 Ref.49 Ref.50

VAR_023593

Natural variant

399

1

S → P in PDB. Ref.48

VAR_023594

Natural variant

404

1

M → T in PDB. Ref.48

VAR_023595

Natural variant

404

1

M → V in PDB; loss of polyubiquitin-binding. Ref.50 Ref.51

VAR_023596

Natural variant

411

1

G → S in PDB; no effect on polyubiquitin-binding. Ref.51

VAR_023597

Natural variant

425

1

G → R in PDB; loss of polyubiquitin-binding. Ref.48 Ref.50 Ref.51

VAR_023598

Experimental info

Mutagenesis

7

1

K → A: Loss of interactions with PRKCZ, PRCKI and NBR1. Loss of dimerization; when associated with A-69. Ref.20 Ref.21

Mutagenesis

9

1

Y → F: No effect on interaction with LCK. Ref.2

Mutagenesis

13

1

K → A: No effect on interaction with PRKCI. Ref.20

Mutagenesis

21 – 22

2

RR → AA: Loss of interaction with PRKCI. Alters dimerization.

Mutagenesis

67

1

Y → A: No effect on interaction with PRKCZ. Ref.20

Mutagenesis

69

1

D → A: No effect on interactions with PRKCZ, PRKCI and NBR1. Loss of dimerization; when associated with A-7. Ref.20 Ref.21

Mutagenesis

71

1

D → A: No effect on interaction with PRKCI. Ref.20

Mutagenesis

73

1

D → A: No effect on interactions with PRKCZ and PRKCI. Ref.20 Ref.21

Mutagenesis

80

1

D → A: No effect on interaction with PRKCI. Ref.20

Mutagenesis

82

1

E → A: No effect on interaction with PRKCI. Ref.20

Mutagenesis

398

1

L → V: No effect on polyubiquitin-binding. Ref.24

Mutagenesis

406

1

F → V: Loss of polyubiquitin-binding. Ref.24

Mutagenesis

413

1

L → V: No effect on polyubiquitin-binding. Ref.24

Mutagenesis

417

1

L → V: Loss of polyubiquitin-binding. Ref.24

Mutagenesis

431

1

I → V: Partial loss of polyubiquitin-binding. Ref.24

Sequence conflict

321

1

R → A in AAA93299. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

440

Helix Strand Turn

Details...

Helix

392 – 402

11

Helix

412 – 419

8

Turn

420 – 422

3

Helix

424 – 431

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 462D94C171F337CD	FASTA	440	47,687
	10 20 30 40 50 60 MASLTVKAYL LGKEDAAREI RRFSFCCSPE PEAEAEAAAG PGPCERLLSR VAALFPALRP 70 80 90 100 110 120 GGFQAHYRDE DGDLVAFSSD EELTMAMSYV KDDIFRIYIK EKKECRRDHR PPCAQEAPRN 130 140 150 160 170 180 MVHPNVICDG CNGPVVGTRY KCSVCPDYDL CSVCEGKGLH RGHTKLAFPS PFGHLSEGFS 190 200 210 220 230 240 HSRWLRKVKH GHFGWPGWEM GPPGNWSPRP PRAGEARPGP TAESASGPSE DPSVNFLKNV 250 260 270 280 290 300 GESVAAALSP LGIEVDIDVE HGGKRSRLTP VSPESSSTEE KSSSQPSSCC SDPSKPGGNV 310 320 330 340 350 360 EGATQSLAEQ MRKIALESEG RPEEQMESDN CSGGDDDWTH LSSKEVDPST GELQSLQMPE 370 380 390 400 410 420 SEGPSSLDPS QEGPTGLKEA ALYPHLPPEA DPRLIESLSQ MLSMGFSDEG GWLTRLLQTK 430 440 NYDIGAALDT IQYSKHPPPL
	Isoform 2. Checksum: 56E985FFBF86EC1B	FASTA	356	38,629
	10 20 30 40 50 60 MAMSYVKDDI FRIYIKEKKE CRRDHRPPCA QEAPRNMVHP NVICDGCNGP VVGTRYKCSV 70 80 90 100 110 120 CPDYDLCSVC EGKGLHRGHT KLAFPSPFGH LSEGFSHSRW LRKVKHGHFG WPGWEMGPPG 130 140 150 160 170 180 NWSPRPPRAG EARPGPTAES ASGPSEDPSV NFLKNVGESV AAALSPLGIE VDIDVEHGGK 190 200 210 220 230 240 RSRLTPVSPE SSSTEEKSSS QPSSCCSDPS KPGGNVEGAT QSLAEQMRKI ALESEGRPEE 250 260 270 280 290 300 QMESDNCSGG DDDWTHLSSK EVDPSTGELQ SLQMPESEGP SSLDPSQEGP TGLKEAALYP 310 320 330 340 350 HLPPEADPRL IESLSQMLSM GFSDEGGWLT RLLQTKNYDI GAALDTIQYS KHPPPL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel interleukin-12 p40-related protein induced by latent Epstein-Barr virus infection in B lymphocytes." Devergne O., Hummel M., Koeppen H., Le Beau M.M., Nathanson E.C., Kieff E., Birkenbach M. J. Virol. 70:1143-1153(1996) [PubMed: 8551575] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 345-361 AND 394-411, INTERACTION WITH EBI3. Tissue: B-cell.
[2]	"Molecular cloning of a phosphotyrosine-independent ligand of the p56lck SH2 wdomain." Joung I., Strominger J.L., Shin J. Proc. Natl. Acad. Sci. U.S.A. 93:5991-5995(1996) [PubMed: 8650207] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 51-96; 184-187; 213-217; 239-264 AND 268-281, TISSUE SPECIFICITY, INTERACTION WITH LCK, MUTAGENESIS OF TYR-9. Tissue: Cervix carcinoma.
[3]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Caudate nucleus and Trachea.
[4]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed: 15372022] [Abstract] 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Pancreas, Placenta, Skin and Uterus.
[6]	"Genomic structure and promoter analysis of the p62 gene encoding a non-proteasomal multiubiquitin chain binding protein." Vadlamudi R.K., Shin J. FEBS Lett. 435:138-142(1998) [PubMed: 9762895] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-72, INDUCTION.
[7]	"Analysis of intracytoplasmic hyaline bodies in a hepatocellular carcinoma. Demonstration of p62 as major constituent." Stumptner C., Heid H., Fuchsbichler A., Hauser H., Mischinger H.-J., Zatloukal K., Denk H. Am. J. Pathol. 154:1701-1710(1999) [PubMed: 10362795] [Abstract] Cited for: PROTEIN SEQUENCE OF 51-60; 166-174 AND 379-388, SUBCELLULAR LOCATION.
[8]	"Phosphotyrosine-independent binding of a 62-kDa protein to the src homology 2 (SH2) domain of p56lck and its regulation by phosphorylation of Ser-59 in the lck unique N-terminal region." Park I., Chung J., Walsh C.T., Yun Y., Strominger J.L., Shin J. Proc. Natl. Acad. Sci. U.S.A. 92:12338-12342(1995) [PubMed: 8618896] [Abstract] Cited for: INTERACTION WITH LCK AND RASA1.
[9]	"p62, a phosphotyrosine-independent ligand of the SH2 domain of p56lck, belongs to a new class of ubiquitin-binding proteins." Vadlamudi R.K., Joung I., Strominger J.L., Shin J. J. Biol. Chem. 271:20235-20237(1996) [PubMed: 8702753] [Abstract] Cited for: INTERACTION WITH UBIQUITIN.
[10]	"A p56(lck) ligand serves as a coactivator of an orphan nuclear hormone receptor." Marcus S.L., Winrow C.J., Capone J.P., Rachubinski R.A. J. Biol. Chem. 271:27197-27200(1996) [PubMed: 8910285] [Abstract] Cited for: INTERACTION WITH NR2F2.
[11]	"Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62." Sanchez P., De Carcer G., Sandoval I.V., Moscat J., Diaz-Meco M.T. Mol. Cell. Biol. 18:3069-3080(1998) [PubMed: 9566925] [Abstract] Cited for: INTERACTION WITH PRKCI AND PRKCZ, SUBCELLULAR LOCATION.
[12]	"The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation." Sanz L., Sanchez P., Lallena M.-J., Diaz-Meco M.T., Moscat J. EMBO J. 18:3044-3053(1999) [PubMed: 10356400] [Abstract] Cited for: INTERACTION WITH RIPK1; PRKCZ; PRKCI; IKBKB; TRADD AND TNFRSF1A, FUNCTION.
[13]	"p62 functions as a p38 MAP kinase regulator." Sudo T., Maruyama M., Osada H. Biochem. Biophys. Res. Commun. 269:521-525(2000) [PubMed: 10708586] [Abstract] Cited for: INTERACTION WITH MAPKAPK5, SUBCELLULAR LOCATION.
[14]	"The atypical PKC-interacting protein p62 channels NF-kappaB activation by the IL-1-TRAF6 pathway." Sanz L., Diaz-Meco M.T., Nakano H., Moscat J. EMBO J. 19:1576-1586(2000) [PubMed: 10747026] [Abstract] Cited for: INTERACTION WITH TRAF6 AND RIPK1, DOMAIN, FUNCTION.
[15]	"The atypical protein kinase C-interacting protein p62 is a scaffold for NF-kappaB activation by nerve growth factor." Wooten M.W., Seibenhener M.L., Mamidipudi V., Diaz-Meco M.T., Barker P.A., Moscat J. J. Biol. Chem. 276:7709-7712(2001) [PubMed: 11244088] [Abstract] Cited for: INTERACTION WITH NTRK1; TRAF6; NGFR AND PRKCZ, FUNCTION.
[16]	"p62 Is a common component of cytoplasmic inclusions in protein aggregation diseases." Zatloukal K., Stumptner C., Fuchsbichler A., Heid H., Schnoelzer M., Kenner L., Kleinert R., Prinz M., Aguzzi A., Denk H. Am. J. Pathol. 160:255-263(2002) [PubMed: 11786419] [Abstract] Cited for: SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY.
[17]	"p62 forms a ternary complex with PKCzeta and PAR-4 and antagonizes PAR-4-induced PKCzeta inhibition." Chang S., Kim J.H., Shin J. FEBS Lett. 510:57-61(2002) [PubMed: 11755531] [Abstract] Cited for: INTERACTION WITH PAWR AND PRKCZ.
[18]	"Mallory body -- a disease-associated type of sequestosome." Stumptner C., Fuchsbichler A., Heid H., Zatloukal K., Denk H. Hepatology 35:1053-1062(2002) [PubMed: 11981755] [Abstract] Cited for: SUBCELLULAR LOCATION.
[19]	"Association of the atypical protein kinase C-interacting protein p62/ZIP with nerve growth factor receptor TrkA regulates receptor trafficking and Erk5 signaling." Geetha T., Wooten M.W. J. Biol. Chem. 278:4730-4739(2003) [PubMed: 12471037] [Abstract] Cited for: INTERACTION WITH NTRK1; NTRK2 AND NTRK3, SUBCELLULAR LOCATION, FUNCTION.
[20]	"Interaction codes within the family of mammalian Phox and Bem1p domain-containing proteins." Lamark T., Perander M., Outzen H., Kristiansen K., Oevervatn A., Michaelsen E., Bjoerkoey G., Johansen T. J. Biol. Chem. 278:34568-34581(2003) [PubMed: 12813044] [Abstract] Cited for: INTERACTION WITH PRKCI; PRKCZ; MAP2K5 AND NBR1, DOMAIN, MUTAGENESIS OF LYS-7; LYS-13; 21-ARG-ARG-22; TYR-67; ASP-69; ASP-71; ASP-73; ASP-80 AND GLU-82, DIMERIZATION.
[21]	"PB1 domain-mediated heterodimerization in NADPH oxidase and signaling complexes of atypical protein kinase C with Par6 and p62." Wilson M.I., Gill D.J., Perisic O., Quinn M.T., Williams R.L. Mol. Cell 12:39-50(2003) [PubMed: 12887891] [Abstract] Cited for: INTERACTION WITH PRKCZ, DOMAIN, OLIGOMERIZATION, MUTAGENESIS OF LYS-7; ASP-69 AND ASP-73.
[22]	"p62 overexpression in breast tumors and regulation by prostate-derived Ets factor in breast cancer cells." Thompson H.G.R., Harris J.W., Wold B.J., Lin F., Brody J.P. Oncogene 22:2322-2333(2003) [PubMed: 12700667] [Abstract] Cited for: INDUCTION.
[23]	"Transcriptional activation of p62/A170/ZIP during the formation of the aggregates: possible mechanisms and the role in Lewy body formation in Parkinson's disease." Nakaso K., Yoshimoto Y., Nakano T., Takeshima T., Fukuhara Y., Yasui K., Araga S., Yanagawa T., Ishii T., Nakashima K. Brain Res. 1012:42-51(2004) [PubMed: 15158159] [Abstract] Cited for: SUBCELLULAR LOCATION.
[24]	"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 TRAF6; PSMC2 AND PSMD4, DOMAIN, MUTAGENESIS OF LEU-398; PHE-406; LEU-413; LEU-417 AND ILE-431, FUNCTION.
[25]	"Sequestosome 1/p62 shuttles polyubiquitinated tau for proteasomal degradation." Babu J.R., Geetha T., Wooten M.W. J. Neurochem. 94:192-203(2005) [PubMed: 15953362] [Abstract] Cited for: INTERACTION WITH MAPT, DOMAIN, SUBCELLULAR LOCATION, FUNCTION.
[26]	"Global phosphoproteome of HT-29 human colon adenocarcinoma cells." Kim J.-E., Tannenbaum S.R., White F.M. J. Proteome Res. 4:1339-1346(2005) [PubMed: 16083285] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-269 AND SER-272, MASS SPECTROMETRY.
[27]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-148, MASS SPECTROMETRY.
[28]	"The p62 scaffold regulates nerve growth factor-induced NF-kappaB activation by influencing TRAF6 polyubiquitination." Wooten M.W., Geetha T., Seibenhener M.L., Babu J.R., Diaz-Meco M.T., Moscat J. J. Biol. Chem. 280:35625-35629(2005) [PubMed: 16079148] [Abstract] Cited for: FUNCTION.
[29]	"The LIM protein Ajuba influences interleukin-1-induced NF-kappaB activation by affecting the assembly and activity of the protein kinase Czeta/p62/TRAF6 signaling complex." Feng Y., Longmore G.D. Mol. Cell. Biol. 25:4010-4022(2005) [PubMed: 15870274] [Abstract] Cited for: INTERACTION WITH JUB AND LIMD1.
[30]	"Inhibition of sequestosome 1/p62 up-regulation prevents aggregation of ubiquitinated proteins induced by prostaglandin J2 without reducing its neurotoxicity." Wang Z., Figueiredo-Pereira M.E. Mol. Cell. Neurosci. 29:222-231(2005) [PubMed: 15911346] [Abstract] Cited for: INDUCTION, FUNCTION.
[31]	"The kinase domain of titin controls muscle gene expression and protein turnover." Lange S., Xiang F., Yakovenko A., Vihola A., Hackman P., Rostkova E., Kristensen J., Brandmeier B., Franzen G., Hedberg B., Gunnarsson L.G., Hughes S.M., Marchand S., Sejersen T., Richard I., Edstroem L., Ehler E., Udd B., Gautel M. Science 308:1599-1603(2005) [PubMed: 15802564] [Abstract] Cited for: INTERACTION WITH NBR1 AND TRIM55, PHOSPHORYLATION, DOMAINS, FUNCTION.
[32]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-269; SER-272 AND SER-332, MASS SPECTROMETRY. Tissue: Epithelium.
[33]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-269 AND SER-272, MASS SPECTROMETRY. Tissue: Epithelium.
[34]	"Phosphoproteome analysis of the human mitotic spindle." Nousiainen M., Sillje H.H.W., Sauer G., Nigg E.A., Koerner R. Proc. Natl. Acad. Sci. U.S.A. 103:5391-5396(2006) [PubMed: 16565220] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-269 AND SER-272, MASS SPECTROMETRY. Tissue: Epithelium.
[35]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-176, MASS SPECTROMETRY. Tissue: Epithelium.
[36]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-269; SER-361; SER-365 AND SER-366, MASS SPECTROMETRY.
[37]	"Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis." Wang B., Malik R., Nigg E.A., Korner R. Anal. Chem. 80:9526-9533(2008) [PubMed: 19007248] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-170; SER-266; SER-272 AND SER-366, MASS SPECTROMETRY.
[38]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-269 AND SER-272, MASS SPECTROMETRY.
[39]	"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-170; SER-207; THR-269; SER-272; SER-276; SER-328; SER-332; SER-355 AND SER-366, MASS SPECTROMETRY.
[40]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[41]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-269; SER-272; SER-277; SER-366 AND SER-370, MASS SPECTROMETRY.
[42]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-272, MASS SPECTROMETRY.
[43]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-272; SER-355 AND SER-361, MASS SPECTROMETRY. Tissue: T-cell.
[44]	"Structure of the ubiquitin-associated domain of p62 (SQSTM1) and implications for mutations that cause Paget's disease of bone." Ciani B., Layfield R., Cavey J.R., Sheppard P.W., Searle M.S. J. Biol. Chem. 278:37409-37412(2003) [PubMed: 12857745] [Abstract] Cited for: STRUCTURE BY NMR OF 387-436, CHARACTERIZATION OF VARIANT LEU-392, DOMAIN.
[45]	"Recurrent mutation of the gene encoding sequestosome 1 (SQSTM1/p62) in Paget disease of bone." Laurin N., Brown J.P., Morissette J., Raymond V. Am. J. Hum. Genet. 70:1582-1588(2002) [PubMed: 11992264] [Abstract] Cited for: VARIANT PDB LEU-392, VARIANTS VAL-117 AND GLN-274.
[46]	"Domain-specific mutations in sequestosome 1 (SQSTM1) cause familial and sporadic Paget's disease." Hocking L.J., Lucas G.J.A., Daroszewska A., Mangion J., Olavesen M., Cundy T., Nicholson G.C., Ward L., Bennett S.T., Wuyts W., Van Hul W., Ralston S.H. Hum. Mol. Genet. 11:2735-2739(2002) [PubMed: 12374763] [Abstract] Cited for: VARIANT PDB LEU-392.
[47]	"Three novel mutations in SQSTM1 identified in familial Paget's disease of bone." Johnson-Pais T.L., Wisdom J.H., Weldon K.S., Cody J.D., Hansen M.F., Singer F.R., Leach R.J. J. Bone Miner. Res. 18:1748-1753(2003) [PubMed: 14584883] [Abstract] Cited for: VARIANT PDB LEU-387.
[48]	"Familial Paget's disease in The Netherlands: occurrence, identification of new mutations in the sequestosome 1 gene, and their clinical associations." Eekhoff E.W.M., Karperien M., Houtsma D., Zwinderman A.H., Dragoiescu C., Kneppers A.L.J., Papapoulos S.E. Arthritis Rheum. 50:1650-1654(2004) [PubMed: 15146436] [Abstract] Cited for: VARIANTS PDB LEU-392; PRO-399; THR-404 AND ARG-425.
[49]	"Identification of SQSTM1 mutations in familial Paget's disease in Australian pedigrees." Good D.A., Busfield F., Fletcher B.H., Lovelock P.K., Duffy D.L., Kesting J.B., Andersen J., Shaw J.T.E. Bone 35:277-282(2004) [PubMed: 15207768] [Abstract] Cited for: VARIANT PDB LEU-392.
[50]	"Two novel mutations at exon 8 of the Sequestosome 1 (SQSTM1) gene in an Italian series of patients affected by Paget's disease of bone (PDB)." Falchetti A., Di Stefano M., Marini F., Del Monte F., Mavilia C., Strigoli D., De Feo M.L., Isaia G., Masi L., Amedei A., Cioppi F., Ghinoi V., Maddali Bongi S., Di Fede G., Sferrazza C., Rini G.B., Melchiorre D., Matucci-Cerinic M., Brandi M.L. J. Bone Miner. Res. 19:1013-1017(2004) [PubMed: 15125799] [Abstract] Cited for: VARIANTS PDB LEU-392; VAL-404 AND ARG-425.
[51]	"Novel UBA domain mutations of SQSTM1 in Paget's disease of bone: genotype phenotype correlation, functional analysis, and structural consequences." Hocking L.J., Lucas G.J.A., Daroszewska A., Cundy T., Nicholson G.C., Donath J., Walsh J.P., Finlayson C., Cavey J.R., Ciani B., Sheppard P.W., Searle M.S., Layfield R., Ralston S.H. J. Bone Miner. Res. 19:1122-1127(2004) [PubMed: 15176995] [Abstract] Cited for: VARIANTS PDB VAL-404; SER-411 AND ARG-425, CHARACTERIZATION OF VARIANTS VAL-404; SER-411 AND ARG-425.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U41806 mRNA. Translation: AAA93299.1.
U46751 mRNA. Translation: AAC52070.1.
AK098077 mRNA. Translation: BAG53577.1.
AK312451 mRNA. Translation: BAG35358.1.
AC008393 Genomic DNA. No translation available.
BC000951 mRNA. Translation: AAH00951.1.
BC001874 mRNA. Translation: AAH01874.1.
BC003139 mRNA. Translation: AAH03139.1.
BC017222 mRNA. Translation: AAH17222.1.
BC019111 mRNA. Translation: AAH19111.1.
AF060494 Genomic DNA. Translation: AAC64516.1.

IPI

IPI00179473.
IPI00784104.

RefSeq

NP_001135770.1.
NP_001135771.1.
NP_003891.1.

UniGene

Hs.437277

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Q02	NMR	-	A	387-436	[»]
2JY7	NMR	-	A	387-436	[»]
2JY8	NMR	-	A	387-436	[»]
2K0B	NMR	-	X	387-436	[»]
2KNV	NMR	-	A/B	387-436	[»]

SMR

Q13501. Positions 4-102, 118-164.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13501. 14 interactions.

STRING

Q13501.

PTM databases

PhosphoSite

Q13501.

Proteomic databases

PRIDE

Q13501.

Genome annotation databases

Ensembl

ENST00000389805; ENSP00000374455; ENSG00000161011; Homo sapiens. [Genome view]

GeneID

8878.

KEGG

hsa:8878.

UCSC

uc003mku.1. human.
uc003mkw.2. human.

Organism-specific databases

CTD

8878.

GeneCards

GC05P179181.

H-InvDB

HIX0005490.
HIX0080543.

HGNC

HGNC:11280. SQSTM1.

HPA

CAB004587.

MIM

601530. gene.
602080. phenotype.

PharmGKB

PA36109.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG05341.

HOVERGEN

Q13501.

InParanoid

Q13501.

OMA

SEDPSVN.

Enzyme and pathway databases

Pathway_Interaction_DB

il1pathway. IL1-mediated signaling events.
trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.
p75ntrpathway. p75(NTR)-mediated signaling.
tnfpathway. TNF receptor signaling pathway.

Reactome

REACT_11061. Signalling by NGF.

Gene expression databases

ArrayExpress

Q13501.

Bgee

Q13501.

CleanEx

HS_SQSTM1.

Genevestigator

Q13501.

GermOnline

ENSG00000161011. Homo sapiens.

Family and domain databases

InterPro

IPR000270. OPR_PB1.
IPR009060. UBA-like.
IPR015940. UBA/transl_elong_EF1B_N_euk.
IPR000433. Znf_ZZ.
[Graphical view]

Pfam

PF00564. PB1. 1 hit.
PF00569. ZZ. 1 hit.
[Graphical view]

SMART

SM00666. PB1. 1 hit.
SM00165. UBA. 1 hit.
SM00291. ZnF_ZZ. 1 hit.
[Graphical view]

PROSITE

PS50030. UBA. 1 hit.
PS01357. ZF_ZZ_1. 1 hit.
PS50135. ZF_ZZ_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

33335.

SOURCE

Search...

Entry information

Entry name

SQSTM_HUMAN

Accession

Primary (citable) accession number: Q13501
Secondary accession number(s): A6NFN7 , B2R661, B3KUW5, Q13446, Q9BUV7, Q9BVS6, Q9UEU1

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2005
Last sequence update:	November 1, 1996
Last modified:	February 9, 2010
This is version 99 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.