Reviewed, UniProtKB/Swiss-Prot Q9HD26 (GOPC_HUMAN)

Names and origin

Protein names

Recommended name:
    Golgi-associated PDZ and coiled-coil motif-containing protein
Alternative name(s):
    PDZ protein interacting specifically with TC10
      Short name=PIST
    CFTR-associated ligand
    Fused in glioblastoma

Gene names

Name:	GOPC
Synonyms:	CAL, FIG

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

General annotation (Comments)

Function	Plays a role in intracellular protein trafficking and degradation. May regulate CFTR chloride currents and acid-induced ACCN3 currents by modulating cell surface expression of both channels. May also regulate the intracellular trafficking of the ADR1B receptor. May play a role in autophagy. Overexpression results in CFTR intracellular retention and degradation in the lysosomes. Ref.3 Ref.10 Ref.12
Subunit structure	Homooligomer. Interacts with FZD5, FZD8, GRID2, BECN1, CSPG5 and CLCN3. May interact with CACNG2 By similarity. Interacts with STX6, CFTR, ACCN3, GOLGA3 and RHOQ. Ref.3 Ref.12 Ref.2 Ref.11 Ref.13 Ref.14
Subcellular location	Cytoplasm. Golgi apparatus membrane; Peripheral membrane protein. Golgi apparatus › trans-Golgi network membrane; Peripheral membrane protein. Cell junction › synapse By similarity. Cell junction › synapse › postsynaptic cell membrane › postsynaptic density By similarity. Cell projection › dendrite By similarity. Note: Enriched in synaptosomal and postsynaptic densities (PSD) fractions By similarity. Expressed in cell bodies and dendrites of Purkinje cells By similarity. Localized at the trans-Golgi network (TGN) of spermatids and the medulla of round spermatides By similarity. Ref.3 Ref.2 Ref.14
Tissue specificity	Ubiquitously expressed. Ref.3 Ref.2 Ref.1
Domain	The PDZ domain mediates interactions with FZD5, FZD8, ACCN3, GRID2, CLCN3 By similarity. Mediates also interaction with CFTR and ADRB1. Ref.3 Ref.12 The coiled-coil region probably mediates association to membranes, targeting to the Golgi, and interactions with GOLGA3, and STX6. May also mediate interaction with RHOQ By similarity. Ref.3 Ref.12
Involvement in disease	A chromosomal aberration involving GOPC is found in glioblastoma multiform (GBM). An homozygous deletion in chromosome 6q21 results in expression of a GOPC-ROS1 chimeric protein which has a constitutive receptor tyrosine kinase activity. Ref.8
Sequence similarities	Contains 1 PDZ (DHR) domain.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Cell junction Cell membrane Cell projection Cytoplasm Golgi apparatus Membrane Postsynaptic cell membrane Synapse
Coding sequence diversity	Alternative splicing Chromosomal rearrangement
Domain	Coiled coil
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	ER to Golgi vesicle-mediated transport Ref.3 Non-traceable author statement. Source: UniProtKB Golgi to plasma membrane transport Ref.3 Non-traceable author statement. Source: UniProtKB apical protein localization Ref.3 Non-traceable author statement. Source: UniProtKB cytoplasmic sequestering of CFTR protein Ref.3 Non-traceable author statement. Source: UniProtKB protein homooligomerization Ref.3 Inferred from physical interaction. Source: UniProtKB protein transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW dendrite Inferred from electronic annotation. Source: UniProtKB-SubCell extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell postsynaptic density Inferred from electronic annotation. Source: UniProtKB-SubCell postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-KW trans-Golgi network transport vesicle Ref.2 Ref.3 Inferred from direct assay. Source: UniProtKB
Molecular function	cystic fibrosis transmembrane conductance regulator binding Ref.3 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ADRB1	P08588	1	EBI-349832,EBI-991009
CFTR	P13569	1	EBI-349832,EBI-349854
CLCN3	P51790	1	EBI-349832,EBI-349797

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9HD26-1)

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: Q9HD26-2)

The sequence of this isoform differs from the canonical sequence as follows:
     150-157: Missing.

Isoform 3 (identifier: Q9HD26-3)

The sequence of this isoform differs from the canonical sequence as follows:
     305-319: GGKEHGVPILISEIH → VRSSTSSIIFYSYLV
     320-462: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 462

462

Golgi-associated PDZ and coiled-coil motif-containing protein

PRO_0000087542

Regions

Domain

288 – 371

84

PDZ

Coiled coil

83 – 200

118

Potential

Sites

Site

419 – 420

2

Breakpoint for translocation to form GOPC-ROS1 fusion protein

Amino acid modifications

Modified residue

457

1

Phosphotyrosine Ref.9

Modified residue

462

1

Phosphotyrosine Ref.9

Natural variations

Alternative sequence

150 – 157

8

Missing in isoform 2.

VSP_016062

Alternative sequence

305 – 319

15

GGKEH…ISEIH → VRSSTSSIIFYSYLV in isoform 3.

VSP_016063

Alternative sequence

320 – 462

143

Missing in isoform 3.

VSP_016064

Experimental info

Mutagenesis

175

1

L → V: No effect on subcellular location; when associated with V-182; V-189 and V-196. Ref.2

Mutagenesis

182

1

L → V: No effect on subcellular location; when associated with V-175; V-189 and V-196. Ref.2

Mutagenesis

189

1

L → V: No effect on subcellular location; when associated with V-175; V-182 and V-196. Ref.2

Mutagenesis

196

1

L → V: No effect on subcellular location; when associated with V-175; V-182 and V-189. Ref.2

Secondary structure

1

.

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462

Helix Strand Turn

Details...

Beta strand

286 – 292

7

Beta strand

295 – 297

3

Beta strand

301 – 306

6

Helix

307 – 309

3

Beta strand

311 – 318

8

Helix

323 – 327

5

Beta strand

332 – 339

8

Beta strand

342 – 344

3

Helix

349 – 358

10

Beta strand

361 – 369

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 8A19DDC376DCD0F4	FASTA	462	50,520
	10 20 30 40 50 60 MSAGGPCPAA AGGGPGGASC SVGAPGGVSM FRWLEVLEKE FDKAFVDVDL LLGEIDPDQA 70 80 90 100 110 120 DITYEGRQKM TSLSSCFAQL CHKAQSVSQI NHKLEAQLVD LKSELTETQA EKVVLEKEVH 130 140 150 160 170 180 DQLLQLHSIQ LQLHAKTGQS ADSGTIKAKL SGPSVEELER ELEANKKEKM KEAQLEAEVK 190 200 210 220 230 240 LLRKENEALR RHIAVLQAEV YGARLAAKYL DKELAGRVQQ IQLLGRDMKG PAHDKLWNQL 250 260 270 280 290 300 EAEIHLHRHK TVIRACRGRN DLKRPMQAPP GHDQDSLKKS QGVGPIRKVL LLKEDHEGLG 310 320 330 340 350 360 ISITGGKEHG VPILISEIHP GQPADRCGGL HVGDAILAVN GVNLRDTKHK EAVTILSQQR 370 380 390 400 410 420 GEIEFEVVYV APEVDSDDEN VEYEDESGHR YRLYLDELEG GGNPGASCKD TSGEIKVLQG 430 440 450 460 FNKKAVTDTH ENGDLGTASE TPLDDGASKL DDLHTLYHKK SY
	Isoform 2. Checksum: 7D02D85423A31BAB	FASTA	454	49,721
	10 20 30 40 50 60 MSAGGPCPAA AGGGPGGASC SVGAPGGVSM FRWLEVLEKE FDKAFVDVDL LLGEIDPDQA 70 80 90 100 110 120 DITYEGRQKM TSLSSCFAQL CHKAQSVSQI NHKLEAQLVD LKSELTETQA EKVVLEKEVH 130 140 150 160 170 180 DQLLQLHSIQ LQLHAKTGQS ADSGTIKAKL ERELEANKKE KMKEAQLEAE VKLLRKENEA 190 200 210 220 230 240 LRRHIAVLQA EVYGARLAAK YLDKELAGRV QQIQLLGRDM KGPAHDKLWN QLEAEIHLHR 250 260 270 280 290 300 HKTVIRACRG RNDLKRPMQA PPGHDQDSLK KSQGVGPIRK VLLLKEDHEG LGISITGGKE 310 320 330 340 350 360 HGVPILISEI HPGQPADRCG GLHVGDAILA VNGVNLRDTK HKEAVTILSQ QRGEIEFEVV 370 380 390 400 410 420 YVAPEVDSDD ENVEYEDESG HRYRLYLDEL EGGGNPGASC KDTSGEIKVL QGFNKKAVTD 430 440 450 THENGDLGTA SETPLDDGAS KLDDLHTLYH KKSY
	Isoform 3. Checksum: 54A09D9CC46A245D	FASTA	319	35,130
	10 20 30 40 50 60 MSAGGPCPAA AGGGPGGASC SVGAPGGVSM FRWLEVLEKE FDKAFVDVDL LLGEIDPDQA 70 80 90 100 110 120 DITYEGRQKM TSLSSCFAQL CHKAQSVSQI NHKLEAQLVD LKSELTETQA EKVVLEKEVH 130 140 150 160 170 180 DQLLQLHSIQ LQLHAKTGQS ADSGTIKAKL SGPSVEELER ELEANKKEKM KEAQLEAEVK 190 200 210 220 230 240 LLRKENEALR RHIAVLQAEV YGARLAAKYL DKELAGRVQQ IQLLGRDMKG PAHDKLWNQL 250 260 270 280 290 300 EAEIHLHRHK TVIRACRGRN DLKRPMQAPP GHDQDSLKKS QGVGPIRKVL LLKEDHEGLG 310 ISITVRSSTS SIIFYSYLV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"PIST: a novel PDZ/coiled-coil domain binding partner for the rho-family GTPase TC10." Neudauer C.L., Joberty G., Macara I.G. Biochem. Biophys. Res. Commun. 280:541-547(2001) [PubMed: 11162552] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Brain.
[2]	"Association of a novel PDZ domain-containing peripheral Golgi protein with the Q-SNARE (Q-soluble N-ethylmaleimide-sensitive fusion protein (NSF) attachment protein receptor) protein syntaxin 6." Charest A., Lane K., McMahon K., Housman D.E. J. Biol. Chem. 276:29456-29465(2001) [PubMed: 11384996] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH STX6, MUTAGENESIS OF LEU-175; LEU-182; LEU-189 AND LEU-196. Tissue: Myeloid leukemia cell.
[3]	"A Golgi-associated PDZ domain protein modulates cystic fibrosis transmembrane regulator plasma membrane expression." Cheng J., Moyer B.D., Milewski M., Loffing J., Ikeda M., Mickle J.E., Cutting G.R., Li M., Stanton B.A., Guggino W.B. J. Biol. Chem. 277:3520-3529(2002) [PubMed: 11707463] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, OLIGOMERIZATION, INTERACTION WITH CFTR, DOMAIN. Tissue: Lung.
[4]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Brain.
[5]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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] (ISOFORM 2). Tissue: Pancreas.
[8]	"Fusion of FIG to the receptor tyrosine kinase ROS in a glioblastoma with an interstitial del(6)(q21q21)." Charest A., Lane K., McMahon K., Park J., Preisinger E., Conroy H., Housman D. Genes Chromosomes Cancer 37:58-71(2003) [PubMed: 12661006] [Abstract] Cited for: DISEASE, CHROMOSOMAL TRANSLOCATION WITH ROS1.
[9]	"Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry." Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C. Anal. Chem. 76:2763-2772(2004) [PubMed: 15144186] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-457 AND TYR-462, MASS SPECTROMETRY. Tissue: T-cell.
[10]	"Modulation of mature cystic fibrosis transmembrane regulator protein by the PDZ domain protein CAL." Cheng J., Wang H., Guggino W.B. J. Biol. Chem. 279:1892-1898(2004) [PubMed: 14570915] [Abstract] Cited for: FUNCTION.
[11]	"PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+- gated current." Hruska-Hageman A.M., Benson C.J., Leonard A.S., Price M.P., Welsh M.J. J. Biol. Chem. 279:46962-46968(2004) [PubMed: 15317815] [Abstract] Cited for: INTERACTION WITH ACCN3.
[12]	"Interaction with cystic fibrosis transmembrane conductance regulator-associated ligand (CAL) inhibits beta1-adrenergic receptor surface expression." He J., Bellini M., Xu J., Castleberry A.M., Hall R.A. J. Biol. Chem. 279:50190-50196(2004) [PubMed: 15358775] [Abstract] Cited for: INTERACTION WITH ADRB1, DOMAIN, FUNCTION.
[13]	"Regulation of cystic fibrosis transmembrane regulator trafficking and protein expression by a Rho family small GTPase TC10." Cheng J., Wang H., Guggino W.B. J. Biol. Chem. 280:3731-3739(2005) [PubMed: 15546864] [Abstract] Cited for: INTERACTION WITH RHOQ.
[14]	"Isoform-specific interaction of golgin-160 with the Golgi-associated protein PIST." Hicks S.W., Machamer C.E. J. Biol. Chem. 280:28944-28951(2005) [PubMed: 15951434] [Abstract] Cited for: INTERACTION WITH GOLGA3, SUBCELLULAR LOCATION.
[15]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF287894 mRNA. Translation: AAG00572.1.
AY033606 mRNA. Translation: AAK57733.1.
AF450008 mRNA. Translation: AAL47160.1.
AB209385 mRNA. Translation: BAD92622.1. Different initiation.
AL589939, Z85999 Genomic DNA. Translation: CAH70198.1.
AL589939, Z85999 Genomic DNA. Translation: CAH70199.1.
Z85999, AL589939 Genomic DNA. Translation: CAI43172.1.
Z85999, AL589939 Genomic DNA. Translation: CAI43173.1.
CH471051 Genomic DNA. Translation: EAW48205.1.
BC009553 mRNA. Translation: AAH09553.1.

IPI

IPI00186721.
IPI00556252.
IPI00843890.

RefSeq

NP_001017408.1.
NP_065132.1.

UniGene

Hs.191539

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2DC2	NMR	-	A	278-371	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9HD26. 4 interactions.

STRING

Q9HD26.

PTM databases

PhosphoSite

Q9HD26.

Proteomic databases

PRIDE

Q9HD26.

Genome annotation databases

Ensembl

ENST00000368498; ENSP00000357484; ENSG00000047932; Homo sapiens. [Genome view]

GeneID

57120.

KEGG

hsa:57120.

UCSC

uc003pxu.1. human.
uc003pxv.1. human.

Organism-specific databases

CTD

57120.

GeneCards

GC06M117988.

HGNC

HGNC:17643. GOPC.

HPA

HPA019477.
HPA024018.

MIM

606845. gene.

PharmGKB

PA134904944.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG07124.

HOGENOM

HBG716543.

HOVERGEN

Q9HD26.

OMA

KAVTDGH.

PhylomeDB

Q9HD26.

Gene expression databases

ArrayExpress

Q9HD26.

Bgee

Q9HD26.

CleanEx

HS_GOPC.

Genevestigator

Q9HD26.

GermOnline

ENSG00000047932. Homo sapiens.

Family and domain databases

InterPro

IPR001478. PDZ/DHR/GLGF.
[Graphical view]

Pfam

PF00595. PDZ. 1 hit.
[Graphical view]

SMART

SM00228. PDZ. 1 hit.
[Graphical view]

PROSITE

PS50106. PDZ. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

62999.

SOURCE

Search...

Entry information

Entry name

GOPC_HUMAN

Accession

Primary (citable) accession number: Q9HD26
Secondary accession number(s): A6NM30, Q59FS4, Q969U8

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 8, 2005
Last sequence update:	March 1, 2001
Last modified:	January 19, 2010
This is version 79 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.