Q8IWJ2 (GCC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 96.
History...
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: GRIP and coiled-coil domain-containing protein 2 Alternative name(s): 185 kDa Golgi coiled-coil protein Short name=GCC185 CLL-associated antigen KW-11 CTCL tumor antigen se1-1 Ran-binding protein 2-like 4 Short name=RanBP2L4 Renal carcinoma antigen NY-REN-53 | ||||
| Gene names |
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| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 1684 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Golgin which probably tethers transport vesicles to the trans-Golgi network (TGN) and regulates vesicular transport between the endosomes and the Golgi. As a RAB9A effector it is involved in recycling of the mannose 6-phosphate receptor from the late endosomes to the TGN. May also play a role in transport between the recycling endosomes and the Golgi. Required for maintenance of the Golgi structure, it is involved in the biogenesis of noncentrosomal, Golgi-associated microtubules through recruitment of CLASP1 and CLASP2. Ref.9 Ref.11 Ref.12 |
| Subunit structure | Homodimer. Interacts (via GRIP domain) with RAB6A (preferentially in its GTP-bound form). May interact (RAB6A-dependent) with ARL1; according to Ref.16, RAB6A and ARL1 are not involved in GCC2 Golgi localization as proposed by Ref.17. Interacts (probably via GRIP domain) with RAB9A (preferentially in its GTP-bound form). Interacts with CLASP1 and CLASP2; recruits both proteins to membranes of the TGN. Interacts with STX16. Ref.9 Ref.11 Ref.13 Ref.16 Ref.17 |
| Subcellular location | Cytoplasm. Golgi apparatus › trans-Golgi network membrane; Peripheral membrane protein Ref.8 Ref.9 Ref.12 Ref.16 Ref.17. |
| Tissue specificity | Ubiquitous. Ref.6 |
| Domain | Extended rod-like protein with coiled-coil domains. |
| Sequence similarities | Contains 1 GRIP domain. |
| Sequence caution | The sequence AAG34902.1 differs from that shown. Reason: Frameshift at positions 694, 700, 937 and 940. The sequence AAH37774.1 differs from that shown. Reason: Wrong choice of CDS. The sequence AAI46790.1 differs from that shown. Reason: Wrong choice of CDS. The sequence AAL99918.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence AAX88838.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence BAA20794.2 differs from that shown. Reason: Wrong choice of CDS. The sequence EAW53882.1 differs from that shown. Reason: Erroneous gene model prediction. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| itself | 2 | EBI-1645320,EBI-1645320 | ||
| RAB6A | P20340 | 4 | EBI-1645320,EBI-1052826 |
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q8IWJ2-1) 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: Q8IWJ2-3) The sequence of this isoform differs from the canonical sequence as follows: 22-45: LETLPKEDLIKFAKKQMMLIQKAK → NWRKKLKNSDQNLLLKELVILLRH 46-1684: 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 | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1684 | 1684 | GRIP and coiled-coil domain-containing protein 2 | PRO_0000190074 | |||||||
Regions | |||||||||||
| Domain | 1609 – 1659 | 51 | GRIP | ||||||||
| Region | 1574 – 1684 | 111 | Mediates interaction with RAB9A | ||||||||
| Region | 1574 – 1613 | 40 | Mediates interaction with RAB6A | ||||||||
| Coiled coil | 110 – 1618 | 1509 | Potential | ||||||||
Amino acid modifications | |||||||||||
| Modified residue | 287 | 1 | Phosphoserine Ref.14 | ||||||||
| Modified residue | 1483 | 1 | Phosphoserine Ref.10 Ref.15 | ||||||||
| Modified residue | 1542 | 1 | Phosphoserine Ref.15 | ||||||||
| Modified residue | 1649 | 1 | Phosphoserine Ref.14 Ref.15 | ||||||||
Natural variations | |||||||||||
| Alternative sequence | 22 – 45 | 24 | LETLP…IQKAK → NWRKKLKNSDQNLLLKELVI LLRH in isoform 2. | VSP_040106 | |||||||
| Alternative sequence | 46 – 1684 | 1639 | Missing in isoform 2. | VSP_040107 | |||||||
| Natural variant | 1134 | 1 | Q → E. Ref.3 Corresponds to variant rs2718698 [ dbSNP | Ensembl ]. | VAR_046635 | |||||||
| Natural variant | 1298 | 1 | R → G. Corresponds to variant rs1061202 [ dbSNP | Ensembl ]. | VAR_016101 | |||||||
Experimental info | |||||||||||
| Mutagenesis | 1588 | 1 | I → A: Slightly decreases RAB6A binding affinity. Decreases RAB9A binding affinity by 2-fold. Strongly decreases RAB6A or RAB9A binding affinity and abolishes Golgi localization; when associated with A-1595. Ref.17 | ||||||||
| Mutagenesis | 1595 | 1 | L → A: Decreases RAB6A binding affinity by 2-fold. Strongly decreases RAB9A binding affinity. Strongly decreases RAB6A or RAB9A binding affinity and abolishes Golgi localization; when associated with A-1588. Ref.17 | ||||||||
| Mutagenesis | 1618 | 1 | Y → A: No effect on interaction with RAB6A and RAB9A. Ref.9 Ref.17 | ||||||||
Secondary structure | |||||||||||
Helix Strand Turn | |||||||||||
| Helix | 1574 – 1605 | 32 | |||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 4:141-150(1997) [PubMed: 9205841] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain. |
| [2] | "Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. Wilson R.K.Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [3] | 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. Venter J.C.Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLU-1134. |
| [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain. |
| [5] | "Identification of tumor-associated antigens in chronic lymphocytic leukemia by SEREX." Krackhardt A.M., Witzens M., Harig S., Hodi F.S., Zauls A.J., Chessia M., Barrett P., Gribben J.G. Blood 100:2123-2131(2002) [PubMed: 12200376] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-448 (ISOFORM 1). |
| [6] | "Serological detection of cutaneous T-cell lymphoma-associated antigens." Eichmueller S., Usener D., Dummer R., Stein A., Thiel D., Schadendorf D. Proc. Natl. Acad. Sci. U.S.A. 98:629-634(2001) [PubMed: 11149944] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 161-946 (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Testis. |
| [7] | "Antigens recognized by autologous antibody in patients with renal-cell carcinoma." Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., Old L.J. Int. J. Cancer 83:456-464(1999) [PubMed: 10508479] [Abstract] Cited for: IDENTIFICATION AS A RENAL CANCER ANTIGEN. Tissue: Renal cell carcinoma. |
| [8] | "GRIP domain-mediated targeting of two new coiled-coil proteins, GCC88 and GCC185, to subcompartments of the trans-Golgi network." Luke M.R., Kjer-Nielsen L., Brown D.L., Stow J.L., Gleeson P.A. J. Biol. Chem. 278:4216-4226(2003) [PubMed: 12446665] [Abstract] Cited for: SUBCELLULAR LOCATION. |
| [9] | "A functional role for the GCC185 golgin in mannose 6-phosphate receptor recycling." Reddy J.V., Burguete A.S., Sridevi K., Ganley I.G., Nottingham R.M., Pfeffer S.R. Mol. Biol. Cell 17:4353-4363(2006) [PubMed: 16885419] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RAB9A, MUTAGENESIS OF TYR-1618. |
| [10] | "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 SER-1483, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [11] | "Asymmetric CLASP-dependent nucleation of noncentrosomal microtubules at the trans-Golgi network." Efimov A., Kharitonov A., Efimova N., Loncarek J., Miller P.M., Andreyeva N., Gleeson P., Galjart N., Maia A.R., McLeod I.X., Yates J.R. III, Maiato H., Khodjakov A., Akhmanova A., Kaverina I. Dev. Cell 12:917-930(2007) [PubMed: 17543864] [Abstract] Cited for: FUNCTION, INTERACTION WITH CLASP1 AND CLASP2. |
| [12] | "The trans-Golgi network golgin, GCC185, is required for endosome-to-Golgi transport and maintenance of Golgi structure." Derby M.C., Lieu Z.Z., Brown D., Stow J.L., Goud B., Gleeson P.A. Traffic 8:758-773(2007) [PubMed: 17488291] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION. |
| [13] | "A syntaxin 10-SNARE complex distinguishes two distinct transport routes from endosomes to the trans-Golgi in human cells." Ganley I.G., Espinosa E., Pfeffer S.R. J. Cell Biol. 180:159-172(2008) [PubMed: 18195106] [Abstract] Cited for: INTERACTION WITH STX16. |
| [14] | "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 SER-287 AND SER-1649, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [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-1483; SER-1542 AND SER-1649, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [16] | "The localization of the Golgin GCC185 is independent of Rab6A/A' and Arl1." Houghton F.J., Chew P.L., Lodeho S., Goud B., Gleeson P.A. Cell 138:787-794(2009) [PubMed: 19703403] [Abstract] Cited for: INTERACTION WITH RAB6A, SUBCELLULAR LOCATION. |
| [17] | "Rab and Arl GTPase family members cooperate in the localization of the golgin GCC185." Burguete A.S., Fenn T.D., Brunger A.T., Pfeffer S.R. Cell 132:286-298(2008) [PubMed: 18243103] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 1557-1612, SUBCELLULAR LOCATION, INTERACTION WITH ARL1; RAB6A AND RAB9A, MUTAGENESIS OF ILE-1588; LEU-1595 AND TYR-1618. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EMBL GenBank DDBJ | AB002334 mRNA. Translation: BAA20794.2. Sequence problems. AC012487 Genomic DNA. Translation: AAX88838.1. Sequence problems. AC068941 Genomic DNA. No translation available. CH471182 Genomic DNA. Translation: EAW53882.1. Sequence problems. BC037774 mRNA. Translation: AAH37774.1. Sequence problems. BC146789 mRNA. Translation: AAI46790.1. Sequence problems. AF432211 mRNA. Translation: AAL99918.1. Different initiation. AF273042 mRNA. Translation: AAG34902.1. Frameshift. | ||||||||||||
| IPI | IPI00005631. IPI00947067. | ||||||||||||
| RefSeq | NP_852118.1. NM_181453.3. | ||||||||||||
| UniGene | Hs.436505. Hs.469630. | ||||||||||||
3D structure databases | |||||||||||||
| PDBe RCSB PDB PDBj |
| ||||||||||||
| ProteinModelPortal | Q8IWJ2. | ||||||||||||
| SMR | Q8IWJ2. Positions 1570-1607. | ||||||||||||
| ModBase | Search... | ||||||||||||
Protein-protein interaction databases | |||||||||||||
| IntAct | Q8IWJ2. 13 interactions. | ||||||||||||
| STRING | Q8IWJ2. | ||||||||||||
PTM databases | |||||||||||||
| PhosphoSite | Q8IWJ2. | ||||||||||||
Polymorphism databases | |||||||||||||
| DMDM | 158931162. | ||||||||||||
Proteomic databases | |||||||||||||
| PRIDE | Q8IWJ2. | ||||||||||||
Protocols and materials databases | |||||||||||||
| StructuralBiologyKnowledgebase | Search... | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENST00000309863; ENSP00000307939; ENSG00000135968. ENST00000409325; ENSP00000386860; ENSG00000135968. | ||||||||||||
| GeneID | 9648. | ||||||||||||
| KEGG | hsa:9648. | ||||||||||||
| UCSC | uc002tec.1. human. | ||||||||||||
Organism-specific databases | |||||||||||||
| CTD | 9648. | ||||||||||||
| GeneCards | GC02P109065. | ||||||||||||
| H-InvDB | HIX0023314. | ||||||||||||
| HGNC | HGNC:23218. GCC2. | ||||||||||||
| HPA | HPA035849. | ||||||||||||
| MIM | 612711. gene. | ||||||||||||
| neXtProt | NX_Q8IWJ2. | ||||||||||||
| HUGE | Search... | ||||||||||||
| GenAtlas | Search... | ||||||||||||
Phylogenomic databases | |||||||||||||
| GeneTree | ENSGT00600000084031. | ||||||||||||
| HOGENOM | HBG278534. | ||||||||||||
| HOVERGEN | HBG045522. | ||||||||||||
| InParanoid | Q8IWJ2. | ||||||||||||
| OMA | CQIEASA. | ||||||||||||
| OrthoDB | EOG4RFKS0. | ||||||||||||
| PhylomeDB | Q8IWJ2. | ||||||||||||
Gene expression databases | |||||||||||||
| ArrayExpress | Q8IWJ2. | ||||||||||||
| Bgee | Q8IWJ2. | ||||||||||||
| CleanEx | HS_GCC2. | ||||||||||||
| Genevestigator | Q8IWJ2. | ||||||||||||
| GermOnline | ENSG00000135968. Homo sapiens. | ||||||||||||
Family and domain databases | |||||||||||||
| InterPro | IPR000237. GRIP. [Graphical view] | ||||||||||||
| Pfam | PF01465. GRIP. 1 hit. [Graphical view] | ||||||||||||
| SMART | SM00755. Grip. 1 hit. [Graphical view] | ||||||||||||
| PROSITE | PS50913. GRIP. 1 hit. [Graphical view] | ||||||||||||
| ProtoNet | Search... | ||||||||||||
Other | |||||||||||||
| NextBio | 36215. | ||||||||||||
| SOURCE | Search... | ||||||||||||
Entry information
| Entry name | GCC2_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q8IWJ2 Secondary accession number(s): A6H8X8 Q9H2G8 | ||||||||
| Entry history |
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| 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. | ||||||||
Relevant documents
| Human chromosome 2 Human chromosome 2: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with