Q96SL1 (DIRC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Disrupted in renal carcinoma protein 2

Alternative name(s):
Disrupted in renal cancer protein 2

Gene names

Name:

DIRC2

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

General annotation (Comments)

Function	Electrogenic metabolite transporter. Ref.5
Subcellular location	Lysosome membrane; Multi-pass membrane protein Ref.5.
Tissue specificity	Ubiquitous. Expressed in proximal tubular cells of the kidney. Ref.4
Post-translational modification	Cleaved in lysosomes by cathepsin L between Leu-214 and Ala-261, generating a N-glycosylated N-terminal and a non-glycosylated C-terminal fragment. Ref.5
Involvement in disease	A chromosomal aberration involving DIRC2 has been found in a family with renal carcinoma. Translocation t(2;3)(q35;q21).
Sequence similarities	Belongs to the major facilitator superfamily.

Ontologies

Keywords
Biological process	Transport
Cellular component	Lysosome Membrane
Coding sequence diversity	Alternative splicing Chromosomal rearrangement
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW lysosomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q96SL1-1)

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: Q96SL1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     380-411: VTLYASCILLGVFLNSSVPIFFELFVETVYPV → EMGFRHVVQAGLELLSLSDSPTLASQNVGIAD
     412-478: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 478	478	Disrupted in renal carcinoma protein 2		PRO_0000271338
Regions
	Topological domain	1 – 51	51	Cytoplasmic Potential
	Transmembrane	52 – 72	21	Helical; Potential
	Topological domain	73 – 89	17	Lumenal Potential
	Transmembrane	90 – 110	21	Helical; Potential
	Topological domain	111 – 117	7	Cytoplasmic Potential
	Transmembrane	118 – 138	21	Helical; Potential
	Topological domain	139 – 155	17	Lumenal Potential
	Transmembrane	156 – 176	21	Helical; Potential
	Topological domain	177 – 184	8	Cytoplasmic Potential
	Transmembrane	185 – 205	21	Helical; Potential
	Topological domain	206 – 229	24	Lumenal Potential
	Transmembrane	230 – 250	21	Helical; Potential
	Topological domain	251 – 281	31	Cytoplasmic Potential
	Transmembrane	282 – 302	21	Helical; Potential
	Topological domain	303 – 314	12	Lumenal Potential
	Transmembrane	315 – 335	21	Helical; Potential
	Topological domain	336 – 347	12	Cytoplasmic Potential
	Transmembrane	348 – 368	21	Helical; Potential
	Topological domain	369 – 384	16	Lumenal Potential
	Transmembrane	385 – 405	21	Helical; Potential
	Topological domain	406 – 414	9	Cytoplasmic Potential
	Transmembrane	415 – 435	21	Helical; Potential
	Topological domain	436 – 442	7	Lumenal Potential
	Transmembrane	443 – 463	21	Helical; Potential
	Topological domain	464 – 478	15	Cytoplasmic Potential
	Motif	14 – 15	2	Mediates lysosomal localization
Amino acid modifications
	Glycosylation	209	1	N-linked (GlcNAc...) Ref.5
Natural variations
	Alternative sequence	380 – 411	32	VTLYA…TVYPV → EMGFRHVVQAGLELLSLSDS PTLASQNVGIAD in isoform 2.		VSP_022302
	Alternative sequence	412 – 478	67	Missing in isoform 2.		VSP_022303
Experimental info
	Mutagenesis	14 – 15	2	LL → AA: Abolishes lysosomal localization. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: B752B98647711B89	FASTA	478	52,088
	10 20 30 40 50 60 MGSRWSSEEE RQPLLGPGLG PGLGASWRSR EAAAAALPAA VPGPGRVYGR RWLVLLLFSL 70 80 90 100 110 120 LAFVQGLVWN TWGPIQNSAR QAYGFSSWDI ALLVLWGPIG FLPCFAFMWL LDKRGLRITV 130 140 150 160 170 180 LLTSFLMVLG TGLRCIPISD LILKRRLIHG GQMLNGLAGP TVMNAAPFLS TTWFSADERA 190 200 210 220 230 240 TATAIASMLS YLGGACAFLV GPLVVPAPNG TSPLLAAESS RAHIKDRIEA VLYAEFGVVC 250 260 270 280 290 300 LIFSATLAYF PPRPPLPPSV AAASQRLSYR RSVCRLLSNF RFLMIALAYA IPLGVFAGWS 310 320 330 340 350 360 GVLDLILTPA HVSQVDAGWI GFWSIVGGCV VGIAMARFAD FIRGMLKLIL LLLFSGATLS 370 380 390 400 410 420 STWFTLTCLN SITHLPLTTV TLYASCILLG VFLNSSVPIF FELFVETVYP VPEGITCGVV 430 440 450 460 470 TFLSNMFMGV LLFFLTFYHT ELSWFNWCLP GSCLLSLLLI LCFRESYDRL YLDVVVSV
	Isoform 2 [UniParc]. Checksum: 79709AEBBBA7E31A	FASTA	411	44,146
	10 20 30 40 50 60 MGSRWSSEEE RQPLLGPGLG PGLGASWRSR EAAAAALPAA VPGPGRVYGR RWLVLLLFSL 70 80 90 100 110 120 LAFVQGLVWN TWGPIQNSAR QAYGFSSWDI ALLVLWGPIG FLPCFAFMWL LDKRGLRITV 130 140 150 160 170 180 LLTSFLMVLG TGLRCIPISD LILKRRLIHG GQMLNGLAGP TVMNAAPFLS TTWFSADERA 190 200 210 220 230 240 TATAIASMLS YLGGACAFLV GPLVVPAPNG TSPLLAAESS RAHIKDRIEA VLYAEFGVVC 250 260 270 280 290 300 LIFSATLAYF PPRPPLPPSV AAASQRLSYR RSVCRLLSNF RFLMIALAYA IPLGVFAGWS 310 320 330 340 350 360 GVLDLILTPA HVSQVDAGWI GFWSIVGGCV VGIAMARFAD FIRGMLKLIL LLLFSGATLS 370 380 390 400 410 STWFTLTCLN SITHLPLTTE MGFRHVVQAG LELLSLSDSP TLASQNVGIA D

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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). Tissue: Placenta.
[2]	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].
[3]	"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: Skin.
[4]	"Disruption of a novel MFS transporter gene, DIRC2, by a familial renal cell carcinoma-associated t(2;3)(q35;q21)." Bodmer D., Eleveld M., Kater-Baats E., Janssen I., Janssen B., Weterman M., Schoenmakers E., Nickerson M., Linehan M., Zbar B., van Kessel A.G. Hum. Mol. Genet. 11:641-649(2002) [PubMed] [Europe PMC] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION, TISSUE SPECIFICITY.
[5]	"Disrupted in renal carcinoma 2 (DIRC2), a novel transporter of the lysosomal membrane, is proteolytically processed by cathepsin L." Savalas L.R., Gasnier B., Damme M., Lubke T., Wrocklage C., Debacker C., Jezegou A., Reinheckel T., Hasilik A., Saftig P., Schroder B. Biochem. J. 439:113-128(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, GLYCOSYLATION AT ASN-209, PROTEOLYTIC PROCESSING, MUTAGENESIS OF 14-LEU-LEU-15, SUBCELLULAR LOCATION.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK027690 mRNA. Translation: BAB55300.1. AK075158 mRNA. Translation: BAC11440.1. AK291176 mRNA. Translation: BAF83865.1. CH471052 Genomic DNA. Translation: EAW79462.1. BC039821 mRNA. Translation: AAH39821.1.
IPI	IPI00045792. IPI00168349.
RefSeq	NP_116228.1. NM_032839.2.
UniGene	Hs.477346.
3D structure databases
ProteinModelPortal	Q96SL1.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000261038.
PTM databases
PhosphoSite	Q96SL1.
Polymorphism databases
DMDM	74732717.
Proteomic databases
PaxDb	Q96SL1.
PRIDE	Q96SL1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000261038; ENSP00000261038; ENSG00000138463.
GeneID	84925.
KEGG	hsa:84925.
UCSC	uc003efw.4. human.
Organism-specific databases
CTD	84925.
GeneCards	GC03P122513.
H-InvDB	HIX0030821.
HGNC	HGNC:16628. DIRC2.
MIM	602773. gene.
neXtProt	NX_Q96SL1.
Orphanet	151. Familial renal cell carcinoma.
PharmGKB	PA27341.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG298320.
HOGENOM	HOG000294083.
HOVERGEN	HBG060348.
InParanoid	Q96SL1.
KO	K15381.
OMA	VLYAEFG.
OrthoDB	EOG46T31W.
PhylomeDB	Q96SL1.
Gene expression databases
ArrayExpress	Q96SL1.
Bgee	Q96SL1.
CleanEx	HS_DIRC2.
Genevestigator	Q96SL1.
Family and domain databases
InterPro	IPR016196. MFS_dom_general_subst_transpt. [Graphical view]
SUPFAM	SSF103473. MFS_gen_substrate_transporter. 1 hit.
PROSITE	PS50850. MFS. False negative. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	84925.
NextBio	75346.
SOURCE	Search...

Entry information

Entry name

DIRC2_HUMAN

Accession

Primary (citable) accession number: Q96SL1
Secondary accession number(s): A8K561, Q8NBX9

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 9, 2007
Last sequence update:	December 1, 2001
Last modified:	April 3, 2013
This is version 78 of the entry and version 1 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.