Q13432 (U119A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein unc-119 homolog A

Alternative name(s):
Retinal protein 4
Short name=hRG4

Gene names

Name:	UNC119
Synonyms:	RG4

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

General annotation (Comments)

Function	Myristoyl-binding protein that acts as a cargo adapter: specifically binds the myristoyl moiety of a subset of N-terminally myristoylated proteins and is required for their localization. Binds myristoylated GNAT1 and is required for G-protein localization and trafficking in sensory neurons. Binds myristoylated NPHP3; however, in contrast to UNC119B, does not seem to play a major role in ciliary membrane localization of NPHP3. Does not bind all myristoylated proteins. Probably plays a role in trafficking proteins in photoreceptor cells. Ref.12 Ref.13
Subunit structure	Interacts with CABP4; in the absence of calcium. May interact with ARL1, ARL2 and ARL3 GTP-bound forms. Found in a complex with ARL3, RP2 and UNC119; RP2 induces hydrolysis of GTP ARL3 in the complex, leading to the release of UNC119. Interacts with NPHP3 (when myristoylated). Interacts with CYS1 (when myristoylated). Interacts with C5orf30; interaction only takes place when UNC119 is not liganded with myristoylated proteins. Ref.10 Ref.11 Ref.12 Ref.13
Subcellular location	Cytoplasm › cytoskeleton › centrosome Ref.12.
Tissue specificity	Retinal-specific. Localized in photoreceptor synapses in the outer plexiform layer of the retina.
Domain	Adopts an immunoglobulin-like beta-sandwich fold forming a hydrophobic cavity that capture N-terminally myristoylated target peptides (Ref.13). Phe residues within the hydrophobic beta sandwich are required for myristate binding (Ref.12).
Involvement in disease	Defects in UNC119 may be a cause of cone-rod dystrophy. A mutation was found in a 57-year-old woman with late-onset cone-rod dystrophy: from 40 year old, the patient suffered from poor night vision, defective color vision and light-sensitivity. At 57 year old, she displayed reduced visual acuity, myopa, macular atrophy and pericentral ring scotomas. The disease was caused by a heterozygous mutation causing premature termination and truncated UNC119 protein with dominant-negative effect.
Sequence similarities	Belongs to the PDE6D/unc-119 family.
Caution	According to some authors, acts by extracting target proteins from membranes (Ref.13). According to a another report, rather acts by targeting proteins to membranes (Ref.12).

Ontologies

Keywords
Biological process	Protein transport Sensory transduction Transport Vision
Cellular component	Cytoplasm Cytoskeleton
Coding sequence diversity	Alternative splicing
Disease	Cone-rod dystrophy
Ligand	Lipid-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	lipoprotein transport Inferred from direct assay Ref.13Ref.12. Source: UniProtKB phototransduction Traceable author statement PubMed 9538874. Source: ProtInc synaptic transmission Traceable author statement PubMed 9538874. Source: ProtInc visual perception Traceable author statement Ref.3. Source: ProtInc
Cellular_component	centrosome Inferred from direct assay Ref.12. Source: UniProtKB cytosol Traceable author statement PubMed 9538874. Source: ProtInc
Molecular_function	lipid binding Inferred from direct assay Ref.13Ref.12. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform A (identifier: Q13432-1)

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 B (identifier: Q13432-2)

The sequence of this isoform differs from the canonical sequence as follows:
     204-240: ISEMIRHPYETQSDSFYFVDDRLVMHNKADYSYSGTP → SARAGSSGSGEVGASRD

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 240

240

Protein unc-119 homolog A

PRO_0000221212

Sites

Binding site

131

1

Lipid

Amino acid modifications

Modified residue

37

1

Phosphoserine By similarity

Natural variations

Alternative sequence

204 – 240

37

ISEMI…YSGTP → SARAGSSGSGEVGASRD in isoform B.

VSP_004545

Secondary structure

1

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240

Helix Strand Turn

Details...

Helix

62 – 64

3

Turn

65 – 67

3

Helix

79 – 81

3

Beta strand

87 – 95

9

Turn

96 – 98

3

Beta strand

101 – 106

6

Beta strand

128 – 132

5

Helix

135 – 139

5

Beta strand

141 – 150

10

Beta strand

158 – 167

10

Beta strand

170 – 178

9

Beta strand

186 – 195

10

Helix

201 – 209

9

Beta strand

214 – 222

9

Beta strand

225 – 235

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform A [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 22FD19C3518A4446	FASTA	240	26,962
	10 20 30 40 50 60 MKVKKGGGGA GTATESAPGP SGQSVAPIPQ PPAESESGSE SEPDAGPGPR PGPLQRKQPI 70 80 90 100 110 120 GPEDVLGLQR ITGDYLCSPE ENIYKIDFVR FKIRDMDSGT VLFEIKKPPV SERLPINRRD 130 140 150 160 170 180 LDPNAGRFVR YQFTPAFLRL RQVGATVEFT VGDKPVNNFR MIERHYFRNQ LLKSFDFHFG 190 200 210 220 230 240 FCIPSSKNTC EHIYDFPPLS EELISEMIRH PYETQSDSFY FVDDRLVMHN KADYSYSGTP
	Isoform B [UniParc]. Checksum: 70146298DD2628C7	FASTA	220	24,112
	10 20 30 40 50 60 MKVKKGGGGA GTATESAPGP SGQSVAPIPQ PPAESESGSE SEPDAGPGPR PGPLQRKQPI 70 80 90 100 110 120 GPEDVLGLQR ITGDYLCSPE ENIYKIDFVR FKIRDMDSGT VLFEIKKPPV SERLPINRRD 130 140 150 160 170 180 LDPNAGRFVR YQFTPAFLRL RQVGATVEFT VGDKPVNNFR MIERHYFRNQ LLKSFDFHFG 190 200 210 220 FCIPSSKNTC EHIYDFPPLS EELSARAGSS GSGEVGASRD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the cDNA for a novel photoreceptor protein." Higashide T., Murakami A., McLaren M.J., Inana G. J. Biol. Chem. 271:1797-1804(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A). Tissue: Retina.
[2]	"Mammalian orthologs of C. elegans unc-119 highly expressed in photoreceptors." Swanson D.A., Chang J.T., Campochiaro P.A., Zack D.J., Valle D. Invest. Ophthalmol. Vis. Sci. 39:2085-2094(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B). Tissue: Retina.
[3]	"Characterization of the gene for HRG4 (UNC119), a novel photoreceptor synaptic protein homologous to unc-119." Higashide T., Inana G. Genomics 57:446-450(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM A).
[4]	"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] (ISOFORM B). Tissue: Testis.
[5]	"Full-length transcriptome analysis of human retina-derived cell lines ARPE-19 and Y79 using the vector-capping method." Oshikawa M., Tsutsui C., Ikegami T., Fuchida Y., Matsubara M., Toyama S., Usami R., Ohtoko K., Kato S. Invest. Ophthalmol. Vis. Sci. 52:6662-6670(2011) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B). Tissue: Retinoblastoma.
[6]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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 A). Tissue: Lymph.
[9]	"HRG4 (UNC119) mutation found in cone-rod dystrophy causes retinal degeneration in a transgenic model." Kobayashi A., Higashide T., Hamasaki D., Kubota S., Sakuma H., An W., Fujimaki T., McLaren M.J., Weleber R.G., Inana G. Invest. Ophthalmol. Vis. Sci. 41:3268-3277(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN CONE-ROD DYSTROPHY.
[10]	"ADP-ribosylation factors (ARFs) and ARF-like 1 (ARL1) have both specific and shared effectors: characterizing ARL1-binding proteins." Van Valkenburgh H., Shern J.F., Sharer J.D., Zhu X., Kahn R.A. J. Biol. Chem. 276:22826-22837(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ARL1; ARL2 AND ARL3.
[11]	"Specificity of Arl2/Arl3 signaling is mediated by a ternary Arl3-effector-GAP complex." Veltel S., Kravchenko A., Ismail S., Wittinghofer A. FEBS Lett. 582:2501-2507(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH ARL3 AND RP2.
[12]	"An ARL3-UNC119-RP2 GTPase cycle targets myristoylated NPHP3 to the primary cilium." Wright K.J., Baye L.M., Olivier-Mason A., Mukhopadhyay S., Sang L., Kwong M., Wang W., Pretorius P.R., Sheffield V.C., Sengupta P., Slusarski D.C., Jackson P.K. Genes Dev. 25:2347-2360(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, LIPID-BINDING, SUBCELLULAR LOCATION, INTERACTION WITH NPHP3; CYS1 AND C5ORF30.
[13]	"UNC119 is required for G protein trafficking in sensory neurons." Zhang H., Constantine R., Vorobiev S., Chen Y., Seetharaman J., Huang Y.J., Xiao R., Montelione G.T., Gerstner C.D., Davis M.W., Inana G., Whitby F.G., Jorgensen E.M., Hill C.P., Tong L., Baehr W. Nat. Neurosci. 14:874-880(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS) OF 56-240 IN COMPLEX WITH LAURYLATED GNAT1, FUNCTION, INTERACTION WITH GNAT1.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U40998 mRNA. Translation: AAC50360.1.
AF028788 mRNA. Translation: AAD01875.1.
AF028789 mRNA. Translation: AAD01876.1.
AF125998, AF125997 Genomic DNA. Translation: AAD31422.1.
AK292329 mRNA. Translation: BAF85018.1.
AB593014 mRNA. Translation: BAJ83969.1.
AC005726 Genomic DNA. No translation available.
CH471159 Genomic DNA. Translation: EAW51095.1.
BC027176 mRNA. Translation: AAH27176.1.

IPI

IPI00013262.
IPI00220005.

RefSeq

NP_005139.1. NM_005148.3.
NP_473376.1. NM_054035.2.

UniGene

Hs.410455.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3GQQ	X-ray	1.95	A/B/C/D/E/F	56-240	[»]
3RBQ	X-ray	2.00	A/B/C/D/E/F	56-240	[»]
4GOJ	X-ray	2.10	C/D	1-240	[»]
4GOK	X-ray	2.60	C/G	1-240	[»]

ProteinModelPortal

Q13432.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13432. 73 interactions.

MINT

MINT-1372196.

STRING

9606.ENSP00000337040.

PTM databases

PhosphoSite

Q13432.

Polymorphism databases

DMDM

2498854.

Proteomic databases

PaxDb

Q13432.

PRIDE

Q13432.

Protocols and materials databases

DNASU

9094.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000301032; ENSP00000301032; ENSG00000109103.
ENST00000335765; ENSP00000337040; ENSG00000109103.

GeneID

9094.

KEGG

hsa:9094.

UCSC

uc002hbk.2. human.

Organism-specific databases

CTD

9094.

GeneCards

GC17M026873.

HGNC

HGNC:12565. UNC119.

HPA

HPA041912.

MIM

604011. gene.

neXtProt

NX_Q13432.

Orphanet

1872. Cone rod dystrophy.
228000. Idiopathic CD4 lymphocytopenia.

PharmGKB

PA37202.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG305476.

HOGENOM

HOG000258286.

HOVERGEN

HBG108625.

InParanoid

Q13432.

OMA

YKIDFIR.

OrthoDB

EOG441QCD.

PhylomeDB

Q13432.

Gene expression databases

ArrayExpress

Q13432.

Bgee

Q13432.

CleanEx

HS_UNC119.

Genevestigator

Q13432.

GermOnline

ENSG00000109103. Homo sapiens.

Family and domain databases

Gene3D

2.70.50.40. 1 hit.

InterPro

IPR008015. GMP_PDE_delta.
IPR014756. Ig_E-set.
[Graphical view]

Pfam

PF05351. GMP_PDE_delta. 1 hit.
[Graphical view]

SUPFAM

SSF81296. Ig_E-set. 1 hit.

ProtoNet

Search...

Other

ChiTaRS

UNC119. human.

EvolutionaryTrace

Q13432.

GenomeRNAi

9094.

NextBio

34075.

SOURCE

Search...

Entry information

Entry name

U119A_HUMAN

Accession

Primary (citable) accession number: Q13432
Secondary accession number(s): A8K8G4, F1T095, O95126

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 103 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.