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Protein

ADP-ribosylation factor-like protein 4C

Gene

ARL4C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Small GTP-binding protein which cycles between an inactive GDP-bound and an active GTP-bound form, and the rate of cycling is regulated by guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP). GTP-binding protein that does not act as an allosteric activator of the cholera toxin catalytic subunit. May be involved in transport between a perinuclear compartment and the plasma membrane, apparently linked to the ABCA1-mediated cholesterol secretion pathway. Recruits CYTH1, CYTH2, CYTH3 and CYTH4 to the plasma membrane in the GDP-bound form. Regulates the microtubule-dependent intracellular vesicular transport from early endosome to recycling endosome process.3 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi20 – 278GTPBy similarity
Nucleotide bindingi68 – 725GTPBy similarity
Nucleotide bindingi127 – 1304GTPBy similarity

GO - Molecular functioni

  • alpha-tubulin binding Source: UniProtKB
  • GTPase activity Source: ProtInc
  • GTP binding Source: UniProtKB-KW

GO - Biological processi

  • endocytic recycling Source: UniProtKB
  • small GTPase mediated signal transduction Source: InterPro
Complete GO annotation...

Keywords - Biological processi

Transport

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
ADP-ribosylation factor-like protein 4C
Alternative name(s):
ADP-ribosylation factor-like protein 7
ADP-ribosylation factor-like protein LAK
Gene namesi
Name:ARL4C
Synonyms:ARL7
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:698. ARL4C.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • filopodium Source: UniProtKB-SubCell
  • nucleus Source: ProtInc
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi2 – 21G → A: Cytoplasmic localization. 2 Publications
Mutagenesisi27 – 271T → N: Does not interact with alpha tubulin. 1 Publication
Mutagenesisi34 – 341K → N: Cytoplasmic localization. Increases GDP-form. 1 Publication
Mutagenesisi72 – 721Q → L: Does not interact with alpha tubulin. Activates transferrin transport from early endosome to recycling endosome. 1 Publication

Organism-specific databases

PharmGKBiPA24991.

Polymorphism and mutation databases

BioMutaiARL4C.
DMDMi3913085.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedSequence analysis
Chaini2 – 192191ADP-ribosylation factor-like protein 4CPRO_0000207462Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycineSequence analysis

Keywords - PTMi

Lipoprotein, Myristate

Proteomic databases

EPDiP56559.
MaxQBiP56559.
PaxDbiP56559.
PeptideAtlasiP56559.
PRIDEiP56559.

PTM databases

iPTMnetiP56559.
PhosphoSiteiP56559.

Expressioni

Tissue specificityi

Expressed in several tumor cell lines (at protein level). Expressed in lung, brain, leukocytes and placenta.1 Publication

Inductioni

By liver X-receptor/retinoid X receptor agonists or cholesterol loading.1 Publication

Gene expression databases

BgeeiP56559.
CleanExiHS_ARL4C.
ExpressionAtlasiP56559. baseline and differential.
GenevisibleiP56559. HS.

Organism-specific databases

HPAiHPA028927.

Interactioni

Subunit structurei

Interacts with CYTH2. Interacts with alpha tubulin; interaction is independent on the ARL4C GTP or GDP binding status.2 Publications

GO - Molecular functioni

  • alpha-tubulin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115427. 21 interactions.
IntActiP56559. 1 interaction.
MINTiMINT-2867949.
STRINGi9606.ENSP00000375057.

Structurei

3D structure databases

ProteinModelPortaliP56559.
SMRiP56559. Positions 16-175.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the small GTPase superfamily. Arf family.Curated

Phylogenomic databases

eggNOGiKOG0070. Eukaryota.
COG1100. LUCA.
GeneTreeiENSGT00840000129731.
HOGENOMiHOG000163691.
HOVERGENiHBG002073.
InParanoidiP56559.
KOiK07945.
OMAiAYHIQPA.
OrthoDBiEOG7H793N.
PhylomeDBiP56559.
TreeFamiTF105464.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR024156. Small_GTPase_ARF.
IPR006689. Small_GTPase_ARF/SAR.
[Graphical view]
PfamiPF00025. Arf. 1 hit.
[Graphical view]
PRINTSiPR00328. SAR1GTPBP.
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51417. ARF. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P56559-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGNISSNISA FQSLHIVMLG LDSAGKTTVL YRLKFNEFVN TVPTIGFNTE
60 70 80 90 100
KIKLSNGTAK GISCHFWDVG GQEKLRPLWK SYSRCTDGII YVVDSVDVDR
110 120 130 140 150
LEEAKTELHK VTKFAENQGT PLLVIANKQD LPKSLPVAEI EKQLALHELI
160 170 180 190
PATTYHVQPA CAIIGEGLTE GMDKLYEMIL KRRKSLKQKK KR
Length:192
Mass (Da):21,487
Last modified:December 15, 1998 - v1
Checksum:i389BD49CF9E6D10D
GO
Isoform 2 (identifier: P56559-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     192-192: R → RTGDLRSCEV

Show »
Length:201
Mass (Da):22,448
Checksum:iD296525CACD29DA6
GO

Sequence cautioni

The sequence BAA75473.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei192 – 1921R → RTGDLRSCEV in isoform 2. 1 PublicationVSP_055120

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y17804 mRNA. Translation: CAB44355.1.
AJ579850 mRNA. Translation: CAE30322.1.
AJ579851 mRNA. Translation: CAE30323.1.
AF493892 mRNA. Translation: AAM12606.1.
BT019378 mRNA. Translation: AAV38185.1.
BT019379 mRNA. Translation: AAV38186.1.
AK314119 mRNA. Translation: BAG36810.1.
AC105145 Genomic DNA. No translation available.
AC097713 Genomic DNA. Translation: AAX93114.1.
CH471063 Genomic DNA. Translation: EAW71073.1.
BC001051 mRNA. No translation available.
BC089043 mRNA. Translation: AAH89043.1.
AB016811 mRNA. Translation: BAA75473.1. Different initiation.
CCDSiCCDS2512.1. [P56559-1]
CCDS63169.1. [P56559-2]
RefSeqiNP_001269360.1. NM_001282431.1. [P56559-2]
NP_005728.2. NM_005737.3. [P56559-1]
UniGeneiHs.111554.
Hs.730678.

Genome annotation databases

EnsembliENST00000339728; ENSP00000339754; ENSG00000188042. [P56559-2]
ENST00000390645; ENSP00000375057; ENSG00000188042. [P56559-1]
GeneIDi10123.
KEGGihsa:10123.
UCSCiuc002vvm.6. human. [P56559-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y17804 mRNA. Translation: CAB44355.1.
AJ579850 mRNA. Translation: CAE30322.1.
AJ579851 mRNA. Translation: CAE30323.1.
AF493892 mRNA. Translation: AAM12606.1.
BT019378 mRNA. Translation: AAV38185.1.
BT019379 mRNA. Translation: AAV38186.1.
AK314119 mRNA. Translation: BAG36810.1.
AC105145 Genomic DNA. No translation available.
AC097713 Genomic DNA. Translation: AAX93114.1.
CH471063 Genomic DNA. Translation: EAW71073.1.
BC001051 mRNA. No translation available.
BC089043 mRNA. Translation: AAH89043.1.
AB016811 mRNA. Translation: BAA75473.1. Different initiation.
CCDSiCCDS2512.1. [P56559-1]
CCDS63169.1. [P56559-2]
RefSeqiNP_001269360.1. NM_001282431.1. [P56559-2]
NP_005728.2. NM_005737.3. [P56559-1]
UniGeneiHs.111554.
Hs.730678.

3D structure databases

ProteinModelPortaliP56559.
SMRiP56559. Positions 16-175.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115427. 21 interactions.
IntActiP56559. 1 interaction.
MINTiMINT-2867949.
STRINGi9606.ENSP00000375057.

PTM databases

iPTMnetiP56559.
PhosphoSiteiP56559.

Polymorphism and mutation databases

BioMutaiARL4C.
DMDMi3913085.

Proteomic databases

EPDiP56559.
MaxQBiP56559.
PaxDbiP56559.
PeptideAtlasiP56559.
PRIDEiP56559.

Protocols and materials databases

DNASUi10123.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000339728; ENSP00000339754; ENSG00000188042. [P56559-2]
ENST00000390645; ENSP00000375057; ENSG00000188042. [P56559-1]
GeneIDi10123.
KEGGihsa:10123.
UCSCiuc002vvm.6. human. [P56559-1]

Organism-specific databases

CTDi10123.
GeneCardsiARL4C.
HGNCiHGNC:698. ARL4C.
HPAiHPA028927.
MIMi604787. gene.
neXtProtiNX_P56559.
PharmGKBiPA24991.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0070. Eukaryota.
COG1100. LUCA.
GeneTreeiENSGT00840000129731.
HOGENOMiHOG000163691.
HOVERGENiHBG002073.
InParanoidiP56559.
KOiK07945.
OMAiAYHIQPA.
OrthoDBiEOG7H793N.
PhylomeDBiP56559.
TreeFamiTF105464.

Miscellaneous databases

ChiTaRSiARL4C. human.
GenomeRNAii10123.
PROiP56559.
SOURCEiSearch...

Gene expression databases

BgeeiP56559.
CleanExiHS_ARL4C.
ExpressionAtlasiP56559. baseline and differential.
GenevisibleiP56559. HS.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR024156. Small_GTPase_ARF.
IPR006689. Small_GTPase_ARF/SAR.
[Graphical view]
PfamiPF00025. Arf. 1 hit.
[Graphical view]
PRINTSiPR00328. SAR1GTPBP.
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51417. ARF. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "ADP-ribosylation factor (ARF)-like 4, 6, and 7 represent a subgroup of the ARF family characterization by rapid nucleotide exchange and a nuclear localization signal."
    Jacobs S., Schilf C., Fliegert F., Koling S., Weber Y., Schurmann A., Joost H.-G.
    FEBS Lett. 456:384-388(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Testis.
  2. "ADP-ribosylation factor (ARF)-like 7 (ARL7) is induced by cholesterol loading and participates in apolipoprotein AI-dependent cholesterol export."
    Engel T., Lueken A., Bode G., Hobohm U., Lorkowski S., Schlueter B., Rust S., Cullen P., Pech M., Assmann G., Seedorf U.
    FEBS Lett. 566:241-246(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, INDUCTION, MUTAGENESIS OF GLY-2, SUBCELLULAR LOCATION.
  3. "cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
    Puhl H.L. III, Ikeda S.R., Aronstam R.S.
    Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Brain.
  4. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
    Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
    Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  5. "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 1).
    Tissue: Brain.
  6. "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.
    , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
    Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. 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 1).
    Tissue: Kidney and Ovary.
  9. "ADP-ribosylation factor-like protein LAK."
    Abe Y., Nezu K., Ueda N.
    Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 13-192 (ISOFORM 1).
  10. "The Arl4 family of small G proteins can recruit the cytohesin Arf6 exchange factors to the plasma membrane."
    Hofmann I., Thompson A., Sanderson C.M., Munro S.
    Curr. Biol. 17:711-716(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH CYTH2, SUBCELLULAR LOCATION, MUTAGENESIS OF GLY-2 AND LYS-34.
  11. "ADP-ribosylation factor like 7 (ARL7) interacts with alpha-tubulin and modulates intracellular vesicular transport."
    Wei S.M., Xie C.G., Abe Y., Cai J.T.
    Biochem. Biophys. Res. Commun. 384:352-356(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH ALPHA TUBULIN, MUTAGENESIS OF THR-27 AND GLN-72, TISSUE SPECIFICITY.

Entry informationi

Entry nameiARL4C_HUMAN
AccessioniPrimary (citable) accession number: P56559
Secondary accession number(s): Q4A519
, Q53R10, Q9BVN1, Q9UQ34
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: December 15, 1998
Last modified: July 6, 2016
This is version 151 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.