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Q6VY07 (PACS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 98. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Phosphofurin acidic cluster sorting protein 1

Short name=PACS-1
Gene names
Name:PACS1
Synonyms:KIAA1175
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length963 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Coat protein that is involved in the localization of trans-Golgi network (TGN) membrane proteins that contain acidic cluster sorting motifs. Controls the endosome-to-Golgi trafficking of furin and mannose-6-phosphate receptor by connecting the acidic-cluster-containing cytoplasmic domain of these molecules with the adapter-protein complex-1 (AP-1) of endosomal clathrin-coated membrane pits. Involved in HIV-1 nef-mediated removal of MHC-I from the cell surface to the TGN. Ref.5

Subunit structure

Interacts with HIV-1 Nef. Associates with AP-1 and AP-3 but not with AP-2 complexes. Interacts with NPHP1; the interaction is dependent of NPHP1 phosphorylation by CK2. Ref.6 Ref.7 Ref.8 Ref.10

Subcellular location

Golgi apparatustrans-Golgi network By similarity. Note: Localizes in the perinuclear region, probably the TGN By similarity.

Involvement in disease

Mental retardation, autosomal dominant 17 (MRD17) [MIM:615009]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD17 patients have intellectual disability in combination with distinct craniofacial features and genital abnormalities.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.17

Sequence similarities

Belongs to the PACS family.

Sequence caution

The sequence AAH09936.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence BAB71164.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q6VY07-1)

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: Q6VY07-2)

The sequence of this isoform differs from the canonical sequence as follows:
     917-963: AKQQQTMLRV...VGLFSGSKAT → SPSLGPSLGP...SQKFLHRTSF
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.13
Chain2 – 963962Phosphofurin acidic cluster sorting protein 1
PRO_0000058171

Regions

Region168 – 1758Involved in binding to AP-1
Coiled coil353 – 37725 Potential
Compositional bias5 – 4440Gly-rich
Compositional bias35 – 406Poly-Gln
Compositional bias55 – 8430Ser-rich
Compositional bias62 – 654Poly-Ala
Compositional bias112 – 1154Poly-Ser
Compositional bias279 – 2835Poly-Glu

Amino acid modifications

Modified residue21N-acetylalanine Ref.13
Modified residue3791Phosphoserine Ref.12
Modified residue4301Phosphoserine Ref.12
Modified residue5041Phosphothreonine Ref.12
Modified residue5291Phosphoserine Ref.12
Modified residue5311Phosphoserine Ref.16
Modified residue5341Phosphoserine Ref.12

Natural variations

Alternative sequence917 – 96347AKQQQ…GSKAT → SPSLGPSLGPDPSSQPGFPP AGSFPPCHLPLTNPGSEPLI PDRPCSQEWLRTQGPSPALC TPQPGHLRPTAPLELFSCPL TPSQKFLHRTSF in isoform 2.
VSP_011557
Natural variant2031R → W in MRD17. Ref.17
VAR_069534
Natural variant3021F → L.
Corresponds to variant rs12798852 [ dbSNP | Ensembl ].
VAR_053797

Experimental info

Sequence conflict171 – 22050Missing in BAC04831. Ref.2
Sequence conflict6491K → M in BAA91491. Ref.2
Sequence conflict7711P → S in BAC04831. Ref.2
Sequence conflict8031S → N in AAQ67682. Ref.1
Sequence conflict8821K → L in AAQ67682. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified September 13, 2004. Version 2.
Checksum: 0F6B2CA24F7CD567

FASTA963104,898
        10         20         30         40         50         60 
MAERGGAGGG PGGAGGGSGQ RGSGVAQSPQ QPPPQQQQQQ PPQQPTPPKL AQATSSSSST 

        70         80         90        100        110        120 
SAAAASSSSS STSTSMAVAV ASGSAPPGGP GPGRTPAPVQ MNLYATWEVD RSSSSCVPRL 

       130        140        150        160        170        180 
FSLTLKKLVM LKEMDKDLNS VVIAVKLQGS KRILRSNEIV LPASGLVETE LQLTFSLQYP 

       190        200        210        220        230        240 
HFLKRDANKL QIMLQRRKRY KNRTILGYKT LAVGLINMAE VMQHPNEGAL VLGLHSNVKD 

       250        260        270        280        290        300 
VSVPVAEIKI YSLSSQPIDH EGIKSKLSDR SPDIDNYSEE EEESFSSEQE GSDDPLHGQD 

       310        320        330        340        350        360 
LFYEDEDLRK VKKTRRKLTS TSAITRQPNI KQKFVALLKR FKVSDEVGFG LEHVSREQIR 

       370        380        390        400        410        420 
EVEEDLDELY DSLEMYNPSD SGPEMEETES ILSTPKPKLK PFFEGMSQSS SQTEIGSLNS 

       430        440        450        460        470        480 
KGSLGKDTTS PMELAALEKI KSTWIKNQDD SLTETDTLEI TDQDMFGDAS TSLVVPEKVK 

       490        500        510        520        530        540 
TPMKSSKTDL QGSASPSKVE GVHTPRQKRS TPLKERQLSK PLSERTNSSD SERSPDLGHS 

       550        560        570        580        590        600 
TQIPRKVVYD QLNQILVSDA ALPENVILVN TTDWQGQYVA ELLQDQRKPV VCTCSTVEVQ 

       610        620        630        640        650        660 
AVLSALLTRI QRYCNCNSSM PRPVKVAAVG GQSYLSSILR FFVKSLANKT SDWLGYMRFL 

       670        680        690        700        710        720 
IIPLGSHPVA KYLGSVDSKY SSSFLDSGWR DLFSRSEPPV SEQLDVAGRV MQYVNGAATT 

       730        740        750        760        770        780 
HQLPVAEAML TCRHKFPDED SYQKFIPFIG VVKVGLVEDS PSTAGDGDDS PVVSLTVPST 

       790        800        810        820        830        840 
SPPSSSGLSR DATATPPSSP SMSSALAIVG SPNSPYGDVI GLQVDYWLGH PGERRREGDK 

       850        860        870        880        890        900 
RDASSKNTLK SVFRSVQVSR LPHSGEAQLS GTMAMTVVTK EKNKKVPTIF LSKKPREKEV 

       910        920        930        940        950        960 
DSKSQVIEGI SRLICSAKQQ QTMLRVSIDG VEWSDIKFFQ LAAQWPTHVK HFPVGLFSGS 


KAT 

« Hide

Isoform 2 [UniParc].

Checksum: 1BA7FD3DBFF57904
Show »

FASTA1,008109,342

References

« Hide 'large scale' references
[1]"Human PACS-1, a endosome-TGN sorting connector."
Wan L., Xiang Y., Simmen T., Thomas G.
Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"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. expand/collapse author list , 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 2).
Tissue: Embryo and Fetal brain.
[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: Brain, Kidney and Uterus.
[4]"Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain."
Hirosawa M., Nagase T., Ishikawa K., Kikuno R., Nomura N., Ohara O.
DNA Res. 6:329-336(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 323-963 (ISOFORM 1).
Tissue: Brain.
[5]"PACS-1 binding to adaptors is required for acidic cluster motif-mediated protein traffic."
Crump C.M., Xiang Y., Thomas L., Gu F., Austin C., Tooze S.A., Thomas G.
EMBO J. 20:2191-2201(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"HIV-1 Nef protein binds to the cellular protein PACS-1 to downregulate class I major histocompatibility complexes."
Piguet V., Wan L., Borel C., Mangasarian A., Demaurex N., Thomas G., Trono D.
Nat. Cell Biol. 2:163-167(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HIV-1 NEF.
[7]"HIV-1 Nef downregulates MHC-I by a PACS-1- and PI3K-regulated ARF6 endocytic pathway."
Blagoveshchenskaya A.D., Thomas L., Feliciangeli S.F., Hung C.-H., Thomas G.
Cell 111:853-866(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HIV-1 NEF.
[8]"Phosphorylation by casein kinase 2 induces PACS-1 binding of nephrocystin and targeting to cilia."
Schermer B., Hoepker K., Omran H., Ghenoiu C., Fliegauf M., Fekete A., Horvath J., Koettgen M., Hackl M., Zschiedrich S., Huber T.B., Kramer-Zucker A., Zentgraf H., Blaukat A., Walz G., Benzing T.
EMBO J. 24:4415-4424(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NPHP1.
[9]"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.
Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic kidney.
[10]"HIV-1 Nef binds PACS-2 to assemble a multikinase cascade that triggers major histocompatibility complex class I (MHC-I) down-regulation: analysis using short interfering RNA and knock-out mice."
Atkins K.M., Thomas L., Youker R.T., Harriff M.J., Pissani F., You H., Thomas G.
J. Biol. Chem. 283:11772-11784(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HIV-1 NEF.
[11]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-379; SER-430; THR-504; SER-529 AND SER-534, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[13]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[14]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[15]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[16]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-531, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]"Recurrent de novo mutations in PACS1 cause defective cranial-neural-crest migration and define a recognizable intellectual-disability syndrome."
Schuurs-Hoeijmakers J.H., Oh E.C., Vissers L.E., Swinkels M.E., Gilissen C., Willemsen M.A., Holvoet M., Steehouwer M., Veltman J.A., de Vries B.B., van Bokhoven H., de Brouwer A.P., Katsanis N., Devriendt K., Brunner H.G.
Am. J. Hum. Genet. 91:1122-1127(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MRD17 TRP-203.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY320283 mRNA. Translation: AAQ67682.1.
AK001071 mRNA. Translation: BAA91491.1.
AK056361 mRNA. Translation: BAB71164.1. Different initiation.
AK096644 mRNA. Translation: BAC04831.1.
BC003173 mRNA. Translation: AAH03173.1.
BC010096 mRNA. Translation: AAH10096.1.
BC009936 mRNA. Translation: AAH09936.1. Different initiation.
BC052577 mRNA. Translation: AAH52577.1.
BC055288 mRNA. Translation: AAH55288.1.
AB033001 mRNA. Translation: BAA86489.1.
RefSeqNP_060496.2. NM_018026.3.
UniGeneHs.644326.

3D structure databases

ProteinModelPortalQ6VY07.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120816. 6 interactions.
IntActQ6VY07. 8 interactions.
MINTMINT-3372090.

PTM databases

PhosphoSiteQ6VY07.

Polymorphism databases

DMDM52000804.

Proteomic databases

PaxDbQ6VY07.
PRIDEQ6VY07.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000320580; ENSP00000316454; ENSG00000175115. [Q6VY07-1]
GeneID55690.
KEGGhsa:55690.
UCSCuc001oha.2. human. [Q6VY07-1]

Organism-specific databases

CTD55690.
GeneCardsGC11P065837.
HGNCHGNC:30032. PACS1.
HPAHPA038914.
MIM607492. gene.
615009. phenotype.
neXtProtNX_Q6VY07.
Orphanet329224. Intellectual deficit - craniofacial dysmorphism - cryptorchidism.
PharmGKBPA134989529.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG279176.
HOVERGENHBG053488.
InParanoidQ6VY07.
OMATPAPVQM.
OrthoDBEOG7VHSX0.
PhylomeDBQ6VY07.
TreeFamTF314240.

Enzyme and pathway databases

ReactomeREACT_116125. Disease.

Gene expression databases

ArrayExpressQ6VY07.
BgeeQ6VY07.
GenevestigatorQ6VY07.

Family and domain databases

InterProIPR019381. Phosphofurin_acidic_CS-1.
[Graphical view]
PfamPF10254. Pacs-1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPACS1. human.
GeneWikiPACS1.
GenomeRNAi55690.
NextBio60497.
PROQ6VY07.
SOURCESearch...

Entry information

Entry namePACS1_HUMAN
AccessionPrimary (citable) accession number: Q6VY07
Secondary accession number(s): Q6PJY6 expand/collapse secondary AC list , Q6PKB6, Q7Z590, Q7Z5W4, Q8N8K6, Q96MW0, Q9NW92, Q9ULP5
Entry history
Integrated into UniProtKB/Swiss-Prot: September 13, 2004
Last sequence update: September 13, 2004
Last modified: April 16, 2014
This is version 98 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM