Q6VY07 (PACS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Phosphofurin acidic cluster sorting protein 1
Short name=PACS-1

Gene names

Name:	PACS1
Synonyms:	KIAA1175

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	963 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.9 Ref.12
Subcellular location	Golgi apparatus › trans-Golgi network By similarity. Note: Localizes in the perinuclear region, probably the TGN By similarity.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.8 Ref.10 Ref.11 Ref.13 Ref.14
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.

Ontologies

Keywords
Biological process	Host-virus interaction
Cellular component	Golgi apparatus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW regulation of defense response to virus by virus Traceable author statement. Source: Reactome viral reproduction Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	protein binding Inferred from physical interaction Ref.6. Source: UniProtKB
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed
	Chain	2 – 963	962	Phosphofurin acidic cluster sorting protein 1		PRO_0000058171
Regions
	Region	168 – 175	8	Involved in binding to AP-1
	Coiled coil	353 – 377	25	Potential
	Compositional bias	5 – 44	40	Gly-rich
	Compositional bias	35 – 40	6	Poly-Gln
	Compositional bias	55 – 84	30	Ser-rich
	Compositional bias	62 – 65	4	Poly-Ala
	Compositional bias	112 – 115	4	Poly-Ser
	Compositional bias	279 – 283	5	Poly-Glu
Amino acid modifications
	Modified residue	2	1	N-acetylalanine Ref.14
	Modified residue	28	1	Phosphoserine By similarity
	Modified residue	46	1	Phosphothreonine Ref.8 Ref.14
	Modified residue	251	1	Phosphotyrosine Ref.10
	Modified residue	379	1	Phosphoserine Ref.13
	Modified residue	381	1	Phosphoserine Ref.13
	Modified residue	407	1	Phosphoserine Ref.11
	Modified residue	410	1	Phosphoserine Ref.11
	Modified residue	429	1	Phosphothreonine By similarity
	Modified residue	430	1	Phosphoserine Ref.13
	Modified residue	495	1	Phosphoserine Ref.13
	Modified residue	504	1	Phosphothreonine Ref.13
	Modified residue	528	1	Phosphoserine Ref.13
	Modified residue	529	1	Phosphoserine Ref.13
	Modified residue	534	1	Phosphoserine Ref.13
Natural variations
	Alternative sequence	917 – 963	47	AKQQQ…GSKAT → SPSLGPSLGPDPSSQPGFPP AGSFPPCHLPLTNPGSEPLI PDRPCSQEWLRTQGPSPALC TPQPGHLRPTAPLELFSCPL TPSQKFLHRTSF in isoform 2.		VSP_011557
	Natural variant	302	1	F → L. Corresponds to variant rs12798852 [ dbSNP | Ensembl ].		VAR_053797
Experimental info
	Sequence conflict	171 – 220	50	Missing in BAC04831. Ref.2
	Sequence conflict	649	1	K → M in BAA91491. Ref.2
	Sequence conflict	771	1	P → S in BAC04831. Ref.2
	Sequence conflict	803	1	S → N in AAQ67682. Ref.1
	Sequence conflict	882	1	K → L in AAQ67682. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 13, 2004. Version 2. Checksum: 0F6B2CA24F7CD567	FASTA	963	104,898
	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
	Isoform 2 [UniParc]. Checksum: 1BA7FD3DBFF57904	FASTA	1,008	109,342
	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 SRLICSSPSL GPSLGPDPSS QPGFPPAGSF PPCHLPLTNP GSEPLIPDRP 970 980 990 1000 CSQEWLRTQG PSPALCTPQP GHLRPTAPLE LFSCPLTPSQ KFLHRTSF

References

	« Hide 'large scale' referencesShow '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. , 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: 14702039] [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: 15489334] [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: 10574461] [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: 11331585] [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: 10707087] [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: 12526811] [Abstract] Cited for: INTERACTION WITH HIV-1 NEF.
[8]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-46, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"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: 16308564] [Abstract] Cited for: INTERACTION WITH NPHP1.
[10]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-251, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[11]	"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: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407 AND SER-410, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[12]	"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: 18296443] [Abstract] Cited for: INTERACTION WITH HIV-1 NEF.
[13]	"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-379; SER-381; SER-430; SER-495; THR-504; SER-528; SER-529 AND SER-534, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"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: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-46, MASS SPECTROMETRY. Tissue: Embryonic kidney.
+	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.
IPI	IPI00376229. IPI00456262.
RefSeq	NP_060496.2. NM_018026.3.
UniGene	Hs.644326.
3D structure databases
ProteinModelPortal	Q6VY07.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6VY07. 2 interactions.
MINT	MINT-3372090.
STRING	Q6VY07.
PTM databases
PhosphoSite	Q6VY07.
Polymorphism databases
DMDM	52000804.
Proteomic databases
PRIDE	Q6VY07.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000320580; ENSP00000316454; ENSG00000175115.
GeneID	55690.
KEGG	hsa:55690.
UCSC	uc001oha.1. human.
Organism-specific databases
CTD	55690.
GeneCards	GC11P065837.
H-InvDB	HIX0009824.
HGNC	HGNC:30032. PACS1.
HPA	HPA038914.
MIM	607492. gene.
neXtProt	NX_Q6VY07.
PharmGKB	PA134989529.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG16580.
HOVERGEN	HBG053488.
InParanoid	Q6VY07.
OMA	KSTWIKN.
OrthoDB	EOG4RV2QT.
PhylomeDB	Q6VY07.
Enzyme and pathway databases
Reactome	REACT_6185. HIV Infection.
Gene expression databases
ArrayExpress	Q6VY07.
Bgee	Q6VY07.
Genevestigator	Q6VY07.
GermOnline	ENSG00000175115. Homo sapiens.
Family and domain databases
InterPro	IPR019381. Phosphofurin_acidic_CS-1. [Graphical view]
Pfam	PF10254. Pacs-1. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	60497.
SOURCE	Search...

Entry information

Entry name

PACS1_HUMAN

Accession

Primary (citable) accession number: Q6VY07
Secondary accession number(s): Q6PJY6 , 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:	January 25, 2012
This is version 78 of the entry and version 2 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.