Q9UBP9 (GULP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
PTB domain-containing engulfment adapter protein 1

Alternative name(s):
Cell death protein 6 homolog
PTB domain adapter protein CED-6
Protein GULP

Gene names

Name:	GULP1
Synonyms:	CED6, GULP

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

General annotation (Comments)

Function	May function as an adapter protein. Required for efficient phagocytosis of apoptotic cells. Modulates cellular glycosphingolipid and cholesterol transport. May play a role in the internalization and endosomal trafficking of various LRP1 ligands, such as PSAP. Increases cellular levels of GTP-bound ARF6. Ref.1 Ref.2 Ref.8 Ref.10
Subunit structure	Homodimer. Interacts with clathrin. Interacts with GDP-bound ARF6, but not with GTP-bound ARF6. Part of a complex composed of GULP1, ACAP1 and ARF6. Interacts with ACAP1, LRP1, MEGF10 and STAB2. Ref.7 Ref.9 Ref.10 Ref.11 Ref.12
Subcellular location	Cytoplasm. Note: May associate with the cytoplasmic side of the plasma membrane and early endosomes. Ref.8
Tissue specificity	Widely expressed. Detected in macrophages, pancreas, kidney, skeletal muscle, heart, colon, intestine, lung, placenta and ovary. Ref.2
Sequence similarities	Belongs to the ced-6 family. Contains 1 PID domain.

Ontologies

Keywords
Biological process	Apoptosis Lipid transport Phagocytosis Transport
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Domain	Coiled coil
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Traceable author statement Ref.2. Source: ProtInc lipid transport Inferred from electronic annotation. Source: UniProtKB-KW phagocytosis, engulfment Inferred from direct assay PubMed 11729193. Source: MGI
Cellular_component	cytoplasm Inferred from direct assay. Source: HPA
Molecular_function	signal transducer activity Traceable author statement Ref.2Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9UBP9-1)

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: Q9UBP9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     134-167: AEEITLTIGQAFDLAYRKFLESGGKDVETRKQIA → VSIPDVVGWFVLFYKPGIVLLLALAKYLKMNNFL
     168-304: Missing.

Isoform 3 (identifier: Q9UBP9-3)

The sequence of this isoform differs from the canonical sequence as follows:
     31-133: Missing.

Note: No experimental confirmation available.

Isoform 4 (identifier: Q9UBP9-4)

The sequence of this isoform differs from the canonical sequence as follows:
     282-304: EGFKMGLTLEGTVFCLDPLDSRC → RQRWRGSKWD

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 304	304	PTB domain-containing engulfment adapter protein 1		PRO_0000296679
Regions
	Domain	21 – 176	156	PID
	Coiled coil	158 – 202	45	Potential
Amino acid modifications
	Modified residue	223	1	Phosphoserine Ref.13
Natural variations
	Alternative sequence	31 – 133	103	Missing in isoform 3.		VSP_044703
	Alternative sequence	134 – 167	34	AEEIT…RKQIA → VSIPDVVGWFVLFYKPGIVL LLALAKYLKMNNFL in isoform 2.		VSP_027250
	Alternative sequence	168 – 304	137	Missing in isoform 2.		VSP_027251
	Alternative sequence	282 – 304	23	EGFKM…LDSRC → RQRWRGSKWD in isoform 4.		VSP_045540
Experimental info
	Mutagenesis	176	1	L → P: Loss of dimerization; when associated with P-183. Ref.7
	Mutagenesis	183	1	L → P: Loss of dimerization; when associated with P-176. Ref.7
	Sequence conflict	292	1	G → S in BAG60802. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 6FCDE040073DBE8B	FASTA	304	34,490
	10 20 30 40 50 60 MNRAFSRKKD KTWMHTPEAL SKHFIPYNAK FLGSTEVEQP KGTEVVRDAV RKLKFARHIK 70 80 90 100 110 120 KSEGQKIPKV ELQISIYGVK ILEPKTKEVQ HNCQLHRISF CADDKTDKRI FTFICKDSES 130 140 150 160 170 180 NKHLCYVFDS EKCAEEITLT IGQAFDLAYR KFLESGGKDV ETRKQIAGLQ KRIQDLETEN 190 200 210 220 230 240 MELKNKVQDL ENQLRITQVS APPAGSMTPK SPSTDIFDMI PFSPISHQSS MPTRNGTQPP 250 260 270 280 290 300 PVPSRSTEIK RDLFGAEPFD PFNCGAADFP PDIQSKLDEM QEGFKMGLTL EGTVFCLDPL DSRC
	Isoform 2 [UniParc]. Checksum: 6A33DC720CB9A2DE	FASTA	167	19,423
	10 20 30 40 50 60 MNRAFSRKKD KTWMHTPEAL SKHFIPYNAK FLGSTEVEQP KGTEVVRDAV RKLKFARHIK 70 80 90 100 110 120 KSEGQKIPKV ELQISIYGVK ILEPKTKEVQ HNCQLHRISF CADDKTDKRI FTFICKDSES 130 140 150 160 NKHLCYVFDS EKCVSIPDVV GWFVLFYKPG IVLLLALAKY LKMNNFL
	Isoform 3 [UniParc]. Checksum: 139143B94E5121C4	FASTA	201	22,567
	10 20 30 40 50 60 MNRAFSRKKD KTWMHTPEAL SKHFIPYNAK AEEITLTIGQ AFDLAYRKFL ESGGKDVETR 70 80 90 100 110 120 KQIAGLQKRI QDLETENMEL KNKVQDLENQ LRITQVSAPP AGSMTPKSPS TDIFDMIPFS 130 140 150 160 170 180 PISHQSSMPT RNGTQPPPVP SRSTEIKRDL FGAEPFDPFN CGAADFPPDI QSKLDEMQEG 190 200 FKMGLTLEGT VFCLDPLDSR C
	Isoform 4 [UniParc]. Checksum: 2736C095A6140AB5	FASTA	291	33,333
	10 20 30 40 50 60 MNRAFSRKKD KTWMHTPEAL SKHFIPYNAK FLGSTEVEQP KGTEVVRDAV RKLKFARHIK 70 80 90 100 110 120 KSEGQKIPKV ELQISIYGVK ILEPKTKEVQ HNCQLHRISF CADDKTDKRI FTFICKDSES 130 140 150 160 170 180 NKHLCYVFDS EKCAEEITLT IGQAFDLAYR KFLESGGKDV ETRKQIAGLQ KRIQDLETEN 190 200 210 220 230 240 MELKNKVQDL ENQLRITQVS APPAGSMTPK SPSTDIFDMI PFSPISHQSS MPTRNGTQPP 250 260 270 280 290 PVPSRSTEIK RDLFGAEPFD PFNCGAADFP PDIQSKLDEM QRQRWRGSKW D

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human CED-6 encodes a functional homologue of the Caenorhabditis elegans engulfment protein CED-6." Liu Q.A., Hengartner M.O. Curr. Biol. 9:1347-1350(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION.
[2]	"The human homologue of Caenorhabditis elegans CED-6 specifically promotes phagocytosis of apoptotic cells." Smits E., Van Criekinge W., Plaetinck G., Bogaert T. Curr. Biol. 9:1351-1354(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY.
[3]	"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; 3 AND 4). Tissue: Neuroblastoma and Trachea.
[4]	"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].
[5]	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].
[6]	"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 2). Tissue: Placenta.
[7]	"Identification and characterization of a dimerization domain in CED-6, an adapter protein involved in engulfment of apoptotic cells." Su H.P., Brugnera E., Van Criekinge W., Smits E., Hengartner M., Bogaert T., Ravichandran K.S. J. Biol. Chem. 275:9542-9549(2000) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT, MUTAGENESIS OF LEU-176 AND LEU-183.
[8]	"The lipoprotein receptor-related protein-1 (LRP) adapter protein GULP mediates trafficking of the LRP ligand prosaposin, leading to sphingolipid and free cholesterol accumulation in late endosomes and impaired efflux." Kiss R.S., Ma Z., Nakada-Tsukui K., Brugnera E., Vassiliou G., McBride H.M., Ravichandran K.S., Marcel Y.L. J. Biol. Chem. 281:12081-12092(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[9]	"Cooperation between engulfment receptors: the case of ABCA1 and MEGF10." Hamon Y., Trompier D., Ma Z., Venegas V., Pophillat M., Mignotte V., Zhou Z., Chimini G. PLoS ONE 1:E120-E120(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MEGF10.
[10]	"Regulation of Arf6 and ACAP1 signaling by the PTB-domain-containing adaptor protein GULP." Ma Z., Nie Z., Luo R., Casanova J.E., Ravichandran K.S. Curr. Biol. 17:722-727(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH ARF6 AND ACAP1, IDENTIFICATION IN A COMPLEX WITH ACAP1 AND ARF6.
[11]	"MEGF10 is a mammalian ortholog of CED-1 that interacts with clathrin assembly protein complex 2 medium chain and induces large vacuole formation." Suzuki E., Nakayama M. Exp. Cell Res. 313:3729-3742(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MEGF10.
[12]	"Requirement of adaptor protein GULP during stabilin-2-mediated cell corpse engulfment." Park S.Y., Kang K.B., Thapa N., Kim S.Y., Lee S.J., Kim I.S. J. Biol. Chem. 283:10593-10600(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH STAB2.
[13]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-223, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]	"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF200715 mRNA. Translation: AAF08006.1. AF191771 mRNA. Translation: AAF18975.1. AK055718 mRNA. No translation available. AK298626 mRNA. Translation: BAG60802.1. AK314498 mRNA. Translation: BAG37098.1. AC092598 Genomic DNA. Translation: AAX93242.1. AC125490 Genomic DNA. Translation: AAY24122.1. AC104131 Genomic DNA. No translation available. AC108493 Genomic DNA. No translation available. AC133606 Genomic DNA. No translation available. CH471058 Genomic DNA. Translation: EAX10913.1. CH471058 Genomic DNA. Translation: EAX10914.1. CH471058 Genomic DNA. Translation: EAX10915.1. CH471058 Genomic DNA. Translation: EAX10917.1. BC001103 mRNA. Translation: AAH01103.1.
IPI	IPI00008468. IPI00790010. IPI00910196. IPI00915753.
RefSeq	NP_001239597.1. NM_001252668.1. NP_001239598.1. NM_001252669.1. NP_057399.1. NM_016315.3.
UniGene	Hs.470887. Hs.712910.
3D structure databases
ProteinModelPortal	Q9UBP9.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UBP9. 3 interactions.
MINT	MINT-259085.
STRING	9606.ENSP00000352047.
PTM databases
PhosphoSite	Q9UBP9.
Polymorphism databases
DMDM	74720076.
Proteomic databases
PaxDb	Q9UBP9.
PRIDE	Q9UBP9.
Protocols and materials databases
DNASU	51454.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000359135; ENSP00000352047; ENSG00000144366. ENST00000409580; ENSP00000386289; ENSG00000144366. ENST00000409609; ENSP00000386867; ENSG00000144366. ENST00000409637; ENSP00000386402; ENSG00000144366. ENST00000409805; ENSP00000387171; ENSG00000144366. ENST00000409830; ENSP00000386732; ENSG00000144366. ENST00000409843; ENSP00000387144; ENSG00000144366. ENST00000410051; ENSP00000387013; ENSG00000144366.
GeneID	51454.
KEGG	hsa:51454.
UCSC	uc002uqc.4. human. uc002uqd.3. human. uc002uqf.3. human. uc010zfw.2. human.
Organism-specific databases
CTD	51454.
GeneCards	GC02P189156.
H-InvDB	HIX0022389.
HGNC	HGNC:18649. GULP1.
HPA	HPA020587.
MIM	608165. gene.
neXtProt	NX_Q9UBP9.
PharmGKB	PA134993283.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG314249.
HOGENOM	HOG000039986.
HOVERGEN	HBG056801.
InParanoid	Q9UBP9.
OMA	SNGCPPP.
OrthoDB	EOG4FR0S8.
PhylomeDB	Q9UBP9.
Enzyme and pathway databases
Pathway_Interaction_DB	arf6cyclingpathway. Arf6 signaling events.
Gene expression databases
ArrayExpress	Q9UBP9.
Bgee	Q9UBP9.
CleanEx	HS_GULP1.
Genevestigator	Q9UBP9.
Family and domain databases
Gene3D	2.30.29.30. 1 hit.
InterPro	IPR011993. PH_like_dom. IPR006020. PTyr_interaction_dom. [Graphical view]
Pfam	PF00640. PID. 1 hit. [Graphical view]
SMART	SM00462. PTB. 1 hit. [Graphical view]
PROSITE	PS01179. PID. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	GULP1. human.
GenomeRNAi	51454.
NextBio	55065.
SOURCE	Search...

Entry information

Entry name

GULP1_HUMAN

Accession

Primary (citable) accession number: Q9UBP9
Secondary accession number(s): B2RB51 , B4DQ40, B8ZZ72, D3DPH1, E9PB86, Q53PC1, Q53RF3, Q9BVL3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 24, 2007
Last sequence update:	May 1, 2000
Last modified:	May 29, 2013
This is version 89 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.