Q8N4B1 (SESQ1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sesquipedalian-1
Short name=Ses1

Alternative name(s):
27 kDa inositol polyphosphate phosphatase-interacting protein A
Short name=IPIP27A

Gene names

Name:

FAM109A

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

General annotation (Comments)

Function	Plays a role in endocytic trafficking. Required for receptor recycling from endosomes, both to the trans-Golgi network and the plasma membrane. Ref.5
Subunit structure	Forms homodimers and heterodimers with FAM109B. Interacts with OCRL and INPP5B. Ref.4 Ref.5
Subcellular location	Early endosome. Recycling endosome. Golgi apparatus › trans-Golgi network. Cytoplasmic vesicle › clathrin-coated vesicle. Note: Interaction with OCRL may be crucial for targeting to endosome and to the trans-Golgi network. Also found on macropinosomes. Not detected in late endosomes, nor in lysosomes. Ref.4 Ref.5
Domain	The F&H motif, an approximately 12-13 amino-acid sequence centered around Phe and His residues, is essential for binding to OCRL and INPP5B (Ref.6).
Miscellaneous	Was named after 'sesquipedalian', an unnecessarily long description of a simple thing (Ref.4).
Sequence similarities	Belongs to the sesquipedalian family. Contains 1 PH domain.

Ontologies

Keywords
Cellular component	Cytoplasmic vesicle Endosome Golgi apparatus
Coding sequence diversity	Alternative splicing
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	endosome organization Inferred from mutant phenotype Ref.5. Source: UniProtKB receptor recycling Inferred from mutant phenotype Ref.5. Source: UniProtKB retrograde transport, endosome to Golgi Inferred from mutant phenotype Ref.5. Source: UniProtKB
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell clathrin-coated vesicle Inferred from direct assay Ref.5. Source: UniProtKB early endosome Inferred from direct assay Ref.5. Source: UniProtKB recycling endosome Inferred from direct assay Ref.5. Source: UniProtKB trans-Golgi network Inferred from direct assay Ref.5. Source: UniProtKB
Molecular_function	phospholipid binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q8N4B1-1)

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: Q8N4B1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-123: Missing.
     124-138: EQQLAAVRGGGGMAL → MQKQRPREMNSLPGV

Note: No experimental confirmation available.

Isoform 3 (identifier: Q8N4B1-3)

The sequence of this isoform differs from the canonical sequence as follows:
     64-88: EGCTVELVEAAEEFAFAVRFAGTRA → VAVALWPRALSVSPWWLSQGSPDTP
     89-249: Missing.

Note: No experimental confirmation available.

Isoform 4 (identifier: Q8N4B1-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MAPGSPPGPAIATM
     81-249: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 249

249

Sesquipedalian-1

PRO_0000254572

Regions

Domain

17 – 113

97

PH

Motif

223 – 235

13

F&H

Compositional bias

139 – 223

85

Pro-rich

Natural variations

Alternative sequence

1 – 123

123

Missing in isoform 2.

VSP_021239

Alternative sequence

1

1

M → MAPGSPPGPAIATM in isoform 4.

VSP_044836

Alternative sequence

64 – 88

25

EGCTV…AGTRA → VAVALWPRALSVSPWWLSQG SPDTP in isoform 3.

VSP_021241

Alternative sequence

81 – 249

169

Missing in isoform 4.

VSP_044837

Alternative sequence

89 – 249

161

Missing in isoform 3.

VSP_021242

Alternative sequence

124 – 138

15

EQQLA…GGMAL → MQKQRPREMNSLPGV in isoform 2.

VSP_021240

Experimental info

Mutagenesis

224

1

F → A: Loss of OCRL-binding. Drastically reduces membrane targeting. Ref.4 Ref.5

Mutagenesis

228

1

H → A: Loss of OCRL-binding. Ref.4 Ref.5

Mutagenesis

234 – 235

2

EI → AA: Loss of OCRL-binding.

Secondary structure

1

.

.

.

.

249

Helix Strand Turn

Details...

Helix

224 – 231

8

Turn

232 – 234

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: 73410C946DA6113A	FASTA	249	27,215
	10 20 30 40 50 60 MKLNERSLAF YATCDAPVDN AGFLYKKGGR HAAYHRRWFV LRGNMLFYFE DAASREPVGV 70 80 90 100 110 120 IILEGCTVEL VEAAEEFAFA VRFAGTRART YVLAAESQDA MEGWVKALSR ASFDYLRLVV 130 140 150 160 170 180 RELEQQLAAV RGGGGMALPQ PQPQSLPLPP SLPSALAPVP SLPSAPAPVP ALPLPRRPSA 190 200 210 220 230 240 LPPKENGCAV WSTEATFRPG PEPPPPPPRR RASAPHGPLD MAPFARLHEC YGQEIRALRG QWLSSRVQP
	Isoform 2 [UniParc]. Checksum: 8AAF24512D83EDF9	FASTA	126	13,610
	10 20 30 40 50 60 MQKQRPREMN SLPGVPQPQP QSLPLPPSLP SALAPVPSLP SAPAPVPALP LPRRPSALPP 70 80 90 100 110 120 KENGCAVWST EATFRPGPEP PPPPPRRRAS APHGPLDMAP FARLHECYGQ EIRALRGQWL SSRVQP
	Isoform 3 [UniParc]. Checksum: A855A284B01643EF	FASTA	88	9,957
	10 20 30 40 50 60 MKLNERSLAF YATCDAPVDN AGFLYKKGGR HAAYHRRWFV LRGNMLFYFE DAASREPVGV 70 80 IILVAVALWP RALSVSPWWL SQGSPDTP
	Isoform 4 [UniParc]. Checksum: 55A361D87B86DA8C	FASTA	93	10,200
	10 20 30 40 50 60 MAPGSPPGPA IATMKLNERS LAFYATCDAP VDNAGFLYKK GGRHAAYHRR WFVLRGNMLF 70 80 90 YFEDAASREP VGVIILEGCT VELVEAAEEF AFA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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 2). Tissue: Prostate.
[2]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] (ISOFORMS 1; 3 AND 4). Tissue: Brain.
[4]	"Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1." Swan L.E., Tomasini L., Pirruccello M., Lunardi J., De Camilli P. Proc. Natl. Acad. Sci. U.S.A. 107:3511-3516(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH OCRL AND INPP5B, SUBCELLULAR LOCATION, F&H MOTIF, MUTAGENESIS OF PHE-224 AND HIS-228.
[5]	"The PH domain proteins IPIP27A and B link OCRL1 to receptor recycling in the endocytic pathway." Noakes C.J., Lee G., Lowe M. Mol. Biol. Cell 22:606-623(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH OCRL AND INPP5B, SUBUNIT, SUBCELLULAR LOCATION, MUTAGENESIS OF PHE-224; HIS-228 AND 234-GLU-ILE-235.
[6]	"Recognition of the F&H motif by the Lowe syndrome protein OCRL." Pirruccello M., Swan L.E., Folta-Stogniew E., De Camilli P. Nat. Struct. Mol. Biol. 18:789-795(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 223-235 IN COMPLEX WITH OCRL, F&H MOTIF.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AK056918 mRNA. Translation: BAB71310.1.
AC005805 Genomic DNA. No translation available.
BC014091 mRNA. Translation: AAH14091.1.
BC034809 mRNA. Translation: AAH34809.1.
CX758147 mRNA. No translation available.

IPI

IPI00171062.
IPI00789570.
IPI00789670.

RefSeq

NP_001171468.1. NM_001177997.1.
NP_653272.2. NM_144671.4.

UniGene

Hs.173088.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3QIS	X-ray	2.30	B	223-235	[»]

ProteinModelPortal

Q8N4B1.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000354461.

PTM databases

PhosphoSite

Q8N4B1.

Polymorphism databases

DMDM

74728832.

Proteomic databases

PaxDb

Q8N4B1.

PRIDE

Q8N4B1.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000392658; ENSP00000376426; ENSG00000198324.
ENST00000547838; ENSP00000447353; ENSG00000198324.
ENST00000548163; ENSP00000449994; ENSG00000198324.

GeneID

144717.

KEGG

hsa:144717.

UCSC

uc001tsc.3. human.

Organism-specific databases

CTD

144717.

GeneCards

GC12M111798.

H-InvDB

HIX0010998.

HGNC

HGNC:26509. FAM109A.

neXtProt

NX_Q8N4B1.

PharmGKB

PA143485466.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG117159.

HOVERGEN

HBG061708.

OMA

TRARTYV.

Gene expression databases

ArrayExpress

Q8N4B1.

Bgee

Q8N4B1.

CleanEx

HS_FAM109A.

Genevestigator

Q8N4B1.

GermOnline

ENSG00000198324. Homo sapiens.

Family and domain databases

Gene3D

2.30.29.30. 1 hit.

InterPro

IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
[Graphical view]

Pfam

PF00169. PH. 1 hit.
[Graphical view]

SMART

SM00233. PH. 1 hit.
[Graphical view]

PROSITE

PS50003. PH_DOMAIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

144717.

NextBio

35535063.

Entry information

Entry name

SESQ1_HUMAN

Accession

Primary (citable) accession number: Q8N4B1
Secondary accession number(s): J3KP50, Q6PJL9, Q96MH8

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 31, 2006
Last sequence update:	October 1, 2002
Last modified:	May 1, 2013
This is version 73 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.