Q9H902 (REEP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Receptor expression-enhancing protein 1

Gene names

Name:	REEP1
Synonyms:	C2orf23

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

General annotation (Comments)

Function	Required for endoplasmic reticulum (ER) network formation, shaping and remodeling; it links ER tubules to the cytoskeleton. May also enhance the cell surface expression of odorant receptors. Ref.8
Subunit structure	Interacts with SPAST and ATL1; it preferentially interacts with SPAST isoform 1. Interacts (via C-terminus) with microtubules. Interacts with odorant receptor proteins By similarity. Ref.8
Subcellular location	Membrane. Mitochondrion membrane; Multi-pass membrane protein. Endoplasmic reticulum Ref.8 Ref.10.
Involvement in disease	Spastic paraplegia autosomal dominant 31 (SPG31) [MIM:610250]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.10 Ref.11 Ref.12 Distal hereditary motor neuronopathy 5B (HMN5B) [MIM:614751]: A disorder characterized by distal muscular atrophy mainly affecting the upper extremities, in contrast to other distal motor neuronopathies. These constitute a heterogeneous group of neuromuscular diseases caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. HMN5B is characterized by onset in the first or second decade of distal muscle weakness and atrophy, primarily affecting the intrinsic hand muscles, but also affecting the lower legs, resulting in abnormal gait and pes cavus. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9
Sequence similarities	Belongs to the DP1 family.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane Mitochondrion
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Hereditary spastic paraplegia Neurodegeneration
Domain	Transmembrane Transmembrane helix
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell death Inferred from electronic annotation. Source: UniProtKB-KW endoplasmic reticulum tubular network organization Inferred from mutant phenotype Ref.8. Source: UniProtKB protein insertion into membrane Inferred from direct assay Ref.1. Source: HGNC
Cellular_component	endoplasmic reticulum Inferred from direct assay Ref.8. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW membrane Inferred from direct assay Ref.8. Source: UniProtKB mitochondrial membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	microtubule binding Inferred from direct assay Ref.8. Source: UniProtKB olfactory receptor binding Inferred from mutant phenotype Ref.1. Source: HGNC
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q9H902-1)

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: Q9H902-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-35: MVSWIISRLVVLIFGTLYPAYYSYKAVKSKDIKEY → MDHLQAGG

Note: No experimental confirmation available.

Isoform 3 (identifier: Q9H902-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-11: MVSWIISRLVV → MQKVLSNGQTEEVRSGSR

Note: No experimental confirmation available.

Isoform 4 (identifier: Q9H902-4)

The sequence of this isoform differs from the canonical sequence as follows:
     62-201: FPFYYELKIA...SESASSSGTA → DRVPYRRDCG...STSSSATETT

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 201	201	Receptor expression-enhancing protein 1		PRO_0000101821
Regions
	Transmembrane	1 – 21	21	Helical; Potential
	Transmembrane	35 – 55	21	Helical; Potential
	Compositional bias	170 – 173	4	Poly-Pro
Amino acid modifications
	Modified residue	150	1	Phosphoserine By similarity
	Modified residue	152	1	Phosphoserine Ref.7
Natural variations
	Alternative sequence	1 – 35	35	MVSWI…DIKEY → MDHLQAGG in isoform 2.		VSP_042573
	Alternative sequence	1 – 11	11	MVSWIISRLVV → MQKVLSNGQTEEVRSGSR in isoform 3.		VSP_043251
	Alternative sequence	62 – 201	140	FPFYY…SSGTA → DRVPYRRDCGASACRTSPPS GETAPLLPRAPHHRGLGGPA ANTASLRCPGVLLRALAAQA PPRILRSRFRKKSTSSSATE TT in isoform 4.		VSP_043252
	Natural variant	19	1	P → L in SPG31. Ref.12		VAR_067265
	Natural variant	20	1	A → E in SPG31; loss of function mutation; shows severely altered localization to numerous punctate small structures throughout the cytoplasm and no localization to the endoplasmic reticulum; does not colocalize with ATL1. Ref.9 Ref.10 Ref.11		VAR_027351
	Natural variant	23	1	S → F in SPG31. Ref.12		VAR_067266
	Natural variant	42	1	W → R in SPG31. Ref.12		VAR_067267
	Natural variant	56	1	D → N in SPG31. Ref.12		VAR_067268

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 98F120DE100276A9	FASTA	201	22,255
	10 20 30 40 50 60 MVSWIISRLV VLIFGTLYPA YYSYKAVKSK DIKEYVKWMM YWIIFALFTT AETFTDIFLC 70 80 90 100 110 120 WFPFYYELKI AFVAWLLSPY TKGSSLLYRK FVHPTLSSKE KEIDDCLVQA KDRSYDALVH 130 140 150 160 170 180 FGKRGLNVAA TAAVMAASKG QGALSERLRS FSMQDLTTIR GDGAPAPSGP PPPGSGRASG 190 200 KHGQPKMSRS ASESASSSGT A
	Isoform 2 [UniParc]. Checksum: A640F3EDC043D8C1	FASTA	174	18,937
	10 20 30 40 50 60 MDHLQAGGVK WMMYWIIFAL FTTAETFTDI FLCWFPFYYE LKIAFVAWLL SPYTKGSSLL 70 80 90 100 110 120 YRKFVHPTLS SKEKEIDDCL VQAKDRSYDA LVHFGKRGLN VAATAAVMAA SKGQGALSER 130 140 150 160 170 LRSFSMQDLT TIRGDGAPAP SGPPPPGSGR ASGKHGQPKM SRSASESASS SGTA
	Isoform 3 [UniParc]. Checksum: 74EEC9189C8D5229	FASTA	208	22,958
	10 20 30 40 50 60 MQKVLSNGQT EEVRSGSRLI FGTLYPAYYS YKAVKSKDIK EYVKWMMYWI IFALFTTAET 70 80 90 100 110 120 FTDIFLCWFP FYYELKIAFV AWLLSPYTKG SSLLYRKFVH PTLSSKEKEI DDCLVQAKDR 130 140 150 160 170 180 SYDALVHFGK RGLNVAATAA VMAASKGQGA LSERLRSFSM QDLTTIRGDG APAPSGPPPP 190 200 GSGRASGKHG QPKMSRSASE SASSSGTA
	Isoform 4 [UniParc]. Checksum: 13E3F4B75BFF1C96	FASTA	143	16,036
	10 20 30 40 50 60 MVSWIISRLV VLIFGTLYPA YYSYKAVKSK DIKEYVKWMM YWIIFALFTT AETFTDIFLC 70 80 90 100 110 120 WDRVPYRRDC GASACRTSPP SGETAPLLPR APHHRGLGGP AANTASLRCP GVLLRALAAQ 130 140 APPRILRSRF RKKSTSSSAT ETT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"RTP family members induce functional expression of mammalian odorant receptors." Saito H., Kubota M., Roberts R.W., Chi Q., Matsunami H. Cell 119:679-691(2004) [PubMed] [Europe PMC] [Abstract] 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2; 3 AND 4). Tissue: Brain.
[3]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[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 1). Tissue: Testis.
[7]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-152, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[8]	"Hereditary spastic paraplegia proteins REEP1, spastin, and atlastin-1 coordinate microtubule interactions with the tubular ER network." Park S.H., Zhu P.P., Parker R.L., Blackstone C. J. Clin. Invest. 120:1097-1110(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SPAST; ATL1 AND MICROTUBULES.
[9]	"Exome sequencing identifies a REEP1 mutation involved in distal hereditary motor neuropathy type V." Beetz C., Pieber T.R., Hertel N., Schabhuttl M., Fischer C., Trajanoski S., Graf E., Keiner S., Kurth I., Wieland T., Varga R.E., Timmerman V., Reilly M.M., Strom T.M., Auer-Grumbach M. Am. J. Hum. Genet. 91:139-145(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN HMN5B, CHARACTERIZATION OF VARIANT SPG31 GLU-20.
[10]	"Mutations in the novel mitochondrial protein REEP1 cause hereditary spastic paraplegia type 31." Zuechner S., Wang G., Tran-Viet K.-N., Nance M.A., Gaskell P.C., Vance J.M., Ashley-Koch A.E., Pericak-Vance M.A. Am. J. Hum. Genet. 79:365-369(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SPG31 GLU-20, SUBCELLULAR LOCATION.
[11]	"Mutation screening of spastin, atlastin, and REEP1 in hereditary spastic paraplegia." McCorquodale D.S. III, Ozomaro U., Huang J., Montenegro G., Kushman A., Citrigno L., Price J., Speziani F., Pericak-Vance M.A., Zuchner S. Clin. Genet. 79:523-530(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SPG31 GLU-20.
[12]	"REEP1 mutations in SPG31: frequency, mutational spectrum, and potential association with mitochondrial morpho-functional dysfunction." Goizet C., Depienne C., Benard G., Boukhris A., Mundwiller E., Sole G., Coupry I., Pilliod J., Martin-Negrier M.L., Fedirko E., Forlani S., Cazeneuve C., Hannequin D., Charles P., Feki I., Pinel J.F., Ouvrard-Hernandez A.M., Lyonnet S. , Ollagnon-Roman E., Yaouanq J., Toutain A., Dussert C., Fontaine B., Leguern E., Lacombe D., Durr A., Rossignol R., Brice A., Stevanin G. Hum. Mutat. 32:1118-1127(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS SPG31 LEU-19; PHE-23; ARG-42 AND ASN-56.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY562239 mRNA. Translation: AAT70684.1. AK023172 mRNA. Translation: BAB14444.1. AK297201 mRNA. Translation: BAH12523.1. AK297287 mRNA. Translation: BAH12538.1. AK299334 mRNA. Translation: BAH13005.1. CR457301 mRNA. Translation: CAG33582.1. AC009408 Genomic DNA. Translation: AAX93132.1. AC009309 Genomic DNA. No translation available. CH471053 Genomic DNA. Translation: EAW99457.1. CH471053 Genomic DNA. Translation: EAW99458.1. BC064846 mRNA. Translation: AAH64846.1.
IPI	IPI00009673. IPI00917387. IPI00922152. IPI00924625.
RefSeq	NP_001158202.1. NM_001164730.1. NP_001158203.1. NM_001164731.1. NP_001158204.1. NM_001164732.1. NP_075063.1. NM_022912.2.
UniGene	Hs.368884.
3D structure databases
ProteinModelPortal	Q9H902.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9H902. 1 interaction.
STRING	9606.ENSP00000165698.
PTM databases
PhosphoSite	Q9H902.
Polymorphism databases
DMDM	74733929.
Proteomic databases
PaxDb	Q9H902.
PRIDE	Q9H902.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000165698; ENSP00000165698; ENSG00000068615. ENST00000535845; ENSP00000437567; ENSG00000068615. ENST00000538924; ENSP00000438346; ENSG00000068615. ENST00000541910; ENSP00000442681; ENSG00000068615.
GeneID	65055.
KEGG	hsa:65055.
UCSC	uc002srh.4. human.
Organism-specific databases
CTD	65055.
GeneCards	GC02M086441.
HGNC	HGNC:25786. REEP1.
MIM	609139. gene. 610250. phenotype. 614751. phenotype.
neXtProt	NX_Q9H902.
Orphanet	101011. Autosomal dominant spastic paraplegia type 31. 139536. Distal hereditary motor neuropathy type 5.
PharmGKB	PA134906680.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5052.
HOGENOM	HOG000007472.
HOVERGEN	HBG056861.
InParanoid	Q9H902.
OMA	RTSGKHG.
OrthoDB	EOG4D7Z6W.
Gene expression databases
ArrayExpress	Q9H902.
Bgee	Q9H902.
CleanEx	HS_REEP1.
Genevestigator	Q9H902.
GermOnline	ENSG00000068615. Homo sapiens.
Family and domain databases
InterPro	IPR004345. TB2_DP1_HVA22. [Graphical view]
PANTHER	PTHR12300. PTHR12300. 1 hit.
Pfam	PF03134. TB2_DP1_HVA22. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	65055.
NextBio	67222.
SOURCE	Search...

Entry information

Entry name

REEP1_HUMAN

Accession

Primary (citable) accession number: Q9H902
Secondary accession number(s): B7Z4D7 , B7Z4F2, B7Z5R9, D6W5M2, Q53TI0

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 20, 2005
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 95 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.