Q7Z699 (SPRE1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sprouty-related, EVH1 domain-containing protein 1
Short name=Spred-1
Short name=hSpred1

Gene names

Name:

SPRED1

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

General annotation (Comments)

Function	Tyrosine kinase substrate that inhibits growth-factor-mediated activation of MAP kinase. Negatively regulates hematopoiesis of bone marrow By similarity.
Subunit structure	Interacts with Ras. Interacts with TAOK2 and TESK1 By similarity. Homodimer and heterodimer. Interacts with CAV1. Able to interact with SPRED2 to form heterodimers. Ref.1 Ref.6
Subcellular location	Cell membrane; Peripheral membrane protein. Membrane › caveola; Peripheral membrane protein. Nucleus. Note: Localized in cholesterol-rich membrane raft/caveola fractions. Ref.6
Tissue specificity	Weakly expressed in embryonic cell line HEK293. Ref.5
Post-translational modification	Phosphorylated on tyrosine By similarity.
Involvement in disease	Neurofibromatosis 1-like syndrome (NFLS) [MIM:611431]: A disorder characterized mainly by cafe au lait macules without neurofibromas or other tumor manifestations of neurofibromatosis type 1, axillary freckling, and macrocephaly. Additional clinical manifestations include Noonan-like facial dysmorphism, lipomas, learning disabilities and attention deficit-hyperactivity. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.8 Ref.9 Ref.10
Sequence similarities	Contains 1 KBD domain. Contains 1 SPR (sprouty) domain. Contains 1 WH1 domain.
Sequence caution	The sequence AAH18015.1 differs from that shown. Reason: Contaminating sequence. Potential poly-A sequence.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Nucleus
Disease	Disease mutation
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	inactivation of MAPK activity Inferred from sequence or structural similarity. Source: UniProtKB multicellular organismal development Inferred from electronic annotation. Source: InterPro negative regulation of peptidyl-threonine phosphorylation Inferred from mutant phenotype PubMed 20736167. Source: BHF-UCL negative regulation of phosphatase activity Inferred from direct assay PubMed 19389623. Source: UniProtKB positive regulation of DNA damage response, signal transduction by p53 class mediator Inferred from sequence or structural similarity PubMed 20736167. Source: BHF-UCL regulation of protein deacetylation Inferred from sequence or structural similarity PubMed 20736167. Source: BHF-UCL
Cellular_component	caveola Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasm Inferred from direct assay. Source: HPA nucleus Inferred from direct assay. Source: HPA plasma membrane Inferred from direct assay. Source: HPA
Molecular_function	phosphatase binding Inferred from direct assay PubMed 19389623. Source: UniProtKB protein serine/threonine kinase inhibitor activity Inferred from sequence or structural similarity PubMed 20736167. Source: BHF-UCL stem cell factor receptor binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PPP1CA	P62136	3	EBI-5235340,EBI-357253

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 444

444

Sprouty-related, EVH1 domain-containing protein 1

PRO_0000076907

Regions

Domain

6 – 123

118

WH1

Domain

233 – 285

53

KBD

Domain

334 – 442

109

SPR

Compositional bias

147 – 150

4

Poly-Ser

Amino acid modifications

Modified residue

238

1

Phosphoserine By similarity

Natural variations

Natural variant

31

1

W → C in NFLS. Ref.10

VAR_064827

Natural variant

44

1

V → D in NFLS. Ref.8 Ref.9

VAR_064828

Experimental info

Sequence conflict

6 – 7

2

AT → GL in AAP59414. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

444

Helix Strand Turn

Details...

Beta strand

13 – 24

12

Beta strand

26 – 29

4

Beta strand

31 – 37

7

Beta strand

40 – 51

12

Beta strand

54 – 64

11

Turn

65 – 67

3

Beta strand

70 – 75

6

Beta strand

81 – 86

6

Beta strand

89 – 94

6

Beta strand

97 – 105

9

Helix

106 – 121

16

Helix

122 – 124

3

Sequences

	Sequence		Length	Mass (Da)
	Q7Z699 [UniParc]. Last modified January 4, 2005. Version 2. Checksum: 6FFDECCE590DB311	FASTA	444	50,477
	10 20 30 40 50 60 MSEETATSDN DNSYARVRAV VMTRDDSSGG WLPLGGSGLS SVTVFKVPHQ EENGCADFFI 70 80 90 100 110 120 RGERLRDKMV VLECMLKKDL IYNKVTPTFH HWKIDDKKFG LTFQSPADAR AFDRGIRRAI 130 140 150 160 170 180 EDISQGCPES KNEAEGADDL QANEEDSSSS LVKDHLFQQE TVVTSEPYRS SNIRPSPFED 190 200 210 220 230 240 LNARRVYMQS QANQITFGQP GLDIQSRSME YVQRQISKEC GSLKSQNRVP LKSIRHVSFQ 250 260 270 280 290 300 DEDEIVRINP RDILIRRYAD YRHPDMWKND LERDDADSSI QFSKPDSKKS DYLYSCGDET 310 320 330 340 350 360 KLSSPKDSVV FKTQPSSLKI KKSKRRKEDG ERSRCVYCQE RFNHEENVRG KCQDAPDPIK 370 380 390 400 410 420 RCIYQVSCML CAESMLYHCM SDSEGDFSDP CSCDTSDDKF CLRWLALVAL SFIVPCMCCY 430 440 VPLRMCHRCG EACGCCGGKH KAAG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Distinct requirements for the Sprouty domain for functional activity of Spred proteins." King J.A.J., Straffon A.F.L., D'Abaco G.M., Poon C.L.C., I S.T.T., Smith C.M., Buchert M., Corcoran N.M., Hall N.E., Callus B.A., Sarcevic B., Martin D., Lock P., Hovens C.M. Biochem. J. 388:445-454(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH SPRED2. Tissue: Glioblastoma.
[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]. Tissue: Tongue.
[3]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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]. Tissue: Brain.
[5]	"Expression and subcellular localization of Spred proteins in mouse and human tissues." Engelhardt C.M., Bundschu K., Messerschmitt M., Renne T., Walter U., Reinhard M., Schuh K. Histochem. Cell Biol. 122:527-538(2004) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[6]	"The Sprouty-related protein, Spred-1, localizes in a lipid raft/caveola and inhibits ERK activation in collaboration with caveolin-1." Nonami A., Taketomi T., Kimura A., Saeki K., Takaki H., Sanada T., Taniguchi K., Harada M., Kato R., Yoshimura A. Genes Cells 10:887-895(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CAV1, SUBCELLULAR LOCATION.
[7]	"Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype." Brems H., Chmara M., Sahbatou M., Denayer E., Taniguchi K., Kato R., Somers R., Messiaen L., De Schepper S., Fryns J.-P., Cools J., Marynen P., Thomas G., Yoshimura A., Legius E. Nat. Genet. 39:1120-1126(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN NFLS.
[8]	"SPRED1 mutations (Legius syndrome): another clinically useful genotype for dissecting the neurofibromatosis type 1 phenotype." Spurlock G., Bennett E., Chuzhanova N., Thomas N., Jim H.P., Side L., Davies S., Haan E., Kerr B., Huson S.M., Upadhyaya M. J. Med. Genet. 46:431-437(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT NFLS ASP-44.
[9]	"Novel human pathological mutations. Gene symbol: SPRED1. Disease: Legius syndrome." Jim H.P., Upadhyaya M. Hum. Genet. 127:112-112(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT NFLS ASP-44.
[10]	"Legius syndrome in fourteen families." Denayer E., Chmara M., Brems H., Kievit A.M., van Bever Y., Van den Ouweland A.M., Van Minkelen R., de Goede-Bolder A., Oostenbrink R., Lakeman P., Beert E., Ishizaki T., Mori T., Keymolen K., Van den Ende J., Mangold E., Peltonen S., Brice G. , Rankin J., Van Spaendonck-Zwarts K.Y., Yoshimura A., Legius E. Hum. Mutat. 32:E1985-E1998(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT NFLS CYS-31.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY299089 mRNA. Translation: AAP59414.1.
AK091222 mRNA. Translation: BAC03614.1.
CH471125 Genomic DNA. Translation: EAW92368.1.
BC018015 mRNA. Translation: AAH18015.1. Sequence problems.
BC137480 mRNA. Translation: AAI37481.1.
BC137481 mRNA. Translation: AAI37482.1.

IPI

IPI00166291.

RefSeq

NP_689807.1. NM_152594.2.

UniGene

Hs.525781.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3SYX	X-ray	2.45	A	13-131	[»]

ProteinModelPortal

Q7Z699.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q7Z699. 2 interactions.

MINT

MINT-1198540.

STRING

9606.ENSP00000299084.

PTM databases

PhosphoSite

Q7Z699.

Polymorphism databases

DMDM

57013078.

Proteomic databases

PaxDb

Q7Z699.

PRIDE

Q7Z699.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000299084; ENSP00000299084; ENSG00000166068.

GeneID

161742.

KEGG

hsa:161742.

UCSC

uc001zka.4. human.

Organism-specific databases

CTD

161742.

GeneCards

GC15P038545.

HGNC

HGNC:20249. SPRED1.

HPA

HPA042193.

MIM

609291. gene.
611431. phenotype.

neXtProt

NX_Q7Z699.

Orphanet

137605. Legius syndrome.

PharmGKB

PA134897382.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG277322.

HOGENOM

HOG000220886.

HOVERGEN

HBG057556.

InParanoid

Q7Z699.

KO

K04703.

OMA

CVTVFKV.

OrthoDB

EOG40CHH0.

PhylomeDB

Q7Z699.

Enzyme and pathway databases

Pathway_Interaction_DB

kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).

Gene expression databases

ArrayExpress

Q7Z699.

Bgee

Q7Z699.

CleanEx

HS_SPRED1.

Genevestigator

Q7Z699.

GermOnline

ENSG00000166068. Homo sapiens.

Family and domain databases

Gene3D

2.30.29.30. 1 hit.

InterPro

IPR000697. EVH1.
IPR023337. KBD.
IPR011993. PH_like_dom.
IPR007875. Sprouty.
[Graphical view]

Pfam

PF05210. Sprouty. 1 hit.
PF00568. WH1. 1 hit.
[Graphical view]

PROSITE

PS51488. KBD. 1 hit.
PS51227. SPR. 1 hit.
PS50229. WH1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

SPRED1. human.

GenomeRNAi

161742.

NextBio

88102.

SOURCE

Search...

Entry information

Entry name

SPRE1_HUMAN

Accession

Primary (citable) accession number: Q7Z699
Secondary accession number(s): B2RPJ8, Q05D53, Q8N256

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 4, 2005
Last sequence update:	January 4, 2005
Last modified:	May 1, 2013
This is version 91 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.