Q7Z698 (SPRE2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sprouty-related, EVH1 domain-containing protein 2
Short name=Spred-2

Gene names

Name:

SPRED2

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	418 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.
Subunit structure	Interacts with Ras By similarity. Homodimer and heterodimer. Able to interact with SPRED1 to form heterodimers. Ref.1
Subcellular location	Membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Cytoplasmic vesicle › secretory vesicle membrane; Peripheral membrane protein; Cytoplasmic side Potential. Cytoplasm. Note: Especially found in the cytoplasm of the stratum spinosum cells called membrane-coated granules.
Tissue specificity	Expressed in liver, skin, small intestine, salivary gland and prostate. Ref.6
Post-translational modification	Phosphorylated on tyrosine. Phosphorylation of Tyr-228 and Tyr-231 are required for ubiquitination. Ref.7 Ubiquitinated; leading to degradation by the proteasome. Ref.7
Sequence similarities	Contains 1 KBD domain. Contains 1 SPR (sprouty) domain. Contains 1 WH1 domain.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoplasmic vesicle Membrane
Coding sequence diversity	Alternative splicing
PTM	Phosphoprotein Ubl conjugation
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 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	plasma membrane Inferred from electronic annotation. Source: Compara transport vesicle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	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...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q7Z698-1)

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: Q7Z698-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-9: MTEETHPDD → MASPGS

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 418

418

Sprouty-related, EVH1 domain-containing protein 2

PRO_0000076910

Regions

Domain

5 – 122

118

WH1

Domain

201 – 257

57

KBD

Domain

308 – 416

109

SPR

Amino acid modifications

Modified residue

228

1

Phosphotyrosine Probable

Modified residue

231

1

Phosphotyrosine Probable

Natural variations

Alternative sequence

1 – 9

9

MTEETHPDD → MASPGS in isoform 2.

VSP_043755

Experimental info

Sequence conflict

33

1

Q → R in BAH12943. Ref.2

Sequence conflict

202

1

Y → C in AAP59415. Ref.1

Secondary structure

1

.

.

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418

Helix Strand Turn

Details...

Beta strand

5 – 8

4

Beta strand

11 – 23

13

Beta strand

27 – 32

6

Beta strand

39 – 44

6

Beta strand

57 – 67

11

Beta strand

69 – 77

9

Beta strand

81 – 85

5

Beta strand

88 – 92

5

Beta strand

94 – 104

11

Helix

105 – 123

19

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 25, 2006. Version 2. Checksum: CA4FE80C45008851	FASTA	418	47,558
	10 20 30 40 50 60 MTEETHPDDD SYIVRVKAVV MTRDDSSGGW FPQEGGGISR VGVCKVMHPE GNGRSGFLIH 70 80 90 100 110 120 GERQKDKLVV LECYVRKDLV YTKANPTFHH WKVDNRKFGL TFQSPADARA FDRGVRKAIE 130 140 150 160 170 180 DLIEGSTTSS STIHNEAELG DDDVFTTATD SSSNSSQKRE QPTRTISSPT SCEHRRIYTL 190 200 210 220 230 240 GHLHDSYPTD HYHLDQPMPR PYRQVSFPDD DEEIVRINPR EKIWMTGYED YRHAPVRGKY 250 260 270 280 290 300 PDPSEDADSS YVRFAKGEVP KHDYNYPYVD SSDFGLGEDP KGRGGSVIKT QPSRGKSRRR 310 320 330 340 350 360 KEDGERSRCV YCRDMFNHEE NRRGHCQDAP DSVRTCIRRV SCMWCADSML YHCMSDPEGD 370 380 390 400 410 YTDPCSCDTS DEKFCLRWMA LIALSFLAPC MCCYLPLRAC YHCGVMCRCC GGKHKAAA
	Isoform 2 [UniParc]. Checksum: 2E6F7236B9F0FB3C	FASTA	415	47,033
	10 20 30 40 50 60 MASPGSDSYI VRVKAVVMTR DDSSGGWFPQ EGGGISRVGV CKVMHPEGNG RSGFLIHGER 70 80 90 100 110 120 QKDKLVVLEC YVRKDLVYTK ANPTFHHWKV DNRKFGLTFQ SPADARAFDR GVRKAIEDLI 130 140 150 160 170 180 EGSTTSSSTI HNEAELGDDD VFTTATDSSS NSSQKREQPT RTISSPTSCE HRRIYTLGHL 190 200 210 220 230 240 HDSYPTDHYH LDQPMPRPYR QVSFPDDDEE IVRINPREKI WMTGYEDYRH APVRGKYPDP 250 260 270 280 290 300 SEDADSSYVR FAKGEVPKHD YNYPYVDSSD FGLGEDPKGR GGSVIKTQPS RGKSRRRKED 310 320 330 340 350 360 GERSRCVYCR DMFNHEENRR GHCQDAPDSV RTCIRRVSCM WCADSMLYHC MSDPEGDYTD 370 380 390 400 410 PCSCDTSDEK FCLRWMALIA LSFLAPCMCC YLPLRACYHC GVMCRCCGGK HKAAA

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] (ISOFORM 1), INTERACTION WITH SPRED1. 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] (ISOFORM 2).
[3]	"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].
[4]	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].
[5]	"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: Brain and Ovary.
[6]	"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.
[7]	"Spred-2 steady-state levels are regulated by phosphorylation and Cbl-mediated ubiquitination." Lock P., I S.T.T., Straffon A.F., Schieb H., Hovens C.M., Stylli S.S. Biochem. Biophys. Res. Commun. 351:1018-1023(2006) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION, PHOSPHORYLATION AT TYR-228 AND TYR-231.
[8]	"1H, 13C and 15N resonance assignment of the human Spred2 EVH1 domain." Zimmermann J., Jarchau T., Walter U., Oschkinat H., Ball L.J. J. Biomol. NMR 29:435-436(2004) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 1-124.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY299090 mRNA. Translation: AAP59415.1.
AK299079 mRNA. Translation: BAH12943.1.
AC012370 Genomic DNA. No translation available.
AC097503 Genomic DNA. No translation available.
CH471053 Genomic DNA. Translation: EAW99905.1.
CH471053 Genomic DNA. Translation: EAW99906.1.
BC111495 mRNA. Translation: AAI11496.1.
BC130292 mRNA. Translation: AAI30293.1.
BC136334 mRNA. Translation: AAI36335.1.

IPI

IPI00375554.
IPI00896542.

RefSeq

NP_001121682.1. NM_001128210.1.
NP_861449.2. NM_181784.2.

UniGene

Hs.59332.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2JP2	NMR	-	A	1-124	[»]

ProteinModelPortal

Q7Z698.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-8020116.

STRING

9606.ENSP00000348753.

PTM databases

PhosphoSite

Q7Z698.

Polymorphism databases

DMDM

110825745.

Proteomic databases

PaxDb

Q7Z698.

PRIDE

Q7Z698.

Protocols and materials databases

DNASU

200734.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000356388; ENSP00000348753; ENSG00000198369.
ENST00000443619; ENSP00000393697; ENSG00000198369.

GeneID

200734.

KEGG

hsa:200734.

UCSC

uc002sdr.4. human.
uc010fcw.3. human.

Organism-specific databases

CTD

200734.

GeneCards

GC02M065537.

HGNC

HGNC:17722. SPRED2.

HPA

CAB037223.

MIM

609292. gene.

neXtProt

NX_Q7Z698.

PharmGKB

PA134956365.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG277322.

HOGENOM

HOG000220886.

HOVERGEN

HBG057556.

InParanoid

Q7Z698.

KO

K04703.

OrthoDB

EOG4K6G44.

Enzyme and pathway databases

Pathway_Interaction_DB

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

Gene expression databases

ArrayExpress

Q7Z698.

Bgee

Q7Z698.

CleanEx

HS_SPRED2.

Genevestigator

Q7Z698.

GermOnline

ENSG00000198369. 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

SPRED2. human.

EvolutionaryTrace

Q7Z698.

GenomeRNAi

200734.

NextBio

89969.

SOURCE

Search...

Entry information

Entry name

SPRE2_HUMAN

Accession

Primary (citable) accession number: Q7Z698
Secondary accession number(s): A1L3V4 , B7Z5K7, D6W5F7, E9PEP0, Q2NKX6

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 4, 2005
Last sequence update:	July 25, 2006
Last modified:	May 29, 2013
This is version 89 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.