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Protein

Granulins

Gene

GRN

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Granulins have possible cytokine-like activity. They may play a role in inflammation, wound repair, and tissue remodeling.
Granulin-4 promotes proliferation of the epithelial cell line A431 in culture while granulin-3 acts as an antagonist to granulin-4, inhibiting the growth.

GO - Molecular functioni

  • cytokine activity Source: UniProtKB-KW
  • growth factor activity Source: ProtInc
  • RNA binding Source: UniProtKB

GO - Biological processi

  • neutrophil degranulation Source: Reactome
  • signal transduction Source: ProtInc

Keywordsi

Molecular functionCytokine

Enzyme and pathway databases

ReactomeiR-HSA-6798695. Neutrophil degranulation.
SIGNORiP28799.

Names & Taxonomyi

Protein namesi
Recommended name:
Granulins
Alternative name(s):
Proepithelin
Short name:
PEPI
Cleaved into the following 9 chains:
Alternative name(s):
Glycoprotein of 88 Kda
Short name:
GP88
Short name:
Glycoprotein 88
Progranulin
Alternative name(s):
Granulin G
Alternative name(s):
Granulin F
Alternative name(s):
Granulin B
Alternative name(s):
Granulin A
Alternative name(s):
Granulin C
Alternative name(s):
Granulin D
Alternative name(s):
Granulin E
Gene namesi
Name:GRN
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:4601. GRN.

Subcellular locationi

GO - Cellular componenti

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Ubiquitin-positive frontotemporal dementia (UP-FTD)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionFrontotemporal dementia (FTD) is the second most common cause of dementia in people under the age of 65 years. It is an autosomal dominant neurodegenerative disease.
See also OMIM:607485
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0444519A → D in UP-FTD; no significant difference in the total mRNA between cases and controls; although the mutant protein is expressed it is not secreted and appears to be trapped within an intracellular compartment. 2 PublicationsCorresponds to variant dbSNP:rs63751243Ensembl.1
Ceroid lipofuscinosis, neuronal, 11 (CLN11)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of neuronal ceroid lipofuscinosis characterized by rapidly progressive visual loss due to retinal dystrophy, seizures, cerebellar ataxia, and cerebellar atrophy. Cognitive decline may also occur. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material.
See also OMIM:614706

Keywords - Diseasei

Neurodegeneration, Neuronal ceroid lipofuscinosis

Organism-specific databases

DisGeNETi2896.
GeneReviewsiGRN.
MalaCardsiGRN.
MIMi607485. phenotype.
614706. phenotype.
OpenTargetsiENSG00000030582.
Orphaneti275864. Behavioral variant of frontotemporal dementia.
314629. CLN11 disease.
100070. Progressive non-fluent aphasia.
100069. Semantic dementia.
PharmGKBiPA28998.

Polymorphism and mutation databases

BioMutaiGRN.
DMDMi77416865.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 17Sequence analysisAdd BLAST17
ChainiPRO_000001269318 – 593AcrograninAdd BLAST576
PeptideiPRO_000001269418 – ?47ParagranulinAdd BLAST30
PeptideiPRO_0000012695?58 – ?113Granulin-1Add BLAST56
PeptideiPRO_0000012696123 – 179Granulin-2Add BLAST57
PeptideiPRO_0000012697206 – 261Granulin-3Add BLAST56
PeptideiPRO_0000012698281 – 336Granulin-4Add BLAST56
PeptideiPRO_0000012699364 – 417Granulin-5Add BLAST54
PeptideiPRO_0000012700442 – ?496Granulin-6Add BLAST55
PeptideiPRO_0000012701?518 – ?573Granulin-7Add BLAST56

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi118N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi126 ↔ 1391 Publication
Disulfide bondi133 ↔ 1491 Publication
Glycosylationi236N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi265N-linked (GlcNAc...) asparagine2 Publications1
Disulfide bondi284 ↔ 2961 Publication
Disulfide bondi290 ↔ 3061 Publication
Disulfide bondi297 ↔ 3141 Publication
Disulfide bondi307 ↔ 3211 Publication
Disulfide bondi315 ↔ 3281 Publication
Disulfide bondi322 ↔ 3351 Publication
Disulfide bondi366 ↔ 3781 Publication
Glycosylationi368N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi372 ↔ 3881 Publication
Disulfide bondi397 ↔ 4101 Publication
Disulfide bondi404 ↔ 4161 Publication
Glycosylationi530N-linked (GlcNAc...) asparagine1 Publication1

Post-translational modificationi

Granulins are disulfide bridged.

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiP28799.
MaxQBiP28799.
PaxDbiP28799.
PeptideAtlasiP28799.
PRIDEiP28799.
TopDownProteomicsiP28799-2. [P28799-2]
P28799-3. [P28799-3]

PTM databases

iPTMnetiP28799.
PhosphoSitePlusiP28799.

Miscellaneous databases

PMAP-CutDBiP28799.

Expressioni

Tissue specificityi

In myelogenous leukemic cell lines of promonocytic, promyelocytic, and proerythroid lineage, in fibroblasts, and very strongly in epithelial cell lines. Present in inflammatory cells and bone marrow. Highest levels in kidney.

Gene expression databases

BgeeiENSG00000030582.
CleanExiHS_GRN.
ExpressionAtlasiP28799. baseline and differential.
GenevisibleiP28799. HS.

Organism-specific databases

HPAiCAB019394.
HPA008763.
HPA028747.

Interactioni

Subunit structurei

Acrogranin/Progranulin is secreted as a homodimer.1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • cytokine activity Source: UniProtKB-KW
  • growth factor activity Source: ProtInc

Protein-protein interaction databases

BioGridi109153. 105 interactors.
DIPiDIP-41742N.
IntActiP28799. 89 interactors.
MINTiMINT-271687.
STRINGi9606.ENSP00000053867.

Structurei

Secondary structure

1593
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi137 – 141Combined sources5
Beta strandi143 – 145Combined sources3
Beta strandi147 – 151Combined sources5
Beta strandi282 – 285Combined sources4
Beta strandi288 – 290Combined sources3
Beta strandi294 – 298Combined sources5
Beta strandi304 – 308Combined sources5
Beta strandi315 – 319Combined sources5
Turni330 – 333Combined sources4
Turni367 – 369Combined sources3
Beta strandi377 – 380Combined sources4
Beta strandi382 – 384Combined sources3
Beta strandi386 – 389Combined sources4
Turni399 – 402Combined sources4
Beta strandi409 – 411Combined sources3
Turni412 – 414Combined sources3
Beta strandi415 – 417Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1G26NMR-A281-311[»]
2JYENMR-A281-337[»]
2JYTNMR-A364-417[»]
2JYUNMR-A364-417[»]
2JYVNMR-A123-179[»]
ProteinModelPortaliP28799.
SMRiP28799.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP28799.

Family & Domainsi

Sequence similaritiesi

Belongs to the granulin family.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiKOG4296. Eukaryota.
ENOG410XR6S. LUCA.
GeneTreeiENSGT00470000042293.
HOGENOMiHOG000067856.
HOVERGENiHBG000845.
InParanoidiP28799.
OMAiCCPLVKA.
OrthoDBiEOG091G0H2Q.
PhylomeDBiP28799.
TreeFamiTF319678.

Family and domain databases

InterProiView protein in InterPro
IPR000118. Granulin.
PfamiView protein in Pfam
PF00396. Granulin. 7 hits.
SMARTiView protein in SMART
SM00277. GRAN. 7 hits.
PROSITEiView protein in PROSITE
PS00799. GRANULINS. 7 hits.

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P28799-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MWTLVSWVAL TAGLVAGTRC PDGQFCPVAC CLDPGGASYS CCRPLLDKWP
60 70 80 90 100
TTLSRHLGGP CQVDAHCSAG HSCIFTVSGT SSCCPFPEAV ACGDGHHCCP
110 120 130 140 150
RGFHCSADGR SCFQRSGNNS VGAIQCPDSQ FECPDFSTCC VMVDGSWGCC
160 170 180 190 200
PMPQASCCED RVHCCPHGAF CDLVHTRCIT PTGTHPLAKK LPAQRTNRAV
210 220 230 240 250
ALSSSVMCPD ARSRCPDGST CCELPSGKYG CCPMPNATCC SDHLHCCPQD
260 270 280 290 300
TVCDLIQSKC LSKENATTDL LTKLPAHTVG DVKCDMEVSC PDGYTCCRLQ
310 320 330 340 350
SGAWGCCPFT QAVCCEDHIH CCPAGFTCDT QKGTCEQGPH QVPWMEKAPA
360 370 380 390 400
HLSLPDPQAL KRDVPCDNVS SCPSSDTCCQ LTSGEWGCCP IPEAVCCSDH
410 420 430 440 450
QHCCPQGYTC VAEGQCQRGS EIVAGLEKMP ARRASLSHPR DIGCDQHTSC
460 470 480 490 500
PVGQTCCPSL GGSWACCQLP HAVCCEDRQH CCPAGYTCNV KARSCEKEVV
510 520 530 540 550
SAQPATFLAR SPHVGVKDVE CGEGHFCHDN QTCCRDNRQG WACCPYRQGV
560 570 580 590
CCADRRHCCP AGFRCAARGT KCLRREAPRW DAPLRDPALR QLL
Length:593
Mass (Da):63,544
Last modified:October 11, 2005 - v2
Checksum:i4E5947F1B4EDE619
GO
Isoform 2 (identifier: P28799-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     377-531: Missing.

Show »
Length:438
Mass (Da):46,991
Checksum:i558B72CBAF3B991F
GO
Isoform 3 (identifier: P28799-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-71: MWTLVSWVAL...QVDAHCSAGH → MAITAAHGAS...LPAVKTGCTA
     72-251: Missing.

Note: No experimental confirmation available.
Show »
Length:413
Mass (Da):44,132
Checksum:i0E3767A44BE314EC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti219S → H AA sequence (PubMed:2268320).Curated1
Sequence conflicti290C → S AA sequence (PubMed:8471426).Curated1
Sequence conflicti386W → H AA sequence (PubMed:2268320).Curated1
Sequence conflicti428K → E in BAD96242 (Ref. 8) Curated1
Sequence conflicti454Q → G in AAA58617 (PubMed:1542665).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0444519A → D in UP-FTD; no significant difference in the total mRNA between cases and controls; although the mutant protein is expressed it is not secreted and appears to be trapped within an intracellular compartment. 2 PublicationsCorresponds to variant dbSNP:rs63751243Ensembl.1
Natural variantiVAR_06462519R → W1 PublicationCorresponds to variant dbSNP:rs63750723Ensembl.1
Natural variantiVAR_06462655R → W1 Publication1
Natural variantiVAR_06462769A → T1 PublicationCorresponds to variant dbSNP:rs199944486Ensembl.1
Natural variantiVAR_064628119Missing 1 Publication1
Natural variantiVAR_064629120S → Y1 PublicationCorresponds to variant dbSNP:rs63750043Ensembl.1
Natural variantiVAR_064630182T → M1 PublicationCorresponds to variant dbSNP:rs63750479Ensembl.1
Natural variantiVAR_064631221C → S1 PublicationCorresponds to variant dbSNP:rs758322775Ensembl.1
Natural variantiVAR_064632275P → L1 PublicationCorresponds to variant dbSNP:rs529849967Ensembl.1
Natural variantiVAR_064633376D → N1 PublicationCorresponds to variant dbSNP:rs143030899Ensembl.1
Natural variantiVAR_064634398S → L1 PublicationCorresponds to variant dbSNP:rs148213321Ensembl.1
Natural variantiVAR_064635433R → Q1 PublicationCorresponds to variant dbSNP:rs114248177Ensembl.1
Natural variantiVAR_014830515G → A1 PublicationCorresponds to variant dbSNP:rs25647Ensembl.1
Natural variantiVAR_064636564R → H1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0534721 – 71MWTLV…CSAGH → MAITAAHGASTAVQTGDPAS KDQVTTPWVPSSALIVSSNA RTSPRAVLWSMAPGGAAPCP RLPAVKTGCTA in isoform 3. 1 PublicationAdd BLAST71
Alternative sequenceiVSP_05347372 – 251Missing in isoform 3. 1 PublicationAdd BLAST180
Alternative sequenceiVSP_001837377 – 531Missing in isoform 2. 2 PublicationsAdd BLAST155

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X62320 mRNA. Translation: CAA44196.1.
AF055008 mRNA. Translation: AAC09359.1.
M75161 mRNA. Translation: AAA58617.1. Sequence problems.
AY124489 mRNA. Translation: AAM94026.1.
BT006844 mRNA. Translation: AAP35490.1.
AK023348 mRNA. Translation: BAB14535.1.
AK222522 mRNA. Translation: BAD96242.1.
CH471178 Genomic DNA. Translation: EAW51599.1.
CH471178 Genomic DNA. Translation: EAW51600.1.
BC000324 mRNA. Translation: AAH00324.1.
BC010577 mRNA. Translation: AAH10577.1.
CCDSiCCDS11483.1. [P28799-1]
PIRiJC1284. GYHU.
RefSeqiNP_002078.1. NM_002087.3. [P28799-1]
XP_005257310.1. XM_005257253.1. [P28799-1]
UniGeneiHs.514220.

Genome annotation databases

EnsembliENST00000053867; ENSP00000053867; ENSG00000030582. [P28799-1]
ENST00000639447; ENSP00000492014; ENSG00000030582. [P28799-2]
GeneIDi2896.
KEGGihsa:2896.
UCSCiuc002igp.2. human. [P28799-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiGRN_HUMAN
AccessioniPrimary (citable) accession number: P28799
Secondary accession number(s): D3DX55
, P23781, P23782, P23783, P23784, Q53HQ8, Q53Y88, Q540U8, Q9BWE7, Q9H8S1, Q9UCH0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: October 11, 2005
Last modified: August 30, 2017
This is version 190 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families