Q86UX7 (URP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Fermitin family homolog 3

Alternative name(s):
Kindlin-3
MIG2-like protein
Unc-112-related protein 2

Gene names

Name:	FERMT3
Synonyms:	KIND3, MIG2B, URP2

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

General annotation (Comments)

Function	Plays a central role in cell adhesion in hematopoietic cells. Acts by activating the integrin beta-1-3 (ITGB1, ITGB2 and ITGB3). Required for integrin-mediated platelet adhesion and leukocyte adhesion to endothelial cells. Required for activation of integrin beta-2 (ITGB2) in polymorphonuclear granulocytes (PMNs) By similarity. Ref.5 Ref.9 Ref.10 Ref.11 Isoform 2 may act as a repressor of NF-kappa-B and apoptosis. Ref.5 Ref.9 Ref.10 Ref.11
Subunit structure	Interacts with ITGB1, ITGB2 and ITGB3 (via cytoplasmic tails) By similarity.
Subcellular location	Cell projection › podosome By similarity. Note: Present in the F-actin surrounding ring structure of podosomes, which are specialized adhesion structures of hematopoietic cells By similarity. Ref.4
Tissue specificity	Highly expressed in lymph node. Expressed in thymus, spleen and leukocytes. Weakly expressed in placenta, small intestine, stomach, testis and lung. Overexpressed in B-cell malignancies. Ref.1 Ref.4
Domain	The FERM domain is not correctly detected by PROSITE or Pfam techniques because it contains the insertion of a PH domain.
Involvement in disease	Leukocyte adhesion deficiency 3 (LAD3) [MIM:612840]: A disorder characterized by recurrent bacterial infections without pus formation, leukocytosis and major bleeding disorders. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.8 Ref.9 Ref.10 Ref.11
Sequence similarities	Belongs to the kindlin family. Contains 1 FERM domain. Contains 1 PH domain.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell junction Cell projection
Coding sequence diversity	Alternative splicing
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	integrin activation Inferred from mutant phenotype Ref.11Ref.10. Source: UniProtKB leukocyte cell-cell adhesion Inferred from mutant phenotype Ref.11. Source: UniProtKB platelet aggregation Inferred from sequence or structural similarity. Source: UniProtKB regulation of cell-cell adhesion mediated by integrin Inferred from mutant phenotype Ref.10. Source: UniProtKB
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW cell projection Inferred from electronic annotation. Source: UniProtKB-KW podosome Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	integrin binding Inferred from sequence or structural similarity. Source: UniProtKB phospholipid binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q86UX7-1)

Also known as: Long; URP2LF;

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: Q86UX7-2)

Also known as: Short; URP2SF;

The sequence of this isoform differs from the canonical sequence as follows:
     360-363: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 667

667

Fermitin family homolog 3

PRO_0000219454

Regions

Domain

229 – 558

330

FERM

Domain

354 – 457

104

PH

Compositional bias

147 – 155

9

Poly-Lys

Amino acid modifications

Modified residue

11

1

Phosphotyrosine Ref.7 Ref.12

Modified residue

504

1

Phosphotyrosine Ref.12

Natural variations

Alternative sequence

360 – 363

4

Missing in isoform 2.

VSP_009226

Experimental info

Sequence conflict

472

1

A → P in BAC04220. Ref.2

Sequence conflict

480

1

Q → R in BAC04220. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

667

Helix Strand Turn

Details...

Beta strand

370 – 373

4

Beta strand

377 – 380

4

Beta strand

385 – 390

6

Turn

391 – 395

5

Turn

404 – 406

3

Beta strand

408 – 411

4

Helix

415 – 417

3

Beta strand

419 – 427

9

Beta strand

429 – 441

13

Helix

442 – 456

15

Helix

465 – 478

14

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Long) (URP2LF) [UniParc]. Last modified June 1, 2003. Version 1. Checksum: 5ACE15EB689B91B5	FASTA	667	75,953
	10 20 30 40 50 60 MAGMKTASGD YIDSSWELRV FVGEEDPEAE SVTLRVTGES HIGGVLLKIV EQINRKQDWS 70 80 90 100 110 120 DHAIWWEQKR QWLLQTHWTL DKYGILADAR LFFGPQHRPV ILRLPNRRAL RLRASFSQPL 130 140 150 160 170 180 FQAVAAICRL LSIRHPEELS LLRAPEKKEK KKKEKEPEEE LYDLSKVVLA GGVAPALFRG 190 200 210 220 230 240 MPAHFSDSAQ TEACYHMLSR PQPPPDPLLL QRLPRPSSLS DKTQLHSRWL DSSRCLMQQG 250 260 270 280 290 300 IKAGDALWLR FKYYSFFDLD PKTDPVRLTQ LYEQARWDLL LEEIDCTEEE MMVFAALQYH 310 320 330 340 350 360 INKLSQSGEV GEPAGTDPGL DDLDVALSNL EVKLEGSAPT DVLDSLTTIP ELKDHLRIFR 370 380 390 400 410 420 IPRRPRKLTL KGYRQHWVVF KETTLSYYKS QDEAPGDPIQ QLNLKGCEVV PDVNVSGQKF 430 440 450 460 470 480 CIKLLVPSPE GMSEIYLRCQ DEQQYARWMA GCRLASKGRT MADSSYTSEV QAILAFLSLQ 490 500 510 520 530 540 RTGSGGPGNH PHGPDASAEG LNPYGLVAPR FQRKFKAKQL TPRILEAHQN VAQLSLAEAQ 550 560 570 580 590 600 LRFIQAWQSL PDFGISYVMV RFKGSRKDEI LGIANNRLIR IDLAVGDVVK TWRFSNMRQW 610 620 630 640 650 660 NVNWDIRQVA IEFDEHINVA FSCVSASCRI VHEYIGGYIF LSTRERARGE ELDEDLFLQL TGGHEAF
	Isoform 2 (Short) (URP2SF) [UniParc]. Checksum: 243CA27636C67079	FASTA	663	75,430
	10 20 30 40 50 60 MAGMKTASGD YIDSSWELRV FVGEEDPEAE SVTLRVTGES HIGGVLLKIV EQINRKQDWS 70 80 90 100 110 120 DHAIWWEQKR QWLLQTHWTL DKYGILADAR LFFGPQHRPV ILRLPNRRAL RLRASFSQPL 130 140 150 160 170 180 FQAVAAICRL LSIRHPEELS LLRAPEKKEK KKKEKEPEEE LYDLSKVVLA GGVAPALFRG 190 200 210 220 230 240 MPAHFSDSAQ TEACYHMLSR PQPPPDPLLL QRLPRPSSLS DKTQLHSRWL DSSRCLMQQG 250 260 270 280 290 300 IKAGDALWLR FKYYSFFDLD PKTDPVRLTQ LYEQARWDLL LEEIDCTEEE MMVFAALQYH 310 320 330 340 350 360 INKLSQSGEV GEPAGTDPGL DDLDVALSNL EVKLEGSAPT DVLDSLTTIP ELKDHLRIFR 370 380 390 400 410 420 PRKLTLKGYR QHWVVFKETT LSYYKSQDEA PGDPIQQLNL KGCEVVPDVN VSGQKFCIKL 430 440 450 460 470 480 LVPSPEGMSE IYLRCQDEQQ YARWMAGCRL ASKGRTMADS SYTSEVQAIL AFLSLQRTGS 490 500 510 520 530 540 GGPGNHPHGP DASAEGLNPY GLVAPRFQRK FKAKQLTPRI LEAHQNVAQL SLAEAQLRFI 550 560 570 580 590 600 QAWQSLPDFG ISYVMVRFKG SRKDEILGIA NNRLIRIDLA VGDVVKTWRF SNMRQWNVNW 610 620 630 640 650 660 DIRQVAIEFD EHINVAFSCV SASCRIVHEY IGGYIFLSTR ERARGEELDE DLFLQLTGGH EAF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"URP1: a member of a novel family of PH and FERM domain-containing membrane-associated proteins is significantly over-expressed in lung and colon carcinomas." Weinstein E.J., Bourner M., Head R., Zakeri H., Bauer C., Mazzarella R. Biochim. Biophys. Acta 1637:207-216(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY.
[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). Tissue: Thymus.
[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] (ISOFORM 2). Tissue: Lung and Lymph.
[4]	"Proteomic analysis of the cell-surface membrane in chronic lymphocytic leukemia: identification of two novel proteins, BCNP1 and MIG2B." Boyd R.S., Adam P.J., Patel S., Loader J.A., Berry J., Redpath N.T., Poyser H.R., Fletcher G.C., Burgess N.A., Stamps A.C., Hudson L., Smith P., Griffiths M., Willis T.G., Karran E.L., Oscier D.G., Catovsky D., Terrett J.A., Dyer M.J.S. Leukemia 17:1605-1612(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-35; 424-438 AND 569-577, IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[5]	"URP2SF, a FERM and PH domain containing protein, regulates NF-kappaB and apoptosis." Wang L., Deng W., Shi T., Ma D. Biochem. Biophys. Res. Commun. 368:899-906(2008) [PubMed] [Europe PMC] [Abstract] Cited for: POSSIBLE FUNCTION (ISOFORM 2).
[6]	"Kindlin-3: a new gene involved in the pathogenesis of LAD-III." Mory A., Feigelson S.W., Yarali N., Kilic S.S., Bayhan G.I., Gershoni-Baruch R., Etzioni A., Alon R. Blood 112:2591-2591(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN LAD3.
[7]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-11, MASS SPECTROMETRY. Tissue: Platelet.
[8]	"Loss of Kindlin-3 in LAD-III eliminates LFA-1 but not VLA-4 adhesiveness developed under shear flow conditions." Manevich-Mendelson E., Feigelson S.W., Pasvolsky R., Aker M., Grabovsky V., Shulman Z., Kilic S.S., Rosenthal-Allieri M.A., Ben-Dor S., Mory A., Bernard A., Moser M., Etzioni A., Alon R. Blood 114:2344-2353(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN LAD3.
[9]	"LAD-1/variant syndrome is caused by mutations in FERMT3." Kuijpers T.W., van de Vijver E., Weterman M.A.J., de Boer M., Tool A.T.J., van den Berg T.K., Moser M., Jakobs M.E., Seeger K., Sanal O., Uenal S., Cetin M., Roos D., Verhoeven A.J., Baas F. Blood 113:4740-4746(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN LAD3, FUNCTION.
[10]	"Leukocyte adhesion deficiency-III is caused by mutations in KINDLIN3 affecting integrin activation." Svensson L., Howarth K., McDowall A., Patzak I., Evans R., Ussar S., Moser M., Metin A., Fried M., Tomlinson I., Hogg N. Nat. Med. 15:306-312(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN LAD3, FUNCTION.
[11]	"A point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans." Malinin N.L., Zhang L., Choi J., Ciocea A., Razorenova O., Ma Y.-Q., Podrez E.A., Tosi M., Lennon D.P., Caplan A.I., Shurin S.B., Plow E.F., Byzova T.V. Nat. Med. 15:313-318(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN LAD3, FUNCTION.
[12]	"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 TYR-11 AND TYR-504, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[13]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]	"Solution structure of the PH domain of kindlin-3 from human." RIKEN structural genomics initiative (RSGI) Submitted (FEB-2009) to the PDB data bank Cited for: STRUCTURE BY NMR OF 349-478.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY093951 mRNA. Translation: AAM19736.1.
AY093952 mRNA. Translation: AAM19737.1.
AK093719 mRNA. Translation: BAC04220.1.
BC004347 mRNA. Translation: AAH04347.2.
BC013366 mRNA. Translation: AAH13366.1.
BC015584 mRNA. Translation: AAH15584.1.

IPI

IPI00216699.
IPI00397834.

RefSeq

NP_113659.3. NM_031471.5.
NP_848537.1. NM_178443.2.

UniGene

Hs.180535.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2YS3	NMR	-	A	349-478	[»]

ProteinModelPortal

Q86UX7.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q86UX7. 6 interactions.

STRING

9606.ENSP00000279227.

PTM databases

PhosphoSite

Q86UX7.

Polymorphism databases

DMDM

41018464.

Proteomic databases

PaxDb

Q86UX7.

PRIDE

Q86UX7.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000279227; ENSP00000279227; ENSG00000149781.
ENST00000345728; ENSP00000339950; ENSG00000149781.

GeneID

83706.

KEGG

hsa:83706.

UCSC

uc001nyl.2. human.
uc001nym.2. human.

Organism-specific databases

CTD

83706.

GeneCards

GC11P063975.

HGNC

HGNC:23151. FERMT3.

MIM

607901. gene.
612840. phenotype.

neXtProt

NX_Q86UX7.

Orphanet

99844. Leukocyte adhesion deficiency type III.

PharmGKB

PA162388384.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG277845.

HOGENOM

HOG000231715.

HOVERGEN

HBG020688.

InParanoid

Q86UX7.

OMA

EINRKQD.

PhylomeDB

Q86UX7.

Gene expression databases

ArrayExpress

Q86UX7.

Bgee

Q86UX7.

CleanEx

HS_FERMT3.

Genevestigator

Q86UX7.

GermOnline

ENSG00000149781. Homo sapiens.

Family and domain databases

Gene3D

1.20.80.10. 2 hits.
2.30.29.30. 2 hits.

InterPro

IPR019749. Band_41_domain.
IPR014352. FERM/acyl-CoA-bd_prot_3-hlx.
IPR019748. FERM_central.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
[Graphical view]

Pfam

PF00373. FERM_M. 1 hit.
PF00169. PH. 1 hit.
[Graphical view]

SMART

SM00295. B41. 1 hit.
SM00233. PH. 1 hit.
[Graphical view]

SUPFAM

SSF47031. FERM_3-hlx. 2 hits.

PROSITE

PS00660. FERM_1. False negative.
PS00661. FERM_2. 1 hit.
PS50057. FERM_3. False negative.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q86UX7.

GenomeRNAi

83706.

NextBio

72692.

PMAP-CutDB

Q86UX7.

SOURCE

Search...

Entry information

Entry name

URP2_HUMAN

Accession

Primary (citable) accession number: Q86UX7
Secondary accession number(s): Q8IUA1, Q8N207, Q9BT48

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 16, 2004
Last sequence update:	June 1, 2003
Last modified:	May 1, 2013
This is version 100 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.